Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

Gut, 1980, 21, A443-A468

The British Society of Gastroenterology

A joint meeting of the Association of Surgeons, the British Society ot Gastroenterology, and the British Society for Digestive took place in Bournemouth on Wednesday, 26 to Saturday, 29 March. The very full and varied scientific programme was preceded and followed by Symposia, teaching days, and satellite sessions and supported by a varied social programme. Abstracts of scientific communications read before the Societies follow.

usual with CDCA but rare with UDCA. risk' for the spread of HBV, independent CLINICAL I We concluded that outcome of dis- of the crowding and social level. Probably solution therapy may be predicted from a as a result of their depressed immuno- six month cholecystogram; UDCA is no responsiveness, the aged, when infected more efficacious than CDCA. with HBV at a late age, tend to have mild, often subclinical, hepatitis and to remain Can a six-month cholecystogram predict HBsAg+ve. eventual response to gallstone dissolution therapy? Hepatitis B virus infection in the elderly: an underestimated problem?

M C BATESON, D B TRASH, AND A D 0 http://gut.bmj.com/ BOUCHIER (University Department of M CHIARMONATE, A FLOREANI, AND R NAC- The immune response to bacterial gastro- Medicine, Ninewells Hospital and Medical CARATO (Cattedra di Gastroenterologia, enteritis School, Dundee, and Walsall Manor Clinica Medica 10, Universita di Padova, Hospital, Walsall) Results of treatment Italy) Four hundred and five elderly J LABROOY, D J C SHEARMAN, AND D with chenodeoxycholic acid (CDCA) and subjects (aged 66-98 years) without overt ROWLEY (Department of Medicine and ursodeoxycholic acid (UDCA) for radio- disease were tested for HBsAg, Microbiology and Immunology, University lucent stones were analysed to antiHBs, antiHBc (radioimmunoassay, of Adelaide, South Australia) The anti- assess whether it was possible to predict Abbott Lab): 214 subjects lived at home, body response in serum and intestinal on September 25, 2021 by guest. Protected copyright. individual response, avoiding prolonged 191 in three homes for the aged (one of secretions after Salmonella and Shigella ineffective therapy. In 46 courses of treat- high and two of poor socioeconomic gastroenteritis has been measured using ment where no response occurred at six level). sensitive radioimmunoassay in 15 adults months, continuation on unchanged dose The three HBV markers' cumulative and 12 controls. Intestinal antibody, for at least another six months showed prevalence is significantly higher in mainly of the IgA class, was consistently subsequent complete dissolution in only (1) the total group of aged compared with detected in paired samples taken one to two patients. Twenty-three patients 1055 randomly selected adults (55.3% vs 10 weeks after infection, whereas antibody achieved complete stone dissolution, 14 21.6 %); (2) the institutionalised people was undetectable in intestinal secretions of at six months, five at one year and four at (without differences between the three most controls. While serum antibody, two years. Seven out of the nine with institutions) compared with the non- mainly of the IgG class, was similarly in- delayed total dissolution had evidence of institutionalised group (72-2 % vs 40.1 %). creased in the patients as a group, there partial response at six months. Of the 24 HBsAg+ve institutionalised was marked dissociation of serum and Using response at six months as a guide subjects, two (8.3 %) had evidence of intestinal antibody responses in indivi- to successful outcome, analysis of treat- chronic liver disease; 18 (75%) were duals. Although serum and salivary IgA ment in 35 patients with CDCA starting asymptomatic carriers; four (16.6%) antibody responses are easier to measure at 1000 mg daily showed eight complete belonged to the group of 15 who had re- than intestinal antibody responses they and 11 partial responses. Sixteen patients covered from acute hepatitis in the last did not correlate with intestinal antibody reviewed similarly after UDCA 1000 mg three years. The HBsAg+ve prevalence responses. Eight patients were studied daily had one complete and five partial increases with age and length of in- again after one to two years and intestinal responses. Nine patients treated with stitutionalisation. antibody was still detectable in the UDCA 500 mg daily had two complete In conclusion, aged people are highly majority. Patients were found to be and one partial response; two had non- exposed to HBV infection and institu- carrying the pathogen responsible for functioning . Diarrhoea was tionalisation in itself represents a 'high their infections months after sympto- A443 Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A444 The British Society of Gastroentterology matic recovery and in spite of a marked is unlikely to affect PG synthesis by multiple gastric apudomas, and was also local antibody response. homogenates, we have examined its effect found to have an asymptomatic para- The feasibility of measuring intestinal on PG synthesis in tissue culture. thyroid adenoma. One female, aged 53 antibody over a prolonged period of time Rectal biopsies from 28 patients with years, had an early mucosal in the and its dissociation from the immune ulcerative colitis or irritable colon syn- antrum, and underwent total . response at other sites emphasise the im- drome were bisected and put into tissue Thirteen of the patients were also portance of its measurement in the study culture, with or without prednisolone, studied by barium meal examination, of intestinal infection. This is particularly concentration 8.33 x 10-7 M. The super- which revealed abnormalities in only one relevant to programmes aimed at develop- natant was sampled at 16, 26 and 40 of five patients with endoscopically ing effective vaccines against bacterial hours, subjected to extraction and thin visible lesions. disease of the gut. layer chromatography, and assayed bio- The study is continuing, and patients logically for PG E2 using laminar flow with moderate and severe dysplasia are superfusion. Two biopsies not showing a being followed up. Controlled trial of alternate day pred- significantly linear rate of production of nisolone as a maintenance treatment for PG E2 were excluded. ulcerative colitis in remission Mean synthesis of PG E2 over 40 hours Low lgA plasma cell counts in the jejunal by biopsy halves not exposed to predniso- mucosa of atopic children J POWELL-TUCK, R L BOWN, T J CHAMBERS, lone was 2665 pmol/mg wet weight AND J E LENNARD-JONE,S (St Mark 's Hospit- (0-537 pmol,!~g protein). Biopsy halves K SLOPER, D SMITH, C G D BROOK, AND S al, London) Prednisone, 15 mg daily in exposed to prednisolone synthesised 10-26 HERMAN (Department of Paediatrics, divided doses, did not prevent relapse in pm/mg wet weight (0.217 pmol,',ug pro- Central Middlesex Hospital, London, and patients with ulcerative colitis in remission tein), representing significant inhibition D KINGSTON, J R PEARSON, AND M SHINER and some patients experienced trouble- (61-5%, P<0-001, and 59.6%, P<<0001, (Intestinal Stuidies Group, Division of some side-effects. In other diseases, respectively). Clinical Sciences, Clinical Research Centre, higher doses of corticosteroids have Biopsies from inflamed mucosae syn- Harrow, Middlesex) IgA deficiency has proved beneficial without increasing side- thesised more PG E2 than from unin- been postulated as a cause of gastro- effects when given in single doses on flamed mucosae (mean 33-87 pmol tmg intestinal allergy and diarrhoea in atopic alternate days. An alternative to sul- vs 9-70 pmol/!mg, wet weight P< 0.05, and infants. We studied, by immunofluo- phasalazine is needed to prevent frequent 0-674 pmol/,ug vs. 0-195 pmol '~tg pro- rescence, the plasma cells of the jejunal relapses of ulcerative colitis in a small tein, P< 0 05). mucosa obtained by peroral biopsy of all group of patients intolerant to the drug This is the first demonstration that children referred for symptoms of diar- http://gut.bmj.com/ or for whom it is ineffective. A randomised therapeutic concentrations of predniso- rhoea and,'or failure to thrive, who had double-blind crossover trial has therefore lone can inhibit PG synthesis by rectal eczema (n 15) or atopy in first degree been performed among such patients of mucosa, an action which may underly its relatives (n=four). Patients' ages were: prednisolone, 40 mg given orally in one clinical effectiveness in ulcerative colitis. 0-5 months: four; 6-11 months: four; dose on alternate mornings, against 12-23 months: six; 24 months onwards: control tablets. Results were assessed on five. The histology of the jejunal mucosa the basis of symptoms, sigmoidoscopic was normal in four (only two were under Gastroscopy survey in pernicious anaemia and rectal biopsy appearances. The study 23 months) and showed a partial villous on September 25, 2021 by guest. Protected copyright. was conducted over two periods of three atrophy (PVA) in 15 (12 under 23 months). months with a two-week crossover R W STOCKHRUGGER, G G MENON, R R Compared with the IgA and IgM plasma period. Of 24 patients who completed MASON, J 0 W BEILBY, R BOURNE, AND cell counts of non-eczematous children both periods, 11 relapsed while taking PB COTTON (Gastrointestinal Unit and under 23 months with PVA (n= 12) a control tablets but did not while taking Department of Radiology, The Middlesex significantly lower IgA cell count prednisolone, and one relapsed while Hospital, London, Bland Sutton Institute of (P< 0001) was found in eczematous (or taking prednisolone but did not while Pathology, The Middlesex Hospital atopic family history) children of the same taking control tablets (P< 0-01). One Medical Sc.hool) We have performed age group. IgM plasma cell counts were patient had to stop prednisolone because gastroduoder.oscopywith multiplebiopsies comparable in the two groups. We con- of hyperglycaemia; other side-effects and brushing cytology specimens in 50 clude that atopic infants are unable to noted were mild. Cautious use of predniso- patients with pernicious anaemia with no mount an adequate IgA plasma cell re- lone 40 mg on alternate days appears significant abdominal symptoms. There sponse under conditions which lead to a justified for a few patients whose disease were 26 women and 24 men, mean age partial villous atrophy. Thus a defect in relapses frequently despite sulphasalazine. 62-3 years, mean duration of pernicious the protective mechanism of local IgA, anaemia 4-2 years. Gastroscopy was not hitherto reported, could lead to normal (apart from gastric atrophy) in increased antigen absorption. Prednisolone inhibits prostaglandin syn- only 17 patients. Twenty-five showed thesis by intact rectal mucosa gastric mucosal dysplasia (mild 17, moderate five, severe three), which was Short stature a primary manifestation of C J HAWKEY AND S C TRUELOVE (John more severe in the body than the antrum, coeliac disease: a feature in need of Radeliffe Hospital, Oxford) Sulphasala- and rrmore frequently detected by biopsy emphasis zine has been shown to inhibit prostag- than cytology. Nine patients had polyps, landin (PG) synthesis by rectal mucosa; four of which were treated by endoscopic A GROLL, D C A CANDY, M A PREECE, AND corticosteroids have not. As prednisolone polypectomy; one of these patients had J T HARRIES (The Hospital for Sick Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of GastroeniterologyA A445

Chlildreni, Gr)eat Ornmond Street, and Using a whole-body counter we have in the rectal mucosa at the start of the Institute of Child Health, London) It is measured the absorption of 59Fe in seven trial and the treatment effect. generally accepted that children with normal subjects, 10 iron deficient con- No prophylactic or therapeutic effect of coeliac disease (CD) almost invariably trols and 13 iron deficient colitics. Iron DSCG in ulcerative colitis was demon- present with gastrointestinal symptoms deficiency was confirmed in patients with strated. which, if an early diagnosis is not estab- hypochromic microcytic anaemia by the lished, may ultimately result in short presence of low transferrin saturations, stature (height <3rd centile). Short low serum ferritins and reduced or absent Impact of endoscopy on outcome of gastric stature in the complete absence of gastro- marrow iron stores. cancer intestinal symptoms, however, has not The iron deficient controls and the iron been emphasised as a presenting feature. deficient colitics absorbed 66.7 + 30.9 % G HOLDSTOCK AND S BRUCE (Professorial We have studied 37 patients with short (mean ± 1 SD) and 66.0 ± 26.5 respec- Medical Unit, Southampton General Hos- stature with no gastrointestinal symptoms tively of the administered 59Fe. These pital, Southampton) In an attempt to in whom endocrinological investigations values did not differ significantly from study the effect of upper gastrointestinal were normal; mean chronological and each other but were raised to a highly endoscopy on the diagnosis and prognosis bone ages were 11-35 (range 4-82-16-96) significant extent (P< 0.001) above the of patients with gastric cancer, we have and 7-36 (range 2-98-12-60) years re- absorption values of the normal subjects studied a total of 300 patients with histo- spectively. Eight of the patients had sub- (12-3 ±9.3%/). logically proven gastric cancer in three total or severe partial villous atrophy on We conclude from these findings that different centres. In Centre A, endoscopy jejunal biopsy, and a gluten-free diet iron deficient colitics have an increased was freely available to hospital doctors resulted in accelerated growth. Haemato- iron absorption comparable with that of only, while in Centre B it was also avail- logical investigations were the only dis- other iron deficient subjects and that their able to general practitioners by direct criminating parameters: five of the eight deficiency should be correctable with oral referral. In Centre C, there was no regular patients were anaemic (haemoglobin 7.3- iron. endoscopy service. Patients were referred 10.29'dl), serum iron was decreased in initially for endoscopy in 52, 49, and 8 % four of the five anaemic patients and of cases in Centres A, B, and C respec- normal in two non-anaemic ones, serum tively. The remainder initially underwent folate was reduced in six including two Controlled study of disodium cromoglycate barium studies. The mean duration of non-anaemic patients, and RBC folate (DSCG) in the treatment of ulcerative symptoms before diagnosis (A=27 weeks, reduced in four including one non- colitis B=26 weeks, C=27 weeks) and survival after surgery (A =21 weeks, B=20 weeks, anaemic patient. V BINDER, L ELSBORG, J GREIBE, C HEND- http://gut.bmj.com/ This study emphasises the importance C=22 weeks) did not differ between the RIKSEN, L H0J, K B JENSEN, E KRISTENSEN, three centres. The outcome for patients of jejunal biopsy in the investigation of B MARNER, J RASK MADSEN, P RIIS, AND children with short stature, who have no initially diagnosed endoscopically did not L WILLUMSEN (Herlev University Hospital, differ from those diagnosed radiologically gastrointestinal symptoms. We suggest University of Copenhagen, Denmark) One that all such children should be subjected and was independent of the means of hundred and forty-one patients with referral-that is, GP or hospital referral. to biopsy, even if haematological investi- ulcerative colitis completed a double- gations are normal. Prognosis was not related to the duration blind trial of either disodium cromo- of symptoms before diagnosis. In terms of glycate (DSCG) (800 mg/day) or placebo. false positives and false negatives, radio- on September 25, 2021 by guest. Protected copyright. The treatment was continued for one year logy proved almost as reliable as endo- or until other treatment was considered scopy as a first-line measure in the CLINICAL 11 necessary. One hundred and one patients diagnosis. This study suggests that endo- on sulphasalazine continued that treat- scopy has had little if any effect on the ment during the trial. No patient had outcome of gastric cancer. Is iron absorption impaired in patients with received corticosteroids during a period of ulcerative colitis? one month before the trial. Eighty-one patients had active ulcera- Effect of cimetidine on the gastric bacterial I G BARRISON, P D ROBERTS, AND S P KANE tive colitis, whereas the disease in 60 flora (Departments of Gastroenterology and patients was clinically inactive. Haematology, West Middlesex Hospital, Thirty-three per cent of the patients on W S J RUDDELL, J M FINDLAY, A T R AXON, Isleworth, Middlesex) Iron deficiency DSCG and 390% of those on placebo im- B A BARTHOLOMEW, AND M J HILL (Depart- anaemia is a common complication -of proved clinically. Improvement was noted ment of Gastroenterology, Leeds General chronic ulcerative colitis, but guidelines by in 230 of the patients Infirmary, Department ofGastroenterology, are lacking as to the optimal route of iron on DSCG and in 34 % of those on placebo. Bradford Royal Infirmary, and Bacterial replacement. Since the small intestinal The differences are statistically non- Metabolism Research Laboratory, Colin- mucosa is sometimes histologically and significant. dale, London) The therapeutic efficacy functionally abnormal in active colitis, The relapse rate was recorded in in- of cimetidine is presumably related to its oral iron therapy might be inappropriate. active cases: 380% of patients on DSCG potent anti-secretory action, and we have The aim of the present study was to relapsed compared with 21 % of those on investigated the changes that this produces establish whether iron absorption is im- placebo. The difference is non-significant. on the gastric bacterial flora. paired, normal, or enhanced in iron de- No relationship was found between the Gastric juice from 31 patients was ficient colitics. occurrence of eosinophils and mast cells studied before and after a month's course Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A446 The British Society of Gastroenterology

of cimetidine. As expected, there was a patients. Mucosal abnormalities were de- Haematology, West Middlesex Hospital, highly significant increase in pH tected in 14 (18%) patients. London and Department of Haematology, (p< 0001). Total bacterial count (log1o A previous study having shown that Hammersmith Hospital, London) Con- organisms per ml) increased from 1-81 + biopsies from this site are comparable to troversy surrounds the cause and natural 0-46 (mean±SEM) to 4-58±0 54 (P< those from the conventional site at the history of hyposplenism in coeliac disease. 0-001). There was a significant increase in duodenojejunal junction, it is concluded In contrast with previous studies it is our Gram+ve cocci (P<0-005), Enterococci that endoscopic duodenal biopsy is a valid experience that the features of hypo- (P< 0005), Strep. salivarius (p< 0001) alternative to conventional suction biopsy splenism are not reversed by treatment and Lactobacilli (P<0-005). This pattern of and, moreover, has a number of ad- with a gluten-free diet. In 28 patients with change suggests the development of a vantages. adult coeliac disease we found no cor- resident and metabolically active gastric relation between the half-life of heat- flora, including important numbers of damaged red cells and either the duration 'faecal' organisms, rather than merely an Nocturnal growth hormone secretion in of treatment with a gluten-free diet or the increase in transients derived from food growth failure due to Crohn's disease length of pretreatment exposure to gluten. and saliva. That this change is secondary A significant inverse correlation was found to the therapeutically induced hypo- M J G FARTHING, C A CAMPBELL, C R W between splenic area and duration of chlorhydria is confirmed by a strong cor- EDWARDS, AND LESLEY REES (St Bar- treatment. films from 11 of relation between changes in pH and total tholonmew's Hospital, London) The role the 28 patients taken before treatment bacterial counts (r=0-8, P< 0001). of growth hormone (GH) in growth failure were compared with those taken up to 15 A short course of cimetidine profoundly due to Crohn's disease remains contro- years after the start of treatment. There alters the gastric flora and its metabolic versial. Reported GH responses to was no tendency for the hyposplenic potential. Caution is appropriate before insulin-induced hypoglycaemia have been changes to regress. In the majority the emdorsing its long-term use, particularly variable. We have measured, therefore, changes became more prominent with in view of suggestions that the intragastric the GH response to the physiological treatment. All patients were judged to be formation of carcinogenic N-nitroso stimulus of sleep by continuous venous keeping to a strict gluten-free diet. In the compounds may be catalysed by meta- for 12 hours in five children with two patients with the longest red cell bolically active bacteria in the hypo- severe growth retardation and compared half-lives repeat jejunal biopsies showed a chlorhydric , and by recent re- these findings with the GH response to normal mucosal pattern. These findings ports associating cimetidine with gastric hypoglycaemia. suggest that splenic atrophy in coeliac cancer. In three of the five children the peak disease is not reversed by treatment with a

heights of GH during sleep were reduced, gluten-free diet and is unlikely to behttp://gut.bmj.com/ resulting in a low mean five-hour GH related to the state of the jejunal mucosa secretion (3.8, 5.0, and 8-5 mu/l, normal or the duration of initial exposure to Are endoscopic small-intestinal forceps range 10-43 mu/l), although the pulsatile gluten. biopsies suitable for histological inter- pattern of secretion, assessed by peak pretation? frequency, appeared normal. The GH response to hypoglycaemia was inade- Peptic ulcer and gastric cancer B B SCOTT AND D JENKINS (Departments of quate in two children but in only one case Medicine and Pathology, Lincoln County did this concur with GH responses to C R GILLIS, D J HOLE, AND G WATKINSON on September 25, 2021 by guest. Protected copyright. Hospital, Lincoln) Although, conven- sleep. During the first six months follow- (West of Scotland Cancer Surveillance tionally, a peroral suction biopsy capsule up two children failed to demonstrate Unit, Ruchill Hospital, Glasgow, and is used for small-intestinal biopsy, forceps significant linear growth. Both had sub- University Department of Medicine, biopsy via a fibreoptic endoscope is being normal nocturnal GH secretion despite Western Infirmary, Glasgow) Clinical used increasingly. This study was designed normal responses to hypoglycaemia. The and epidemiological studies have pro- to assess the success of this technique in three other children, during this period, duced conflicting evidence of the role of obtaining suitable sections for histological have grown (growth velocities 8.0, 9.0, peptic ulceration in gastric cancer. An interpretation. and 13.0 cm/yr). Two had abnormal GH analysis of two major necropsy studies Seventy-eight patients with suspected responses to hypoglycaemia and one also (the first, consisting of some 13 000 small bowel disease were investigated by had abnormal nocturnal G H secretion. necropsies for all causes of death per- duodenal forceps biopsy via a fibreoptic We conclude that in some children with formed between 1930 and 1949 in Leeds endoscope. An average of three biopsies Crohn's disease, nocturnal GH secretion under the supervision of Professor was taken from the distal end of the is reduced but this abnormality is not Matthew Stewart, the second, of some second part of duodenum, orientated on necessarily associated with subsequent 8000 cases from nine geographically a square of plastic mesh, and examined by growth failure. distinct centres throughout the United stereomicroscopy and histology. There Kingdom in 1956) has been carried out in were no failures or complications. Using relation to two distinct groups: (1) cases strict criteria, sections from 53 % of the Splenic atrophy in adult coeliac disease: where a peptic ulcer was an incidental 246 biopsies were satisfactory for histo- is it reversible? finding at necropsy and was described logical interpretation compared with 76 % pathologically as chronic; (2) cases where of 346 biopsies taken with a hydraulic P N TREWBY, P M CHIPPING, S J PALMER, no evidence of peptic ulceration was multiple biopsy capsule. At least one P D ROBERTS, S M LEWIS, AND J S STEWART found. biopsy was satisfactory from 86 % of (Departments of Gastroenterology and Age and sex specific rates of stomach Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastroenterology A447 cancer were compared between the two be involved. Thiamine deficiency and It is suggested that it is caused by the groups. The frequency of gastric car- reduced availability of 5-PLP may be deposition of bile acids in the skin and is cinoma for both post-mortem studies among the factors contributing to brain relieved by the administration of choles- showed a marked reduction for the group damage. tyramine which interrupts their entero- where a chronic ulcer was present. This hepatic circulation. No other therapy has observation was consistent in each age been shown to be effective. group and for both males and females. Hepatitis B and other viral antibodies in One of our patients observed that she The clinical and pathological features of alcoholic lost all her pruritus and the need for these ulcers reveal no distinctive feature cholestyramine while sun bathing in Italy. which accounts for these findings. P R MILLS, E A C FOLLETT, G E D URQUHART, We have followed this observation by T H PENNINGTON, G ROBINSON, AND R N M treating six patients with ultraviolet light. MACSWEEN (Departments ofGastroentero- Fasting serum bile acids were measured logy, Virology and Pathology, Western before and after one week's treatment with Inifirmary, and Regional Virus Laboratory, ultraviolet light. Cessation of itching was LIVER Ruchill Hospital, Glasgow) We have observed in five patients with a fall in bile previously reported an increased in- acids in three of five in whom levels are cidence of antibody to the hepatitis B available. Pruritus usually returns within Mechanisms of brain damage in alcoholic surface antigen (anti-HBs) in sera from weeks of stopping therapy. One patient liver disease patients with alcoholic cirrhosis, especially has continued on intermittent ultraviolet when associated with portal hyper- light the dose being titrated to keep her tension. In a series of 250 patients with free of pruritus. She has not required A D THOMPSON, S K MAJUMDAR, G K SHAW, chronic liver disease, sera were W A LISHMAN, M RON, AND W ACKER assayed for further cholestyramine. (Department of Gastroenterology/Alcohol HBsAg, anti-HBc, and anti-HBs by In this pilot study five of six patients Unit, Greenwich District Hospital and radioimmunoassay and for antibodies to with severe pruritus due to primary Bexley Hospital, Maudsley Hospital and influenza A/B, adenovirus, Mycoplasma biliary cirrhosis had remarkable relief Institute ofPsychiatry, London) Investiga- pneumoniae, psittacosis, Coxiella burnetii, from (he very simple measure of irradia- tions were undertaken to examine the re- herpes simplex, cytomegalovirus, vari- tion by ultraviolet light. Further studies lationship between brain damage, liver cella-zoster, mumps, and measles by are under way to clarify the mechanisms 100 complement fixation test and to rubella by involved. injury, and vitamin deficiency in haemagglutination-inhibition test. Con- alcoholics. Brain damage was assessed by trol groups consisted of hospital patients computerised axial tomography (EMI http://gut.bmj.com/ scan) and a battery of psychometric tests. without liver disease, and blood donors. Delayed referral in patients developing Circulating and intracellular (RBC) levels All sera were negative for HBsAg. fulminant hepatic failure after paracetamol Antibodies to hepatitis B virus antigens overdose of folate, vitamins B12, thiamine (B1), were found in 34% of 82 patients with riboflavine (B2), vitamin B,, and pyridoxal alcoholic cirrhosis (20-both anti-HBc -5-phosphate (5-PLP) were measured by J CANALESE, A GIMSON, M DAVIS, AND ROGER microbiological and enzymatic methods. and anti-HBs, seven-anti-HBs alone, WILLIAMS (The Liver Unit, King's College one-anti-HBc alone). The antibody Hospital and Medical School, Over half of the patients showed neuro- frequency was 47 % in the 38 patients with London) radiological changes indicative of atrophy Of 50 consecutive treated cases of ful- on September 25, 2021 by guest. Protected copyright. and impaired intellectual activity. Patients alcoholic cirrhosis associated with portal minant hepatic failure from paracetamol with cirrhosis tended to have particularly hypertension. These results were highly overdose, only nine had presented early large ventricles but advanced brain significant when compared with age- and enough to benefit from protective agents sex-matched controls. Other forms of (within 12 hours of ingestion) and in four changes were also observed in patients chronic liver disease did not differ from with minimal liver damage. the control There of these cases they were not administered. By comparison with a normal popula- population. was no Two patients were admitted to surgical significant difference between the alcoholic wards with acute abdominal and one tion alcoholics had significantly lower cirrhosis and control for all the pain levels of folate, thiamine (ETKo:- 62.1 ± groups underwent . During the first 72 other viral antibody titres. Therefore the hours of sudden deterioration 2.5: 89-7 ± 15.0 ,umol), riboflavine and increased incidence of B ingestion in pyridoxal-5-phosphate (7.9 ± 0-42: 12 ± 1 hepatitis virus consciousness occurred on six occasions, ng/ml). Highly significant correlations antibodies seems likely to be a specific but was always due to hypoglycaemia were found between reduced availability response and not the result of generalised rather than . Sub- of thiamine and pyridoxal-5-phosphate immune hyperreactivity. sequently, in all 50 cases, deterioration to and brain damage. Transamination reac- grade I1l to IV encephalopathy occurred tions (EGOT) were raised alcoholics between 72 and 140 hours of overdose and (470±18: 356±87,ugll) and were signi- Phototherapy for pruritus in primary the best prediction of such progression ficantly correlated with low levels of biliary cirrhosis was a rapid deterioration in the prothrom- pyridoxal-5-phosphate. Decarboxylation bin time. This was prolonged by at least and neurotransmitter synthesis may thus M A HANID AND A J LEVI (Northwick Park 25 seconds at 48 hours and 38 seconds at be inhibited. Hospital and Clinical Research Centre, 72 hours. Structural brain changes often precede Harrow, Middlesex) Pruritus is a major Comparison of the 28 patients referred significant histological liver damage, feature of primary biliary cirrhosis and for treatment of liver failure before or suggesting that different mechanisms may causes considerable distress to the sufferer. soon after development of encephalopathy Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A448 The British Society of Gastroeniterology,

(grade l-II) with the 22 who had pro- disease process than the P or x cell in hepatic injury from severe paracetamol gressed to grade III-IV showed that the cystic fibrosis. The pattern of abnor- overdose. These were sequentially rando- latter patients tolerated travel poorly, malities of the gastrointestinal endocrine mised into three treatment groups: intra- five suffering brainstem herniation during system was similar to those seen in coeliac venous cysteamine (3-6 g/20 h, n= 14), travel or soon after arrival. Overall sur- disease and tropical sprue and may there- oral methionine (10g/16h, n 13) or vival was better in those referred early fore reflect a similar response to mucosal supportive therapy only (intravenous (43 %) than those transferred when signs of damage. dextrose, n= 13). Groups were matched as grade III-IV encephalopathy had already regards age, treatment delay, and severity developed (22%). of poisoning as estimated by dose ingested The results show that not all who could and blood paracetamol level. have benefited from protective agents Is primary biliary cirrhosis induced by One death fell in the supportive therapy received them. Hypoglycaemia must be environmental factors? (S) group. Mean peak serum aspartate distinguished from early hepatic ence- aminotransferase levels in S were 2489 phalopathy, and transfer to a specialist D R TRIGER (Departmnent of Medicinie, Ul ± SD 2269, in cysteamine therapy (C) unit for the severe cases has to be done Royal Hallamshire Hospital, Sheffield) 232 ± 361 U/I and in methionine treatment early. A rapid deterioration in pro- Primary biliary cirrhosis (PBC) is a rare (M) 350 ± 359 Ull (Wilcoxon sum of ranks thrombin time is the best guide to the disorder of unknown aetiology but en- test versus S: P<001 for M, <0 002 for likely progression to grade IV encephalo- vironmental factors have not hitherto C). Differences in favour of active therapy pathy. been systematically examined. During the were seen also for 'blind' assessed liver three year period 1977-79, 32 unrelated histology (exact P< 0-05 for M, <0-01 cases of this disease have been identified for C). in the City of Sheffield alone. Clinical, Side-effects were more frequent for Pancreatic and gut hormone abnormalities biochemical, serological, and histological cysteamine, metoclopramide for vomiting in cystic fibrosis features of these patients were similar to being given in 50%0 of instances. those reported in other series. Analysis We conclude that (1) a hepatoprotective T E ADRIAN, J MCKIERNAN, D I JOHNSTON, of these cases has revealed a striking effect in paracetamol poisoning has been E J HILLER, H VYAS, D L SARSON, AND geographical clustering which appears to demonstrated for cysteamine and methio- S R BLOOM (Department of Medicine, be related to the domestic water supply. nine; (2) in this trial no significant Royal Postgraduate Medical School, Lon- Twenty-eight of 32 patients derive their difference in efficacy could be shown don, and Department of Child Health, water from a single reservoir and the pre- between cysteamine and methionine; (3) University Hospital, Nottingham) Fibro- valence of PBC in the area supplied by this the use of methionine in paracetamol http://gut.bmj.com/ cystic disease is the most common cause reservoir is more than 10 times that overdose is associated with fewer un- of pancreatic insufficiency in children observed in the rest of Sheffield (11-6 per desirable side-effects. and is associated with an increased in- 100000 population vs. 11/100000: cidence of diabetes mellitus. We have p< 002). Analysis of water from the six investigated the effect of cystic fibrosis on reservoirs supplying Sheffield shows that Pancreatic hyposecretion in primary alimentary hormone secretion after a milk water from the PBC linked reservoir is biliary cirrhosis (PBC)-a 'dry gland' drink in 10 affected children and compared particularly soft. Excessive water copper disease the responses with a control group of simi- does not appear to be associated with on September 25, 2021 by guest. Protected copyright. lar age. PBC but other factors may play a role. O EPSTEIN, G LAKE-BAKAAR, S MCKAVANAGH, Plasma insulin and glucose-dependent It is suggested that (I) study of the AND S SHERLOCK (Academic Department insulinotrophic peptide responses were prevalence of primary biliary cirrhosis in ofMedicine, Royal Free Hospital, London) significantly reduced (p< 0.05 and relation to water supplies in other areas Cirrhosis is associated with pancreatic P< 0.005 respectively) in patients with should be considered; (2) more detailed hypersecretion. PBC is closely associated cystic fibrosis, even though the early examination of domestic water may pro- with the 'sicca' syndrome, which is glucose rise was greater. vide clues to the aetiology of this disease. characterised by lacrimal, salivary, and Fasting levels of pancreatic poly- pancreatic hyposecretion. To evaluate peptide were significantly lower in the pancreatic secretory function in PBC, we fibrocystic children (p< 001) and the have measured the pancreatic response to normal response to milk was completely Prevention of hepatic necrosis in sever an intravenous bolus of pancreozymin- abolished in these patients (P< 0-001). paracetamol (acetaminophen) poisoning: cholecystokinin (100 U) and secretin Fasting plasma enteroglucagon concen- prospective controlled trial of early treat- (100 U) in eight patients and seven trations were grossly raised in the cystic ment with cysteamine or methionine healthy controls. The pancreatic volume fibrosis patients and these remained high response was measured by continuous throughout the test (P<0-001). No A N HAMLYN, M LESNA, C 0 RECORD, P A duodenal juice aspiration, and the significant differences were seen in basal SMITH, A J WATSON, T MEREDITH, B WIDDOP, tryptic activity by TAME hydrolysis. PBC or post-milk responses of plasma gluca- G N VOLANS, AND P CROME (University patients had a significantly reduced gon, gastrin, secretin, vasoactive in- Departments of Medicine, Clinical Bio- volume response (PBC median 65 ml/30 testinal peptide, or motilin in cystic chemistry and Histopathology, Royal minutes, range 27-1 10; controls 166 ml/30 fibrosis. Victoria Infirmary, Newcastle upon Tyne, minutes, range 60-210; P<0-01). In PBC It would thus appear that the PP cell is and Poisons Unit, Guy's Hospital, London) patients the median duodenal juice tryptic more susceptible to the effects of the We have studied 40 patients at risk of activity was 17 729 U/1, and in controls, Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastroenterology A449

26 81 1 U/I (p< 0.05). Trypsin output was pmol/1, P< 0 02) and 49%o (reduction M BARKER, AND M J A JENKINS (Depart- significantly reduced in PBC patients 28 ± 7 pmol/l, P< 0.01) respectively. ment of Gastroenterology, Central Middle- (PBC median 59.93 U/minute, controls We conclude that enteroglucagon re- sex Hospital, London; Department of the 177-20 U/minute; P<0-05), indicating lease stimulated by carbohydrate malab- Regius Professor of Medicine, Radcliffe that pancreatic hyposecretion rather than sorption may be reversed by unabsorbable Infirmary and University Laboratory of cholestasis was responsible for the reduced agents which have been shown to delay Physiology, Oxford) Carbohydrate in volume response. Measurement of duo- mouth to caecum transit. Such substances individual foods differs in its chemical denal juice tryptic activity and enzyme allow more time for absorption, reducing composition, ranging from starches to mass (radioimmunoassay) indicates a malabsorption and the necessity for monosaccharides, and in its physical normal trypsinogen to trypsin ratio in enteroglucagon release. associations with fat, protein, and dietary PBC (1:3). The demonstration of pan- fibre. All these factors may affect the bio- creatic hyposecretion in PBC indicates availability of carbohydrate for absorp- that this disease is a 'dry gland' syndrome Elemental diets and small bowel structure tion. Low bioavailability will be reflected (cholestasis + 'sicca' complex), and sug- and function: effect of diet composition on in delayed release and a reduced peak rise gests a possible role for pancreatic changes induced in normal rat jejunum of blood glucose. enzyme supplementation. and ileum Digestion of 2 g carbohydrate portions from leguminous and cereal sources in an L M NELSON, R I RUSSELL, AND F D LEE in vitro dialysis system using human (Gastroenterology Unit and Department of salivary and intestinal enzymes at three Pathology, Royal Infirmary, Glasgow) hours liberated 24% of the carbohydrate PHYSIOLOGY I The use of elemental diets has been from bread, but only 140% and 5 % re- advocated in many clinical situations and spectively from lentils and soya beans. controlled intragastric administration may When these carbohydrates were given Enteroglucagon release stimulated by provide an alternative to intravenous as standard tolerance tests to six healthy carbohydrate malabsorption: a clue to its nutrition with less associated risks. subjects, the mean peak rise in blood physiological role? It has been suggested that peptides are glucose was reduced by 74±20° preferable to amino acids in diets for (p<0 001) for lentils and 85±60% R H TAYLOR, D J A JENKINS, D V GOFF, patients with fluid malabsorption but the (P < 0001) for soya compared with R NINEHAM. S R BLOOM, AND D SARSON basic physiological effects of elemental bread. Areas under the glucose response (Department of Gastroenterology, Central diets, particularly comparison of the Middlesex Hospital, London; Department curve were reduced by 58 ± 5 % (p< 0.001) different formulations available, has re- and 86±6% (p<0 001) respectively. http://gut.bmj.com/ of the Regius Professor of Medicine, ceived little attention. and University Labora- In six diabetics the mean peak rise of Radcliffe Infirmary In this study normal rats were fed blood glucose after a meal of soya and tory of Physiology, Oxford, and Royal Vivonex (V; amino acid based 1.3%0 fat) London) lentils was reduced by 3-4 ± 04 mmol/l Postgraduate Medical School, or Flexical (F; hydrolysed casein, 30% (p< 0-001) with a reduction in the glucose Knowledge of the physiology of gut fat) for one month, and jejunal and ileal of the area of 72± 11 0% (P< 0 002) compared hormones is limited because morphology and in vivo absorption com- with bread. difficulty of isolating and purifying them pared with controls (C) (n=12 for each to be in sufficient quantities. Disease states Leguminous sources appear diet). effective in slowing carbohydrate release on September 25, 2021 by guest. Protected copyright. therefore provide most of the information Both diets significantly reduced crypt in vitro, in normal subjects and diabetics. on their actions. Immunocytochemistry height: villus height ratio in jejunum and in cells Digestibility may therefore be more im- has demonstrated enteroglucagon ileum compared with controls (p< 0002). portant than composition shown by in the ileum and proximal colon. Part of Absorption of water and glucose over chemical analysis in determining the its function there may be to slow small the 60 minute in vivo perfusion period was glycaemic response to food. intestinal transit in response to luminal depressed in the rats fed Flexical com- carbohydrate and to stimulate mucosal pared with the other two groups. During growth in the long term, so minimising the second half-hour, jejunal water malabsorption. absorption (mean ± SEM) was 77± 13 p1l Human intestinal mucosa: a novel site for We have examined the effect of carbo- cm-1 for F (n=6) which was significantly bile acid metabolism hydrate malabsorption induced by an less than 137±12 for V (n=5) and ol-glycoside hydrolase inhibitor, acarbose 138 + 15 for C (n =5). A similar relation- M J DEW, P C HAWKER, S NUTTER, AND R N (BAY g 5421), on serum enteroglucagon. ALLAN (Gastroenterology Unit, The ship between the three dietary groups Litho- When eight healthy male subjects took (n =6) was found for the ileum. General Hospital, Birmingham) 50 g acarbose with a test breakfast Small intestinal absorptive function is cholate, a secondary bile acid, is effectively containing 85 g carbohydrate, the mean thus influenced by elemental diet com- detoxified by sulphation in healthy man. 90 and 120 minute serum enteroglucagon position. It has been assumed that sulphation occurs level was 71 % above control levels after predominantly in the liver, although breakfast without acarbose (rise 17 ±6 steroid sulphating enzymes are present pmol1l, P<0-05). However, addition of Effect of leguminous carbohydrate sources in the human . guar to the meal given with acarbose on absorption Accordingly we have examined the reduced this rise to below the control meal capacity of healthy and diseased ileal and response, the levels at 90 and 120 minutes R H TAYLOR, D J A JENKINS, T M S WOLEVER, colonic mucosa to sulphate lithocholate. being reduced by 76o% (reduction 33 ± 10 H GHAFARI, At EXANDRA L JENKINS, HELEN Samples of colonic mucosa were obtained Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A450 The British Society of Gastroenterology

at laparotomy from 10 patients (ulcerative efficient stimulant to water and electrolyte 0 13 ±tmol kg 1/h histamine for 2-2k hours. colitis three, Crohn's disease two, normal transport, there could be advantages in At the start of the final hour an intra- mucosa five) and ileal mucosal samples using this type of relatively hypoosmolar venous bolus of 200 mg cimetidine was from seven patients (Crohn's disease five, energy source in enteric feeds especially given. Secretion during the maximal 1-11 normal mucosa two). when the digestive and absorptive capacity hours and during the post-cimetidine hour The mucosal samples were studied in of the intestine is impaired. were expressed both as average output vitro after mounting in Perspex chambers (mmol H+/h) and after correction for perfused with oxygenated Ringer's solu- pyloric losses and duodenogastric reflux tion at 37°C. Either 1 tic of 24-14C In vitro bile acid inhibition of vitamin B 12 (ml V G/h). In two patients there was no lithocholate or 3H-glycolithocholate was binding by intrinsic factor reduction after cimetidine. By acid output, added to the mucosal side of the chamber the average reduction was 70.9 %, and the and recovered radioactivity was analysed N H TEO, B REED, G NEALE, J M SCOTT, AND reduction exceeded 60% in 16 patients. by thin layer chromatography. D G WEIR (Departments of Medicine and However, by VG it was only 50-2 % and Lithocholate and glycolithocholate were Biochemistry, Trinity College, Dublin) the reduction exceeded 60% only in 12. sulphated in the healthy and diseased Little is known of the intraluminal phase The discrepancy was produced by a ileal mucosal samples, but in none of the of B12 transport, although it has been greater percentage contribution of duo- colonic mucosal samples. We conclude shown that duodenal juice (DJ) contains denogastric reflux after cimetidine (sign that the ileal mucosa is an important site an unidentified substance which strongly test 16/19, P< 001). Three patients ap- for lithocholate metabolism and that the inhibits the binding of vitamin B12 by peared to have a satisfactory reduction in capacity of the intestinal mucosa to intrinsic factor (IF). In this study the role terms of acid output, but V G showed that metabolise other bile acids should be of bile acids (BA) has been examined. the true reduction was minimal. explored. Gastric juice (GJ) containing vitamin Cimetidine does not reduce gastric B12 binders (90% of which are IF) was secretion as powerfully as might appear; incubated with solutions of BA (1-10 investigations linking the acid reduction mmol/l), pH 7-2 at 37°C for two hours. produced by cimetidine with its effect on Intestinal absorption of glucose polymers 57Co B12 was added and the IF-bound in man healing of peptic ulcer should take duo- fraction was assayed by the method of denogastric reflux into account. Gottlieb. B J M JONES, A K BEAVIS, D EDGERTON, AND Conjugated (glycine-and taurine-) and D B A SILK (Department of Gastroenter- unconjugated, deoxycholic and chenode- ology, Central Middlesex Hospital, Effect of an intravenous aminoacid mixture oxycholic acids inhibited binding by IF. http://gut.bmj.com/ London) Recent perfusion experiments The degree of inhibition increased with (Aminoplex 14) on gastric secretion in have shown that glucose is absorbed faster the concentration of BA (maximum of healthy subjects and patients with duodenal from maltose than equivalent glucose 90%o at 10 mmol/l) and was also time de- ulcer solutions. The present study was under- pendent (maximum at two hours). In taken to determine if higher glucose contrast, conjugated and unconjugated J V PSAILA, D M BRADLEY, AND M H WHEELER oligosaccharides also confer a kinetic cholic acid caused no inhibition. Using a (University Department of Surgery, Llan- advantage on glucose absorption. similar method BA did not inhibit the dough Hospital, Penarth, Cardiff) Recent Six normal subjects were intubated studies have suggested that aminoacid

binding activity of R protein. on September 25, 2021 by guest. Protected copyright. with a double lumen perfusion tube with Subsequently DJ was eluted through mixtures given parenterally stimulate the an occlusive balloon and the proximal Sephadex G50 gel and fractions were parietal cell directly, without mediation jejunum perfused with three isotonic incubated with GJ. Two peaks of inhibi- of gastrointestinal hormones. We have saline solutions which contained 140 mM tion were found coinciding with those for conducted studies to determine the secre- glucose; 70 mM maltose, and 21 mM bile acids. One peak was consistent with tory response to intravenous aminoacids glucose polymer (mean chain length of mixed micelles; the other with BA micelles (Aminoplex 14, Geistlich Sons Ltd., seven glucose molecules). The absence of or free BA. Chester) in normal subjects, and duodenal o-amylase from the test segment was These experiments suggest that bile ulcer patients before and after . confirmed. acids under physiological conditions are Studies were carried out on 12 normal Glucose was absorbed at similar rates the inhibitors of the binding of B12 by IF subjects and eight duodenal ulcer patients. (mMol/25 cm/h ± SE) from glucose (65.75 in duodenal juice. This may have im- Aminoplex 14 was administered at + 12.78) and polymer (6342 ± 6.54) but portant physiological implications. 125 ml/h (0-17 g/min) over a two hour faster from maltose (84-90 ± 12.2; period. Mean acid output (mEq/30 min) P< 005). Water absorption was similar rose from a basal value of 0.58 ±0.16 to from all three solutions. Sodium was Reduction of acid secretion induced by 2.74±0.37 (p<0001) in normal subjects; absorbed faster from the polymer (44-6 cimetidine is less than it seems and from 1.2 ±0-43 to 4.50 ± 1-03 + 8.78) than from maltose (28-25 ± 4.27; (P< 0-005) in duodenal ulcer patients, P < 0 05) or glucose (4-01 ± 1*14; P< 0-01). S I SULEIMAN, P F WHITFIELD, J V PARKIN, after 60 minutes' infusion. Although the polymer did not confer a T 0 NWABUNIKE, AND M HOBSLEY (Depart- Mean serum gastrin levels showed no kinetic advantage on glucose absorption, ment of Surgical Studies, The Middlesex rise from a basal value of 168 ± 14 pg/ml luminal hydrolysis was not a prerequisite Hospital Medical School, London) In 19 to 165 ± 32 pglml in normal subjects, and for absorption and glucose uptake was subjects (three normal subjects, two from 226.2 ± 26 pg/ml to 221 ± 26 in DU not limited by brush border hydrolysis. gastric ulcers, and 14 duodenal ulcers) patients, 60 minutes after infusion. Blood As the glucose polymer also acted as an maximal gastric secretion was evoked with glucose, serum osmolality and PCV Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastroenterology A45 1 estimations did not alter significantly ments of which were found in association Interactions of an antimuscarinic and an throughout. Blood aminoacid levels de- with free intact tonofilaments. H2 receptor antagonising drug in man monstrated a marked rise from 3759+ 0.l1% pepsin at pH 1.1 caused wide- 628-6 t±mol/l to 7693 ± 1595 ,umol/l spread severe damage after five minutes, W LONDONG, V LONDONG, TH WEBER, AND (P< 0.05) paralleling the rise in acid whereas 0.1 N HCI caused only minor K VON WERDER (introduced by J B Elder) output. changes at 15 minutes. (Medizinische Klinik Innenstadt, University Cimetidine (200 mg orally, 30 minutes We conclude that (1) TEM after short- of Munich/FRG) Combined application before infusion) suppressed the secretory term tissue incubation is a feasible new of pirenzepine and cimetidine was shown response to intravenous aminoacids. The technique for study of the oesophagus; to suppress almost completely stimulated marked stimulation in acid secretion after (2) most gastroduodenal constituents gastric acid secretion in healthy subjects AA infusion in DU patients was not may be toxic to the oesophageal mucosa. and duodenal ulcer patients without any elicited after truncal or highly selective effect on serum gastrin. vagotomy. In this double-blind study we looked for We conclude that parenteral amino- an optimal therapeutic regime in order acids stimulate acid output in the normal to minimise side-effects by reducing the stomach, and to a greater extent in duo- combined dosages. Four combinations denal ulcer patients. This response is not Adhesion characteristics of strains of using 0.075 and 0.15 mg/kg pirenzepine associated with a rise in serum gastrin, is E. coli isolated from children during an with 1.5 respectively 3.0 mg/kg cimetidine susceptible to H2 blockade, and absent outbreak of acute diarrhoea: isolation of were given as intravenous bolus to 10 after truncal or highly selective vagotomy. a colonisation factor II-producing strain healthy volunteers in random order. Peptone-stimulated acid secretion and D C A CANDY, T S M LEUNG, W C MARSHALL, prolactin were measured and compared M M LEVINE, R ROBINS-BROWNE, A D with placebo. PHILLIPS, R H K MAK, M V CHADWICK, AND Within 15 to 30 minutes and for more J T HARRIES (Institute of Child Health and than three hours after intravenous injec- PHYSIOLOGY 11 The Hospitals for Sick Children, London, tion all combinations suppressed stimu- and The University ofMaryland, Baltimore, lated acid output almost completely, USA) Mucosal adhesion of bacteria is though the combinations containing the Ultrastructure of oesophageal mucosa after probably an absolute prerequisite in the higher cimetidine dosage were statis- short-term tissue incubation pathogenesis of diarrhoea. Recent studies tically more effective (p 00l). Using the lower dose-combinations, undesirable have implicated two surface antigens, http://gut.bmj.com/ M C BATESON, G MILNE, S GIBB, D HOPWOOD, colonisation factor I (CFA/1) and colo- side-effects could be eliminated (blurred AND I A D BOUCHIER (Departments of nisation factor JI (CFA/II) in mediating vision) or significantly reduced (prolactin Medicine and Patihology, Ninewells the adhesion of certain human strains of stimulation). No dose-related differences Hospital and Medical School, Dundee) enterotoxigenic E. coli. We have studied were observed in salivation. Reflux oesophagitis is a common problem, the adhesive properties of E. coli isolated Reduced doses of an antimuscarinic and the mechanisms have not been fully from children during an acute outbreak of and an H2 receptor antagonising drug elucidated. Transmission electron micro- diarrhoea in a paediatric ward, using given in combination come close to the 'optimal effective dosage'. As cimetidine scopy (TEM) was performed to assess human buccal epithelial cells (BEC), on September 25, 2021 by guest. Protected copyright. changes in cell junctions and organelles human fetal enterocytes (FE), electron- side-effects could not be abolished com- after incubation for up to 15 minutes with microscopy. pletely, further experiments with new H2 autologous gastric and duodenal juice and E. coli from six patients were adhesive to blockers are needed. some of their components. BEC, adhesion was mannose resistant, After incubation for up to 30 minutes and all six produced CFAIII but not in Hams FIO culture medium ultra- CFA/I; none of the non-adhesive E. coli structure of cells was preserved intact. from four patients produced CFA/II or Gastric juice produced widespread cel- CFA/I. CFA/II E. coli were excreted by Intestinal stimulation of pancreatic poly- ular destruction with free cells in the patients with and without diarrhoea; peptide release in dogs medium, even in patients where gastric pH however, the patients without diarrhoea was 7. Duodenal juice caused generalised were significantly (P< 0.0005) older than P G DEVITT, A AYALON, P L RAYFORD, AND changes with internalisation of desmo- those with diarrhoea. The CFA/II E. coli J C THOMPSON (introduced by R C N somes and microvesiculation of cell adhered less well (P< 0.005) to FE com- Williamson) (Department of Surgery, membrane. The last change was also pro- pared with an E. coli (026K60) known to The University of Texas Medical Branch, duced by incubation with model 0-2- adhere to human fetal intestine. Galveston, Texas, and The Department of 20 mM bile acid solutions, which also This is the first report of a human Surgery, Bristol Royal Infirmary) Pan- released DNA into the medium. 0. 1% enteropathogenic CFA/II strain of E. coli creatic polypeptide (PP) plasma levels trypsin released cells from the biopsy into in the UK, and our results emphasise the remain raised for several hours after a the medium and produced apparently importance of assessing the adhesive meal. The mechanism for this prolonged leaky cell membranes, as did all the properties of bacteria in any investigation release of PP is not clear. Direct release is enzymes tested. 01 0% lipase caused of potential pathogenicity in view of the unlikely: (l) there are few PP cells in the marked cell membrane damage with importance of this property as a deter- gut, and (2) intravenous nutrients do not intracellular whorls, intercellular frag- minant of virulence. release PP. We have shown release of PP Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A452 The British Society of Gastroenterology

by exogenous cholecystokinin in physio- isolated strips of both longitudinal and Effect of cimetidine and pentagastrin logical doses. circular smooth muscle in which the stimulation on the histamine concentration In six dogs with duodenal fistulae we mucosa had been removed. Deoxycholic in the gastric mucosa of patients with have studied the effects of intraduodenal acid again increased motility but other peptic ulcer infusion of nutrients, pancreatic enzymes, bile acids had no effect. and bile on the plasma levels of PP and These studies suggest that deoxycholic J H SAUNDERS, W K MAN, AND J SPENCER cholecystokinin. acid increases force and motility by a (Department of Surgery, Royal Post- Results showed that basal values of PP direct action on colonic smooth muscle graduate Medical School, Hanmmersmith were 242 ± 67 pg/ml and the peak re- and may be important in the regulation of Hospital, London) It has been postulated sponse to a phenylalanine/tryptophan co-ordinated colonic motility in man. that changes in the histamine content of mixture was 1190 ± 118 pg/ml. Peak values the gastric mucosa may be causally related with oleate were 1837 ± 361 pg/ml and to the pathogenesis of human peptic with 10 % liver extract were 826 ± 177 ulceration. Patients with duodenal ulcer pg/ml. The PP response to liver extract have a significantly lower gastric mucosal was greatest at neutral pH. These sub- histamine concentration than normal stances also released significant quantities Viscosity and glucose diffusion: potential controls. Proximal gastric vagotomy raises of cholecystokinin. Infusion of dextrose, for modification of absorption in the small the histamine levels in these patients to pancreatic enzymes or bile did not alter intestine above control levels. The aim of the basal levels of PP or cholecystokinin. present study was to determine the Saline (300, 1800, 2700 mosmol) did not R H TAYLOR, T M S WOLEVER, D J A JENKINS, mucosal histamine response to pentagas- alter the basal levels. H GHAFARI, AND M J A JENKINS (Depart- trin stimulation and the effect of H2 We conclude that there is an intestinal menit oJ Gastroentterology, Central Middle- blockade with cimetidine. phase of PP release, related to the sex Hospital, London; University Labora- Gastric mucosal biopsies were obtained presence of fat or amino acids in the small tory of Physiology and Department of the at oesophagogastroduodenoscopy and bowel. The mechanism of release appears Regius Professor of Medicine, Radcliffe assayed for histamine concentration. The to be pH sensitive and may in part Infirmary, Oxford) Absorption of carbo- patients were grouped according to involve cholecystokinin. hydrate may be modified by the physical whether or not they were receiving cime- properties of dietary fibre resulting in a tidine therapy. Nine patients, after a flatter glycaemic response curve and a standard 90-minute pentagastrin infusion reduction in insulin release. test (6 tg kg/h), were re-gastroscoped to Motor response of isolated human colon We have studied the effect of five fibres obtain biopsies of the gastric mucosa in ahttp://gut.bmj.com/ to bile acids or fibre analogues (wheat bran, pectin, stimulated state. methylcellulose, gum tragacanth, and The histamine concentration of patients M FLYNN, P HAMMOND, C DARBY, AND I guar) in an in vitro model using a dialysis on cimetidine was significantly higher, TAYLOR (Departments of Suirgery and membrane to compare the effects of the averaging 58 %, than in those patients not Bioengineering, University of Liverpool) physical properties of the fibre on glucose receiving cimetidine. In the stimulated Evidence is accumulating to suggest that diffusion. Solutions of 3.5 g glucose with state, there was an average 20% fall in or I in 30 ml water mucosal histamine concentration after secondary bile acids are implicated in the without g fibre distilled on September 25, 2021 by guest. Protected copyright. regulation of ordered colonic motility. were placed in dialysis tubing in a stirred pentagastrin whether or not the patient Deoxycholic acid (15 mM) stimulates bath for three hours. Glucose diffusion was on cimetidine. colonic motility in man and the dog and was 920O of control for bran, 72O% pectin, It is concluded that cimetidine, in a may be responsible for the abnormal 67 % methylcellulose, 50 % guar, and 45 % similar fashion to vagotomy, significantly myoelectrical pattern in both the irritable gum tragacanth. raises the gastric mucosal histamine colon syndrome and diverticular disease. When the same fibres were given to concentration, while stimulation of gastric In this study human colon. removed healthy volunteers with a standard 50g acid secretion reduces the mucosal hista- during resection for either carcinoma or glucose tolerance test there was a reduc- mine stores. diverticular disease, was constantly per- tion in the area under the one hour fused with oxygenated Krebs solution at glycaemia curve of 68±210% (p<0-05) 37°C. Using a single electrode sutured to for guar, 34±8%0 (p<00l) gum traga- serosa both motility and electrical activity canth, 29 ± 8 % (p< 0.05) methylcellulose, Inhibition of leucocyte motility by drugs were monitored. A strain gauge was II ±l 7 % (NS) pectin and 27 ± 11 % (NS) used in inflammatory bowel disease attached to measure changes in force. bran. The one hour curve areas correlated Deoxycholic acid (15 mM) added to with viscosity (r=0-904, P<0 02). J M RHODES AND D P JEWELL (Academiic the perfusion statistically significantly Thus the most viscous fibres, guar and Department of Medicine, Royal Free increased colonic force and motility' gum tragacanth, have the greatest effect Hospital, Hampstead, London) In in- (control percentage motility 201 ± 5-4 in v'ivo and in vitro. Although increasing flammatory bowel disease (IBD), leuco- after deoxycholic acid 55-4 ±4-9p< 0O00l). the viscosity of gastric contents slows cyte lysosomal enzymes probably con- The increase was similar to that obtained emptying, the flatter glycaemic response tribute to mucosal damage so reduction with carbachol (2-5 tiglml). Neither in viro may also be dependent on slower of leucocyte migration into the mucosa chenodeoxycholic acid nor cholic acid diffusion of sugars across the unstirred should be beneficial. We have studied the altered colonic motility. layer to the luminal surface of the small effects of drugs used in IBD on leucocyte The studies were repeated using intestine. random motility and chemotaxis. Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastroenterology A453

The drugs studied were prednisolone, under 5 cm is largest in the specimens of Delay in diagnosis caused delay in treat- sulphasalazine, its metabolites sulphapyri- the multiple fraction group, followed by ment by several months with important dine and 5 amino-salicylic acid (5ASA), the single fraction and the no radiotherapy consequences. and also hydroxychloroquine (as chloro- groups in that order (x2 = 14.43 on 4 df; quine is a potent inhibitor of chemotaxis). 001> P>0 001); (b) there is a lower We measured the distance moved by proportion of Dukes' stage C tumours normal peripheral blood neutrophils and in the multiple fraction group; the Prospective study of colorectal cancer monocytes (2 x 106 cells/ml) chemotaxing difference does not quite attain statistical through millipore filters towards casein significance (A2=8.00 on 4 df, 0l10>p> J GUEST, C B WOOD, D HOLE, C S MCARDLE, (4 mgiml). Serial dilutions of test drug 0.05); (c) there appeared to be a slightly C R GILLIS, L B BLUMGART, AND D C CARTER were added. higher mortality in the single fraction (University Department of Surgery, Royal Fifty per cent inhibition of neutrophil group, particularly the patients given ab- Infirmary, Glasgow) A study of the chemotaxis occurred with prednisolone dominoperineal excisions, although this is natural history of colorectal cancer 700 uig/ml, sulphasalazine 1 mg/ml, 5ASA not quite statistically significant; (d) there presenting to one centre started in 1974. 5 mglml, and hydroxychloroquine 100 does not appear to be an increase of Nine hundred patients have presented Lg,'ml. Similar drug concentrations in- morbidity-for example, wound healing, with a clinical or pathological diagnosis of hibited monocyte chemotaxis. Sulphapy- pelvic sepsis, fistula- after radiotherapy. colorectal cancer and the first 493 cases ridine up to a concentration of 10 mg,!ml Clinical follow-up is proceeding and have been analysed. had no effect on chemotaxis. Inhibition of survival will be assessed at two and five The incidence of colorectal cancer in the random motility was assessed in the years. Eastern District of Glasgow was approxi- absence of casein. Fifty per cent inhibition mately 50 per 100 000 population (com- occurred with pared with 39 per 100 000 in Scotland). of neutrophil motility Nineteen per cent of patients presented prednisolone 1-2 mg/mi, sulphasalazine with signs of obstruction. Of non- 650 ,ug/ml, SASA 3 mg/mi, and hydroxy- Accuracy of , sigmoido- 600 but again sulpha- obstructed patients, 70 % gave a history chloroquine Vg/ml, scopy, and barium enema in the diagnosis of altered bowel habit and 46% a history pyridine had no effect tip to 10 mg/ml. of rectosigmoid carcinoma Drug concentrations of this order, of blood PR. A rectal mass was palpable obtainable in of in 32%0 and an abdominal mass in 46%. although not plasma T H WALSH AND M SPIRO (Rush Green and Overall postoperative mortality was treated patients, may occur locally in the Oldchurch Hospitals, Romford, Essex) at least with hydroxychloro- 13 %. Permanent or temporary or, Thirty-nine cases of rectosigmoid car- was performed in 390% of all cases. quine, in leucocytes. cinoma which presented to two district http://gut.bmj.com/ of may be There was no difference in operative Inhibition leucocyte motility hospitals during the five year period July mortality or four-year survival between one explanation why prednisolone, sul- 1974-June 1979 have been reviewed. The and 5ASA are effective in IBD patients treated by resection plus colos- phasalazine diagnostic accuracy of the initial rectal tomy or resection alone. Operative mor- while sulphapyridine is not. Hydroxy- examination, sigmoidoscopy, and barium has similar tality was unexpectedly high after right chloroquine inhibitory potency enema (initial assessment) has been hemicolectomy. Correcting for operative to prednisolone and is now under trial estimated and the extent to which negative in mortality, overall survival after right IBD. findings caused delays in treatment is hemicolectomy did not differ from that considered. after resection. on September 25, 2021 by guest. Protected copyright. The results showed that 200% of cases were diagnosed on rectal examination alone, 46% on rectal examination plus sigmoidoscopy and 77 % on rectal exami- Bladder function after excision of the SESSION A nation, sigmoidoscopy, and barium rectum for low rectal carcinoma enema. While cases diagnosed by initial rectal examination and sigmoidoscopy N S WILLIAMS, D E NEAL, AND D JOHNSTON Preoperative radiotherapy in operable were treated on average 2-6 weeks after (University Department of Surgery, rectal cancer attendance, the nine cases not diagnosed General Infirmary at Leeds) With after the initial rectal examination, modern techniques it is now possible to A N SMITH, W DUNCAN, AND L FREEDMAN sigmoidoscopy and barium enema were perform sphincter-saving resections (SSR) (on behalf of the Medical Research treated on average 36-6 weeks after first for most patients with low rectal car- Council Working Party) Eight hundred attendance. Surprisingly, in spite of this cinoma. While there is known to be a high and twenty-four patients with rectal delay, there was no evidence that the incidence of bladder disturbance after cancer have been entered into the study in tumours in the latter group were more abdominoperineal excision (APER), little 14 centres and information is available on advanced at the time of operation or that information exists about bladder function 815, randomly allocated to three treat- prognosis was worsened. after low SSR. ment options in addition to surgery: no We conclude that one in four recto- Bladder function was studied in 14 radiotherapy; a single fraction group given sigmoid carcinomas was not diagnosed patients after APER, 13 patients after 500 rads in the 24 hours before operation; at initial assessment. Although this was SSR, and 14 control subjects (C) matched a multiple fraction group given 2500 rads only one case every 3-3 years per surgical for age and sex. The mean distance of the in the 14 days before operation. Definitive team, if repeated throughout Britain it carcinoma from the anal verge was equal results are: (a) the number of tumours represents over 400 cases annually. in the two groups of patients (APER Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A454 The British Society of Gastroenterology

±8SD8 2.4cm; SSR 93 +3 cm) and the mmHg (p< 0.05). Some clinical improve- Rectal excision and endo-anal anastomosis period of follow-up was similar (APER ment was noted in all and none required 2.2 +±28 yrs; SSR 1.6 ± 1.6 yr). surgery. M R B KEIGHLEY AND D MATHESON (The Seven patients had developed acute re- Eight other patients had normal anal General Hospital, Birmingham) Ten tention of urine after operation, six after canal pressures (mean 33.2 ± 11.7 mmHg). patients have undergone rectal excision APER (43 %) and one after SSR (8%, These patients were treated with frequent with endo-anal anastomosis since March P< 0.05). Urinary symptoms such as enemas and suppositories. The mean anal 1978. In six patients, the operation was frequency, incomplete emptying, or in- canal pressure on follow-up showed no performed for low rectal carcinoma (6-9 continence were noted in 13 patients, statistically significant change (mean cm from the anal verge), in two the opera- eight after APER and five after SSR, and 38.3 ± 7.1 mmHg). Little overall clinical tion was for extensive villous papilloma in three controls. improvement has occurred and one with malignant change, two patients had Residual volume was 20 ± 31 ml (C) and patient has undergone sub-total co- excision of a Crohn's stricture. Recon- 108+190 ml in patients (P< 0 05), but lectomy. struction was achieved with the Parks patients after APER did not differ from In conclusion, measurement of ano- retractor and covered with a loop patients after SSR. Flow rate, however, rectal motility assists in the management colostomy. was significantly less after APER (11 ± of adult megacolon. Of the six patients operated upon for 4 ml/s) than after SSR (20 ± 11, p< 0 05); invasive carcinoma all had tumour ex- cf controls (22±12 ml/s, P< 002). tension to perirectal fat. One patient died The cystometrogram was abnormal in three weeks after hospital discharge from seven patients (five APER, two SSR). Prognosis of colonic carcinomas diagnosed bronchopneumonia and two have already Detrusor instability was the commonest by developed local recurrences three and 12 abnormality, but two patients after APER months after operation. Two of the re- developed neurogenic bladders. J D BUCHANAN, ANTONIA LIGHTFOOT, J R mainder have stenosis of the 'neo rectum' These findings suggest that disturbances THORNTON, R H TEAGUE, C B WILLIAMS, above the suture line associated with of bladder function occur after both types G J MILTON-THOMPSON, AND RICHARD H episodes of urgency and incontinence. ofrectal excision, but are less frequent and HUNT (Departments of Gastroenterology, Of the four patients with villous papilloma less severe after low SSR than after APER. Royal Naval Hospital, Haslar, Bristol or Crohn's disease, three have been Royal Infirmary and St Mark's Hospital, followed up for more than six months and London) Colonoscopy will make a diag- all have a narrow 'neo rectum' compli- nosis in 450% of patients with persistent cated by episodes of incontinence. Al- Assessment of anorectal motility in the rectal bleeding in whom conventional though normal sphincter pressures have http://gut.bmj.com/ management of adult megacolon investigations have been reported normal. been maintained after operation maximal At three referral centres 652 such patients rectal capacity was less than 60 ml in five I TAYLOR, C DARBY, AND P HAMMOND have undergone colonoscopy and 66 of seven patients. (Departments of Surgery and Bioengineer- patients (10%) were found to have colonic These results indicate that the functional ing, University of Liverpool) The diag- cancer. results of endo-anal anastomosis are im- nosis of adult megacolon is made on This group of cancer patients has been paired because of stenosis of the 'neo clinical history and plain abdominal studied to determine whether colonoscopy rectum' and that early recurrence is com- radiograph. However, the differentiation detected smaller, earlier tumours. Analysis mon after operations for invasive car- on September 25, 2021 by guest. Protected copyright. between adult Hirschsprunig's disease and by size and Dukes' staging was possible in cinoma. idiopathic megaeolon is difficult. We have 50 patients (760%). Invasion by pelvic measured anorectal myoelectrical profiles carcinoma was the cause in a further two in 19 patients with adult megacolon over a cases and in three the barium enema was follow-up period of 15 months and com- considered positive. Records were un- Toxic megacolon in ulcerative colitis: a pared the results with an age-matched available for 11 patients. medico-surgical audit group of normal volunteers. Duration of symptoms exceeded three Adult Hirschsprung's disease (four months in 18 and six months in 10 T J MUSCROFT, P M WARREN, R D MONT- patients) was recognised by the absence patients. Mean delay from reporting GOMERY, P ASQUITH, AND G S SOKHI of inhibition of pressure on symptoms to barium enema was four (Departments of Medicine and Suirgery, rectal distension (normal mean inhibition weeks (range 1-16) and to colonoscopy East Birmingham Hospital, Birmingham) 219 ± 2.3 mmHg). A fast 'ectopic' slow 10 weeks (range 2-55). The benefits of early surgical intervention wave rhythm was recognised in rectal The mean tumour size was 4 cm (1.5- in some cases of severe ulcerative colitis smooth muscle. All these patients required 15) comprising Dukes A 14 (28 %) Dukes (UC) are well-recognised, but the pre- surgery. B 25 (500') Dukes C nine (18%) 'Dukes dictive features, exact timing, and long- Seven patients with non-Hirschsprung's D' two (4%). Only five Dukes A lesions term justification for emergency surgery (idiopathic) megacolon had a raised were less than 2 cm diameter. There was are still debatable. Toxic megacolon (TM) anal canal pressure (mean 90.4 ± 7.0 no correlation between tumour size and remains one of the gravest of medical mmHg, control 41-7 ± 7.6 mmHg duration of symptoms. emergencies. p< 0.01). These patients were treated with In this highly selected group colono- The incidence, predisposing factors, repeated anal dilatation and, after a mean scopy detected 78 % of colonic management and outcome of TM have follow-up period of 15 months, the anal in Dukes' stage A or B with probable im- been reviewed in 65 cases of severe UC, canal pressure had fallen to 67.2 ± 6-3 provement in prognosis. and compared in two successive six-year Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastroenterolog'A4 A455 periods before and after January 1973. The overall results are good. PGV has Double-blind comparison of ranitidine and Nineteen episodes of TM occurred in 18 largely abolished the unpleasant sequelae, cimetidine in the treatment of duodenal patients. Despite a conscious aim towards but at the expense of a relatively high in- ulceration earlier surgery in recent years, this cidence of recurrent symptoms and re- objective was not achieved, and despite current ulceration. Familiarisation with J H B SAUNDERS, N R PEDEN, E J S BOYD, AND more intensive medical therapy the in- the technique will perhaps reduce the K G WORMSLEY (Department of Thera- cidence of TM was unchanged. Emergency risk of recurrent ulceration to a level peutics, Ninewells Hospital, Dundee) operative mortality in UC fell from 36% comparable with that reported by the Ranitidine, a new histamine H2 receptor to 21 % but the overall mortality of TM pioneers of the operation. antagonist, has been shown strongly to remained at 30%. inhibit gastric secretion of patients with Mortality was associated with increased duodenal ulcer. We have therefore under- age, longer preoperative hospital stay, and taken a double-blind comparison of the lower levels of serum albumin. The serum Comparison of medical and surgical re- healing of duodenal ulcers in 40 patients albumin was the only investigative para- duction in intragastric acidity in duodenal using cimetidine 800 mg daily and meter of predictive value. Levels less than ulcer ranitidine 320 mg daily. No patient had 30 g/l indicated a 48 % chance of requiring received any ulcer-healing drug for at least surgery, a 32% incidence of TM and a R H HUNT, DIANA VINCENT, J M KELLY, three months before study. Treatment 44% operative mortality. M PERRY, AND G J MILTON-THOMPSON started within four days of endoscopy. These findings re-emphasise the need (Royal Naval Hospital Hasler and Queen Progress was assessed during visits at 14 for earlier surgery to prevent TM, but Alexander Hospital, Cosham, Portsmouth) and 28 days. Ulcer healing was determined follow-up shows that this policy must Both medical and surgical reduction of endoscopically at 28 days after starting result in some unnecessary emergency intragastric acidity have their place in the treatment. Seventy-nine per cent of the . management of duodenal ulcer (DU). patients receiving ranitidine had healed To compare their relative effectiveness ulcers after one month, compared with we have studied six DU patients (mean 42% of those receiving cimetidine. After age 51, range 42-66 years) using a tech- 14 days, 85 % of the ranitidine-treated nique previously described. Hourly in- patients were symptom free, compared SESSION B tragastric H+ activity was studied during with 47 % of the cimetidine-treated group. two separate 24-hour periods, patients Antacid consumption was significantly receiving placebo or cimetidine 1 g/day greater in the cimetidine-treated patients. There were no clinical, haematological, or Long-term results of proximal gastric in random order. Six months after proxi- http://gut.bmj.com/ vagotomy mal gastric vagotomy (PGV) 24-hour biochemical adverse reactions. We con- intragastric acidity was again measured. clude that ranitidine is at least as effective as cimetidine in healing duodenal ulcers D W STOREY, P B BOULOS, J H WYLLIE, AND Cimetidine reduced mean 24-hour and in producing symptomatic relief. C G CLARK (Department of Surgery and intragastric H+ activity from 30.75 ± SEM Gastroenterology, The Rayne Institute, 11-97 to 14-11 ±1.71 mmol 1-1 (p<0-001) University College Hospital Medical and nocturnal acidity (0100-0700) from School, University Street, London) 40-6±4+04 to 17.3±3+35mmol 1-1 (P< Long-term results of highly selective

Proximal gastric vagotomy (PGV) is 0.001). After PGV all patients were vagotomy (HSV) in the treatment of on September 25, 2021 by guest. Protected copyright. designed to obviate the sequelae after classified as Visick grades I or II and benign gastric ulcer (GU) other gastric operations for duodenal operation further reduced mean 24 hours ulcer disease without increasing the risk of acidity to 6.25 ± 1.73 mmol 1 -1. D JOHNSTON AND AT R AXON (University recurrent ulceration. An incidence of re- In 31 DU patients studied with this Department of Surgery and Gastric current symptoms of about 15 % after technique, two patterns of nocturnal Follow-Up Clinic, Leeds General Infirmary) PGV has been reported, with a frequency response to cimetidine have been observed. The results of 104 HSVs, with excision of of proven recurrent ulceration of only In 19 patients cimetidine reduced noctur- the ulcer, for benign gastric ulceration 9 % and 4-3 %. There is doubt about nal acidity (0100-0700) from 420±201 over the past 11 years are reported. Two- whether similar results can be repeated to 5.11 ± 1-02 mmol 1-1 (88 %), while in 12 thirds of the patients had GU alone, the in other surgical hands. acidity was reduced from 59.2 + 27 to rest had DU+GU. The GU was proved During 1970-74, 120 patients with 32.3 ± 2-27 mmol 1-1 (45 %). benign by preoperative endoscopic biopsy duodenal ulcer were treated by PGV Our six patients studied preoperatively and by frozen section examination at without postoperative death. Of 93 included three in whom cimetidine re- operation. patients who could be followed up for duced mean nocturnal acidity by 840% Operative mortality was 1 %. The results five to nine years (mean 6-7 years) after and three by 460%. There was no signi- of HSV for GU+ DU were similar to those their operations, 76% had good results; ficant difference between the two groups previously reported after HSV for DU 51 Visick I and 20 Visick II. Four patients postoperatively. alone. After HSV for GU alone, 36 had dumping, two diarrhoea, and of six PGV is effective in reducing intragastric patients were followed up for between who developed gastric stasis a drainage acidity and compares favourably with four and 10 years (mean, six years). One procedure was necessary in three. Twenty cimetidine 1 g/day. PGV appears to be developed recurrent ulceration (3%) and patients had recurrent symptoms (21.5 %) equally effective in reducing nocturnal in another recurrence was suspected but and recurrent ulceration was proven in acidity in patients showing both patterns not proved. The total incidence of re- 14 (15 %). of response to cimetidine. currence is 5 %. After four to 10 years of Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A456 The British Society of Gastroenterology

follow-up, no patient had symptoms of gow Royal Infirmary and Department of of the 55 patients (67 %) was there a early dumping or bilious vomiting and Pathology, University of Edinburgh) Bile history of preceding reflux dyspepsia. only one had mild episodic diarrhoea. salts such as taurocholate and non- Thirty-two patients have required only Patients regained their best weight after steroidal anti-inflammatory compounds one dilatation, and have not required re- HSV, whereas after partial gastrectomy damage the gastric mucosa, but may do peat dilatation after periods ranging from (PG) for GU on the same surgical unit so by differing mechanisms. one month to four years (mean 18 they remained significantly underweight Using five antrectomised dogs prepared months). Ten patients have required four by a mean of 9 kg. with denervated fundic pouches the effect or more dilatations. In the 23 patients These findings suggest that HSV of the following solutions on H+ ion per- requiring more than one dilatation, relief provides effective therapy for benign GU meability was studied: (a) acid solutions between each dilatation ranged from two in the long term. Its side-effects and of varying concentrations; (b) acid: weeks to three years (mean six months). nutritional sequelae are significantly less taurocholate solutions of varying acid Six patients have subsequently undergone than after partial gastrectomy. concentration but all containing 5mM surgery. sodium taurocholate (ATS), and (c) acid- All of the eight patients with carcinoma indomethacin solutions of varying acid have died. Mean time to restricture after Assessment of the secretin provocation test concentrations all containing 7-63 mM dilatation in this group was two weeks. in the diagnosis of gastrinomas and other indomethacin (AIS). We conclude that dilatation of benign forms of hypergastrinaemia Permeability of H+ across the gastric oesophageal stricture by this technique is mucosa (KH) was assessed from the safe, is the treatment of choice, and only a J N PRIMROSE, S N JOFFE, AND J G RATCLIFFE slope of the regression line of net H+ loss small proportion will require definitive (University Departments of Surgery and against acid concentration. surgery. Strictures which recur rapidly Biochemistry, Royal Infirmary, Glasgow) The level of KH (as concentration inde- after dilatation should arouse suspicion of The secretin provocation test is reported pendent permeability coefficient in umol malignancy. to be a reliable test for gastrinoma and a H+/30 min) with the solution acid alone greater than 500% rise in the plasma was -6.76, with ATS was -13-74, and gastrin level is said to be diagnostic of a with AIS was -10-35. Perforation of the cardia by pneumatic gastrinoma. We have performed the Histological appearances were studied secretin provocation test in the following dilatations can be treated by conservative in the rat after instillation of the various means situations; gastrinomas (n=3), recurrent solutions into the stomach for varying peptic ulcer (n= 50), on symptomatic periods of time. G VANTRAPPEN, J HELLEMANS, AND G

patients after DU surgery (n-=20), un- http://gut.bmj.com/ Acid-taurocholate solutions produced a COREMANS (Department ofMedicine, Uni- operated primary DU (n= 10), pernicious generalised gastritis with loss of the sur- anaemia (n= 2) and control subjects versity Hospital St Rafail, Untiversity of face epithelial cells, while acid-indo- Leuven, B-3000 Leuven, Belgium) Per- (n= 10). methacin solutions produced focal lesions foration of the oesophagus is generally Tests were positive (rise of greater than with ischaemic appearances. 50) in all patients with gastrinoma who considered to be a life-threatening com- It is concluded that sodium tauro- plication necessitating urgent surgical also had raised basal plasma gastrin. cholate and indomethacin both alter Sixteen of the 50 recurrent ulcer patients treatment. Our experience indicates that gastric mucosal permeability to H+ ions, perforation of the cardia caused by pneu- had positive tests, six had a raised basal but that the associated histological on September 25, 2021 by guest. Protected copyright. gastrin but only one subsequently was matic dilatations for achalasia can usually changes confirm that they damage the be successfully treated by conservative shown to have a gastrinoma. Two mucosa by different mechanisms. asymptomatic post DU surgery patients means. From 1957 to 1979 we treated by had positive tests with normal basal pneumatic dilatation 537 patients with gastrin. Four primary DU ulcer patients achalasia. Perforation of the oesophagus had a positive test but none had a raised occurred in 13 patients (2.6%). The basal gastrin level and none of the 10 Conservative management of benign oeso- diagnosis of perforation was made when- control patients had positive tests. The phageal strictures ever extraluminal accumulation of con- two patients with pernicious anaemia had trast material could be demonstrated hypergastrinaemia and no response to D B JONES AND P M SMITH (Llandough on radiological examination. Other com- secretin. Hospital, Glamorgan, S. Wales) Over plications such as prolonged pain, a peak It is concluded that, although the secre- a four-year period, 63 patients have of fever, or a sterile pleural effusion were tin provocation test is positive in gastri- undergone dilatation by the Eder-Puestow observed in 10 other patients, which noma patients, it is also frequently positive technique for endoscopically confirmed brings the rate of complications to 4.9%. in other DU patients, and regardless of benign peptic oesophageal strictures. Ten of the 13 patients with proven per- the criteria used is not a reliable test for Eight patients were subsequently shown to foration healed completely with parenteral the conclusive diagnosis of a gastrinoma. have carcinoma of the oesophagus despite alimentation and broad spectrum anti- the initial impression of a benign lesion. biotics for one to two weeks. In four of The remaining 55 patients (M:F ratio them a pleural effusion was evacuated by Mechanisms of gastric mucosal damage by 3:2) have undergone a total of 119 dila- puncture or drainage under local anaes- bile salts and indomethacin tations, with only one perforation which thesia. Two other patients had to be healed with conservative treatment. The treated by surgical drainage of the H J E LEWI, H GILMOUR, AND D C CARTER mean age at initial presentation was 67 mediastinum (one had active Hodgkin's (University Department of Surgery, Glas- years (range 15 to 89 years). In only 37 disease, the other had eaten normally Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastroeniter-ology A457 before the perforation was recognised). Cholangiocarcinoma-a survey of 42 cases benign biliary obstruction. Percutaneous Only one patient died, a woman of 83, to catheterisation of the stricture succeeded whom food was given by mistake, in spite P C G WHEELER, J L DAWSON, H B NUN- in 16 and an endoprosthesis was inserted. of a radiologically demonstrated per- NERLEY, J W LAWS, D BRINKLEY, AND The only significant complication was an foration. In all other patients the late ROGER WILLIAMS (The Liver Unit and the external biliary fistula in one patient. This results of the treatment were excellent or Departments ofSurgery, Diagnostic Radio- closed 14 days later. In one patient the good. log), and Radiotherapy, King's College prosthesis displaced into the duodenum. Hospital and Medical School, London) Three patients later had elective The clinical course of 42 consecutive surgery, of whom one died. Of the re- patients with primary cholangiocarcinoma maining 13, jaundice improved in 11, of the main hepatic and extrahepatic itching when present was relieved, and SESSION C ducts, seen during the past six years, has eight were able to leave hospital. Six been analysed to determine whether new are alive at a mean follow up of four techniques of diagnosis and treatment months (range one to 11). Seven patients have improved the outcome. Initial all with malignant disease have died, five Endoscopic pancreatic and biliary mano- symptoms may be misleading being non- within four weeks of the procedure. All metry in health and in pancreatic, biliary cholestatic in 33.3 % of patients, 19 % the patients with benign stricture are and papillary disease starting with pain, and marked weight loss alive. D L CARR-LOCKE AND J A GREGG (New was a frequent finding. The mean age Percutaneous transhepatic insertion of England Baptist Hospital, Boston, Mas- at diagnosis was 55.8 years (690% male) an endoprosthesis to drain obstructed sachusetts, USA) An endoscopic mano- and one-third were aged less than 50 bile-ducts is a valuable alternative to metric technique was used to measure years, two of the youngest having long- surgery in patients with recurrent stricture pancreatic duct (PD), common standing ulcerative colitis of which there after biliary surgery, and in the sympto- (CBD), pancreatic duct sphincter (PDS) were four (955%) cases altogether. matic patient with malignant obstruction, and bile duct sphincter (BDS) pressures With respect to a preoperative diag- when the risk of operation is considered in 43 healthy volunteers, 11 patients with nosis, all the 29 patients having percu- unacceptable. The prognosis depends on CBD stones (group CDS), 11 patients taneous cholangiograms were correctly the underlying pathology. with pancreatitis (group P) and 40 patients diagnosed, and in only 250% was a pre- with papillary stenosis (group S), defined operative diagnosis not considered. by endoscopic, radiological, and bio- Eighteen patients underwent at hospitals where they were chemical criteria. The system employed Short duration megadosage IV Trasylol in http://gut.bmj.com/ a modified ERCP catheter, Hewlett- initially seen and the diagnosis was missed in 11 (61 %) despite operative cholangio- primary acute pancreatitis a double-blind Packard transducer and recorder and trial syringe pump perfusing at 0.62 ml.min. graphy, none having preoperative percu- Normal PD and CBD pressures were tanous . C W IMRIE, A J MCKAY, J 0 NEILL, F C 10.7 ± 39 mmHg (mean ± SD) and 20 + Median survival in those where opera- CAMPBELL, D A GORDON, AND J A LANG 1.7 mmHg respectively. PD pressure was tive treatment was impossible (34%) was (Surgical Division, Royal Infirmary, significantly raised in group S (19-3 ± 70 three months, whereas that with treatment Glasgow) Recent double-blind controlled by T- or U-tube drainage (21) or bypass mmHg, P< 0-001) but not in groups CDS trials have shown no benefit from the on September 25, 2021 by guest. Protected copyright. or P. CBD pressure was significantly (three) was nine months. Radiotherapy addition (over five days) of 4.5 million KI raised in groups CDS (15.2528± mmHg), and tube drainage (nine), including the units of intravenous Trasylol to the S (101l±3.8mmHg) (P<0-001), and P new technique of inserting a radioactive therapy of patients with acute pancreatitis (8.1 ±6.3 mmHg, P<0.01). In all groups iridium wire through the tumour, im- (AP). From the known half-life of the except group CDS, PD pressure was proved the chance of surviving the first drug and experimental AP studies in the higher than CBD pressure. 12 months compared with tube drainage dog it was suggested that very high dosage Distinct PDS and BDS zones were alone. Trasylol given for a shorter time might be identified, 4 to 5 mm from the papilla, as beneficial clinically. phasic patterns of 6 to 7 waves/min. Fifty patients with primary AP ad- Peak and trough PDS pressures (normal mitted within 48 hours of onset of 47.2 ± 8.4 and 15.9 ± 6.6 mmHg) were Relief of benign and malignant biliary symptoms were randomly allocated in a significantly higher in groups CDS and S stricture by percutaneous insertion of an double-blind trial to receive placebo or 2 (69.6±20.3 and 235 + 12.0 mmHg. endoprosthesis million KI units of Trasylol on diagnosis P< 0.001) and peak and trough BDS and repeated four hours later. Patients pressures (normal 51 2± 6-7 and 13-4 ± 6-2 J S DOOLEY, R DICK, AND S SHERLOCK were evenly distributed between treatment mmHg) were significantly higher in groups (Departments of Medicine and Radiology, groups in respect of severe (42 %-at least S (65.9±21.2 and 27-0±15-OmmHg, Royal Free Hospital, London) Percu- three prognostic factors) and mild disease P< 0.001) while peak pressure was lower taneous transhepatic insertion of an endo- (58 %). All received a standard albumin in group CDS. prosthesis has been used to relieve replacement therapy of 34 g in the initial This technique facilitates the diagnosis obstructive jaundice in selected patients. 24 hours and 17 g daily thereafter. of papillary stenosis and provides a This technique has been used in 18 No significant advantage in terms of method for studying the pathophysiology patients in whom surgery was contraindi- serum albumin conservation, incidence of of sphincter disorders. cated, 15 with malignant and three with hypoxaemia or pleural effusions or other Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A458 4The British Societv of Gastroenter-ologi, complications was associated with mega- carry a high mortality and untreated are patients had recurrent bleeding; one died, dosage intravenous Trasylol therapy and usually fatal. Established surgical teaching the other was controlled by further in- the only death occurred in the drug group. stresses the need for complete drainage jections. Ten of the 15 control patients It is concluded that very high dosage, often at open operation. Percutaneous underwent surgery; one died, and one short duration Trasylol therapy confers no aspiration is established in the manage- developed recurrent bleeding. Further advantage in the management of patients ment of simple amoebic liver abscess but bleeding occurred in four of the five with primary AP. is controversial in pyogenic abscess. patients who were managed by medical Nine patients presenting with the measures alone, and three had died within clinical features of pyogenic liver abscess two months. had ultrasound scans. The diagnosis was These early results indicate that in- confirmed and the abscess localised in all jection sclerotherapy can be effective in Combined use of arteriography and cases. Under ultrasound control a needle urgent and elective situations, and ap- venography in the assessment of resecta- was passed percutaneously into the pears to have advantages over conven- bility of hepatic tumours abscess. Pus was aspirated as com- tional medical and surgical treatments. pletely as possible and taken for im- The trial is continuing. B W A WILLIAMSON AND L H BLUMGART mediate aerobic and anaerobic culture. (University Departments ofSurgery, Royal Appropriate antibiotic therapy was used Infirmary Glasgow and Hammersmith in all cases. Further ultrasound scans Hospital, London) The place of pre- monitored the reduction in size of the operative radiology in defining the re- cavity. Value of under local anaes- sectability of hepatic tumours and par- The best results were obtained in three thesia in two hundred medical and surgical ticularly of hilar lesions has been studied. patients with solitary large abscesses (the patients Twenty-seven primary and secondary largest being 350 ml) in whom resolution malignant hepatic tumours were assessed was by crisis. Cases in which the scan T J HALL, D R DONALDSON, AND T G preoperatively by combined hepatic showed multiple abscesses in diffuse areas BRENNAN (St James's University arteriography and portal venography. of inflammation resolved more slowly. Hospital, Leeds) Laparoscopy allows The resectability of the lesions as judged Anaerobic organisms were cultured in surface inspection of most of the ab- radiologically was compared with the in- seven patients, all seven organisms dominal viscera and parietal traoperative findings. Only one of seven sensitive to metronidazole. from diaphragm to pelvis. We have per- peripheral non-hilar tumours was ir- No patient required open drainage or formed laparoscopy in 200 patients using resectable, in contrast with 11 of 20 further aspiration and recovery was local anaesthesia combined with intra- http://gut.bmj.com/ tumours involving the hilus. In every complete in every case. venous diazepam and pentazocine. It is an case the operative findings confirmed easy procedure to perform and in our the preoperative radiology. In the group of opinion is safer than employing a general nine resectable hilar cancers, five had anaesthetic. In patients with jaundice, isolated unilateral involvement of either a hepatomegaly, or suspected liver disease lobar artery or vein. In a further four both Randomised controlled trial of injection laparoscopy allowed inspection of the an artery and a vein were involved sclerotherapy for bleeding oesophageal liver and gall-bladder, percutaneous needle ipsilaterally. None of the 11 hilar cancers varices biopsies under direct vision, and wedge on September 25, 2021 by guest. Protected copyright. with bilateral or stem involvement of the biopsies from both lobes of the liver per- vasculature was resectable. Y M YASSIN, S M SHERIF (introduced by Dr mitting an accurate histological diagnosis. Inferior vena cavography was per- P B Cotton) (Kobri-El-Kobba Hospital, In patients with intra-abdominal neo- formed in 10 patients. Five tumours were Cairo, Egypt Oesophageal varices are plasms diagnosed by other procedures defined as resectable and five as irre- the commonest cause of acute upper laparoscopy often revealed liver or peri- sectable. gastrointestinal bleeding in Egypt, because toneal metastases and thereby avoided Combined hepatic angiography yields of the prevalence of schistosomiasis. Poor 'open and close' laparotomy. In patients information on diagnosis, anatomical results of conventional treatment and with we found early laparoscopy abnormalities and concurrent disease. shunt surgery led us to evaluate injection after paracentesis valuable as it differen- It is also important in assessing tumour sclerotherapy, using a fibreoptic endo- tiated carcinomatosis peritonei from pri- resectability and operative procedure. scope and mild sedation. Encouraged by mary liver diseases and avoided extensive good results in a pilot study, we are now investigations including laparotomy. In performing a controlled trial, in which most patients with undiagnosed abdom- patients are randomly allocated to in- inal pain laparoscopy yielded no further jection sclerotherapy, or to conventional information but in some cases unsuspected Managenment of pyogenic liver abscess by treatment (medical measures, with modi- pathology was detected. Laparoscopy has percutaneous aspiration using ultrasound fied splenectomy and oesophago-gastric also proved helpful in patients with acute devascularisation in selected cases). abdominal conditions. In this series of 200 D R OSBORNE AND L BERGER (introduced by We are able to report the results in the patients laparoscoped under local anaes- Professor K E F Hobbs) (Academic De- first 32 patients, with a follow-up period thesia there have been no complications. partment of Surgery, Royal Free Hospital of six to 16 months. Seventeen patients It is a safe and valuable procedure which School of Medicine, London) Pyogenic received injection sclerotherapy (three as warrants more widespread use than liver abscesses from whatever cause still urgent procedures). Only two of the 17 is so at present. Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastroenterology A459

the irritable colon syndrome (ICS) to numbers expected in the general SESSION D assess the effect on human colonic population. motility. The myoelectrical responses were The excess deaths were confined to the analysed by automated frequency analysis digestive system and due principally to and the investigator did not know which sepsis, perioperative complications, or Pathology and management of persistent bile acid was being perfused. cancer of the digestive tract. The deaths postoperative enterocutaneous fistulae Patients with ICS had a high resting have been analysed to determine how 2-4 c/m electrical activity (mean: ICS changes in clinical management might L E HUGHES AND K ROGERS (Welsh 61.6 + 3.2 %; normal 37-7 + 3.7 %, reduce overall mortality rates. National School ofMedicine, Heath Park, P< 0.001) whereas in normal subjects The relative mortality risk decreased Cardiff) The pathological basis of such 6-9 c/m activity was higher (mean: with the increasing length of follow-up fistulae has been studied prospectively in normal 59.7 ± 3-8 % ICS 35.7 ± 4-2 %, refuting claims that the disease becomes 22 consecutive cases, 11 after operation for P< 0-001). In normal subjects only 15 mM more dangerous with time. Crohn's disease. In the remaining 11 DOC statistically significantly increased (ulcerative colitis, three; diverticulitis, percentage motility (control 25.0+6.4%0 four; and miscellaneous conditions, four) during perfusion 71.4±7.2%, P<0.05). the diagnosis of Crohn's disease was raised Other bile acids including 5 mM DOC, because of persistent fistula, but was not Screening of hospital patients for occult had no effect. However, in patients with bleeding substantiated in any case. Fistulae were ICS both 5 mM DOC (control 29-8 + multiple in 13 and single in nine. 4.2% perfusion 57.4+65, P<0-05) and IG BARRISON, E R LITTLEWOOD, A SHARPLES, Of 18 transabdominal fistulae, only 15 mM DOC (control 19.4-5.7 % per- three were due to active Crohn's disease. J PRIMAVESI, AND R A PARKINS (Depart- fusion 578 ± 9-6, P< 005) statistically ment of Gastroenterology, Charing Cross Fifteen were due to a chronic abscess significantly increased motility. Neither eroding into one or more loops of small Hospital, London) Two hundred and CDC nor Ch had any effect on colonic forty-five general medical and gastro- bowel and maintained by dense fibrosis motor activity. of the wall of the abscess cavity. Of four enterology outpatients and 140 hospital In conclusion, further evidence is inpatients were tested for occult gastro- peri- fistulae, three were related presented to implicate deoxycholic acid as to active Crohn's disease and one to a intestinal bleeding using Haemoccult an important factor in the alteration of cards (Eaton Labs) and Haemostix strip chronic abscess. normal colonic motility and a possible All fistulae were successfully closed. tests (Ames). causative agent in the irritable colon Nineteen outpatients (7.7 %) were found Two patients died within 12 weeks, both syndrome. http://gut.bmj.com/ from associated disease and the remainder to be Haemoccult positive; of these 17 are alive at up to six years. Adjuvant had an identifiable source of bleeding, parenteral nutrition was used in four including seven patients with alimentary cases. cancer. Thirty-three outpatients (13.4%) It is concluded that the pathogenesis Mortality rates in Crohn's disease gave a positive test for Haemostix; these militates against spontaneous closure and included one patient with carcinoma of an aggressive surgical approach, appro- SYLVIA GYDE, PAT PRIOR, J A H WATER- the stomach whose Haemoccult tests were HOUSE, AND R N ALLAN (Gastroenterology negative. priate to the underlying pathology, is on September 25, 2021 by guest. Protected copyright. indicated. Adjuvant parenteral nutrition Unit, The General Hospital, Birmingham Thirty-three inpatients (23 6%) gave a has a small, clearly defined place in and Cancer Epidemiology Unit, University positive Haemoccult test: these included management. of Birmingham, Birmingham) The in- four patients with alimentary cancer. creased mortality risk among patients Thirty-two patients were found to have an with Crohn's disease is uncertain because identifiable source of blood loss. Sixty- inter-series comparisons are confounded five inpatients (46-4 %) gave a positive Bile acid perfusion in normal subjects and by variations in criteria for selection and Haemostix reaction. patients with the irritable colon syndrome follow-up and crude rates unrelated to age The Haemoccult testing of inpatients -a double-blind randomised study and survival are difficult to interpret. did not lead to a diagnosis of unsuspected Actuarial analysis has been restricted to alimentary cancer. All patients in whom I TAYLOR, M FLYNN, P HAMMOND, AND selected patient groups. No data are the diagnosis of colonic cancer was con- ? BASU (Departments of Surgery and available for a large unselected series. firmed were found to be Haemoccult Bioengineering, Liverpool) Studies in the We have therefore examined mortality positive. The techniques were quick and canine colon have suggested that only rates among 513 patients with Crohn's acceptable to all the patients and only deoxycholic acid (15 mM concentration) disease under long-term review between nine outpatients failed to return a has the ability to increase normal colonic 1944-76 by comparing observed deaths Haemoccult pack. motility, whereas all bile acids inhibit from all causes with the numbers that We consider the Haemoccult test too colonic absorption. In this study, two would be expected in a group drawn from insensitive for hospital use and the different concentrations (5 mM and 15 the general population matched for age, Haemostix too sensitive. There is a need mM) of three bile acids (deoxycholic acid sex, and years at risk. for a method of intermediate grade. -DOC, chenodeoxycholic CDC, and There was a two-fold excess in mor- We found that patients with chronic cholic acid-Ch) were randomly and tality rates among patients with Crohn's intermittent gastrointestinal bleeding separately perfused into the sigmoid colon disease. Half the deaths were from could use the Haemoccult cards and de- of 30 normal subjects and 30 patients with natural causes and closely matched the veloper daily to identify the onset of Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A460 The British Society of Gastroenterology bleeding enabling them to report to LANGMAN (University Department of 1965. Two patients had aortic valve hospital promptly. Therapeutics andDepartment ofPathology, disease. City Hospital, Nottingham) Half of all Single caecal lesions were seen in two patients admitted to district general patients; two had double lesions and the hospitals with acute colitis have had the remaining two multiple ectasias of the Abnormalities of neural and hormonal disease for less than a year. The mortality caecum and ascending colon. peptides in Hirschsprung's disease is greatest in this group and this seems, Fulguration of these lesions by the hot in part, to be due to failure of recognition biopsy technique has been successful with ANNE E BISHOP, JULIA M POLAK, B LAKE, of the patient's condition. no further bleeding in four patients. At M G BRYANT, AND S R BLOOM (Depart- It would be expected that sigmoido- repeat colonoscopy in three patients the ments of Histochemistry and Medicine, scopy would show clear evidence of lesions have remained healed. One patient Hammersmith Hospital, and Department abnormality in such patients, but we have underwent right hemicolectomy for 14 of Pathology, The Hospital for Sick found that this is not so. Since 1972 11 angiodysplasia lesions. Children, Great Ormond Street, London) patients with acute colitis of recent onset Confirmatory histology has been ob- The aetiology and pathophysiology of (mean total length of history 7X2 weeks) tained in four patients by 'hot biopsy' Hirschsprung's disease remain ill-under- have come to urgent surgery or have died (three) and operation (one). stood. with the condition in Nottingham. The Mucosal angiodysplasis may cause Biologically active peptides, affecting blood loss the elderly and be gut motility, are known to be present in sigmoidoscopy was reported as normal in success- high concentrations in the large bowel. in six of these patients, and there were fully diagnosed and treated at colono- Their involvement in Hirschsprung's consequential delays in instituting treat- scopy. disease was studied, by immunocyto- ment. In five of these cases a rectal biopsy chemistry and radioimmunoassay, in the was taken and histological examination of colon and rectum of eight children (ages this supported the clinical findings. In 6 months to 2 years) and compared contrast, the or post mortem with age-matched controls. specimens showed gross disease above the Elastic band ligation for treatment of first The diseased specimens were sampled rectum which was typical of ulcerative and second degree haemorrhoids a com- colitis. In those who survived, the parison with sclerosant injection from the distinctly dilated and constricted subsequent course was that of ulcerative areas and from the transitional margins. and not Ganglion cell bodies were counted in each colitis Crohn's disease. A J W SIM, J A MURIE, and I MACKENZIE specimen. We conclude that, contrary to general (C W IMRIE) (University Department ofhttp://gut.bmj.com/ belief, sigmoidoscopic appearances are Surgery, Western Infirmary, Glasgow) VIP and substance P nerves were con- of siderably reduced in all areas of diseased unreliable indicators acute severe For many years a widely used treatment bowel, in proportion to the extent of colitis; greater weight should be placed for first and second degree haemorrhoids aganglionosis. on plain abdominal radiographic findings. has been sclerosant injection (SI). Re- Comparable large reductions in entero- cently elastic band ligation (EBL) has glucagon and somatostatin cells were also been suggested as an alternative treatment. observed in both the dilated and transi- Fifty patients who would normally have tional regions. They were decreased from been treated by injection have been on September 25, 2021 by guest. Protected copyright. 82.8 (±3.9) (mean±SEM) and 10.2 randomly allocated to either SI (26) or (± 098) cells/mm2, respectively, in con- Angiodysplasia an important cause of EBL (24). The groups were comparable trols to ranges of 3.2 to 80-2 (29±315) gastrointestinal bleeding in the elderly for age, sex distribution, duration of (mean ± SEM) and < 1 to 6.7 (15 ± 024) symptoms, and previous treatments. cells/mm2 in aganglionic regions. R H HUNT (Royal Naval Hospital, Haslar) Twenty-four SI and 22 EBL patients were Comparison of bowel peptide content Vascular ectasias of the caecum and right available for assessment at one year. revealed similar changes for example, colon are well recognised at angio- All patients except one in the EBL group VIP content was reduced from 142 ( ± 18) graphy. In the last 500 consecutive presented with rectal bleeding; after (mean ± SEM) pmol/g wet weight of , six patients with mucosal treatment 15 SI and five EBL patients still tissue to 69 ( ± 10.6) pmol/g, a range of 6-0 angiodysplasia were seen (three females, bled (P< 005). Prolapse of haemorrhoids to 98 pmol/g depending on the extent of three males, mean age 72 years (range occurred before treatment in seven aganglionosis. 47-84 years). patients in each group; three SI and five Thus, this study indicates that gross The patients all presented with episodic EBL patients obtained relief; however, a alterations in regulatory peptides occur in rectal bleeding or melaena. Four had further six patients in the SI group de- Hirschsprung's disease and may be of recurrent iron deficiency anaemia, mean veloped prolapse during the study. The major importance in its pathophysiology. Hb 6-9 g % (5 6-8 5). All patients had been treatment produced discomfort in nine SI extensively investigated by barium studies, and 18 EBL patients (P< 001). Eighteen upper GI endoscopy, and sigmoidoscopy. of the SI and 16 of the EBL patients two patients had undergone gastric thought the results of treatment were Normal sigmoidoscopic findings in severe surgery for duodenal ulcer. One female either excellent or good. ulcerative colitis: an important and had a resection for rectal carcinoma six We conclude that EBL, despite in- common occurrence years previously and a male patient aged creased discomfort, is a more effective 47 with myxoedema had a right orchidec- treatment for first and second degree W R BURNHAM, I D ANSELL, AND M J S tomy and radiotherapy for seminoma in haemorrhoids. Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of GastroeniterologyA A461

preventing the major changes in gastric cers were actively bleeding, 35 showed pro- spots. PLENARY SESSION emptying normally seen after gastric truding vessels, and 78 had central surgery. However, the symptoms of These 136 patients were randomly allo- epigastric fullness and distension still cated to a control group or photocoagula- persist after PGV and are thought to be tion with a Spectra-Physics 770 Argon ion Whole body protein synthesis and break- due to impairment of the normal adaptive laser. All patients received cimetidine and down in patients with large bowel carcinoma relaxation of the corpus-fundus area of were followed personally for at least the stomach. This reflex is now known to seven days. M J CARMICHAEL, M B CLAGUE, I D A be mediated via the non-adrenergic, non- There were no statistically significant JOHNSON (Newcastle upon Tyne) The cholinergic inhibitory fibres of the vagus differences between the two groups in metabolic relationships between the grow- nerve. Although the pharmacology of terms of re-bleeding, the need for surgery, ing neoplasm and the host are not fully neurotransmission in this reflex is still and overall mortality. Eleven of 13 control understood. The presence of a tumour unknown, recent evidence has suggested patients with ulcers actively bleeding at often causes changes in nitrogen equili- that dopamine may be involved. the time of endoscopy required surgery brium disproportionate to the size of To investigate this theory, the adaptive for continuing or recurrent bleeding, the tumour and difficult to interpret relaxation of the human stomach in against seven of 15 with laser treatment; with urinary nitrogen balance studies. response to rapid distension with air was for patients with protruding vessels, the Tumour bearing animals fed protein studied in normal healthy volunteers and figures were: controls, five of 16; laser, excrete less nitrogen and are in a positive patients at one month and one year after six of 19; and, in those with a central spot: nitrogen balance because of the accu- PGV. The effect of domperidone, a peri- controls, five of 39; laser, two of 34. mulation of increased amounts of pheral dopamine blocker, was also This method of Argon laser photo- nitrogen in the tumour. studied. In addition the effect of dopamine coagulation can stop active bleeding in A study was planned to measure whole on human isolated gastric smooth muscle some patients, but this small study casts body protein synthesis and breakdown tissue was examined, and compared with doubt on its overall clinical contribution (gKg-1d-1) preoperatively using a con- that of known inhibitors. and suggests that prophylactic treatment stant rate infusion of l_1- '4C) leucine. Dopamine was found to be an inhibitor of non-bleeding lesions is not worth Twelve apyrexial patients with varying of human gastric smooth muscle, pro- while. stages of colorectal carcinoma, seven of ducing relaxation, which was blocked by whom had normal appetites and five with domperidone. In the clinical studies, it was anorexia, were given clinifeed 400 (0.8 ml shown that, in response to rapid distension kg-1h-') for the duration of the study. the in the body of the http://gut.bmj.com/ The extent of their disease was assessed by by air, pressure Remedial surgery for disabling symptoms stomach rose and then returned to normal after gastric surgery-a 12-year experience the percentage incorporation of the 20 minutes. This labelled amino acid into plasma proteins during the following response was similar in patients at one A CUSCHIERI (Department of Surgery, (Clague et al., unpublished), and subse- year after a proximal gastric vagotomy, Ninewells Hospital and Medical School, quent Dukes' classification. but severely impaired in patients one Dundee) One hundred and twelve Protein synthesis increased with ad- It was also of disease in both groups month after the operation. patients with severe and persistent vancement found that under the influence of intra- symptoms after gastric surgery were

r=0-85, P=0 06, on September 25, 2021 by guest. Protected copyright. (r=0.95, P=0001, n=7; venous domperidone, the pressure profile treated surgically after detailed investiga- n=5) as did protein breakdown (r=0.91, in normal subjects closely resembled that tions: Galactomin radiological meals, P=0.004, n=7; r=0.79, P=0.1, n-5). after PGV. Protein synthesis and breakdown were less at one month gastric secretory studies, upper GI endo- suggesting These results show that dopamine re- scopy and biopsy, kinin provocation tests, raised in the anorectic group ceptors exist in the human stomach and oesophageal function studies, and tests some degree of starvation adaptation. that dopamine is a possible mediator of for malabsorption. The series consists of These results suggest that increase in reflex. with advancement of the adaptive relaxation 35 patients with severe dumping symp- protein synthesis toms (26 treated by proximal isoperistaltic disease may be due to tumour utilisation. the As all patients in this study were in jejunal interposition and nine by anti- Randomised study of endoscopic Argon peristaltic procedure), 51 patients with positive balance this suggests that the iso- tumour was 'trapping' significant amounts laser photocoagulation in bleeding peptic reflux alkaline gastritis (proximal ulcers peristaltic jejunal interposition) and 21 of protein for tumour growth. cases of severe diarrhoea, 17 ofwhom were A G VALLON, J-R ARMENGOL-MIRO, J C treated by distal anti-peristaltic inter- SALORD-OSES, B H LAURENCE, AND P B position (12 without reversal). Effect of proximal gastric vagotomy and COTTON (Gastrointestinal Unit, The Mid- The abnormal preoperative findings dopamine on adaptive relaxation of the dlesex Hospital, London, Endoscopy varied with the nature of the dominant human stomach Department, Francisco Franco Hospital, symptom(s). In patients with dumping, Barcelona) Emergency endoscopy showed rapid gastric emptying and rapid in- H D SINNETT (Char inig Cross Hospital that peptic ulcers were the source of bleed- testinal transit and dilatation were present Medical School, London) The operation ing in 178 of 332 patients admitted with in 100% but only 13 (37%) had a small of proximal gastric vagotomy (PGV) haematemesis or melaena to the Francisco stomach remnant. In patients with bilious preserves the normal innervation and Franco Hospital, Barcelona, between April vomiting, gastro-oesophageal reflux was function of the antroduodenal junction, and August 1979. Twenty-eight of the ul- found in 19/22 cases (86%), histological Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A462 The British Society oJ Gastroeniterology oesophagitis in 41/50 (80%), and histo- Invasion of veins by carcinoma of rectum output with the specific H2-agonist im- logical gastritis in 51/51. No abnormality and its clinical significance promidine, we administered SK&F 92994 other than rapid transit was found in 17 intravenously (0.8 mg kg-1h-') for 30 patients with diarrhoea, coeliac disease I C TALBOT, SHEILA RITCHIE, MONICA minutes to six subjects and intraduo- was diagnosed in two patients (9%), LEIGHTON, A 0 HUGHES, H J R BUSSEY, AND denally (200 mg) to four, the latter stagnant loop in one patient (4.5%) and B C MORSON (Department of Pathology, receiving cimetidine 200 mg on another gastro-ileostomy was discovered in School ofMedicine, University ofLeicester occasion. A separate group received another. and St Mark's Hospital, London) To re- cimetidine intravenously (2-0 mg kg-1h-1). The results of remedial surgery were as solve uncertainties over the incidence and Ten minutes after termination of the follows: relief of dumping symptoms in significance of venous invasion by rectal infusion of SK&F 92994 acid output was 63% (22/35), bilious vomiting in 95% cancer a prospective histopathological reduced by a mean of 960%, H+ concen- (48/51) and diarrhoea in 53% (9/17). study and follow-up of 703 surgically tration by 81.6o% and volume by 77%. treated patients was undertaken. Venous Cimetidine infusion resulted in a mean spread was found in 52 % of cases and was maximum inhibition of stimulated acid associated with development ofmetastases output of 65 %. and worsening of prognosis; when extra- After intraduodenal administration mural venous invasion was present the both SK&F 92994 and cimetidine reduced corrected five-year survival rate was gastric acid output, volume, and H+ Ultrasonically guided percutaneous aspira- halved to 33 % compared with when concentration to the same extent. tion biopsy of liver and venous invasion was not observed, Response half-lives after intravenous although invasion of intramural veins and intraduodenal administration showed R H TAYLOR, H FIELDEN, AND J J MISIEWICZ was less significant in this respect. no difference in the duration of action of (Department of Gastroenterology, Central Invasion of thick-walled veins is related to the two antagonists. We suggest that, Middlesex Hospital, London) The tech- a particularly high incidence of metastases under these experimental conditions, nique of ultrasonically guided percu- and low survival rate. Venous spread was SK&F 92994 given by intravenous in- taneous aspiration biopsy (UGPAB) was found to proceed in parallel with local fusion may be about eight times as potent developed for both diagnostic aspiration invasion but appears to exert an influence as cimetidine on a molar basis but only of cells and drainage of cysts. Despite the on prognosis independent of the Dukes' twice as potent after intraduodenal ad- simplicity, safety, and convenience re- stage. Subdivision of the 'B' cases ac- ministration. This difference is probably cording to extent of venous invasion due to first pass metabolism of SK&F ported, UGPAB has not been used widely http://gut.bmj.com/ in gastroenterology. provides a useful increase in the precision 92994. We report 23 patients who had UGPAB of prognostic assessment. A group with a of hepatic (13) and pancreatic (10) particularly poor prognosis within the lesions using a 2.5 MHz transducer with a stage 'C' category can also be identified by central channel for the 18 G outer needle identification of invasion of thick-walled Healing of mucosal lesions in early gastric and 23 G biopsy needle. The smallest extramural veins (corrected five year cancer (EGC) lesions were less than 2 cm diameter. All survival rate 8-5 %). Venous spread in rectal cancer is easily detected by rela- biopsies were carried out under local R FARINI, F DI MARIO, G LEANDRO, A on September 25, 2021 by guest. Protected copyright. anaesthesia with no sedation. Four tively simple pathological procedures CECCHETTO, N PENNELLI, AND R NACCARATO patients experienced local discomfort but which can and should be performed in (Istituto Clinica Medica I, Policlinico there were no immediate or late complica- any histopathology laboratory. Universitario, Padova, Italy) The gastric tions. In two patients who had surgery mucosal lesion in EGC can rapidly change and two with carcinomatosis who had in its macroscopical appearance. Mucosal necropsies within two weeks of the ulceration of type III or erosion sometimes biopsy, the needle track was not de- present in type IIC can progress towards tectable. SESSION F healing, with consequent difficulty in Malignant cells were aspirated from identifying the nature of the disease. Our nine of 11 tumours, whereas no malignant experience in this field is reported. cells were found in six benign lesions of Six cases of EGC (histological diag- liver and pancreas. The two false negatives SK&F 92994-a new histamine H2- nosis on the resected specimens) were occurred where inflamed pancreatic tissue receptor antagonist detected in a series of 3000 consecutive was aspirated from the vicinity of car- upper gastrointestinal (Olym- cinomas of the pancreas. No false posi- JANE G MILLS, M A MELVIN, R GRIFFITHS, pus GIF D2 or D3). They constituted tives were found. In six of six patients H HUNT, W L BURLAND, AND G J MILTON- 0.2%0 of the material and 7.9% of the with abscesses, pus was aspirated. THOMPSON (Smith Kline and French Re- observed gastric cancers (76 cases). Twenty out of 23 were of value in clinical search Ltd., Welwyni Garden City, Herts Two consecutive examinations (after management. Royal Naval Hospital, Haslar, Gosport, seven to 120 days) were carried out in UGPAB can provide a tissue diagnosis Hants) SK&F 92994 is a specific H2- five out of the six EGCs. A substantial in small lesions in liver and pancreas and receptor antagonist. Unlike cimetidine it modification of the lesion was observed provide a clinically useful and safe aid exhibits variation in potency and duration in four cases: three type III EGCs were in the management of patients with of action between animal species. endoscopically classified as type lic or Ilb suspected malignancies. After establishing maximal gastric acid at the second observation and one of type Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastr-oenterologA4 A463 lIc as llb. One type III was unchanged. Elizabeth Hospital, Birmingham) Cime- denitis was significantly less after HSV In three type III EGCs the diagnosis of tidine heals ulcers recurring after gastric than in DU patients (P<0-002). malignancy was made only at the follow- surgery, but the effectiveness of long-term Antral gastritis, seen in all DU patients, up examination, while the ulcer had been treatment is uncertain. In an open trial we was not significantly altered in severity considered benign in nature when first treated 25 patients with recurrent ulcers, after HSV. seen (negative histology). 17 after vagotomy and eight after resec- Gastritis of the corpus was seen in 52O° The following conclusions may be tion, with cimetidine 200 mg three times of DU patients, 50 % after HSV and in all drawn: (1) ulceration or erosion in EGC a day and 400 mg at night. Two died of patients after PG. This gastritis was can often heal; (2) it is necessary to unrelated conditions before completing significantly greater after PG than HSV, perform multiple biopsies on the repaired treatment. Of the remaining 23, endo- P< 005. Thus BACs in the stomach are gastric mucosa because of the possibility scopic healing had occurred in 20 by six lower after HSV than in DU patients be- of a false benign diagnosis at the first weeks and in 22 by 12 weeks. All patients fore operation and much lower than after observation. then had 400 mg cimetidine each night. PG. Four patients have since died, one, a The more severe gastritis after PG renal transplant recipient, from a massive than after HSV correlates with high bile Clinical study of the features associated upper gastointestinal haemorrhage. Six acid concentrations after PG. with failure and success of cimetidine in the have stopped treatment, after five to 15 treatment of peptic ulcer months (mean 8-8 months); one has minor symptoms and five are asympto- Bile reflux, gastritis, and gastric ulceration: M HASAN AND W SIRCUS (Gastro-intestinal matic. Thirteen have continued cimetidine, effects of partial gastrectomy and highly Unit, Western General Hospital, Edin- 400 mg at night, for from 25 to 40 months selective vagotomy burgh) Biological and social factors (mean 33-2 months). Of these, seven are which may influence ulcer healing were symptom free and six have trivial symp- E P DEWAR, M F DIXON, C BURUL, AND examined in two consecutive groups of toms only. No endoscopic recurrences of D JOHNSTON (University Departments of patients who were failures or successes as ulcer have been detected and no unto- Surgery and Pathology, General Infirmary regards ulcer healing in response to treat- ward effects of the drug observed. at Leeds) The aetiology of gastric ment with cimetidine. There were 80 The surgical treatment of recurrent ulceration (GU) remains obscure, but patients in each group. Mean age and age ulcers is difficult and can be dangerous. some believe it to be an end stage of of onset of symptoms were found to be Long-term low dose cimetidine may be an severe gastritis. The gastritis may be significantly lower in the failure group acceptable alternative, although it is not caused by excessive reflux of duodenal than in the successes. The proportion of known how long it should continue. content through an 'incompetent' pylorus, http://gut.bmj.com/ manual workers and artisans was signifi- rendering the gastric mucosa more cantly higher in the failure group. The vulnerable to acid-pepsin attack. Highly proportion with a positive family history selective vagotomy (HSV), when used in and the proportion with habits of smok- Bile acid concentrations in the stomach and the treatment of GU, should reduce both ing, and analgesic-taking were higher in gastritis in preoperative duodenal ulcer these factors, whereas both partial the failure group. There were more acid patients and in patients after highly gastrectomy (PG) and vagotomy with hypersecretors in the failure group. selective vagotomy and partial gastrectomy drainage increase bile reflux. However, the percentage reduction of Oesophagogastroduodenoscopy, with on September 25, 2021 by guest. Protected copyright. maximal acid output after a dose of E P DEWAR, M F DIXON, AND D JOHNSTON multiple biopsy and 'blind' histological cimetidine tested in 20 patients in the (University Departments of Surgery and assessment, was performed in 14 preopera- failure group and 10 patients in the Pathology, General infirmary at Leeds) tive GU patients and in asymptomatic success group was not significantly Gastritis, possibly as a result of 'bile' patients more than one year after HSV different. reflux, is a recognised sequel of partial (12) and PG (nine, seven BI, two Bl1). Our findings indicate that each of these gastrectomy (PG) and of vagotomy and Bile acid concentrations (BAC) in the factors namely, early onset, occupation drainage, and may predispose to gastric stomach were measured in eight preop- as a manual worker or artisan, family ulceration or gastric carcinoma. Highly erative GU patients, 12 patients after history of peptic ulcer, smoking, drinking selective vagotomy (HSV) by preserving HSV, five after PG and nine normal and abuse of analgesics and acid hyper- antral and pyloric function should subjects. secretion - contributes to non-respon- minimise this complication. Severe antral gastritis was present in all siveness to cimetidine treatment. Oesophagogastroduodenoscopy with preoperative GU patients and was not These factors, therefore, assist identi- multiple biopsy and 'blind' histological altered after HSV. Gastritis of the corpus fication of those patients in whom assessment wasper formed in 17 preop- was present in all patients and was not cimetidine treatment is likely to succeed erative DU patients and in asymptomatic significantly altered by either operation. or fail. patients more than two years after HSV BAC in the stomach after HSV are (12) and PG (seven). significantly less than after PG, and also Bile acid concentrations (BAC) in significantly less than in preoperative GU Long-term treatment with cimetidine of gastric juice during a standard Lundh meal patients. However, the severity of gastritis ulcers recurring after gastric operations were measured by the steroid dehydro- is no different after HSV than after PG, genase method in 10 DU patients, 10 suggesting that other aetiological factors G V H BRADBY, A M HOARE, C F HAWKINS, patients after HSV, seven patients after are involved in the gastritis associated AND J ALEXANDER-WILLIAMS (Queent PG, and nine normal subjects. Duo- with gastric ulcer. Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A464 The British Society of Gastroenterology

firmary, Leeds) The preoperative levels 60.8 mg/h (mean ± SEM) preoperatively SESSION G of a, antichymotrypsin (ACT), a, acid to 94.1 ± 18.9 mg/h postoperatively (p< glycoprotein (AGP), and carcino- 0.005); the galactose content of NDM embryonic antigen (CEA) have been from 73.6 ± 13-7 Hm Gal/h to 47.2 ± 10.6 found to have a highly significant relation Hm Gal/h (P< 0-05) and the galactose Effects of somatostatin on provoked to survival in 92 cases of gastric cancer content of high MW glycoprotein from flushing and plasma gut hormones in the studied for a minimum of 12 weeks and a 25-6 ± 6-1 Hm Gal/h to 7.9 ± 2.4 Hm carcinoid syndrome maximum of 88 weeks, 57 of whom had Gal/h (P< 0-01). There was no significant R G LONG, J R PETERS, D G GRAHAME-SMITH, died at the time of analysis. The Gehan difference in mucus secretion after AND S R BLOOM (Department ofMedicine, test (Generalised Wilcoxon) was used to pentagastrin stimulation. Royal Postgraduate Medical School, Ham- test significance of differences in survival We conclude that the rate of mucus mersmith Hospital, London, and the MRC curves. Simultaneous adjusting for ex- secretion is under some degree of vagal Unit and University Department ofClinical planatory variables was achieved by log control, and that after vagotomy mucus Pharmacology, Radeliffe Infirmary, Ox- rank methods. The discriminant levels of secretion is significantly reduced. ford) Somatostatin has a wide range of these variables, the median survival time inhibitory actions and a recent report in weeks and the number of patients (in suggested an effect on carcinoid flushing. parentheses) in each subgroup was as Cimetidine in the prevention of stress- The aim of this study was further to assess follows: ACT <0x8 g/1, 45 weeks (37); induced upper gastrointestinal bleeding this observation and to determine whether >0 8 g/l, 10 weeks (55); AGP < 1.4 g/1, gastrin or vasoactive hormones might, in 28 weeks (40); > 1.4 g/l, 10 weeks (48) and B VAN DEN BERG AND M VAN BLANKENSTEIN CEA <10 ng/ml, 28 weeks (57); >10 (Department of Internal Medicine II, part, mediate the flushing. Erasmus University, Rotterdam) The pre- Five patients with hepatic metastases ng ml, 10 weeks (35). The CEA and ACT provide different information about sur- vention of upper gastrointestinal tract hae- and frequent spontaneous flushing attacks morrhage in patients with respiratory were each given intravenous noradrenaline vival. This system can closely predict the in- stage found at operation. When stage is sufficiency by continuous cimetidine infu- and pentagastrin and oral alcohol on sions was evaluated in a consecutive days with and without intra- adjusted for preoperative ACT level, the double-blind con- overall accuracy of the prediction of trolled trial in 34 patients admitted to a venous somatostatin infusion. Flushing medical or surgical intensive care unit. All was quantified with skin temperature survival is greater than that given by stage alone. patients received assisted ventilation for measurement. Blood was taken basally at least three days. Risk factors (respira- and throughout the flushing episodes. tory insufficiency, shock, sepsis, jaundice,http://gut.bmj.com/ Hormones were measured by radio- renal insufficiency, and ) were immunoassay. Effect of vagotomy on gastric mucus assessed on admission and Cr51-labelled On the control saline day, noradrenaline secretion in man autologous erythrocytes injected. After provoked flushing in four patients, randomisation patients were treated in alcohol in four and pentagastrin in two. P BROWN, J R CLAMP, A E READ, AND J double-blind fashion with either cimeti- When somatostatin was infused, no BARRETT (Department of Medicine, Uni- dine 20 mg/kg/2 4h by continuous in- patient had even a minor flush with any versity of Bristol) Although gastric fusion or an equivalent volume of saline. stimulus. On stopping the infusion re- mucus is thought to be a major protective Gastrointestinal blood loss was estimated on September 25, 2021 by guest. Protected copyright. bound flushing occurred in one patient. factor in preventing mucosal damage, by measuring radioactivity in the con- Flushing attacks were not associated with little is known about factors influencing tinuously aspirated gastric contents. changes in plasma concentrations of mucus secretion. Gastric mucus secretion Twenty-eight patients completed the trial. gastrin, vasoactive intestinal polypeptide, has been measured in nine healthy The mean gastric pH in the cimetidine neurotensin, pancreatic polypeptide, or volunteers and in patients with chronic treated group was 4-8 as against 3.0 in the gastric inhibitory polypeptide. Somato- duodenal ulceration before and after placebo group (p< 001). Six patients had statin infusions, however, resulted in vagotomy. Gastric juice was collected a gastric bloodloss greater than 15 ml/24 h. markedly reduced plasma gut hormone under basal fasting conditions, after All had at least three risk factors. Five concentrations. intravenous insulin (0-1 units,lkg) and were receiving cimetidine, one placebo. Thus somatostatin inhibits carcinoid after subcutaneous pentagastrin (6 Of these six patients five died. flushing irrespective of the type of 11g/kg). Mucus secretion was assessed This study suggests that cimetidine in stimulus and independent of its effects on (1) by measuring the dry weight of non- this dosage, while increasing mean the gut hormones measured, but pre- dialysable soluble material (NDM), (2) by gastric pH, is ineffective in preventing sumably by preventing the release of a estimating the carbohydrate content of upper gastrointestinal bleeding in patients flush-producing substance. NDM and the high MW glycoprotein on assisted ventilation with multiple risk fraction obtained from NDM by factors. Sepharose 2B gel permeation chromato- Preoperative prediction of survival in graphy of NDM. gastric cancer Basal and stimulated mucus secretion Computer-aided duodenal ulcer surgery in the control group and in patients decision S A RASHID, E H COOPER, J O QUIGLEY, AND before vagotomy was very similar. How- A T R AXON (The Unit for Cancer Re- ever, after vagotomy there was a signi- R EARLAM AND S EVANS (The London search, University of Leeds and The Unit ficant reduction in insulin stimulated Hospital, Whitechapel, London) Three for Gastroenterology, The General In- mucus secretion. NDM fell from 298-3 ± hundred and nineteen patients with the Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society of Gastroenterology A465 radiological diagnosis of duodenal ulcera- five years after operation (146 imol/l vs The fat-encrusted colon can be dis- tion under the care of five different 14.4 ,umol/l). tinguished from inflammatory bowel surgeons filled in a questionnaire about Before operation there was a significant disease by familiarity with the radio- their symptoms. Data were transferred loss of weight in both groups (P< 0.01) logical appearances demonstrated and by on to five IBM cards. A sixth card con- (HSV: mean, 65.3 kg->59.6 kg; B1: 68.5 repeating the barium enema examination tained their pentagastrin test results. The kg->612 kg). After operation a steady after five days of fat restriction when the decision to operate was taken inde- weight gain was found for five years in colon returns to normal. pendently by each of the surgeons, not HSV group (p< 0-05, 59.6 kg ± SEM-> influenced by the questionnaire. One 64.6 ±25), whereas after B1PG weight hundred and ninety-six had an operation declined still further (P=NS, 612 kg + Campylobacter colitis: differentiation from and 124 did not. Multivariate analysis 2 0-+58.3 ± 15). Thus, at the end of five ulcerative colitis using stepwise regression with discrimi- years, patients after HSV had regained nant functions for each factor was carried their best weight, whereas, after B1PG, A S MEE AND M SHIELD (Gastrointestinal Unit out by computer. Using all variables 84 % patients were still significantly below and Bland Sutton Institute of Pathology, could be correctly placed into the cate- weight (p< 001). Between five and 10 The Middlesex Hospital and Medical gories of surgical or non-surgical treat- years, the HSV group did not lose weight, School, London) It has been suggested ment. If the 44 variables with a p value nor did the B1PG group gain. that campylobacter colitis may be difficult <0.2 were used, 76% were predicted These findings, taken with previous to distinguish from ulcerative colitis rightly. When the length of the history in evidence that faecal fat output is greater clinically, and on sigmoidoscopy and years, the amount of night waking and the after B1PG than after HSV, suggest that biopsy. During the past nine months we pentagastrin studies were used 71 % went long-term nutrition in GU patients is have seen eight patients, all female, with into the correct category. Using history better after HSV than after B1PG. campylobacter colitis. Each gave a con- length and nocturnal waking alone 660% sistent and characteristic history of a were correct. Five years later 23 patients sudden onset of fever, watery diarrhoea had changed status from non-operative to with blood and mucus, and of colicky surgery without altering the discriminant abdominal pain which was sufficiently functions significantly. At present nobody SESSION H severe to be the reason for referral in four measures each surgeon's threshold for patients. Proctosigmoidoscopy showed advising surgery, but assessment of these marked mucosal oedema, hyperaemia, two clinical factors alone, without any The fat encrusted colon and widespread aphthous ulceration. gastric function tests, will enable com- Biopsy at this stage confirmed an active http://gut.bmj.com/ parisons to be made. E M M QUIGLEY, P R MILLS, T P COLE, colitis with oedema, but relative preserva- T GIRDWOOD, W G SCOTT-HARDEN, AND tion of goblet cells. Stool examination was G WATKINSON (Department of Gastro- negative in one patient who presented enterology, Western Infirmary, Glasgow, with abdominal pain as the diarrhoea was Long-term effects on body weight and and the Departments of Radiology and settling; her serum contained high titres haematological measurements of Billroth 1 Surgery, Cumberland Infirmary, Carlisle) of flocculating antibody. Two patients partial gastrectomy (B1PG) and highly The clinical and radiological features of suffered relapses despite treatment with selective vagotomy with ulcer excision six cases of fat-encrusted colon are de- doxycycline and erythromycin, and one on September 25, 2021 by guest. Protected copyright. (HSV) for gastric ulcer (GU) scribed. In patients with steatorrhoea, fat remained symptomatic for seven weeks. may adhere to colonic mucosa producing In the acute stage, campylobacter D NEAL AND D JOHNSTON (University De- a radiological appearance which may lead colitis is readily distinguishable from partment ofSurgery, The General Infirmary to an erroneous diagnosis of inflammatory ulcerative colitis on the clinical, sigmoido- at Leeds) Patients with DU treated by bowel disease. scopic and histological features. A high or HSV tend to regain their preoperative Steatorrhoea was due to coeliac disease rising antibody titre is helpful where weights whereas after PG on average in five patients, the sixth being a case of doubt exists. they do not. primary sclerosing cholangitis. The radio- We measured weight, Hb, serum iron, logical appearances of the colon examined and B12 at yearly intervals for five to 10 by double contrast technique in four Preparation of the colon for double years after both BIPG (n=39) and HSV patients and by conventional barium contrast barium enema-a comparison of (n=40) for benign GU. The two groups enema in two patients led to initial diag- four regimens were matched for mean preoperative noses of ulcerative colitis or Crohn's weight (612 kg vs 59.6 kg) ideal weight, disease of the colon. On the basis of this G DE LACEY AND R WILKINS (Department (67 kg vs 66 kg), Hb (l 3.4 g/dl vs 14 g/dl), appearance surgery was advised in three of Diagnostic Radiology, Northwick Park age, sex, duration ofdyspepsia, and size of patients, one of whom proceeded to Hospital and Clinical Research Centre, ulcer. Ideal weight-for-height and recalled laparotomy with a view to colectomy. Harrow) It has been estimated that 75 0 best weights were recorded. The correct diagnosis was established by of the carcinomas of the colon missed on No significant differences were found complete return of the barium enema barium enema have been mistaken for, or between the two groups with respect to appearances to normal after five days of hidden by, faecal material. Though the Hb, B12, and serum iron. Mean serum fat restriction in five of the patients and by double contrast barium enema is an iron was low-normal in each group before establishing the diagnosis of coeliac dis- accurate examination, many departments (Bl, 12-5 ,umol vs HSV, 14-2 ,umolll) and ease in the sixth. do not perform this study because they Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A466 The British Society of Gastroeiterology cannot obtain nursing staff to perform KEIGHLEY, G D OATES, AND J ALEXANDER- areas were studied, the Cowal District of wash-outs or because wash-outs are per- WILLIAMS (The General Hospital, Bir- Argyll where bracken fern was abundant formed unsatisfactorily. mingham) The Autosuture end-to-end and the County of Ayrshire where it was A prospective study was performed on anastomosis (EEA) stapling instrument sparse. The human cancer incidence and 400 outpatients to evaluate the efficacy of was used by five consultant surgeons to mortality rates for sites in the alimentary four different regimens for preparing the perform 50 rectal anastomoses. Anasto- tract were similar in the two areas. colon. moses followed 28 anterior resections, 11 However, the geographical distribution of The results indicate that the colon is as sigmoid colectomies, three left hemi- alimentary tract cancer cases revealed well prepared by salax novum (a mixture colectomies, six total colectomies, and patterns suggestive of clustering in both of saline and contact cathartics) without two reconstructions after Hartman's areas. Statistical evaluation of this pheno- a wash-out, as it is by colonic lavage. procedures. menon, using a technique which examines In addition to having no advantage Successful anastomoses with the instru- the geographical proximity of cases which over salax novum, lavage has the dis- ment alone were completed in 41 patients. occur close in time, substantiated this advantage of expense, patient discomfort, In the first 25 patients three failed anasto- finding in five rural areas of Ayrshire and and an adverse effect on barium coating. moses were sutured by hand and three re- Argyll with stable and homogeneous quired reinforcement by sutures. In the populations. There was no significant next 25 patients two anastomoses were increase in farmers on whose farms the Aetiology of pruritus ani-a hypothesis sutured completely and one reinforced. cattle cancers had been detected. How- The reasons for these failures are ever, the demonstration of space time A A EYERS AND J P S THOMSON (St Mark s discussed. clustering suggests the possibility of some Hospital for Diseases of the Rectum and Defunctioning were already common aetiological factor. Colon, London) Persistent exposure of established in three patients and one loop the perianal skin to faeces (exposure) may ileostomy protected an ileorectal anasto- be central in the pathogenesis of pruritus mosis, all in the first 25 patients. ani. Of 48 patients with pruritus ani, 25 There were three deaths, one associated frequently found faecal stains on their with leakage from the anastomoses and SESSION I underwear (staining)-significantly more two from unrelated causes, all in the first than in 16 controls (x2 =415, P<0.05). 25 patients. Examination revealed faeces on the Urograffin contrast enemata on the What is 'acute cholecystitis'? perianal skin (soiling) in nine of the 23 tenth postoperative day indicated radio- com- http://gut.bmj.com/ patients without staining-indicating that logical leaks in 10 patients (20%), A W HALL, R A B WOOD, AND A CUSCHIERI staining underestimates the incidence of pared with clinical leaks apparent in three (Department of Surgery, Ninewells exposure. No soiling was found in 12 of patients (6%), and there was no signi- Hospital and Medical School, Dundee) the 25 patients with staining-indicating ficant difference in the incidence between Two recent controlled trials showed that soiling underestimates exposure. the first and next 25 patients. early surgery in acute gallbladder disease Anal pathology was present in 26 The EEA stapling instrument allowed to be associated with a reduced overall patients. This might produce exposure by more rapid anastomoses than by hand morbidity and hospital stay with no con- interfering with anal canal closure or ease suture and there was an acceptable leakage comitant increase in mortality. Such a on September 25, 2021 by guest. Protected copyright. of cleaning. Eighteen had either staining rate lower than in most reported hand- policy of early operative intervention was or soiling. sewn series. Successful anastomoses with adopted in patients with gallbladder Profound sphincter relaxation in re- the instrument increased with experience disease presenting as emergencies to a sponse to rectal distension, was present in of the operator. The instrument allowed teaching hospital unit. 10 of the 22 patients without pathology- very low anastomoses and avoided the To date 100 such cases have been treated significantly more often than in those with need for permanent colostomy in some surgically. They have been analysed with pathology (x2=3.86, P<0-05). Nine had patients with consequent decrease in respect to their mode of presentation and either staining or soiling. morbidity and cost. the extent of gallbladder disease de- Flatulence or poor cleanliness may be termined from operative findings and the responsible for the staining found in seven histology. of the 12 patients with neither pathology Clustering in human alimentary tract Examination of the gallbladder at nor profound sphincter relaxation. cancer operation confirmed gallbladder patho- Thus a mechanism for persistent ex- logy in all but two. The findings were as posure of the perianal skin to faeces was CR GILLIS, D J HOLE, AND J MCHARDY follows: acute gangrenous cholecystitis, 9; present in 43 of the 48 patients studied (West of Scotland Cancer Surveillance acute cholecystitis, 8; acute on chronic (89-6 %). Is this the main prerequisite Unit, Ruchill Hospital, Glasgow) The cholecystitis, 31; severe chronic chole- for the development of pruritus ani? observation of a high level of incidence of cystitis, 10; (total with severe symptoms, alimentary tract cancers in cattle in 58); moderate chronic cholecystitis, 25; Argyll, Scotland, and the putative link mild chronic cholecystitis, 13; chole- Fifty rectal anastomoses with the EEA with bracken fern exposure and bovine lithiasis without histological changes in stapling instrument: clinical and radio- cutaneous papilloma virus invited con- wall, 2; no abnormality, 2; (total with less logical leak rates sideration of the implication of these severe symptoms, 42). factors in the aetiology of human ali- Serious gallbladder pathology was N J DORRICOTT, R M BADDELEY, M R B mentary tract cancer. Two geographical therefore present in 58 cases presenting Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

The British Society, of GastroetiterologA4 A467

acutely. Jaundice, acute pancreatitis and 98.3 ± 15.8 to 39.2 ± 8.7 mmHg, P< 0.001). serum containing these antibodies stimu- severe right upper abdominal pain with This technique allows accurate assess- lates normal lymphocytes to become acute tenderness and pyrexia were signi- ment of the effects of sphincter surgery cytotoxic to halothane pretreated hepato- ficantly more frequent in this group with which to correlate clinical response. cytes. (54/64) than when the presenting symp- In order to determine whether the toms were biliary colic or upper abdo- oxidative or reductive route of halothane minal pain without tenderness (7/29). metabolism is involved in the production We conclude that (1) the majority of Diagnosis of pancreatic disease by endo- of the membrane alterations, rabbits were patients presenting as emergencies with scopic retrograde pancreatography and the exposed to 1 % halothane in oxygen con- gallbladder disease have severe inflam- secretin-CCK test-a surgical opinion centrations ranging from 100%X to 14%. mation and in 9 % perforation is imminent While these antibodies induced normal (one actually perforated); (2) there is a D E F TWEEDLE, J A HEYWORTH, AND M M lymphocytes to become cytotoxic to good correlation between the severity of RAVENSCROFT (University Hospital of hepatocytes isolated from rabbits anaes- symptoms and the severity of gallbladder South Manchester, West Didsbury, Man- thetised at 100%0 oxygen, the cytotoxicity pathology. chester) The diagnostic efficacy of endo- was not detected against hepatocytes scopic retrograde pancreatography (ERP) isolated from rabbits anaesthetised at and the secretin-cholecystokinin test 14%o oxygen. The absence of the halo- (SCCK) has been compared in 37 patients thane-altered neoantigen detected by this Endoscopic manometric evaluation of the with suspected pancreatic disease. The technique correlated with increasing effects of endoscopic sphincterotomy and ultimate diagnoses of these patients were: oxygen tension (r=0-82, P< 0 01). Ad- surgical sphincteroplasty on pancreatic carcinoma, three; chronic pancreatitis, 10; ministration of phenobarbitone, which and biliary ductal and sphincteric pressures acute relapsing pancreatitis, 10; and nor- stimulates the reductive pathway, caused mal pancreas, 14. Each report was a significant loss of cytotoxicity (P< 0-01) D L CARR-LOCKE and J A GREGG (New scored on a scale of -2 to +2 (modified and conversely, administration of 3- England Baptist Hospital, Boston, Mas- from Cotton et al.). ERP scored 60 out of naphthoflavone, which stimulates the sachusetts, USA) An endoscopic mano- 74 points, but SCCK only 29. SCCK oxidative pathway, increased cytotoxicity. metric technique was used to measure was useful in the diagnosis of chronic These results demonstrate that a meta- pancreatic duct (PD), common bile duct pancreatitis and patients with a normal bolite of halothane produced by the (CBD), pancreatic duct sphincter (PDS), pancreas. Surprisingly, five patients with oxidative pathway is involved in the im- and bile duct sphincter (BDS) pressures in acute relapsing pancreatitis had an munological component of halothane-

43 healthy volunteers, 15 patients after abnormal SCCK test. induced hepatic damage. http://gut.bmj.com/ surgical sphincteroplasty (group PSS), The difference was due to greater pre- 50 patients after endoscopic sphinctero- cision in diagnosis of ERP which was of tomy (group PES), performed for CBD particular benefit to the surgeon. The Acute pancreatitis in minipigs-treatment stones in 13 and papillary stenosis in 37, correct diagnosis was also established at and results with somatostatin and eight patients after PD sphincterotomy ERP in five out of 14 patients without for stenosis. The system employed a pancreatic disease. However, SCCK was M CLEMENS, J 0 JOST, G WITTRIN, AND H modified ERCP catheter, Hewlett-Packard abnormal in five out of 10 patients with WAGNER (From the Surgical Clinic of the acute relapsing pancreatitis, all of whom transducer and recorder and syringe pump University of Muenster, Muenster, W on September 25, 2021 by guest. Protected copyright. perfusing at 0-62 ml/mn. had normal ERP. It is suggested that Germany) Acute pancreatitis was in- Normal PD and CBD pressures were all patients with suspected pancreatic duced in minipigs by implanting T-tubes. disease require at least one assessment 10.7 ± 3.9 mmHg (mean ± SD) and 2O0 + The volume of the lower branch of the 1.7 mmHg respectively. After endoscopic of the anatomical and one of the physio- T-tube was reduced to one-third of its sphincterotomy (ES) for CBD stones, logical status of the organ. original diameter followed by intraductal CBD pressure fell from 15.2 ± 5-8 mmHg application of contrast medium. After to 1.8 ± 1.8 mmHg and when performed surgery the animals were divided in two for papillary stenosis, CBD and PD pres- Oxidative metabolism of halothane in the groups: nine animals were kept without sures fell significantly from 101 ± 3.8 to immunopathogenesis of the associated further treatment, while 11 animals were 0.8±0.8mmHg and 19.3±7.0 to 11l4+ liver damage interoperatively and subsequently treated 5.6 mmHg respectively (P< 0 001). After with somatostatin. With subtotal steno- PD sphincterotomy for stenosis, PD J M NEUBERGER, G MIELI-VERGANI, M sis of the pancreatic duct, the actual pressure fell from 22-4 ± 8.5 to 8-0 + TREDGER, M DAVIS, AND ROGER WILLIAMS causative factors for the development of 5.9 mmHg (p< 0.005). (The Liver Unit, King's College Hospital the acute hemorrhagic pancreatitis is seen In nine patients of group PSS and 12 of and Medical School, Denmark Hill, in an oedema provoked by impaired group PES, BDS activity was recorded. London) Patients with severe hepatic drainage resulting from congestion and PDS pressure fell significantly after ES for necrosis after halothane anaesthesia have enhanced by intraductal application of CBD stones (peak pressure from 67-3 + been shown to develop circulating anti- contrast medium. The secretory conges- 23-0 to 53.1 ±63 mmHg) and papillary bodies specifically directed against halo- tion together with an impairment of stenosis (peak from 69-6 ±20-3 to 51.3 + thane-altered hepatocyte membranes, in- cellular metabolic function leads to the 15.0 mmHg) (normal peak 47-2 ± 8.4 dicative of an immune reaction as a basis full picture of acute hemorrhagic pan- mmHg). PD sphincterotomy also reduced for the hepatotoxicity. This can be de- creatitis with confluent extended necroses. PDS pressure significantly (peak from tected by a cytotoxicity assay, whereby That the development of acute pancreatitis Gut: first published as 10.1136/gut.21.5.A443 on 1 May 1980. Downloaded from

A468 The British Society of Gastroenterology is much less pronounced under somato- quiring hospitalisation were treated by the The patient showed a marked clinical statin influence is explained by reduction withdrawal of all food and its replacement improvement in all 29 of the episodes in of the salivary volume resulting in lower with an elemental diet (Vivonex). A total which the course was completed with secretory pressure. The effect of somato- of 32 exacerbations in 27 patients, five significant rises in the haemoglobin statin to the laboratory findings ended being treated twice, were studied. The (p< 0.005), serum albumin (p< 0.005) and after cessation of somatostatin infusion. diet, containing 8-10 g of nitrogen and a fall in the ESR (P<0.005). 10-15 MJ of energy/day was taken orally Eighteen out of the 24 patients were for four weeks and was well tolerated in still in clinical remission after six months. all but two of the patients who were Five adolescents with growth failure re- withdrawn from the study. One other gained normal centiles on Tanner tables patient was withdrawn for resection of a for both height and weight. Elemental diets in the treatment of Crohn's chronic ileal obstruction. In addition to This pilot study indicates that an ele- disease the dietary treatment of the remaining two mental diet may offer an effective, non- patients, eight received no other therapy, toxic primary treatment of active Crohn's C O'MORAIN, A W SEGAL, AND A J three had steroids, intermittent levamisole disease. Its mechanism of action has not LEVI (Division of Clinical Sciences, Clini- therapy was introduced after two weeks been determined, but is relevant to an cal Research Centre, Harrow, Middlesex) in nine, and three continued on their pre- understanding of the pathogenesis of the Patients with active Crohn's disease re- trial drugs. disease. http://gut.bmj.com/ on September 25, 2021 by guest. Protected copyright.