April 1995 Pancreatic Disorders A397

• RELAPSING PANCREATITIS IN GARDNER'S SYNDROME: STONE, TUMOR, OR ANATOMIC VARIANT?. DIAGNOSTIC APPROACH AND RESULTS OF INTERVENTIONAL THERAPY. S. Uriyima, R. Kozarak. S .L Raltz, L.W. Trav~rso, D. Wechter, R. Thirlby. Virginia Mason Medical Center, Seattle, WA

Panereatitis as a consequence of ampullary neoplasm has infrequently been reported in Gardner's syndrome. We describe the diagnostic and therapeutic approach to a series of such patients (pts) referred to a large multiapecialty clinic. Materials and Methods: A retrospective chart review (1/86-12/94) was undertaken and defined pt demographics, PMH presentation, diagnostic evaluations undertaken, and subsequent response to sequential therapy. Results: 7 pts (5 F, 2 M, ~ age 42) with Gardner's syndrome and relapsing pancreatitis were defined. All had undergone subtotal (5) or total (2) colectomy and 4/7 had had prior cholecystectomy. Biliary ultrasound, and metabolic studies were negative and no pt was taking pancreatico-toxic medication. Median duration of pancreatitis attacks was 8 months (3d-3yr). ERCP and treatment results are summarized in the table:

ERCP Rx Pancreatitis Subsequent Rx Panereatitis relief relief

1. AMP tumor ES-CBD + Whipple NA (dysplasia)

2. AMP tumor ES-CBD/PD + Adhesionolysis NA

3. AMP tumor ES-CBD/PD + Whipple NA papillectomy (dysplasia)

4. Pap stannsis ES-CBD PD aphinctero- + plasty

5. N o r m a l ES-CBD/PD Whipple

6. CBD stone ES-CED + NA

7. Divisum ES-CBD/PD a. Surgical ACC aphinctoplasty

b. Whipple + ES = endoscope aphincterotomy; NA =not applicable

Conclusions: 1) Although ampullary tumors are a cause of obstructive panereatitis in Gardner's syndrome, additional etiologias should be sought and treated. Endotherapy alone resolved pancseatitis attacks in 4 of 7 pts, although additional surgery was ultimately required in most (C loop dysplasia 2, small bowel obsmlction 1).

DEFICIENCY IN ANTIOXYDANT FACTORS IN PATIENTS WITH ALCOHOL-RELATED CHRONIC PANCREATITIS (ACP). A. Van Gossum, Ph. Closset, E. No~l, J. N~ve and M. Cremer. Dept of Gastroenterology, ULB, H6pital Erasme, B-1070 Brussels, Belgium ; Lab. Chemistry, Ambroise Par~, B-7000 Mons, Belgium ; Section of Pharmacology, ULB, B-I070 Brussels, Belgium.

Background : oxygen-derived free radicals could participate in the pathogenesis of ACP and in the higher risk of pancreatic cancer in ACP. Material and methods : thirty-five patients with ACP (mean age : 48 ± 8 years ; 23 males and 12 females) and 14 healthy controls (C) (mean age : 45 ± 13 years ; 6 males and 8 females) were included in the study. The following parameters were studied : alcohol intake, diabetes mellitus, steatorrhea, dietary intakes in vitamin E and selenium. Biochemical tests were : Hb, WBC, CRP, triglycerides, cholesterol, iron, copper, zinc, selenium, Se-GSHPx, vitamin E, vitamin A and MDA test. Statistical analyses were accomplished using Mann-Witney two-tailed U-test. Results : the blood levels of vitamin E (15.7 ± 9.6 vs 8.0 ± 5.5 pg/ml), vitamin A (48 ± 12 vs 30 ± ii Ng/100 ml), Se-GSHPx plasm. (1326 ± 168 vs 903 ± 313 U/l) and Hb (14.3 ± 1.4 vs 13.0 ± 1.6 g/dl) were significantly lower in ACP than in C. The levels of WBC, Copper and CRP were significantly higher in ACP than in C. In ACP group, the level of vitamin E was significantly decreased in presence of steatorrhea but higher in case of active alcohol abuse. The level of vitamin A was significantly lower in diabetic ACP patients. A 5 days diet interrogatory showed no difference in dietary intakes between ACP and C. Conclusions : ACP patients are deficient in several antioxydant factors (vitamin E, A and selenium) despite adequate dietary intakes. Supplementation in antioxydant factors is recommended in ACP patients°

• CHRONIC PANCREATIC FIBROSIS INDUCED BY TRANSFORMING GROWTH FACTOR BAFTER RECURRENT ACUTE PANCREATITIS IN MICE. J.L. Van Laethem, J. Devi~re, A. R~sibois and P. Robberecht. Dept of Hepatogastroenterology, ULB, H6pital Erasme, B-1070 Brussels, Belgium.

Transforming growth factor 8 (TGFB) is a multipotential cytokine involved in the regulation of inflammation, tissue repair and cell growth and is the putative mediator of fibrosis in hepatic cirrhosis. Recently, chronic pancreatitis (CP) was challenged to be related to acute pancreatitis (AP) in the so-called necrosis fibrosis sequence hypothesis. The aim of the present study was to investigate whether TGFS is able to promote chronic fibrosis after repeated episodes of AP induced by cerulein in mice. Six necrotizing AP were repeatedly induced at weekly intervals : animals (i0 in each group) received at each induction either recombinant TGFB (4 ~g administered in 4 days) or saline solution, and were sacrificed one week after the last induction. Results : during the acute phase of pancreatitis, no difference was seen between both groups in terms of amylase release or histologic alterations. After 6 courses of PA, only mild inflammatory changes were observed in the control group without necrosis or fibrosis. In the TGFB group, important areas of peri and intralobular fibrosis were observed in all animals and were adjacent to inflammatory and necrotic areas. It is concluded that TGFB could promote fibrosis after repeated courses of AP and might be a potential mediator involved in the acute necrosis - chronic fibrosis sequence hypothesis.

• INTERLEUKIN-10 (IL-10) DECREASES SEVERITY OF AcuTE NECROTIZING PANCREATITIS IN MICE. J.L. Van Laethem, A. Marchant, A. Delvaux, M. Goldman, P. Robberecht, T. Velu and J. Devi~re. Depts of Gastroenterology and Immurkology, and IRIBHN, Erasme University Hospital, Brussels, Belgium.

Background/aims : inflammatory and necrotic events are thought to be involved in the pathogenesis of acute pancreatitis (AP). IL-10 is a potent anti-inflammatory cytokine, able to inhibit the production of proinflammatory cytokines by mono/ macrophages. The present study has tested the potential protective effect of IL-10 in necrotizing AP induced in mice by cerulein. Methods : animals (n=30/group) received 2 intra- peritoneal (i.p.) injections of i000 U recombinant IL-10 or control supernatant before and during induction of AP with seven i.p. injections of 50 Ng/kg cerulein at hourly intervals. Serum amylase, lipase and TNF were assessed as well as histo- logical scoring of pancreatitis ; TNF mRNA expression was examined in pancreatic tissues by RT-PCR. Results : systemic amylase and lipase peaks were significantly reduced by IL-10 treatment (p<0.01 at 9 and 12 hours). Histologically, edema and inflammation of the pancreas were observed in both groups while necrosis was dramatically reduced in IL-IO treated animals. Serum TNF levels were undetectable in this model; TNF mRNA was significantly expressed at 9 hours in the control group whereas it was undetectable in the IL-10 group. Conclusions : IL-10 is able to prevent the development of necrosis in experimental AP and decreases its severity. One of the suggested mechanisms is the inhibition of TNF production by mono/macrophages infiltrating the pancreas.