Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

Gut, 1988, 29, A1429-A1496

The British Society of

The 49th Meeting of the British Society of Gastroenterology was held at the University of Sheffield on 14-16 September, 1988, under the Presidency of Dr J J Misiewicz. Below are printed the abstracts of the 285 oral and poster communications selected for presentation at the meeting.

nine enkephalin, but not the much larger work up two, chance necropsy finding one. peptide 1-endorphin, is increased in hepatic Diagnostic work up revealed alcohol as the disease. Administration of an opioid likely aetiology in 10, primary biliary cirr- Investigation of hepatic disease by echo antagonist to patients with pro- hosis (PBC) in four. Serum AAT concen- planar imaging duces a withdrawal reaction, and relieves trations were low in 8/24, phenotyping pruritus and fatigue, indicating that (available in 23) revealed: PiZ, five R M CHARNLEY, M K STEHLING, D F EVANS, increased opioid activity contributes to (0.03%); PiM, one (80.5%); PiMZ, 12 R COXON, A M HOWSEMAN, R J ORDRIDGE, J D some of the manifestations of hepatic (3.0%); PiSZ, one (0.17%); and PiMS, HARDCASTLE, P MANSFIELD (Departments failure. three (9%) (population frequency). of Physics and Surgery, Nottingham To determine whether another small Histology: cirrhosis 16, PBC four, CAH University, Nottingham) Conventional opioid peptide, pentapeptide leucine three, CPH two, central fibrosis one, magnetic resonance imaging of the liver is enkephalin, is increased in , fibrosis and steatosis one, normal two (lung hampered by the motion related problems venous blood samples were collected from transplant one, necropsy one) 14/21 of blurring and image artefact which are six groups, each of 15 subjects: (i) acute patients followed for two years survived. caused by respiration. In addition, the long liver disease, (ii) cirrhosis with ascites, (iii) There was no discernable relationship image acquisition time means imaging one cirrhosis without ascites, (iv) severe chronic between phenotype, type or severity of liver liver may take up to 45 minutes. renal failure, (v) disease controls, (vi) disease and age at presentation. The Echo planar imaging (EPI) variant healthy controls. Leucine enkephalin was Serum AAT deficiency is not seen in the MBEST (Modulus Blipped Echo-Planar measured by a highly specific radioimmuno- majority of patients with periportal AAT Single Shot Technique) is a rapid magnetic assay. It was raised significantly (p<0.001) granules. A rare Z related liver disease resonance imaging technique which pro- in group (i) (median 1490 pmolIl, range occurs but in routine practice the finding of duces a complete image in 62 ms, allows up 830-2420) and group (ii) (960, 470-2900) AAT granules may not carry any important http://gut.bmj.com/ to 200 frames to be taken per minute and is compared with the other four groups (iii) diagnostic or prognostic implications. not subject to distortion by respiration. The 415, 180-620; (iv) 560, 180-1020; (v) 325, whole depth of the liver can be imaged in 180-740; (vi) 305, 180-560). In acute liver transverse slices during one breath hold. disease, plasma leucine enkephalin corre- Sympathetic activity and atrial natriuretic We have carried out EPI of the liver on lated with the prothrombin time (r=0.691, peptide (ANP) in cirrhosis three patients with focal liver lesions and p<0.01) and alanine aminotransferase (r= on one healthy volunteer. Focal lesions 0-502, p<0-05) measured in same sample. A J MACGILCHRIST, C HAWKSBY, J BROWN, J L

(hepatic metastases and one cyst) were Plasma leucine enkephalin is increased in REID (University Department of Materia on September 24, 2021 by guest. Protected copyright. imaged without blurring or image artefact acute liver disease in proportion to its Medica, Stobhill General Hospital, Glasgow, and blood flow in the hepatic could severity and in cirrhosis with ascites. and Department of Clinical Pharmacology, also be visualised by producing a cine loop. The Royal Infirmary, Edinburgh) This Echo planar imaging has the potential to study addresses two questions relating to revolutionise magnetic resonance imaging Alpha-l-antitrypsin granules in the liver - a the pathogenesis of ascites. First, does the of the liver in that a complete scan of the discrete entity? sympathetic overactivity that we and others liver can be carried out in less than a minute. have demonstrated in cirrhosis with estab- The intrinsic T2 weighting of the MBEST A M BRIND, M F BASSENDINE, M K BENNEilT, lished ascites also occur in cirrhosis without technique ensures good soft tissue contrast O F W JAMES (University of Newcastle Upon ascites? Second, does a deficiency of atrial and is very sensitive to pathological tissue Tyne) It has been hypothesised that AAT natriuretic peptide (ANP) contribute to the changes so enabling imaging of focal accumulation, demonstrated as periportal sodium retention of ascites? lesions. AAT granules leads to chronic liver disease. We measured plasma noradrenaline Review of our liver clinic records from (NA), plasma renin activity (PRA) and 1978-1988 revealed 29 patients whose ANP in 23 cirrhotics with ascites, 17 cirr- Plasma leucine enkephalin is increased in biopsies contained granules by both PAS hotics without ascites and 34 matched con- liver disease diastase resistent and specific immuno- trol subjects. Values quoted are median peroxidase staining. Age range 19-85 with the range and have been compared by J R THORNTON, M S LOSOWSKY (Department of years, 14 over 65 years, 15 men and 14 one way AoV on log values; p values are Medicine, St James's Hospital, Leeds) The women. compared with controls. NA was signific- liver may play a role in elimination of blood Clinical presentation: symptoms sugges- antly higher both in cirrhotics with (4.7, 1-4 borne, small, opoid peptides. In favour of tive of liver disease and abnormal LFTs 19, to 17 4 nmol/l, p<0.01) and without (3.8, this hypothesis, the pentapeptide methio- portal seven, lung transplant 0-9 to 10-4, p<0-05) ascites than in controls A1429 Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1430 The British Society ofGastroenterology

(1.9, 0.7 to 5.3). In contrast, PRA was condition remains controversial the present Natural history and mortality in primary increased in cirrhotics with ascites (32-0, 3.2 studies providing support both for and sclerosing cholangitis to 419 ngAI/ml/h, p<0.001) but not without against the hypothesis. ascites (4.5, 0.9 to 52, p=0-52) compared R HERRMANN, J S DOOLEY, S SHERLOCK, with controls (3.0, 0-7 to 17 1). ANP tended N MCINTYRE (Royal Free Hospital School of to be increased in cirrhosis with ascites Medicine, Pond Street, London) Recent (50-0, 20 to 238 pg/ml, p=0.065) compared Natural history of chronic non-A, non-B reports suggest that primary sclerosing to cirrhosis without ascites (29.2, 8.1 to : immunosuppressive therapy may cholangitis (PSC) progresses slowly particu- 67.2) or controls (33.3, 5.6 to 81.2). accelerate disease progression larly in asymptomatic patients, and that the We conclude that (1) sympathetic over- overall 10 yr survival from diagnosis is 75- activity is present in cirrhosis even in the M SCHOEMAN, M BILOUS, J GRIERSON, 80% (Gastroenterology 1987; 92: 1869; preascitic stage, lending further support to C LIDDLE, R G BATEY, G C FARRELL (Liver Scand J Gastroenterol 1987; 22: 665). We the 'underfilling' theory of ascites and (2) a Research Unit, Departments of Medicine reviewed the course of 70 patients (46 men, lack of ANP does not appear to directly and Anatomical Pathology, Westmead 24 women) with PSC diagnosed by accepted contribute to the sodium retention of Hospital, Westmead, NSW 2145, Australia) criteria. Major presenting symptoms were ascites, and tends to be higher in the ascitic Chronic non-A, non-B hepatitis (NANB) is jaundice (39%), pruritus (34%) and group suggesting a normal response to an increasingly common condition and lethargy (26%); 17 patients (24%) formed sodium overload. management of this disorder remains an asymptomatic group. Cholangiography problematical. We studied 43 patients (25 showed combined extrahepatic and intra- men, 18 women; median age 32 years) with hepatic disease (EH) in 44 patients (63%) chronic NANB hepatitis over an eight year and intrahepatic changes (IH) alone in 21 Plasma levels and brain receptors of gamma period and followed for a mean of 27-7 patients (30%). Asymptomatic patients amino butyric acid in human hepatic months to determine: (1) severity of disease, were more likely to have IH disease alone encephalopathy and (2) impact of immunosuppressive (59%). The mean follow up was 8-3 yr therapy on progression of disease. NANB (range 0 5-25 yr). The condition deterior- H ALMARDINI, K BARTLETT, R WILLIAMS, C 0 hepatitis was diagnosed by exclusion of all ated in 28 (53%) of the symptomatic group: RECORD (Liver Units, Royal Victoria other causes of chronic liver disease. Risk 24 (45%) developed decompensated liver Infirmary, Newcastle and Kings College factors for infection included iv drug abuse disease (mean 5.7 yr), and three cholangio- Hospital, London) In recent years there has (63%), transfusion of blood products carcinoma (mean 10.3 yr). Ten (59%) of the been much interest in the role of the gamma (30%), tattoos (5%), and nosocomial asymptomatic group showed clinical pro- amino butyric acid (GABA) system in spread (3%0). 63% had anti-HBc and/or gression (mean 3 1 yr); seven developed

. GABA is the anti-HBs while ll1% had low titre ANA jaundice, five pruritus, four hepatic decom- http://gut.bmj.com/ principal neuroinhibitory transmitter in the (1:40). Fifty six per cent of patients had pensation, and one died. The overall esti- central nervous system and an excess of constitutional symptoms, usually tiredness, mated 10 yr survival (Kaplan-Meier) was gabaergic transmission could account for and the remainder were asymptomatic. 55%. Twenty one patients (40%) in the the development of coma. As GABA is Physical signs of chronic liver disease were symptomatic group died; the mean time to degraded in the brain within one minute of present in 42% and none exhibited hepatic death after diagnosis was 7.2 yr (range 0.5- death previous studies in hepatic encephal- decompensation. Liver biopsies were 20 yr). 20 of 49 (41%) patients with EH opathy have relied heavily on animal obtained in 33 patients; chronic persistent disease died, compared with two of 21

models where an increase in brain GABA hepatitis was present in four chronic active (10%) of those with IH disease alone on September 24, 2021 by guest. Protected copyright. receptors has been demonstrated. In the hepatitis (CAH) in 21 and CAH and (p<0Ol). In conclusion. PSC progresses present study we have determined GABA cirrhosis in eight. Neither presence of more rapidly than recently reported receptors in the brain of patients dying of symptoms nor serum ALT correlated with whether or not patients are initially acute and chronic hepatic encephalopathy histology. Among eight patients treated asymptomatic. Combined intra- and extra- using a radioreceptor assay. We have also with prednisolone or prednisolone/ hepatic duct disease was associated with a determined GABA concentrations in the azathioprine, only one had sustained worse prognosis. blood of patients sequentially during the three year normalisation of ALT (not course of the disease. rebiopsied). Seven others had minor falls in Two GABA receptors (KD1 and KD2) ALT but in six rebiopsied patients (six to 96 Controlled trial of prophylactic sclero- were demonstrated in frontal cortex in eight months) progression of fibrosis was evident therapy for oesophageal varices in England: patients and compared with eight controls with cirrhosis present in four. In contrast, Interim analysis of 103 patients dying of ischaemic heart disease but no progress biopsies (eight to 30 months) in significant alterations in either the affinity four untreated patients with histologically D R IRIGER, H L SMART, S W HOSKING, A G or number was seen (KD1 14 3 (SE) 0.8 v similar disease showed progression in only JOHNSON (Departments of Medicine and 12-7 (0.7) nmolIl; KD2 148 (18) v 113 (10) one. Surgery, Royal Hallamshire Hospital, nmol/l; BMAX1 1-6 (0.2) v 1-2 (0.1) pmol/ Histological assessment is required in all Sheffield) One hundred and three consecu- mg; BMAX2 1.9 (0.3) v 1.8 (0. ) pmol/mg). patients with suspected chronic NANB tive patients with cirrhosis and oesophageal Plasma GABA concentrations were hepatitis as ALT and symptoms are unreli- varices which had not bled were invited to significantly increased in 57 patients with able in following progress. In biopsied enter a prophylactic sclerotherapy trial. liver disease and hepatic encephalopathy patients CAH+cirrhosis was present in the Seven declined and the remaining 96 under- (3.3 (0.3) v 0(7 (0. 1) [imoUl; 2 p<0 001) the majority. Immunosuppressive therapy is went wedge hepatic vein catheterisation. highest values being seen in those deeply not only unhelpful, but may accelerate Those with WHVP gradient <12 mmHg unconcious. Thus the role of GABA in this disease progression. were not randomised (group I), the others Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1431 were allocated to prophylactic sclero- control of bleeding was achieved in 19 of the A K BURROUGHS, P BUTLER, M BIAGINI, G R therapy (group II), or no treatment (group 21 patients randomised to injection sclero- FLANNERY, W BRUMFITI, H BAUM (Academic III). Forty patients (41.3%) had alcoholic therapy. There was no significant difference Departments of Medicine and Micro- liver disease (ALD). Patients who bled (p=0.52 Fischer's Exact Test) between the biology, Royal Free Hospital and School of were treated by injection sclerotherapy two forms of treatment. Medicine and Department of Biochemistry, irrespective of randomisation. During a The initial results of this trial suggest that Kings College, London) Antimitochondrial median follow up of 44 months (1-88), 38 SRIF is as effective as injection sclero- antibodies in PBC sera have a variable have died and three underwent transplanta- therapy in controlling acute variceal pattern of reactivity against mitochondrial tion for . Thirty three patients haemorrhage. peptides on immunoblots corresponding to suffered 78 variceal bleeds, which led to the M2 antigen, which is also present in a death in nine. Bleeds occurred in all groups variety of bacteria. The three most com- (group 1 8/31, group II 11/32, group III 14/ M2 autoantigens in primary biliary cirrhosis monly reacting mitochondrial antigens have 32), but only four were related to injection. (PBC) MW of c 70, 50, and 40 Kd. The 70 Kd Variceal size was not an accurate predictor antigen has variable MW according to of bleeding (small 8/39, medium 20/46, large D J MUTIMER, S P M FUSSEY, S J YEAMAN, species. The 70Kd and 50 Kd are distinct 5/11). In non- survival P KELLY, 0 F W JAMES, M F BASSENDINE polypeptides, which has recently been con- in groups II and III was identical, with (University of Newcastle Upon Tyne) firmed after their identification as the trans- slightly better survival rate in group I. In Primary biliary cirrhosis is characterised by acetylase (E2) and component X of the ALD survival in groups I and 11 was signific- AMA directed against trypsin sensitive pyruvate dehydrogenase complex respect- antly longer than in group III (p<0.05). We antigens (M2) of the inner mitochondrial ively. This evidence, together with the find- conclude that in non-alcoholic cirrhosis pro- membrane. We have shown that two M2 ing that a cloned gene product of part of the phylactic sclerotherapy does not prolong autoantigens are the E2 component and 70 Kd antigen absorbs from PBC sera only survival. The difference in survival between protein X of pyruvate dehydrogenase com- AMA reacting with this band, and that ALD and non-ALD suggests that factors plex (PDC) (Lancet 1988, i: 1067). Pyruvate there is variability of immunoblot patterns other than sclerotherapy may be res- dehydrogenase complex is one of three between PBC sera tested against the same ponsible. related 2-oxo acid dehydrogenase com- mitochondria, confirm that AMA represent plexes within mitochondria, the others are a complex and variable family of peptide 2-oxoglutarate dehydrogenase (OGDC) specific antibodies. A prospective randomised controlled clinical and branched-chain 2-oxo acid dehydro- We have, however, consistently found trial comparing somatostatin and injection genase (BCOADC) complexes. that AMA from PBC sera eluted from the sclerotherapy in the control of acute variceal Purified E2 components of PDC, OGDC, main bands of immunoblots of both mito- haemorrhage: preliminary results and BCOADC were prepared and used in chondria and E coli react with each of the

immunoblotting against sera from the other bands of the M2 antigen. This sug- http://gut.bmj.com/ S A JENKINS, J N BAXTER, S ELLENBOGEN, R following: 129 PBC patients (abnormal gests that AMA contain not only specific SHIELDS (University Department ofSurgery, LFTs, AMA +ve: 1:40 by immunofluores- antibodies, but cross reacting antibodies Royal Liverpool Hospital, Liverpool) cence, 37 histological Stage I, 42 Stage II- recognising a common M2 epitope. We Recent studies have suggested that somato- III, 50 Stage IV; follow up 1-19 years, have shown that this epitope is not free statin (SRIF) may be of value in the control medianS years); 50 AMA -ve patients with lipoic acid or lipoamide - the co-factor of of bleeding oesophageal varices. In view of other chronic liver diseases; 12 healthy pyruvate dehydrogenase. This finding the efficacy of injection sclerotherapy in women. should help to understand the nature of AMA and thus the of controlling variceal bleeding, however, it Primary biliary cirrhosis patients: 118 pathophysiology on September 24, 2021 by guest. Protected copyright. has been suggested that this treatment (92%) +ve immunoblot against E2 (+X) of primary biliary cirrhosis. should be the 'gold' standard against which PDC, 87 (67%) +ve against E2 of OGDC, new therapies are evaluated. Therefore, the 70 (54%) +ve against E2 of BCOADC, 59 aim of this study was to compare the efficacy (47%) +ve for all four proteins. Three- Symptom development and prognosis in of SRIF with emergency injection sclero- quarters -ve for all four proteins were asymptomatic primary biliary cirrhosis therapy in the control of acute variceal Stage I. Sixty two control sera -ve for all (PBC). haemorrhage. four proteins. In PBC, no correlation Forty three consecutive patients admitted between pattern of immunoblotting and H MITCHISON, P KELLY, J NEUBERGER, with endoscopically proven, severe, bleed- histological stage or disease progression M BASSENDINE, R WILLIAMS, 0 JAMES ing oesophageal varices were randomised to (p=NS). (University of Newcastle Upon Tyne and either emergency injection sclerotherapy or The E2s of OGDC and BCOADC are King's College Hospital, London) The SRIF (bolus dose of 250 Fg followed by a also M2 autoantigens in PBC. Ninety seven prognosis of patients with PBC but without continuous infusion of 250 [sglh for five per cent of PBC patients reacted with one or symptoms of liver disease at the time of days. The aetiology of the portal hyperten- more E2 (M2 antigen) but these reactions diagnosis is uncertain. We present data on sion was similar in the two groups as was the showed no histological or clinical 95 patients with PBC confirmed histologic- distribution of the patients among the cate- correlates. ally, immunologically, and biochemically gories of the Child's classification. (14 with normal LFTs but diagnostic Twenty two patients received SRIF and histology) from two centres. Seventy 21 injection sclerotherapy. The initial Antimitochondrial antibodies (AMA) in patients from centre A (regional referral variceal haemorrhage was controlled in all primary biliary cirrhosis (PBC) recognise units), 25 from centre B (international 22 patients receiving SRIF but three rebled both specific peptides and shared epitopes of tertiary referral unit). Mean age at presen- during the five day trial period. Overall the M2 antigen tation: centre A 59.6 years, centre B 53-5 Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1432 The British Society ofGastroenterology years, overall 58 years. Follow up three to (n=14; 106 U/I; (0-1264 U/I)) compared increases possibly because of portal venous 16 years: centre A 69 months, centre B 70 with other causes of graft dysfunction washout from normal liver tissue. months, overall 69 months. (n=10; 24 U/lI; (0-291 U/I)), p<0024 and (i) Symptoms: 19/0 centre A, 17/25 stable grafts (n=5; 0; (0-27 U/I)); p<0-0025. centre B developed symptoms of liver Serial studies showed that IL2R rose pro- disease (p<0-001); mean time to symptom gressively in bile and serum before rejection appearance 43 months, centre A, 35 and fell after treatment. These data suggest months, centre B (p=NS). (ii) Deaths: (1) IL2R may be a useful marker of rejec- centre A 15/70; 8/19 who had developed tion after liver transplantation, (2) biliary Modulation of intestinal tone by visceral symptoms (all liver deaths), 7/57 remaining levels may be more specific than serum, (3) reflexes in man asymptomatic (all non-liver deaths). Centre lymphocyte activation is a feature of early B 10/25; 9/17 who had developed symptoms chronic rejection but is less important in J M ROUILLON, F AZPIROZ, J R MALAGELADA (all liver deaths) 1/8 asymptomatic (non- end stage disease suggesting that treatment (Digestive System Research Unit, Hospital liver). Total 25/95 died: 17/36 who had with immunosuppression at this stage is General Vall d'Hebron, Barcelona, Spain) developed symptoms v 8/59 remaining inappropriate. Intestinal tonic muscular activity (intestinal asymptomatic (p<0-001). Comparison of tone) has never been quantified in man these patients developing symptoms with because of the lack of appropriate method- 103 patients presenting with symptoms from Will biodegradable microspheres enhance ology. We have developed an original tech- centre A and 165 from centre B (FU 3-18 regional delivery of a cytotoxic to hepatic nique to investigate the modulation of years) suggests no difference in survival tumour? intestinal tone by intestino-intestinal once symptoms appear. reflexes. In six healthy volunteers intestinal (i) Differences in mortality of initially D CHANG, S A JENKINS, D M NOTU, J S GRIME, tone responses were quantified as variations asymptomatic patients and in proportion P MALTBY, L HAKANSSON, T COOKE (Depart- in the air volume within a flaccid bag (12 cm developing symptoms may be due to differ- ments of Surgery and Nuclear Medicine, long) maintained at a constant pressure by ent referral patterns. (ii) Mortality is Royal Liverpool Hospital and Depart- an electronic barostat. The bag was located strongly related to symptomatic develop- ment of Oncology, University Hospital, in the proximal and balloon- ment: Patients developing symptoms have Lingkoping, Sweden) The aim of this study distentions (one min duration at 10 min similar prognosis to 'classical' symptomatic was to investigate the mechanisms whereby intervals) were randomly performed 8 cm patients. degradable starch microspheres (DSM) orad (A) and 8 cm (R1) and 20 cm (R2) enhance hepatic tumour uptake of cyto- caudad to the bag. Perception was scored by toxics given concomitantly. a graded (0-6) questionnaire. Distentions Soluble interleukin 2 receptors in serum and Overt hepatic tumour was induced in were done in 8 ml stepwise increments until bile of patients following liver transplanta- Lister rats by intraportal injection of HSN the participants reported discomfort (score http://gut.bmj.com/ tion fibrosarcoma cells, its vascularity character- >5). Stimuli below the threshold for dis- ised and the optimum dose of DSM to comfort (3.5 (0.3) perception score for A, D H ADAMS, L WANG, S G HUBSCHER, E ELIAS, minimise the passage of a labelled marker, 3-5 (0.2) for R, and 3-7 (0.2) for R2; mean J M NEUBERGER (Liver Unit, Queen Elizabeth 9Tcm methylene diphosphonate (MDP), (SE) elicited significant intestinal reflex Hospital, Edgbaston, Birmingham) After representing a cytotoxic drug, established. relaxation; interestingly the responses were liver transplantation 80% of patients Methylene diphosphonate alone and in similar for antegrade and retrograde develop acute rejection and 15% progress combination with DSM was injected region- reflexes (11 (3) ml A intestinal vol for A, 14 to chronic irreversible rejection. Rejection ally to determine the distribution of the (1) ml for R, and 12 (3) ml for R2; p<0-05 on September 24, 2021 by guest. Protected copyright. is most reliably diagnosed histologically; a marker to tumour and normal liver tissue for all). We conclude that antegrade as well sensitive, less invasive test would aid immediately after injection, and 90 minutes as retrograde distention triggered reflexes management of graft dysfunction. As later. modulate the tonic contractile activity of the lymphocytes are involved in the inflamma- The tumour was hypovascular and the human jejunum. tory response of rejection we used an distribution expressed in % injected dose/ enzyme linked immunosorbent assay to mg for 'Tcm-MDP injected alone (n=8) was measure interleukin 2 receptor (IL2R) a 1-04 (0.10) in tumour compared with 0-77 Does somatostatin analogue (SMS 201-995) stable, soluble product of activated lympho- (0.04) in normal liver. When given with reduce high output stoma effluent? A con- cytes, in bile and serum after liver trans- DSM the distribution of marker immedi- trolled trial plantation. Serum concentrations of IL2R ately after injection (n-6) was significantly were raised in acute rejection (n=20; greater (p<0.001, Mann-Whitney) in J L SHAFFER, T O'HANRAHAN, S ROWNTREE, median 3433 U/l; (range 1427-4667 U/I)) tumour 16-52 (1.63) compared to normal K SHIPLEY, M H IRVING (Hope Hospital, compared with liver dysfunction due to liver tissue 7.11 (0.71). Ninety minutes later Salford and Sandoz Products Ltd, Feltham, other causes (n=10; 2370 U/I; (1267-3213 when DSM degradation was complete (n= Middlesex) Uncontrolled observations have U/I)); p<0-0025 and stable grafts (n=12; 8) the distribution of marker to tumour was suggested a role for somatostatin analogue 1410 U/I (45-2495 U/1)); p<0*0001. In further increased 10-73 (1.06) compared to (SMS 201-995) in reducing stoma effluent in chronic rejection higher levels were seen in normal liver tissue 0-67 (0.07). These results patients with the . We patients with early severe progressive show that DSM immediately increases the have carried out a randomised placebo disease (n=7; 3500 U/I; (2200-3853 U/I)) retention of a marker in tumour probably controlled crossover trial in six patients with than in end stage chronic rejection (n=5; because of its redistribution from normal a persistently high stoma effluent (1-3-6 140 U/I; (44-2200 U/I)) p<0-001. Biliary tissue blocked by DSM. After degradation Ilday). After a two day control period, the levels were also raised in acute rejection of the DSM, the T:N ratio of marker patients received 50, 100, and then 150 [tg Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1433 of SMS 201-995 or matching placebo on corresponding values were 93 (14) mg/day Hospital, Manchester) The pathogenesis of three successive days. After a 14 day wash- and 49 (4) mg/day, respectively (p<0.05). chronic tropical diarrhoea with severe mal- out period the patients repeated the study In contrast the fractional rates of contractile nutrition probably depends on multiple with the alternative medication. protein synthesis were relatively unaltered environmental factors, although small Somatostatin analogue markedly by ethanol treatment suggesting at least a intestinal damage is likely to be its final reduced stomal volume, median 2-39 I/day partial adaptation to the ethanol feeding. common pathway. To characterise this syn- (range 0.62-4-48) active; 4-03 I/day (1-28- Chronic ethanol administration reduces drome, the immunopathologic features of 5.98) placebo (p<0-001) (Wilcoxon); intestinal myofibrillary protein content and jejunal biopsies from 52 Gambian children sodium output, median 153 mmolUday this may be pathogenic mechanism of alchol (ages 6-33 months) with chronic diarrhoea, (range 27-271) active; 311 (94-594) induced motility disturbances. protein energy malnutrition and anergy to placebo (p<0.001). Potassium output, standard recall antigens, were quantified by median 39 mmollday (8.3-58) active; 54 computerised image analysis and compared (23-154) placebo; (p<0.01). There was a Studies of gastrointestinal drug absorption with further jejunal biopsies (from 28 corresponding increase in urine volume, patients) after three weeks' intensive 2-09 Ilday (0.75-6.62) active; 1-16 (0.47- S A RILEY, F A SUTCLIFFE, M ROWLAND, L A nutritional rehabilitation. A broad 5.13) placebo (p<0-002) and body weight TURNBERG (Departments of Medicine and spectrum of pathologic changes was 57-6 kg (46.5-65.7) active 56-3 (45-4-61.9) Pharmacy, University of Manchester, Hope observed, ranging from 'normal' to flat, placebo (NS). There was no improvement Hospital, Salford and Coupland Building 3, coeliac like mucosae. The majority of speci- in nitrogen, magnesium zinc or copper Oxford Road, Manchester) Hydrophilic mens revealed crypt hypertrophy (<95% balance. Two patients have been on SMS drugs are variably absorbed from the confidence limits for control mucosae), 201-995 therapy for >2 years without . We have therefore increased crypt cell mitotic activity and developing any longterm adverse effects or studied physiological factors which may lymphocytic infiltration. Surface epithelium showing an evidence of pharmacological influence absorption. from villus-bearing mucosae contained tolerance. Twelve subjects participated in 46 increased numbers of small, non-mitotic Somatostatin analogue significantly experiments. After oral ingestion of multi- lymphocytes, but as surface epithelial reduces high stoma effluent and may be of component solutions of atenolol, hydro- volumes progressively diminished epithelial value predominantly in improving water chlorothiazide, frusemide and salicylic acid lymphocyte populations fell in parallel. and electrolyte balance. drug absorption was assessed by 24 hour Lamina propria was expanded by increased urinary excretion. In six subjects, studies numbers of mast cells, eosinophils and were designed to manipulate luminal water occasional basophils: neutrophils were Are alcohol-induced disturbances in small- shifts using: glucose (glu), isotonic electro- rarely encountered. After hospitalisation, bowel motility due to a preferential loss of lytes (iso), or hypertonic electrolytes responsiveness of peripheral lymphocytes smooth-muscle apparatus? (hyper). Solution composition had a to PHA and candidin increased, whereas http://gut.bmj.com/ marked effect on the excretion of atenolol the intestinal mucosal abnormalities failed VICTOR R PREEDY, TIMOTHY J PETERS (Division (glu>Iso: p<002, iso>hyper: p<0.005), to improve or worsened. The intestinal of Clinical Cell Biology, MRC Clinical and hydrochlorothiazide (glu>iso: p<0-07, lesion appears to be a reaction to environ- Research Centre, Watford Road, Harrow, iso>hyper: p<0-02) but no effect on mental challenge which is modulated by Middlesex) A distinguishing feature of frusemide or salicylic acid. Between subject nutritional status rather than a response to chronic alcohol abuse is altered small bowel comparison revealed individuals who were protein energy malnutrition per se. motility. A reduction in the amount of consistently 'good absorbers' of all study contractile apparatus may be a contributing drugs irrespective of solution composition. on September 24, 2021 by guest. Protected copyright. factor. This hypothesis was tested in rats In a further six subjects variations in Characterisation of experimental rotavirus chronically fed a liquid diet containing gastric emptying and orocaecal transit were (RV) diarrhoea in rat ethanol as 36% of total calories. Controls studied. Surprisingly, neither emptying were pair fed the same diet in which ethanol (CoV 54%) nor transit (CoV 51%) corre- A F M SALIM, J A WALKER-SMITH, M J G was substituted by isocaloric glucose. lated with drug excretion (except hydro- FARTHING (Departments ofGastroenterology Studies were done in young (80-90 g body chlorothiazide excretion and gastric and Child Health, St Bartholomew's weight) and mature (280-290 g body emptying, r=0-47, p<0-01). Codeine pre- Hospital, London) Rotavirus is the most weight) animals. After six weeks total con- treatment doubled transit (p<0.05) but left common cause of acute gastroenteritis in tractile protein content in the small bowel of drug excretion unchanged. children worldwide. We have established a young rats was reduced from 72 (7) mg to 49 Although gastrointestinal transit appears rat model for RV diarrhoea and character- (5) mg (mean (SE), n=6, p<0.01). In unimportant in the absorption of hydro- ised it with respect to clinical impact, virus mature rats total contractile protein content philic drugs, luminal water shifts (solvent excretion and water and electrolyte trans- fell from 95 (7) mg to 69 (3) mg (p<0.01). In drag) may be an important determinant. port. Eight to 10 day old neonatal rats (12- young and mature rats, small bowel stomal 20 g) were inoculated orally with rat RV. At protein contents were not significantly 24-36 h all animals developed diarrhoea. altered (p>0-05). Significant reductions in Immunopathologic aspects of small By 96 h clinical recovery had occurred. protein synthesis measured with L[4-3H]- intestinal mucosae in Gambian children with Weight gain was significantly less than con- phenylalanine were obtained for absolute chronic diarrhoea - malnutrition syndrome trol animals during the first 72 h, but by 96 h rates of contractile protein synthesis. In 'catch-up' growth had occurred. Rotavirus young rats values were 60 (6) mg/day and 42 P B SULLIVAN, G NEALE, M N MARSH (Dunn was excreted during the first 72 h of infec- (6) mg/day in control and ethanol fed rats, Nutrition Unit, University ofCambridge and tion, being maximal at 48 h. Rotavirus respectively (p<0-05). In mature rats University Department of Medicine, Hope recovered from infected rat faeces caused Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1434 The British Society ofGastroenterology infection in non-infected neonatal rats. inal permeability observed in coeliac iron deficiency which is so common in these Water and electrolyte transport was studied disease and also in the pathogenesis of the patients. We assessed whether sulphasala- in control and infected rats by in situ steady condition. zine and other second line drugs for state perfusion of the entire small intestine. rheumatoid arthritis (RA) affected the A plasma electrolyte solution (Na 140, K 4, and the blood loss. Patients Cl 104, HCO3 40 mmol/l; 300 mOsmlkg) Coeliac ? - a prospective morpho- with RA requiring a second line agent produced net absorption of water in con- metric study underwent simultaneous study with trols (+67-9±8-5 dI/minIg; n=7), whereas in "'Indium leucocytes and "'Cr red cells infected animals there was a net secretory D E LOFT, M N MARSH, P T CROWE (Hope before and after three to seven months state for water between 18-48 h being Hospital (University of Manchester School treatment with sulphazalazine (N14) or maximal at 24 h (-21.5±7.1; n=6). By 72 h ofMedicine), Eccles Old Road, Salford) An gold, penicillamine or chloroquine (N20), RV-infected intestine was recovering association between (CD) while maintaining an unchanged intake of (water absorption +19*9±4.9; n=7), and proctitis has been suggested but there NSAID's. Faecal "'Indium excretion although still subnormal. This rat model has have been no prospective studies of rectal (n<1%/4 D), which quantitates the inflam- close parallels with human RV infection histology in CD. We report a prospective mation, fell significantly in the sulphasala- since it causes reversible secretory diarr- morphometric analysis of rectal mucosa in zine group (2.5 (0.6)% to 1.5 (0.3)%, mean hoea and impaired weight gain. This model CD. (SE), p<0-01) and this was matched by may be useful for studying the pathogenesis Forty five patients (n=10 untreated CD reduced intestinal blood loss (9.6 (3.2) ml/4 of RV diarrhoea and examining new (UCD); 14 treated CD (TCD); 21 disease D to 5-1 (1.9) ml/4 D p<0-05). No such methods of treatment. controls (C)) referred consecutively for changes were found with the other second jejunal biopsy also underwent rectal biopsy. line agents: "'In excretion 2-0 (0.5)%, 2-2 Patients with beyond rectosigmoid (0.7)% and `Cr red cells 8-8 (2.6) mlV4 D, In vitro mucus glycoprotein synthesis and were excluded. 1 [tm toluidine blue stained 7-9 (3.0) mlU4 D respectively (p>0-1). secretion in normal and coeliac jejunal epon sections were measured by computer- Studies (N12) with "1Fe labelled red cells mucosa ised image analysis in terms of: mucosal over six weeks and after six weeks sulpha- compartment volumes; enumeration of salazine treatment indicate a delayed onset J E CRABTREE, R V HEATLEY, M S LOSOWSKY lamina propria cell types; and surface and of action. (Department of Medicine, St James's crypt intraepithelial lymphocytes. Sulphasalazine reduces small intestine University Hospital, Leeds) Mucus is an No difference in lamina propria, surface inflammation and blood loss caused by important factor in intestinal defences. or crypt epithelial volume; lamina propria NSAID's and may be indicated in rheuma- Evidence from animal models suggests that neutrophils or basophils; nor surface or toid patients who are prone to iron inflammatory mediators can influence crypt intraepithelial lymphocytes. The deficiency. mucus secretion and that T lymphocytes can following were increased in CD: Mast cells http://gut.bmj.com/ induce goblet cell hyperplasia. Immuno- (M (SE) UCD=63-8 (6) p<0-02, TCD= logical abnormalities have been identified in 661 (11) p<0-05, C=388 (6)). Plasma cells Does a somatostatin analogue (Octreotide) coeliac mucosa which might be expected to (UCD=468 (30) p<0-002, TCD=273 (33) reduce the need for parenteral fluids in influence intestinal mucus production. p=NS, C=257 (38)). The following showed patients with a short bowel? To investigate mucus synthesis and secre- a non-significant trend: T lymphocytes tion in coeliac disease, 24-hour in vitro (UCD=62 (7), TCD=52 (9), C=46 (4)). J M D NIGHTINGALE, E R WALKER, W R cultures of jejunal biopsies from 19 patients Eosinophils (UCD=23 (12), TCD=8-3 (4), BURNHAM, M J G FARTHING, J E LENNARD- with histologically normal mucosa and 22 C=6 (3)). JONES (St Mark's Hospital, City Road, on September 24, 2021 by guest. Protected copyright. patients with coeliac disease (13 treated and In this prospective study, UCD was London and Oldchurch Hospital, Romford, nine untreated) were undertaken. The associated with a mild chronic inflammatory Essex) Four patients with a residual small incorporation of 3H glucosamine into infiltrate which was not apparent in TCD. intestine length of 50-100 cm, each with a tissue and secreted trichloroacetic acid There was no oedema, glandular distortion, very high stomallfaecal output and all need- precipitable glycoproteins was measured as surface or crypt epithelial atrophy, and no ing home parenteral nutrition were studied an assessment of mucus production increase in intraepithelial lymphocytes. to see if Octreotide would reduce their fluid (DPMx 103/mg biopsy protein). Mast cells were increased in both UCD and requirements. Each patient was taking Total incorporation of glucosamine into TCD. some oral nutrition and needed 4 or 5 1 tissue and secreted mucus glycoproteins was intravenous fluid daily. The test consisted of significantly greater (p<0-01) in patients two control and two test days during which with untreated coeliac disease (mean (SE) The treatment of NSAID induced small dietary intake remained constant and 414-5 (41.7)) than in patients with histo- intestinal inflammation measurements were made of fluid, electro- logically normal jejunal tissue (248 (13)) or lyte, and calorie balance. Octreotide was treated coeliac patients (264 (15.3)). The I BJARNASON, N HOPKINSON, G ZANELLI, given by a slow intravenous injection ratios of tissue to secreted glycoproteins in T SMITH, P SMETHURST, M J GUMPEL, A J LEVI through the central feeding line. normal, treated, and untreated coeliac (MRC Clinical Research Centre, Watford In every patient the fluid output from the mucosa were 3-15:1, 2-63:1, and 1-56:1 Road, Harrow, Middlesex) Longterm bowel exceeded the oral intake (intake 1-4- respectively. ingestion of NSAIDs causes small intestinal 4-7 kg, output 3-5-6-4 kg). Octreotide at a These results show that intestinal mucus inflammation in 70% of patients. Clinically dose of 50 Fg bd reduced the mean output production is enhanced in patients with the most important consequence of the in every patient by 1-2-1 kg. Mean calorie untreated coeliac disease. This phenome- itflammation is chronic blood loss (Lancet absorption for each patient before and after non may be relevant to the increased intest- 1987; ii: 711) which may contribute to the therapy was 0, 6, 29, 34% and 0, 20, 41, 26% Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1435 respectively. The results were of possible Ireland) Upper GI haemorrhage remains a HCO3 concentrations measured. A con- clinical benefit in two patients though treat- serious cause of morbidity and mortality in sistent and significant decrease was ment at home was continued in only one. patients with despite observed from two minutes to 70 minutes in This patient underwent repeat testing after modern therapy. Factors affecting the pH (ApH=-0.112 (0.027), p<0-005) as three months with almost identical results. maintenance of a formed fibrin clot bathed well as HCO3 concentration (AHCO3= In two patients a dose increase of in gastric juice are felt to be important in the -1.65 mM (0.60), p<002) while pCO2 Octreotide to 100 ,tg tds intravenously gave high incidence of rebleeding. increased (ApC02=0.224 mmHg (0.090), no additional benefit. In a series of in vitro experiments the p

therefore studied the effect of CP on again to be independent of any change in to liver regeneration is uncertain. In vivo http://gut.bmj.com/ isolated guinea pig parietal cells. Guinea pH. after partial hepatectomy there is a striking pig parietal cells were isolated by collage- This work confirms the presence of down regulation of hepatocyte EGF- nase digestion of the gastric mucosa, and fibrinolytic activity in gastric juice and receptors. We therefore studied changes in Percoll density centrifugation. Acid pro- suggests that factors other than acid and EGF binding to hepatocyte membranes, duction was assessed using the [14C] amino pepsin may be primarily responsible for when EGF or insulin and glucagon induced pyrine uptake technique. including clot lysis in the upper GI tract. proliferation in vitro, and compared these Campylobacter pylori caused a reduction with changes induced by 70% hepatectomy of basal acid secretion (80%). Histamine in rats. '21I-EGF binding to cultured adult stimulated acid production was reduced to rat hepatocytes was measured after stimula- on September 24, 2021 by guest. Protected copyright. 50% of maximal stimulation by addition of Evidence of acid secretion by the human tion with EGF (10 ng/ml), or insulin (350 ng/ CP after 15 min. Only a partial return of gall bladder mucosa in vitro ml) and glucagon (400 ng/ml), and com- responsiveness to histamine was observed pared with binding to membranes from when cells were washed after 15 min incuba- J N PLEVRIS, P C HAYES, I A D BOUCHIER animals sacrificed after partial hepatec- tion with CP, indicating recovery of some (University Department of Medicine, Royal tomy. We confirmed EGF receptor down cells. EM also showed some CP attached to Infirmary, Edinburgh) It is recognised that regulation in membranes after 70% resec- parietal cells. gall bladder bile is more acidic than hepatic tion, with binding decreasing within four Campylobacter pylori reduces basal and bile and this has been attributed to HCO3 hours to a maximum (43%) at 24 h. In vitro histamine stimulated acid production. The reabsorption by the gall bladder. The aim of EGF induced a similar magnitude of effect is only partially reversible, and we this study was to investigate in vitro the acid receptor down regulation within 24 h. In conclude that the reduction in acid secretion base changes that occur across the gall contrast insulin and glucagon, despite is not solely the result of cytotoxicity or bladder mucosa. Fresh gall bladder mucosa inducing similar increases in DNA synthe- mechanical damage caused by CP. was obtained at cholecystectomy and placed sis, did not alter EGF binding. Insulin and in an Ussing Chamber and perfused with glucagon in vitro thus fail to reproduce the Ringer Krebs glucose bicarbonate solution. changes in EGF binding seen during Assessment of the fibrinolyfic activity of The viability of the gall bladder was regeneration in vivo, and this study there- gastric juice assessed by measuring the potential differ- fore supports EGF as a major mediator of ences across the gall bladder mucosa. In 10 hepatic regeneration. Differences in time S PATCHETT, H ENRIGHT, L O'CONNELL, N H gall bladder specimens aliquots from the course of receptor down regulation in vivo AFDHAL, D P O'DONOGHUE (St Vincent's mucosal solutions were taken at two probably reflect delays before in vivo EGF Hospital and University College, Dublin, minutes and 70 minutes and pH, pCO2, and binding. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1436 The British Society ofGastroenterology

between normal and coeliac duodenal Serum Na+,K+ATPase activity. Hepatic copper Serum copper caeruloplasmin Group Age group (ugig) (ug/ml) (A U) Adenylate cyclase concentrations were not significantly different between normal I (n=10) Neonates 0-24 h 164-2+35.0* 0.51+0.11* 0.20±0.04* and coeliac or jejunum. Normal II (n=5) Neonates 24-48 h 100.0+27.7*t 0.75+0.07** 0.23±0.02* duodenum and jejunum fluoride stimulated III (n=12) Adult rats 49-9±8-31 1-26±0-17t 0.69±0-16t activities were 47-67 (3.65) (n=28) and 41.88 (9.30) (n=8) respectively. Corres- ponding coeliac values were 54-69 (7.60) (n=8) and 47-28 (18-13) (n=4). Jejunal Expression of the caeruloplasmin gene in studies in mice have provided indirect Na+,K+ATPase activity appears to be adult and neonatal rat liver evidence that soluble mediators derived adversely affected in coeliac disease (CD) from local immune cells are responsible for whereas adenylate cyclase activity is not, L BARROW, M S TANNER (Department ofChild intestinal damage in GvHR and we have even though both are situated on the BLM. Health, University of Leicester, Leicester) now examined directly the role of inter- Like the human newborn, the neonatal ferons in intestinal GvHR. Wistar rat was found to show features of Administration of the interferon inducer, An inhibitor of interleukin-1 in Crohn's copper metabolism which resemble polyinosinic:polycytidylic acid (poly I:C) disease Wilson's disease. Values significantly accelerated weight loss in neonatal mice different from group III are denoted by with GvHR and mice given poly I:C had C C DALLEY, J A AVERY, NA PUNCHARD, J *p

The British Society ofGastroenterology A1437

N K BOUGHTON-SMITH, B J R WHIITLE (Depart- cell free hypochlorite generating system, of 20 NUD patients with confirmed DGE ment of Pharmacology, Wellcome Research hypoxanthine and xanthine oxidase in the did not have GCLO. This implies that Laboratories, Beckenham, Kent) The lipid presence of peroxidase. Neutrophils stimu- GCLO-related gastritis is not associated mediator PAF-acether induces gastro- lated with f-met-leu-phe plus cytochalasin B with DGE and emphasises the need to intestinal damage and may be involved in also reduced 5ASA fluorescence. The time categorise NUD patients into separate inflammatory bowel disease (IBD). The course was coincident with oxidase activity groups that may respond to different relationship between PAF formation and as measured by oxygen consumption. The therapies. inflammation has now been investigated in reaction with 5ASA was abolished by 1 mM models of colitis. Colonic PAF concentra- sodium azide, a peroxidase inhibitor, con- tions were measured by bioassay, after lipid sistent with a role for hypochlorite. extraction and TLC separation, using the These results show that hypochlorite Campylobacter pylori (CP) in abbatoir aggregation of rabbit washed platelets. A reacts rapidly with SASA to produce a non- workers chronic model of IBD was induced in rats by fluorescent product (as yet unidentified). intrarectal administration of trinitro- This provides evidence for the mechanism D VAIRA, C D'ANASTASIO, J HOLTON, J DOWSEUT, M LONDEI, F BERTONE, M MALDINI, benzene sulphonic acid (TNB, 30 mg in of hypochlorite scavenging by SASA and A P R 0-25 ml of 20% ethanol). Control levels of suggests the possibility of monitoring this POLI, SALMON, L GANDOFLI (Depart- PAF (179 (19) pg/g tissue, n=8) were reaction of SASA in vivo. ments of Gastroenterology and Micro- increased at day 1 (eight fold, p<0-01) and biology, The Middlesex Hospital, London, day 7 (three-fold, p<0-01) after TNB, as and Departments of Gastroenterology, VI were levels of immunoreactive LTB4 Geriatric Section, Histopathology and at 1 Chemical Pathology, M Malpighi, Bologna (three-fold, day and 7, p<0-01) and Sunley Research Centre, London) Although leucocyte infiltration, measured as myelo- OESOPHAGO/GASTRODUODENAI1 POSI ERS peroxidase (MPO) activity (11 and 15-fold a strong association has been shown at day 1 and 7 respectively, p<0-01). In Dysmotility-type non-ulcer dyspepsia is between CP and gastritis little is is known colitis in guinea pigs induced by skin sensiti- negatively associated with Campylobacter- about the source and the spread of this sation and intracolonic challenge with like organisms (GCLO) organism. To increase our understanding of dinitrochlorobenzene 1% the transmission of CP we looked for anti- (DNCB, bodies to CP in 97 abattoir workers. The there were increases in PAF A CHUA, N P KENNEDY, D HAMILTON, J J Orabase), workers were divided in five groups: formation (1.5 fold p<0-05, n=12), MPO KEATING, P W N KEELING (Departments of clerks activity (2-7-fold, p<0-01), but not LTB4. Clinical Medicine and Nuclear Medicine, (1) (n= 11), (2) slaughterers (n=41), (3) porters (n=20), (4) gut men (n=18), Increases in colonic PAF concentrations in Trinity College Dublin and St James's rabbit these models may be derived from infiltrat- Hospital, Dublin) Non-ulcer dyspepsia (5) slaughterers (n=7). The sera of all were tested for IgG against CP, C jejuni ing leucocytes. Interaction of PAF with (NUD) patients can be categorised into and http://gut.bmj.com/ other proinflammatory mediators including those with symptoms suggesting oeso- (CJ) Klebsiella (K) by the ELISA be of in the technique. We found a significant differ- LTB4 may importance patho- phageal reflux, gastric dysmotility, peptic ence in of IBD. or antibody levels between the first genesis ulceration, idiopathic dyspepsia. group (clerks) and all the other four groups Although GCLO are associated with peptic (p

A1438 The British Society ofGastroenterology

J WEIL, G D BELL, G HARRISON, J TROWELL, P was significant (p<0-05). In the lamina J S DE CAESTECKER, 1 BATES (INTRODUCED BY GANT, P JONES (Departments of Medicine, propria, a raised percentage of CD4+ R C HEADING) (Department of Medicine, Medical Physics, Pathology, and Micro- T-cells expressed the CD7 marker of T- School of Medical Sciences, UST, Kumasi, biology, The Ipswich Hospital, Heath Road blastogenesis (37% v 26%: p<005) and Ghana, W Africa) Duodenal ulceration is Wing, Ipswich, Suffolk) Successful eradica- there was a decrease of CD8+ T-cells which reported to be more common amongst tion of C pylori appears to reduce duodenal co-expressed CD5 (46% v 63%; p<0-05). young men with homozygous sickle cell ulcer relapse. In agreement with other Similar trends were also observed in the disease (Hb SS). We performed haemo- groups we have found recrudescence of C epithelial compartment. The alterations in globin electrophoresis on 70 healthy univer- pylori one month after treatment with con- T-subset distribution and phenotype sity students and 207 consecutive patients ventional dose De-Nol (seven successes of considerably exceed those observed in undergoing oesophagogastroduodenoscopy 35) or De-Nol plus Amoxil (15 successes of intestinal mucosae in coeliac disease and in a West African centre. In the endoscopy 39). , thereby suggesting a pro- group, 70 had peptic ulcer (PU) disease The aim of the present study was to found perturbation of the local mucosal (duodenal ulcer 42, gastric ulcer two, duo- determine if short termlhigh dose De-Nol immune system in response to C pylori denal five, severe seven, would be more effective than the standard colonisation of the gastric mucosa. duodenal scarring 14). Of the remainder, 92 regime. A total of 37 patients were treated had a normal endoscopy, 23 gastric cancer, with either De-Nol tabs (n=17) or De-Nol 10 oesophagitis and 12 miscellaneous condi- liquid (n=20) both at 240 mg qds for two Duodenal secretion ofcampylobacter pylori- tions. There were no significant differences weeks. specific antibodies in patients with gastritis between the three groups in the prevalence C pylori was confirmed on antral biopsy and duodenitis of haemoglobin phenotype (x2=2.15, before entry to the study and subsequent p>0-45: PU (70): AA52, AS8, AC7, SSO, follow up was with the '4C-urea breath test. J E CRABTREE, B J RATHBONE, T M SHALLCROSS, SC2, CC1; other endoscopy (137): AA105, The 17 patients treated with De-Nol J I WYATr, R V HEATLEY, M S LOSOWSKY AS17, AC14, SS1, SCO, CCO; students (70); tablets all had positive '4C-urea breath tests (Departments ofMedicine and Pathology, St AA51, AS11, AC7, SSO, SC1, CC1). The before treatment, 82% were negative at the James's University Hospital, Leeds) Gastric M:F ratio for PU was 27:1 (p<0-05 v other end of treatment but within a month all had secretion of C pylori specific antibodies by endoscopies). Mean age for PU was relapsed and were again positive. The 20 cultured biopsies in vitro is strongly associ- 428+± 14-6 years. Significantly more patients patients treated with De-Nol had a ated with gastric C pylori colonisation and with PU were current or liquid non-autoimmune gastritis. To investigate exsmokers single '4C-urea breath test one month after in (p<0-005) compared to other endoscopies, treatment. Only one of the 20 was negative. regional variations the mucosal humoral but there was no difference in alcohol C pylori was eradicated from one of 37 response to Cpylori, the duodenal secretion consumption or domicile (urban or rural) patients receiving high dose De-Nol. These of Cpylori antibodies has been examined. between the two endoscopy groups. Sickle results are significantly inferior to conven- Duodenal endoscopic biopsies were cell disease does not play a major role in the http://gut.bmj.com/ tional dose De-Nol regimes (p<0-02). taken from 25 patients for histology and aetiology of peptic ulcer disease in West culture in vitro. C pylori-antibodies Africa. secreted during three-day cultures were Mucosal T-cell subsets in normal gastric measured by ELISA using a soluble antigen antrum and C chronic from one strain of Cpylori. A pylon-associated In 12 patients with antral gastritis but comparative study of dyspepsia in coal gastritis normal duodenal histology (group A) miners and the general population significantly (p<0-05) raised levels of C B J RATHBONE, J WYATr, L K TREJDOSIEWICZ, J D HARRISON, D L on September 24, 2021 by guest. Protected copyright. and were MORRIS (Department of R V HEATLEY, M S LOSOWSKY (Departments pylori specific IgG IgA antibodies Surgery, Queen's Medical Centre, Notting- of Medicine and Pathology, St James's secreted relative to control subjects (B) ham) Miners are known to have a higher University Hospital, Leeds) Chronic with normal antral and duodenal histology incidence of gastric cancer. We are screen- gastritis is a common condition of uncertain (n=8). In five patients with both antral ing for gastric cancer using a dyspepsia aetiology. We have studied 29 patients (10 gastritis and active duodenitis (C) the levels questionnaire, and have therefore investi- with normal histology, 19 with C pylori of secreted C pylori specific IgA antibodies gated the prevalence of dyspepsia in a group associated chronic endo- were significantly higher (p<0.01) than gastritis) being A or mean of 670 retired miners aged 50-75 years, scoped for epigastric pain. Two antral biop- group B, optical density values comparing them with a randomly selected sies were taken for routine histology (H&E for C pylori specific IgA antibodies being group of 743 age matched men identified and modified Giemsa staining) and for cryo- 169 (59) (A), 16-1 (7) (B), and 802 (201) from general practitioner records. All sub- stat sections for double label immuno- (C). Secretion of C pylori specific IgG jects were sent a selfadministered upper GI fluorescence with monoclonal antibodies to antibodies in group C was comparable to symptom questionnaire. One hundred and T-cell subsets. The T-cell subsets of normal group A, but significantly greater than that seventy two (77%) miners replied, com- gastric antrum comprised 68-8% (14.5) of control subjects (p<005). pared with 195 (76.7%) in the control CD8+ (suppressor/cytotoxic) T-cells in the These results demonstrate that C pylori group. One hundred and seventy two and specific antibodies are secreted by the duo- epithelium, 52-9% (19-8) CD8+ T-cells denal of (37.8%) of the miners questionnaires were in the lamina propria. In chronic gastritis, mucosa colonised subjects, and this positive for at least one of the symptoms, there were reduced percentages of CD8+ may have particular relevance for those whilst 195 (30.2%) of the general popula- cells (53 8% (15.6)% intra-epithelial; colonised with duodenitis. tion were symptomatic (X2=588. p=0.05). 43.7% (15.9)% in lamina propria) due to Significantly more miners complained of infiltration by CD4+ (helper/inducer) cells. Does sickle cell disease cause peptic ulcera- anorexia (24.3% v 8.9%. t=3-49. p= The increase of intraepithelial CD4+ cells tion? 0.0006). weight loss (22.6% v 3.6%, Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1439 t=4-77, p=0.0000), and dysphagia (13% v G BIANCHI PORRO, M LAZZARONI, A PRADA, A 300 mg nocte (2000 h). Median daytime 8- 1%, t= 1 -96, p=0.05), whilst there was no FERRARA, E COLOMBO, P R DAL MONTE, F intragastric pH pretreatment was 1-8 (range significant difference between the groups SABBATINI, G JAQUINTO, V BENVESTITO, B P 1.0-3.2) and remained similar on the final for vomiting (18-3% v 12-6%, t=1-70, IMBIMBO (GI Unit, L Sacco Hospital, Milan, day of treatment at 1-3 (1-2-2.3) and two p=0.09), heartburn (75.7% v 75-3%, Gastroenterology Service, Bellaria Hospital, days after completing therapy at 1-7 (1-1- t=0-01, p=0.99), and epigastric pain Bologna, and Chair of Gastroenterology, 1.8). The fasting serum gastrin was similar (51.3% v 44-9%, t= 1-42, p=0.16). Signific- University of Naples, Italy) H2-receptor during therapy and post-therapy compared antly more miners had undergone surgery antagonists administered together with with pretreatment values. The median inte- for peptic ulcer disease (t=3.65, p=0.0004). pirenzepine suppress acid output more than grated gastrin response (pg/mllmin) pre- We conclude that coal miners have a higher either agent alone. The purpose of this treatment was 4875 (range 4225-7375) and prevalence of serious dyspeptic symptoms study was to determine whether pirenze- was not significantly altered on treatment and previous peptic ulcer surgery than the pine and ranitidine given together are being 5950 (range 3900-10000) (p=0.1) or general population. superior to ranitidine alone in inducing two days after treatment being 5200 (3000- healing of duodenal ulcers. One hundred 9300) (p=0.07). On the final day of treat- and sixty six patients from seven centres ment median nocturnal acid output (mmol) is neutral in established duo- Duodenal pH were randomised to receive either raniti- was 11-6 (range 0.4-26.7) compared with denal ulceration dine 300 mg (R), ranitidine 300 mg plus the pretreatment value of 39-4 (9-8-91-2), pirenzepine 50 mg (R+P50), or ranitidine representing a median inhibition of 78% D D KERRIGAN, L A HOUGHTON, S R BROWN, M E 300 mg plus pirenzepine 100 mg (R+P100), (p<0-01). Two days posttreatment median TAYLOR, N W READ, AG JOHNSON (Depart- all at night, under double blind conditions nocturnal acid output was 74-1 (11-181) Human ment of Surgery/Sub-Department for four weeks. One patient on R, two compared with the pretreatment value of K Hallamshire GI Physiology, Floor, Royal patients on R+P50, and two patients on R+ 39.4 (9-8-91-2) representing median Hospital, Sheffield) We have recorded fast- P100 did not complete the treatment. The rebound hypersecretion of 77% (p<0-05). ing (75±3 min) and post-prandial (224±18 healing rates for all treatments did not This was the result of an increase in the min) intraluminal pH at three sites (antrum, differ significantly within each centre. (H+) concentration and volume of secre- duodenal bulb and duodenal loop) in 21 After two weeks, amongst the patients who tion. This rebound nocturnal hypersecretion male subjects: seven healthy volunteers, completed treatment, healing was 42% on may be relevant to the high ulcer relapse active eight healed DU, and six untreated R, 43% on R+P50, 35% on R+P100. At rates after discontinuation of H2 receptor DU. Accurate positioning of the pH probe four weeks these proportions had risen to antagonist therapy. was ensured by attaching the pH electrodes 74, 94, and 76%, with significant (p<0-03) trans- to a multilumen catheter recording differences in favour of the R+P50 group mucosal potential difference (PD) continu- compared with the other two groups.

ously at two sites 4 cm apart. By maintaining Analysis by intent-to-treat yielded similar Antibiotics potentiates colloidal bismuth http://gut.bmj.com/ the PD within the duo- distal port just results. Patients in the three groups experi- subcitrate (CBS) effect in peptic ulcer 2 cm denum, bulb pH (measured distally) enced a similar degree of relief of daytime disease could be recorded. Additional pH elec- and night time pain. Significantly (p<0-05) were 6 cm the duo- trodes located beyond more patients (29%) on R+P100 com- C O'MORAIN, G COGHLAN, D MCKENNA, D and 2 cm to the denal PD port proximal plained of side effects than patients on R GILLIGAN, A TOBIN, R WARD, C KEANE, E C gastric port. (5%) and on R+P50 (10%). It is concluded SWEENEY (Department of Gastroenterology, During fasting, the % of time pH fell to that treatment with ranitidine combined Meath/Adelaide Hospitals, Trinity College, <4 in both the duodenal bulb and loop was with low dose pirenzepine in patients with Dublin, Ireland) Eradication of Campylo- on September 24, 2021 by guest. Protected copyright. greater in healed than in active DU (bulb duodenal ulcer results in significantly better bacter pylori (CP) results in a lower relapse pH: 12-6% (0-45.7) v 1-5% (0-7-2), healing than the H2-antagonist alone. The rate of DU over a period of one year. Duodenal acidi- median (range); p=003]. failure to achieve a significantly higher heal- Colloidal bismuth subcitrate, an effective fication was similar in active DU and con- ing rate with the combination including the ulcer healing reduces CP infection by 20 to trols Meal did not (p= 1.0). ingestion higher dose of pirenzepine may have been 50%. The aim of this study was to see if significantly alter the % time that duodenal due to side effects that reduced compliance. adjuvant antibiotic therapy with CBS pH was reduced. Bulb pH was <4 for 16% improves healing rates of DU, the associ- of the postprandial period in healed DU, ated gastritis and eradication of CP. compared with 4-5% (normals) and 1-7% Rebound nocturnal hypersecretion after One hundred and ten patients with endo- (active DU). A similar pattern was noted in four weeks H2 antagonist therapy scopically proven DU were randomised to the duodenal loop (healed v active: 1-4% v receive CBS 120 mg qid for six weeks. 0-2%; p=0.05). No significant differences G M FULLARTON, G MCLAUCHLAN, A n=56, CBS 120 mg qid for six weeks+ were seen in antral pH throughout fasting MACDONALD, G P CREAN, K E L MCCOLL amoxycillin, (A) 250 mg tds for the first and fed periods. Active DU is associated (University Departments of Medicine and week (n=24) or CBS 120 mg qid for six with normal bulb pH; once healing has Surgery, Western Infirmary, Glasgow and weeks+metronidazole 200 mg tds for the occurred bulb pH is significantly reduced. Gastrointestinal Centre, Southern General first week (n=26). At endoscopy before and This finding may explain the typical cycle of Hospital, Glasgow) Daytime intragastric after treatment two antral biopsies were spontaneous healing, yet frequent relapse stimulated taken. One was placed in formalin stained in DU disease. pH, fasting and Oxo meal gastrin response and nocturnal acid output were with haematoxylin and eosin and Warthin studied in eight male duodenal ulcer Starry silver stain and assessed to document Combined ranitidine and pirenzepine in the patients before, during, and two days after the presence of gastritis and CP. The other treatment of duodenal ulcer completing a four week course of nizatidine biopsy was assessed microbiologically by Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1440 The British Society ofGastroenterology gram stain and culture for the presence of mean antacid usage in the two groups being and Hepatology, University Hospital, CP. 142 v 64, 84 v 63, 97 v 07, and 72 v 03 Leiden, The Netherlands) Oral omeprazole There was no significant difference in for the four fortnights (NS for any period). treatment for one week has been shown to duodenal ulcer healing rates for the three Our results indicate that the administra- significantly increase serum pepsinogen groups. Eighty eight of 110 (82%) patients tion of CBS benefited non-ulcer dyspepsia (PG) A levels. This study was undertaken to were CP positive and 97 of the 110 (89%) patients with gastritis but had no effect on determine whether intravenous administra- had antral gastritis before treatment. After those without. We suggest that histological tion of repeated doses of omeprazole for treatment 33% of the CBS treated group gastritis is one of several causes of non-ulcer only 24 hours affects serum concentrations became CP negative compared with 53% in dyspepsia. of PGA and PGC or the PGA/PGC ratio. the CBS+A and 62% in the CBS+M The results were related to serum gastrin treated groups. Gastritis was healed in 42% and intragastric pH. Eight fasting men, of patients in the CBS treated group com- Double blind comparative study of ome- median age 22 (19-62) yrs, received an iv pared with 64% in the CBS+A and 56% in prazole (40 mg od) vs cimetidine (400 mg bolus injection of 80 mg omeprazole the CBS+M treated groups. There was a qds) in the treatment of erosive reflux followed by injection of 40 mg of the drug significant improvement in CP eradication oesophagitis every six hours for a total period of 24 and gastritis (p<0.05) in the antibiotic+ hours. Serum concentrations of PGA, CBS treated groups compared with CBS T C B DEHN, H A SHEPHERD, D COLIN-JONES, PGC, and gastrin were measured before alone. This study suggests that antibiotic M G W KETTLEWELL (John Radcliffe Hospital, and at 3, 6, 12, 18, and 24 hours by therapy is a useful adjuvant treatment in Oxford, The Royal Hampshire County radioimmunoassay. Intragastric pH was duodenal ulcer disease. Hospital, Winchester, and Queen Alexandra recorded continuously by an ambulatory Hospital, Portsmouth) The use of cimeti- pH monitor (PROXIMA Light). Statistical dine (cim) is established in the management analysis was done by Wilcoxon's test. The effect of colloidal bismuth subeitrate on of oesophagitis: no study has compared the PGA increased (p<0O05) from a basal symptoms and gastric histology in non-ulcer efficacy of this drug with that of omeprazole value of 47 (6) Fg/l to 83 (20) [tg/l at 12 h, dyspepsia - a double-blind placebo- (om) in the treatment of non-refractory 130 (39) jIg/l at 18 h, and 134 (44) jig/I at controlled study oesophagitis. Sixty seven symptomatic 24 h. PGC was 19 (5) jig/l basally and patients with endoscopically and histologic- showed non-significant increases to 29 (11), J Y KANG, H H TAY, A WEE, R GUAN, M V MATH, ally verified reflux oesophagitis were 57 (31), and 35 (12) Ig/l, at 12, 18, and 24 h, YAP (Division of Gastroenterology, Depart- randomly allocated eight weeks of con- respectively. The PGA/PGC ratio did not ment of Medicine and Department of tinuous treatment with either cim 400 mg change. Serum gastrin increased (p<0.05) Pathology, National University Hospital, qds (n=31) or om 40 mg od (n=36). Clinical from 35 (7) to 94 (31), 59 (14), and 85 (27) Singapore) The aim of this study was to assessment was made pre-entry by scoring ng/l, at 12, 18, and 24 h. Intragastric pH was determine the effect of collidal bismuth symptomatic, endoscopic and histological 1 1(0. 1), significantly rising to 3-8 (0.8), 2 6 http://gut.bmj.com/ subcitrate (CBS, De-Nol) on symptoms and severity. Symptoms were repeated twice (0.6), 39 (0.9), 45 (0.9), and 58 (0.5) at 3, gastric histology in patients with non-ulcer weekly thereafter: endoscopy and histology 6, 12, 18, and 24 h, respectively. dyspepsia. Patients with food related upper at four and eight weeks. Healing was Intravenous administration of repeated abdominal pain not caused by ulcer disease defined as complete epithelialisation of all doses of omeprazole increases serum PGA were randomised to receive one tablet of oesophageal lesions. as early as 12 hours after the first dose. The CBS or matching placebo four times daily At four and eight weeks, healing had increase in serum PGA coincides with a for eight weeks. Fifty one patients com- occurred in 57% (om) v 29% (cim) significant rise in serum gastrin, but is pleted the trial: 28 patients in the bismuth (p=0.0028) and 74% (om) v 28% (cim) preceded by a significant increase of intra- on September 24, 2021 by guest. Protected copyright. group and 23 in the placebo group. Overall (p=O.000l) respectively. At two weeks gastric pH for nine hours. Thus, the effect of there was no difference between the two complete relief of heartburn was achieved antisecretory drugs on serum PGA may groups in terms of symptom relief, reduc- by om in 75% and cim in 42% of patients occur much earlier than previously shown. tion of gastritis or eradication of gastric (p=0 007) and at eight weeks in 92% and spiral organisms. Amongst patients with 59% (p=0005) respectively. At entry there histological gastritis, however (n=23), was no significant difference in severity of Omeprazole provides faster ulcer healing those who took CBS used fewer antacid histological scoring between groups. At and symptom relief than cimetidine in the tablets (number of tablets used being 3 1 v four weeks a significantly greater propor- treatment of gastric ulcer 19 3 for the first fortnight, p<0-02 using the tion of patients on om were healed histo- Wilcoxon's rank-sum test: 1.8 v 22.4 for the logically with 16/26 (61%) v, 9/29 (31%) C M BATE, G V H BRADBY, S P WILKINSON, second, p<0-02: 0-7 v 19-2 for the third, healed on om and cim respectively (p= M C BATESON, W S HISLOP, J P CROWE, C P p<0(025: and 0.3 v 10.5 for the fourth, NS); 0 0028). Omeprazole is superior to full dose WILLOUGHBY, E M PEERS, P D I RICHARDSON, they were more likely to become asympto- cimetidine in the treatment of reflux OPUS-OGUT TRIAL INVESTIGATORS GROUP (UK matic (8 of 11 v 3 of 12 p<0.05); their oesophagitis. AND EIRE) (Gastroenterology Department of gastritis was more likely to resolve (5 of 10 v Hospitals in Wigan, Sandwell, Gloucester, 0 of 12, p<0025) and their gastric spiral Bishop Auckland, Paisley, Dublin and organisms were more likely to be eradicated Effects of intravenous omeprazole on serum Orsett and Astra Pharmaceuticals Ltd, (8 of 9 v 0 of 12, p<0.001) when compared pepsinogens, serum gastrin and intragastric Kings Langley) This first large study in the with patients taking placebo. In contrast, pH British Isles of omeprazole in gastric ulcer patients who did not have gastritis in their aimed to compare endoscopically assessed index biopsies (n=28) fared similarly I BIEMOND, J B M J JANSEN, L C BAAK, C B H W ulcer healing, symptomatic relief and toler- whether they received CBS or placebo, the LAMERS (Department of Gastroenterology ability of omeprazole (20 mg om) with Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1441 cimetidine (400 mg bd). One hundred and 5% of cases, respectively. The recurrence Functional dyspepsia (FD): a meta-analysis ninety seven patients aged 18-80 years with rate was 45% among smokers (95% CL: 36- of randomised placebo controlled clinical symptomatic gastric ulcers (94% B5 mm 53%) compared with 25% among non- trials (RPCCT) diameter) were randomised to receive smokers (95% CL: 15-35%; p<0.05). double blind treatment with omeprazole Similarly, ulcers recurred more rapidly G DOBRILLA, P VALLAPERTA, M COMBERLATO (105) or cimetidine (92) for four, or if (p<0.05) in patients with a healed pre- (Division of Gastroenterology, General unhealed after four weeks, for eight weeks. pyloric ulcer (49%, 95% CL: 40-57%) than Regional Hospital 39100 - Bolzano, Italy) The groups were comparable at randomisa- in patients with a healed ulcer in the body of The aim of this study was to produce a meta- tion. Patients found later to have pre- the stomach (23%; 95% CL: 14-33%). analysis of the results of short-term PRCCT existing carcinoma were excluded from In conclusion, the ulcer recurrence rates on the drug treatment of FD with antisecre- analyses (three omeprazole and five are similar after six weeks' treatment with tives (AS) and gastrokinetics (GK). Trials cimetidine). omeprazole and cimetidine in patients with were retrieved from computerised data On an intention-to-treat analysis, after gastric ulcer disease. Smoking and a pre- bases, by scanning of published reviews and four weeks 74/102 (73%) of omeprazole pyloric ulcer location indicate an increased Current Contents. Of a total of 74 retrieved patients and 48/87 (55%) of cimetidine risk of early relapse. trials, 23 proved eligible for meta-analysis patients had healed ulcers (p<005; 95% on the basis of six essential selection criteria confidence interval (CI) for the therapeutic defined a priori. Results of treatment were gain of 18% being +4% to +31%). After Why refractory duodenal ulcers do not heal expressed in terms of 'therapeutic success' eight weeks the cumulative numbers of (TS) ('symptom-free patients', 'patients patients with healed ulcers were 86 (84%) M J ROGERS, J HOLMFIELD, J PRIMROSE, T with significant improvement in symptoms', for omeprazole and 64 (74%) for cimetidine GLEDHILL, D JOHNSTON (University Depart- 'patients with excellent results'). Differ- (ns; CI -1% to +22%). ment of Surgery, The General Infirmary, ences in TS rates between the various drugs After four weeks treatment 81% of Leeds) After three months therapy with H2 and placebo were calculated in each trial as omeprazole patients and 60% of cimetidine receptor antagonists (H2RA's), 7% of duo- the algebraic difference together with the patients were symptom free (p<0-01), and denal ulcers remain unhealed; why these respective 95% confidence interval (95% the omeprazole patients took fewer 'refractory' ulcers (RFDU) do not heal is CI); the pooling of results of all eligible antacids than the cimetidine patients. Both not clear but H2RA's may not suppress trials was done using Cochran's weighted drugs were well tolerated and the two nocturnal acid in patients with RFDU. method. With AS the mean difference in TS groups of patients had a similar pattern of Thirty eight consecutive patients referred rates v placebo was +20% (95% CI: 14- adverse events. Omeprazole once daily pro- for operation for duodenal ulcer (24 non- 24%). The therapeutic gain for the single vides faster healing of the lesion, and swifter RFDU, 14 RFDU) had 24 hour ambulatory AS was 25% (95% CI: 14-36%) for pirenze- relief of the symptoms of gastric ulcer than intragastric pH recorded on placebo and on pine and 18% (95% CI: 12-24%) for H2- cimetidine twice daily. 300 mg ranitidine nocte (RAN). Median antagonists. Meta-analysis of trials with GK http://gut.bmj.com/ 24 h, night time (0000-0800) and daytime also showed superior efficacy of these (08 00-00 00) pH and 24 h, night time and agents compared to placebo, with a mean Gastric ulcer recurrence after six weeks' daytime [H+] (area under [H+] v time curve) difference in TS rates of +46% (95% CI: treatment with omeprazole and cimetidine - were calculated for each recording. 40-52%). Singly, the mean differences in six months double blind comparative follow- Twenty four hour, night time and day- TS rates v placebo were +43% (95% CI: up study time pH (on placebo and RAN) of patients 27-59%) for metoclopramide, +56% (95% with non-RFDU did not differ significantly CI: 46-74%) for domperidone, and +39% K BEHALF A LAURITSEN ON OF DANISH MULTI- from patients with RFDU. Ranitidine nocte (95% CI: 30-48%) for cisapride, respect- on September 24, 2021 by guest. Protected copyright. CENTRE STUDY GROUP (INTRODUCED BY J reduced 24 hour (H+] a median (quartile) ively. RASK-MADSEN) (Department of Medical 41% (28-61) in patients with RFDU and Gastroenterology, Odense University 61% (36-67) in those with non-RFDU Hospital, Odense, Denmark) To compare (NS); night time [H+] 87% (56-98) in Famotidine (F) in single morning (SM) v ulcer recurrence after six weeks' double patients with RFDU and 95% (83-99) in single nocturnal (SN) dose (D) in the treat- blind treatment with omeprazole (30 mg those with non-RFDU; daytime [H+] 32% ment ofduodenal ulcer (DU) daily) and cimetidine (1 g daily) in patients (5-58) in patients with RFDU and 25% with gastric ulcers those with healed ulcers (1-46) in those with non-RFDU (NS). G DOBRILLA, G DE PRETIS, G FONTANA, P were seen after two, four, and six months, Ranitidine nocte suppressed acid as MAIOLO, G MARENCO, G MENARDO, F P ROSSINI,. or more often if warranted. Endoscopy was potently in patients with RFDU as in A FERRARI, A SAGGIORO, P PALLINI (GI Units done if the patient had experienced ulcer patients with non-RFDU; but reduced of Bolzano, Bologna, Pietra Ligure, pain on at least four days during the same nocturnal [H+] less than 50% in three of 14 Torino, Mestre, Italy) In 1986 some of us week and after six months, regardless of the patients with RFDU but in 0 of 24 patients reported an open study on 41 DU patients presence or absence of symptoms. with non-RFDU (NS). suggesting that the healing effect of SMD of Eleven centres contributed 218 patients Ranitidine nocte adequately suppresses cimetidine and ranitidine was comparable of whom 110 had received omeprazole and nocturnal acid in most patients with RFDU; with that of the respective SND. 108 cimetidine. Ulcers recurred in 35% of we suggest these patients are erratic tablet Aim of this multicentre study was to the patients from the omeprazole group takers. In a few patients with RFDU, RAN verify these results by a randomised double (95% confidence limits (CL): 26-44%) and affords inadequate inhibition of acid; acid blind trial with F 40 mg in SMD v SND. in 41% (95% CL: 31-50%) of those from suppression sufficient to heal ulcers in these One hundred and eighteen of 127 DU the cimetidine group (p>0-05; log-rank patients may be achieved with higher doses patients, informed and consenting, com- test) and were asymptomatic in 15% and of ranitidine, other drugs or surgery. pleted the four to eight week trial. By week Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1442 The British Society ofGastroenterology four the healing rate at endoscopy was C J SHORROCK, L GIBBONS, W D W REES than after placebo (no aspirin, no omepra- 77-2% (44/57) in patients on SMD com- (Department of Gastroenterology, Hope zole, p<0.01), whereas after omeprazole 40 pared with 78-6% (48/66) of patients on Hospital, Eccles Old Road, Salford) Prosta- mg bd plus aspirin (2.4 (1.3-4.4) pl/10 SND (95% IC for the difference: -15+ 18, glandins have been shown to protect gastro- mins) it was not. The effect of omeprazole p=0.84). By week eight these percentages duodenal mucosa from damage by a variety on intragastric acidity was dose dependent were 85.7% (48/56) and 91% (55/60), of noxious agents. Enhancement of the (pH 2-26 (interquartile range 2-11-2.58)), respectively (95% IC for the difference: protective 'mucus-bicarbonate' barrier may aspirin alone; 3-67 (2.66-6-52), omeprazole -7+19, p=0.31). be an important mechanism of prosta- 20 mg; 6-65 (5-59-6-88), omeprazole 40 mg This study confirms the results of the glandin action on gastric mucosa and there- bd (p<0-01) and the reduction in bleeding previous open study and shows that the fore we have examined the influence of correlated with intragastric pH (p<001). single morning dose of F (and probably of enprostil, a synthetic dihydroprostaglandin Omeprazole 20 mg, like H2 receptor the H2-blockers) is equally effective as the E2, on gastric bicarbonate secretion in vitro antagonists, reduces acute aspirin induced single nocturnal dose in healing DU. Such and by the intact human stomach. microbleeding to levels which are still a result suggests that the inhibition of Addition of enprostil (10-6M) to the higher than with placebo. With omeprazole nocturnal acidity has a significant but not luminal side of isolated amphibian gastric 40 mg bd, pH approaches anacidity and essential pathogenetic role in ulcer healing. mucosa, mounted in an Ussing chamber, bleeding is not significantly different from produced a 28% increase in bicarbonate placebo, suggesting that gastric injury can secretion (0.25 (0.08) to 0-32 (0.07) ltmoll be abolished. This has therapeutic potential cm2/h, n=6, p<0-05; mean (SE)). for elderly patients taking NSAIDs. Sucralfate (S) v H2-antagonists (H2-A) in DU Using a perfusion technique the effect of non-responders (non-R) to initial treatment enprostil (35 ig) on human gastric bicarbo- with sucralfate nate secretion was studied. Bicarbonate A new model of human gastric mucosal secretion was calculated from pH and pCO2 injury - protection by prostaglandin E2 and F CHILOVI, L PIAZZI, G DOBRILLA (Division of gastric aspirates while acid secretion was carbopol of Gastroenterology, General Regional suppressed by intravenous ranitidine. After Hospital 39100- Bolzano, Italy) The aim of a basal hour, enprostil (35 Fg) was added to C J HAWKEY, N K BHASKAR, P W DETTMAR, T K this study was to compare the efficacy of the perfusate and bicarbonate secretion DANESHMEND (Department of Therapeutics, either S or H2-A in non-R to an initial four measured for a further hour. This thera- University Hospital, Nottingham and Reckitt week treatment with S 1 g qid. peutic dose of enprostil produced a 78% and Coleman, Dansom Lane, Kingston Forty eight DU patients non-R to S were increase in bicarbonate secretion (489 (95) upon Hull) Carbopol, a new mucoprotec- randomly allocated over the period 1981- to 853 (136) itmollh, n=6, p<0-01; means tive polyacrylate, prevents gastric mucosal 1987 either to S 1 g qid (24) of H2-A (24: (SE)). injury by alcohol in rats. We developed an cimetidine (C) 1 g/day five; ranitidine (R) In conclusion, enprostil stimulates gastric analagous human model, in which 80% http://gut.bmj.com/ 150 mg bid eight; R 300 mg/nocte, four; bicarbonate secretion in vitro and in man ethanol is sprayed directly onto dependent famotidine (F) 40 mg/nocte, seven). Treat- and this may be one of the mechanisms gastric body mucosa and serial changes ment groups were comparable for the whereby this agent protects the mucosa evaluated by continuous endoscopic inspec- following variables: age, sex, ulcer dura- from damaging agents. tion in unsedated volunteers. tion, and size, smoking habits, alcohol con- Ethanol caused mucosal reddening, sumption, BAO, MAO, PAO, and serum superficial white slough and intramucosal gastrin levels. Endoscopy was repeated in Abolition by omeprazole of aspirin-induced haemmorhage during five minutes after all patients after eight weeks of treatment. gastric mucosal injury in humans application; these changes were scored on on September 24, 2021 by guest. Protected copyright. Healing was defined as the complete dis- 10 point scales, five minutes later. Prosta- appearance of the ulcer lesion at endo- T K DANESHMEND, A G STEIN, N K BHASKAR, C J glandin (PG)E2, 500 pg, given 20 minutes scopy. Healing rates were 45-8% (11/24) in HAWKEY (Department of Therapeutics, before 20 ml of 80% ethanol, reduced patients on S and 95*8% (23/24) in those on University Hospital, Nottingham) The best intramucosal haemorrhage scores from 4-5 H2-A (XI=l4.5; p 0.001). The 95% confid- strategy for prophylaxis of non-steroidal (median, interquartile range 3-5-5.5) to 2-5 ence interval of the difference (50% units) anti-inflammatory drug (NSAID) associ- (1.5-2.5) but did not reduce white slough (5 was 28-5-75-5. Five non-R, who initially ated ulcer disease is unclear. H2 receptor (3-5-5) v 5 (3-5-5.5)), or erythema. had ulcer pain in each treatment group, antagonists reduce gastric mucosal injury Carbopol 0-67%, 80 ml, 20 minutes before were pain free after four weeks treatment partially. We attempted to abolish acute 40 ml of 80% ethanol, also reduced both on S and H2-A. No dropouts, no aspirin induced gastric mucosal injury with haemorrhage scores from 6 (1-5-8.0) to 2-5 protocol violators and no relevant side omeprazole. (0-5), compared with water control (n= 10, effects were registered during the study. Sixteen volunteers aged 19-36 (eight p

The British Society ofGastroenterology A1443

Asymptomatic versus symptomatic gastric been carried out on 48 patients (42 women - with one of eight (12.5%) controls (p= ulcers in patients with rheumatoid arthritis six men, age 23-75 years) suffering from 0.0035). Thirty eight per cent of patients receiving non-steroidal anti-inflammatory rheumatoid arthritis, 44 of whom have com- with bleeding and perforated gastric ulcers drugs (NSAID) pleted the trial. After an initial esophago- had received NSAID compared with 13% gastroduodenoscopy to exclude the of bleeding and perforated duodenal ulcers R UPADHYAY, A HOWATSON, A W MCKINLAY, presence of gastric mucosal lesions, patients (p<0.002). Forty two per cent of the bleed-

C GEMMELL, R D STURROCK, R I RUSSELL were randomly allocated to a double blind ing gastric ulcers had received NSAID com- (Gastroenterology Unit, Department of treatment, either with etodolac 200 mg bid pared with 13% of the bleeding duodenal Pathology, Department of Bacteriology and or with naproxene 500 mg bid for a period of ulcers (p=0.003). A significantly higher Centre for Rheumatic Diseases, Royal four weeks; followed by endoscopic control proportion of patients with gastric ulcers Infirmary, Glasgow) There is a high preval- at the end of this treatment period. The had received NSAID than duodenal ulcers. ence of gastric (antral) ulcers in patients endoscopic evaluation of the gastroduo- with rheumatoid arthritis receiving NSAID, denal mucosal lesions has been carried out who often present with dyspeptic symp- according to the Lanza 0-4 scale. Both toms, but, may be asymptomatic. We have drugs proved efficacious in relieving clinical Peptic ulcer (PU) deaths: how many occur tried to identify the factors associated with symptoms, without any statistically signific- at home or after non-steroidal anti- asymptomatic and symptomatic gastric ant difference. Gastric mucosal lesions were inflammatory drug (NSAID) prescribing? ulceration. Thirty four patients with gastric observed in 15% of etodolac-treated ulcer were included of whom 17 (50%) were patients (all of grade 2) and in 46% of KEYA QUADER, RICHARD F A LOGAN (Depart- asymptomatic. There was no significant patients treated with naproxene (70% of ment of Community Medicine and difference in the mean age (asymptomatic grade 2-3, 30% of grade 4; p<0-005). Epidemiology, Queen's Medical Centre, 57-1 years, symptomatic 56-8 years), sex Painful dyspepsia has been observed in 15% University of Nottingham, Nottingham) distribution (asymptomatic F 14, M 3; of patients treated with etodolac v 38% of Recent studies have suggested that much of symptomatic F 16, M 1), or the mean patients on naproxene therapy. This study the increase in elderly PU mortality could duration of rheumatoid disease (asympto- shows that etodolac is at least as active as be due to over a third of deaths occurring matic 12-1 years; symptomatic 10-4 years) naproxene in relieving rheumatic symp- suddenly at home and to increases in non- between the two groups. Eight patients toms, but its administration results in steroidal anti inflammatory drug (NSAID) with dyspepsia as compared with three in a significantly lesser degree of gastric prescribing. We have identified all death the asymptomatic group were smokers damage. certificates issued in South Derbyshire (0-5

number, site and size of the ulcers or their retrospective study of bleeding and perfor- practitioner (GP) records and relevant http://gut.bmj.com/ association with gastric erosions and sub- ated peptic ulcers hospital records. When PU was given as the mucosal haemorrhages differed significantly underlying (part I) cause the GP records of between the two groups and there was no F H SMEDLEY, M TAUBE, R LEACH, C WASTELL the next two deaths registered of the same association with ingestion of any particular (Academic Surgical Unit, St Stephen's age and sex have also been obtained. Of 69 NSAID. Hospital, Chelsea, London) The ingestion deaths mentioning PU or unspecified bleed- Thus, asymptomatic gastric ulcers are of non-steroidal anti-inflammatory drugs ing this was given as the underlying cause in common in patients with rheumatoid (NSAID) in 272 patients with bleeding and 48; 79% had occurred in hospital and only arthritis receiving NSAID. We have been perforated peptic ulcer was compared with 14% at home, figures comparable with the unable to identify any specific factors that 272 age/sex matched controls. Twenty three 76% and 16% respectively reported for on September 24, 2021 by guest. Protected copyright. distinguishes asymptomatic gastric ulcers of 116 (20%) patients with bleeding peptic England and Wales (OPCS Mortality from those presenting with dyspeptic ulcers were receiving NSAID and seven of Statistics 1985). Thirty (63%) had had an symptoms. Smoking may be weakly associ- 116 (6%) controls (p=0.003). Sixteen of 132 autopsy and on review death was directly ated with dyspeptic symptoms. The Cpylori (12%) patients with perforated ulcer were caused by a PU in at least 30. In 20 (42%) of prevalence is similar to that of gastric ulcers taking NSAID compared with six of 132 part I deaths the GP records mentioned a in the general population, although a higher (5%) controls (p=0.045) and 10 of 35 NSAID prescription in the previous 12 prevalence is seen in younger age group. (28.5%) above the age of 65 compared with months compared with 6 (29%) of part II two of 35 (6%) controls (p=0.026). Twelve deaths and 17 (20%) of control deaths of 90 (13%) patients admitted with bleeding giving a relative risk estimate of dying from Naproxene v etodolac: a controlled endo- duodenal ulcers had received NSAID com- PU after a NSAID prescription of 2-9 (95% scopic study in patients with rheumatoid pared with five of 90 (6%) controls (p= cl 1-4-6.3). A NSAID had been prescribed arthritis 0.126) and six of 18 (33%) over 65, com- in 43% of deaths where review had con- pared with one of 18 (5.5%) controls firmed a PU . Using these G BIANCHI PORRO, M PETRILLO, S ARDIZZONE, I (p=0.0038). Eleven of 26 (42%) patients figures, the proportion of PU mortality CARUSO (Gastrointestinal Unit, Rheuma- with bleeding gastric ulcer had received attributable to NSAID prescribing is about tological Unit, L Sacco Hospital, Milano, NSAID compared with two of 26 (8%) in 25%. Italy) Aim of this clinical, endoscopical the matched controls (p=001). Eight of 24 study has been to evaluate the therapeutic (33%) patients with perforated gastric ulcer efficacy and the gastric tolerability of had received NSAID compared with two of etodolac, a new anti-inflammatory, non- 24 (8%) controls (p=0.019) and four of Intragastric fibrinolysis and tryptic activity steroidal drug, v naproxene. The study has eight (62.5%) over the age of 65 compared in bleeding peptic ulcer disease Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1444 The British Society ofGastroenterology

K E WHEATLEY, VALERIE A POXON, P W DYKES, endoscopy suite. All patients with upper GI treatment only. Recurrent ulcer was no M R B KEIGHLEY (The General Hospital, haemorrhage are admitted to the Unit more likely in ulcers resistant to H2 blockers Birmingham) It has been known for over 30 under the care of one of two gastroentero- (RU rate 16.2%) than in those which had years that rebleeding is the most important logists. All patients are seen by the duty previously responded (RU rate 16.9%). risk factor for mortality from bleeding surgical team. Strict protocols for manage- When symptoms were analysed 21-4% peptic ulcers. Little is known of the factors ment have been devised. Strict criteria for of patients with RU experienced episodes responsible for rebleeding, but disorders of transfusion and surgery are also used. of epigastric pain while overall 8-9% of fibrinolysis may be involved. Trypsin is a patients had this symptom. The results for powerful proteolytic enzyme and prelimi- other dyspeptic symptoms were similar; nary studies have suggested that it is more Mortality of perforated peptic ulcer 10-8% of patients took H2 receptor antago- commonly found in gastric juice of patients nists regularly or frequently. We conclude with bleeding than non-bleeding ulcers. We T T IRVIN (Department of Surgery, Royal that the presence of a recurrent ulcer does obtained gastric juice samples from seven Devon and Exeter Hospital (Wonford), not necessarily correlate with a bad result in patients with non-bleeding ulcers (DU five, Exeter) There has been a decline in the symptomatic terms; that failure to respond GU two) and six with bleeding ulcers (DU incidence of perforated peptic ulcer since to H2 blockers should not be regarded as a four, GU two) over 24 hour periods through the introduction of the histamine antagonist contra-indication to surgical treatment. The nasogastric intubation. Fibrinolytic activity drugs but the epidemiology of this compli- results at five to 15 years suggest that HSV was assessed using fibrin plates, and tryptic cation is changing, and it is increasingly remains a useful treatment for duodenal activity measured using a colourimetric encountered in elderly subjects. ulcer disease. technique. pH was also recorded. In a consecutive series of perforated Fibrinolytic activity was found in three of peptic ulcer (229 pyloroduodenal; 55 seven controls and all patients with bleeding gastric) the average age of the patients was Advantages of anterior lesser curvature ulcers (p=0.049). It was found in only 18/ 70 years (range 19-98), and there was a seromyotomy with posterior truncal 168 samples from controls, and 71/144 26% hospital mortality. Patients aged >70 vagotomy for chronic duodenal ulcer samples from patients with bleeding (x2= years (176) had a significantly higher 56, p<0-005). Fibrinolytic activity corre- mortality (34%) compared with patients T V TAYLOR, P E THOMAS, J P LYTHGOE, J B lates well with tryptic activity (r=0.84) and aged <70 (14%) (p<0.001). Multiple MACFARLAND (Manchester Royal Infirmary, is significantly commoner at pH>4 (x2=28, clinical variables were significantly more Royal Preston Hospital, and Royal Liver- p0-05). oesophageal varices 4-8%. The operative at 14-18 years, the majority of the ulcers In this first randomised controlled trial of a rate was 16%. being 'malevolent' (bleeding or requiring new operation for duodenal ulcer, the The mortality rate found for upper GI operation or continual H2 blockers) and (2) results compare favourably with the V and P haemorrhage is considerably lower than the that ulcers resistant to H2 blockers have a in that morbidity has been less and the average figures recorded in most series in 30% RU rate at five years. In a prospective tendency for an increased incidence of the last 30 years. This lower rate may result study of 291 patients followed up between recurrent ulcer remains less than that which from the use of a specialised GI unit, five and 15 years, the RU rate was 16-8%. has been observed after highly selective comprising both high dependancy ward and Of these 38-7% required no or occasional vagotomy. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1445

Foregut screening in familial adenomatous accompanied by an increase in the numbers P R TAYLOR, R C MASON, G M MURPHY, S VAJA, polyposis (FAP) of oesophageal adenocarcinomata (both R H DOWLING, I MCCOLL (Departments of middle and lower third) but not of Surgery and Gastroenterology, UMDS, A D SPIGELMAN, R K S PHILLIPS, C B WILLIAMS, squamous tumours, making spurious diag- Guy's Hospital, St Thomas Street, London) H J R BUSSEY (St Mark's Hospital and St nostic re-allocation from the oesophagus Surgically induced duodenogastric reflux Bartholomew's Hospital, London) Duo- unlikely. Furthermore the proportions of results in adenocarcinoma of the rat glandu- denal adenomas may account for foregut pancreatic tumours did not rise unduly lar stomach. In tissues which have a high malignancy in FAP. Their reported incid- suggesting that the slow rise in numbers of proliferative rate, ornithine decarboxylase ence ranges from 20% to 100%. tumours of pyloric subsite does not repre- (ODC) activity and polyamine concentra- We report a prospective upper gastro- sent preferential re-allocation to the tions are high. This study was undertaken to intestinal endoscopic screening programme pancreas. The data indicate possible assess the effect of chronic duodenogastric in 35 patients with FAP (men 23, women 12; changes in aetiological influences pre- reflux on these factors in the gastric mucosa. age range 19-67, mean 42). Gastric polyps disposing to upper gastric disease despite an Isoperistaltic gastrojejunostomy was were found in eight patients (23%) of which overall fall in gastric cancer incidence as carried out in 47 male Wistar rats and seven were biopsied, five being hamartomas measured by age specific rates [as opposed compared with 67 rats with gastrotomy and two normal. Duodenal polyps were to total case numbers which have risen alone. The animals were killed at eight found in 32 patients (91%; adenomas 31, slightly in association with the aging weekly intervals. Gastric mucosal samples hamartoma 1; size range <1-20 mm, mean population]. adjacent to the anastomosis or gastrotomy 5-7 mm). Biopsies of macroscopically were excised and ODC activity and poly- normal mucosa in six patients showed amine concentrations were estimated. The microscopic adenomas in three. Of the results show that ODC activity is signific- duodenal adenomas, 27 were tubular Does gastrectomy for incurable carcinoma antly increased by 36% in gastrojejuno- (dysplasia: 25 mild, two moderate; size improve quality of life? stomy rats compared with gastrotomy rats range <1-20 mm, mean 5-8 mm), and four (p<0-05 Mann Whitney). This is accom- tubulovillous (dysplasia: three mild, one M V MADDEN, D M DENT, P M AINSLIE, S BAILEY, panied by an increase in putrescine concen- moderate; size range 1-11 mm, mean 8-3 D J DE VILLIERS (INTRODUCED BY M R B tration of 44% (p<0-05). No difference was mm). Adenomas were commonest at the KEIGHLEY) (Surgical Gastroenterology and found in spermidine concentrations and papilla. Department of Surgery, Groote Schuur spermine was lower in gastrojejunostomy Duodenal adenomas are probably inevit- Hospital and University of Cape Town) animals. Ornithine decarboxylase activity able in FAP and the papilla is particularly When malignant disease cannot be cured by was always higher at each eight weekly susceptible, perhaps stimulated by surgical intervention, quality of life after interval in gastrojejunostomy rats with two pancreatico-biliary contents. Screening operations assumes great importance. peaks of activity at 24 and 48 weeks. These should aim to identify high risk factors (? We assessed quality oflife pre-operatively coincided with significant rises in putrescine http://gut.bmj.com/ large size, villous/tubulovillous histology, and at 1, 2, 3, 6, and 9 months in 46 patients concentration. The results suggest that duo- degree of dysplasia) rather than whether or who underwent palliative gastrectomy (35 denogastric reflux causes an increase in not polyps are present. partial, 11 total) by using linear analogue gastric mucosal proliferation adjacent to scales for 10 symptom variables. The quality surgical anastomoses, and indicate a poss- of life scores (median (SD), maximum 100) ible mechanism for carcinongenesis. Increasing numbers of gastric cardial at 0, 1, 2, 3, 6, and 9 months were: Overall tumours are aetiological factors changing? 59 (18), 71 (16), 80 (19), 85 (24), 75 (22), 68

(26); partial gastrectomy 54 (18), 73 (16), CA 72-4 in comparison with CA 19-9 and on September 24, 2021 by guest. Protected copyright. W ALLUM, J FIELDING, JEAN POWELL, M J S 80 (18), 85 (23), 78 (25), 61 (27); total CEA LANGMAN (Queen Elizabeth Hospital, gastrectomy 61 (17), 70 (18), 80 (20), 85 Birmingham and West Midlands Cancer (27), 68 (16), 75 (26). There were no S DOMSCHKE, G HEPTNER, W DOMSCHKE Registry) The causes of gastric cancer are operative deaths and the median postopera- (Department of Medicine, University of poorly understood, but the assumption tive stay was 10 days. Total and partial D-8520 Erlangen, FR Germany) Immuno- tends to be made that the disease can be gastrectomies had major complications in histochemically CA 72-4 binds to gastric considered as a unity. Examination of data 50% and 0% respectively with minor cancer (Int J Cancer 1986; 38: 643). We from the West Midlands Regional Cancer complications in 50% and 35%. Survival at examined the diagnostic accuracy of Registry suggest that when tumours are 3, 6, and 9 months was 93%, 73%, and 70% CA 72-4 as a serum tumour-associated considered by subsite within the stomach an respectively. marker. increasing proportion of disease of the In incurable gastric cancer, partial In 673 patients with benign (n=410), upper stomach is being detected. In the gastrectomy improved quality of life for at malignant (n=199), and without (n=64) quinquennia 1957-61 and 1977-81 the num- least nine months with minimal morbidity. gastrointestinal diseases, serum concentra- ber of tumours described as cardiac by Total gastrectomy achieved a smaller tions of CA 72-4, CA 19-9, and CEA were subsite rose from 281 to 923 - that is, by improvement in quality of life with substan- determined by CIS-RIAs. 228%, whereas the numbers described as tial morbidity. In 64 controls, a cut off limit of B6.7 U/m] pyloric rose from 1143 to 1436 - that is, by was established for CA 72-4. The specificity 25%, the total numbers of tumours des- of CA 72-4 was hardly reduced by benign cribed for all sites being 5562 in the first and diseases like liver cirrhosis, or 6307 in the second quinquennium. This Is gastric carcinogenesis mediated by (99%) in contrast with that of large and disparate increase in the propor- changes in ornithine decarboxylase activity CA 19-9 (86%) and CEA (90%). Oeso- tion of disease described as cardiac was and polyamine concentrations? phageal carcinomas (n=24) were barely Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1446 The British Society ofGastroenterology detected by CEA (<5 ng/ml; 17%) or CA Effect of longterm treatment with M MCCULLAGH, J C LINSELL, A ANGGIANSAH, 19-9 (>37 U/ml; 8%) and not by CA 72-4 omeprazole on serum pepsinogens in reflux W J OWEN (Department of Surgery, Guy's (0%). Gastric cancer (n=27) was indicated oesophagitis Hospital, London) Diffuse oesophageal by CA 72-4 in 56% of cases, by CEA in only spasm (DOS) and nutcracker oesophagus 25%, by CA 19-9 in 52%, and by combined J B M J JANSEN, E C KLINKENBERG-KNOL, I may produce disabling symptoms of chest measurement of CA 72-4 and CA 19-9 in BIEMOND, H P M FESTEN, G F NELIS, P SNEL, pain and dysphagia. The response to 70%. In pancreatic and S G M MEUWISSEN, CB H W LAMERS (Depart- medical treatment is variable. This work carcinomas (n=68 and n=21, resp) CA 19-9 ment of Gastroenterology, University investigates the efficacy of balloon dilata- (82% and 90% sensitivity, resp) was Hospital, Leiden andAmsterdam and Groot tion and attempts to correlate success with superior to CEA (47% and 62%, resp) and Ziekengasthuis Den Bosch, Sophis Hospital the presence or absence of gastroeso- CA 72-4 (22% and 29%, resp). In colonic Zwolle, Slotervaart Hospital, Amsterdam, phageal reflux (GOR). Using Castell's carcinomas (n=53) CEA was positive in The Netherlands) Short term administration criteria, the diagnosis of DOS and nut- 58%, CA 19-9 in 36% and CA 72-4 in 32%. of omeprazole (OME) to healthy volun- cracker oesophagus was made in 11-3% of For hepatocellular cancer the data were: teers has been shown to increase both serum 600 patients investigated. All patients 67% each for CEA and CA 19-9,0% for CA pepsinogen (PG) A and serum gastrin underwent manometry (Gaeltec system) 72-4. levels. Studies on the effect of longterm and 24-hour pH monitoring (Lectromed). A high specificity makes raised CA 72-4 OME on serum PG are not available and Twenty five per cent of this group (17 concentrations relevant. CA 72-4 indicates studies on the effect of longterm OME on patients) failed to respond to nifedipine gastric cancer best, especially in combina- serum gastrin are scarce. We therefore and/or H2 antagonists and underwent tion with CA 19-9, and may supplement studied serum PGA, PGC, and gastrin dilatation with a Keymed balloon dilator. usual methods of tumour search and concentrations in 10 patients (four women, Complete remission of symptoms was seen monitoring. six men; age 67 (2) yrs, mean (SE)) with in 10 patients (60%) - 20% of these had severe reflux oesophagitis during 18 months GOR. The remaining seven had a poor maintenance treatment with 20 mg OME response though without deterioration or daily. Before the start of this maintenance complication -83% had GOR. Mean follow Ranitidine therapy in peptic oesophagitis: treatment, the reflux oesophagitis was up is 2½/2 years (four months-4 years). The doubling the dose or duration oftreatment? initially healed with 40 mg OME daily for presence of GOR correlates with a high four to 12 weeks. Fasting serum PGA, incidence of poor response (0.02

conventional doses of H2-blockers on peptic and 18 months of maintenance treatment http://gut.bmj.com/ oesophagitis have shown that the healing with 20 mg OME daily. rates after six to 12 weeks are quite dis- Serum PGA significantly (p<0.01) Simultaneous monitoring of gastroeso- appointing when compared, for example, increased from 42 (6) to 104 (13), 94 (14), 94 phageal reflux and respiratory function in with those observed with the same therapy (14), 100 (18), 95 (19), and 106 (21) [tg/l, near miss cot death infants in patients with duodenal ulcer. while serum PGC increased (p<0-01) from We have, therefore, decided to carry out 19 (4) to 41 (6), 39 (7), 38 (6), 40 (4), 38 (6), C W SHORE, M SAMUELS, D BENTLEY, B K a clinical single centre, double blind trial and 42-8 /tgfl at 3, 6, 9, 12, 15, and 18 SANDHU, D SOUTHAL, M J BRUETON (Depart- investigating the effect of doubling: (a) the months, respectively. Serum gastrin ment of Child Health, Westminster Child- study period from the usual 12 to 24 weeks, significantly (p<0.01) rose from 69 (13) to ren's Hospital, London) Some studies of on September 24, 2021 by guest. Protected copyright. and (b) the dose of the agent, namely 198 (37), 164 (26), 271 (49), 236 (45), 265 infants who have suffered an acute life ranitidine (R) from 150 to 300 mg bid. (41), and 250 (37) ng/l, respectively. threatening event, near miss cot death Seventy six patients with oesophagitis, Fasting serum PGA and PGC concentra- (NMCD), have shown abnormalities in grade II to IV according to Savary and tions increased about twice in the first three respiratory function; others have showed Miller, have been studied, 37 of whom months of maintenance treatment with 20 gastrooesophageal reflux (GOR). Apnoea treated with R 150 mg bid and 39 with R 300 mg OME daily, while fasting serum gastrin and bradycardia may be associated with bid. Three patients dropped out in the levels increased about four-fold. When 20 GOR in other circumstances, presumably course of the study period. mg OME treatment was continued for 18 because gastric contents stimulate chemo- After 12 weeks of treatment with R 300 months there were no further rises in fasting receptors in the larynx or upper oeso- mg; 21/37 patients had healed compared to serum PGA and PGC, whereas the slight phagus, or because aspiration occurs. In 11/37 treated with R 600 (p<0-05); after 24 further increases in serum gastrin concen- order to study a possible correlation in weeks the healing rate was 28/36 and 32/36 trations did not reach statistical signific- NMCD, simultaneous 24 hour oesophageal (p<0-05), respectively. As to the sympto- ance. This study suggests that the serum pH and respiratory monitoring including matic response, figures were 25/37 v 22/37 gastrin and PGA and PGC response after measurement of arterial oxygen saturation, (p<0.05) after 12 weeks, and 32/36 v 29/36 three months of OME treatment is indica- and breathing movements were carried out (p<0.05) after 24 weeks. tive of the increases to be anticipated during in 16 children of mean age 12 weeks who Protracting the full dose therapy with longterm OME therapy. had presented with NMCD. Seven of these ranitidine from 12 to 24 weeks allows com- patients had significant GOR. The mean plete additional healing of 23-6% of number of reflux episodes was 58 (20) patients; in the treatment of patients with Is there a place for balloon dilatation in the (normal 27 (8.2)), the mean number of peptic oesophagitis, no advantages emerge treatment of diffuse oesophageal spasm and refluxes lasting more than 5 minutes was 10 when the dose of ranitidine is doubled. related disorders? (3.9) (normal 6 (2)), the mean percentage Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1447 time the pH was >4 was 22-6 (20.5) (normal chemistry, Queen Elizabeth Hospital, myocardial infarction (p>0.05, X2 test with 5 (1.6)). Two of the 16 children had periods Birmingham) This study examined the Yates' correction). Abnormal manometry of periodic breathing, in one patient this effects of hyperventilation (HV) on the was found in three patients: classical diffuse was associated with oxygen desaturation. motor function of the oesophagus in healthy spasm (one), nutcracker oesophagus (one) One of these two children also had GOR volunteers, as HV and abnormalities of - mean peristaltic amplitude >180 mmHg but simultaneous respiratory changes were oesophageal motility have been indepen- and duration >7 sec - and prolonged dura- not apparent. These observations confirm dently implicated in the genesis of atypical tion peristalsis (one). Abnormal acid reflux that GOR occurs frequently in children with chest pain. Six subjects underwent a mano- was detected in two, both with normal NMCD. There appears to be no real time metric study of LOS and oesophageal body manometry. These were the only two association between GOR and respiratory function (duration, amplitude, propagation with frequent (¢x one/month) oesophageal changes. velocity and spontaneous activity) on two symptoms. Major oesophageal abnormali- separate days in random order. On one day ties occur with surprising frequency, measurements were made before, during, although our small sample size may not Electromyography of the oesophagus with and after enforced HV to below 3 Kpa (end- reflect true prevalence. These data empha- intraluminal ring electrodes tidal pCO2). The protocol was repeated sise that oesophageal abnormalities should another day without HV. Venous blood was only be regarded as significant if symptoms M I MARPLES, L J HANKIN, J BANCEWICZ taken for pH, electrolytes, ionised calcium occur concurrently. Prolonged ambulatory (Department of Surgery, Hope Hospital and inorganic phosphate during each motility and pH recordings may prove help- (University of Manchester School of period. ful in this respect. Medicine), Eccles Old Road, Salford) We The amplitude of contractions (3, 8, and have developed a simple catheter which 13 cm above LOS) did not change during allows oesophageal electromyography HV but it rose during the period after HV in Oesophageal peristaltic reflex - its applica- during conventional manometric studies. all three channels in five of six subjects. The tion in the assessment of motility disorders Bipolar ring electrodes were applied to rise in the distal channel amplitude above multilumen manometry catheters in seven baseline (30.7 (8.4) cm H20; x (SE) was T O'HANRAHAN, J BANCEWICZ, D G THOMPSON, different configurations and assessed during significantly greater than on the control day M MARPLES, D WILLIAMS (University Depart- 202 manometric studies in patients and (11.3 (5.0) cm H20; p<0.05). No other ments of Medicine and Surgery, Hope normal volunteers. manometric changes were observed. The Hospital (University of Manchester School The optimum design of catheter is an only biochemical abnormality that persisted of Medicine), Eccles Old Road, Salford) assembly 0.4 cm diameter with two sets of after HV was a fall in inorganic phosphate The nature of many oesophageal rrmotility bipolar ring electrodes 0-8 cm apart at 10 cm (8.2%; p

A1448 The British Society ofGastroenterology

Oesophageal manometry during eating in obtained when sphincter relaxation was Hospital, Nottingham) Use of the the investigation of patients with dysphagia assessed in three channels. One of the seven Angelchik prosthesis (ACP) for gastro- achalasic patients studied after pneumatic oesophageal reflux (GOR) remains contro- P J HOWARD, A PRYDE, R C HEADING (Depart- dilatation appeared to have complete versial and only one randomised study with ment of Medicine, Royal Infirmary, sphincteric relaxation. pH monitoring has been reported and no Edinburgh) Although patients with dys- Assessment of lower sphincteric relaxa- objective assessment of swallowing was phagia are often referred for oesophageal tion rarely provides useful diagnostic made. Seventeen patients with GOR were manometry, the response to eating is rarely information except in patients with total randomised to either Nissen fundoplication examined. We studied oesophageal motility aperistalsis. Routine studies of sphincteric (NFP) n=9 or ACP n=8. Oesophagoscopy, and symptoms in response to eating bread in relaxation should be abandoned. oesophageal manometry, pH monitoring 20 patients with gastro-oesophageal reflux and marshmallow barium swallow (MMBS) and 10 with normal oesophageal motility were performed pre- and six months post- and ambulatory pH. While no patient Does oesophageal motor activity improve operatively. Median follow up in months experienced symptoms with water after surgical treatment of gastro- (range) was 16 ACP (3-40), 15 NFP (6-30). swallows, one control patient experienced oesophageal reflux (GOR)? Two ACP were removed at seven and 40 heartburn, without any change in motility months for severe dysphagia and one NFP and nine reflux patients experienced G GONIS, A ANGGIANSAH, T ROKKAS, M was revised at six months for persistent dysphagia+pain whilst eating. Oeso- MCCULLAGH, W J OWEN (Department of GOR. phageal 'spasm' was evoked by eating in one Surgery, Guy's Hospital, London) It has Control of GOR was significantly more of these patients. In the other eight, been reported that patients with GOR have effective (p<0.01) after ACP than NFP dysphagia was associated with aperistalsis. impaired oesophageal motility but it (ACP preop median (range) Frequency Comparing asymptomatic and symptomatic remains unclear as to whether this is Duration Index=20 (4-30), postop 0 (0-0), periods, there was a slight increase in mean primary or secondary to GOR. The present p<0.002), NFP preop 50 (1-145), postop swallow frequency from 7-5 to 9-0 per study was initiated to investigate oeso- two (0-55), p<0.04). Oesophagitis and minute (NS; n=10). While aperistaltic phageal motility in 18 patients suffering lower oesophageal sphincter pressure were swallows increased from 4*5 (0.96) (SE) to from GOR, pre- and post-Nissen fundopli- similarly improved. MMBS was slower after 6-2 (1.3) per minute (p<0-01; n=10) the cation. Oesophageal manometry was per- ACP than NFP (ACP preop median (range) ratio of aperistaltic to peristaltic swallows formed with a fully computerised system 0-3 mins (0-3-1.5), postop eight mins increased from 1-5:1 to 3-5:1. Aperistalsis (Gaeltec). Mean amplitude (mmHg) and (1-10), p<0-003, NFP preop 0.3 mins (0.3), during symptomatic periods was due mainly duration (sec) of peristaltic contraction postop one min (0-3-10), p=NS). In this to non-conducted, rather than synchronous were elicited by 10 consecutive wet series ACP was better than NFP in control- contractions. Increased non-peristaltic swallows at 5 and 10 cm above lower oeso- ling GOR but the oesophageal transit of swallows in these patients may be a result of phageal sphincter (LOS). Additionally solids was slowed after ACP. http://gut.bmj.com/ short swallow intervals ('deglutitive inhibi- peristaltic velocity (cm/sec) and LOS tion'). Manometry while eating bread can pressure (mmHg) were measured. After show this symptomatic abnormality which is fundoplication all patients were sympto- The Angelchik prosthesis: five years on not revealed by conventional pressure matically relieved and 24 h ambulatory pH studies. monitoring showed satisfactory control of M DEAKIN, D MAYER, J G TEMPLE (Queen reflux. Pre-operative values of LOS pres- Elizabeth Hospital, Birmingham) No single sure, amplitude, duration and velocity of operation has provided the answer for Why measure lower oesophageal sphincter peristaltic waves were 10-5 (1.3), 44-38 gastro-oesophageal reflux. Insertion of the on September 24, 2021 by guest. Protected copyright. relaxation in patients with dysphagia? (4.19), 3-09 (0-18), 3-46 (0.16) respectively. Angelchik prosthesis was suggested to be an After the operation respective values were easy operation that should lead to consist- P J HOWARD, L BENINI, A PRYDE, R C HEADING 15 (2), 76-42 (10.85), 3-83 (0.22), 3-26 ent results. Although the prosthesis has (Department of Medicine, Royal Infirmary, (0.13). The comparison of these results pre- been in use for 15 years there are no well Edinburgh) Assessment of lower sphincter and post-surgery showed that there was documented longer term follow up studies. relaxation is considered a routine part of significant increase in LOS pressure Twenty two Angelchik prostheses were clinical manometry. Criteria of normal (p<0-05), and in amplitude (p=0.001) and implanted between 1981-1982 as primary relaxation are not agreed, however, and the duration (p=0.009) of peristaltic activity of treatment for gastro-oesophageal reflux. diagnostic significance of abnormality has lower 10 cm oesophagus. Velocity was not The median age of the patients was 59 years not been critically assessed. We studied 97 affected. The increase in amplitude and (31-76). The results were assessed by Visick patients referred for oesophageal function duration of peristalsis shows improved grading, manometry and oesophageal pH tests. Relaxation of the lower oesophageal oesophageal motility and suggests that recording. sphincter in response to dry swallows was impaired motility in patients with GOR is The lower oesophageal sphincter pres- measured in a single channel at the point of secondary to increased acid exposure. sure increased from a median of 1; (0-9) to maximum tonic pressure during a station 7 (0-20) mmHg and the time 24-h oeso- pull through using an Arndorfer catheter. phageal pH was <4 decreased from 27 Complete relaxation, defined as a fall in An objective comparison of the Angelchik (5-94)% to 1-7 (0-40)% postoperatively sphincter pressure to intragastric pressure anti-reflux prosthesis and Nissen fundoplica- (p<0-001 for both variables). There were during both swallows, occurred in 29 of the tion two postoperative deaths caused by medical 43 patients with dysphagia (67%) and 26 of problems. At two years 80% of patients the 44 patients without dysphagia (48%) D F EVANS, C S ROBERTSON, D L MORRIS were Visick 1 and 20% Visick 4. Failures (x2=0-018, p=0.88). Similar results were (Department of Surgery, University were the result of complications associated Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1449 with the prosthesis, namely collar disrup- Hospital, Edinburgh) Thirty four volun- days (95% confidence limits [cl] 232-367) tion, two and angulation of the prosthesis teers were studied by ambulatory 24 hour with 41%, 19%, and 12% surviving one, causing dysphagia, two. All four underwent pH monitoring. There were no restrictions two, and three years respectively. Radical reoperation. At five years three patients of diet or activity, but each subject kept a radiotherapy was attempted in 13% and was have died from unrelated causes. Of the diary record. Reflux was defined as a fall in associated with a median survival of 193 remainder, 11 (65%) remain Visick 1, but pH to below 4. Twenty seven were men, and days (cl 136-253) with 15%, 3%, and 3% three patients (18%) are Visick 2 due to the age range was 20-66 years (median 31); surviving one, two, and three years. Intuba- occasional dysphagia. 10 were smokers (three to 30 cigarettes/day, tion alone was done in 41% of whom 44% The Angelchik prosthesis successfully median 10). Occasional heartburn (

each whole pH interval and these values sional heartburn. surgery are given radiotherapy and/or endo- http://gut.bmj.com/ compared to a group of 15 control subjects. scopic intubation. We have carried out a Seventy four had abnormal oesophageal population based study of the survival of acid exposure. Of the remaining 26, six had Oesophageal cancer: a population based oesophageal cancer patients presenting no endoscopic oesophagitis and normal study of survival after treatment from the Nottingham area in the four years gastric profile, 10 had low gastric acidity 1982-85. Of 131 patients with squamous (four vagotomy or gastrectomy, two achlor- S E OLIVER, C S ROBERTSON, R F A LOGAN cell oesophageal cancer, surgical resection hydria, four hypersecretion or bile reflux) to (Departments of Community Medicine and was attempted in 43. Of the remaining 88, explain the negative test. The other 10 had Epidemiology and of Surgery, Queen's 31 (17 men) had endoscopic intubation mild oesophagitis but both pH profiles were Medical Centre, University of Nottingham, alone, 29 (17 men) had radical radiotherapy on September 24, 2021 by guest. Protected copyright. normal. The incidence of gastric acid hyper- Nottingham) While the place of surgery alone (n=6) or combined with endoscopic secretion was 21%. versus radiotherapy for oesophageal cancer intubation (n=23) and 28 had other treat- In this study, combined monitoring is currently subject to controlled trial, the ment combinations, including surgical intu- explained the presence of endoscopic oeso- development of better local treatments of bation and palliative radiotherapy. phagitis in 50% of patients with normal dysphagia has made palliative treatment Patients having intubation alone had a oesophageal acid exposure. Of those with alone a more acceptable option. We have mean age of 75 years and were significantly abnormal exposure, 21 (28%) had gastric studied the survival of oesophageal cancer older (p<0.025) with metastasis more often acid hypersecretion. The high incidence of patients diagnosed during 1982-85 in evident (32%) than patients having radio- abnormal gastric pH profiles in reflux Nottingham - an area where endoscopic therapy (mean age 69 years) of whom 14% disease has important implications in the intubation was pioneered. Of 496 cases had metastasis evident. Despite these choice of both medical and surgical anti- identified from endoscopy, histopathology favourable biases the Kaplan-Meier esti- reflux therapy. and Hospital Activity Analysis records, 268 mate of survival of the radiotherapy group (171 men) lived in the area and had had (median survival 182 days, 95% confident primary oesophageal cancer diagnosed limit [cl] 133-253) was not significantly What characteristics are acceptable in during the four years. Survival was similar greater than that of the intubation alone volunteers to establish normal ranges for 24 (hazard rate ratio= 1.02) whether a group (median survival 99 days cl 73-155). hour oesophageal pH monitoring? squamous cell carcinoma (49%) or an The radiotherapy patients spent a median of adenocarcinoma (36%) was present. Based 46 days in hospital compared with 24 days in J S DE CAESTECKER, J A WILSON, R C HEADING on the original treatment intention surgery the intubation alone patients. We conclude (Department of Medicine, Royal Infirmary was attempted in 34% and was associated that in patients with squamous cell oeso- and Department of Otolaryngology, City with a median survival from diagnosis of 293 phageal cancer, unsuitable for surgery, the Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1450 The British SocietyofGastroenterology survival advantage associated with giving Food stimulated acid secretion is mediated upper extent of the LOS was 44-7 cm (2.0) radiotherapy in addition to intubation is by antral gastrin release. The aim of this (mean SD) in both studies. The mean small and ma, be insufficient to compensate study was to measure the G-cell bearing distance between the incisor teeth and LOS for the extra morbidity. A controlled trial area of the stomach in patients with duo- was 42-3 cm (1.6) and 4-25 cm (1.5) for each of radiotherapy in such patients is now denal ulcer (DU) and to relate this to acid oral manometry. The mean difference needed. output and the IGR to food. between the two routes was 2-4 cm (1.7) Twenty nine patients referred for opera- (p

M J ROGERS, J H M HOLMFIELD, J N PRIMROSE, T vagotomy with Grassi test and biopsies were if endoscopic measurements are used. GLEDHILL, D JOHNSTON (University Depart- taken 2, 4, 6, and 8 cm from the pylorus ment of Surgery, The General Infirmary, along each curvature. After tissue process- Leeds) Intragastric pH (IGpH) measure- ing, G-cells were stained immunohisto- Oesophagitis - a five year review ments made using a non-aspirating pH chemically and their density in each biopsy sensor (NAS) correlate closely with those assessed by an independent observer D L STOKER, J G WILLIAMS, R G LEICESTER, D G made by nasogastric (NG) aspiration if the (normal density 2, absent 0, scanty 1). COLIN-JONES (Royal Naval Hospital, Haslar, NAS is fixed to the tip of the NG tube. It is Normal density G-cells extended 4 cm Gosport, Hants) This study examines the thus assumed that IGpH recordings made along both curvatures in all patients but incidence of a number of diseases seen in using a NAS are also similar to aspiration could be found at 6 cm or more in 13 of 29 the endoscopic practice of two adjacent studies of IGpH. When comparing IGpH patients (Large Gastric Antrum, LGA). district general hospitals over the past five recordings made by NG aspiration and by Median (quartile) IGR was 5 0 ng/min (3.4- years, with special reference to oesopha- NAS, however, it is preferable not to attach 16.7) in patients with LGA and 3-7 (0-3- gitis. Over this period, a total of 12652 the NAS to the NG tube to allow normal 11.6) in those without (NS), but of five upper GI endoscopies were performed, and movement ofeach to occur. As gastric pH is patients with a IGR greater than 15-0 recorded in detail on computer using the not uniform, however, if aspiration and ng/min four had LGA and one did not Micromed data storage system. The results NAS techniques are compared, both must (p<0-05). of this survey are based on 8445 initial aim to study the same region of the Median BAO was 2.9 mmollh in patients diagnostic endoscopies, representing 67% stomach. with LGA and 3-6 mmollh in patients with- of the total number, when repeat examina- The aim of this study was to compare out (NS) and PAOSF and PAOPG did not tions are excluded. There were 1928 cases of IGpH recorded by means of a telemetry differ significantly between patients with macroscopic oesophagitis of all grades diag- capsule with that recorded by simultaneous and without LGA (median 14-8 v 16-3, 56-8 nosed (22.8% of the new patient total). This http://gut.bmj.com/ NG aspiration. v 46-9 mmollh respectively). compared with 1573 cases of gastritis Twelve healthy subjects underwent four Patients with LGA have a greater IGR (18-6%), 777 duodenal ulcers (9.2%), and hours IGpH monitoring with a telemetry than patients without LGA, but their BAO 504 gastric ulcers excluding neoplasms capsule whilst having a 5 ml sample of and acid output to PG and SF does not (6%). There were also 254 benign oesopha- gastric juice aspirated every 15 minutes differ. Intragastric titration could be used to geal strictures (3%), and 247 cases ofbenign through a NG tube. Median pH and four determine if these groups differ in their acid oesophageal ulceration (2-9%). In the oeso- hour [H+] (area under the [H+] versus time secretory response to food. phagitis group, more patients presented in curve) was calculated for each recording the 60-70 age range than in any other. on September 24, 2021 by guest. Protected copyright. with each method of pH measurement. There was an increasing incidence of oeso- Median (quartile) pH was 2-4 (1-8-2-5) Accurate positioning of pH electrodes phagitis with age, starting at 14-7% in the when recorded by aspiration and 2-0 second decade, and peaking in the eighth (1-6-2.1) when recorded by telemetry C S ROBERTSON, S LEDINGHAM, D F EVANS decade with the diagnosis being made in (0O1>p>005). Median (quartile) four hour (Department of Surgery, University 26-7% of cases. These data show that [H+] was 1-2 (0-8-2-2) Mol.min when Hospital, Nottingham) Oesophageal pH oesophagitis is the commonest disease of recorded by aspiration, and 3-2 (2.2-5.6) probes are placed transnasally often using the upper gastrointestinal tract seen in Mol.min when recorded by telemetry measurements taken at gastroscopy. The patients referred for endoscopy. It also (OO5>p>0-025). difference in measurement between the oral suggests that although there is an increasing Thus IGpH recordings made by and nasal route is not known, however, and incidence of the disease with age, it is a telemetry are different from those of aspira- may lead to errors in probe placement, common endoscopic diagnosis in all age tion and direct comparison of results from resulting in the under estimation of acid groups. the two techniques is inappropriate. reflux. To determine the differences between nasal and oral measurement of the lower oesophageal sphincter (LOS) 20 Comparison of the acid/alkaline junction Antral size, acid secretion and the integrated healthy male volunteers aged 21-36 years with the manometrically determined lower gastrin response (IGR) to food underwent oesophageal manometry using a oesophageal sphincter (LOS) triple lumen perfused catheter by the M J ROGERS, M LAGOPOULOS, M F DIXON, J station pull through technique. Four studies D L STOKER, J G WILLIAMS, D G COLIN-JONES PRIMROSE, T GLEDHILL, D JOHNSTON (Univer- were performed, two through the nose and (Royal Naval Hospital, Haslar, Gosport, sity Departments of Surgery, Anatomy, and two through the mouth. Hants) pH Probes should be placed in a Pathology, The General Infirmary, Leeds) The mean distance between the nares and reproducible anatomical position in the Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1451 oesophagus in order to make valid compari- had significantly higher pepsin concentra- In order to determine if GAS reflects the sons between patients. The acid/alkaline tions than 0 or N (p<0-0001). presence of significant (>110 [tmol/l) junction (AAJ) is often used to determine Complicated oesophagitis patients have gastric conjugated bile acid (CBA) con- the position of the LOS when placing oeso- significantly higher pepsin concentrations tamination, nine patients underwent phageal pH probes if manometry is not detected in the oesophagus than patients simultaneous, continuous intragastric pH available. We have examined 125 subjects, with uncomplicated oesophagitis. monitoring and gastric aspiration using a comparing the manometrically determined combined size 14 Salem sump tube and pH position of the LOS with the AAJ. A electrode. Each patient was studied for 16 standard manometric technique was used to Do bile acids (BA) modify the cytopathic hours, including a postprandial (PP) and map the LOS. The mean (1 SD) length of effects of pepsin (P) on oesophageal mucosal nocturnal period, and two hourly aliquots the LOS was 3-5 cm (1.3) (range 1-7 cm). cells? were analysed for pH and CBA by high The AAJ was determined by twice with- performance liquid chromatography drawing a pH probe from the stomach. In D C GOTLEY, B FLAKS, M J COOPER (Department (HPLC). pH traces were examined for most cases there was a rapid change from of Surgery and Pathology, Bristol Royal number and duration of pH rises >3, >4, pH 1-2 to pH 6-7 within 1 cm. The AAJ Infirmary, Bristol) The role of bile acids in >5, and the average pH for each two hourly occurred within the sphincter zone in 72 reflux oesophagitis is controversial. Bile period. subjects (57.6%). In 34 of these subjects the acids have been shown to inhibit peptic Nine PP periods showed GAS due to transition was at the lower end of the activity in vitro suggesting a protective role. buffering by food and were excluded, leav- sphincter. In 53 cases (42.4%) the AAJ fell On the other hand, bile acids and pepsin ing 63 for analysis. The presence of GAS outside the manometrically determined have been shown to have different sites of was significantly associated with intragastric LOS by 1 cm or more. Forty four (34%) action on oesophageal mucosal cells, sug- CBAs (p<0.001), however, there was no cases were below the LOS (range 1-13 cm, gesting an additive effect. Our analytical relationship between magnitude, number mean 3-4 (2.3)), while eight were above studies in patients with gastro-oesophageal and duration of GAS's and level of CBA. (range 1-6 cm, mean 2-8 (1-8)). reflux have shown that smaller quantities of During five periods the pH trace average The variability of the AAJ in relation to these agents reflux into the oesophagus. To was >3 pH points above aliquot pH, indi- the LOS makes it an unreliable technique determine whether these lower concentra- cating possible probe embedding in the for accurately placing pH probes. The prob- tions of BA modify P we incubated 70 gastric alkaline mucus layer. able reasons for this are pH changes in the oesophageal biopsies obtained during endo- Gastric alkaline shift is a non-quantitative fundic gas bubble, and the occurrence of scopy in normal saline (NS), P (100, 200, indicator of CBA reflux. In some patients, acid reflux during withdrawal of the pH 400 Rg/ml), and BA and P (50, 100, 200, GAS may be misleading in the diagnosis of probe through the sphincter zone. 500 Rtmol+ 100, 200, 400 [ig/ml) for five and duodenogastric bile reflux. 22 min periods at pH 2. All specimens were

immediately fixed in glutaraldelyde and http://gut.bmj.com/ Peptic activity in the refluxate of patients examined by electron microscopy. A single The use of an ambulatory cadmium telluride with uncomplicated gastro-oesophageal blinded pathologist assessed each specimen detector to monitor postprandial reflux of reflux (GOR) at four different levels for six different food parameters using a 0-4 scoring system. D C GOTLEY, D BALL, M J COOPER (Depart- Minimal structural damage occurred with N WASHINGTON, H A MOSS, C G WILSON ments of Surgery and Biochemistry, Bristol NS alone and at pH 2, whereas P (p<0-002) (INTRODUCED BY R C SPILLER) (Department of Royal Infirmary, Bristol) Reflux of gastric caused significant cell disruption, cyto- Physiology and Pharmacology, Medical contents the forms the maximal at into oesophagus toxicity being five min. Addi- School, Queen's Medical Centre, Notting- on September 24, 2021 by guest. Protected copyright. basis of the pathophysiology of oesopha- tion of BA to P caused no significant ham) The assessment of gastro-oesophageal gitis. Whilst acid reflux has been extensively alteration in degree or pattern ofcytotoxicity reflux by ambulatory monitoring is an estab- investigated, oesophageal peptic activity compared to that seen with P alone. lished but invasive technique. Gamma has received little attention. We studied 52 'Physiological' concentrations of BA scintigraphy has proved unsatisfactory, patients with symptomatic GOR and do not modify the cytological damage since it is difficult to provoke a reflux abnormal acid exposure, divided into four caused by pepsin on normal oesophageal episode during the imaging period. groups: those with normal oesophagus (N), epithelium. The use of a small collimated gamma erosive oesophagitis (0), stricture (S), and probe has been investigated to detect post- Barrett's oesophagus (B). Each patient prandial reflux of a radiolabelled meal in six underwent 24 hour ambulatory pH moni- Prolonged intragastric pH monitoring in the healthy female subjects. The probe was toring, followed by a 16 hour continuous diagnosis of duodenogastric bile reflux supported 5 cm above the cardia coincident oesophageal aspiration study with a size 14 (DGR) with an oesophageal pH probe. Outputs salem sump tube positioned 5 cm above the from both detectors were connected to an manometric sphincter. Specimens were col- D C GOTLEY, A P MORGAN, M J COOPER (Depart- ambulatory solid state recorder. The test lected in two-hourly aliquots (giving eight ment of Surgery, Bristol Royal Infirmary, meal consisted of a Spanish omelette label- specimens/patient) and total peptic activity Bristol) The phenomenon of 'gastric led with techneitium-99m (3 MBq), lemon- was determined by a haemoglobin substrate alkaline shift' (GAS) seen with prolonged ade, apple pie, ice cream, and coffee (4648 assay. intragastric pH monitoring has been used as kJ). After consumption of the meal, data Groups 0, S, and B had greater acid a measure of DGR and gastric bile acid were collected for four hours and trans- exposure than N (p<0-001), but could not contamination in patients with reflux oeso- ferred to a microcomputer for analysis. The be separated from each other on the basis of phagitis and biliary gastritis. This tech- reflux of the technetium was quantified and pH monitoring. S and B groups, however, nique, however, has not been validated. correlated with changes in oesophageal pH. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1452 The British Society ofGastroenterology

Reflux of radiolabelled food occurred nizatidine, ranitidine, and placebo in an DU the gastroduodenal mucosa is exposed between 30 and 100 minutes after the meal actual practical pharmacological study in 15 to a greater acid concentration only at night. and was associated with a decrease in oeso- normal volunteers. The assembly consisted This abnormalility emphasises the need to phageal pH. Acid reflux was not always of a nasogastric tube with an Ingold com- selectively suppress nocturnal acidity to associated with increase in oesophageal bined glass electrode attached with the tip heal DU. counts, however, suggesting acid does not adjacent to aspiration ports. Aspirates were mix uniformly with the food and is the collected at hourly intervals, and intra- primary aggressive agent in painful reflux. gastric pH was recorded at 6 second Investigation of gastrointestinal motility intervals. with echo planar magnetic resonance Datalogger (D) pH v aspiration (A) pH imaging (EPI) An indirect tubeless test of gastric function confirms a highly significant point correla- tion, but the slope was significantly less than D F EVANS, M K STEHLING, G LAMONT, R C D JOHNSON, P HARRIS, C WASTELL (Depart- 1. There was also significant correlation COXON, A M HOWSEMAN, R J ORDRIDGE, J D ment of Surgery, St Stephen's Hospital, between D and A for mean 24-h, morning, HARDCASTLE, P MANSFIELD (Departments London) Measurement of gastric function afternoon, evening, and night pH, but the of Physics and Surgery, Nottingham requires nasogastric intubation for aspira- correlation was poorer during the day (r= University, Nottingham) Magnetic reson- tion of gastric juice. Gastric acid secretion 0.51) than at night (r=0.83). Differences ance imaging (MRI) is not suitable for entails a compensatory reduction in urinary between methods (D-A) during the day dynamic studies of the gastrointestinal tract acid output (UrAO). We investigated the ranged from 0-4 to 1.4 pH units, but at night because of long image acquisition times and quantitative relationship between these two were -0-2 to +0*2 pH units. Irrespective of subsequent image blurring and artefact. outputs to establish whether changes in the technique used, however, conclusions The EPI variant MBEST produces images UrAO might be useful as a tubeless test of reached on drug efficacy were similar. in only 64 msecs allowing rapid sequential gastric secretion. These results show that datalogging quantitation of gut wall movements. Gastric secretion was measured in 11 devices are suitable for the evaluation of We have evaluated EPI to image gastro- volunteers and six postvagotomy patients, drug effect on 24 hour gastric acidity, but intestinal motility in four volunteers. Three using pentagastrin 6 rig/kg or shamfeeding that the results, especially during the day- fasted subjects were imaged at the trans- (SF) with nasogastric intubation. UrAO time, may substantially differ from those pyloric plane or ligament of Treitz before was measured during the gastric function obtained by aspiration, and cannot there- and after a test meal, after preloading the tests and after a standard meal. fore be directly compared. stomach with 1 1 tap water to improve There was a good correlation between contrast. One subject was similarly imaged total gastric acid output (median 6-4 mmol/ after 10 mg metoclopramide im. Movie h range 0-43.3) and the change in UrAO 24-hour intra-gastric pH profile in healed loops of 40 images/min were produced to during gastric function tests (n= 18, median and in active duodenal ulcer disease identify gastroduodenal peristalsis. Visible http://gut.bmj.com/ -2.0 mmollh, range +0-4--7-6): y= peristalsis was seen in the antroduodenal -0*82-0.11x; r=0-79, and after a test meal B K KAPUR, K D BARDHAN (District General region after the test meal with a frequency (n=11, gastric acid median 4-8 mmollh, Hospital, Rotherham, South Yorkshire) of two/min. Food stimulated duodenal range 0-14-2; change in UrAO median Little is known of changes in the intragastric peristalsis was seen with a wave velocity of -0-4 mmollh, range +0.5--1.4): y= pH profile in duodenal ulcer (DU) when 0 64 cm/sec and a frequency of six/min. -0-11x; r=0*73. active and when healed. We therefore Metoclopramide maximally stimulated UrAO after SF and after a test meal measured the 24-hour intragastric pH pro- antroduodenal peristalsis after 20-25 mins identified the only postvagotomy patient file under standard conditions and off all with a wave velocity of 9 cm/sec and a on September 24, 2021 by guest. Protected copyright. with a recurrent ulcer. drugs using a validated ambulatory moni- frequency of two to three/min. We have demonstrated a linear relation- toring system in 22 healthy volunteers Echo planar imaging is an exciting new ship between measured gastric secretion (HV), in 55 patients with healed DU extension to MRI and shows great potential and changes in urine acidity after a meal. (H-DU) and in 30 patients with active DU in the non-invasive dynamic imaging of This tubeless test of gastric function may be (A-DU). Arcsine transformation was used gastrointestinal motility. a useful screening test for the detection of to normalise the data and the mean percent- incomplete vagotomy. age (and 95% confidence limits) of day time and night time spent at pH <2 and pH >4 Non-invasive assessment of antral motor were calculated. function by high resolution real-time ultra- Validation of pH dataloggers for pharma- The only significant difference (p<0.01) sound in normal subjects and functional cologic studies (analysis of variance) was observed at night dyspeptic patients (2400-0850 h). The time spent at pH <2 D W BURGET, S G CHIVERTON, R H HUNT was in: HV 46% (30-63), H-DU 59% (49- D G THOMPSON, K GAIT, H MAMTORA (Depart- (McMaster University, Division of Gastro- 69), A-DU 80% (71-88); and at pH >4 was, ments of Medicine and Radiology, Hope enterology HSC-4W8, 1200 Main Street W, respectively, 35% (20-53), 23% (15-32), Hospital, Eccles Old Road, Salford) We Hamilton, Ontario, Canada) Twenty four and 8% (4-13). During the day (08 50-24 00 used high resolution real time ultrasound hour gastric aspiration studies have recently h) the time at pH <2 was in; HV 61% (46- (Acuson-128) to assess antral capacity and begun to be superseded by dataloggers 75), H-DU 63% (55-70), A-DU 66% (53- peristaltic function following a standard 400 which continuously record intragastric pH. 77); and at pH >4 was, respectively, 11% ml soup meal in eight normal subjects, and Original reports validating dataloggers used (4-21), 14% (10-18), and 18% (8-30). in seven patients with functional dyspeptic point pH correlations in untreated normal Thus the 24-hour pH profile in patients symptoms (normal endoscopy and biliary subjects. We compared mean responses to with healed DU is normal whereas in active investigations). Antral area was measured Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1453 at 15 minute intervals (using the inbuilt pathology. Twelve of 54 patients with of three, six, and 12 months depending on plotter) during and between peristaltic normal eendoscopies, however, had the degree of the lesion. Each biopsy is waves. In normal subjects, the time to 50% abnormal ultrasound (specificity 78%). reviewed by a panel of pathologists. So far, reduction of post meal antral area was 62-7 UltrasoundA can detect a high proportion of 114 patients (89 men, 25 women, mean age (3.4) min (mean (SE)), % reduction at 90 gastroduodlenal pathology and therefore 59, range 29-83, 0-4% of all patients under- minutes was 65.6 (3.1). In seven normal may be able to screen patients for endo- going endoscopy over the same period of subjects repeated studies (x3) shoed high scopy. time) have been diagnosed and 80 have at reproducibility (mean coefficient of varia- least two examinations. Mean follow up is tion of t/2 8.4%). Values for dyspeptic 17 months (range 3-68), mean number of patients were significantly different, time to endoscopies 3.5 (2-10). Dysplasia was of 50% antral area reduction was 78-2 (4.5) mild degree (MiD) in 69 patients, moderate min, p<0-02, % reduction at 90 minutes ENDOSCOPY (MoD) in 30, Severe (SD) in nine, and non 50-2 (5.9), p<0-05. Aborally synchronised evaluable (NVD) in six. Gastric ulcer peristalsis was identifiable in all normal Endoscopy in the Trent region (32%), chronic (50%), subjects and patients (irrespective of polyps (4%), gastrectomy (7%) were the emptying impairment). The % change in B B SCO1-r, M ATKINSON (County Hospital, associated lesions (no lesions 7%). For the antral area with a peristaltic wave was Lincoln an d University Hospital, Notting- 80 cases currently being followed up, this is similar in both normals (51.1 (10.3)) and ham) A suurvey of gastrointestinal endo- the evolution observed: MiD regression dyspeptics (51.4 (5.1)) p>0.1, indicating scopy in tihe Trent region was made in 73%, persistence 19%, progression 8% similar peristaltic amplitudes. These 1981. A cointinued increase in demand was (two of four cases to cancer); MoD regr changes were urelated to time after meal predicted airnd deficiencies were highlighted. 64%, pers 9%, progr 27% (six of six cases to ingestion. Peristaltic frequency was also It was therefore thought timely to make a cancer); SD regr 9%, pers 9%, prog 72% similar in both groups, 3-25 (0.3)/min further rev]riew. Questionnaires relating to (five of five cases to cancer); NVD regr (normal subjects) v 3-0 (0.4)/min 1986 were ccompleted by all gastroenterolo- 100%. Of the 13 cases of cancer, six were (dyspeptics) p>05. gists in the region. Upper G-I endoscopy early. All had gastric ulcer. Mean time to Real time ultrasound is a convenient, had doubleid to 7-6/1000 of the population/ diagnosis was 9-5 months, mean number reproducible, non-invasive method for year (as ma ny as barium meals). There had of endoscopies 3-4. Ten of 13 were diag- clinical assessment of antral function and been a larrge increase in the proportion nosed within one year offollow up (diagnos- identifies abnormalities in functional dys- (27%) donee by surgeons. Colonoscopy had tic delay), three after 18,24, and 40 months. pepsia patients which are missed by routine increased ffrom 0-40 to 0-94/1000. There In conclusion, gastric epithelial dysplasia is investigation. were 0-37 EERCPs/1000 being done in six of an infrequent finding; MiD and MoD most the 12 disttricts; over half being done in frequently regress or are no longer detect-

Leicester. 1There were 0-17 variceal sclero- able. Association with or evolution to http://gut.bmj.com/ Can ultrasound detect gastroduodenal therapy prcicedures/1000 being done in five cancer is observed in the great majority of disease? districts; ovver half being done in Sheffield. SD patients, who require surgery, but may There was widespread dissatisfaction with be observed even in MiD and MoD, thus S H SAVERYMUTTU, A E A JOSEPH, J D MAXWELL the provisic3n of facilities and staff for endo- indicating the need for careful follow up. (St George's Hospital, London) Increasing scopy. This included lack of a separate unit Such an approach seems to facilitate the numbers of patients are being investigated in seven of 18 hospitals. Designated nurses diagnosis of gastric cancer in its early stage. for suspected gastroduodenal disease and were foundl in only 10 hospitals, secretaries are found to have a normal endoscopy. To in two, and GPCAs for endoscopy in seven. on September 24, 2021 by guest. Protected copyright. reduce the negative endoscopy rate there is Planning grroups should be created in each Fragmentation of gall stones using pulsed a need for a screening investigation. Ultra- district to e]rnsure provision of a well staffed laser light sound has been reported to be abnormal in a and finance d endoscopy unit, to rationalise variety of gastroduodenal diseases but has the endosc4,opy service and determine the N MITCHELL, R NOVAK, M MCLOUGHLIN, J not been systematically compared with techniques to be done locally. HEGARTY, J G LUNNEY, 0 CORRIGAN, W VAN endoscopy. We have compared ultrasound DER PUlTEN, P W N KEELING (Trinity College, with endoscopy in 146 patients - major Dublin 2, Ireland) Gall stones were frac- pathology was present in 54 patients - 22 Gastric epiithelial dysplasia: a prospective tured by irradiations with pulsed excimer, gastric tumours, 14 duodenal ulcers and 18 multicentre follow up study ruby, and Nd:YAG lasers. Fracturing gastric ulcers and minor pathology in 34 occurred by the generation of shock waves patients - 27 with gastric erosions or INTERDISCIP1'LINARY GROUP ON GASTRIC in the material as a result of plasma produc- gastritis and seven with duodenal erosions. EPITHELIAL DYSPLASIA (IGGED), F FARINATI, tion at the irradiated surface by short (30 Fifty eight had normal endoscopies. Ultra- ET AL (INTRRODUCED BY PROF R NACCARATO) nsec) intense pulses. The gall stones were sound of the stomach and duodenum was (Cattedra Malattie Apparato Digerente mounted on a piezoelectric detector which abnormal in 87% of major pathology Policlinico Universitario, Universita di was used to monitor the acoustic pulses including all gastric tumours, 91% gastric Padova, Itcaly) The evolution in time of produced. With the excimer laser, 100-300 ulcers, 64% duodenal ulcers and 72% of gastric dysp lastic lesions has not been fully pulses were necessary for breaking in air. minor pathology. Both major and minor ascertained l. We report here the results of a Less than 10 pulses from the ruby laser pathology caused gastroduodenal wall prospective multicentre follow up study of directed at the gall stone in water was thickening and disruption of mucosal folds gastric epiithelial dysplasia carried out sufficient to cause fracturing. Pulses from a but fixed air collections in ulcer craters and according toto a standardised protocol that Q-switched Nd:YAG laser were able to mass lesions were only found in major calls for re[peated endoscopies at intervals destroy dark, pigmented stones in water Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1454 The British Society ofGastroenterology

with less than 50 pulses. The threshold for tion in patients with inoperable rectosig- colitis because of previous reports that the plasma production and acoustic signal pro- moid carcinomas with low associated histological changes of neoplasia are duced depends on the absorption coefficient morbidity. mimicked by reactive hyperplasia associ- at the irradiating wavelength. We conclude ated with acute inflammation. In a prospec- that plasma formation is essential for frag- tive study of 100 patients with ulcerative mentation; once above plasma threshold, colitis, 82 of whom had extensive colitis, the fragmentation process becomes more carcinoma and dysplasia could be dis- effective as the incident laser fluence COLORECTAL tinguished cytologically from reactive increases. hyperplasia. There were six patients with Low dosage 5-ASA enemas in the treatment carcinoma complicating colitis, and satis- of distal ulcerative colitis factory samples were obtained from five; Palliative endoscopic Nd:YAG laser treat- the cytological appearances were interp- ment of rectosigmoid carcinoma G BIANCHI PORRO, R FASOLI, M PETRILLO, S reted as carcinoma in three and as dysplasia ARDIZZONE (Gastrointestinal Unit, L Sacco in two. There were 78 patients who had not L A LOIZOU, D GRIGG, P B BOULOS, C G CLARK, Hospital, Milano, Italy) Recent studies developed carcinoma or dysplasia; the cyto- S G BOWN (National Medical Laser Centre, suggest that low dosage 5-ASA enemas are logical appearances were interpreted as Department of Surgery, University College as effective as hydrocortisone enemas in negative for dysplasia in 75, and indefinite Hospital, London) Forty patients with treating distal ulcerative colitis of mild to for dysplasia in three. In patients who had rectal or distal sigmoid carcinomas con- moderate activity. We have compared a developed dysplasia, the changes appeared sidered inoperable because of old age, low-dosage (1 g/day) rectal preparation of to be more widespread on cytology than significant concomitant disease or advanced 5-ASA in slightly acidic buffered suspen- histology. Brush cytology may complement tumour stage underwent endoscopic Nd: sion (Pentasa) with a hydrocortisone 100 histological assessment in patients with YAG laser treatment for palliation of mg/day enema (Cortenema) in 41 patients ulcerative colitis who have developed stric- symptoms: diarrhoea, rectal bleeding and with mild to moderate distal ulcerative tures or in whom there is a high suspicion of discharge, tenesmus and obstruction. Four- colitis in a randomised double blind three neoplastic change. teen (35%) of the lesions extended above week study. The two groups were compar- the peritoneal reflection. Five patients had able with regard to age, sex, maintenance tumours <3 cm in diameter; all these therapy, as well as pretreatment clinical, Defunctioned proctitis: a diagnostic patients derived significant improvement endoscopic, and histologic activity. After dilemma which was maintained by repeated treat- three weeks, both types of treatment ment over a mean follow up period of 40 resulted in a statistically significant M C WINSLET, M R B KEIGHLEY (The General weeks. In two patients complete macro- improvement of clinical and endoscopic Hospital, Birmingham) Proctitis in the scopic and histological elimination of the activity; histology improved only in the defunctioned may represent ahttp://gut.bmj.com/ tumour was achieved. The remaining 35 group treated with Pentasa. As regards the normal physicological response or the onset patients had more extensive tumours - 30 comparison between the two drugs, no of inflammatory bowel disease. It is a circumferential, five involving 13-2/3 of the significant difference was observed, common indication for not restoring intes- intestinal circumference. Twenty eight although a numerical trend in favour of tinal continuity. The aim of this study was to patients (80%) derived significant sympto- Pentasa was evident both in clinical (95% v investigate the cause, diagnostic criteria and matic improvement over a mean follow-up 75%) and in endoscopic (76% v 60%) effect of restoring intestinal continuity in period of 23 weeks; mean survival of activity. No side effects were reported in this condition. Eighteen patients underwent patients who died during this period was 16 either group. diversion and 10 had intestinal continuity on September 24, 2021 by guest. Protected copyright. weeks. All treatment failures occurred in Our experience confirms that a short term restored for a non-inflammatory condition. patients with extensive circumferential topical treatment with a low-dosage 5-ASA Macroscopic inflammation occurred in 10 tumours; five were early failures (three in is at least as effective as 100 mg hydrocorti- patients (55%) within three months of patients with obstruction and two in sone enemas in treating mild to moderate diversion with histological confirmation in patients with incontinence) and two late distal ulcerative colitis, and generally well five. Five patients showed macroscopic and failures (both in patients with obstruction). tolerated. histological improvement in restoring con- Of the early failures, only one was con- tinuity. There was no significant difference sidered fit for surgery the remaining in mucosal indices between the proctitis (P) patients receiving terminal care; both late Detection of malignant change in ulcerative and non-proctitis (NP) group (Crypt cell failures were managed by defunctioning colitis by brush cytology of the colon production rate: P=2-5±0-7, NP=2-9±0-9 colostomy. There were no treatment cells/crypt/h. Glucosamine synthetase: related deaths; bowel perforation however, D M MELVILLE, P1 RICHMAN, N A SHEPHERD, C B P= 14-3±3-3, NP= 14-7±2-6 mmol/g/h. occurred in two patients. Treatments were WILLIAMS, J E LENNARD-JONES (ICRF Mucosal lymphocytes: P=1-1x10', NP= performed with simple bowel preparation Colorectal Cancer Unit, St Mark's Hospital, 1-9x10' cells/g). The flora of the excluded and minimal sedation and repeated at mean City Road, London) Surveillance program- colon (aerobic and anaerobic species intervals of eight weeks. Patients required mes for patients with longstanding ulcera- carriage rate, organisms (P=6.8', NP=3.07) an average of 2-5 treatments in order to tive colitis rely on mucosal biopsies for the and species count (P=4, NP+4) was not maintain symptomatic improvement; detection of the premalignant changes of significantly different in the two groups. ambulant patients were treated on an out- dysplasia. Such biopsies only sample a very Colonic permeability was similar (P=8.5%, patient basis. small part of the mucosa and may miss focal NP=6.1%). Defunctioned proctitis is a Laser tumour photoablation provides dysplastic changes. Cytology has not been common complication after faeca; diversion good quality longterm symptomatic pallia- routinely used in patients with ulcerative of unknown aetiology. Its only diagnostic Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1455 feature, to date, is resolution after rectora- tive stools. Stool form was enumerated pectively 612 (46), 594 (77) v 1948 (257)). tion of continuity. It presence is not a from a newly-devised 7-point scale in which When severely dysplastic polyps with contraindication to stoma closure. the stool is classified according to cohesion, invasive growth were compared with the surface cracking, and consistency. Simul- other polyps, u-PA antigen was significantly taneously, whole gut transit time (WGTT) (p=0.005) higher and similar to that in the Cephalic phase ofcolonic motility was measured by ingestion of 20 radio- carcinoma group. No relation was found opaque markers daily on four consecutive between PA and histological type or polyp J ROGERS, A H RAIMUNDO, J J MISIEWICZ days followed by an abdominal radiograph size. (Department of Gastroenterology and on day 5 (Gastroenterology 92: 40). Median In colon carcinogenesis (normal mucosa - Nutrition, Central Middlesex Hospital, stool frequency was 1-7/24 h (range 0-3-5). adenoma - carcinoma), two discrete London) To test the existence of a cephalic Urgency was recorded by 74% of patients. changes in PA content can be distinguished; phase to food induced increase in colonic WGTT ranged from 6 to 96 h. WGTT did one, a decrease of t-PA and an increase of activity five normal subjects (mean age 22-6 not correlate with mean stool frequency (r= u-PA when an adenoma develops; two, a yr (22-24), were studied, on six separate -0-22; NS). It correlated well, however, second increase of u-PA at the appearance occasions in random order, by intraluminal with mean stool form (r=-0-81; p<0-001). of invasive growth. These results point to an pressure recording in the unprepared sig- These data show that patients' records of important role for u-PA in colonic carcino- moid colon. After a 60 minute basal period stool form can be used as a guide to transit genesis. one of five food related cephalic stimuli of time and indicate that in IBS 'diarrhoea' is 30 minute duration or control stimulus was often pseudo-diarrhoea. As patients with given and recordings continued for 120 slow and fast transit may respond differ- minutes. The pressure records were ently to high fibre diets or bulking agents, Evaluation ofa biopsy gun for guided biopsy analysed in 10 minute periods as a study assessment of transit time by patients' of impalpable lesions using intraoperative segment (sum of all four channels), for records of stool form may be a simple and ultrasound activity index (AI=area under curve, useful guide to management options. mmHg/min) by fully automated computer analysis. Constant gastric aspiration by NG- R M CHARNLEY, J P SHEFFIELD, J D HARDCASTLE tube was done to measure the effect of the Association between tumour development (Department of Surgery, University stimuli on gastric acid secretion. Food dis- and plasminogen activators in the human Hospital, Nottingham) Intraoperative ultra- cussion (FD) significantly (p<0.01, t-test) colon sound can detect occult liver metastases increased the mean colonic in up to 10% of patients who undergo pressure activity 'curative' resection for colorectal cancer. compared to control discussion (781 (129) P A F DE BRUIN, H W VERSPAGET, G GRIFFIOEN, Identification of these impalpable lesions mean AI v 340 H F G M VAN DEN INGH, J H (SD) (65)) and was the best VERHEYEN, G not on the lesions but relies only imaging http://gut.bmj.com/ stimulus compared with sight only, smell DOODEWAARD, C B H W LAMERS (Department only, sight and smell, or sham feeding of the of Gastroenterology and Hepatology, also on gaining histological evidence by subjects favourite meal. Increase in colonic Department of Pathology, University biopsy which can be technically difficult pressure activity following FD correlated Hospital and Gaubius Institute TNO, using conventional biopsy needles. We have significantly (r=0.56, p<0.01) with volume Leiden, The Netherlands) Changes in evaluated a biopsy gun which can be of gastric juice aspirated. There was no plasminogen activator (PA) content have operated with one hand by performing correlation in the control study. These data been implicated in the aetiology of malig- guided biopsy of impalpable liver meta- show that there is a cephalic to food a stases at necropsy. phase nancy. We studied PA activities by Twenty impalpable liver metastases induced increase in colonic pressure activity spectrophotometric assay and antigens by on September 24, 2021 by guest. Protected copyright. and suggests it may be related to increased between 2 cm and 5 cm from the liver ELISA in homogenates of adenomatous surface were identified at production of gastric acid. polyps (n=48) from the colon and com- necropsy by con- pared the results with other malignancy tact ultrasound using an intraoperative parameters. Twenty five pairs of normal ultrasound probe. Each lesion was individu- Pseudo-diarrhoea in the irritable bowel syn- mucosalcarcinoma served as controls. ally measured using the light pen attach- drome: patients' records ofstool form reflect Results, activities in mIU/mg protein and ment on the ultrasound machine and was in then biopsied under ultrasound control transit time while stool frequency does not antigens ng/mg protein, are expressed as using a biopsy gun (Biopty-Radiplast AB, mean (SE). Uppsala, Sweden). The 20 core biopsies L J O'DONNELL, J VIRJEE, K W HEATON Activity of u-PA in adenocarcinomas were individually analysed histologically for (Departments of Medicine and Radiology, (126 (21), p<0.001) was three times higher the presence of carcinoma. University of Bristol, Bristol Royal than in the normal mucosa (39 (66)), while Of the 20 impalpable lesions (median Infirmary, Bristol) Patients with IBS often u-PA antigen even showed a ten-fold diameter 12 mm; range 9-18 mm) histology complain of increased stool frequency and increase (respectively 10-7 (1.1) v 1-0 (0.1), was positive for carcinoma in 18 (90%). urgency and this is easily interpreted by p<0.001). The adenomatous polyps con- metastases and doctor as tained u-PA Biopsy of impalpable liver patient diarrhoea. Experi- activity (59 (5)) and antigen down to a diameter of9 mm is possible using enced gastroenterologists know that fre- (4.4 (0.4/) intermediate to, and significantly a under ultra- quent stools can be formed or even hard (p<0.01) different from those of normal biopsy gun intraoperative suggesting intestinal transit is normal or mucosa and carcinomas. t-PA antigen in sound control. slow but evidence for this is scanty. adenomas (3.8 (0.2)) and carcinomas Twenty three unselected IBS patients (16 (4.6 (0.4)) were significantly (p<0.001) women, 7 men; age 18-68 yr) recorded the lower than in the normal mucosa (7.9 (0.4)) Pallation of colorectal cancer with the Nd: form and time of evacuation of six consecu- also noticed in t-PA enzyme activity (res- YAG laser. Which patients are palliated? Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1456 The British Society ofGastroenterology

H BARR, N KRASNER (Gastrointestinal Unit, function. Bias between investigators for These results indicate that rectal contrac- Walton Hospital, Liverpool) Endoscopic each variable, 95% CI of the bias; ±2 SD tile events and sampling episodes occur less laser therapy is a new and simple method for (limits of agreement) and the average range often in CIC compared with controls. the palliative treatment of inoperable of values by both methods follow: Perineal Demonstration of episodic variations in colorectal cancer. Overall 70 patients have descent (cm): -0-07, -0-47 to 0.31; ±1-3, resting pressures in CIC may been treated and had some symptomatic [0.5-2.4]. Anal canal length (cm): -0-1, explain inconsistencies in previous labora- improvement. The subjective assessment of -0-2 to 0-4; ±1-0, [2-4]. Resting pressure tory studies and highlights the importance these patients is difficult, so a prospective (cmH2O): -10, -25 to 4-7; ±42, [30-130]. of more physiological prolonged ambulant quality of life analysis was performed on 20 Squeeze pressure (cmH2O): -9, -32 to 14; studies. patients. The patients were assessed using ±65, [40-250]. Pudendal nerve latency (ms); two methods; the QL index, a physician's 0-1, -0-3 to 0-2; ±0-6, [1-7-2.7]. Fibre assessment examining five items, activity, density: 0-26, -0-04 to 0 57; ±0 35, [1-83- Posterior pelvic floor repair - a new surgical outlook on life, health, relationships, 2-58]. Mucosal electrosensitivity (mA); 0-5, approach for outlet obstruction support; and a patients selfassessment using -3-3 to 4-3; ±19.0, [1.75-23.6]. (obstructed defecation) 25 visual analogue scales (Linear Analogue Repeatability for the calculation of fibre Self Assessment, LASA). Correlation density derived from single muscle fibre I G FINLAY, D BROWN (Department of between the QL and LASA was significant EMG was assessed with each investigator Surgery, Royal Infirmary, Glasgow) Outlet (r=0.79). The quality of life was measured analysing the others tracings blind and obstruction constipation (OOC) is associ- before and at monthly intervals after treat- showed no significant difference, bias ated with puborectalis paradox (1). We ment. There was no improvement in the -0-003, -0-07 to 0.06 95% CI. reported that (a) unobstructed defecation quality of life if the whole group was In this study the standard tests of requires lifting of the posterior pelvic floor examined over their entire remaining life anorectal sensorimotor function show a (PPF) before puborectalis relaxation (2), QL: p=0-33, and LASA: p=0-48). There high degree of repeatability between differ- (b) patients with OOC collapse the PPF on was a significant improvement from the ent investigators. These tests are validated straining at stool (3). mean pretreatment score and the best and allow comparison of data obtained in An operation has been performed in 12 achieved post treatment score in a subgroup different centres employing the same tech- female patients with classical OOC which is of 14 patients (QL: p=0-002, and LASA: niques. designed to support the posterior pelvic p=0.002). The mean quality of life over the floor using a porcine dermis implant. After period excluding the last four to six weeks of an intersphincteric the graft is life was not significantly improved (p= Prolonged ambulant anorectal motility in sutured to the sacrum and to the origin of 0.052). It was apparent that the greatest chronic idiopathic constipation the levator ani muscles. improvement in quality of life (14 patients) Videoproctography was used to study the http://gut.bmj.com/ occurred in those patients who had D J WALDRON, D KUMAR, N S WILLIAMS, R I position of the anorectal junction (ARJ) improvement in the symptoms of diarrhoea, HALLAN (The Surgical Unit, The London and the lowest point of the posterior pelvic mucus discharge and obstructive symptoms. Hospital, Whitechapel, London) Labora- floor with reference to the pubococcygeal Patients, who failed to show improvement tory anorectal manometric studies report line. The mean descent of the ARJ pre- or who showed a deterioration in the quality variable results in chronic idiopathic consti- operatively was 2-2 cm (0.3) (mean (SE)) of life scores, had only a short time to live, pation (CIC) some showing a high pressure compared with 1-4 cm (0.3) one month after severe pain, or sphincter problems. In zone in the anal canal. Six subjects with CIC surgery, p=0-1. The corresponding values selected patients laser therapy provides and 14 controls were studied in an ambulant for the mean descent of the posterior pelvic effective palliation of inoperable colorectal situation for 18-2 and 20-3 hours (mean) floor were 3-5 cm (0.5) and 1-6 cm (0.4) on September 24, 2021 by guest. Protected copyright. cancer. respectively, using a Gaeltec anorectal respectively, p<0-001. probe containing pressure-sensitive micro- All patients were asymptomatic for three transducers placed 10 cm apart to lie in the months. Three have developed minor Validation of the motor and sensory tests of rectum and anal canal. symptoms in the fourth month of follow up. anorectal function: a repeatability study Sampling reflexes occurred significantly These results suggest that posterior pelvic less often in CIC, 2-4 (0.3)/hour (mean floor repair may be of value in patients J ROGERS, S LAURBERG, J J MISIEWICZ, M M (SEM)), compared with controls, 7-4 (2.0)/ with outlet obstruction constipation. HENRY (Department of Gastroenterology hour, (p<0-05). Rectal contractile events, and Nutrition, Central Middlesex Hospital, frequency two to three/minute, occurred at London and Department of Physiology, St intervals of 60-90 minutes in both groups Marks Hospital, London) Anorectal with post prandial contractile frequencies of physiology, used in the management of five to six/minute occurring at shorter inter- PANCREATICOBILIARY patients, has not been validated. Sixteen vals (20-30 minutes). Such events were less subjects (mean age 50-7 yr (12-8), three frequently seen, however, and were of Assessment and monitoring of acute pan- men) were studied on two separate occa- lesser amplitude in the constipated group. creatitis by the APACHE II scoring system sions by two independent investigators in Episodic rises in anal canal resting pressure, random order with anatomical, mano- mean amplitude increase of 12-0 (0.8) D I HEATH, C WILSON, C W IMRIE (Department metric, and electrophysiological assessment mmHg and duration 5-1 (0.7) minutes, of Surgery, Royal Infirmary, Glasgow) of anorectal motor and sensory function. occurred 1-1 (0.2) times/hour only in the Drawbacks of the multifactorial scoring There was no significant difference between constipated group. Otherwise resting anal systems for grading the severity of acute the results obtained by the two investigators canal pressure was not different between pancreatitis include a delay in characteris- in the six separate tests of anorectal both groups. ing disease severity and an inability to Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1457 monitor the disease course. The Acute ence of may be attributed and Gastroenterology, UMDS, Guy's Physiology and Chronic Health Evaluation to an increased diagnostic rate caused by Hospital, St Thomas Street, London) The (APACHE II) scoring system overcomes greater clinical awareness and the avail- factors controlling pancreatic growth are some of these problems but is not a widely ability of a simple reproducible diagnostic poorly understood. Transplantation of the accepted means of assessing severity in test. jejunum between the stomach and duo- acute pancreatitis. We have prospectively denum (pancreaticobiliary diversion) evaluated this system in 155 consecutive causes pancreatic hyperplasia. We describe patients with acute pancreatitis. Thirty The tumour marker CA195 predicts a new model to induce pancreatic hyper- eight (24.5%) had a complicated attack duration ofsurvival in pancreatic cancer plasia and adenoma formation. (including 12 deaths (8%)), the remainder Male Wistar rats underwent either a having an uncomplicated course. O M TAYLOR, E H COOPER, M J MCMAHON, E A simple gastrojejunostomy or a 'split' gastro- The admission APACHE II score dis- BENSON (The Department of Surgery and jejunostomy where the jejunum was tinguished complicated from uncompli- The Unit For Cancer Research, The General divided and the two limbs implanted into cated attacks (mean scores 10.9 v 6-3, Infirmary, Leeds) The carbohydrate the stomach 1 cm apart. When killed at 56 p5 predicted severe antigen, may be raised in the serum of gastrojejunostomy rats was significantly attacks with a sensitivity of 95% and had an patients with carcinoma of the exocrine lower (495 g) compared to those with a overall correct prediction of 64%. A score pancreas. Using an immuno-radiometric simple gastrojejunostomy (643 g, p<0-001 of >9 during the first three days predicts assay (Tandem IRMA Kit) we have deter- Mann Whitney). The 13 simple gastro- severe attacks with a sensitivity of 82%, mined the serum CA195 concentrations in jejunostomy rats had no hyperplasia of the specificity of 74% and overall correct value 35 patients with histologically proven pan- pancreas or small bowel, and the jejunal of 76%. This is comparable with the existing creatic carcinoma. All cases were staged villous to crypt ratio was 1-55, reflecting the systems. using combinations of ultrasound, com- villous atrophy associated with this opera- APACHE II provides continuity of puted tomography, and laparotomy. tion. All 10 'split' gastrojejunostomy rats assessment. All laboratory investigations Twenty four cases were followed up at had pancreatic hyperplasia with nodule are available as part of the 'out of hours monthly intervals until death (median formation. Five animals had hyperplastic service' and the scores calculable within a survival=75 days; quartiles=27-112). nodules, four animals had both hyperplastic few hours of admission. Samples were obtained for CA195 assay at and adenomatous nodules, and one rat had each review. enlarged lymph nodes. Both the afferent Analysis of the data (using X2 with Yates and efferent limbs of the gastrojejunostomy Changing incidence and mortality from correction) suggested that a cut-off CA195 were grossly enlarged and the villous to acute pancreatitis level of 1000 U/ml distinguished both meta- crypt ratio was 3-65. static status and survival of less than three This study shows that separation of the http://gut.bmj.com/ C WILSON, C W IMRIE (Department ofSurgery, months. Of 35 samples taken within three limbs of a gastrojejunostomy in the rat is Royal Infirmary, Glasgow) Few studies months of death (median=38 days, associated with autonomous pancreatic have examined the changing incidence and Q1:Q3=22:67), 25 had CA195>1000 U/m], growth and jejunal hyperplasia. mortality trends from acute pancreatitis. but of 19 samples taken before this time, Studies from Bristol showed an increasing only three had such high levels (p<0.001). incidence over the 30 year period 1950- Only three of 21 cases without metastatic Assessment of exocrine pancreatic function 1979, although case mortality remained disease had CA195>1000 U/mI, compared after gastrectomy unchanged at around 20%. Data on hospital with 10 with levels above this value, of 14 on September 24, 2021 by guest. Protected copyright. admissions in Scotland have been recorded with metastases (p<0.001). Comparing S DOMSCHKE, G HEPTNER, W DOMSCHKE since 1961 as the Scottish Hospital In- metastatic status with survival, we found (Department of Medicine, University of D- Patient Statistics, permitting analysis of only two of 13 with metastases lived for 8520 Erlangen, FR Germany) Gastrectomy such trends. more than three months (median=50 days, may lead to pancreaticochymous asynchro- The annual admissions for acute pan- Q1:Q3=26:75), compared with the survival nia and impair the diagnostic accuracy of creatitis in men have increased 11-fold from of 12 patients without metastases (median= established indirect pancreatic function 69 cases/year in 1961 to 750 cases/year in 102 days, Q1:Q3=70:141) of whom eight tests. We compared intra-individually the 1985 and in women has increased four-fold lived for longer than three months specificity of these tests with that of our new from 112 cases/year to 484 cases/year (p60 indicator of duration of survival than meta- aged 20 to 68 years) a normal pancreatic years). A corresponding change was not static status. Its assay may be useful both function was affirmed by the secretin- seen in mortality which increased only two- clinically and in the study of this disease. pancreozymin test, preoperatively. Before fold in men from 15 cases/year to 30 cases/ and three months after total (n=4; Roux-Y year and in women from 29 cases/year to 37 type) or subtotal (n=6; Billroth II) gastrec- cases/year. Pancreatic adenomas are induced by duo- tomy, in each patient the Pancreolauryl test The largest increase in admissions occur- denogastric reflux (PLT), the NBT-PABA test, the fecal red in the six year period after 1971 coinci- Chymotrypsin (fCh) determination and the dent with the introduction of the Phadebas P R TAYLOR, R C MASON, T PALMER, D C PAAC test were carried out. amylase test (Pharmacia). It is suggested HANLEY, G M MURPHY, R H DOWLING, I MCCOLL Before gastrectomy only one patient had that much of the apparent increase in incid- (Departments of Surgery, Histopathology a falsely pathological result in the PLT Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1458 The British Society ofGastroenterology

(90% specificity), while the results of all S SHANKAR, R C G RUSSELL (Department of of Oddi (SO) manometry in those with other indirect tests were correctly normal Gastroenterology, The Middlesex Hospital, possible cryptic obstructive SO dysfunction (100% specificity). After gastrectomy the London) Distal resection has become (SOD). Of the 100 patients, 31 were judged respective specificities were: PLT 10%, unpopular, yet in patients with defined true positive and 69 true negative. The NBT-PABA 70%, fCh 70%, and PAAC ductal disease the results appear good. To positives included 17 patients with common test 100%. There was no obvious difference test this hypothesis 121 patients operated duct stones (CDS), 10 with SOD and four in the reduction of specificity between sub- upon between 1976 and 1988 are reviewed. with benign stricture, tumour or choledo- total and total gastrectomy. Resection was elective in 110 patients. The chocele. The SOD cases consisted of After gastrectomy, when a direct duo- dominant indication was uncontrolled pain patients with sphincter stenosis or dyskine- denal tube test cannot be performed, only with narcotic abuse in 43, steatorrhoea 33 sia. Overall sensitivity was 78%, including the plasma amino acid consumption test is and loss of work 23. Forty patients had 76% for CDS and 80% for SOD. False unaffected by postoperative anatomical acute pancreatitis at first presentation, 20 positive findings occurred in 14% of the true alterations and appears to be advantageous had non-resolving acute pancreatitis and negatives for a specificity of 86%. We for indirect but correct determination of the remainder chronic disease. ERCP was conclude that: (1) QHS is us.-ul for evaluat- exocrine pancreatic function. successful in 102, showing duct obstruction ing patients with suspected partial common in 53, duct disruption in 18, and diffuse duct obstruction. (2) The test is applicable Exocrine and endocrine function in chronic disease in 31. The resection included in cholecystectomised patients without pancreatitis: relation to pancreatic surgery splenectomy in all and a pancreatojejunos- significant liver dysfunction. (3) In some tomy in 50. Mean length ofstay was 24 days, cases, QHS may obviate the need for SO operative mortality was nil and late deaths manometry. J C THOW, T HAWKINS, K G M M ALBERTI, were three. Using the Visick grading 53 R TAYLOR, C VENABLES (Departments of Medicine and Surgery, University of New- patients had good results (I and II), 10 fair castle upon Tyne) is (III), and 27 poor (IV). Twenty three Endoscopic stenting for malignant biliary associated with progressive loss of endo- patients were excluded as they were not obstruction: how good really? - a review of crine and exocrine function but it is not seen in the last two years, and eight were 641 consecutive patients known to what extent this decline is influ- operated on within the last six months. enced by pancreatic resection. Fifty two Good results were seen in those with duct J F DOWSETr, A POLYDOROU, D VAIRA, S R patients with chronic pancreatitis were obstruction or disruption, and poor results CAIRNS, J CROKER, P B COITON, R C G studied, of whom 25 (48%) had undergone in thosewithout a defined duct abnormality, RUSSELL, A R W HATFIELD (Departments of pancreatic surgery (18 distal pancreatec- 21 of whom went on to have a total Gastroenterology and Surgery, The Middle- tomy (DP); seven Whipples pancreatico- pancreatectomy. sex and London Hospitals, London) During duodenectomy (WP)). Exocrine and It is concluded that distal resection should the last five years at the Middlesex and three residual 3-cell function were assessed by the be performed in these patients with a years at the London, 641 patients had http://gut.bmj.com/ p-amino benzoic acid (PABA), test (normal defined and localised duct abnormality as attempted permanent palliation of unre- range 0.67-1-09) and fasting C-peptide con- shown on the pancreatogram. sectable malignant biliary obstruction by centration (normal range 0. 18-0-52 nmolll) the endoscopic placement of 10 or 12 Fr respectively. There was a significant reduc- endoprostheses. Ninety four of these tion in C-peptide in DP and WP groups Efficacy of quantitative hepatobiliary scinti- patients had attempted combined (0.22 (0.04) (SE) v 0-24 (0.05) nmol/l; NS) graphy (QHS) for evaluating a large series of endoscopic-percutaneous procedures. The compared with the non-operated group patients with suspected partial common duct patients were divided by origin of malig- (0.44 (0.04) nmolIl; p<0.001 and p<0.01 obstruction nancy (primary or secondary) and level of on September 24, 2021 by guest. Protected copyright. respectively). There was a significant reduc- blockage (ampullary, common , or tion in PABA results in the DP and WP J S A COLLINS, W J DODDS, J E GEENAN, W J hepatic duct). Hepatic duct strictures were groups (0.54 (0.07) v 0-43 (0.14); NS) com- HOGAN, R DARWEESH, B D COLLIER, ET further separated into Types I, II, and III pared with the non-operated group (0.83 STEWART (Departments of Radiology and (after Bismuth). Only one stent was placed (0.04); p<0.01 and p<0.05 respectively). Medicine, Medical College of Wisconsin, for hepatic duct lesions, unless evidence of There was a close correlation between Milwaukee, USA) Quantitative hepato- sepsis in undrained segments developed PABA and C-peptide in the operated sub- biliary scintigraphy (QHS) may be a after the initial placement. All patients jects (R=0-66, p<0.01) but poor correla- promising method for evaluating suspected received prophylactic antibiotics and had tion in the non-operated group (R=0.34; partial obstruction. decompression assessed by serum bilirubin NS). Diabetes was more common in both During the past three years, we obtained estimation and ultrasound. DP and WP groups compared to the non- QHS exams in 100 non-jaundiced, chole- There were 37 ampullary, 337 low, 43 operated group (66, 57, and 23% respect- cystectomised patients with unexplained Type I, 62 Type II, and 68 Type III primary ively; X2=94; p<0.01). These results upper abdominal pain. The patient group malignancies and nil (-) ampullary, 23 low, quantify the consequences of surgery on consisted of 80 women and 20 men, age 26 Type I, 21 Type II, and .24 Type III exocrine and residual 3-cell function and 52±15 SD yrs. DISIDA was given iv and the secondary malignancies. For primary malig- show that resection of the distal pancreas time of peak isotope activity and isotope nancies, the success rates were 97%, 84%, and more extensive surgery carry similar clearance curves were derived from a region 94%, 94%, and 88%, the complication rates consequences. over the hepatic hilum. Values from were 32%, 19%, 13%, 18%, and 23%, the patients were compared with those from 22 30 day mortality rates were 3%, 17%, 10%, asymptomatic cholecystectomised controls. 12%, and 28%, and the median survivals Distal pancreatic resection in benign pan- The 'truth' about each patient was derived were 9, 4-5, 5-5, 4, and 3 mths. For second- creatic disease from an ERCP, accompanied by sphincter ary malignancies, the success rates were -, Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1459

86%, 92%, 95%, and 71%, the complica- recently described to measure in less than found to be raised only in the olive oil group tion rates were -, 14%, 8%, 48%, and one minute concentration on a small (p

A1460 The British Society ofGastroenterology

J W L PUNTIS, S KOLACEK, D LLOYD, G A controls (group C). Before treatment at Is an isolated rise in gammaglutamyltrans- BROWN, I W BOOTH (Institute of Child Health, gastroscopy group A showed: four peptic peptidase (y-GT) an indication for liver University of Birmingham, Francis Road, oesophagitis (PO), seven antral gastritis biopsy? Edgbaston, Birmingham) In the newborn (AG), three antral ulcers (AU), six duo- animal intra-uterine malnutrition is a well denal ulcers (DU); group B showed: two A IRELAND, L NEVILLE, A CARMICHAEL, J O'D recognised cause of impaired PEF, but PO, four AG, four AU, four DU; group C MCGEE, J M TROWELL, R W CHAPMAN (Gastro- there are no data in man. We have therefore showed: six PO, one AG, two AU, nine enterology Unit, John Radcliffe Hospital, used faecal chymotrypsin (FCT), a pre- DU. Serum PG I levels (mean (1 SD)) Oxford) y-GT is often the only abnormality viously validated index of PEF, to study the before treatment in group A and B were detected on screening of a patient with ontogeny of PEF and the influence of intra- comparable and significantly (p<0-001) alcoholic liver disease. In order to determine uterine malnutrition (birthweight <3rd higher than in group C (group A: 89 (30), whether an isolated rise of y-GT is sufficient centile), in 15 preterm neonates (mean group B: 79 (22), group C: 53 (13) ng/ml). indication for a liver biopsy, we have gestational age 30 w, range 24-32; birth wt After treatment serum PG I significantly analysed the records of 117 consecutive 1-17 kg, range 0-59-2-1 kg). There was a (p

Whittington Hospital, Highgate Hill, group 2, AST level ranged from 40-358 IU/l http://gut.bmj.com/ London) We have developed a software (normal <35 IU/l), and y-GT level ranged Campylobacter pylori (CP) and serum program (Solubile) for the diagnosis of the from 14-739 lU/l. In addition to the above pepsinogen I (PG I) in children jaundiced patient. The mathematical pro- changes, six of 34 had evidence of hepatitis, gram, although based on Bayes' theorem, 11 fibrosis, and three cirrhosis. In group 3, G ODERDA, D DELL'OLIO, P LERRO, F ALTARE, contains a number of mathematical innova- 19/66 had evidence of hepatitis, 22 fibrosis, I MOORA, N ANSALDI (INTRODUCED BY P J tions. and 15 cirrhosis. MILLA) (Paediatric gastroenterology, A database of 397 patients has been Thus, raised y-GT reveals only reversible

University of Turin and Pathology Depart- entered and the diagnostic ability depends changes on biopsy. However, if AST is also on September 24, 2021 by guest. Protected copyright. ment OIRM, Turin, Italy) In children with solely on this database. There are 24 diag- raised, >50% show fibrosis, hepatitis or peptic ulcer we observed that a raised serum nostic categories. There is a second pro- cirrhosis. PG I, an autosomal dominant trait, was gramme (Auxibile) which automatically associated with ulcer relapse and CP updates the database every week and presence in gastric mucosa and it lowered assesses the performance and accuracy of Interferon mediated impairment of hepatic when the ulcers healed. the Solubile program. The software pro- oxidative drug metabolism in rats To assess the relationship between serum grams are running in the Dept of Gastro- PG I and CP infection, we determined enterology on an IBM compatible micro- S J WILLIAMS, P I CRAIG, E CANTRILL, G C fasting serum PG I by radioimmunoassay in computer. FARRELL (INTRODUCED BY A R W-HATFIELD) 34 CP-positive children before and after Fifty new patients were entered prospec- (Liver Research Group, Department of amoxycillin therapy (50 mg/kg bid for four tively into the programme. Thirty seven Medicine, University of Sydney at West- weeks). Patients were divided into two (74%) were diagnosed accurately, with 47 mead Hospital, Sydney, Australia) We groups according to treatment outcome: in (94%) placed in the three most likely diag- have previously reported that recombi- group A (20 children, mean age 11 years, 11 noses. One hundred patients were entered nant human alpha interferon (rIFN-aA) boys) CP cleared, while in group B (14 prospectively at a nearby teaching hospital: significantly impairs antipyrine (Br J Clin children, mean age 12 years, nine boys) CP 72% were diagnosed accurately and 90% Pharmacol 1986; 22: 610-2) and persisted. CP infection was assessed by were in the first three places. theophylline (Lancet 1987; ii: 939-41) CLO-test and Giemsa staining of endo- Solubile will give reasons for its diagnosis clearance in man. In the present study an scopic antral biopsies before and after treat- and suggest further relevant investigations. animal model was developed to examine the ment. Eighteen CP-negative children The average time needed to enter data and nature of this interferon mediated impair- (mean age 10 years, nine boys) with for the houseman to receive a diagnosis is ment of hepatic oxidative drug metabolism. analogous endoscopic lesions were taken as five and a half minutes. Rats were injected intramuscularly with Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1461 either rIFN-ctA, recombinant human In patients with varices treated by injection evaluating portal vein patency, to compli- IFN-y (rIFN-y), recombinant rat IFN-y or sclerotherapy (15), however, GMBF was ment existing radiological techniques. vehicle and experiments performed 24 h significantly (p<0-05) reduced [12-8 (3.7- later. In intact animals, theophylline 46.0) mi/minute] when compared with those clearance (CLt) was determined twice 10 who were untreated [19.0 (6.9-55.6 ml/ The effect of carbon tetrachloride (CC14) on days apart; once after IFN (2-7.5x 105 U in minute]. is associated the copper-laden rat liver 0-2 ml H20) and once after vehicle (0.2 ml with diminished GMBF. This is related H20). CLt was also determined in the more to bleeding oesophageal varices or L BARROW, M S TANNER (Department ofChild isolated perfused rat liver (IPRL) following their treatment by sclerotherapy than to the Health, University of Leicester, Leicester) IFN (2 x 105 U) or vehicle. Androst-4-ene- presence of congestive gastropathy. This Copper is believed to be hepatotoxic in 3,17dione (androstenedione) hydroxylation finding may be pertinent to the factors Wilson's disease and Indian childhood pathways were used to assess possible IFN predisposing to variceal haemorrhage. cirrhosis. In rats, however, whose liver effects on the activities of individual cyto- copper was raised from 75±13 to 461±13 chrome P-450 isozymes. igll dry weight by copper acetate supple- Rat IFN-y significantly reduced CLt Non-invasive diagnosis of portal vein occlu- mentation of drinking water, hepatic in the intact animal (2.62± 1.25 v 3-76±2-03 sion by radionuclide angiography damage was confined to a mild focal hepa- mllkg/min, p

suppression of multiple isozymes. detecting PVO. position was, however, not reduced. http://gut.bmj.com/ Group I, 10 patients (mean age 47 yrs, Previous copper loading of rats unequivo- M/F 5/5) with PVO (including three patients cally protected against CC14 induced liver Gastric mucosal blood flow in portal hyper- with cavernous transformation (CVT)) con- necrosis, showed biochemically and histo- tension firmed by TMA. Group II, 25 cirrhotic logically, although triglyceride accumu- patients without PVO (Child A n=7, B and lation was apparently unaffected. By inter- J T WALSH, H L SMART, W B TINDALE, D R C n= 18) and group III, 26 control subjects fering with arachidonic acid metabolism, TRIGER (University Departments of Medicine with no evidence of liver disease of PH. copper may reduce prostaglandin mediated and Medical an Physics, Royal Hallamshire After overnight fast, Tc 99 was injected inflammation. Copper cytotoxicity may be on September 24, 2021 by guest. Protected copyright. Hospital, Sheffield) Gastric mucosal bleed- rapidly into a peripheral vein and isotope an insufficient pathological explanation of ing in portal hypertension (PH) is increas- flow curves (IFC) generated for 100 sec at copper storage disorders. ingly recognised but poorly understood. We 0-5 sec intervals over the liver and spleen have investigated the role of gastric mucosal together with heart lung and kidneys. Using blood flow (GMBF) by studying 28 patients computer assisted deconvolutional analysis Antibodies against the hepatic asialoglyco- with oesophageal varices (19 with congestive and gamma variate fit, and assuming that protein receptor preferentially coat per- gastropathy); 12 patients with endoscopy splenic arterial (SA) flow resembles that of portal hepatocytes in the in situ perfused rat negative dyspepsia acted as controls. Both the HA, the SA IFC was superimposed liver groups were well matched for age, sex and upon the total liver IFC to yield the HA weight. Gastric mucosal blood flow was contribution and hence indirectly PV flow. B M MCFARLANE, J SIPOS, C D GOVE, C G measured using a 99Tc-pertechnetate clear- Results for each group were expressed as MCSORLEY, I G MCFARLANE, R WILLIAMS (Liver ance technique involving simultaneous the mean HA/PV ratio. Unit, King's College Hospital, Denmark gastric juice and venous blood sampling Controls: 22/78 consistent with known Hill, London) Antibody-dependent, cell- following the injection of 5 MBq of tracer at physiological estimates; cirrhotics: Child A: mediated cytotoxic (ADCC) reactions may the start of a standard pentagastrin test. 28/72, B and C: 56/54 consistent with contribute to hepatocellular injury in auto- Overall, GMBF was significantly (p<0-05) decreased PV inflow with increasing immune (AI) and hepatitis B virus (HBV) lower in patients with PH [13.5 (3-7-55.6) severity of disease. PVO group: 97/3 con- related chronic active hepatitis (CAH). ml/minute] than in controls [25-8 (10-7- sistent with negligible PV flow and PVO and Circulating autoantibodies against the 49. 1) ml/minute] (valves as median and CVT; 81/19 indicating residual collateral hepatocyte specific, cell surface expressed range). This finding was unrelated to the PV flow. asialoglycoprotein receptor (HL) have been presence of congestive gastropathy and Our results show that non-invasive RA described in both AI- and HBV-CAH and independent of the severity of liver disease. provides a safe and accurate method of correlate with severity of periportal liver Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1462 The British Society ofGastroenterology damage. We have investigated the hypo- both AD and E2 is catalysed by P-450 survival. In selected cases meeting these thesis that periportal hepatocytes are UT-A. Accordingly, the content of P-450 criteria liver transplantation should be con- exposed to high concentrations of anti-HL UT-A was quantified in hepatic microsomes sidered while sufficient time remains to in afferent blood, rendering them particu- by immunoblotting; in PVL it was 56% of locate a donor. larly susceptible to ADCC damage. Eight control levels (p<0-05). Hence down- antegrade (portal vein) and seven retro- regulation of P-450 UT-A occurs in portal grade (hepatic vein via vena cava) in situ bypass. This finding suggests a role for Anorectal varices: prevalence in a cirrhotic perfusions of rat were performed at portal hypertension in mediating the altered population 10°C with 50 mU4 min Krebs-Ringer, then drug and steroid metabolism which occur in 12 ml guinea-pig anti-rabbit-HL or mono- cirrhosis (Mol Pharm 1987; 31: 117). S W HOSKING, H L SMART, A G JOHNSON, D R clonal anti-human-HL or control guinea pig Enhanced E2 production after portal TRIGER (University Surgical and Medical sera washed through with 50 ml Krebs- bypass, however, does not arise from Departments, Royal Hallamshire Hospital, Ringer. The distribution of anti-HL in cryo- hepatic aromatisation of androgens. Sheffield) Anorectal varices (ARV) are stat sections of the snap-frozen livers was Instead, impaired 16ct hydroxylation of AD usually asymptomatic, but sometimes they determined by a sensitive enzyme-avidin- may enhance extrahepatic metabolism of bleed catastrophically. Unlike oesophageal biotin immunohistochemical technique. In androgens by pathways which include E2 varices (OV), their prevalence in cirrhotic all experiments with anti-HL the antibody formation. The reduced hepatic 16a patients is unknown. Furthermore, the was found to be prominently and almost hydroxylation of E2 further enhances the relationship between ARV, haemorrhoids exclusively deposited on periportal hepato- accumulation of this biologically more and portal hypertension is undocumented. cyte surfaces, regardless of the direction of potent oestrogen at the expense of oestriol, One hundred consecutive patients pre- perfusion. This preferential coating of peri- a less potent metabolite. Supported by the senting with either newly diagnosed liver portal hepatocytes is therefore not related NH and MRC of Australia. disease (48), first GI bleed (13), or OV to their location relative to high concentra- rebleeding (39) were examined for ARVs tions of anti-HL in the afferent circulation by anorectoscopy. ARVs were diagnosed but apparently to their particular capacity to Serial prothrombin ratios: a prognostic either by the presence of external compres- bind the antibody and, in vivo, it might indicator in paracetamol-induced acute liver sible anal varices and/or the presence of account for the characteristic histological failure dilated varicosities within the anal canal and lesion of CAH. rectum. Fourty four patients had ARVs (six P M HARRISON, G J ALEXANDER, J G O'GRADY, R anal, 16 anorectal, 22 rectal). They were KEAYS, ROGER WILLIAMS (Liver Unit, King's unrelated to age, sex, or Child's grading. Down-regulation of the hepatic steroid 16a College Hospital and School of Medicine ARVs coexisted with haemorrhoids in 30% hydroxylase, cytochrome P450 UT-A in and Dentistry, London) Mortality in grade 3 of all patients, but were present without male rats with portal bypass or 4 paracetamol induced haemorrhoids in 14%; 33% had haemorr- http://gut.bmj.com/ (P-ALF) remains high (48%), despite hoids alone, while 23% had neither. In E CANTRILL, M MURRAY, I MEHTA, G C FARRELL improved intensive care. Ethical reserva- those patients without oesophageal varices, (Liver Research Group, Sydney University tions have discouraged liver transplanta- ARVs were present in 20%, in patients with and Westmead Hospital, Westmead, NSW tion, in such cases, although it is of proven non-bleeding OVs, 37%, and this increased 2145, Australia) Hepatic microsomal value in viral ALF (71% survival in 33 to 63% in patients with bleeding OVs. Of steroid hydroxylase activities were deter- patients). Peak prothrombin time (PT) those with ARVs and OVs (n=40), mined in control and portal vein ligated >180 and acidosis on admission have been previous oesophageal sclerotherapy had (PVL) male rat liver to test the hypothesis shown to identify patients with P-ALF who been performed in 45%. ARVs become on September 24, 2021 by guest. Protected copyright. that oestradiol (E2) accumulation after are at particular risk; those with acidosis are commoner as complications of portal hyper- portal bypass is related to altered regulation poor candidates for transplantation because tension develop. They do not indicate of sex-dependent cytochrome P-450 (P-450) of their rapid deterioration. To investigate severity of liver disease and their presence is isozymes (JCI 1988; 81: 221). With andro- whether serial estimation of PT comple- not caused by previous oesophageal sclero- stenedione as substrate, total hydroxylation mented peak PT in identification of high- therapy. The natural history, however, of androstenedione (AD) was reduced in risk groups, 100 consecutive patients with remains unknown and merits prospective PVL liver. This was due to reduction of P-ALF were studied retrospectively. The longitudinal study. 16ct hydroxylation (to 55% of control, association between peak PT and mortality p<0-05); 7ct hydroxylation (catalysed by was confirmed (PT >180, 95% mortality; P-450 UT-F), 6p) hydroxylation (P-450 PT 120-179, 45% mortality; PT 90-119, Bleeding varices in the elderly - well worth PCN-E), 160 hydroxylation (P-450 PB-B), 46% mortality; PT <90, 27% mortality). A treating and total oestrogen formation were rise in PT between days 3 and 4, after unaltered. Despite normal total oestrogen overdose, indicated a poor prognosis, S W HOSKING, N C BIRD, D R TRIGER, A G production from AD, there was a seven fold irrespective of absolute PT (86% mortality JOHNSON (University Surgical and Medical greater accumulation of E2 by hepatic compared to 27% if PT falls, p<0-001). Departments, Royal Hallamshire Hospital, microsomes after portal bypass. Experi- Changes in PT on other days, up to day 7, Sheffield) Bleeding from peptic ulcer carries ments measuring E2 hydroxylation directly were uninformative. An increase beyond a worse prognosis in elderly patients and showed that, after PVL, 16a hydroxylation day 7 was uniformly fatal and indicated this influences management. In contrast, of E2 (to oestriol) was decreased (to 44% of sepsis. These data indicate that the peak PT variceal bleeding in the elderly has been control, p<002); catechol oestrogen >180 or an increase in PT on day 4 from barely studied, leaving clinicians often formation and 17a hydroxylation were not overdose identify, at an early stage, those unsure of appropriate management. Since affected. In male rats, 16ct hydroxylation of patients with a less than 15% chance of 1980 we have admitted 207 patients (146 Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1463

.65 and 61>65 years) with a first variceal epithelium were prominent. Biliary find a bile sequestering substance as an bleed. All patients were managed by sclero- obstruction therefore promotes survival of alternative to cholestyramine, which may therapy, usually within 12 hours of admis- implanted hepatocytes and modulates their have significant side effects, we studied sion. Aetiology of portal hypertension and growth pattern. The relative roles of DEAE-Dextran (a MW 500000 polysacc- Child's grade in those s65 and >65 respec- obstructive jaundice, diminished hepato- haride) in a double blind crossover trial v tively were: alcohol, 47 and 20%; crypto- cyte reserve and portal hypertension in this placebo. Twelve female PBC patients with genic 13 and 34%, miscellaneous 40 and modulation is uncertain but this greatly severe pruritus entered the study. DEAE- 45%; Grade A 34 and 31%, B 31 and 46%, enhanced survival of cells in obstructed Dextran or placebo were given alternatively C 35 and 23%. Although first bleed mor- animals encourages further exploration of for 15 days at a dosage of 1000-2000 mg tality was higher in younger patients (27 v hepatocyte transplantation for the treat- three times daily. Pruritus was assayed by 16%) this was not significant when cor- ment of chronic liver disease. an intensity scale. Total bile salts were rected for Child's grade. During median assayed at the beginning and the end of each follow up of 25 and 15 months respectively, cycle. age corrected (life table) survival was virtu- Primary biliary cirrhosis - its prevalence During placebo no changes in itching ally identical for both groups, being 65% at and variceal haemorrhage were observed. With DEAE-Dextran, five one year and 60% at two years. Of the 66 patients experienced complete disappear- deaths in younger patients, 61% were H L SMART, D BULLIMORE, M S LOSOWSKY, ance of pruritus, two showed a decrease, bleeding related compared with only 32% D R TRIGER (University Departments of and five showed no changes. In the seven of the 38 deaths in the older group. Medicine, Royal Hallamshire Hospital, patients who received placebo first, no Rebleeding occurred less often (p<0-01) in Sheffield and St James's Hospital, Leeds) significant modification of bile salts was younger patients (0.09 v 0-12 per patient Primary biliary cirrhosis (PBC) is observed after placebo, while bile salt levels month). uncommon, shows variable geographical decreased significantly after DEAE- These results indicate that an active prevalence and features infrequently in Dextran (from 29-37 (15-98) to 20-2 (12-78) sclerotherapy programme achieves as good reported series of variceal haemorrhage smol/l, p<0.05). In the five patients who results in the elderly as in the young. Any from either Europe and North America. had DEAE-Dextran first, a slow decrease apparent increased mortality is due to inter- We have examined its occurrence as a cause followed by a rebound after placebo was current disease and not (re) bleeding. of portal hypertension in patients admitted observed. The five patients with no relief Active treatment should not be denied on to two referral centres with bleeding oeso- from itching did not show any decrease in the basis of age alone. phageal varices. Over a seven year period, serum bile acid levels. 162 patients were admitted to the Royal In conclusion, DEAE-Dextran was Hallamshire Hospital Sheffield, and 136 to effective in controlling pruritus in 40% of Enhanced survival of hepatocyte implants in St James's Hospital, Leeds with endo- the patients; the introduction of higher bile-duct obstructed rats scopically proven variceal haemorrhage. dosages should increase its efficacy. http://gut.bmj.com/ Case note review revealed that overall PBC V JAFFE, H DARBY, H J F HODGSON (Depart- was second only to alcoholic cirrhosis as a ments ofSurgery and Medicine, Royal Post- cause of portal hypertension in Leeds (15% Psychometric deficits and MRI brain scan graduate Medical School, Hammersmith and 36% respectively) and Sheffield (15% abnormalities in non-encephalopathic Hospital, Ducane Road, London) In and 39% respectively). This finding could patients with cirrhosis syngeneic animals ectopically implanted not be accounted for by supradistrict refer- hepatocytes survive and proliferate despite rals. Moreover, in women, PBC was the A A DUNK, J MOORE, H DEANS, F SMITH, J

an intact recipient liver. An initial phase of single most important underlying cause of BESSON, T S SINCLAIR, N A G MOWAT, P W on September 24, 2021 by guest. Protected copyright. hepatocyte loss is succeeded by prolifera- variceal haemorrhage in both centres BRUNT (Departments of Medicine, Neuro- tion. In this study we examined the fate of (Leeds 32%; Sheffield 31%). The known psychology, Radiology, Nuclear Medicine implanted hepatocytes in animals with high prevalence of PBC in Sheffield con- and Mental Health, Royal Infirmary, severe hepatic dysfunction. Sixteen August tributes significantly to the incidence of Aberdeen) Latent hepatic encephalopathy rats were randomised to bile duct ligation variceal haemorrhage. That a similar pro- is not detectable by current bedside tech- and transection or sham surgery and 2 x 106 portion of variceal bleeds in Leeds are to niques. Nineteen cirrhotic patients with no isolated syngeneic hepatocytes implanted due to PBC suggests that there is a similar overt evidence of encephalopathy have in the spleen 24 hours later. They were prevalence of advanced PBC in the nearby undergone psychometric testing and killed after six weeks, and ligated animals Yorkshire region. The geographical varia- magnetic resonance imaging (MRI) of the had massive bile duct dilatation, compress- tion in the prevalence of PBC would appear brain, in order to determine the frequency ing adjacent liver, and portal venous to be related to the diagnosis of cases before of latent encephalopathy in the 'healthy' collaterals. In eight animals studied by the onset of significant portal hypertension. cirrlhotic population and whether this dis- quantitative splenic histology, there was a order is associated with measurable changes striking increase in cells counted (hepato- in cerebral morphology. Most patients were cytes per 15 random sections; bile duct Diethylaminoethyldextran (DEAE-Dextran) Pugh grade A (n=17), 17 had varices, and ligated, mean 8752+2507 cf sham operated, for itching in primary biliary cirrhosis: a three had previously been encephalopathic. 856+235: p<0.05). Histological assessment double blind trial All alcoholics (n= 10) were abstinent. showed a marked difference in architecture Compared with matched controls with in the areas of hepatocyte colonisation. In A FLOREANI, M CHIARAMONTE, M ZAGOLIN, normal liver function, visual memory and obstructed animals, in addition to cords or R NACCARATO (Department of Gastro- reaction times to light sound and choice markedly polyploid hepatocytes, well- enterology, Institute of Internal Medicine stimuli were all significantly impaired in formed ductules with a characteristic biliary University ofPadova, Italy) In an attempt to cirrhotics, irrespective of aetiology. Sixteen Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1464 The British Society ofGastroenterology of 19 cirrhotics failed two or more of the D H TAYLOR, D L MORRIS (Department of Thirteen patients subsequently underwent seven performance based psychometric Surgery, University Hospital, Nottingham) laparotomy. After reinjection of "'indium tests, compared with 0/19 in the control E multilocularis (alveolar hydatid disease) oxine labelled autologous leucocytes, group, and by the criteria of Schomerus et al remains an almost invariably fatal disease. gamma camera images were accumulated at most cirrhotics would be considered unfit to This is the first comparison of mebendazole approximately four, 24, and 48 hours. drive. Several statistically significant (MEB), albendazole (ALB), and prazi- Images were reviewed to assess: (i) The morphological differences between the quantel (PRAZI) against E multilocularis relationship between the extent of active brains of cirrhotics and controls were found infections in vivo. Fifty infected gerbils disease shown by "'indium leucocyte scinti- on MRI. These changes, indicating cerebral (three months post inoculation) entered, 10 graphy and that shown on barium studies. atrophy, were more apparent in alcoholic were killed to assess parasite weight at week (ii) The presence of intra-abdominal than in non-alcoholic cirrhotics. The degree 0, 10 controls (CONT), 10 MEB 50 mg/kg/ abscesses. of association between psychometric day, 10 ALB 50 mglkg/day, and 10 PRAZI "'Indium leucocyte scintigraphy invari- performance and changes in cerebral 500 mg/kg/day gavage for 25 wks. Animals ably demonstrated the presence of active morphology was poor, suggesting that weighed weekly. In week 25 surviving bowel disease, but underestimated its latent encephalopathy is likely to be a animals underwent necropsy, parasite extent in two patients and overestimated it . material removed and weighed, proto- in three. It correctly identified and localised scolex viability assessed. Cyst weight com- each of six confirmed intra-abdominal pared with week 0 material. CONT and abscesses; computed tomography identified Does HIV infection affect loss of HBeAg PRAZI had more material (p<0.01), MEB five. There were no false positive results. among homosexual men with chronic and ALB not significantly different. ALB Abscesses were consistently distinguishable hepatitis B? material weighed less than CONT, MEB, from inflamed bowel. and PRAZI (p<0-01, 0-05, and 0-001 "'Indium leucocyte scintigraphy respectively). MEB had less material than accurately differentiates between inflamed R H T LOKE, R DAYTON, J C COLEMAN, K bowel and abscesses in with unre- MACRAE, I M MURRAY-LYON (Departments of PRAZI though not of CONT (p<0.01 and patients Gastroenterology and Virology, Charing 0.1). PRAZI no different to control. In sponsive active Crohn's disease, contribut- Cross Hospital, London) Our aim was to mean weight gain of the entire animal ing significantly to the management of these see if HIV infection alters the natural during the period week 10-25, ALB was patients. history of chronic hepatitis B as reflected by less than CONT, MEB, and PRAZI loss of HBeAg. (p

positive greater than six months), followed http://gut.bmj.com/ up at three to six monthly intervals for a 67%, ALB 25%, and PRAZI <2%. mucosa median of 53-5 months (range 5-174). Praziquantel is able to kill protoscoleces Prospective and retrospective testing of of E multilocularis in situ, but not inhibit Y R MAHIDA, K WU, D P JEWELL (Gastro- HBsAg, HBeAg, anti-HBe, anti-HBs, and growth of cysts. Albendazole is better than enterology Unit, Radcliffe Infirmary, anti-HIV were performed using commerci- mebendazole or praziquantel in preventing Oxford) Interkleukin 1 mediates a wide ally available kits. Date of entry taken as six growth and is therefore the drug of choice. variety of biological functions during months from first documented positive test inflammation. Interkleukin 1-r production for HBsAg. Data analysed using SPSS-X by MNC isolated from six normal and 11 programme. IBD colonic mucosal specimens was on September 24, 2021 by guest. Protected copyright. Median age at entry, 31 years (range 17- studied. Mononuclear cells were isolated by IBD 106 64), with anti-HIV positive group younger POSTERS EDTA-collagenase. MNC (in 1 ml) (p=0.001). Forty eight of 109 (44%) were were incubated for 45 hours with or without anti-HIV positive with median duration of "'Indium leucocyte scintigraphy: a simple 10 p.g liopolysaccharide (LPS). Super- 27 months (range 1-77), of which 10 lost test for assessing patients with Crohn's natent was collected and stored at -70°C. the HBeAg compared with 27 of the 61 disease unresponsive to therapy Interleukin 1-r was measured by ELISA anti-HIV negative subjects (p=0.022). and results expressed as median (range) Life-table analysis (Lee-Desu statistic), J G WHEELER, A DUNCAN, N F SLACK, R F ILl-r in pg/ml. however, did not show any statistically HARVEY (Frenchay Hospital, Bristol) There was significantly more ILI-ri pro- significant difference (p=0.1107). Of the Patients with active Crohn's disease duced spontaneously by MNC from active anti-HIV positive subjects, 10 developed respond poorly to treatment with cortico- IBD mucosa [190 (45-700)] compared with the persistent generalised lymphadeno- steroids if they have developed an intra- MNC from normal mucosa [20 (0-165)]. pathy syndrome, four developed the AIDS- abdominal abscess, a complication which Stimulation with LPS significantly related complex and nine developed AIDS. is often difficult to confirm clinically. enhanced IL1-Il production by MNC from HIV does not affect loss of HBeAg in Seventeen patients with Crohn's disease IBD mucosa [250 (70-790)] but not from chronic hepatitis B. unresponsive to therapy underwent normal mucosa [35 (0-145)]. In three colons "'indium leucocyte scintigraphy in an with distal ulcerative colitis, there was more attempt to differentiate between active IL1-ri produced by MNC from inflamed bowel inflammation and abscesses. All mucosa [500 (95-700)] compared with A comparison of albendazole, mebendazole, patients also had barium and/or computed MNC from non-inflamed mucosa [35 (25- and praziquantel in echinococcus multi- tomography studies, mostly within two 120)]. When MNC were depleted of macro- locularis weeks of "'indium leucocyte scintigraphy. phages by panning with monoclonal anti- Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1465 body 3C10, less IL1-, was produced. disease activity in IBD. Compared with pared the mucosa associated (MAF) and Enhanced IL1-13 production by MNC from faecal Indium-111 excretion, they have the faecal flora (FF) in patients with active IBD mucosa is likely to play an important advantage to be less expensive and devoid Crohn's colitis (n=20) and a control group role in mediation of many inflammatory of radiation exposure. (n= 10). responses. The enhanced production is A rectal biopsy and adjacent faecal likely to be due to a recruited population of sample were taken. The biopsy was washed cells as MNC from normal colonic mucosa Intrajejunal prostanoid release in response (x 6) in isotonic diluent and macerated. The appear to be 'desensitised' to the effect of to deoxicolic acid: an adaptative intestinal viable count of MAF and FF was assessed LPS. mechanism to irritative stimuli? by single drop dilution (10-'-10-8) onto selective and non-selective media. Com- F CASELLAS, F GUARNER, R RODRfGUEZ, J R parison of matched mucosal and faecal Faecal lysozyme excretion and alpha-l- MALAGELADA (Digestive System Research samples revealed similar carriage, viable antitrypsin clearance in the assessment of Unit, Hospital General Vall d'Hebron, aerobic and anaerobic counts but a reduc- disease activity in inflammatory bowel Barcelona, Spain) We hypothesised an tion in the number of mucosal aerobic disease adaptative mechanism of the intestinal species (median MAF=2, FF=4, p<0.05) mucosa to luminal irritants and tested it by and total species) p<0.05) in Crohn's colitis G E GRAMA-BOHBOUTH, I BIEMOND, A S PENA, quantifying prostanoid release in response and controls. There was no significant I T WETERMAN, H W VERSPAGET, J BROUWER, to deoxycholic acid (DCA) perfusion in difference in the mucosal or faecal species C B H W LAMERS (Department of Gastro- healthy man. In seven volunteers, we carriage rate or qualitative and quantitative enterology and Hepatology, University placed a triple lumen tube in the jejunum. aerobic and anaerobic viable count between Hospital, Leiden and Department of At the angle of Treitz, we infused at 5 ml/ Crohn's colitis and controls (control faeces Immunology, SSDZ Delft, The Nether- min an isosmotic solution of mannitol 180 2.78 (1.16-7-09); colitis faeces 2.38 (1.36_ lands) We have investigated the value of mM, xylose 100 mM, and PEG4000 2 g/l, 1.1'°) NS. Control mucosa 1.38 (15-3.39); faecal lysozyme excretion and alpha-i- with or without DCA 2.5 mM. This concen- colitis mucosa 2' (3-95-2-69). antitrypsin (a,-AT) clearance in the assess- tration of DCA is similar to that found This study suggests that mucosa associ- ment of inflammatory bowel disease (IBD) postprandially in man. Through the aspira- ated flora represents an independent eco- using the results of faecal Indium-111 tion port (60 cm distally, with air-vent) we system rather than simple contamination excretion as golden standard of gut inflam- collected luminal contents continuously by from adjacent faeces. This study does not mation. Sixty patients with IBD (37 women, siphonage, pooled it at 10 min intervals and support the hypothesis of an abnormal 23 men) were studied. Thirty-three had measured PEG (by turbidometry), colonic flora in active Crohn's colitis. Crohn's disease (CD) of the small bowel 6ketoPGF1,, TXB2, and PGE2 by specific and 27 had IBD with colonic localisation. RIA's. In each volunteer we randomly

Patients were divided into mild, moderate perfused solution with or without DCA for Candidacidal activity of Crohn's disease http://gut.bmj.com/ and severe according to their disease 70 min each (30 min equilibration, 40 min neutrophils activity. Ten patients without intestinal test) with 30 min rest period in between. inflammation were used as a control group. During perfusion without DCA appreci- F T CURRAN, D J YOUNGS, R N ALLAN, M R B The mean faecal lysozyme excretion was able quantities of all three prostanoids were KEIGHLEY (The General Hospital, Birming- significantly higher (p<0-001) in patients constantly released into the lumen. With ham) We have investigated the ability of with colonic (18.4 mg/24 h) and small bowel' DCA perfusion, PGE2 release increased Crohn's disease neutrophils to kill Candida disease (1.3 mg/24 h) than in the control markedly and steadily over time (p<005), albicans. Neurophils were isolated from the group (0-28 mg/24 h). However, after while changes in TXB2 or 6ketoPGFIa were peripheral blood of 20 patients with Crohn's on September 24, 2021 by guest. Protected copyright. division for disease activity only the patients not significant. With DCA, intestinal net disease and 15 healthy volunteers and with moderate and severe colonic disease flow almost doubled from 2-54 mllmin suspended in phosphate buffered saline at had significantly increased lysozyme (without DCA) to 4-58 mllmin, p<0-05 5 x 106 cells/ml. Candida albicans were excretion when compared with controls 6ketoPGFI,, TBX2, and PGE2 are grown to a stationary phase in broth culture (p<0.01). Only colonic disease showed a normally released into the intestinal fluid. and suspended in phosphate-buffered saline significant correlation with the 24 h faecal Intestinal PGE2 release increases markedly at 107 organisms/ml. Neutrophils and Indium-111 excretion (r=0.58, p<0-001). in response to low concentration of DCA as candida were then incubated together at The mean al-AT clearance was significantly fluid secretion is induced. These results 37°C in a shaking water bath in the presence (p

A1466 The British Society ofGastroenterology presence of normal serum. Neutrophils Seventeen patients improved clinically; tion, and in patients with active proctitis, from patients with Crohn's disease have an Harvey and Bradshaw decreasing from 8 (1) and may be a useful index in monitoring impaired ability to kill this granuloma form- (mean (SE)) to 3 (1) (p<0.05). This was inflammatory bowel disease. ing organism. It is not the result of serum matched by a significant decrease in the inhibitors. faecal ...Indium excretion, 11.4 (1.8)% to 2-2 (0.7)% (p<0.001, N<1.0%) of these The next operation for Crohn's disease will two had low initial excretion values (1.2 and not be needed sooner if strictureplasty is High dose methylprednisolone in the treat- 1-6% respectively) both of whom required used rather than resection ment of active ulcerative colitis surgery fox strictures. One patient, who improved clinically, had significant post- J SAYFAN, J ALEXANDER-WILLIAMS, A ALLAN, A IRELAND, W ROSENBERG, D P JEWELL treatment inflammatory activity (faecal H ANDREWS (The General Hospital, (Gastroenterology Unit, John Radcliffe lllIndium 26-0% and 11.4% pre- and post- Birmingham) Crohn's disease is a chronic Hospital, Oxford) Pulsed high dose methyl-. treatment) relapsed within a month of stop- disease characterised by frequent exacerba- prednisolone therapy is effective in various ping the treatment. One patient did not tions and often complicated by stenosis and immunologically mediated diseases. As improve on Vivonex and this was reflected characterised by the need for repeated there has been no recent improvement in by persistently raised faecal "'lIndium operations. We have used strictureplasty the standard treatment of severe ulcerative excretion values (13.3% and 19.0% pre-/ for Crohn's disease strictures since 1981. It colitis (UC), a pilot study was set up to post-treatment). has been shown to be feasible, safe and examine the role of high dose methyl- (1) These studies confirm that clinical suitable for multiple strictures but the long- prednisolone in this group of patients. improvement in Crohn's Disease after term results await evaluation. Therefore, Twenty consecutive patients with severe elemental diet is associated with reduced we have compared the disease free interval active UC were entered. There were nine inflammatory activity. (2) Persistently high between either resection of strictureplasty men and 11 women. Severe disease was post-treatment "'Indium excretion values and the need for another operation for a defined as eight or more stools/day with predicted an early relapse. (3) The use of lesion (usually stenotic) at the site of the blood and mucus, plus evidence of systemic "'Indium leucocytes may help in determin- original strictureplasty or anastomosis. upset. Five patients had total UC, 10 left ing the potential reversibility of radiological In 82 patients, having 130 stricture- sided and five proctitis. After baseline strictures. plasties and 221 resections these criteria measurements, all patients were placed nil were met; 41 having resection with mean by mouth for five days. One gram of methyl- follow up of 17.4 years and 41 having a prednisolone was given daily iv for the first Rectal mucosal blood flow is increased in combination of resection and strictureplasty three days, followed by 100 mg hydrocorti- proctitis or strictureplasty alone, with mean follow sone six hourly for days 4 and 5 of the up of 15.2 years. regime. All patients received a 100 mg G L LAMONT, J D HARRISON, D L MORRIS After resection the mean surgery free http://gut.bmj.com/ hydrocortisone rectal drip twice daily. (Department of Surgery, University interval was significantly longer (7.9 years) Eight of 20 patients failed to respond to iv Hospital, Nottingham) Rectal mucosal than after strictureplasty (2.9 years). This steroids and underwent surgery. The blood flow has been measured in a group of trend was confirmed by an actuarial cumula- remainder settled well on treatment. The normal patients (n= 12) and compared with tive curve of the re-operation rate. surgery group tended to be younger, male, a group with active proctitis (n= 18) to The groups did not have similar disease and with more extensive disease. The assess differences between the groups. distribution or operation indications so con- surgical rate in this unit has been constant at Additionally, the effect of enema adminis- clusions must be guarded. 20-25% during the last 15 years. Hence, the tration on rectal mucosal blood flow has We conclude that, for an intestinal on September 24, 2021 by guest. Protected copyright. surgical rate of 40% was unexpected and been measured in some normal patients stenosis, when the operative choice is has not encouraged a controlled trial to be (n=23). Statistical comparison was made between resection or strictureplasty a set up. using the Mann-Whitney U test. new stricture is likely not to necessitate re- Mucosal blood flow was measured in 53 operation much sooner if strictureplasty is patients before sigmoidoscopy at 10 cm chosen. Elemental diet reduces intestinal inflamma- from the anal margin on the posterior wall tion in Crohn's disease of the rectum. Measurements were made using a 'Laserflo' laser Doppler probe (TSI I BJARNASON, K TEAHON, G ZANELLI, P Inc) interfaced to a BBC microcomputer to SMETHURST, A J LEVI (MRC Clinical Research give a continuous reading. SMALL INTESTINE POSTERS Centre, Watford Road, Harrow, Middlesex) The mean blood flow in mls/100 g tissue/ Elemental diet (Vivonex) is an effective min, was significantly higher in active proc- Delayed stomach to caecum transit time in form of treatment for acute Crohn's titis (Blood flow, median (range): 39.04 the diabetic rat: possible role of hyper- disease. We studied 18 consecutive (14.2-93.3)) than in patients with no rectal glucagonaemia hospitalised patients with acute Crohn's pathology (17.2 (10.7-31.2); p<002). disease, before and after four to six week Patients who had received an enema before J CHESTA, E S DEBNAM, S K S SRAI, 0 EPSiEKIN treatment with Vivonex, with "'lIndium sigmoidoscopy also showed a significant (Departments of Medicine and Physiology, leucocytes, including a four day faecal increase in blood flow when compared with Royal Free Hospital, London) Disturbances collection which provides an objective those without enema preparation (34.4 in gastrointestinal motility in diabetes index of intestinal inflammation, to assess (13.3-70.1) v 17-2 (10.7-31.2); p=0.02). mellitus (DM) are usually ascribed to auto- whether clinical relapse is associated with Rectal mucosal blood flow has been nomic neuropathy. Because DM is associ- reduced inflammatory activity. shown to be increased after bowel prepara- ated with increased secretion of pancreatic Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1467 glucagon, we have investigated the possible sensitises the electrogenic component of for 10 weeks. Measurement of eicosanoids involvement of glucagon on the stomach to duodenal secretion to secretagogues. in the mucosal incubates was by radio- caecum transit time (SCTT) during the immunoassay. After six weeks on the progression of experimental diabetes in the deficient diet gastric prostaglandin E2 pro- rat. Adult Sprague-Dawley rats were Hypersecretion induced by staphylococcus duction fell from a mean of 9-24±2-5 ng/mg injected with streptozotocin (60 mg/kg iv) aureus enterotoxin B in the rat intestine protein to 1-14±0-42 ng/mg protein, gastric which induced glycosuria after two days. thromboxane A2 from 3-71±1-27 ng/mg to Stomach to caecum transit time was A YOUNG, HELEN C NZEGWU, R J LEVIN 0-37±0-13 ng/mg and gastric prostacyclin measured using the non-invasive breath (Department of Biomedical Science, The from29-03±9-60 ng/mg to 3.02±0-83 ng/mg. hydrogen technique. Diabetic rats were University, Sheffield) A major cause of Similar changes occurred in the duodenal studied one, two, four, and eight weeks death in human famine or malnutrition is mucosa. Replacing rats on the standard diet after injection and normal SCTT was estab- diarrhoea. Little is known about the effects reversed the fall in eicosanoid synthesis. A lished in age matched controls. A third of bacterial enterotoxins on intestinal secre- low dietary intake of essential fatty acids group of rats received a single (ip) dose of tion in the malnourished or starved state. may explain the reduced capacity of duo- either 50 [sg or 75 [sg pancreatic glucagon We have investigated the action of S aureus denal ulcer patients to synthesis prosta- or its diluent. enterotoxin B (ET-B, Sigma) on electro- glandins. In diabetic rats, SCTT was prolonged by genic secretion in the rat proximal duo- 46% at one week, 61% at two weeks, 45% denum (D), jejunum (J), (I), most at four weeks, and 64% at eight weeks. At proximal colon (MPC), midcolon (MC), Breath hydrogen testing: an indicator of all time points studied SCTT was signific- and distal colon (DC) removed from fed small bowel overgrowth following ileoanal antly prolonged in comparison with controls controls and 72 h starved rats. Electrogenic pouch formation (p<0.01). In normal rats, glucagon injec- ion secretion was monitored in vitro as the tion was associated with delayed SCTT by short circuit current (Isc, cm`2 serosal area) W KMIOT, J D O'BRIEN, M R B KEIGHLEY (The 25% (50 ptg) and 32% (75 itg) in compari- measuring maximal changes above basal General Hospital, Birmingham) The son with diluent (p<0.05). Autonomic level (AIsc) in response to mucosal ET-B absolute number of bacteria per gram of neuropathy is unlikely to account for challenge. At 5 Fg/ml, ET-B had no effect ileal chyme and the anaerobic: aerobic ratio delayed SCTiT in early stages of diabetes in on Isc but significant increases were seen increases after ileal reservoir construction. the rat and it is possible that hyperglucago- with 10 [tg/ml. In controls, the AIsc never The production of hydrogen by anaerobic naemia may be involved. exceeded 5 [tA.cm-2 but in the starved fermentation is a recognised measure of group the D, J, I, and MC all gave responses small intestinal bacterial overgrowth. above 10 iA.cm-2 significantly greater than After restorative proctocolectomy 30 the fed controls (D, J, and I, p<0-001; MC, patients performed a series of breath hydro-

Proximal duodenal secretion in the acutely p<0.05). The MPC and DC had similar gen estimations at five minute intervals for http://gut.bmj.com/ undernourished rat responses in fed and starved groups (both, one hour. A further 30 age/sex matched p>0-05). The intestinal hypersensitivity to a controls were also tested. All subjects M M C PEREIRA, A YOUNG, R J LEVIN (Depart- bacterial toxin may represent an important remained fasted for a minimum of 20 hours. ment ofBiomedical Science, The University, factor in the aetiology of the diarrhoea of Patients with ileal reservoirs had a higher Sheffield) After starvation for 72 h the malnutrition or famine. mean fasted breath hydrogen value than proximal duodenum (D) becomes hyper- control subjects (16-4 v 5-7 parts per million sensitive to secretagogues both in vivo and (ppm), p<0.05). Six pouch patients did not in vitro, resulting in increased electrogenic Diet deficient in linoleic acid reduces gastric exhibit a breath hydrogen rise either on on September 24, 2021 by guest. Protected copyright. HCO3- and Cl- secretion. The effect of and duodenal mucosal eicosanoid synthesis repeated tests or on instillation of isotonic acute dietary restriction (8 g/d for nine days, in the rat glucose directly into the pouch. The remain- 33% of normal intake) on secretion in the D ing 24 pouch patients exhibited rises of at was investigated. Electrogenic ion secretion P KEATING, I TAYLOR (University Surgical least 20 ppM. All patients with a fasting across sheets of D removed from anaesthe- Unit, Level F, Centre Block, Southampton breath hydrogen level of >10 ppM had tised rats and stripped of external muscle General Hospital, Tremona Road, South- anaerobic bacterial pouch overgrowth was monitored as the short circuit current ampton) Patients with duodenal ulcer have (>10' cfu/g), compared with none of the (Isc). Both basal Isc and maximal increases a reduced ability to synthesise gastric and remainder (p<0-05). There was no relation- above basal level (AIsc) were measured. duodenal mucosal prostaglandins com- ship between ileal overgrowth and the fre- Secretagogues used were dibutyryl cAMP pared to non-ulcer control patients. The quency of defecation. This study confirms (cAMP, 1 mM); 5-hydroxytryptamine aim of this study is to investigate the effect that fasting non-invasive breath hydrogen (5-HT, 50 sM); acetylcholine (Ach, of an essential fatty acid deficient diet on sampling acts as a sensitive indicator of ileal 1 mM); prostaglandin E2 (PGE2, 28 tiM) mucosal eicosanoid synthesis. bacterial overgrowth after pouch forma- and forskolin (F, 5 FM). No differences in Male Wistar rats were raised on a stand- tion. basal Isc between fed controls and the ard diet containing 0-56% of linoleic acid acutely undernourished (AU) animals were and 0-5% of saturated . The rats were seen, but all of the secretagogues induced a then fed an essential fatty acid deficient diet Efamol is trophic to the rat small intestinal significantly greater response in the AU containing 10% hydrogenated coconut oil mucosa group (cAMP +57%, p<0-05; 5-HT and no linoleic acid for six weeks and +88%, p

A1468 The British Society ofGastroenterology

London and Department ofEndocrinology, In contrast, the mean intraepithelial Effect of age on small bowel adaptation and Royal Postgraduate Medical School, lymphocytes number was higher in the pre- growth after proximal enterectomy Hammersmith Hospital, London) To clarify treatment group (23.5) than the post- the roles of individual nutrients in control- treatment (10.3) and the control groups G J POSTON, R SAYDJARI, J P LAWRENCE, R W ling small intestinal mucosal cell prolifera- (12.4), (p<0-01, and <0.001 respectively). ALEXANDER, C M TOWNSEND, J C THOMPSON tion, the effects of the essential fatty These changes could be due to bacterial (INTRODUCED BY 1 S BENJAMIN) (University of acid-rich oil, Efamol (EFA), on mucosal autigenic stimuli of the small intestinal Texas Medical Branch, Galveston, TX, mass, crypt cell production rates (CCPRs) mucosa. The marked and relatively rapid USA) Massive enterectomy may be neces- and plasma enteroglucagon levels were response to therapy demonstrated the sary for Crohn's disease in younger patients compared with glucose (G). reversibility of these changes when bacteria and intestinal infarction in older patients. Two groups of nine female Wistar rats was eliminated or reduced in number. Nothing is known, however, on the effect of (200-250 g) were pair fed Vivonex HN with age on the capacity of the small bowel to 50% calorie substitution by G or EFA for 21 undergo adaptive changes following days. Fasted rats were killed at 25 min massive enterectomy. intervals after intraperitoneal vincristine, Role of superoxide radicals in gut peptide Thirty three month old and 30 24 month keeping plasma for enteroglucagon assay, release from reperfused ischaemic intestine old F344 rats were studied. Half of each and CCPRs determined from arrested group underwent a 60% proximal small metaphases at points 33%, 66%, and 100% L MELEAGROS, R A SPOKES, M A GHATEI, S R bowel resection with end to end anastomo- along the small intestine. The small intesti- BLOOM (Department of Medicine, Royal sis and the other half underwent midsmall nal mucosa was scraped off and weighed. Postgraduate Medical School, Hammer- bowel transection with reanastomosis. Five Despite greater body weight gain with G smith Hospital, Du Cane Road, London) days, 14 days, and 21 days after surgery five than EFA (41.0 g (3.6) v 27-6 g (2.3), means Reperfusion of the ischaemic intestine rats from each age treatment group were (SE), p<0-005), mucosal weight was causes severe vascular and mucosal injury killed. All the ileal mucosa from the increased by EFA (G 16-27 (1.09) v EFA due to the generation of superoxide radicals resected rats and the distal 40% of small 24-19 (1.53), mg/cm p<0-001). CCPR was (SO) and is accompanied by the release of bowel mucosa from the control rats, were greatly increased by EFA at 33% (G 12-60 the powerful vasodilator gut peptides vaso- scraped and analysed for DNA content. (1.26) v EFA 25-20 (3.60) mitoses/h active intestinal polypeptide (VIP) and b- All rats lost weight immediately after p<0-01), and less at 66% (8.94 (2-28) v calcitonin gene related peptide (b-CGRP) surgery but by 21 days both groups of 17-88 (3.48), p=0.06) and 100% (10.62 and the mucosal trophic peptide entero- younger rats achieved similar increases in (2.70) v 12-18 (2-82), NS). Plasma entero- glucagon (EG). Involvement of these body weight from preoperative values. Old glucagon levels were not greatly affected by peptides in reperfusion injury was investi- rats continued to lose weight. Young rats EFA (G 68-44 (4.64) v 82-78 (12.78) pmol/l, gated using allopurinol (Ap) to suppress completed their post resectional small NS). SO and prevent injury. The superior bowel adaptive hyperplasia by 14 days but http://gut.bmj.com/ Compared with glucose, Efamol mesenteric artery (SMA) was occluded for comparable adaptation was not achieved increases mucosal mass and CCPR but not 20 minutes in four groups of anaesthetised until 21 days in the old rats. through enteroglucagon release. Wistar rats (n=6 per group) in two experi- The capacity for bowel mucosal growth ments. The gut was reperfused for 2 in the and adaptation after enterectomy is pre- first (groups A1, B1) or 20 minutes in the served into old age, but is significantly Mucosal changes in elderly patients with second (A2, B2) experiment and arterial delayed and associated with a continuing small bowel bacterial overgrowth blood was collected. Plasma peptides loss of body weight at a time when younger (pmolIl) were measured by radioimmuno- rats are increasing body weight after on September 24, 2021 by guest. Protected copyright. N Y HABOUBI, G S LEE, P ASQUITH (Department assay and results were analysed by surgery. of Geriatric Medicine, Maelor Hospital, ANOVA. Control rats (C1, C2, n=6 in Wrexham and Metabolic Unit, East each) had no SMA occlusion. Groups B1 Birmingham Hospital, Birmingham) Small and B2 received Ap orally (50 mglkg/day) Complement dependent antiepithelial bowel bacterial overgrowth is recognised as for three days and iv (50 mg/kg) before cytotoxic antibodies are present in the serum an important cause of malabsorption in the SMA occlusion. Plasma peptide levels of patients with endemic elderly. (mean (SE)) rose in A1 and A2. VIP was Sixteen elderly patients, four men (mean unaffected by Ap. However, Ap abolished GEORGE KURIAN, D W G BROWN, J R DANIEL, V I age 78 years) with proven small bowel the late rise in b-CGRP: A1 38 (4)*, B1 27 MATHAN (INTRODUCED BY PROFESSOR M S bacterial overgrowth were studied. Endo- (5)*, C1 6 (1) (*p<0.005 v C1); A2 37 (7)*, LOSOWSKY) (Department of Gastro- scopic small bowel mucosal biopsies were B2 18 (4)', C2 15 (4) (*p<0-01 v C2, enterology and The Wellcome Research examined morphometrically before and 'p<0-02 v A2) and reduced both the early Unit, Christian Medical College and four to six months after cyclical courses of and late rise in EG: A1 205 (38)*, B1 104 Hospital, Vellore 632 004, India) Histo- amoxycillin-clavulanic acid. They were (8)+, C1 67 (6); A2 135 (11)*, B2 65 (10) , C2 logical similarities in the small intestinal compared with biopsies from 23 controls, 38 (1) (*p<0-005 v C1 or C2, +p<0-05 v A1 lesion between tropical sprue (TS) and graft nine men (mean age 81 years). Mean villous or A2, C1 or C2). Therefore SO may versus host disease, where antiepithelial height was significantly lower in the pre- mediate their vascular effects by causing antibodies probably have a pathogenic role, treatment group (82-9 rim) than in the post- release of peptides such as b-CGRP, which initiated a search for similar antibodies in treatment (128-3) and control groups is inhibited by allopurinol. Enteroglucagon the sera of patients with endemic tropical (132.9), (p<0.001). Similar significant may be involved in post-injury musocal sprue. Using two colon carcinoma cell lines differences were also found in mean crypt regeneration as its plasma levels relate to (SKCO-1, HT-29) and a control non- and total mucosal heights in these groups. the severity of injury. epithelial rhabdomyosarcoma cell line Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1469

(RD), as target cells in a Cr-51 release Rectal gluten challenge is a simple, safe, proportion of total nitrogen in some amino assay, we found: (a) The sera of 12 of 16 reliable test of gluten sensitivity with high acid solutions used in TPN. Previous data cases of TS (cytolysis range 10% to 70%, sensitivity and specificity. It provides rapid demonstrated that there was no nutritional median 40%) and one of 10 cases of ulcera- confirmation of gluten sensitivity in TCD disadvantage with regard to either nitrogen tive colitis had demonstrable complement and a screening test where jejunal biopsy balance or plasma protein concentrations dependent cytotoxic activity against may be difficult or hazardous. for parenterally fed patients when up to SKCO-1 cells. None of 12 healthy controls 23% of total amino acid N was provided as had such activity. (b) Four samples of glycine. In the present five-day randomised cytotoxic sera from TS also had cytotoxic Evidence against the involvement of adeno- cross-over study, four metabolically stable activity against HT-29 cells but not RD virus 12 in the pathogenesis ofcoeliac disease patients (26-76 years) with gastrointestinal cells, indicating that the cytotoxicity was disease, and requiring TPN, received daily specifically against epithelial cells. (c) Both P D HOWDLE, M E BLAIR ZAJDEL, C J SMART, L K either Vamin 14 or Aminofusin L Forte IgG and IgM fractions, separated on a TREJDOSIEWICZ, G E BLAIR, M S LOSOWSKY supplying 13-5 and 13-7 g N containing 8% sucrose gradient, had similar cytotoxic (Department of Medicine, St James's and 25% of amino acid N as glycine respect- activity. These results suggest that anti- Hospital and Department of Biochemistry, ively in a 2400 kcal lipid/glucose nutritive epithelial cytotoxic antibodies may play a University ofLeeds, Leeds) The description mixture. Twenty-four hour total urinary role in the pathogenesis of the mucosal of an amino acid sequence homology nitrogen was measured continuously for lesion in tropical sprue and may contribute between the ElB-58kDa protein of adeno- nitrogen balance, and on day 5 of each to the persistance of the lesion leading to the virus 12 and gliadin led to the suggestion amino acid infusion, total body protein chronic nature of the disease. that previous infection by this virus and turnover was measured using a primed subsequent exposure to gliadin could constant-infusion of the stable isotope trigger the development of coeliac disease L-(1-'3C) leucine. Results (mean (SE)) for WITHDRAWN-The role of the TNF i in susceptible individuals as a result of the four patients for Vamin and Aminofusin (lymphotoxin) in the aetiology of coeliac immunological crossreactivity. Coeliac respectively were: net total body protein disease patients were subsequently shown to have synthesis rate (mg/kg/h) -6-1 (6.3) v +1-0 (i) raised titres of neutralising antibodies to (5-8); nitrogen balance (last three days and the whole virus and (ii) a cell mediated corrected for blood urea nitrogen) (g N/d) A new diagnostic test of gluten sensitivity: a immune reaction to a synthetic peptide +0-1 (1.3) v 1-7 (1.2). These results provide prospective study of rectal gluten challenge containing the sequence homology. We further evidence to indicate that there is no sought to measure specific antibodies to the significant nutritional disadvantage to using D E LOFT, M N MARSH, P T CROWE (Hope E1B-58kDa protein in coeliac patients and amino acid solutions for TPN that contain Hospital (University of Manchester School normal subjects. high concentrations of glycine. ofMedicine), Eccles Old Road, Salford) We Sera were obtained from seven untreated http://gut.bmj.com/ previously showed (Gut 1987; 28: A1392) and 16 treated adult coeliac patients and 10 that instillation of Frazer fraction III (FF3) normal subjects. They were analysed by increases rectal crypt epithelial lympho- radioimmunoprecipitation using metabolic- Colonic inflow and small bowel motility cytes (CEL) of treated coeliac patients ally labelled adenovirus 12-transformed rat during intraduodenal enteral nutrition (TCD) six hour post-challenge. Since these cells (which express the E1B-58kDa data indicated that a 10% increase in CEL protein), followed by separation on poly- A H RAIMUNDO, T ROGERS, G GRIMBLE, E would have a predictive value of 100%, we acrylamide gels. None of the sera had CAHILL, D B A SILK (Department of Gastro- evaluated this index prospectively in screen- evidence of antibodies to the E1B-58kDa enterology and Nutrition, Central Middlesex on September 24, 2021 by guest. Protected copyright. ing for untreated coeliac disease (UCD) and protein. Eight of 23 coeliac sera had, how- Hospital, London) Diarrhoea occurs in up as a confirmatory test for TCD. ever, raised titres of antigliadin antibodies, to 20% of patients receiving enteral nutri- Forty three subjects referred consecu- of which only one had a raised titre to a tion, but the pathogenesis is not clear. The tively for jejunal biopsy were.studied. On homologous synthetic peptide of gliadin aim of this study was to measure the effect the same day as jejunal biopsy, a rectal and the E1B-58kDa protein. These data of enteral nutrition on colonic inflow of fluid biopsy was taken before and six hour post- suggest that coeliac patients show little and small bowel motility in seven normal challenge with 2 g FF3 instilled rectally. evidence of humoral immunity to the subjects (mean age 22 yr, 21-25) during Total CEL overlying 104 [tm2 muscularis specific adenovirus 12 E1B-58kDa protein constant intraduodenal infusion of an were enumerated by computerised image- implicated in the aetiology of coeliac energy dense polymeric diet. Using an oro- analysis. disease. caecal 11-lumen tube, 3H-PEG was infused There were 21 non-CD, 13 TCD and nine at 1 mllmin into a 20 cm segment terminal UCD established by the 'gold standard' ileum just proximal to the caecum. After a jejunal biopsy criteria. There was no differ- Does glycine content affect the efficacy of steady state, flows were determined at 30 ence in the pre-challenge CEL (means amino acid solutions in TPN? min intervals for four hours before and after (SE): non-CD 46 (3); TCD 41-1 (5.6); UCD continuous intraduodenal infusion (2-8 ml/ 52 (7)). Non-CD did not respond to FF3 (% R G P REES, JJ PAYNE-JAMES, G K GRIMBLE, D min) of the enteral diet (7.8 gN/l, 1500 change -9.4 (3)). CD responded to FF3 HALLIDAY, D B A SILK (Department ofGastro- kcal/l). Small bowel motility was recorded (% change TCD 127 (28) p<0-0005; UCD enterology and Nutrition, Central Middlesex proximally at six sites (30 cm apart), span- 29 (10) p<0.005). The specificity=90%. Hospital, London and Clinical Research ning 150 cm of tube. Mean terminal ileal Sensitive TCD=92%; UCD=88%. CD nor Centre, Harrow) Although the value of flow rates increased significantly (p<0.001) control subjects responded to lacto- glycine nitrogen for protein synthesis is during the diet infusion (20.4 ml/30 (3.8) globulin. disputed, it still represents a significant mean (SE) v 100-7 (7.9)). In the fasting Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1470 The British Society ofGastroenterology period phase III migrating motor complexes Postoperative fatigue - even more real than model (HYPO-ORS +105-1±4-1 ul/min/g; (MMC's) occurred predominantly in the apparent BNF-ORS +2-2±6-9; WHO-ORS +37-8 proximal small bowel. Total number of ±7.7) and rat RV model (HYPO-ORS MMC's were significantly reduced during S E STOCK, M B CLAGUE, I D A JOHNSTON +68-7±1 24; BNF-ORS -38-2±8-0; diet infusion (5 (1-8) v 1.6 (0.2)). Post- (Departments of Surgery, University of WHO-ORS +5.7±4.9). Similar profiles prandial colonic inflow from these data is Newcastle upon Tyne and Newcastle General were found in normal rat and human small equivalent to 4-8 1/24 h which is less than the Hospital) Postoperative fatigue is a well intestine. HYPO-ORS promoted approx- total absorptive capacity of the normal recognised but poorly understood pheno- imately two-fold greater water absorption human colon. These data show intraduo- menon. Ambulatory monitoring of posture in normal rat small intestine than BNF-ORS denal infusion of energy dense diets convert and mobility, using skin sensors and record- or WHO-ORS. the small intestinal motility from fasting to ing of signals on magnetic tape, was carried These findings confirm parallelism fed pattern and the rate of colonic inflow out over 24 hour periods on 80 patients in between human and rat small intestine and does not exceed the normal absorptive their homes before and after abdominal suggest that (1) normal and 'diseased' capacity of the colon. surgery. Fatigue was also assessed subject- intestinal model systems are useful in ively by patients. screening new ORS and (2) that water Patients spent more time lying at 2 (11.56 absorption is improved from hypotonic (2.70) h; p<0-01; mean (SD)) and four ORS. These studies provide the rationale Effect of prefeeding lipid on energy intake weeks (10-83 (2.50) h; p<0-01) than pre- for clinical trials of HYPO-ORS in man. from a meal operatively (9.57 (2.01) h), taking less steps at two (5331 (8121); p<0.01), four (7872 C P SEPPLE, N W READ (Sub-dept Human (6984); p<0.01), and six weeks (9278 Practical aspects of home enteral nutrition Gastrointestinal Physiolgy and Nutrition, (6999); p

The British Society ofGastroenterology A1471 found an improvement or stabilisation in enzyme, red cell glutathione (RCG) per- There is no difference in intraepithelial their life style. oxidase are not widely available. We have lymphocyte counts. used M-mode echocardiography (Hewlett These findings show there is a widespread Packard) to assess cardiac muscle function. enteropathy in IgAN and this may be of Total parenteral nutrition: a metabolic In 32 patients (16 men, on HPN 0-5-8 aetiological significance. study yrs) the mean Se was 0-69 jsmol/1 (95% confidence limits 0-6 to 0-78) and RCG 11-4 E PULLICINO, M ELIA (INTRODUCED BY G U/g Hb (10-12-8). Mean percentage fract- NEALE) (Department of Gastroenterology ional shortening was 32-6% (30-4-34-8), and Clinical Nutrition, Addenbrooke's and ejection fraction was 60-5% (57.2- OESOPHAGO-GASTRODUODENAL Hospital, Cambridge) The optimal rate of 63.8). There was a significant correlation nutritional rehabilitation with total paren- between Se and fractional shortening per- Standardised method of expression of the teral nutrition is uncertain. We took the centage (r=0-448, p<0.005, Spearman) and normal range of oesophageal body peri- opportunity of making detailed measure- ejection fraction (r=0.448, p<0.005) but stalsis ments of energy expenditure and tissue not red cell glutathione peroxidase with the deposition in a cachetic male patient with two cardiac parameters. Nineteen patients S AITWOOD, T NORRIS, L JENKINSON, C BALL, widespread but inactive Crohns disease. had a low ejection fraction (<64%), 17 of A WATSON (Royal Lancaster Infirmary, The patient (weight 53 kg) was studied these had a low Se (<0-8 smolIl). None of Lancaster) Much controversy surrounds the sequentially as energy intake was increased the remaining 13 had an abnormal ejection diagnosis of oesophageal motility disorders from 10-85 MJ/day to 23-21 MJ/day in three fraction of plasma Se (specificity 87%, arising from a lack of agreed normal values. increments (nitrogen intake 12-2 g/day). sensitivity 100%). Few publications have addressed this issue, Total parenteral nutrition was given 15 h/ Echocardiography is a widely available these being mainly confirned to the distal day for 62 days. Basal metabolic rate and non-invasive test that appears to predict the oesophagus. The present study was under- body composition were measured at the effects of selenium status on cardiac muscle taken to establish a standardised form of beginning and end of the study and resting function. Many patients on home paren- manometric assessment of peristaltic ampli- energy expenditure (REE) on 48 occasions teral nutrition have subnormal cardiac tude based on the study of the whole on and off feed using a computerised venti- performance. oesophagus. lated hood technique. The patient received Thirty asymptomatic volunteers (age 1040 MJ (total) of which about 380 MJ was range 19-74 yrs) underwent standard per- deposited as body tissue (8.5 kg fat; 10-7 kg fusion manometry and peristaltic ampli- fat free mass). Resting energy expenditure Intestinal mucosal enzyme deficiency in IgA tude was measured in each of six segments accounted for a little over half of the energy nephropathy (Berger's disease) in the oesophageal body. To express peri- infused. Each increment in energy intake staltic amplitude we compared means http://gut.bmj.com/ (AEI) produced a progressive increase in FIONA M STEVENS, E LAVELLE, M KEARNS, (standard deviation) with median values REE (AREE); AREE/AEI=0.12-0-26). P F FOOTTRELL, B DUFFY (Departments of and percentiles for swallows within each The respiratory exchange ratio exceeded Medicine and Biochemistry, University patient and for the group as a whole. unity throughout the whole period of high College, Galway, Ireland) An association The optimal method of analysis was the energy intake implying lipogenesis from between coeliac disease (CD) and IgA median value of a series of swallows and the glycogen when not being fed. This study nephropathy (IgAN) is well recognised. A range of normality best expressed as within shows that (1) a cachetic subject can be gluten free diet reduces the level of circulat- the 10th and 90th percentiles in the form of a rapidly repleted using high energy infusions; ing immune complexes even in non-coeliac bar chart which represents a 'motility map' on September 24, 2021 by guest. Protected copyright. (2) net lipogenesis from carbohydrate patients with IgAN, resulting in decreased of the oesophagus. persisted during the off feed period; (3) urinary protein loss and improved renal This method produces a quick and easy increases of REE are largely explicable by function. A study has been undertaken to reference of normality when plotting increases in body mass and the cost of tissue determine the frequency of intestinal patient data. It can be readily applied to deposition. abnormalities in IgAN. computer assisted analysis which eliminates Thirty one unselected patients, with observer variation and enables standardisa- IgAN on renal biopsy, had small intestinal tion of measurement technique. This allows How can selenium deficiency be detected in biopsies performed. No patient had intest- direct comparisons of patient data with patients on home parenteral nutrition? inal symptoms or metabolic deficiencies accepted normal values. suggestive of CD. Intestinal biopsies were J L SHAFFER, H CHAMSI-PASHA, M STOKES, examined histologically and biochemically A SHENKIN, M H IRVING (Departments of (lactase, sucrase, and alkaline phosphatase Oesophageal cancer - an epidemiological Medicine and Surgery, Hope Hospital activity). The enzyme results of biopsies study in Transkei (University of Manchester School of (histologically normal) from 31 age/sex Medicine), Eccles Old Road, Salford) matched symptomatic controls undergoing P M SAGAR, E A BENSON (The General Patients on longterm parenteral nutrition investigation to preclude CD were available Infirmary at Leeds, Great George Street, are at risk from developing skeletal and for comparison. One patient with IgAN had Leeds) Oesophageal cancer (OC) has its cardiac myopathies. Selenium (Se) defici- a flat biopsy compatible with untreated CD. highest incidence in Transkei, a South ency has been implicated. The currently A further 16 IgAN patients (51%) had a African homeland state, where, in certain accepted methods for assessing selenium reduction of at least one mucosal enzyme areas, it is the most common cause of death status, monitoring plasma levels of activity compared with five (16%) controls, in adult men. High cereal intake and soil selenium and the selenium dependent the difference is statistically significant. trace element deficiencies have been impli- Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1472 The British Society ofGastroenterology cated but, of greater aetiological signific- present in oesophageal refluxate, and at pH Between 1976 and 1987 there was a progres- ance, are the smoking and drinking habits. levels which may be ignored by conven- sive decline in the number of GC operations Locally grown tobacco ('Dacca') is highly tional pH monitoring. Such enzymes may performed each year (n=718). However, mutagenic and pipe stem juice ('Injonga') have a role in the aetiology of reflux oeso- the percentage of early gastric carcinoma and home brewed maize beer both have a phagitis. (EGC) (n=24, 17 M/7 F, mean age 68-4 high nitrosamine content. The dietary and (2.4) (SE) increased from 1-6% for the smoking habits of a consecutive series of 17 period 1976-82 to 5-6% for the period patients who presented with OC in a 10 Does the timing ofthe evening meal affect the 1982-87 (p<0-01). This increase was associ- week period to one hospital were recorded pattern of 24 hour intragastric acidity? ated with a prospective study on gastric and compared with a group of 200 control biopsies, started in 1982, to assess the patients who attended the hospital in the S LANZON-MILLER, R E POUNDER, RL McISAAC, incidence and distribution of intestinal same period. Study and control groups were J R WOOD (Academic Department of metaplasia (IM) types and to establish their similar with respect to age, sex, race, geo- Medicine, Royal Free Hospital School of value in the selection, for endoscopic sur- graphical origin and cultural background. Medicine, London and Department of veillence, of patients at high risk of develop- Regional prevalence in one 2000 km2 Gastroenterology, Glaxo Group Research ing cancer. All gastric biopsies were district was investigated in a retrospective Ltd, Greenford, Middlesex) Control of examined by the same histopathologist. study of 234 cases of OC. Patients with OC nocturnal acidity has been shown to be an Extensive IM was present in 20/24 (83%) of had both a significantly higher intake of important factor in duodenal ulcer healing. the cases and it was of incomplete type III beer (p<0-001) and a greater consumption Food not only buffers intragastric acid but it (sulphomucin secretion) in 17/20 (85%). In of tobacco (p<0-01) than the control group. also stimulates acid secretion. The aim of five resected specimens (20-8%) there was There was no correlation between OC pre- the study was to determine the effect of submucosal infiltration and in 4 (16.6%) valence and varying soil trace element varying the time of the evening meal on 24 involvement of lymph nodes. Survival data deficiencies. Beer and tobacco consumption hour intragastric acidity. after surgery were available in all 24 EGC in Transkei have a potent carcinogenic Ten healthy volunteers were each studied patients. Twenty one (81%) patients were effect. on three occasions when dietary and alive, followed for a mean 5 (0.54) yrs environmental conditions were identical (range 1-9) after surgery. Of the three except for the timing of the evening meal - deaths, two were cancer related (both one Tryptic and peptic activity in oesophageal 17 15 h (E=early), 19 15 h (N=normal), or year after surgery) and one was not cancer refluxate 2115 h (L=late). Each of the studies was related. Neither submucosal infiltration nor performed in a predetermined random positive nodes significantly reduced D L STOKER, J G WILLIAMS, L J CHUBB, J A order. Hourly gastric studies aspirates were survival. BILLINGS, D G COLIN-JONES (Royal Naval obtained to measure intragastric acidity. EGC is diagnosed with increasing fre-

Hospital, Haslar, Gosport, Hants and There was no significant difference in the quency and this is associated with closehttp://gut.bmj.com/ Queen Alexandra Hospital, Cosham, Ports- integrated 24 h acidity between the three endoscopic surveillance of patients with mouth) The effects of acid, and bile salts on study days (E= 1044; N=906; L=941 mmoll type III incomplete IM. EGC is associated oesophageal mucosa are well documented. h/l). The early meal resulted in little after- with good prognosis despite submucosal There are, however, no data available on noon acidity (115 mmollhll), however, but invasion and node involvement in some the presence of potentially damaging pro- considerable evening and nocturnal acidity cases. teolytic enzymes in the human oesophagus. (746 mmolIhtl); conversely, a late meal The aim of this study was to measure the resulted in higher acidity in the afternoon

activity oftrypsin and pepsin in oesophageal and early evening (360 mmol/h/l), less noc- on September 24, 2021 by guest. Protected copyright. refluxate. turnal acidity (476 mmollh/l), and a delayed Effect of a defined policy on the outcome of Samples of oesophageal refluxate were nocturnal peak of intragastric acidity. bleeding peptic ulcer disease collected from 42 fasted, symptomatic Altering the time of the evening meal patients, using an endoscopic aspiration causes major changes in the pattern of K E WHEATLEY, P W DYKES, M RB KEIGHLEY technique previously described. The pH of intragastic acidity. Regimens using short (The General Hospital, Birmingham) each sample was measured, and these were acting H2 receptor antagonists may need to Bleeding peptic ulcer disease is a common then centrifuged to remove debris, and take account of the patient's dietary habits, problem, with mortality rates of over frozen at -20°C before assay using standard to provide optimal control of intragastric 10% frequently reported. Mortality has laboratory techniques. In 32 cases (76%) acidity. remained around this level for three there was related, endoscopically proven decades, largely due to increasing age of oesophagitis. Twenty one of 42 samples fell patients. into the pH range 4-7. Tryptic activity was Early gastric carcinoma with particular Since 1984 we have had a stable defined present in 24 (56%) of the samples (median reference to the significance of intestinal policy for the management of patients with 1-5, range 0-1-19-6 IU/I). There was a metaplasia as a marker of increased cancer bleeding peptic ulcers. Patients are admit- positive correlation between increasing risk ted to a centralised unit and managed by a tryptic activity and rising pH (r= +0.60, team comprising physicians, surgeons and p

The British Society ofGastroenterology A1473 patients with bleeding from proven peptic Symptomatology in C pylon-positive and validated using the jack knife technique. ulcers, 60% were over age 60, and 11% over -negative non-ulcer dyspepsia The major discriminant between bacterial 80 years old. Twelve patients died (overall colitis and IBD was the number of crypts/ mortality 4%). No patients died under the B J RATHBONE, J WYAYT, R V HEATLEY (Depart- mm mucosal length, the means being 7-8 in age of 50, one under 60 years, and there- ments of Medicine and Pathology, St bacterial colitis, 4-6 in IBD, and 6-6 in after the mortality rose steadily with age. James's University Hospital, Leeds) The controls. Total cellularity, IgG plasma cells, Sixty eight (22%) patients received emerg- role of C pylori associated chronic gastritis and lamina propria polymorphs were also ency operations with only two postopera- in causing dyspeptic symptoms is at present important discriminants, all being higher in tive deaths. Vagotomy and pyloroplasty unclear. To investigate whether CP-positive IBD. Using crypt counts alone it was poss- was the commonest operation for DU, and dyspeptics differ in their symptom complex ible to correctly classify 86% of patients 22 of 36 patients with GU did not receive a from CP-negatives, 193 consecutive dyspep- having bacterial colitis or IBD. This could gastrectomy. tic non-ulcer patients from general practice be increased to 94% by combining other With our defined policy we have main- were studied by structured history, endo- discriminants. The difference was as tained a low overall and operative mortality scopy and biopsy. Cpylori colonisation was marked in the 18 IBD patients in their first of 4% and 3% respectively. assessed by a modified Giemsa stain on acute attack. The crypt changes are found in antral and body sections. One hundred and Crohn's disease and ulcerative colitis and five patients were CP-positive (mean age seem to be present from the early stages of 48-7 years), 88 were CP-negative (mean age the first attack. Crypt counts can be used Endogenous gastric prostaglandins do not 39.7 years). There was no significant differ- simply in routine practice to improve protect the human gastric mucosa ence in presenting symptoms, nor smoking diagnosis. nor drinking habits between the two groups. H W GRANT, K R PALMER (Gastrointestinal In the CP-positive group, previous episodes Unit, Western General Hospital, Crewe of dyspepsia were more common, together Road, Edinburgh) Polyunsaturated fatty with a past history of previous upper GI Why do patients with ulcerative colitis acids increase gastric prostaglandin secre- investigation. Detailed examination ofother relapse? tion and reduce acid output, suggesting that symptoms demonstrated that only oeso- dietary fat could influence the natural phageal reflux symptoms were significantly S A RILEY, V MANI, M J GOODMAN, L A history of peptic ulcer. In this study the more common in the CP-positive group. TURNBERG (University Department of gastric mucosal properties of linoleic acid There was, however, no significant differ- Medicine, Hope Hospital, Salford and (LA) were measured in normal subjects. ence between endoscopic or histological Leigh Infirmary and Bury General Hospital, Gastric mucus output was measured on two oesophagitis in the positive and negative Manchester) In order to determine the occasions in nine volunteers. The mean groups. factors responsible for ulcerative colitis volume of mucus (the dialysable, com- solid This study confirms the high prevalence relapse we have studied a cohort of 92 http://gut.bmj.com/ ponent of gastric juice), increased from 432 of CP positivity in non-ulcer dyspepsia. The patients (18 to 78 years, 50 men) with (47) mg/hour (SE), when subjects had been data show, however, that non-ulcer dyspep- clinically inactive disease over 48 weeks. taking a normal diet, to 593 (83) mg/hour tic patients do not have sufficiently distinct At 12 weekly intervals patients were (p<0-05) after a 14 day period of supple- symptomatology to separate them clinically asked by means of standardised question- mentation with LA, 3 g daily. from CP-negative dyspeptics. The fre- naires about infections, drug ingestion, Gastrointestinal bleeding was measured quency of reflux symptoms in CP-positive anxiety, depression, stressful life events and in 12 volunteers whose red blood cells were patients is of interest and warrants further diarrhoeal episodes in the four weeks labelled with Cr5'. In a randomised cross- investigation. before attendance. Thirty five patients over study, mean faecal blood loss was 35 (38%) relapsed after a mean interval of 17 on September 24, 2021 by guest. Protected copyright. (5) ml/week whilst taking aspirin 1-2 g weeks (range three to 44 weeks). Relapsers 8 hourly, and 36 (6) ml/week when each and non-relapsers were comparable for age, dose of aspirin was preceeded by 1 g of LA. sex, duration, and extent of disease. 60 ml 80% ethanol was infused endoscopic- A clear seasonal pattern of ulcerative ally onto the gastric antrum of six normal IBD colitis relapse emerged. Only nine patients subjects on two occasions separated by 14 relapsed from February to July whereas 26 days. On one occasion each subject was Predicting infective colitis: a quantitative relapsed from August to January (p<0-005) pretreated with 1 g of LA. Endoscopies and statistical approach to the diagnosis of with a peak incidence in September and over 90 mins showed similar degrees of acute colitis on rectal biopsy October. Upper respiratory tract symptoms ulceration and haemorrhage in both situat- also showed a seasonal pattern but these ions. Mucosal biopsies from the damaged B B SCOTT, A GOODALL, K DREW, D JENKINS peaked in January. area were incubated with H3 thymidine and (Departments of Medicine and Pathology, Of the events that preceded colitis relapse subjected to autoradiography. The % County Hospital, Lincoln) Multiple cell between and within group comparisons nuclei in 'S' phase invariably fell transiently counts and morphometric measurements revealed that infections, antibiotic inges- after ethanol but labelling indices were were made blindly on rectal biopsies from tion, analgesic intake, stressful life events similar whether or not LA had been given. 23 controls, 73 patients with inflammatory and diarrhoeal episodes were no more Although LA increases gastric mucus bowel disease (IBD), and 18 with acute common in the four weeks prior to relapse secretion, it does not protect the stomach bacterial colitis. This provided 31 variables than during remission. Anxiety and depres- against the damaging effects of aspirin or on each biopsy which were subjected to sion ratings were similar in the two groups. ethanol. This questions the 'cytoprotective stepwise discriminant analysis. The diag- We conclude that seasonal factors may be effect of endogenous gastric prostaglandins. nostic value of the variables selected was responsible for ulcerative colitis relapse. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1474 The British Society ofGastroenterology

Antigen presenting activity of mononuclear 10 controls was 0-0 ng/ml (range 0-20), in Eleven years experience of elemental diet in cells (MNC) from normal and inflammatory small bowel CD 168 ng/ml, Crohn's colitis acute Crohn's disease bowel disease (IBD) mucosa 1015 ng/ml, and in active UC 1159 ng/ml. Median stool EPIC levels in active UC and K TEAHON, I BJARNASON, A J LEVI (MRC Y R MAHIDA, K WU, D P JEWELL (Gastro- Crohn's colitis were each significantly Clinical Research Centre, Watford Road, enterology Unit, Radcliffe Infirmary, higher than in small bowel CD (p=0.0014 Harrow, Middlesex) Elemental diet is an Oxford) The capacity of mononuclear cells and 0-0024 respectively). Stool EPIC effective form of treatment for acute (MNC) from normal (7) and IBD (7) measurements in UC correlated signific- Crohn's disease. Previous studies have been colonic mucosa to stimulate purified T cells antly with a numerical activity index (r= too small to assess the overall success rate, in an allogeneic mixed lymphocyte reaction 0-87, p=0.0001), but not with ESR, WBC, predictions of success and the long term was studied as a means of assessing antigen and plasma CRP. Stool EPIC in Crohn's prognosis. We reviewed 107 Crohn's presenting activity. colitis correlated significantly with CDAI patients treated with an elemental diet Mononuclear cells were isolated by (r=0-78, p=0.05), ESR (r=0.74, p=0-05), (Vivonex) at Northwick Park Hospital over EDTA-collagenase and treated with and plasma CRP (r=0.9, p=0.003) but not 11 years. Eighty seven per cent obtained mitomycin C. Purified, resting, allogeneic T with WBC. remission, characteristically within 10 days, cells were obtained from peripheral blood Stool EPIC may better characterise regardless of the site and severity of the MNC by adherence to plastic and nylon inflammation in colitics, when plasma EPIC disease. Thirteen per cent did not improve wool and complement lysis with mono- and CRP levels are not raised. but there were no predictions of a poor clonal antibodies to monocytes, B cells, and response. Follow up of successfully treated HLA-D. The allogeneic T cells were used as patients (M: 45 months) shows that 75% of responders and intestinal MNC as stimulat- patients with diffuse small intestinal ors. Mixed lymphocyte reactions were per- Azathioprine in resistant ulcerative colitis involvement maintained remission and the formed in triplicate and incubated for six 25% who relapsed (DEF: clinical change days. Results are expressed as mean (SD) P N FOSTER, A J LOBO, D A BURKE, D JOHNSTON, resulting in alteration of management) did prolifieration per 100 stimulator cells. A T R AXON (Gastroenterology Unit and so within five months. The more distal the There was greater proliferation induced Department of Surgery, The General disease the greater the relapse rate; 90% of by MNC from IBD mucosa compared with Infirmary, Great George Street, Leeds) The perianal disease or fissures relapse within MNC from normal mucosa (34.8 (17) v 22-8 use of azathioprine in ulcerative colitis is two months. Longterm follow up (>five (3.7)), but this did not reach statistical controversial; our policy is to give azathio- years) of patients treated initially and significance. In three colons with distal prine in difficult cases. We present the temporarily with elemental diet (n= 16), ulcerative colitis, significantly greater pro- details and outcome of 46 patients who steroids (n=12), or surgery (n=31) shows liferation was induced by MNC from received azathioprine for either (i) severe, that 38%, 20%, and 50% respectively main-

inflamed mucosa compared with MNC from resistant disease otherwise requiring tain a remission at five years. http://gut.bmj.com/ non-inflamed mucosa (48-5 (8.2) v 25-8 surgery (28) or (ii) steroid dependence/ (1) Treatment with elemental diet (1.7)). intolerance (18) and who have been achieves a 87% remission rate regardless of Mononuclear cells isolated for active IBD followed up for at least 12 months. On site and severity of disease. (2) The more mucosa have enhanced antigen presenting introduction of azathioprine the disease proximal the disease the greater is the activity, which we have previously shown to extended beyond the splenic flexure in 30 duration of remission. (3) Distal disease and be mediated by cells with characteristics of and was total in 22; in the remainder the fistulae require additional treatment. (4) macrophages. disease was confined to the rectum (three) Elemental diet does not appear to alter the

or left side of the colon (13). Duration of natural history of Crohn's disease. on September 24, 2021 by guest. Protected copyright. treatment ranged from one week to 66 months (median 12 months) and the mean Faecal elastase in inflammatory bowel daily dose was 1-9 (0.3) mg/kg. Of the Conservative protocolectomy - is it an disease patients in group (i), 14 (50%) achieved option in ulcerative colitis? remission, 11 of whom had not relapsed E 0 ADEYEMI, H J F HODGSON (Department of during a median follow-up of 22 months R W TALBOT, J K RITCHIE, J M A NORTHOVER (St Medicine, RPMS, Hammersmith Hospital, (range 12 to 58) and 14 underwent surgery Mark's Hospital, City Road, London) A Du Cane Road, London) Plasma neutrophil one week to 12 months (median five weeks) conservative proctocolectomy (CP) pre- elastase complexed to alpha-1-proteinase after commencing azathioprine. In group serves the anus whilst removing all rectal inhibitor (EPIC), rises in active inflamma- (ii), steroids were withdrawn or reduced mucosa and allows a subsequent restorative tory bowel disease but not always in active in 10 (55%) patients and four patients procedure to be performed should this be ulcerative colitis. required colectomy. Side effects necessitat- indicated. Between 1975-1987, 22 patients We therefore assessed the usefulness of ing withdrawal of azathioprine occurred in underwent CP for ulcerative colitis (n= 18), EPIC levels in fresh stool samples in IBD as 12 patients: haematological (six), gastro- Crohn's disease (n=3), or familial adeno- a specific correlate of inflammation in gut intestinal (four), others (two). Two patients matous polyposis (n= 1). The longterm out- mucosa. Using an ELISA technique, EPIC required a reduced dose of azathioprine come of this operation had been studied. and CRP levels were determined in plasma because of leucopenia. We conclude that Healing was uncomplicated in four patients samples of 80 controls, 14 CD patients, 16 azathioprine is a valuable therapeutic including one after removal of an incon- patients with UC, and EPIC in stool super- option in selected patients with ulcerative tinent ileoanal pouch. A persisting dis- natants. colitis, obviating surgery, and sparing charge from a sinus at the top of the anus Plasma EPIC and CRP were raised in steroids, but regular blood counts are occurred in 18 and nine of these had a 50% of UC patients. Median stool EPIC in essential. chronic abscess cavity. Four of these 18 Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1475 patients healed after a mean of two years Six hour post-prandial pH monitoring; an with antral biopsies. The specimens were but the remainder are still unhealed six adequate test for gastro-oesophageal reflux evaluated by microscopy, culture, and months to 10 years later (median three in childhood urease testing. Serum IgG, IgA, and IgM years). Eight patients have undergone a antibodies to CP were also measured by total of 17 operations including six sphincter J PANAYOTOU, S DEVANE, P J MILLA (Hospital ELISA technique, using a sonicated antigen divisions and two anal excisions. Only one for Sick Children, Great Ormond Street, and the results expressed as optical density patient has healed after sphincter division London) Twenty four hour ambulatory pH measurement. alone. Two patients with a discharging sinus monitoring is the 'gold' standard for detect- Nineteen children showed no histological have had a successful ileal pouch anal ing gastro-oesophageal reflux (GOR) but gastritis nor presence of CP on microscopy, anastomosis. These results compare requires an overnight admission. In child- culture and/or urease test. Thirty two child- unfavourably with the healing of perineal ren there are few studies of abbreviated pH ren showed histological gastritis. All those wound after intersphincter excision of the monitoring suitable for day patient use. As 32 had CP on microscopy. Culture was also rectum at our institution. Conservative in infants GOR is mostly postprandial positive in 29 and urease test was positive in proctocolectomy cannot be recommended abbreviated postprandial pH monitoring 24. The sensitivity, compared to microscopy as a definitive operation for ulcerative may be a suitable test. We investigated 45 of culture and urease testing was 90% and colitis even though it may permit a sub- patients by 24 hour (24) and six hour 74% respectively. The specificity was 100% sequent restorative procedure. postprandial (6PP) ambulatory pH moni- and 100% respectively. The mean IgG, IgA toring using a naso-oesophageal probe with levels in the 19 children with no histologi- its tip 5 cm above the lower oesophageal cal, microbiological and no urease testing sphincter and a Synectics Digitrapper. evidence of CP were 97 and 34 respectively, Faecal challenge as a predictor of the effect Twenty five patients were investigated for and in the 32 patients with histological of restoring intestinal continuity in defunc- vomiting, eight with feeding problems and gastritis and associated CP on microscopy, tioned Crohn's colitis 12 respiratory symptoms. All were endo- culture and/or urease test were 253 and 72 scoped and 10 had oesophagitis. Acid respectively. Both levels were significantly M C WINSLET, M RB KEIGHLEY (The General exposure time was calculated as the propor- higher in the CP positive group (IgG: Hospital, Birmingham) The effect of restor- tion of time with pH below 4. A total acid p<0-001; IgA: p<0-01). No difference was ing intestinal continuity in patients with exposure greater than 7% was found in found for IgM titres (mean value 100 in the defunctioned Crohn's colitis is unpredict- 36/45 on 24 and 33/45 on 6PP with a positive group and 99 in the negative group able. The aim of this study was to assess correlation of r=0-78 between tests. There respectively). whether preoperative faecal challenge of were three false negatives, two with only The serum IgG and IgA assay for CP may the defunctioned colon with ileostomy <10% reflux. On 6PP there was a good correctly identify those children with CP effluent can predict those patients likely to correlation between total time and upright associated gastritis, and can be used to

suffer an early disease relapse. or supine reflux (r=0.75 and 0-72 respect- screen non-invasively children for the con- http://gut.bmj.com/ Nine patients (four men, mean age: 39 ively). Those with oesophagitis had longer dition before endoscopy. years) with Crohn's colitis for restoration acid exposure and as many had upright as of intestinal continuity, had a mean volume supine reflux seven of 10 and nine of 10 were of 120 (60-280) ml ileostomy effluent detected by 24 and 6PP respectively. Those Epigastric impedance (EPI) studies: a clinic- inserted into the efferent limb of their loop with severe reflux; (>20%) five of 36 were ally useful method of measuring gastric ileostomy daily for seven days. detected by both tests but upright five of 36 emptying in children (GE) The median time to defecation was 1 was better than supine three of 36. Four of H L SMITH, G W HOLLINS, S J NEWELL, I W (1-2) day. Four patients developed diarr- six patients with feeding problems refluxed on September 24, 2021 by guest. Protected copyright. hoea (x5-10/day) with systemic symptoms and were predicted by both tests. The BOOTH (Institute of Child Health, University and were considered unsuitable for stoma results indicate that 6PP is as good as 24 at of Birmingham, Francis Road, Edgbaston, closure. Two patients developed mild diarr- predicting severe reflux and an adequate Birmingham and The Department of hoea whilst three were asymptomatic. Five prediction of the degree of acid reflux Medical Physics, Birmingham Maternity patients had intestinal continuity restored demonstrable in a 24 hour period for those Hospital) A non-invasive non-isotopic and all remain in clinical remission at six with moderate reflux. means of measuring GE in children has not months. Changes in serum and mucosal been available until recently. We have indices of disease activity after faecal chal- therefore evaluated the measurement of lenge and restoration of continuity were Non-specific abdominal pain in childhood. GE in children using EPI. Forty five normal similar. Can serology detect those with campylo- subjects (1-18 y, median 12-9 y; 27 men, 18 Faecal challenge produces results similar bacter pylori (CP) associated gastritis? women) and 13 cystic fibrosis patients to restoration of intestinal continuity. It is a (7-18 y, median 14 y; seven men, six useful method of predicting patients likely G ODERDA, D VAIRA, J HOLTON, J DOWSE1T, women) were each studied fasting. Baseline to suffer an early relapse in whom intestinal N ANSALDI (INTRODUCED BY N I MCNEIL) EPI was stable and did not correlate with continuity should be avoided. (Pediatric Gastroenterology Section, age, weight, triceps skinfold thickness University ofTorino, Department ofGastro- (TSF), or body surface area (BSA). enterology and Microbiology, The Middle- Ingestion of orange squash (400 mI/m2 sex Hospital, London) Fifty one consecu- BSA) in 50-100 ml increments, revealed a tive children median age 11 years (range highly significant correlation between 1-18), who presented with recurrent volume ingested and stepwise increases in PAEDIATRICS abdominal pain were investigated for CP impedence (r>0-95, p<0-01). AEPI associated gastritis by upper GI endoscopy showed a close, negative curvi-linear Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1476 The British Society ofGastroenterology relationship with BSA, weight, age, and P B SULLIVAN, M B PHILLIPS, P G LUNN, Giardia trophozoites were identified. Anti- TSF. Mean time to half-emptying (t,,) in G NEALE (University of Cambridge and Giardia antibodies (Igm, IgA, and IgG) normal subjects was 14-5 min (SD 6.6) and Medical Research Council, Dunn Nutrition were sought by ELISA; 16/31 had IgM anti- in CF patients was 16-5 m (SD 6; NS); tv, did Laboratory, Cambridge) Children with Giardia antibody titres >500 and of these not correlate with age or sex. The test was postinfectious chronic diarrhoea may nine were biopsy positive. IgM was found to well tolerated and was capable of: (i) dis- develop milk intolerance and improve on be a better indicator of active infection than criminating between test meals of differing casein hydrolysate feeds. We assessed the either IgA or IgG anti-Giardia antibody. viscosity (±Carobel 1% ), andcaloricdensity value of Pregestimil in treating 28 Gambian Detection by ELISA of Giardia antigen in (+Calogen 2.5%) (ii) identifying an infant children with chronic diarrhoea and severe faeces was not helpful in diagnosis. Thus with post-fundoplication dumping syn- malnutrition. Nineteen marasmic and nine 52% (16/31) of patients with chronic diarr- drome (th four min). marasmic-kwashiorkor subjects aged 6-31 hoea were considered to be infected with months, with a mean weight-for-height of Giardia, either by direct parasite identifica- 67-5% of the NCHS median were allocated tion or positive IgM response. Furthermore Experimental rat rotavirus infection: a new alternately to Pregestimil or the routine serial biopsies and serology were performed animal model for studying efficacy of oral formula of skimmed milk, sugar, and corn and of 16 positive cases nine were found rehydration solutions (ORS) oil (SSO). Progress was assessed by clinical to have evidence of persistent infection appearance, anthropometry, stool fre- with Giardia three weeks later despite A F M SALIM, J A WALKER-SMITH, M J G quency, serum proteins, and amino acids. apparently adequate treatment with metro- FARTHING (Departments ofGastroenterology In addition to oral rehydration fluid taken nidazole. This may relate to the poor nutrit- and Child Health, St Bartholomew's ad libitum, the SSO group took an average ional state of these children and associated Hospital, London) Although oral rehydra- of 111 ml/kg/day and the Pregestimil group impaired secretory immunity. This study tion therapy with glucose electrolyte solu- 122 ml/kg/day of milk. This provided a demonstrates the difficulties associated with tions is of proven efficacy in RV diarrhoea, mean daily intake for SSO of 111 kcal and diagnosis of giardiasis and confirms the the optimal composition of ORS had not 3-1 g protein/kg/day and for Pregestimil of value of specific serum IgM responses in been established. We have developed a 83-0 kcal and 2-3 g protein/lkg/day. After a detecting active infection. model of RV infection using eight day old week on SSO mean albumin rose from 38-41 neonatal rats innoculated orally with rat to 43-19 g/l and mean essential amino acids RV. Rats were anaesthetised and the entire rose from 708 to 1197 [tmolRl. With Risk factors in Gastrointestinal complica- small intestine was perfused with a plasma Pregestimil mean albumin and essential tions in children after orthotopic liver trans- electrolyte solution (PES), (Na 140, K 4, amino acids were virtually unchanged plantation HCO3 40 mmol/l; 300 mOsmlkg), WHO- (34.65 to 35.64 g/l and 679 to 666 [tmol/l ORS (Na 90, K 20, HCO3 30, Glu 111 respectively). There was no apparent differ- D A KELLY, S S KAUFMAN, B SHAW, P WOOD, D J mmol/l; 331 mOsmlkg) and an isotonic ence between the groups in either short or SCRIVNER, M BROWN, J GUEST, D L ANTONSON, http://gut.bmj.com/ experimental (EXP) ORS (Na 60, K 25, longterm resolution of symptoms, relapse J A VANDERHOOF (University of Nebraska citrate 10, Glu 111 mmol/l; 289 mOsmlkg) or weight gain, but in the early weeks, those Medical Center, Omaha, Nebraska, USA) at 18, 24, 48, 72, and 96 h after infection. given Pregistimil showed biochemical Gastrointestinal (GI) complications after Net water secretion occurred with PES at evidence of persisting protein deficiency. orthotopic liver transplantation (OLT) are 18, 24, and 48 h (-20.9±6.8, -21-5±7-1, We conclude from this study that in the common in children at this centre. To -19-1±6+3 ld/min/g dry wt, respectively; rehabilitation of infants from chronic diarr- identify risk factors, all children were nB6). This was reversed to absorption by hoea and severe malnutrition, casein hydro- graded according to nutritional status and both ORS but EXP-ORS produced more lysate made up at the recommended hepatic dysfunction at OLT. From 1985-87, on September 24, 2021 by guest. Protected copyright. water absorption than WHO-ORS at 18,24, dilution offered no advantages over the 53 children were transplanted. Thirty four and 48 h (p<0-01), the most impressive standard milk formula and may have children (64%) developed GI complica- difference being at 48 h (+58 7±5.8 v delayed recovery of protein status. tions. Ninety one per cent had behavioural +8-6±4-6; p<0-001). Following resolution feeding problems. Seventeen of 34 of diarrhoea at 72 h and 96 h net water developed small bowel or colonic perfora- absorption occurred from PES (19.9±5.0) Diagnosis of Giardia infection in the tropics tions. GI bleeding was present in 12/34 and there was no difference in the efficacy of children, 11 of whom had acid-peptic WHO and EXP-ORS. In these studies P B SULLIVAN, G NEALE, A K J GOKA, M J G disease and one died. Infectious colitis sodium movement paralleled water move- FARTHING (Dunn Nutrition Laboratory, developed in 17/34 children and pneumato- ment. This study shows that the rat RV University of Cambridge and Department of sis intestinalis in nine of 34. Twenty two had model closely mimics human RV infection Gastroenterology, St Bartholomew's previous abdominal surgery, 12 of whom and may be used to compare the efficacy of Hospital, London) Infection with Giardia is developed intestinal perforation. Children ORS. Our findings in this model indicate highly prevalent in many underdeveloped with GI complications were more likely to that the isotonic EXP-ORS is more effec- countries, but assessment of its clinical have had previous surgery (67%), be mal- tive in promoting water absorption than the impact has been limited by the unreliability nourished (60%), and to have decompen- WHO-ORS. of diagnostic methods. This was confirmed sated liver disease (69%) than those who when 120 stool samples from 31 mal- did not (52%, 35%, and 37% respectively). nourished Gambian children were There was no significant difference in A comparison of a casein hydrolysate examined microscopically in the routine immunosuppression between the groups. formula with a standard rehabilitation milk MRC laboratory; none were reported posi- Thus, children with decompensated liver in the management ofchronic diarrhoea and tive for Giardia. Twenty five of these disease who are malnourished are at risk of malnutrition in Gambian infants patients underwent jejunal biopsy and in 11 GI complications with substantial morbidity Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1477 but low mortality. The risk of perforation is were prepared with the stomach divided vitamin C secretion in normal subjects, but increased with previous surgery. into extrinsically innervated antral and this is impaired in patients with chronic proximal segments. Access to each segment gastritis. In hypochlorhydric subjects, very was through cannulae. Continuity was re- little of the vitamin C present is 'useful' Does intensive enteral feeding in children established with a gastroenterostomy from ascorbic acid and this suggests that ocida- with advanced cirrhosis cause nitrogen corpus to jejunum. After recovery (four to tion by nitrite has already occurred. Thus intolerance? six weeks) motility patterns from corpus low levels of ascorbic acid in gastric juice and antrum showed periods of activity and may contribute to the increased cancer risk C P J CHARLTON, M A EDWARDS, A BAKER, E quiescence in the fasting state with the in chronic gastritis and hypochlorhydria. BUCHANAN, C HOLDEN, A GREEN, I W BOOTH, characteristics of migrating motor com- M J TARLOW (Liver Unit, Birmingham Child- plexes. Ten cycles were studied in two ren's Hospital, Institute of Child Health, animals with activity occurring in the corpus Somatostatin (SMS 201.995) reduces growth University of Birmingham) We have pre- over a period of 45-7 (3.9) mins (SEM) and of human gastric cancer (MKN45) xeno- viously demonstrated that intensive enteral a quiescent period of 34-2 (3.0) min (SEM) grafts feeding of malnourished children with with a cycle time of 79-9 (5.4) min (SEM). advanced cirrhosis can dramatically The corresponding figures for the second D L MORRIS, S A WATSON, J D HARRISON, improve nutritional status. Concern has dog were 36-2 (4.0), 36-4 (4.3), and 68-8 L DURRANT (Department of Surgery, been expressed, however, about the bio- (3.6) min respectively. Activity recorded in University Hospital, Nottingham) We have chemical effects of increasing the dietary the antrum was similar, but it was phase previously reported that gastrin stimulates protein load by a mean of 33% (range 5%- locked with that of the corpus. A similar in vitro growth of human gastric and 54%). Fasting blood ammonia and quanti- phenomenon could be demonstrated when colorectal cancer cells. MKN45, a human tative aminoacid concentrations were there- activity was induced in the corpus in a phase gastric cancer cell line, maintains this fore measured before and at the end of eight of quiesence. These experiments support response to gastrin in vitro and in vivo. We weeks enteral feeding in 10 children with the view that although the pacemaker have reported that enprostil (a prosta- advanced cirrhosis. Initially ammonia con- potentials may govern the rate and progres- glandin which reduces gastrin release) can centrations were raised (>40 pimolll) in sion of the peristaltic wave, vago-vagal reduce in vivo growth. eight of 10, and rose significantly with reflexes originating in tension receptors in In this study SMS 201.995 (long acting feeding (before feeding: mean 59-3 ,umol/l, the corpus play an essential role in the somatostatin analogue which reduces serum range 30-86 [tmoll; after eight weeks: propagation of perstalsis in the stomach. gastrin concentration) was investigated. mean 77-1 ,imol/l; range 50-141 [tmol/l; Nude mice received MKN45 xenografts and p<0.05). This increase was not, however, were allocated to control (n=10) (saline associated with any deterioration in cogni- First measurement of gastric juice ascorbic infusion) or one of two treatment groups

tive function and parents actually reported acid levels (SMS 201.995 infusion by implanted http://gut.bmj.com/ increased well being. osmotic mini pump for days 0-7 at 25 Despite the use of a formula containing G M SOBALA, C J SCHORAH, M SANDERSON, P (n=10) or 240 (n=5) [ig/kg/day). Tumour 31% of total N as branched chain amino- GODWIN, M F DIXON, A T R AXON (Gastro- diameter was measured daily, blind of acids (normal diet 15-20%), plasma levels enterology Unit and University Departments treatment group, for the 22 day experiment. of these were not significantly raised during of Microbiology, Chemical Pathology, and Tumour growth was significantly slowed in the study, suggesting that branched chain Histopathology, The General Infirmary, both treatment groups, and remained aminoacids are well metabolised in these Leeds) Ascorbic acid may protect against depressed for some seven days after therapy patients. Other aminoacids (particularly gastric cancer by inhibiting intragastric before recovering (p<0-01 days 13-17). For on September 24, 2021 by guest. Protected copyright. methionine tryosine, phenylalanine, lysine, nitrosation, being oxidised to inactive example, at day 15 mean tumour diameter and threonine) were generally high, dehydroascorbic acid as it destroys nitrite. was 1-99 (0.73) in the control group, 1-35 although no consistent trend related to Only gastric juice total vitamin C (GVC), (0.65) and 0-98 (0.23) in the low and high feeding was observed. These data confirm however - that is, ascorbic acid plus dose SMS groups respectively Mean post the biochemical safety of nutritional dehydroascorbic acid, has been measured prandial serum gastrin at five days was 217 support in 10 children with advanced liver before. In this study gastric juice ascorbic (66) in controls and 110 (32) and 47 (26) disease, and the ability of the patients, acid (GAA) was quantified for the first (p<002) in SMS treated groups. despite a severely compromised liver, to time, together with GVC, plasma vitamin C SMS 201.995 significantly reduces in vivo metabolise high concentrations of branched (PVC), and dietary intake of vitamin C in 75 growth of MKN45, a human gastric cancer chain aminoacids. We recommend that patients endoscoped for dyspepsia. Patients cell line. This may be related to its effect on blood ammonia levels be regularly with chronic gastritis had lower GVC and serum gastrin concentrations. monitored in these patients. GAA than normals (medians: GVC: 0-95 mg/dl v 2-45; p<0001; GAA: 0.40 v 1-79; p<0-001), but not PVC or intake. The ratio Chronic enterogastric reflux (EGR) in- of GVC to PVC was significantly greater creases the gastrotoxicity of an acute bile than unity only in normals (mean ratios acid challenge in the rat BASIC SCIENCE POSTERS normals: 3-28; p<0-02; gastritis 1-125; p>0.2). The proportion of GVC that was P J VAN EEDEN, D ARMSTRONG, P TAYLOR, Control of gastric peristalsis present as GAA was lower when gastric M MAGHSOUDLOO, G M MURPHY AND R H juice pH >=4 (medians 11% v 62%; p= DOWLING (Gastroenterology Unit, Guy's T SCRATCHERD, D GRUNDY (Department of 0.0001). Campus, UMDS of Guy's and St Thomas' Physiology, Sheffield University) Four dogs These results suggest that there is active Hospitals, London) Using the ex vivo rat Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1478 The British Society ofGastroenterology gastric chamber model, we found that overlying the mucosa however conflicting oxidase (DAO) but the relative importance 'virgin' stomachs responded to acute (10 reports exist regarding the thickness of the of these 'accelerator and brake' enzymes is min) challenges with bile acids and lyso- unstirred layer in CF. These data show the unknown and the possibility of feed back lecithin by loss of transmucosal potential enhanced glucose absorption is an active inhibition of ODC by putrescine, uncertain. difference (APD) and loss of superficial process and give no support to the conten- To study this, we measured jejunal epithelial cells on scanning electron micro- tion that the absence of chloride channels in (proximal 10 cm) and ileal (distal 10 cm) scopy causing nucleic acid accumulation in the apical membrane of the CF enterocyte mucosal DAO and ODC activities and chamber fluid (A[NA]). Chronic EGR, impairs glucose adsorption. polyamine levels two hours after injecting however, induces mucosal hyperplasia and either saline (controls; n=7) or a large (4()X) the response of this 'adapted' stomach to U/kg BW) bolus of IV heparin to deplete the gastrotoxins is unknown. Therefore, in Abnormal jejunal potential difference intestinal mucosal DAO stores (n=6). 13 controls (gastrotomy) and 11 rats with records in cystic fibrosis As expected. ileal mucosal DAO (mU/g chronic EGR studied 16-20 weeks after protein) was higher in ileum (26.9 (SEM) gastrojejunostomy, we measured APD and P S BAXTER, A J WILSON, N W READ (Depart- (3.2)) than in jejunum (7.6 (0.5); p

The British Society ofGastroenterology A1479

Epidermal growth factor was measured in any mucosal extract. TGFt levels were the EGF-receptor pathway is involved in amniotic fluid by radioimmunoassay. closely similar in gastric, duodenal and tumour growth is currently under investiga- In proximal and distal small intestine jejunal mucosae (mean 8200 pg/g tissue); tion in our laboratory. TGFa has been EGF was membrane associated along the 5042 pg/g in the ileum; ascending colon) described as an embryonic EGF and is luminal surface and within apical endo- 3043, transverse colon 3685, descending reported to be expressed by tumour cells. somal compartments. Epidermal growth colon 3530 and sigmoid colon 5119 pg/g. Using a mouse model of transplantable factor was detected free of the membrane in Validity of the RIA systems was further colonic adenocarcinoma we have examined multivesicular bodies, in some basal vesicles supported by the separation of extracted eight histologically distinct solid murine and beyond the basolateral membrane. peptides using reverse phase chromato- adenocarcinomas and control normal Concentration of EGF in amniotic fluid was graphy. These results show for the first time mouse colonic tissues for the presence of 0.4 ng/ml. We demonstrated that EGF is the presence of TGFa throughout the EGF and TGFa. The entire colon was transported across the epithelium of fetal normal adult and in far greater quantity in removed from 20 male and 20 female 10 rats. It is likely that amniotic fluid EGF juvenile G-I tract mucosa. week old MNRI mice. The tissues from plays a part in intestinal mucosal develop- each sex were pooled and acid soluble ment, and may be active systemically after proteins from each batch were extracted transepithelial passage in utero. A cell kinetic study on the effects of oestra- using the method of Roberts et al 1980. diol and oestramustine on gastrointestinal Solid tissues from each tumour line (mini- cell lines mum 3 g) were similarly extracted. Each Distribution of EGF and TGFa throughout extract was assayed for mEGF and TGFct the normal human gastrointestinal tract J D HARRISON, S WATSON, 10 ELLIS, D L MORRIS activity using specific RIA systems. MEGF (Departments of Surgery and Pathology, RIA had a sensitivity of 6 pg per tube and S CARTLIDGE, J B ELDER, H GREGORY (Depart- Queen's Medical Centre, Nottingham) the TGFa RIA could detect 24 pg per tube. ment of Postgraduate Medicine, University Gastric and colorectal carcinomas have There was no cross reactivity between the of Keele, Staffordshire and Department of been shown to be oestrogen receptor posi- assays. EGF was found in greater quantity Biochemistry, ICI Pharmaecuticals, tive in up to 50% of cases; sex hormones in normal male mouse colonic extract (2.716 Alderley Edge, Cheshire) The levels of EGF may be a factor stimulating the growth of ng/g of tissue) than in female colonic extract present in normal gastrointestinal mucosa gastric malignancy. We have studied the (1-305 ng/g tissue). Even greater amounts of are unknown. It is possible that this peptide effect of serial dilutions of oestradiol, the TGFct, previously thought to be an embryo plays a role in the maintenance and renewal combined oestradiol nitrogen mustard com- and tumour specific peptide, were found in of cells of the gut epithelium. A closely pound oestramustine (Estracyt, AB Leo) both normal male (3.768 ng/g) and normal related peptide, TGFa, has hitherto been and a combination of the two compounds on female colon (1-589 ng/g). TGFa was associated only with normal foetal and neo- the in vitro growth of two human gastric present in all tumour lines but not in

natal tissues, or with transformed cells. and five colorectal cell lines by 75Se amounts greater than normal tissues. EGF http://gut.bmj.com/ Epidermal growth factor receptors are Selenomethionine incorporation. Signifi- levels were lower in general and in one case widely distributed throughout the G-I tract cant stimulation of the two gastric (both (T line 26) was not detected. Neither mucosa. The aim of this study was to seek 24% greater than control) and two absolute values nor ratios of growth factors evidence for the presence of EGF or the colorectal cell lines (20% and 34% greater in the tumours, or between tumour and related ligand TGFa in gut mucosa. We than control) occurred at physiological con- control tissues could be related to the have extracted acid soluble proteins from centrations of oestradiol (nanomolar). degree of histologic differentiation. A normal human gastrointestinal mucosae Oestramustine showed an inhibitory effect negative correlation was found between the Colon freshly obtained from three healthy adult in all of the cell lines at 10 [g/l, and a direct ratio: Tumour (TGFa)/Control on September 24, 2021 by guest. Protected copyright. organ donors (two men, one woman) and dose dependent inhibition was seen in two (TGFa) and tumour doubling time in days from one juvenile (girl aged 7 years). of the cell lines. The inhibitory effect of (r=-0.560, p<005), implying that the Mucosal extracts from stomach, duo- oestramustine at 2 iglml (15% and in one nearer (TGFa) is to normal mucosal denum, jejunum, ileum, ascending colon, gastric and 24% in one colorectal line) was (TGFa) the tumour doubling time shortens. transverse colon, descending and sigmoid lost with increasing concentrations of colon were subjected to protein estimation oestradiol, suggesting that the effects of and specific radioimmunoassays for human oestramustine may be linked to oestrogen Intestinal permeability: osmolarity revisited EGF and TGFa. These assays can detect 25 receptors. We conclude that oestradiol pg peptide per tube. There was no cross stimulates gastric and colorectal cell lines P SMETHURST, I S MENZIES, A J LEVI, I reactivity at 20000-fold addition in either and that oestramustine has an inhibitory BJARNASON (MRC Clinical Research Centre, assay. effect which can be competitively blocked Watford Road, Harrow, Middlesex) There In normal adults TGFa was detected in by oestradiol. is much controversy regarding the effect of every sample. Levels were lowest in duo- test dose osmolarity on the permeation of denal and jejunal mucosa (400 pg/g tissue). permeability markers. Ten to 12 volunteers Stomach mucosa contained 2457 (484 pg/g; EGF and TGFa levels in a mouse model of ingested 100 ml containing 3-O-methyl-D- ileum (1290 (191); ascending colon (3040 adenocarcinoma of the colon glucose (3MG) 0-2 g, D-xylose (Dx) 0-5 g, (814)); transverse colon (2122 (781)); L-Rhamnose (LRh) 1.0 g and 11CrEDTA descending colon (1033) and sigmoid colon S CARTLIDGE, J B ELDER, J DOUBLE, M BIBBY 100 pCi to assess active and passive carrier (616 (51)). In contrast EGF levels were (Department of Postgraduate Medicine, mediated transport and trans- and para- significantly low throughout the G-I tract University of Keele, Staffordshire and cellular permeability respectively, as (A) mucosa (51-154 pg/g tissue, p<0-001). In Department of Clinical Oncology, baseline; (B) with absorbed osmotic fillers the juvenile tissues no EGF was detected in University ofBradford) The hypothesis that B1: glycerol 1400 mosm/l; B2: glycerol 2800 Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1480 The British Society ofGastroenterology mosm/l; B3: urea 3500 mosm/l; (C) with pattern of high amplitude peaks lasting E BEUBLER, G BURG, I M COUPAR, P 1 'non-absorbed' osmotic fillers; C,: lactulose *3.53 (0.1) mins alternating with quiescence HARDCASTLE, J HARDCASTLE, A J KITCHIN 300 mosmll; C2: lactulose 1400 mosmll, with lasting 4-6 (0.3) mins, in all patients with (INTRODUCED BY R J LEVIN) (Sheffield 5H urines. proven obstruction. The SVA response in University, University of Graz, Austria, The excretion of 3MG was unaffected. volunteers and non-obstructed patients was Victorian College of Pharmacy, Melbourne, BI-3 did not affect DX but C2 decreased it sustained, with few individual peaks (6.2 Australia) 5-Hydroxytryptamine (5-HT)- significantly (37.9 (2.9)% to 19-2 (2.7)%, M (0.7) volunteers v 13-1 (1-8) obstructed induced changes in transintestinal electrical (SE)). B1_3 did not affect LRh but C1-2 p<001)t of low amplitude (total SVA activity are used increasingly to characterise decreased it significantly (21.0 (1-8)% to energy 195-4 (19) volunteers v 405-7 (52) the 5-HT receptors that regulate intestinal 10-6 (0.9)% and 5-7 (0.7)% respectively). obstructed p0.05). Fluid the nature of the osmotic filler. of two isolated hemichambers linked by a transport determinations produced con- 2-5 mm diameter porthole in the centre of trasting data. Under control conditions an otherwise impermeable perspex sheet. 5-HT (1-5-2.6x10 mol/kg/min IA) Detection of partial gastrointestinal (GI) We have studied 135 human ileal speci- induced a secretion of 246±36 (22) [d/g wet obstruction by surface vibration analysis mens, orientated such, that the mucosal and weight/30 min. This was unaffected by (SVA) serosal surfaces were in their own separate cisapride (2.1x 10 6, 8.3x 10 6 mol/kg SC, hemichamber. Both surfaces were main- p>005), but was reduced by ketanserin http://gut.bmj.com/ P T CULLEN, F C CAMPBELL, B E STOREY, A tained in hyperoxygenated Krebs buffer (60% inhibition at 7 6x 10 6 mol/kg, 68% CUSCHIERI, D L WINGATE (University Depart- solution, at 37°C. Repeatable, trans- at 3-0x10 7 mol/kg, 90% at 1.2x10 6 mol/ ment of Surgery, Ninewells Hospital and mucosal potential differences (PD) were kg SC, p<0.01) and BRL 43694 (39% at Medical School, Dundee and GI Science maintained for three hours 3 8 mV (0.8 2-9x10" mol/kg, p<005, abolished Unit, The London Hospital) Gastro- mV-5 9 vM)*. Glucose caused a significant, at 2 9x10` and 2.9x10` mol/kg SC, intestinal contraction 'clusters' with reproducible rise in PD (p<005) and p<001). Different receptors mediate the alternating quiescence occur in partial Ouabain/sodium fluoride, a significant fall actions of 5-HT on transintestinal PD and intestinal obstruction (PIO) but are only in PD (p<0.05). Wet tissue weight fluid movement. These intestinal receptors on September 24, 2021 by guest. Protected copyright. detected by invasive intraluminal mano- remained unchanged throughout the study do not conform to the current classification metry. Surface vibration analysis is a non- (NS), indicating no cell disruption and of 5-HT receptor subtypes. invasive test of GI activity patterns, which structural oedema. This was confirmed on may be useful in PIO. In this study SVA histological examination. Complete port- recordings were taken: (1) In two volun- hole occlusion by the preparation was Specific 5-HT3 receptor antagonist (GR- teers with partial obstruction induced by demonstrated by transchamber poly- 38032) Slows colonic transit and reduces intrajejunal balloon distension, and evalu- ethylene glycol (PEG) marker passage of neurotensin (NT) response in man ated against simultaneous manometry. (2) less than 0-5%. Human ileal extracellular In nine patients with suspected partial space valves were comparable to those of N J TALLEY, S F PHILLIPS, L J MILLER, A obstruction. Results were compared with the guinea pig model, using two labelled HADDAD (Division of Gastroenterology, those of 36 non-obstructed volunteers. PEG markers of differing molecular weights: Mayo Clinic, Rochester, MN 55905, USA) Part 1: manometry showed contraction (1) 3HPEG 900 14-42 (11.14-17.37)% GR-38032 (Glaxo) is a selective antagonist 'clusters' with alternating quiescence, in *n=62; (2) '4`PEG 4000 10-00 (6.41- of 5-hydroxytryptamine (5-HT) type three jejunum proximal to the obstructing 14.82)% *n=70. These studies validate the receptors on enteric neurones. To deter- balloon. The bowel distal, was totally Lauterbach system for study of human ileal mine if GR-38032 affects small intestinal quiescent. The SVA response of alternating mucosal transport. andlor colonic transit, randomised, double hyperactivity and quiescence corresponded *=median (range). blind placebo controlled crossover studies exactly with proximal jejunal manometry. were performed. Using a radio-opaque Part 2: partial obstruction was proved in marker technique, colonic transit was seven patients and disproved in two quantified in 10 healthy volunteers (four (laparotomy). Surface vibration analysis 5-HT actions on intestinal fluid and electro- men, six non-pregnant women) aged 23-70, after a test meal, showed an obstructive lyte transport on a standard 25 g fibre diet; 16 mg tds of Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1481

GR-38032 was given orally. A further 10 tion in vitro may reflect inhibition of pro- the treatment group received seven sessions volunteers were assessed after a single dose duction of pro-inflammatory lipid peroxides of explorative psychotherapy and relaxa- of GR-38032 (0.15 mg/kg; iv). Gastro- in vivo. 5-ASA is more potent than sulpha- tion training, by a trained psychiatrist. intestinal peptides (NT, HPP, PYY, salazine. This effect may underly their Abdominal symptoms were assessed at gastrin-CCK, motilin) were measured therapeutic properties. the beginning and end of the three months fasting and postprandially, and small bowel trial period, by selfassessment question- transit was assessed by appearance of naires, and daily completion of bowel sulphapyridine in plasma after salicylazo- charts. In addition, ratings were made by sulphapyridine was instilled into the the gastroenterologist, blind to both treat- duodenum. COLORECTAL POSTERS ment groups, at the beginning and end of Mean left colonic transit time with the trial. Psychological symptoms were placebo was 9 7 h (2.7) (SE); with GR- Effects of inert plastic particles on human assessed by self rating scales of mood and 38032 was 17 8 (3.6) h, (p=0-.02). Total colon function anxiety, and by a standardised psychiatric colonic transit time was similarly pro- interview. longed. No changes in small bowel transit J TOMLIN, N W READ (Sub-Department of After three months, there was a signifi- were observed. The postprandial integrated Human Gastrointestinal Physiology and cant improvement in bowel symptoms in the response to NT was reduced from 6 3 to 3-3 Nutrition, K Floor, Royal Hallamshire treatment group, according to both self pg/mlx 10W (p=0.02). Though postprandial Hospital, Glossop Road, Sheffield) Part of ratings by patients and objective ratings by levels of HPP and PYY were not changed by the mechanism by which coarse wheat bran the gastroenterologist. There was also a the drug, times to their peaks was decreased affects bowel function may involve significantly greater improvement in (p

The therapeutic actions of sulphasalazine compared with control periods without treatment of http://gut.bmj.com/ and its component 5-ASA in inflammatory particles. Ease of defecation and the (IBS), but whilst local application in the bowel disease may be due to oxygen radical number of flatulent episodes were colon has been observed to reduce motility, scavenging ability. The erythrocyte pro- unchanged but stool consistency, assessed visually at colonoscopy and manometric- vides a cellular model for evaluating the with standard photographs, was signific- ally, the effects of oral preparations have effects of these compounds on non-enzymic antly softer. In comparison a supplement of not been studied. In a randomised, double lipid peroxidation. 37.5 g/d wheat bran (calculated to provide blind crossover study, we studied the effect Aliquots (5 ml) of 1/40 (v/v) suspension of 15 g/d indigestible residue to the caccum) of enteric coated PO capsules on sigmoid washed v packed, erythrocytes of known increased stool mass (1.56 1 14 kg/wk, motility, using perfused tubes placed via on September 24, 2021 by guest. Protected copyright. haemoglobin (Hb) concentration, in 10 p<0O05), accelerated transit time from 53 0 flexible sigmoidoscope at 20, 25, and 30 cm mmol sodium azide, 15 mmol phosphate to 42.3 h (p<0.05), but had no effect on from the anus connected via a pressure buffered 0 14 mol/l saline, from five human other parameters. The comparable effect of transducer to a pen recorder. Ten patients subjects were preincubated for one hour at plastic particles on transit time and stool with IBS were studied. After one week's pH 7-4 with 1 ml of 0 (control), 10 , 10 5, output to coarse bran, suggests part of dosing (1 capsule tid) with PO or placebo, 10 4, 10 ', or 10 2 mol/l sulphasalazine or bran's action on the colon may be through fasting recordings were made for 30 minutes 5-ASA in 0.02 mol/l sodium hydroxide. mechanical stimulation of multimodal before and after a standard breakfast. The Lipid peroxidation, measured as malon- mucosal receptors. study was repeated one week later after dialdehyde (MDA) production at 90 crossover of treatment. Motility Index minutes, was initiated with 0 75 mmolll (MI =mean peak pressuresx percentage t-butyl hydroperoxide. A controlled trial of phychological treatment duration of activity) was calculated for each Lipid peroxidation was significantly in patients with the irritable bowel syndrome period and results compared using paired t (p<0.001, paired t-test) inhibited by 10` test. Although PO reduced MI pre and mol/l sulphasalazine (0.32 (0. 10) nmol E A GUTHRIE, F H CREED, D DAWSON (Depart- postprandially in 80% of patients overall, MDA/mg Hb; mean (SD) versus control ment of Psychiatry, Manchester Royal the difference between treatments was not incubations (0-80 (0.15) nmol MDA/mg Infirmary, Rawnsley Building, Manchester) statistically significant (mean MI prepran- Hb). Whereas 5-ASA significantly One hundred and four consecutive out- dial, postprandial: placebo 191-3, 240; PO (p<0 001) inhibited MDA production, patients with the irritable bowel syndrome. 1505, 243: t=07, p=02, t=-65, p=0.4). even at 10 5 molIl (0.48 (0.12) nmol unimproved by routine medical treatment, The lack of difference may be explained MDA/mg Hb). were randomly allocated to a treatment and either by the heterogenous nature of IBS The ability of 5-ASA and sulphasalazine a control group. Both groups received patients or PO is released too high in the dose dependently to inhibit lipid peroxida- similar medical treatment, but patients in small bowel to affect colonic motility. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1482 The British Society ofGastroenterology

Colonic motility in the irritable bowel quent bowel actions than controls (p<0.05) tents? A combined manometric and scinti- syndrome and considered themselves constipated graphic study more often. Although more cases than J M HAMDORF, D M INGRAM, R W SALLIE, N E controls used laxatives and had hard J ROGERS, H H TAY, J J MISIEWICZ, G WALKER HOFFMAN (IN IRODUCED BY D J C SHEARMAN) motions, these differences did not reach (Department of Gastroenterology and (Department of Surgery, University of statistical significance. Significantly more Nutrition Central Middlesex Hospital, Western Australia, Gastroenterology/Liver cases than controls, however, had consulted London) Nine normal subjects (mean age Unit, Sir Charles Gairdner Hospital, a doctor because of constipation. There was 22 yrs (0.5) (SD) with normal bowel habit Nedlands, Western Australia) Colonic intra- a highly significant correlation between were studied without bowel preparation. luminal pressures were measured continu- altered bowel habit and altered urinary Transit was measured by quantitative ously for 24 hour periods at multiple sites in frequency after hysterectomy (p<001). dynamic scintigraphy of a 39 MBq semisolid patients with the irritable bowel syndrome The results support the hypothesis that bolus of 'Tc-DTPA labelled Regulan (1 g (IBS) defined as abdominal pain with hysterectomy increases the risk of constipa- in 5 ml H20) instilled at 40 cm from the alteration in bowel habit. An 8-lumen tion and that there may be a common anus. Intracolonic pressures were measured recording catheter was passed over a flex- mechanism causing both the bowel disturb- with open-ended water perfused tubes at ible guidewire introduced at colonoscopy ance and the altered urinary function. 50, 40, 30, and 15 cm from the anus, under light sedation in subjects following analysed electronically for pressure activity bowel cleansing. Digitised data were in mmHg/min (area under curve). After a filtered to remove movement artefact and 30 min basal period, a standard meal of 1040 corrected for baseline shift. Motility Index Prospective evaluation of Manning's criteria Kcal was taken and records continued for 90 (MI), defined as the 'area under the curve' for irritable bowel syndrome (IBS) min. The meal stimulated a significant over five minute intervals, was calculated (p<0 02, manova) increase in pressure N J TALLEY, S F PHILLIPS, L J MELTON, A R for each of right, transverse, descending, ZINSMEISTER (Division of activity in all subjects. In five subjects there and sigmoid colons, and rectum during Gastroenterology, was no transit of the marker from the sleep, on waking, preprandially and post- Mayo Clinic, Digestive Diseases Core sigmoid colon over the 2 h period of study prandially. Five patients (mean age=33.2 Center, Rochester, MN 55905, USA) Can (97 (2.7) v 92-6 (6.2) mean (SD)% residual the symptoms of IBS lead to a positive In contrast there was years) were compared with eight normal diagnosis, without using expensive tests? counts). significant subjects (mean age=25.5 years). The only Whilst the six criteria of Manning (987 (09) v 449 (12.3) p<00002, paired t- significant difference during sleep was in the (Br Med J test) transit of the marker distally in three right colon where activity in patients with 1978; ii: 653) are used widely, data on their and proximal in one. The onset of transit validity are limited. To evaluate this, we coincided with a in IBS was significantly greater than in studied 340 outpatients with a bowel disease marked increase normals (p<0-01). The major abnormality questionnaire (BDQ), which objectively pressure activity at 50 cm, proximal to the seen in IBS was the marked increase in MI bolus. The increase in colonic pressure http://gut.bmj.com/ in the postprandial period where the values measured Manning's criteria, abdominal activity in the sigmoid colon following a were seen to be at least three times greater pain, and bowel habits. The patients meal is predominantly non-propulsive. than normal (p<0.01). Abdominal pain included 81 IBS, 35 non-ulcer dyspepsia, 89 Transit of contents from the sigmoid is reported by patients with IBS was seen to organic GI disease and 135 healthy controls. associated with increased pressure activity occur concurrently with synchronous Diagnoses were based on full and indepen- in the descending colon. pressure rises in adjacent segments in the dent clinical evaluations, not on BDQ colon. responses. Reliability was assessed by a test-retest procedure. Logistic regression

Anal cancer and the human papillomavirus on September 24, 2021 by guest. Protected copyright. was used to analyse the discrimination of Manning's criteria alone, as against a com- The effect of hysterectomy on bowel function J H SCHOLEFIELD, J G PALMER, L V CRAWFORD, 10 item IBS on an a posite score, based J M A NORTHOVER, introduced by R J Nicholls I TAYLOR, A N SMITH, P M FULTON (Gastro- priori grouping of questions. Individual Manning criteria were all (ICRF Colorectal Cancer Unit, St Mark's intestinal Unit, Department of Surgeryl reliable. As the number of positive criteria Hospital, City Road, London and Imperial Urology, Department of Community increased, so did the probability of IBS (any Cancer Research Fund Laboratories, Medicine, University ofEdinburgh) Hyster- three, probability IBS=50%, all six, proba- Lincoln's Inn Fields, London) Epidemiol- ectomy is a common, relatively safe opera- bility IBS=80%). But, sensitivity and ogical evidence suggesting an association tion but longterm sequelac on bladder 27% and between anal squamous cell carcinoma and function have been recorded. Possible specificity for all six criteria were receptive anal intercourse, together with effects bowel function 87%, respectively. The composite IBS on have been less score discriminated IBS from other groups case reports of malignant change in condy- well studied. A retrospective case control that were often loose and lomata, led us to hypothesise that there may study compared the present bowel habit of (p=0.01). Stools be an aetiological association between anal 91 women who had had a in watery provided additional independent SCC and the human hysterectomy criteria for distinguishing among groups papillomavirus. the years 1978-1983 with 91 other women can We have collected fresh tissue from a who had not. The bowel habit of the (p=0.002). Thus, symptoms diagnose of 41 cases invasive control IBS positively, but Manning's criteria are prospective series of group was comparable with that of the sensitive. anal squamous cell carcinomas, which we previous study by Connell et al (1965). Use not highly have examined for evidence of HPV DNA of criteria for constipation and diarrhoea sequences using Southern blot analysis. gave relatively close agreement with the This is the most sensitive and informative subjects' own perception of bowel habit. Does postprandial increase in sigmoid molecular biological technique available for The posthysterectomy cases had less fre- colonic motility cause transit of colonic con- the analysis of DNA sequences. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1483

We have found evidence of HPV type 16 p<0.05. MTV in group 1 (235 (82) ml) and computerised axial tomography (CT), DNA in 23/41 invasive anal squamous cell although larger than in group 2, did not and compared with the pathology of the carcinomas and evidence of HPV 18 DNA reach statistical difference. operative specimen. Extrarectal extension in two further cases. These results have These data suggest that poor functional of the tumour was demonstrated by CS, close parallels with those found from similar results after CAA with colonic reservoir are ELU, and CT with a sensitivity of 59, 91, studies of cervical carcinomas. mainly due to small MTV and contractions and 73; specificity of 100, 100, and 60; We have examined our series further in colonic reservoir and not to an impair- positive predictive value of 100, 100, and 80, using in situ hybridisation to demonstrate ment of sphincterian function nevertheless and a negative predictive value of 53, 83, that the viral DNA is within the nuclei of the excision of anal mucosa. Mechanisms of and 50%. Pararectal nodes with a diameter malignant epithelial cells. reservoir contractions need further >1 cm were demonstrated by CS, ELU, and The evidence from these studies supports informations. CT, with a sensitivity of 18, 64, and 82; the hypothesis that human papillomavirus specificity of 95, 90, and 90; positive may be an aetiological factor in squamous predictive value of 67, 78, and 82; negative cell carcinoma of the anus. Left-sided colonoscopy highlights the failure predictive value of 69, 83, and 90%. of haemoccult to detect colorectal neoplasia Other authors have previously reported that the presence and nature of tumour Functional results of colo-anal anastomosis D P FOLEY, P DUNNE, T D RYAN, M CODD, fixity can be distinguished preoperatively by with colonic reservoir and excision of anal P DERVAN, J CROWE, T O'CALLAGHAN, J R serum levels of carcinoembryonic antigen mucosa for rectal carcinoma LENNON (Louth County Hospital, Dundalk (CEA), a, acid glycoprotein (AGP), and C and Mater Hospital, Dublin) The usefulness reactive protein (CRP). In this study, there F GUILLEMOT, J LEROY, A CORTOT, J MUNDRY, R of haemoccult as a screening test for were no significant differences in the levels MARTI, P QUANDALLE, M D LAMBLIN, J D GUIEU colorectal neoplasia was evaluated by per- of CEA, AGP, and CRP in relation to (Clinique des Maladies de lAppareil forming left sided colonoscopy on 900 Duke's stage or tumour fixity (none, inflam- Digestif, Service de Chirurgie adult Ouest, asymptomatic subjects 244 years who were matory or malignant). Patients with liver service d'exploration fonctionnelles neuro- given three haemoccult II envelopes for metastases had significantly higher serum chirurgicales, CHU Lille 59037, Lille, completion. Subjects with neoplasia at left CEA levels. Cedex, and Clinique de Bully les Mines sided colonoscopy underwent full colono- 62160, France) Although well described, scopy and polypectomy or surgical excision. coloanal anastomosis (CAA) with constitu- Those with positive haemoccult and nega- tion of a colonic reservoir has been func- tive endoscopy had double contrast barium Colonoscopic surveillance after surgery for tionally poorly evaluated. The aim of this enema. colorectal cancer? A rational approach study was to assess ano-rectal continence Of 880 (98%) returning four or more

after CAA and to elucidate the mechanism smears - 75 (8-5%) were positive of whom S PATCHETT, D P O'DONOGHUE, A LONG, N H http://gut.bmj.com/ of incontinence in some patients with CAA. three had carcinoma and 21 adenoma at left AFDHAL (Department of Gastroenterology Sixteen consecutive patients (65.2 yrs, sided colonoscopy. Colonic investigation and Liver Unit, St Vincent's Hospital and eight men) operated on for rectal carcinoma was negative in 48. Among haemoccult University College, Dublin, Ireland) Early were studied six months at least and as a negative subjects three had carcinoma and detection of locally recurrent or meta- mean 17-4 months (nine) after closure of 141 (18%) adenoma (2 mm-5 cm). chronous tumours with an aggressive sur- temporary loop colostomy after confection Sensitivity of haemoccult for carcinoma is veillance programme has been advocated to of a J shaped reservoir of 8 cm with excision 50% and for neoplasia 14%; specificity - improve the overall outcome of colorectal of anal mucosa from 5 mm under the dental 92% and 93% respectively; positive predic- cancer (CRC) following surgery. Because line up to the superior limit of the levators tive value 4% and 34%; negative predictive of the different practices among clinicians on September 24, 2021 by guest. Protected copyright. insertion on the ano-rectal junction. value 99-6% and 82%; false negativity 50% within our institution, it has been possible to Patients and six controls (65.8 yrs) under- and 86% and false positivity 96% and 66%. assess the efficacy of such a programme in a went: (1) anal manometry; (2) determina- To our knowledge this is the only study to consecutive series of patients admitted with tion of maximum tolerable volume (MTV). evaluate haemoccult in asymptomatic sub- CRC between April 1983 and December Patients underwent measurement of colonic jects by using left sided colonoscopy as the 1987. There were 336 patients with CRC of reservoir pressure during liquid continence reference test. The failure of haemoccult to whom 244 (72.6%) underwent curative test (60 mllmin of a saline solution for 25 detect 50% of malignant and 86% of benign surgery. Follow up was complete in 234 min) (LCT). neoplasms clearly demonstrates its limita- (95%). Sixty eight patients were enrolled in Twelve of 16 patient (group 1) were tions as a screening method. a regular colonoscopic surveillance pro- continent and able to defecate spontane- gramme with six monthly colonoscopies for ously (bowel frequency=2-5/24 h); four of 18 months and yearly thereafter (group A). 16 were not continent (group 2). Colonic Conventional versus extended pre-operative The remaining 176 patients were reviewed reservoir pressure before LCT was signific- staging in rectal carcinoma clinically and investigated if symptomatic antly higher in group 2 (30 (10-8) mmHg) (group B). Both groups were similar with than in group 1 (18-75 (9.1) mmHg): W P MORGAN, M BULL, R NAKIELNY, S A C respect to age, sex, Duke's staging, tumour p<0-05. Reservoir contractions were DUNDAS. A MILFORD-WARD (Departments staging, and mean duration of follow up (A recorded significantly more often in group 2 of Surgery, Radiology, Pathology and - 22-5: B - 25.6 months). (four of four) than in group 1 (four of 12) Immunology, Royal Hallamshire Hospital, Anastomotic recurrence without during LCT: p<005. MTV was signific- Sheffield) Thirty two rectal carcinomas were evidence of extra colonic spread has been antly lower in group 2 (165 (46.5) ml) (mean staged preoperatively by clinical examina- found in 13 patients to date (2 - group A: 10 (SE)) than in controls (261 (50.8 ml), tion (CS), endorectal ultrasound (ELU), - group B). Ten of the 13 recurrences were Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1484 The British Society ofGastroenterology rectal tumours. Both patients in the surveil- London and Institute of Cancer, Sutton, tumour cells staining with each antibody lance group were symptomatic at the time of Surrey) For the immunoscintigraphy or was assessed on a four point scale. review colonoscopy. There were no meta- targetting of colorectal cancer, monoclonals All tumours expressed CEA whereas five chronous tumours. with a greater affinity for the tumour than of 34 (15%) did not express EMA. CEA In group A, 10 patients were found to normal tissues are required. Owing to stained >50% of tumour cells in 24 of 34 have adenomatous polyps at the first post tumour heterogeneity, any one monoclonal sections (71%) which was significantly operative colonoscopy. Only one patient will only react with a proportion of color- greater than EMA (six of 34=18%) had a polyp at a second or subsequent ectal cancers; a cocktail of monoclonals may (p<0.01). CEA expression was greater in colonoscopy. be necessary for effective targetting. Anti- well differentiated tumours (p<0.05) These results imply that surveillance after bodies with greater tumour specificity and whereas EMA expression was not signific- curative surgery for CRC may, with safety, reactivity are thus in demand. We have antly different. One hundred and sixty three be restricted to a single colonoscopy to raised monoclonal antibodies to colorectal lymph nodes were examined (median 6/ ensure a clean colon. These findings apply cancer using a crude membrane extract patient, range 2-11) on H&E with 31 nodal only to the early post operative years. (CME) of tumours obtained from 13 metastases being found in 13 patients. patients. Balb C mice were immunised with Immunohistochemistry of nodal deposits CME and the spleen cells fused with the was negative in three sections with CEA myeloma cell line NSO. A total of 10 fusions and in two with EMA. Occult metastatic Hepatic perfusion index (HPI) in diagnosis produced 893 hybridomas. Initial screening tumour not visualised on routine H&E and follow up ofmetastatic colorectal cancer with an enzyme linked immunosorbant staining was located with anti-CEA in one assay (ELISA) on CME showed that 245 patient but not with anti-EMA. K C BALLANTYNE, R M CHARNLEY, G PYE, A C were positive. Secondary screening with PERKINS, D R WHALLEY, M L WASTIE, J D immunocytochemistry on frozen sections of HARDCASTLE (Departments of Surgery and colorectal cancer identified 67 reactive anti- Effects of cytochalasin B and colchicine on Medical Physics, University Hospital, bodies, five of which show membrane react- colonic restitution Nottingham) Previous work has suggested ivity. One antibody UC-ICR 20-3 reacts that up to 90% of patients with metastatic with 11 of 13 (85%) different colorectal P H ROWE, C HANLEY, R C MASON (Department liver disease have a raised HPI and that cancer sections. It has no reaction with of Surgery, Guy's Hospital, UMDS, St dynamic liver imaging is of value in the connective tissue and a minimal reaction Thomas, London) Restitution is restoration identification of occult hepatic metastases. with normal colon and a few other epithelial of the continuity of the surface epithelium We have evaluated this technique in 180 cells. Flow cytometer analysis shows that it by cell migration. It has been previously patients, 109 with primary colorectal reacts with three colorectal cancer cell lines reported to occur in colonic mucosa in vitro. cancer, 38 with suspected recurrent disease (LoVo, SW480, Colo 205) but not with We investigated the effects of colchicine, a and 33 after curative resection of colorectal blood cells or fibroblast. UC-ICR 20-3 is potent inhibitor of DNA synthesis and cyto- http://gut.bmj.com/ cancer, to determine its role in the detection therefore suitable for the immunoscinti- chalasin B, an inhibitor of cell migration on and follow up of this disease. Serial imaging graphy or targetting of colorectal cancer. the process of restitution in colonic mucosa. studies were performed in 21 patients with Using chambered bull frog colonic mucosa metastatic disease. Hepatic perfusion index (n= 10) exposed to molar NaCI in the was determined using peak of the left luminal chamber exhibited an immediate kidney time activity curve to define the Carcinoembryonic antigen (CEA) and fall in potential difference (PD) and a fall in division of arterial and portal blood flow. epithelial membrane antigen (EMA) in resistance (R). Tissues removed (n=5) after

Hepatic perfusion index was raised colorectal cancers NaCl exposure exhibited severe mucosal on September 24, 2021 by guest. Protected copyright. (>0.37) in 54/115 (47%) patients with no injury with denudation of the basal lamina. evidence of hepatic metastases, 17/27 B R DAVIDSON, V R SAMS, J STYLES, C G CLARK After 10 minute NaCI exposure and (63%) patients with hepatic metastases at (Departments of Surgery and Pathology, replacement of NaCI with standard luminal initial presentation, 21/25 (84%) with meta- University College London and Institute of solution, when tissues were allowed to static disease detected during follow up. Cancer Research, Sutton, Surrey) Carcino- recover for four hours, there was histo- Four of 12 (31%) of those with local recur- embryonic antigen and EMA are tumour logical reconstitution of the surface epithe- rence and CT scan disease free livers had an associated antigens which may be expressed lium and the PD and R returned to values, elevated HPI. In 18/21 (86%) patients with by colorectal cancers. Their expression has not significantly different from the PD and metastatic liver disease serial imaging not previously been compared in a consecu- R in controls. Tissues (n=7) pretreated with demonstrated a rising HPI with disease tive series of colorectal cancers. The role of colchicine (10` M) for 90 minutes, treated progression. antibodies to CEA and EMA in localising with NaCI and four hour incubation in the This study confirms the association of a occult metastatic deposits was also assessed. chambers also exhibited electrical and raised HPI with hepatic metasta5es and Adjacent sections of cancer, normal histological recovery. Tissues (n=5) pre- suggests that a rising HPI on serial studies is colon and lymph nodes from 34 consecutive treated with cytochalasin B (10` M) associated with progression of disease. patients undergoing excision of a colorectal exhibited no evidence of recovery. In con- cancer were examined by the indirect clusion, cytochalasin B but not colchicine immunoperoxidase method using mono- inhibits the process of restitution in amphi- clonal antibodies to CEA and EMA in bian colonic mucosa after injury by molar Monoclonal antibodies to colorectal cancer addition to conventional H&E staining. .NaCl. This supports our hypothesis that Immunohistochemistry was carried out restitution of the colonic mucosa involves C Y YIU, L BAKER, M J O'HARE, C G CLARK using standardised titres of both antibodies epithelial cell migration and not rapid cell (Department of Surgery, University College and incubation times. The percentage of division. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1485

Restitution occurs in colonic mucosa in vitro caused a reduction in both the number of with colorectal cancer. In contrast, how- after bile salt injury mice with tumours and the number of ever, colorectal tumours have a decreased macroscopic tumours and microadenomas NK cell activity compared with normal Q ZHANG, C HANLEY, R C MASON, P H ROWE, per animal. intestinal mucosae. These observations are I McCOLL (Department of Surgery, Guy's Whilst we have failed to reproduce the indicative for a deficient immune surveil- Hospital, UMDS, St Thomas Street, phenomenon of tumour regression in this lance at the tumour level in colorectal London) Restitution is restoration of the experimental model, we have demonstrated cancer. continuity of the surface epithelium by a protective effect with regard to the epithelial cell migration and has been pre- development of new tumours. The fact that viously reported to occur in colonic mucosa impaired development of new tumours was in vitro after injury by hyperosomlar NaCl. paralleled by a reduction in the incidence Application of plasminogen activator We investigated whether restitution in and number of microadenomata suggests measurements to endoscopical biopsies as colonic mucosa occurs following injury by that sulindac exerts its effect at a stage in the markers of gastrointestinal malignancy bile salts. Using chambered bull frog tumorigenesis process before micro- colonic mucosa exposed to 10 mM sodium adenoma formation. P A F DE BRUIN, H W VERSPAGET, G GRIFFIOEN, deoxycholate (DOCA) in the luminal J H VERHEYEN, G DOOIJEWAARD, C B H W chamber, exhibited an immediate fall in LAMERS (Department of Gastroenterology potential difference (PD) from 83 (16) Natural killer cell activity of peripheral and Hepatology, University Hospital and (mean (SE)) to 8-0 (4) mV and fall in blood, mucosa, and tumour infiltrating Gaubius Institute TNO, Leiden, The resistance (R) from 200 (7) to 60 (20) ohm mononuclear cell! in patients with colorectal Netherlands) In resection specimens of cm2. Tissues removed (n=6) following cancer colorectal adenocarcinomas, the concentra- DOCA exposure exhibited severe mucosal tion of urokinase-type plasminogen injury with denudation of the basal lamina. M N APARICIO-PAGES, H W VERSPAGET, activator (u-PA) is markedly increased After 10 minute DOCA exposure and A S PENA, C B H W LAMERS (Department when compared with the normal parent replacement of DOCA with standard of Gastroenterology and Hepatology, mucosa, while on the contrary, the tissue- luminal solution, when tissues (n=11) were University Hospital Leiden, The Nether- type plasminogen activator (t-PA) shows a allowed to recover for four hours, there was lands) Natural killer (NK) cell activity has decrease in malignant colonic tissues. histological reconstitution of the surface been reported to be decreased in peri- In this study, assays for u-PA and t-PA, epithelium and the PD and R returned to pheral blood mononuclear cells of cancer antigen as well as activity, were analysed on values, not significantly different from the patients. We have studied the NK cell their efficacy to distinct between endoscopi- PD and R in controls (n= 10). activity not only from the peripheral blood, cal biopsies from normal and malignant We conclude restitution occurs in colonic but also from the. intestinal mucosa and tissues. For reference, u-PA and t-PA were

mucosa in vitro after bile salt injury. the tumour of patients with colorectal also investigated in the ultimate resection http://gut.bmj.com/ Restitution is therefore an important repair carcinomas. specimens of the same patients (n= 14), process and probably occurs after a variety Peripheral blood mononuclear cells from which were all proven to have a carcinoma. of injurious agents. patients and controls (both n= 15) were The results were compared with the histo- isolated by Ficoll/Hypaque density gradient logy of adjacent biopsies as well. centrifugation. Mononuclear cells from In the tumour biopsies, a significant A protective effect of sulindac against 1,2 intestinal mucosa and tumour (n= 12) were (p<0.00l) and more than six-fold increase dimethylhydrazine (DMH)-induced colonic isolated by a multistep isolation procedure of u-PA antigen (12.6 (2.0) v 2-1 (0.4) ng/mg tumours in nice using DTT-EDTA-Collagenase incuba- protein) was found when compared with the tions and density gradient centrifugation. normal tissue biopsies. Combined with the on September 24, 2021 by guest. Protected copyright. M MOORGHEN, P INCE, KAREN J FINNEY, Natural killer cell activity was determined t-PA antigen level (3.1 (0.5) v 3-8 (0-8)) D R APPLETON, J P SUNTER, A J WATSON by an 18-h chromium-51 release assay at which was equal or lower than in the normal (University Departments of Pathology and effector:target cell (E:T) ratio of 50:1 mucosa, the ratio of u-PA/t-PA antigen in Medical Statistics, University of Newcastle (blood) and 500:1 (intestine and tumour). the biopsies was found to be a good upon Tyne) Sulindac, a non-steroidal anti- The targets used were the erythromyeloid (p2.2) with a sensitivity of disappearance of tumours in cases of human carcinoma cell lines CaCo-2 and HT-29. 86% and a specificity of 100%. In the adenomatosis coli. We used the DMH The results are expressed in % cytotoxicity. resection specimens, these figures were model of colonic carcinogenesis using Balb/ Peripheral blood mononuclear cells from both 100%. Among the biopsies, only two c mice in a controlled study to investigate the patients showed a similar NK cell false negatives out of fourteen cases were the effects of sulindac on carcinogenesis and activity, compared with the controls, found, similar as to the histological evalua- on established tumours. In one cohort of against all three targets (K-562 52 (11) v 58 tion. Discrimination between normal and animals sulindac was administered for up to (2), CaCo-2 25 (4) v 28 (5), and HT-29 13 (5) tumour tissue based upon u-PA and t-PA 11 weeks after the initial period of tumour v 12 (2), respectively). Tumour infiltrating activities was less efficient than by the induction. In a separate cohort sulindac and mononuclear cells had a significantly respective antigens. DMH were administered concurrently for a (p<0-01) lower NK activity compared with Determination of plasminogen activators period of up to 24 weeks in order to assess the normal intestinal mucosa mononuclear can effectively be applied to endoscopical any possible effect on tumour development. cells (K-562 14 (2) v 33 (7) and CaCo-2 12 colonic biopsies. Assays for u-PA and t-PA Sulindac failed to cause the regression of (2) v 34 (6) respectively). antigen in endoscopical biopsies may con- established colonic tumours, whereas when The present study shows no defect in tribute to the detection of malignancies in administered concurrently with DMH, it peripheral blood NK cell activity in patients the colon. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1486 The British Society ofGastroenterology

Familial aggregation of tumours of the large of inflammation (r=0.72, p<0-01 and Spontaneous anal relaxation - a cause of bowel r=0.49, p<0-001). Fourteen patients (15%) faecal incontinence? developed pouchitis. The time of onset M PONZ DE LEON, R SASSATELLI, C SACCHETTI, ranged from 0 to 36 months from closure of WEI MING SUN, D D KERRIGAN, N W READ, T C G ZANGHIERI, A SCALMATI, L RONCUCCI the temporary ileostomy. Inflammation DONNELLY (Sub-Department of Human (Instituto di Patologia Medica, Universita di fluctuated over weeks to months from mild Gastrointestinal Physiology and Nutrition, Modena, via del Pozzo 71, 41100 Modena, (grade 0-2) to severe (grade 5-6). All 14 University of Sheffield) Multiport anal Italy) Genealogical trees of 389 patients cases of pouchitis occurred in patients with manometry and external anal sphincter with colorectal cancer registered in 1984-86 total colitis (n=68) significantly more fre- (EAS) electromyography in 25 of 140 and of 389 controls were analysed with the quently than in those with left sided colitis patients with faecal incontinence and six of objectives: (a) to determine whether there (n= 15) (p<0.05 Fishers exact test). No 35 age and sex matched healthy controls is an increased frequency of cancer among patient with polyposis (n=7) developed during a 20-30 min period of rest, showed first degree relatives, (b) to identify pouchitis. Extent of colitis appears to be a periods of spontaneous anal relaxation last- kindreds with hereditary colorectal cancer marker for pouchitis. ing >15 sec and reducing pressure in the (Lynch syndrome). Eighty nine cases of outermost anal channels by >20 cm water. colorectal cancer were observed among first The patients exhibited more episodes of degree relatives of patients and 19 among relaxation than the controls (4.0 (0.6) v 2-2 control relatives (cumulative incidence What is the role of vascular pressure in high (0.2) per subject; mean (SE); p<0-05) and ration 4.48, p<0.001). In 182 patients there anal pressure in patients with haemorroids? the pressure fell to lower values (19 (1) v 42 were one or more cases of cancer (of all (5) cmH2O; p<0.01), but the duration of sites) among relatives; similarly, in 68 WEI MING SUN, N W READ, T C DONNELLY, A G relaxation was not significantly different (47 patients (v 18 controls) there were one JOHNSON (Department of Surgery and Sub- (5) v 40 (5) seconds; p>0-05). Fifty per cent or more relatives affected by colorectal Department of Human Gastrointestinal and 68% of the episodes of spontaneous cancer. In patients without or with only one Physiology and Nutrition, University of relaxation in normal subjects and patients neoplasm in their family members tumours Sheffield) Multiport anal manometry and respectively were associated with simul- were mostly located in the left colon; how- anal sphincter electromyography were con- taneous rectal contractions. Eighty three ever, cancer of the right colon (a feature of ducted in 26 male patients (aged 31-77 per cent of episodes in normal subjects were Lynch syndrome) was frequently observed years) with non-prolapsing haemorrhoids associated with compensatory increases in in patients with two or more cancers of all and eight matched controls. Fifty per electrical activity of the EAS, and leakage organs among relatives and even more often cent patients complained of a feeling of did not occur. Only 31% of patients showed in patients with two or more colorectal obstructed defecation. The basal pressures increased EAS activity (p<0-05) and leak- cancers in their families. In conclusions, our were significantly higher in patients than in age only occurred in those patients who did findings suggest that a genetic susceptibility normals (66 (2) v 43 (7) cmH2O, mean (SE); not show this response. When internal http://gut.bmj.com/ to colorectal cancer may exist in approxi- p<0-05), but there was no significant differ- sphincter slow waves were apparent on the mately 15-20% of the registered patients. ence in maximum squeeze pressures (280 EMG records, these were abolished or Moreover, in a further subgroup of about (13) v 257 (20) cmH2O). During rectal attenuated during spontaneous relaxation. 5% of all cases the marked excess of distension, 92% of patients showed no The rectal volumes required to elicit anal colorectal cancer among relatives (two or relaxation in the most caudad channel, even relaxation (10 (0) v 28 (7) ml; p<0-05), to more) and the frequent location of tumours when relaxation occurred in the inner anal induce sustained relaxation (60 (8) v 82 (5) in the right colon strongly support the channels, the internal anal sphincter elec- ml; p<0-05), and to cause a desire to diagnosis of Lynch syndrome. trical oscillations were abolished and the defecation (36 (4) v 63 (9) ml; p<0.05) were on September 24, 2021 by guest. Protected copyright. external sphincter EMG was not increased all lower in incontinent patients who above pre-distension values. Residual anal showed spontaneous relaxation compared Ileal reservoir inflammation (Pouchitis) pressures during balloon distension were with those who did not. In conclusion spon- after restorative proctocolectomy ileal significantly higher in patients than normals taneous relaxation of the internal sphincter reservoir (51 (1) v 34 (4) cmH2O; p<0-01). When may be a cause of incontinence in patients subjects increased their intra-abdominal with a sensitive rectum. P A FARRANDS, N A SHEPHERD, R J NICHOLLS pressures to inflate a balloon, the rectal (St Mark's Hospital, City Road, London) pressure was significantly higher in patients Inflammation of the reservoir is a recog- than in normals (132 (10) v 94 (7) cmH2O; Chronic constipation is associated with nised complication of restorative procto- p<0.05). Pressures in the anal cushions (30 evidence of impaired urethrovesical and colectomy with ileal reservoir. Ninety (2) cmH2O) were measured in 10 patients; sacral reflex function patients treated between 1979 and 1987 they were much higher than normal capil- were followed at three to six monthly inter- liary or venous pressure, and showed DD KERRIGAN, W M SUN, T C DONNELLY, N W vals for a mean of 4-2 years (range 0.9-9 respiratory oscillation, and pressure READ (Department of Surgery/Sub- years). Function and endoscopic findings increases during coughing (64 (7)) and Department of Human GI Physiology, K were recorded and inflammation in biopsies straining (61 (6)). Pressures after straining Floor. Royal Hallamshire Hospital, from the reservoir was graded histologically were higher than before straining (39 (3) v Sheffield) Sixteen chronically constipated on a scale 0-6. Pouchitis was defined by 30 (2) cmH20; p<0-05). This study suggests female patients (aged 20-66 yrs) underwent clinical, endoscopic, and histologic criteria that the abnormally high anal pressures in combined multiport anorectal manometry as previously described. the anal canal in patients with haemorrhoids with external anal sphincter (EAS) EMG, Frequency of defecation was correlated may be related to an increased vascular video-urodynamic assessment and neuro- with both endoscopic and histologic severity pressure in the anal cushions. physiological studies of evoked pelvic spinal Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1487

reflexes. For the latter, the dorsal nerve of Using this index it is possible to predict S H SAVERYMUTrU, A E A JOSEPH, J D MAXWELL the clitoris was stimulated electrically and the extent of pathological changes and (St George's Hospital, London) A thick- the latency of the evoked reflex activity in suggest management. Mild ened gall bladder wall is often seen on the external anal and urethral sphincters (<25%) produced minimal complaints; ultrasound in alcoholic cirrhosis. Hypo- was measured using concentric needle and moderate (25-50%) responds to conserva- albuminaemia is thought to be the cause as surface electrodes. tive measures (suppositories, dilator). there is a strong association between bowel Resting and squeeze anal pressures and Severe anismus (>50%) was associated wall thickening and low serum albumin. the threshold rectal distension required to with secondary pathological changes, most The stomach is also frequently thickened in cause internal anal sphincter relaxation of which required a pelvic floor repair or cirrhosis, however, but in this situation - the were similar in constipated patients and subtotal colectomy. recently described congestive gastropathy - healthy female controls. Constipated portal hypertension is the cause. To deter- women, however, required a higher volume mine the role of portal hypertension in to elicit a desire to defecate (p=0-001) producing gall bladder wall thickening we and 73% failed to relax their EAS when PANCREATICOBILIARY POSTERS studied 37 consecutive stable cirrhotics. attempting to expel a simulated stool. Fifty Ultrasound assessment of the gall bladder six per cent of the constipated woinen Predictive value of computed tomography wall was made after an overnight fast using a displayed urodynamic abnormalities (CT) scanning of the gall bladder in deter- Technicare autosector. Wall thickness (increased bladder capacity, obstructed mining gall stone type 4 mm or greater was considered abnormal. voiding and stress incontinence). Complete Twenty six patients had a thickened gall absence of clitoro-anal and/or clitoro- S RAJAGOPAL, P BILLS, A KEIGHTLEY, G M bladder wall and all had evidence of portal urethral evoked sacral reflexes was found in MURPHY, R H DOWLING (Gastroenterology hypertension. Hypoalbuminaenia was not 75% of constipated subjects (compared Unit, Guy's Campus, UMDS of Guy's and an important factor since it was only present with 20% of healthy controls, p<0.02). It St Thomas' Hospitals, London) Non- in five cases. These results suggest that was notable that each of the five patients surgical treatment of gall bladder stones is portal hypertension, not hypoalbuminae- who had related the onset of their constipa- confined to -rich stones and mia is the dominant factor in causing gall tion to hysterectomy had absent sacral although 80-85% of radiolucent (plain bladder wall thickening in cirrhosis. Ultra- reflexes and impaired urodynamics. radiograph+OCG) stones are cholesterol- sound demonstration of gall bladder wall rich, the remaining 15-20% are not, often thickening in chronic liver disease should do not dissolve and are sometimes CT- suggest the presence of portal hypertension. An electromyographically derived (anismus) dense. To study this further, we used a index in pelvic floor outlet obstruction Philips Tomoscan 350 to measure stone during defaecation straining attenuation in preoperative patients Optimising wavelengths for common duct

(Hounsfield units: HU) and correlated this laser lithotripsy http://gut.bmj.com/ B M KAWIMBE, N R BINNIE, AN SMITH subsequently with analysis (chemical, (University Department of Surgeryl atomic absorption, infra-red spectroscopy, A MURRAY, R BASY, P D FAIRCLOUGH, R F M Urology, Western General Hospital, electron probe and scanning EM) of stones WOOD (St Bartholomew's Hospital, Edinburgh) Obstructive defecation due to obtained at surgery. London) Laser energy has been shown to failure of relaxation of the pelvic floor There were significant linear correlations have the potential to fragment gall stones in muscles during straining, or anismus, between HU score and (i) stone total the common bile duct, but the optimal may be associated with abdominal pain, calcium (CaTOT: r=0-853; p<0-001) and parameters in terms of efficiency of frag-

excessive straining, constipation and patho- (ii)calcium carbonate content (CaCO3: mentation nad safety have yet to be defined. on September 24, 2021 by guest. Protected copyright. logical changes such as pelvic neuropathy, r=0-826; p<0.005) but not with (iii) We report in vitro studies of gall stone faecal incontinence, and rectal cholesterol content (r= -0-278: NS). fragmentation to determine these parame- prolapse. Although stone CaTOT correlated signific- ters. From 10 patients with multiple stones, An anismus index of the pelvic floor antly with CaCO3 (r=0-84; p<0.001) and 55 gall stones with a mean weight of 1-1 g muscles recorded non-invasively relates the most CT-dense stones were CaCO3-rich, and a mean maximal diameter of 12 mm anal sphincter EMG activity during strain- some CT-dense stones contained little or no were randomised into six groups. One stone ing to the anal sphincter EMG activity CaCO3. Stones with >3% CaTOT by weight from each patient was analysed for bile during voluntary squeezing. (n= 12) invariably had >90 HU: only two of pigment, cholesterol and inorganic salt con- EMG activity during straining - EMG 15 with <3% CaTOT had >90 HU. Stones tent. Each group was subjected to laser activity at rest/EMG activity during squeez- with <60 HU (n= 10) were invariably energy from a Pulsed Dye laser at a wave- ing - EMG activity at restx 100. cholesterol-rich and had <1-5% CaTOT: length of 440, 480, 504, 560, 590, or 635 nm. The anismus index (normals 0% or less) those with >110 HU (n=8) always had .The energy was conveyed by a 0-4 mm was calculated for patients (n=60) with >4% CaTOT, with overlap in the inter- flexible optical fibre held in direct contact distal bowel problems. The correlation mediate group (>60, <110 HU). with the stone held under saline. Pulse between the mean anismus index and Computed tomography scanning has high energy was increased until gross fragmenta- associated conditions was as follows - sensitivity and specificity in predicting gall tion occurred. There was no direct correla- perineal descent 33-8%, pelvic/perineal stone type: CT-dense stones are mainly tion between fragmentation energy and pain 59%, faecal incontinence 64-7%, CaCO3-rich. stone weight or chemical composition. megacolon 76 1%, intractable constipation Fragmentation was most efficient at 440 nm. 80-8%, 86-7%, pelvic The energy required was significantly neuropathy 108-6%, and 'occlusive' Gall bladder wall thickening in chronic liver greater at all the longer weavelengths (p= defaecation straining 114%. disease - a new sign of portal hypertension? <0.01). Furthermore at short wavelengths Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1488 The British Society ofGastroenterology bile acts maximally as an absorber of stray year period ending June 1988, 94 patients were jaundiced and 18 also had clinical laser light, thus minimising risk to the duct. with malignant biliary obstruction had cholangitis. The mean age of treated These effects are consequent upon the attempted combined percutaneous- patients was 79-7 years (range 27-92) and absorption peak of bilirubin at 450 nm. Our endoscopic endoprosthesis insertion (CP) only 13 were aged less than 60. Sphincter- results suggest that the Pulsed Dye laser at after failed endoscopy alone insertion otomy was successful in 185 (99%) and short wavelengths is likely to be optimal for (ERCP). All neoplasms were not amenable complete clearance in 172 (92.5%). Early gall stone lithotripsy. to attempted curative resection. Only one complications occurred in nine patients stent was placed unless evidence of sepsis in (4.8%) of whom three died (1.6%). The undrained segments developed. Strictures patients have been followed for a mean of Efficacy and cost of extracorporeal shock were divided into common bile duct (low) 32 months (range 6-72 months). Eighteen wave lithotripsy (ESWL) for cholelithiasis and hepatic duct (hilar) groups. The latter patients have required subsequent chole- were subdivided into types I, II, or III (after cystectomy (9.6%), with six major compli- T D RYAN, J R LENNON, J P CROWE (Hepato- bismuth). Success was defined as a fall in cations, but no deaths. There have been 27 Biliary Unit, Mater Misericordiae Hospital, bilirubin >30% and loss of pruritus. unrelated deaths and 156 patients remain Dublin) Gall stones can be successfully There were 59 low, eight type I, 12 type alive and symptom free. treated by ESWL using the Siemens II, and 15 type III strictures. The mean age Endoscopic treatment alone is safe and Lithostar. Whether it represents a reason- was 71 years and the mean bilirubin 370 effective in the majority of frail and elderly able alternative to surgery has yet to be itmolll. PTBD was successful in 90 patients patients and can reduce the need for surgery determined. (96%). CP was successful in 76 patients in this high risk group. Twenty one patients (mean age 43 years) (81%). For low, type I, type II, and type III with stones in a functioning gall bladder, strictures, the success rates were 80%, have been treated by ESWL. There were 10 100%, 83%, and 73% respectively, toe total solitary (1-3 cm in diameter) and 11 (ERCP+PTBD+CP) procedural morbidi- multiple (2-10 in number) stones. In three ties were 27, 2, 11, and 10 events respect- ENDOSCOPY POSTERS patients the stones had a calcified rim and ively or 46%, 25%, 92%, and 67% respect- three a calcified centre. Gall bladder ively and the 30 day mortalities were 22%, Is routine sedation appropriate for upper opacification to allow stone localisation was 13%, 42%, and 13% respectively. The gastrointestinal endoscopy (UGE)? achieved with oral iopanoic acid. Nine mean survivals of deceased patients (70) patients had one treatment session and 12 were 2.5, 7.4, 1-2, and 7-3 mths respect- P A CANN, DD KERRIGAN (Departments of had two. A mean of 8000 (2000-14000) ively. Only four of the deaths within 30 days Gastroenterology and Surgery (J Floor), shock waves were delivered per patient. of CP were directly procedure related and Royal Hallamshire Hospital, Sheffield) One Stone fragmentation was achieved in 14 44% of complications were related to the hundred and twenty consecutive out- patients (66%) but five had fragments 5 mm initial ERCP. Five hilar stricture patients patients (76 men) undergoing their first http://gut.bmj.com/ and one patient developed pancreatitis (14%) needed a further CP to deal with UGE were randomised to receive xylocaine because of fragment impaction and septic undrained segments. Endoprosthesis spray plus 10 mg diazepam, or spray alone. required urgent cholecystectomy and change has been required on 20 occasions Upper gastrointestinal endoscopy was per- exploration of the common duct. To date with ERCP successful in 16 and repeat CP in formed by either an experienced or a rela- eight patients have been reviewed at six four. tively inexperienced endoscopist, making weeks, two had complete gall bladder clear- The combined procedure improves the four subgroups of 30 patients. Patients com- ance of fragments. Of the seven failures success rate of endoscopic stenting but pleted postal questionnaires; endoscopists three underwent cholecystectomy and three increases procedural morbidity and is rated patients' reaction to the spray and on September 24, 2021 by guest. Protected copyright. cholecystolithotomy. associated with considerable disease related UGE. Because of the significant failure rate, the early mortality. Four questionnaires were not returned, in-hospital costs of gall stone management four patients allocated spray alone required by ESWL were 24% greater than that of a sedation, and one allocated sedation surgical approach. Late results of endoscopic bile duct clear- declined it. Patients in both groups reported This audit reveals that substantial ance in patients considered unfit for surgery similar tolerance for each endoscopist. improvements have yet to be achieved When asked if sedation would be preferred before ESWL can be accepted as a treat- C J H INGOLDBY, J EL-SAADI, R I HALL, M E at any subsequent UGE, 29% of non- ment option for cholelithiasis. DENYER (Departments of Medicine and sedated patients would prefer to receive Surgery, St James's University Hospital and diazepam (v 88% of the sedated group, Seacroft Hospital, Leeds) Endoscopic clear- p50 yrs (p=0-01). Reaction to CAIRNS, J CROKER, P B CO-TON, RR MASON, Endoscopic sphincterotomy was per- spray did not predict UGE tolerance. R C G RUSSELL, A R W HATFIELD (Depart- formed on 186 patients with common bile Despite endoscopists' impression that ments of Gastroenterology, Radiology, and duct stones and gall bladders paresent ease of UGE was similar in each group, Surgery, The Middlesex and London who were considered unfit for surgery. sedated patients reported excellent toler- Hospitals, London) During the three One hundred and seventy one patients ance more frequently than non-sedated Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1489

(83% v 44%; p<0.001). Time that patients All patients had longterm dysphagia and categories were used to cover the spectrum spent in the endoscopy room differed attempted nasogastric feeding had failed. of hospital services directly and indirectly between endoscopists (median 10 min v 17 After administration of prophylactic anti- relevant to the patients' care, and individual min; p<0.0001) but not between those biotic and oral antiseptic, stomach is patient profiles were constructed to cover patients sedated and those who were not. inflated until endoscope can be palpated all items of expenditure from the time of We feel that patients should be offered an and transillumination seen through abdomi- admission to discharge or death. Excluding informed choice. Many have reasons to nal wall. 'Medicut' plastic cannula is L and HP costs, the mean costs per day for decline sedation, readily accepting inserted into distended stomach, monofila- L, HP, and C treated patients were £132, increased discomfort during the examina- ment thread is inserted, snared, and pulled £141, and £180 respectively, the mean tion. out through mouth. Thread is passed lengths of hospital stay were 13, 14, and 26 through smaller plastic cannula and sewn days, and the mean costs per case were onto 18 F Malecot selfretaining catheter. £1758, 1940, and £4616. Eight cases each Reversal of midazolam sedation for gastro- Thread is pulled until smaller cannulamates costing more than £5000 accounted for 50% scopy by flumazenil inside larger and catheter can then be pulled of the total costs. Assuming an equipment through anterior abdominal wall using life span of seven years and that 35 patients R C PEARSON, P MORRIS, P F MCCLOY, K D cannula as dilator. Indications: brainstem per year are treated by either endoscopic BARDHAN (Manchester Royal Infirmary, stroke (22), cancer or cachexia (four), technique, the data suggest that L would Oxford Road, Manchester and District motor neurone disease (two), duodeno- pay for itself within five months and HP General Hospital, Moorgate Road, jejunal obstruction (two). within five weeks, giving seven year dis- Rotherham) Flumazenil, a benzodiazepine Gastrostomies were placed in 30/30 pts, counted values of approximately £600000 antagonist, was used to reverse midazolam 26/30 (87%) gained or maintained weight, for each form of therapy. Both forms of induced sedation in a double blind placebo 8/30 (27%) went home with gastrostomy in therapy appear to offer the possibility of controlled study in patients undergoing situ, in 4/30 (13%) swallowing improved substantial economies to the NHS. gastroscopy. Assessments were made up to and tube was removed. Median survival of one hour after reversal and again 18-24 these patients was 6/12 months; 22/30 (73%) hours later. Eighty patients in two centres died, 26/30 (87%) were alive 3/12 months received midazolam 5 mg iv before gastro- after procedure. Three had tube in for more Endoscopic sphincterotomy: how safe and scopy. After endoscopy half (n=40) than two years. successful in the 1980s? received flumazenil (0.5 mg iv) and the There was no procedural mortality. others (n=40) placebo. Significantly more Single major complication was necrotising D VAIRA, L M D'ANNA, J DOWSE1T, S R CAIRNS, patients were fully conscious in the fascitis 1/30 (3%). Minor complication was A POLYDOROU, S WILLIAMS, A HATFIELD, P R flumazenil group at five minutes (77.5% v peristomal inflammation 4/30 (13%). SALMON (Department of Gastroenterology, 27.5%; p<0001) and 30 minutes (80% v Technical problems included broken string The Middlesex Hospital, London) Recent http://gut.bmj.com/ 42.5%; p<0.001) after reversal, but not at (one) and tube blockage (two). One patient studies suggest that endoscopic sphincter- 60 minutes. Times to complete Trieger (dot with recurrent reflux required endoscopic otomy may not be as safe as previously jointing) tests were significantly faster in the pergastrostomy jejunal feeding tube. Endo- stated. There is, however, no recent large flumazenil group at 5, 30, and 60 minutes. scopic gastrostomy is a useful technique for single centre study where prophylactic anti- Recall of the endoscopy after sedation was feeding occasional patients who cannot biotics are used routinely and where a policy the same in each group (30% and 25% swallow or tolerate nasogastric tube of nasobiliary or stent placement for failed p=0.62), but significantly more of the feeding. duct clearance exists. Since November flumazenil treated group remembered 1983, sphincterotomy was the treatment on September 24, 2021 by guest. Protected copyright. transfer to recovery area (95% v 56%, intention in 1007 consecutive patients at our p

A1490 The British Society ofGastroenterology ing 3-6%, pancreatitis 0-7%, cholangitis Successful endoscopic management of post- poor colonic cleansing means repeated 0-3%, perforation 0.3%). Procedure- operative bile leak tests. related mortality was 0-6% (4/667: Our own experience suggested that it was haemorrhage two, pancreatitis one, cardio- S R CAIRNS, A HEAGERTY, J DOWSEfT, D VAIRA, not necessary to reduce the dose of Picolax respiratory arrest one) and 30 day mortality A POLYDOROU, A HATFIELD (Department of in IBD patients and, to confirm this, we 1%. There was no biliary related death in Gastroenterology, Middlesex Hospital, studied the adverse effects in patients the medium term follow up. London) Sixteen patients (MWF 4/12) mean undergoing colonic investigation. All This review confirms the clinical impres- age 61 years were referred for endoscopic received full dose Picolax and 55 out of a sion that endoscopic sphincterotomy is a management of postoperative biliary leak- total of 267 examinations were in IBD safe and effective procedure. age persisting for between three and 52 subjects. weeks after surgery. Presenting features Picolax precipitated or exacerbated were bilicutaneous fistula in nine, perihe- abdominal pain in a smaller proportion of patic abscess in four, and persistent T-tube IBD patients than in other diagnostic Needle knife sphincterotomy (N-KS) - an drainage in three patients. Six patients were groups (p<0.01). Inflammatory bowel initial experience jaundiced at the time of referral. Endo- disease patients also had less increase in scopic retrograde cholangiography (ERC) stool frequency (p<0.001) and gave a lower A A POLYDOROU, J F DOWSETr, D VAIRA, S R demonstrated site and cause of biliary leak- score for nuisance resulting from Picolax CAIRNS, L D'ANNA, H M ASHRAF, P R SALMON age in all patients. The cause of biliary (p<0-05) than those with diverticular (Department of Gastroenterology, The leakage was retained common duct stones disease or the irritable bowel syndrome. Middlesex Hospital, London) Many studies (five cases), benign biliary stricture (five There was no evidence of disease exacerba- have shown that endoscopic sphineter- cases), and malignant biliary obstruction tion. We conclude that Picolax bowel prep- otomy (ES) is a safe and effective pro- (six cases). Treatment was endoscopic aration can be safely used in full dosage in cedure. The success rate is over 90%. This sphincterotomy in six, endoscopic place- patients with inflammatory bowel disease. procedure is difficult, however, or imposs- ment of a 10 French polyethylene stent in ible in a certain proportion of patients with nine, and 6-5 French polyethylene stents in difficult bile duct cannulation as well as one patients. There were no complications A new light delivery system for the treatment those with difficult access - for example, of sphincterotomy or stent placement. Bile of obstructing gastrointestinal cancer Billroth II, periampullary diverticulum, leakage ceased in all patients with resolu- minor papilla sphincterotomy, ampullary tion of jaundice and sepsis. Patients with J T ALLARDICE, A C ROWLAND, C P SWAIN, M F tumour, impacted common bile duct stones cleared from the duct remain well up GRAHN, N S WILLIAMS (The London Hospital (CBD) stones, low CBD strictures. We to 34 months (mean 19) after endoscopic Laser Centre, Surgical and Gastro- have successfully used the needle knife thereapy. Stents were removed in patients enterology Units, The London Hospotal, sphincterotome (N-KS) to improve the with benigh strictures after between two Whitechapel, London) Laser treatment of http://gut.bmj.com/ success rate of the CBD cannulation and and nine months with resolution of the GI neoplasms is severely hampered by the ES. In this study we report our results for stricture in all but one case. Three patients inability to deliver a predetermined energy the period January 1986 to May 1988. stented for malignant biliary obstruction density to constrictions. We have therefore During that period we performed 760 endo- died after mean five months. designed and constructed a new light scopic sphincterotomies. N-KS was Retrograde cholangiography is highly delivery system (LDS) which overcomes attempted in 85 patients in whom the ES effective in determining the stie and cause this problem. failed. The reason for ES failure was duo- of postoperative biliary leakage. Endo- Our system uses a polytetrafluoro- denal diverticulum in nine, distorted scopic therapy can provide immediate and ethylene diffuser, mounted on an optical on September 24, 2021 by guest. Protected copyright. duodenum in 23, ampullary tumour in nine, in some cases, definitive treatment. fibre to scatter laser light cylindrically. A low common bile duct stricture in 25, perspex window encloses the system in a impacted stone in six, previous Billroth II modified Eder-Puestow dilator. A specially gastrectomy in two and no obvious reason developed computerised densitometry in 11. N-KS was successful in 67 (80%) Safety of sodium picosulphate/magnesium method shows that longitudinal and circum- patients and resulted in CBD access and/or citrate mixture (Picolax) in the bowel prep- ferential fluxes provided by the LDS are completion of the ES using the ordinary aration of patients with inflammatory bowel uniform, optical density 2±0-5 units. sphincterotome in all cases the same day or disease (IBD) Stricture dilation equalises target and LDS three to five days later. Complications after surface areas and provides fluxes in the the use of the N-KS were: cholangitis in A J G MCDONAGH, P SINGH, W J PILBROW, G R order of 200 mW/cm2. A central guidewire one, bleeding in five (one death), pancreati- YOUNGS (Departments of Gastroenterology channel allows accurate endoscopic and tis in two (one death), retroperitoneal per- and Radiology, Chester Royal Infirmary, radiological placement. Stainless steel caps foration in four. The N-KS increased the Chester) The adverse effects of Picolax are define a closed system ensuring that all light success rate of the ES by 9% (67/60) but milder than those of earlier agents such as is absorbed by tumour target. Interchange- was followed by high number of complica- sennosides and, in a survey of consultant able sizes (10-15 mm diam and 2-7 cm tions. It provides CBD access in patients members of the North of England Gastro- length) suit stricture parameters, the system with difficult CBD cannulation when con- enterology Society, we found that 89% of is durable and easily cleaned. ventional techniques failed. This approach respondents routinely use Picolax to pre- Patients with obstructing oesophageal or adds an extra dimension beyond conven- pare the colon for radiology or endoscopy. rectal malignancies treated with photo- tional cannulation. It is effective but must Ninety two per cent of these clinicians still dynamic therapy improved by at least one be used only by the experienced endo- reduce or omit the laxative in patients with grade when assessed by quantitative barium scopists. known or suspected IBD. For some patients examinations and symptomatic improve- Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1491 ment. The closed system concept has for oesophagus by colonoscopy and compared prandial hypoglycaemia. Hunger occurred the first time enabled accurate dosimetry to results with 56 age and sex matched con- when plasma glucose was still raised in two the entire stricture length and ensures that trols, presenting with symptoms suggestive subjects, and continued to increase when a predetermined light energy dose is of irritable bowel syndrome. Barrett's oeso- plasma glucose levels were constant or even absorbed by tumour. phagus was defined as histologically con- increasing. The stomach had emptied over firmed columnar epithelium at least 3 cm 80% of the meal when hunger occurred in above the superior margin of a manometric- seven subjects. Fullness was more closely Endoscopic evaluation of human colonic ally defined lower oesophageal sphincter. related to gastric emptying, but in four of 10 blood flow in health and inflammatory bowel Eleven of 28 patients were identified only subjects, fullness had declined to zero for disease after a follow up gastroscopy and biopsy. between 0 and 120 minutes before an No patient had symptoms suggestive of increase in hunger. The data are perhaps D E LOFT, C J SHORROCK, S A RILEY, W D W REES colonic neoplasia. more compatible with the idea that hunger (Department of Gastroenterology, Hope No patients had oesophageal tumours can be evoked by a reduction in the stimula- Hospital, Eccles Old Road, Salford) Altera- or high grade dysplasia. Six patients with tion of small intestinal receptors by nutri- tion in blood flow may play a pathogenic Barrett's oesophagus had colonic tumours ents. Peak hunger scores were achieved role in colonic mucosal disease. Using the (21%) (one Duke's B carcinoma, one only when gastric emptying levels had technique of laser doppler flowmetry (LDF) Duke's A carcinoma, two multiple adeno- ceased, phase III of the interdigestive we have measured colonic mucosal blood matous polyps, two solitary adenomatous migrating motor complex, which usually flow (CMBF) during colonoscopy in 17 polyps) compared with one control (2%) returns when the exposure of the upper healthy subjects and six patients with (solitary adenomatous polyp) (p<0-01%). small intestine to nutrients is minimal, was inflammatory bowel disease. We conclude that (1) This study confirms always associated with peak or near peak Colonic mucosal blood flow was the high prevalence of colonic neoplasia in levels of hunger. measured using a Peri flux PF2 LDF with Barrett's oesophagus. The yield from endoscopic probe passed down an Olympus screening colonoscopy in Barrett's oeso- CFLB3R colonoscope. Blood flow was phagus is higher than in other groups at Acute stress affects oesophageal function measured at various sites (rectum, sigmoid, 'high risk' from colonic neoplasia such as descending, transverse) in the colon of eight long standing inflammatory bowel disease. D A F ROBERTSON, K NAYLOR, R C S AYRES, C L subjects prepared with a phosphate enema (2) Barrett's oesophagus may be more SMITH (Department of Medicine II, South- and nine prepared with X prep and 500 ml of common than appears at a first endoscopy. ampton General Hospital, Tremona Road, 10% Mannitol. Rectal blood flow was (3) Colonoscopy is more important than Southampton) Stress can affect gastro- measured in six patients with inflammatory gastroscopy in screening for cancer in intestinal function but the mechanisms bowel disease; five with ulcerative colitis Barrett's oesophagus. involved in its effect on oesophageal func- and one with Crohn's colitis. tion are not clear. Abnormal oesophageal http://gut.bmj.com/ In the normal subjects there was no motility may be responsible for some symp- significant regional variation in CMBF toms in the irritable bowel syndrome. We (means (SE): rectum=22-7 (3.5); sigmoid have studied the effect of three different 20-8 (2.6); descending colon 21-9 (5.1); PLENARY SESSION stressful stimuli - hyperventilation, dichotic transverse colon 22-0 (5.0) arbitrary units). hearing and the forearm cold pressor test on Coefficient of variation was <10%. Bowel Investigation into the physiological mecha- oesophageal function in healthy volunteers preparations used did not influence CMBF nisms that determine the development of (n= 15, mean age 22 years). Persistalsis in (22-8 (5.9), n=8 and 22-5 (4.5), n=9). hunger in man the lower oesophagus was measured in Rectal blood flow was significantly response to swallows of 4 ml cold water on September 24, 2021 by guest. Protected copyright. increased in the six patients with inflamma- C P SEPPLE, N W READ (Sub-Department using a triple lumen perfusion tory bowel disease (53.8 (8.4), p<0-002, Human Gastrointestinal Physicology and catheter with ports 5 cm apart, the lowest 2 tailed Mann Whitney U test). Nutrition, University of Sheffield, Royal being 5 cm above the lower oesophageal The technique of laser doppler flowmetry Hallamshire Hospital, Sheffield) The sphincter, under control conditions and may be used to assess colonic blood flow in purpose of this study was to test the validity during each stressful stimulus. man. Preliminary observations suggest that of the various factors, thought to be Hyperventilation produced marked blood flow is significantly increased in involved with the onset of hunger in man. tachycardia but no demonstrable change in patients with inflammatory bowel disease. Experiments were carried out in 10 healthy oesophageal function. Dichotic heating volunteers, who were intubated nasally with produced no change in pulse or blood a triple lumen manometric intestinal tube. pressure but a marked increase in the fre- Screening for colonic cancer in patients with The subjects ate 300 g mashed potato, quency of non-peristaltic waves (10.5% to Barrett's oesophagus labelled with 25 [tCie Tc tin colloid. We 26-7%, p<0.001) and of the amplitude of monitored gastric emptying of this meal, peristaltic waves (70.9 mmHg to 88-7 D A F ROBERTSON, C L SMITH (Department duodenal and jejunal pressure activity, mmHg, p<0-01). of Medicine II, Southampton General plasma glucose concentrations and assessed The cold pressor test produced systolic Hospital, Tremona Road, Southampton) hunger and fullness at regular intervals on and diastolic hypertension and increased An association between Barrett's oesopha- visual analogue scales. The study lasted amplitude of peristalsis (85.6 mmHg, gus and the development of colonic neo- from five to six hours until hunger had p<0.01), and increased frequency of non- plasia has been described (Sontag, Lancet increased to high levels. peristaltic contractions (34.7%, p<0-01). 1985) but not confirmed. We have prospec- Our results did not indicate that the onset Stressful stimuli can markedly affect tively screened 28 patients with Barrett's of hunger was strongly correlated with post- oesophageal functions in normal subjects. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1492 The British Society ofGastroenterology

During the cold pressor test this is associ- intubation. We prospectively compared 45 the A or B and 29 in the C risk group ated with sympathetic overactivity, but not patients with carcinomas of the oesophagus according to Child. Forty patients (13%) during dichotic hearing challenge. and gastric cardia treated with endoscopic dropped out of the study and 12 died from Nd:YAG laser therapy at UCH with 12 liver failure but in no one HCC was demon- patients treated by endoscopic intubation in strated at autopsy. Mean follow up is Comparison of indomethacin and fenbufen Nottingham; the two groups were compar- presently 17 months. Twenty six cases of on morphology and blood flow in human able for mean age, tumour position and HCC have been diagnosed and incidence, gastric mucosa length, and proportion ofsquamous cell and on the bases of mean follow-up, is 6-7% per adenocarcinomas. Dysphagia was graded year, FP levels were below 100 ng/ml in 13 C J SHORROCK, W D W REES (Department on a scale of 0-4 (0=normal swallowing, patients (50%), and 25 ng/ml in five (19%). of Gastroenterology, Hope Hospital 4=dysphagia for liquids). Mean dysphagia Twenty nine other patients with FP ranging (University of Manchester School of grade (DG) pre-treatment was 3 (SD= 1) in from 25 to 100 nglml and negative US are Medicine), Eccles Old Road, Salford) both groups. Dysphagia was initially being screened for HCC. Ultrasound was Thirty four healthy volunteers were gastro- improved by at least 1 grade in 75% of laser diagnostic in 26126 patients. False posi- scoped before, one, seven, and 28 days treated cases and 83% of intubated patients tives at US were relatively low (2.5%). during treatment with indomethacin 50 mg (NS). Successful overall long term pallia- Seven cases of HCC were diagnosed in tds or the NSAI prodrug fenbufen 450 mg tion of dysphagia was achieved in 59% of HBsAg+ve (7.9% per year), four in bd. Mucosal integrity was scored [0 laser treated patients and 83% of intubated alcoholic cirrhosis (3.7% per year), three in (normal) to 4 (severe damage)] and gastric patients (NS); the mean DG over the haemochromatosis (25%), one in PBC mucosal blood flow measured using a laser remainder of the patients lives (mean (2.3%), 11 in cryptogenic cirrhosis (5.7%). doppler technique. survival 18 weeks) was 1-6 (SD=0-5) for Only three of 26 were eligible for surgery. With indomethacin, all had mucosal both groups (p<:005 compared with pre- Survival periods in the three operated damage at day 1 (scores: 1-7 (0.2), n=24). treatment DG for both groups). Laser patients are six, 10 and 32 months respect- Damage persisted at day 7 (score: 0-96 (0.2) treated patients however, required an ively. Mean survival in non-operated HCC with two subjects developing discrete average of 4-7 procedures compared with patients is 4-8 months (range 1-15). In ulcers. Virtually all damage had resolved at 1-2 for intubated patients (p<005). Twenty conclusion, US seems to be more useful 28 days (n= 18). Fundal and antral mucosal per cent of laser treated and 27% of intu- than FP in screening for HCC. Even FP blood flows were reduced at day 1 (arbitrary bated patients could eat most or all solids values 100 ng/ml must be regarded as diag- units; 64 (4) pre v 52 (4) post indomethacin (NS). Treatment induced perforation nostic; in cirrhosis an incidence of HCC in fundus, n=12, p<0-01; 40 (3) pre v 31 (4) occurred in 17% of patients undergoing higher than 6% per year is to be expected, post indomethacin in antrum, n=12, intubation but in only 2% of laser treated particularly in haemochromatosis and p<0.05). At 28 days values had returned to patients. HBsAg+ve patients; finally, although the baseline. The longterm quality of palliation is very survival rate is encouraging for operated http://gut.bmj.com/ With fenbufen, there was mild damage at similar with both endoscopic techniques but patients, even a careful follow-up does not day 1 (score: 0.2 (0.14), n=10), significantly laser treatment requires more frequent seem to improve the resectability rate. less than with indomethacin (p<0.0001). endoscopy. Laser therapy should be con- Damage was more marked at day 7 (score: sidered as complementary to endoscopic 0*6 (0.3), n=9). At 28 days all damage had intubation particularly for recanalising Liver membrane phosphorylation by resolved. Fundal and antral blood flows tumour overgrowth of tubes and strictures hepatic growth factors were unchanged at day 1 but at day 7 fundal initially impassable with a guide wire. Laser flow had fallen, corresponding to the treatment alone can be used when oeso- A C SELDEN, D A VESEY, H J F HODGSON on September 24, 2021 by guest. Protected copyright. greater damage (62 (3) v 50 (3), n=9, phageal endoprostheses are poorly (Department of Medicine, Royal Post- p<0-05). Mucosal recovery was associated tolerated. graduate Medical School, London) Partial with return of blood flow to normal. hepatectomy in man and rats induces a high In conclusion, gastric mucosal function is molecular weight growth factor in serum, disrupted by indomethacin and to a lesser Does an early diagnosis of hepatocellular hepatotropin, capable of stimulating extent by the prodrug, fenbufen. The carcinoma (HCC) improve survival in hepatocyte proliferation in culture. To mucosa adapts to continued damage by cirrhotic patients? characterise the early membrane events both agents. initiated by hepatotropin, we incubated rat F FARINATI, M ZAGOLIN, M CHIARAMONTE, A liver membranes with purified preparations FLOREANI, S FAGIUOLI, R NACCARATO (Depart- of rat hepatotropin for 15-30 minutes, at Longterm palliation of malignant dysphagia ment of Gastroenterology, Institute of 0'C before the addition of 12PATP, terminat- - laser v intubation Internal Medicina, University of Padova, ing phosphorylation after 1 min-12 h, and Italy) In the attempt to improve the severe analysing the phosphorylated membrane L A LOIZOU, D GRIGG, C ROBERTSON, M prognosis of HCC we carefully followed up proteins by SDS-PAGE and autoradio- ATKINSON, S G BOWN (National Medical a group of 315 consecutive cirrhotic patients graphy. Changes were compared with the Laser Centre, University College Hospital, with fetoprotein (FP) determination and effects of the hepatic mitogen EGF. Hepa- London and Queen's Medical Centre, ultrasound (US) every six months; 199 men totropin did not phosphorylate the EGF Nottingham) The short term efficacy of laser (mean age 54, range 17-81 yrs, 62 receptor, visible in 5% SDS-PAGE at MW palliation of malignant dysphagia is well HBsAg+ve, 72 alcoholics, eight with 170 kD, but enhanced phosphorylation of a documented; few groups, however, have haemochromatosis, 29 with PBC, and 135 17kD band visualised in 15% PAGE. analysed the follow up in sufficient detail to with cryptogenic cirrhosis) entered the Quantitative analysis by digitising auto- give a true comparison with endoscopic study. Two hundred and eighty six were in radiography confirmed significant phos- Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1493 phorylation. Epidermal growth factor shown, however, in terms of success, 30 day University, NY, USA) Fetal human gut is caused the expected phosphorylation at 170 mortality, in hospital stay nor survival. inaccessible to direct study in vivo. We kD, but did not alter phosphorylation of transplanted small intestine from nine the 17 kD protein. Further characterisation fetuses of 18 to 20 week gestation (obtained of this protein, phosphorylated by hepato- Selection, organisation, and follow up of with permission after therapeutic abortion) tropin, should elucidate the mechanism children on home parenteral nutrition subcutaneously into athymic nulnu mice. of hepatic regeneration after partial (HPN) Mucosal morphology and CCPR were hepatectomy. measured by microdissection, and meta- P STAPLEFORD, W M BISSET, P J MILLA phase arrest after administration of (Hospital for Sick Children, Great Ormond colchicine to host mice 35-150 g post- Malignant obstructive jaundice: what is the Street, London) Some children require PN transplant. Enterocyte surface character- best management? - A prospective random- for prolonged periods of time. Recent istics were studied with a panel of immuno- ised trial ofsurgery v endoscopic stenting advances have made the use of HPN in such luorescent monoclonal antibodies to human children possible. We present experience of microvillus membrane antigens. J F DOWSEIT, R C G RUSSELL, A R W HATFIELD, five children (age 14 months to 15 years) Mean crypt depth of transplanted tissue P B COlTON, A G SPEER, J HOUGHTON, T who suffered from chronic intestinal was 240 [sm. Crypt cell production rate was LENNON, L STANESBY, K MACRAE, R AHERN pseudo-obstruction (three), congenital 4-4 cells/crypt/h and net villus influx 12-2 (The Departments of Gastroenterology and enteropathy (one), and short gut syndrome cells/villus/h. Crypt cell production rate of Surgery, The Middlesex and London (one). They were all developmentally athymic mice was 15-5 cell/crypt/h, compar- Hospitals, London and The Cancer normal, from a stable family and had at least able with balb/c mice. Untransplanted Research Campaign Trials Centre) During a 20% residual absorptive function. All child- tissue expressed sucrase, peptidase and two and a half year period to June 1988, 103 ren received a single bag amino acid/ aminopeptidase. Transplanted tissue patients with obstructive jaundice (bilirubin glucose/electrolyte solution ± a lipid expressed these antigens plus maltase and >100 [smol/l) caused by primary unre- emulsion, which supplied between 40-80% lactase within 130 days. Immunoprecipita- sectable low common duct malignancy of their nutrient requirements. The tion of proteins from brush border isolated (pancreas, ampulla) and no contraindica- nutrients are prescribed by the GP on a from fetal intestinal membranes confirmed tions to surgery, were prospectively FP10, the district health authority supply these findings. randomised to surgical bypass or endo- the infusion pumps and disposable and the Human fetal small intestine regenerates scopic stent insertion. Fifty two were nutrients are delivered by a commercial after subcutaneous transplant to athymic allocated surgery and 51 stenting. All had home care company. We have followed up mice, exhibits epithelial cell turnover and normal duodenums and no previous endo- these children for two to 18 months (av maturation of expression of a range of scopic nor surgical intervention. There were 10.4) at monthly intervals. All are growing surface antigens. The model represents a no significant differences in age, sex, nor and developing normally. Catheter related means to study the ontogeny of the prenatal http://gut.bmj.com/ risk factors between the two groups. Two complications include one line infection human gastrointestinal tract. surgical and one stenting patient were not (patient receiving additives to PN) and two treated because of rapid clinical deteriora- blocked lines due to fat sludging where lipid tion after randomisation. was added to single bag of nutrients. Non- Indomethacin induced increased small Surgical bypass was successful in 47/52 catheter related complications were equally intestinal permeability: the role of prosta- (90%) and stenting in 47/51 (92%) [NS]. few, three patients developed subclinical glandins The three surgical failures were stented selenium deficiency and one thiamine (two successful, one failed) and the three Oral of I BJARNASON, P SMETHURST, G C FENN, C E LEE, deficiency. supplementation on September 24, 2021 by guest. Protected copyright. stenting failures had surgery (all success- vitamins and trace elements successfully I S MENZIES, A J LEVI (MRC Clinical Research ful). There were 44 surgical complications reversed the deficiencies. Our experience Centre, Searle Pharmaceuticals and St in 21 patients (seven major) and 15 stenting suggests that parenteral nutrition can Thomas's Hospital, London) Increased complications in 14 patients (three major) successfully be carried out at home in child- intestinal permeability is thought to be an [p<0-01]. The 30 day mortality of surgery ren in the UK, that additives should be important initiating factor in the develop- was 13% and of stenting 8% [NS]. Twenty given orally whenever possible, that lipid ment of NSAID induced small intestinal eight surgical and 30 stenting patients are should not be used in a single bag system inflammation but the role of prostaglinds is dead. The mean survival was 3-5 months for and that unusual deficiency states may uncertain. surgery and 5-0 months for stenting (alive: occur. We recommend that a multi- Twelve volunteers ingested a 100 ml test mean 5-5 months for surgery and 4.5 disciplinary approach on a regional basis solution containing 3-O-M-glucose (3 MG, months for stenting). Average hospital stay should be used. 0.2 g), D-xylose (DX, 0.5 g), L-rhamnose was 15 days for surgery and 11 days for (LRh, 1.0 g) and 5'EDTA (100 [tCi) stenting [NS]. Two stented patients have followed by five hour urines to assess active required gastroenterostomy. Malignancy Crypt cell production rate (CCPR) and and passive carrier mediated transport and was biopsy proven in 63% of surgical surface membrane characteristics of trans- trans- and paracellular permeability patients and 76% of stenting patients. planted human fetal small intestine respectively. Each was assessed as (A) base- Stents have been changed on 14 occasions line; (b) following 200 [&g misoprostol (10 patients). L T WEAVER, RB HENDREN, A QUARONI, J (-16, -12, -81/2, -4, -11/2, -1/2); (C) Endoscopic stenting for malignant low FOLKMAN, W A WALKER (INTRO G NEALE) indomethacin 75 and 50 mg (-8, -1 h); (D) biliary obstruction has a significantly lower (Departments of Gastroenterology and B+C combined. procedural complication rate than surgical Surgery, Childrens Hospital, Boston, Mass Baseline urine excretion (mean (SE)) of bypass. No significant difference has been and Division ofBiological Sciences, Cornell 3 MG, DX, LRh, and I'EDTA was 45.8 Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1494 The British Society ofGastroenterology

(3.2)%, 31-5 (2.0)%, 10-2 (0.6)%, and 0 75 Colonic inflammation and HLAIDR Ag been determined using isolated peripheral (0.07)% respectively. B, C, and D had no expression in the colon of children with blood neutrophils. In the PSC group (n=32) significant effects of 3 MG, DX, LRh. B had idiopathic protracted diarrhoea (IPD) and ANNA was present in 84% with a median no effect on 5'EDTA (0.66 (0.08)%, C autoimmune enteropathy titre of 1 in 1000. In the group with IBD increased the excretion significantly (1.96 alone (n=76) ANNA was present in 86%, (0-31)%, p<0-001) with 11 of 12 above the S HILL, R MIRAKIAN, G R BOTTAZZO, P J MILLA with a median titre of 1 in 100. In contrast, normal range. Excretion of 51EDTA follow- (The Middlesex Hospital and Hospital For only 12% of controls (n=41) were ANNA ing D was 1-16 (0.17)% which was signific- Sick Children, London) Some children with positive and none had a titre of more than 1 antly different from A and C. These IPD, circulating enterocyte antibodies (Ec in 10. In the IBD group, titres were signific- changes were mirrored by changes in Ab), and enteropathy also have a colitis. antly higher in patients with recently active 1'EDTAILRh ratios which reflect altera- We have examined the colon endoscopic- disease. In the PSC group, high titre ANNA tions in intestinal permeability. ally in 17 such patients. Multiple biopsies correlated with raised plasma concentra- These studies suggest that indomethacin were studied histologically and by immuno- tions of aspartate transaminase (p<0-01), induced increased intestinal permeability is cytochemistry for HLA Class II expression alkaline phosphatase (p<0.01) and total mediated by reduced mucosal prosta- by the colonocytes and compared with immunoglobulin (p<0.01). Binding of glandins. Coadministation of misoprostol histologically normal colon from control ANNA to intact blood neutrophils in vivo with NSAID's may in the long term prevent subjects. Seven patients had cytoplasmic Ec could not be demonstrated and neutro- the frequency and severity of small intest- Abs, seven patients brush border Ec Abs, paenia was not a feature. The results pro- inal inflammation due to NSAID. and three patients both. In three of seven vide further evidence of involvement of patients who only had cytoplasmic Ec Abs autoimmune mechanisms in IBD and PSC. no colitis was present. The remaining 14 patients had evidence of a colitis character- Evidence for an increased driving force for ised by inflammatory infiltrate of lympho- active glucose transport across the jejunal cytes and plasma cells and an absence of Surveillance in extensive ulcerative colitis brush border membrane (BBM) in chronic epitheloid granulomas, crypt dysplasia, or improves prognosis without always prevent- diabetes goblet cell changes. Class II (DR complex) ing cancer expression was absent in both surface and E S DEBNAM, H Y EBRAHIM (Department of crypt colonocytes of control biopsies. In 14 D M MELVILLE, J E LENNARD-JONES, B C Physiology, Royal Free Hospital School of patients with colitis aberant expression of MORSON, J K RITCHIE, C B WILLIAMS (St Mark's Medicine, Rowland Hill Street, London) DR molecules was seen in crypt and surface Hospital, City Road, London) Over 22 Although studies in man and experimental colonocytes together with DR+ve cells in years, 401 patients with extensive ulcerative animals have reported a stimulation of the lamina propria. In the three patients colitis entered a surveillance programme intestinal glucose uptake in diabetes without colitis DR expression was absent. with the aim of detecting precancer orhttp://gut.bmj.com/ mellitus, the mechanisms involved remain Our data show that in over 80% of children carcinoma at a curable stage. Of 344 unclear. Here we describe the effects of with IPD and an autoimmune enteropathy patients who remained with the pro- diabetes on BBM potential difference (Vm) that inflammatory changes occur in the gramme, 12 were operated upon at stage of in intact tissue and glucose uptake by BBM colon. We suggest that analogous to similar high grade dysplasia but 17 had a carcinoma vesicles. Rats were injected with strepto- phenomena in the glands of patients with (Duke's A 9, B 3, C 4, disseminated 1). zotocin (60 mg/kg, iv) and were glycosuric classical autoimmune disease that DR+ve Excluding nine patients who emigrated, five and hyperglycaemic when used four to six colonocytes would be able to act as antigen carcinomas developed in 48 patients who weeks later. Microelectrode studies using presenting cells, by passing macrophage left the programme (Duke's A 1, B 1, C 1, on September 24, 2021 by guest. Protected copyright. tissue bathed in gassed bicarbonate saline requirements and could lead to auto- disseminated 2) at intervals of four to six revealed a hyperpolarisation of Vm in immune disease. years. The cumulative risk of carcinoma jejunal (control, -47-2 (1.0) mV (42); dia- among all patients was 3% (CI 0-13) at 15 betic, -57-4 (1.5) mV (54), p<0-001) but years, 5% (CI 0-18) at 20 years, and 9% (CI not ileal tissue (control, -40-2 (1.5) mV Anti-neutrophil nuclear antibody in inflam- 0-32) at 25 years. There were two deaths (30); diabetic -40-2 (1.6) mV (25)). Ion matory bowel disease and primary scleros- from carcinoma among patients within the substitution studies during these studies ing cholangitis programme and three among those who left implied a reduced Na permeability in it. The main reasons why surgery was jejunal, but not ileal BBM in diabetes. J A SNOOK, R W CHAPMAN, K FLEMING, D P not performed before development of Brush border membrane vesicles were pre- JEWELL (Departments of Gastroenterology carcinoma were dysplasia and undetected pared from jejunal mucosa and 3H-D- and Pathology, John Radcliffe Hospital, carcinoma (eight), carcinoma without pre- glucose (1 mM) uptake, expressed per mg Oxford) Some patients with primary ceding high grade dysplasia (six), and protein, measured in the presence of a 100 sclerosing cholangitis (PSC) and inflamma- failure of patient compliance (six). The mM NaSCN gradient. The peak: equilib- tory bowel disease (IBD) have circulating limitations of dysplasia as a marker of pre- rium ratio was unaffected by diabetes (con- autoantibodies to an antigen in the portal cancer and patient compliance make it trol, 4-4 (0.6) (10); diabetes, 4-5 (0.5) (nine) tracts of obstructed human liver. In this unlikely that any surveillance programme but initial uptake (>6 sec) was increased by study we have demonstrated with an will achieve complete prevention of 51% in this condition (p<0-05). immunoperoxidase/APAAP double- carcinoma in ulcerative colitis. The crude We conclude that the more rapid glucose labelling technique that the antigen is 5 year survival rate in this series up to 1983 movement across the BBM is a conse- specifically located within the nuclei of after operation for carcinoma was 84%, quence of an enhanced driving force for Na- tissue neutrophils. The serum titre of anti- however, and 12 patients were operated glucose cotransport. neutrophil nuclear antibody (ANNA) has upon at a stage of precancer. Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

The British Society ofGastroenterology A1495

The presence of sialomucin at the resection The median plasma bismuth concentra- alcohol. Its superiority to conventional margin identifies patients at risk of local tion before treatment (2 ng/ml) rose signific- laboratory markers suggests that it may be recurrence ofcolorectal cancer antly during treatment at three and six useful in clinical practice. weeks to 12 and 17 ng/ml respectively P M DAWSON, H C REES, N A HABIB, T G ALLEN- (p<0-01). At three, six, nine, and 12 weeks MERSH, C B WOOD (Departments of Surgery after treatment there were non-significant Randomised double-blind placebo control- and Histopathology, Charing Cross and changes of median plasma bismuth (5, 4, 2, led study of somatostatin for control of Westminster Medical School and the Royal and 4 ng/ml), compared with before treat- variceal bleeding Postgraduate Medical School, London) We ment. The median 24 h urine bismuth have previously shown that a sialomucin excretion before treatment (2.9 ptg/24 h) A K BURROUGHS, P A MCCORMICK, D band extending for >3 cm from a colorectal rose significantly during treatment at three SPRENGERS, M HUGHES, F D'HEYGERE, N cancer is significantly associated with and six weeks to 698-4 and 1012-2 ,ig/24 h MCINTYRE (Academic Departments of tumour penetration into adjacent struc- respectively (p<001). At three, six, nine, Medicine and Clinical Epidemiology, Royal tures. This study has assessed whether the and 12 weeks after treatment there was a Free Hospital and School of Medicine, presence of sialomucin in the surgical resec- persisting significant rise of bismuth excre- London) Use of vasoactive drugs for tion margin might predict those patients at tion (110.0, 30-4, 11-6, and 9.5 [tg/24 h variceal bleeding is controversial. Somato- risk of local recurrence. respectively, p<0.01). statin (250 ,ug bolus; 250 sg/h infusion) Sialomucin at the resection margin was Bismuth is absorbed during acute treat- versus placebo bolus/infusion, was assessed estimated by the high iron diamine - alcian ment with DeNoltabs, causing an 8-5-fold double-blind for control of bleeding and blue stain in 358 patients undergoing rise of plasma bismuth concentration and a prevention of early rebleeding from varices 'curative' excision of primary colorectal 349-fold rise of 24 h urinary bismuth excre- over five days. Therapy failure occurred carcinoma. Patients were scrutinised for tion. Sequestration of bismuth in the body when (i) blood/plasma 6 units transfused local recurrence during a median follow up for at least 12 weeks could party explain the over six hours at any time within first 24 h or of 24 months from operation by clinical persisting action of the compound. (ii) between 18 h and five days: haemateme- examination and sigmoidoscopy, and where sis, or melaena with either change in vital appropriate, ultrasound, CT scan, or signs or 2 g/dl haemoglobin drop. Sclerosis colonoscopy. Carbohydrate deficient (de-sialyated) or transection followed. There were 198 Sialomucin was detected at one or other transferrin - a specific test for detecting variceal bleeding episodes in trial period. colonic resection margin in 106 patients alcohol abuse Exclusions, 22 (prior failure); 19 (previous (29.6%). Local recurrence occurred randomisation 30 days); 16 (no haemo- significantly (x2=1419, p<0.001) more A KAPHUR, G WILD, D R TRIGER (Departments dynamic change); 21 (others). often in the sialomucin group (32.0%) than of Medicine and Immunology, Royal Randomised 120 episodes (92 patients): among patients in whom sialomucin was Hallamshire Hospital, Sheffield) We have ST (61), Pugh ABC grade (15, 26, 20); http://gut.bmj.com/ absent from the resection margin (18-6%). investigated the clinical balue of carbo- placebo (59), grades (14, 24, 21). Failure Multivariate analysis (Cox models) hydrate deficient transferrin (CDT) as an was significantly different: placebo 35 suggested that sialomucin at the resection indicator of alcohol abuse. Carbohydrate (59%) v ST 22 (36%), p=0033 (log rank margin was the strongest predictor of local deficient transferrin was measured by iso- test on curves of failure times). In ST recurrence coming above Duke's stage and electric focussing on agarose gel in 84 patients less blood/plasma transfused length of distal margin of excision from patients with alcohol related liver damage (p<0-004). No differences in complications tumour. and in 57 controls. In 15 alcoholics admit- or 30 day mortality per episode. Cox's

Sialomucin at the resection margin is 70% ting to at least 80 g alcohol daily for more model was used to assess clinical, endo- on September 24, 2021 by guest. Protected copyright. accurate as a predictor of local recurrence than three weeks, CDT was detectable in scopic and time factor variables - for and could be used in determining the need 13, being absent in two subjects consuming example, interval-admission to start of for adjuvant treatment. 80-100 g daily. Serial samples in nine infusion, influencing trial failure. Only patients withdrawing from alcohol under Pugh's score and trial group were signifi- hospital supervision showed disappearance cant. Somatostatin reduced the risk of Does oral tripotassium dicitrate bismuthate of the protein after three to 17 days. Carbo- failure to control bleeding by 41% (95% CI, (TDB) provide a depot preparation of hydrate deficient transferrin was detected in 66% reduction to 01% increase p=0.0503), bismuth? 8/63 outpatient alcoholics claiming to have regardless of liver disease severity. Somato- stopped drinking; in 0/31 patients with non statin is more effective than placebo and is C J GAVEY, M-L SZETO, C NWOKOLO, alcoholic liver disease; and 0/26 controls safe in acute variceal bleeding. R E POUNDER (Academic Department of with non-hepatic disorders. Sensitivity and Medicine, Royal Free Hospital School of specificity of CDT in detecting alcohol Medicine, London) The mechanism of abuse was 86% and 100%, considerably Vasoactive intestinal peptide (VIP) stimula- delayed ulcer relapse after healing with superior to yGT (93% and 38%) and MCV tion of natural killer cell activity against a tripotassium dicitrato bismuthate is (71% and 74%). Carbohydrate deficient human colon carinoma cell line unclear, as bismuth alone often fails to transferrin related to alcohol abuse rather sterilise the gastric mucosa. This study than to alcoholic liver damage. E A F VAN TOL, H W VERSPAGET, A S APENA, measured plasma bismuth concentration We conclude that CDT is highly sensitive J B M J JANSEN, M N APARICIO-PAGES, C B H W and 24 h urinary bismuth excretion before. and specific for detecting alcohol consump- LAMERS (Department of Gastroenterology during, and after six weeks of treatment tion in excess of 80 g daily for at least three and Hepatology, University Hospital, with DeNol tab 2 bd in nine patients (24-66 weeks. After alcohol cessation it is detect- Leiden, The Netherlands) Neuropeptides years, with normal hepatorenal function). able for much longer than urine or blood are directly involved in certain aspects of Gut: first published as 10.1136/gut.29.10.A1429 on 1 October 1988. Downloaded from

A1496 The British Society ofGastroenterology regulation of both the cellular and the target cell lines. Moreover, VIP preincuba- the Candela flash lamp excited dye laser in humoral immune response. In the present tion studies revealed that the actual stimula- seven patients, who had failed standard study the effect of different concentrations tion of the cytotoxic response is dependent endoscopic approaches (including mechani- of vasoactive intestinal peptide (10`2 106M on the influence of the neuropeptide on cal lithotripsy). All were high risk for VIP) on spontaneous cell mediated cyto- both effector and target cells simul- surgery, aged 64 to 80 years. Two had failed toxicity of peripheral blood mononuclear taneously. external shockwave lithotripsy, and one had cells (PBMC) against two tumour cell lines, Vasoactive intestinal peptide stimulates had three unsuccessful percutaneous pro- colon CaCo-2 and erythroleukemia K-562, the cytotoxicity against colon tumour cells cedures. In that case the laser energy was was evaluated by using the 5'Cr-release through specific activation of CD16' NK- applied through a percutaneous miniscope. assay. The mechanism of VIP modulating cells. Tumour cell lysis might be facilitated In the remainder, an Olympus prototype cytotoxicity was studied by NK-cell deple- by simultaneous binding of VIP to both mother and baby system was used (mother tion experiments with anti CD16 and com- effector and target cells. Hormonal regula- channel 5 5 mm, baby scope 4 5 mm, plement lysis, and effector or target cell tion of the immunesurveillance could thus channel 17 mm). A nasobiliary tube was preincubation. be of relevance in the development of used for flushing during lithotripsy. Vasoactive intestinal peptides signific- colorectal tumours. Energies of 30-60 mJ were used usually at antly (0.05