A386 AGA ABSTRACTS GASTROENTEROLOGY, VOI. IO8, No. 4

• PANCREATIC HEMODYNAMICS IN CHRONIC PANCREATITIS: A COMPARTMENT SYNDROME PU Reber, AG Patel, AM Kusske, MT Toyama, HA Rebel SW Ashley. Depts of surgery, UCLA and Sepulved a VAMC, Los Angeles, Ca. Chronic pancreatitis (CP) is associated with an increase in interstitial pressure (IP) and a reduction in pancreatic blood flow (PBF). We have previously suggested that this situation may be akin to a compartment syndrome in which the elevated IP, in the setting of a fibrotic, noncompliant pancreas, increases venous pressure. By reducing the arterio,venous pressure gradient, this in turn reduces PBF. TO test this hypothesis, we employed the isolated perfused pancreas model to compare the relationships between perfusion rate (PR), perfusion pressure (PP), and IP in normal and CP glands. Methods: CP was created in cats by partially narrowing the main pancreatic duct. After 6 wks normal and CP glands were isolated and perfused at varying rates and the changes in PP and IP, measured with an interstitial needle, compared. Results: (at a flow of 70 ml.min "l 100g "1)

NORMALS (5) CV (5) PP (mmHg) 41+4 104+1. IP (mmHg) 0.65_+0.2 3_+0.2*

*p<0.05 vs Normal ( Similar results were obtained at all other flow rates studied.) Conclusions: In the normal pancreas, increases in flow were associated with minimal alterations in PP or IP. In contrast, in the CP glands, increases in perfusion were accompanied by a marked increase in PP. This lack of compliance was reflected in a parallel increase in IP. These hemodynamit~ alterations are consistent with the concept that the CP pancreas is a closed compartment, In vivo, where perfusion pressure but not flow is constant, this pattern would markedly compromise the ability the pancreas to increase PBF in response to changing physiologic demands.

STENTING DOitS NOT DECOMPRESS THE PANCREATIC DUCT AS EFFECTIVELY AS SURGERY IN EXPERIMENTAL CHRONIC PANCREATITIS PU Reher_, AG Patel, AM Kusske, MT Toyama, SW Ashley, HA Reber. Depts of Surgery, UCLA and Sepulveda VAMC, Los Angeles, Ca. , Chronic pancreatitis (CP) is associated with a compartment syndrome in which the pancreatic interstitial pressure (IP) is high and the pancreatic blood flow (PBF)is low because of a decre~ed artetio-venous pressure gradient. The efficacy of surgical pancreatic duet decompression is believed to be due tO its ability to effectively decrease IP and increase PBF. Pancreatic duct stents would also be expected to reduce duct and IP, but their ability to relieve pain is controversial. Because we doubted that stents lowered duet and IP as effectively as surgical duct decompression (SD), we compared the effects of each on IP and pancreatic vascular perfusion pressure in an experimental model of chronic pancreatitis in cats. Methods: CP was createdby narrowing the main pancreatic duct. After 6 wks, the pancreas was isolated and perfused ex vivo at different flow rates. In normal and CP groups, IP and perfusion pressure (PP) were measured at different flow rates under basal conditions, after stenting (2 cm, 5F Geenen), and after SD. SD Consisted of complete transection of the duct with longitudinal capsulotomy. Results: (at a flow of 70 ml.min "1.100 g-l)

CONTROL (5) CP(5) STENT(5) SD(5) PP (mmHg) 41_+4 104+1. 96+_2# 86-+2© IP (mmHg) 65+0.2 3_+0.2 * 2.7_+0.2# 1.3_+0.4© • p<0.05vs Control, #p<0.05 vs CP, ©p<0.05 vs STE and CP (Similar results were obtained at all other flow rates studied.) Conclusions: The elevated PP and IP are consistent with the existence of a compartment syndrome in the model. Both pancreatic duct stenting and surgical decompression lowered the IP and the PP (ie, the pressure required to maintain PBF constant). However, surgical decompression was significantly more effective than stenting.

• LAPAROSCOPIC BILIARY AND GASTRIC BYPASS- A USEFUL ADJUNCT IN THE MANAGEMENT OF CARCINOMA OF THE PANCREAS

M;Rhodes, L.Nathanson, G.Fielding. University Department of Surgery, Royal Brisbane Hospital, Brisbane, Australia:

Over 90%of patients with inoperable c~cirioma of the pancreas are successfully palliated by ERCP and stent insertion. Management of the residual 10% of patients often involves a lapkrotomy which is difficult to justify when median survival of these patients is only i5fl days. Laparoscopic biliary and gastric bypass offers a less invasive alternative than open surgery with shorter hospital stay and more rapid return to normal activity.

Between.August 1991 and March 1994, 16 patients (median age 69 years, range 31-85) underwent laparoscopic bypass surgery. The indications for surgery were gastric outlet obstruction at initial presentation (n--4), blocked biliary stentt (n=8) and metastatic tumour at laparoscopy (n=4). Surgery took the form of cholecystjejunostomy (n=7), gastroenterostomy (n=5), both procedures (n=3) and failed operation (n=l).

Operative duration was 75 minutes (range 45-190) and hospital stay 4 days (range 3-33) and all apart from two patients were discharged from hospital in 7 days or less. Morbidity occurred in 2 patients (13%) in the form of a CVA and delayed gastric emptying. Median survival in ten patients who have died is 201 days (range 20 - 525).

Laparoscopic biliary and gastric bypass is possible in the majority of patients in whom endoscopic stenting has failed and in those who subsequently develop gastric outlet obstruction. Hospital stay is shorter than after open surgery and recovery more rapid•

ANALYSIS OF K-RAS MUTATIONs IN CHRONIC PANCREATITIS WITH DUCTAL HYPERPLASIA J.A. Rivera 1,2, C. Ferngmdez-del Castillo 2, C.J.N. Rail ~, F. Graeme- CookS, A.L. Warshaw 2 and A.K~:Rustgi 1, Gastrointestinal Unit I and Depts. of Surgery 2 and Pathology s, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Mutations in the K-ras oncogene at codon 12 have been identified in up to 95 % of pancreatic cancer specimens. They represent the highest rate of oncogene mutation identified in any cancer, and are thought to be an early event in the pathogenesis 6f pancreat, ic cancer. However, the earliest stage in which K-ras mutations can be fotind in potential precursor lesions is unclear Pancreatic ductal hyperplasia has been proposed as one such precursor lesion. Chronic pancreatitis, which often has focal areas of ductal hyperplasia, is also associated with pancreas cancer• This study evaluated chronic pancreatitis specimens with and without ductal hyperplasia for the presence of K-ras mutations. METHODS:Paraffin embedded surgical specimens from 42 patients with chronic pancreatitis were examined microscopically for the presence of ductal hyperplasia. Both hyperplastic and non-hyperplastic pancreatic ducts were microdissected from the specimens which had hyperplasia (11/42). Six specimens without hyperplasia served as controls. Genomic DNA was isolated and PCR amplification of K-ras was performed. Slot blots of the PCR products were prepared and evaluated for codon 12 mutations by hybridization to wild type and six different mutant specific oligomer probes. RESULTS: Amplification of K-ras ~'as possible in 8/11 patients with hyperplasia and in 6/6 controls. Each of the specimens successfully hybridized to the wild type (gl~cine) probe. However none of the specimens hybndlzed to the mutant specific probes. CONCLUSIONS: K-ras codon 12 mutations were not found in this group of patients with chronic pancreatitis and ductal hyperplasia, despite enrichment through microdissection. This suggests that mutations in K-ras are not required for the development of ductal hyperplasia and that K-ra~ mutations may be preceded by other genetic changes in the progression to pancreatic cancer.