Gut: first published as 10.1136/gut.25.6.693 on 1 June 1984. Downloaded from

Gut, 1984, 25, 693-696 Pancreatic Society of Great Britain and Ireland The Eighth Annual Meeting of the Pancreatic Society of Great Britain and Ireland was held at the Clinical Lecture Theatre, Manchester Royal Infirmary on 18 November 1983, under the Presidency of Mr Bruce Torrance. Abstracts of the papers presented at the meeting are printed below.

Pathology of the endocrine and exocrine BRAGANZA (University Department of pancreatic disease. Does hepatic damage pancreas in insulin dependent diabetes Gastroenterology, Manchester Roval have any influence? mellitus (IDDM) Infirmary, and Department of Pathology. Manchester University, Manchester) High R FARINI, A PANUCCI, G DE SILVESTRO, C A K FOULIS AND J A STEWART (Departtnent concentrations of lipid peroxidation (free FABRIS, A PICCOLI, G DEL FAVERO, U of Pathology, Western Infirmarv, radical oxidation) products have recently BACCAGLINI, G CERIOTTI, AND R NACCARATO Glasgow) Islet cell antibodies have been been discovered in from patients with (Istituto Cliniica Medica I, Istituto Clinica found up to three years before presentation pancreatic disease:' the principal product Chirurgica II, Universitd di Padova, Italia; in insulin dependent diabetes mellitus. has been identified as free radical damaged Laboratorio Centrale Analisi, Ospedale suggesting a prolonged latent period in the linoleic acid. Products with identical Civile Padova, Italy) Tissue polypeptide disease. As pathological material is not chromatographic characteristics have been antigen (TPA) described as significantly available during this time the best chance generated in vitro by peroxidising linoleic increased in various malignant growths, of observing the morphological expression acid in the presence of albumin. These was studied using a RIA procedure of the disease in the pancreas is in patients observations, the wide range of bioactive (Prolifigen, AB Sangtec Medical, who die at or near presentation. In a substances generated from free radical Bromma, Sweden) in the serum of 10 necropsy review of deaths from diabetes oxidation products and the suspected control subjects, 10 patients with pancre- mellitus. nine children died within 24 hours importance of 'reflux'- -4 in the patho- atic cancer, 10 with chronic pancreatitis of diagnosis of diabetes (acute diabetes). genesis of pancreatic disease lead to the and 14 with non-pancreatic digestive Two children who survived several years current investigation. diseases of non-malignant origin. The aim were termed chronic diabetics. In these Male 200 g Sprague Dawley rats were of the investigation was to ascertain the two. pancreatic islets were uniformly anaesthetised with intraperitoneal inactin, value of TPA in the detection of pancreatic shrunken and insulin deficient. All of the tracheotomised and the bile duct ligated cancer and the possible influence of hepatic http://gut.bmj.com/ acute cases showed a marked reduction in proximal to its junction with the pancreatic involvement in affecting its serum levels. islets containing insulin but in eight of the duct. A cannula was tethered in the A statistically significant difference nine cases large islets containing hyper- pancreatic duct at its duodenal entry point. among groups was found (F=5.57, trophic B cells were also present. Insulitis One hundred microlitres of the test p<0l 1): raised values were detected in all was present in eight of the acute cases but substance were delivered by a syringe the pancreatic cancer patients studied with was absent from the chronic cases. Islets pump (50 ,ul/m). Surviving animals were a significant difference in respect of control containing B cells were inflamed much killed at 12 hours, the macroscopic appear- subjects (p<001), chronic pancreatitis more frequently than insulin deficient ance of the pancreas recorded and the (p<00l1) and non-pancreatic digestive on September 28, 2021 by guest. Protected copyright. islets. Severe exocrine atrophy was present gland removed for histology. diseases (p

694 Pancreatic Society of Great Britain and Ireland receptor mediates the response to both infusion of , but increased it when methods and subsequent attacks appear hormones, then simultaneous administra- secretin and atropine were given. Phenoxy- more lethal. tion should show competitive inhibition, benzamine abolished the effects of DA on * 2=35 56 DF=1) but in man gastrin inhibits CCK-stimulated both protein and bicarbonate output. References protein secretion non-competitively.' whereas propranolol did not affect the I Trapnell JE, Duncan EHL. Patterns of incidence in Dose response curves to gastrin were acute pancreatitis. Br Med J 1975; 2: 179-83. action of DA on protein output, but 2 Death from acute pancreatitis. MRC. Multicentre trial obtained in conscious fasting dogs, abolished its action on bicarbonate output. of glucagon and aprotinin. Lancet 1977; 2: 632-5. previously provided under general anaes- These results indicate that two entero- 3 Cooper MJ, Williamson RCN, Pollock AV. The role of thesia with gastric and duodenal Thomas pancreatic reflexes are involved in the peritoneal lavage in the prediction and treatment of acute pancreatitis. Ann R Coll Surg EngI 1982: 64: cannulae. During infusion of secretion 0 5 effect of DA on secretin-stimulated 422-7. CU/kg/h, with or without CCK 0 75 IDU/ pancreatic secretion. The predominant one kg/h, increasing doses of gastrin (0.1-8 is cholinergic and stimulatory, and its ,ukg/h) were given. The results were linear- blockade by atropine unmasks a second, Acute pancreatitis in China: aetiological ised with the Dowd and Riggs transforma- inhibitory reflex, the suppression of which associations and outcome tion (R vs R/RD) to enable calculation of by DA leads to a rise in pancreatic secre- the maximal response (Rmax) and the dose tion. Both reflexes appear to contain a- producing half Rmax CHEN MING-CHAI, XU QING-FENG, YANG (ED50,). adrenergic receptors, and that controlling HONG-SHENG, CHANG ZHI-DE, AND CAI YI- Gastrin produced a dose-related bicarbonate secretion also has a /3- LANG (Departments of Surgery & response of fluid and protein secretion adrenergic component. The precise loca- Medicine, Suzhou Medical College which was inhibited by CCK. This effect tion of these receptors is not known. Hospital, Sozhou Ju 215006, People's was purely non-competitive for protein Republic of China) Presented by M J output (reduced Rmax, unchanged ED50,), Cooper and R C N Williamson (University but fluid secretion was inhibited by a Increased incidence and deaths from acute Department of Surgery, Royal Infirmary, combination of competitive and non- pancreatitis disturbing trends Bristol) Acute pancreatitis is one of the competitive mechanism (Rmax reduced, commoner causes of an acute in ED5, increased). A P CORFIELD, M J COOPER, AND R C N the People's Republic of China with an These results suggest either that the WILLIAMSON (University Department of incidence similar to that of acute appendi- actions of CCK and gastrin on pancreatic Surgery, Bristol Royal Infirmary, Bristol) citis. To determine the aetiological associ- http://gut.bmj.com/ fluid and protein secretion are mediated by The comprehensive review of acute ation and natural history of the disease all more than one receptor, or else that CCK pancreatitis in Bristol (1950-69) described patients admitted to Suzhou Medical has a much higher affinity than gastrin for 590 cases with mortality rates of 20.5% College Hospital between 1965-1981 with pancreatic receptors, particularly for (first attack) and 15% (subsequent acute pancreatitis were studied. There protein secretin. attacks).' For the past eight years 'all' were 213 men 383 women with an age Reference patients have entered prospective clinical I Duffaut M. Vasvsse N. Laval J et al. Simultaneous range of 15-86 years. Aetiological factors effects of secretin. cholecvstokinin and pentagastrin on trials with a lower mortality rate.' 3 in these 596 patients with acute pancreatitis the human exocrine pancreas. Biol Gastroenterol 1972; To determine the true natural history of were as follows: dietary surfeit (40.6%), on September 28, 2021 by guest. Protected copyright. 5: 71-78. acute pancreatitis a retrospective update biliary lithiasis and ascariasis (21.7%), (1969-79) revealed 737 admissions by 650 alcoholism (2.7%), pregnancy (2.6%), patients: 318 men, 332 women with a mean miscellaneous (2.7%), unknown (5-7%) Adrenergic blockade and enteropancreatic age of 60 years (range 3-94 years). The and idiopathic (24.1%). The course of the reflexes incidence has increased from 54 cases/ disease was mild and uneventful in 812% million/year (1961-67) to 73 cases (1969- of cases. Fulminating necrotising pancrea- C D JOHNSON, T M BIEDZINSKI, M A DEVAUX, G 79). Aetiological factors included gall titis requiring surgical treatment occurred ROBLES-DIAZ, H SARLES, AND D SCHMIDT stones (50%: 130 men, 189 women), alco- in 4.5%. There was an overall hospital (INSERM U31, Marseille, France) It is holism (8%: 45 men, six women), opera- mortality of 2-9%. Most of the survivors known that anaesthesia of the duodenum tions (3%) and idiopathic (23%). (80 8% overall) were followed up for >10 (DA) with lignocaine leads to a fall in Incidence of alcohol-related acute pancrea- years, and there was a 22 7% risk of secretin stimulated pancreatic secretion of titis has increased progressively over 30 relapsing pancreatitis. Ingestion of a large both protein and bicarbonate. This is years (1950-54: two cases 1975-79: 35 meal of cold rice, particularly after a thought to be a result of interruption of the cases). Mortality rates were 19.6% (first prolonged fast in individuals who are afferent arc of enteropancreatic reflexes. attack) and 12-1% (subsequent attacks). physically exhausted, was closely The properties of these reflexes were Death was commoner over age 60 years associated with the onset of an acute attack studied in conscious fasting dogs previously (102) of 370 patients: 28%) than under age in many patients. Moreover, relapse could provided, under general anaesthesia, with 60 years (23 of 268: 9%), p<0001.* Forty be avoided by appropriate dietary gastric and duodenal Thomas cannulae. four patients were diagnosed at necropsy measures. Secretin 1 CU/kg/h was given in a (32% of all deaths). continuous intravenous infusion of saline, There has been an absolute increase on with the addition of atropine 40 ,ug/kg/h, both the incidence and number of deaths Delayed diagnosis of pancreatic necrosis: phenoxybenzamine 1 mg/kg/h or propra- from acute pancreatitis in Bristol with an presentation and management nolol 0 25 mg/kg/h, alone or in increase in alcohol related disease. The combination. case mortality of a first attack has remained M NARENDRANATHAN, R LENDRUM, AND C W DA inhibited pancreatic secretion during the same despite modern resuscitative VENABLES (introduced by Professor I D A Gut: first published as 10.1136/gut.25.6.693 on 1 June 1984. Downloaded from

Pancreatic Society of Great Britain and Ireland 695

Johnston) (Medical and Surgical Gastro- report on the effect of intrapancreatic duct two consecutive scans with saline substi- intestinal Units, Freeman Hospital, pressure alone on the rat pancreas. tuted for morphine and neostigmine. Time Newcastle-upon- Tyne) It is recognised At laparotomy a fine cannula was activity curves over the liver were analysed that patients develop cysts and abscesses as inserted transduodenally into the common for all three groups. a complication of acute pancreatitis, mostly bile pancreatic duct with prior ligation of All healthy subjects and all postchole- within a few weeks of the acute attack. the proximal bile duct to prevent biliary cystectomy patients had a decrease in the Since 1972 we have seen 21 patients in contamination. Each animal received 50 ,ul slope on the second washout curve whom the diagnosis of previous pancreatic sterile saline via a constant infusion pump compared with the first, but there was no necrosis was made at operation. Fifteen at pressures of 0-50 cmH20, with mainten- difference between the groups. By had documented preceding pancreatitis, ance of pressure for either five or 60 contrast, amylase rose four- to eight-fold in four an acute onset not requiring minutes. The cannula was then removed six out of 10 healthy subjects but only hospitalisation and two no acute onset. and the animals allowed to recover, then two-fold in three out of nine postchole- There was a mean delay between onset and killed at 24 hours. Pancreatic damage was cystectomy patients; this difference was surgery of 16 5 months (range 3-72 assessed by histology, enzyme concentra- significant (p=0-05, Mann-Whitney U months). At presentation the clinical tions and pancreatic weights (degree of Test). None of the healthy subjects, but features were pain (20), weight loss (18), oedema). seven out of nine postcholecystectomy and raised amylase (15). All animals survived the 24 hour period. patients, developed severe abdominal ERCP established the need for surgery Five minutes of pressure increased serum pain. Control subjects had no pain, in 19 cases. In two, incomplete filling of the and peritoneal fluid amylase above 15 amylase rise or change in washout curve pancreatic tail went unrecognised at cmH.O (p<0-01) and pancreatic weight slope. ERCP. The diagnostic features were a above 20 cmH.O (p<0.02). Histological Amylase rise or the development of sudden block in an otherwise normal duct changes of oedema increased progressively abdominal pain after morphine- (six); extravasation of contrast from main with pressure. A pressure of 50 cmH20 neostigmine testing will not necessarily duct (eight); failed filling of pancreatic duct increased pancreatic weights (p<0.001) identify sphincteric disease as both despite ampullary cannulation (three) and and amylase levels (p<0-01) with mild duct phenomena occurred in asymptomatic duodenal stenosis/oedema (two). changes. Sixty minutes of pressure individuals. Washout curve slopes changed At operation the commonest finding was produced higher pancreatic weights consistently. however, and independently a cyst/abscess with necrosis of the adjacent (p<0-02) than at corresponding pressures of amylase rise or pain after morphine and pancreas (neck, nine; tail, six). In three the for five minutes. Pancreatic weights and neostigmine. Slope changes may therefore neck of the pancreas was replaced by a amylase concentrations were higher at reflect sphincter of Oddi tone, and adding

fibrous band and in three there was a pressures above 15 cmH.O (p<0.001). the dimension of radionuclide scanning http://gut.bmj.com/ leak (neck, two; head one) Histological changes in the acini and ducts may improve the specificity of the without cyst/abscess. were evident at 50 cmH.O. morphine-neostigmine test in disease. Independent review of 15/16 more than This study indicates that increased intra- References one year after operation (x=43.6, range pancreatic duct pressure alone for short I Nardi GL and Acosta JM. Ann Surg 1966; 164: 611-8. 2 LoGiudice JA. Geenen JE. Hogan WJ. Dodds WJ. Dig 14-116 months) showed complete pain periods of time has a significant effect on Dis Sci 1979; 24: 455-8. relief in 10; marked improvement in four; the pancreas. The changes seen, though 3 Steinberg WM, Salvato RF. Toskes PP. Gastro- no change in one. The remaining patient marked at 50 cmH.0 are apparent above 15 enterologsy 1980: 78: 728-31.

reported no improvement at earlier follow cmH.0. on September 28, 2021 by guest. Protected copyright. up. Patients with continuing symptoms after Resection for pancreatitis in patients with pancreatitis should undergo ERCP with Changes in liver 99mTc-EHIDA washout pancreas divisum immediate surgery available; the outlook during morphine/neostigmine stimulation in this group is then excellent. of the sphincter of Oddi R C G RUSSELL, A J BLAIR, AND P B COfrTON (Department of Gastroenterology, The G S CLAYDEN, ROSEMARY LAWRENCE, AND G Middlesex Hospital, London) One Effect of varying intrapancreatic duct GLAZER (St Mary's Hospital, Praed Street, hundred and fifty patients with pancreatitis pressure on the pancreas London) A positive morphine- in association with the duct anomaly of neostigmine test (raised serum amylase pancreas divisum have been investigated; C P ARMSTRONG, T V TAYLOR, AND H B and/or reproduction of abdominal pain) most of these patients have been managed TORRANCE (Department of Surgical has been advocated as a test or sphincter of conservatively, but a few required Gastroenterology, Royal Infirmary, Oddi disease,' but lacks specificity2 and intervention. The early results of accessory Manchester) Biliary pancreatitis is most reproducibility.3 spincterotomy (endoscopic and surgical) likely to be initiated by the temporary Ten normal volunteers and nine have been published, but no report obstruction of the common channel by a asymptomatic postcholecystectomy describes resection. gall stone resulting in increased pancreatic patients received two intravenous bolus Fifteen resections in 14 non-alcoholic duct pressure. After an initial rise in doses of 99mTc-EHIDA separated by one patients (mean age 43 years) were pressure, reflux of bile and/or duodenal hour. Fifteen minutes before the second performed for recurrent acute attacks of juice containing infection may produce dose, 10 mg morphine and 1 mg neostig- pancreatitis (mean symptom duration nine further insult to the gland thus promoting mine were administered intramuscularly. years); 12 patients also had persistent pain. pancreatitis. The relative importance of Amylase was measured half hourly for two All had normal ventral ducts and six had these factors requires to be elucidated. We and a half hours. Five control subjects had abnormal dorsal systems. A pancreato- Gut: first published as 10.1136/gut.25.6.693 on 1 June 1984. Downloaded from 696 Pancreatic Society of Great Britain and Ireland duodenectomy was performed in 10 has a place in the management of some R J L ANDERSON, A K KHULLAR, F S STEVEN, patients, 70-80% resection with drainage patients with chronic pancreatitis. R M CASE, AND J M BRAGANZA (University in three, and a 70% resection followed by a References Department of Gastroenterology, 95% resection in one. All patients are alive 1 White 1T. Pancreatitis. London: Arnold. 1966: 201. Manchester Royal Infirmary; and Depart- 2 Sarles JC and Delacourt P. The surgery of chronic one to seven years later with only three pancreatitis in the exocrine pancreas. Philadelphia: ments of Physiology and Biochemistry, patients having troublesome pain, all of Saunders, 1979. Manchester Medical School, Manchester) whom had normal size dorsal ducts. One 3 Warren KW. Surgical management of chronic relapsing Trypsin inhibitor provides a primary patient developed diabetes (after 95% pancreatitis. Am J Surg 1969; 117: 24-32. defence against premature intrapancreatic resection). activation of trypsinogen: inadequate avail- Histology showed chronic pancreatitis in ability of trypsin inhibitor would thus set the dorsal pancreas with a normal ventral Prospective comparison of clinical assess- the stage for pancreatitis. Alternatively, in pancreas in those who had a pancreato- ment and peritoneal lavage for the predic- this autodigestive process, the normal duodenectomy. tion of systemic and local components of route for zymogen activation might be Resection is satisfactory treatment, severe acute pancreatitis circumvented. especially in patients with dilated ducts. We are exploring these possibilites by We are currently evaluating accessory A D MAYER AND M J MCMAHON (University monitoring the levels of trypsin inhibitor sphincterotomy as a less radical Department of Surgery, The General and of chymotrypsin - which is unaffected alternative. Infirmary, Leeds) Death from acute by trypsin inhibitor' - in human pancreatic pancreatitis may be a consequence of a secretions collected endoscopically after fulminant early systemic illness or of later stimulation by secretin and pancreozymin. Effective trans-ampullary extraction of local complications within the pancreas. It The preliminary results from studies in pancreatic calculi in the management of should be possible to identify the early volunteers, patients with recurrent chronic pancreatitis component soon after the onset of the pancreatitis, pancreatic cancer (which may attack but prediction of later complications present as acute pancreatitis2) and biliary D T MANSELL, G GILLESPIE, AND C W IMRIE may be more difficult. This study was disorders have been compared. (Departments of Surgery, Victoria and designed to compare clinical assessment Pancreatic secretions from volunteers Royal Infirmaries, Glasgow) Most with peritoneal lavage in the recognition of did not contain any free trypsin or chymo- authors ' 2 consider transduodenal these two components of severe trypsin and trypsin inhibitor was detectable sphincteroplasty (TDS) inappropriate to pancreatitis. in most samples: the concentrations of the management of chronic pancreatitis, Three hundred and two patients with a chymotrypsinogen and trypsin inhibitor although Warren3 believed this procedure clinical diagnosis of acute pancreatitis were increased sharply after pancreozymin. By of some value in proximal pancreatic duct studied prospectively. Eighty nine were contrast trypsin inhibitor was markedly http://gut.bmj.com/ obstruction. We report five patients (four asymptomatic at the time of referral and reduced or undetectable in the secretions men) with chronic pancreatitis who were were not lavaged. The remainder were from patients with pancreatic disease, so each shown on ERCP to have stones in the assessed clinically as 'mild' or 'severe and that some free trypsin was present in most pancreatic duct system. All suffered from then subjected to peritoneal lavage which samples: free chymotrypsin accounted for pain ranging from two to 16 years duration was successful in 181. revealing an 20-75% of the potential chymotryptic and this was relieved in each after stones erroneous clinical diagnosis of acute activity. Free trypsin and chymotrypsin were removed from the pancreatic duct. pancreatitis in six patients. were noted sporadically in the secretions Stone removal was achieved after TDS There were 36 early severe attacks with from patients with biliary disorders. using either Fogarty balloon catheter, 12 deaths. Thirty (12 deaths) were recog- These findings support the idea3 ' that a on September 28, 2021 by guest. Protected copyright. Dormia basket or surgical forceps. nised by peritoneal lavage and 20 (eight defect in synthesis, or pathological Pancreatic function was measured pre- deaths) by clinical assessment (p<0.05). Of degradation, of trypsin inhibitor may be a operatively in three patients and 24 attacks (two deaths) which were severe common denominator in the pathogenesis marginally improved subsequently in two; solely because of late complications only of pancreatic disease. The secretory abnor- coinciding with clinical improvement which six (no deaths) were recognised by perito- malities detected in the patients with was surprisingly good in all but one patient. neal lavage and six (no deaths) by clinical biliary pathology are in keeping with the He alone failed to gain weight and suffered assessment. Nine of 115 mild attacks were recently noted association between chronic recurrent pain in the follow up of six to 30 wrongly assessed by peritoneal lavage and pancreatitis and biliary diseases5 6 (primary months (median 22 months). Further four by clinical assessment. biliary , sclerosing cholangitis). ERCP revealed a recurrent calculus in the This study shows that peritoneal lavage pancreatic duct and this was removed may correct an erroneous clinical diagnosis References endoscopically. The Fogarty balloon of acute pancreatitis and predict early I Keller PJ and Allan BJ. J Biol Chem 1967; 242: 281. 2 Gambill EE. Mayo Clin. Proc 1971; 46: 174. catheters tended to rupture against calcium severity before the clinical features of 3 Renner IG et al. Gastroenterology 1978: 75: 11)90. carbonate stones and other instruments are fulminant pancreatitis become apparent. 4 Geokas MC and Rinderknecht H. Dig Dis 1974; 19: better used in these cases where calcified 591. 5 Klass HJ et al. Gut 1979; 20: A433. stones are present. 6 Axon AT et al. Clin Radiol 1969: 30: 179. Contrary to widely held views, simple Chymotrypsin and trypsin inhibitor in RJLA and AKK were supported by Amelie Waring stone extraction from the pancreatic duct pancreatic disease fellowships of the British Digestive Foundation.