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221. ASSESSMENT OF IMMUNE RESPONSE IN PATIENTS WITH PANCREATIC CANCER VACCINATED WITH GASTRIN-DIPHTHERIA TOXOID (G17DT)
  1. S.J. McAree1-1,
  2. A.P. Catterall1-11-2,
  3. S.M. Greenfield1-11-2,
  4. P.B. McIntyre1-1
  1. 1-1QE 2 Hospital, Welwyn Garden City; 1-2Lister Hospital, Stevenage, UK
  1. D. Watts,
  2. N. Anderson,
  3. S. Campbell,
  4. G. Brydon,
  5. S. Ghosh
  1. Gastrointestinal Unit, University of Edinburgh, Western General Hospital, UK

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G17DT is a conjugate of an epitope derived from gastrin 17 linked to Diphtheria toxoid (DT). Gastrin is an autocrine growth factor in pancreatic and other GI tract cancers. In a phase II study of G17DT for advanced pancreatic cancer only 6/13 (45%) formed antibody to 100mcg of G17DT however 15/18 (83%) formed antibody to the higher dose of 250mcg. The median survival of the whole group was 7 months. Side effects were limited to mild local pain and erythema with 3 patients forming an abscess. Patients with pancreatic cancer are thought to have a suppressed immune response compared to other GI cancers.

Aim: To assess anti-DT antibody level pre and post vaccination to determine its correlation with Gastrin antibodies and relationship with immunogen side effects.

Methods: 26 of the 31 vaccinated patients had serum available. 18 had developed antibody to gastrin (G+) and 8 had not (G-). Anti-DT antibody level was determined by in-vitro tissue culture neutralisation of purified DT.

Results: 16 (88%) of the G+ group had non-protective levels of anti-DT antibody before vaccination compared with 7 (87%) of the G- group. In cases given 100mcg of G17DT and remaining G-, 3/6 (33%) produced protective levels of antibody to DT; the median rise in DT antibody was 1 fold. Both of the 2 cases given 250mcg and remaining G- failed to become DT protected. In those who became G+ after 100mcg of G17DT, 16/18 (89%) were DT immune. The rise in the DT titre was 64 fold in the 100mcg group and 256 fold in the 250 mcg group. In the 3 who formed an abscess, all achieved high anti-gastrin antibody levels and had non-protective anti-DT baseline titre, with a median increase of 256 fold in anti-DT antibody.

Conclusion: 250mcg of G17DT produces higher titres of anti-DT as well as a higher proportion of G+ patients. Response to G17DT is not dependent on pre-vaccine DT antibody. An anti-DT response was seen in some G- patients therefore suggesting that this group is not uniformally immunosuppressed.

222. ONE-YEAR AUDIT OF THE MANAGEMENT OF PANCREATIC CANCER AT A DISTRICT GENERAL HOSPITAL

Introduction: The treatment of Pancreatic cancer remains a challenge to a good endoscopic service. Three Gastroenterologists provide the ERCP service for the 500 000 population of East and North Hertfordshire NHS Trusts. Over 300 ERCP's are performed annually. In common with other units, we are finding that an increasing number of ERCP's are therapeutic. We wished to review the efficacy of our diagnosis and endoscopic treatment of pancreatic cancer.

Methods: Patients were identified between 31.03.1999 and 31.03.2000 from the endoscopic database and from diagnostic coding. 51 patients were identified, all with complete ERCP data. 10 patients notes were incomplete with regard to non ERCP data and have been excluded.

Results: 92% presented with recent onset jaundice and a background of weight loss. 72% presented as medical emergencies to the on call medical team. Of the techniquely feasible procedures ERCP alone provided palliation of jaundice in 77% of patients within a mean of 10 days. Of the remainder of non-palliated cases PTC provided relief in 91%. ERCP alone provided a tissue diagnosis in 29% of patients. 100% of bile duct brushings and small bowel biopsies were adequate. 67% of Pancreatic fluid samples were adequate. PTC provided a tissue diagnosis in one patient with 66% adequate samples. In 12 ERCP's and 2 at PTC's there was no attempt at tissue diagnosis. 25% of stents needed to be replaced with a mean survival of 89 days.

Conclusion: Pancreatic cancer tends to present as a medical emergency with icterus. The success of palliation with ERCP and PTC is comparable with other studies (J R Coll Surg Engl 1992;74:338–42.). The adequacy of samples taken at ERCP and PTC is also comparable as was stent survival (Gut 1997;40:671–8). Our referrals to the surgeons seemed appropriate, however only 6 were referred to an oncologist. After discussion it was felt that we should: a) Endeavour to collect brushings and small bowel biopsies at ERCP, to improve our tissue diagnosis rate. b) That we were under referring patients to our oncology service.

223. FAECAL CALPROTECTIN IS ELEVATED IN PANCREATIC INSUFFICIENCY

Background: Calprotectin is a stable 36kDa neutrophil derived bactericidal protein. Elevated faecal calprotectin has been reported by us and others, in inflammatory and neoplastic diseases of the intestinal tract. It has been suggested that faecal calprotectin might be a useful screening tool in distinguishing organic from functional bowel disease, especially in children. We report, for the first time, elevated faecal calprotectin in patients with diarrhoea due to pancreatic insufficiency.

Method: A total of 115 patients (77 women: 38 men; age 19–85) with chronic non bloody diarrhoea were screened in this study. Both pancreatic elastase and calprotectin were assayed by ELISA in faecal samples (normal : calprotectin < 30 μg/g. elastase >150 μg/g.) Pancreatic imaging in those with low faecal elastase was carried out by a combination of CT scanning, endoscopic pancreatograms and endoscopic ultrasonography.

Results: Twenty six (21%) patients had low faecal elastase. Of these, 5 were confirmed radiologically to have chronic pancreatitis. All 5 patients were shown to have abnormally high faecal calprotectin levels (90–534 μg/g). 14 patients had suspected pancreatic insufficiency in the absence of other causative pathology. 13 (93%) of these patients had elevated faecal calprotectin (73–799 μg/g). 7 patients with low faecal elastase and ‘watery’ faecal samples were subsequently shown to have probably normal pancreatic function and an alternative explanation for symptoms (adenoma, Clostridial colitis, small bowel bacterial overgrowth, diverticular disease). Of these patients, 2 (29%) had abnormally high faecal calprotectin (176 μg/g=adenoma, 2670 μg/g=C.diff colitis) (table 1).

Abstract 223, Table 1

Conclusion: Pancreatic insufficiency may be associated with high faecal calprotectin in the absence of neoplastic or inflammatory intestinal disease. Low faecal elastase may also be associated with watery diarrhoea secondary to inflammatory intestinal disease, itself associated with an elevated faecal calprotectin concentration.

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