April 2000

5308

SHOULD UNDERLYING PANCREATIC DISEASE BE A RELA·TIVE CONTRAINDICATION FOR THE USE OF PROPOFOL?Jyoti Ramakrishna, Jesse Joad, Michael Haight, UC Davis Med Ctr,Sacramento, CA.

Introduction: Propofol was introduced in 1982 and it has been used in over250 million patients. From 1991 to 1994, seven cases of postoperativepancreatitis related to propofol use were reported to the FDA. In a series of4 patients with no underlying pancreatic disease undergoing non-abdomi­nal surgery, 2 died due to severe pancreatitis. The manufacturer claims thata causal relationship between propofol and postoperative pancreatitis isunlikely. However, in a sub-population of high risk patients with a pasthistory of pancreatic disease this could be a potentially dangerous drug.Methods: We cared for LB, a 16 y/o female with cystic fibrosis andpancreas divisum. She had multiple procedures including ERCPs, with andwithout propofol. We retrospectively extensively reviewed her chart. Ather initial presentation in 6/96, 3 ERCPs were performed using Demeroland Versed. She underwent stent placement, sphincterotomy, stent replace­ment and stent removal. After the first procedure her amylase and lipaseincreased dramatically and took 3 days to return to baseline. No problemswere noted after the second ERCP. In 7/97 her pancreatitis recurred, andfor the first time she received propofol for ERCP with dilatation of theminor papilla. Her amylase did not increase much, but she did take longerto recover. In 1/99 she had 2 procedures with propofol induction, sinussurgery using 90 mg of propofol. and 10 days later a PASport placementwith 150 mg of propofol. After the first procedure she had minor com­plaints and a slight increase in amylase, and after the second procedure shedeveloped pancreatitis. Her enzyme elevation and symptoms lasted 2months. She eventually underwent 2 more ERCPs without propofol, onewith sphincterotomy of the minor papilla and stent placement, and one forstent removal. Neither of these procedures gave her more than a smallelevation in amylase which lasted less than a day. Results: We find that inthis high risk patient 2 procedures for non-abdominal problems usingpropofol precipitated severe pancreatitis. Subsequent ERCPs avoidingpropofol did not cause such problems. Discussion: Propofol is often usedfor sedation and is considered safe. Previous pancreatitis is not currentlyconsidered a contraindication for its use. We feel that propofol should besuitably labelled to caution against its use in patients with known orsuspected pancreatic disease. Also, amylase and lipase should be checkedin any patient who complains of abdominal pain after they have receivedpropofol.

5309

IS ENDOSCOPIC SPHINCTEROTOMY USEFUL IN PREVENT­ING RECURRENCE OF ACUTE BILIARY PANCREATITIS?Santiago J. Rodriguez-Gomez, Carlos de la Serna-Higuera, Isabel Martin­Arribas, Juan Martinez-Moreno, Antonio Perez-Villoria, Alejandro Betan­court-Gonzalez, Hosp Virgen de la Concha, Zamora, Spain.

AIM: The aim of this study was to investigate whether endoscopic sphinc­terotomy (EE) may be useful in preventing recurrence of acute biliarypancreatitis (ABP). PATIENTS AND METHODS: Nineteen patients withan episode of ABP were included. Five of them, suffered from anotherepisode and four of them from another two episodes of ABP in the previousmonths. The diagnosis of ABP was stablished by the presence of anelevated serum amylase level (>600 UIL, normal <100 UIL) together witha typical clinical presentation and ultrasound and contrast enhanced com­puted tomography scan data. Gallbladder stones were demonstrated byultrasounds in all patients. We considered that our patients had highanesthesiological risk for cholecystectomy (elderly patients or cardiopul­monary diseases) and we decided to treat them with ES. In all the patientsERCP was performed within 2-7 days from hospital admission. ES wassuccessful in all the cases. RESULTS: Eight males and eleven femaleswere included. The mean age was 73.6 years (range 40-88). The follow-upperiod was 10.5 months (range 3-23). ERCP demonstrated gallbladderstones in the nineteen cases. In ten patients the ERCP proved common bileduct (CBD) stones and in nine the CBD was normal. Successful clearing ofthe CBD was achieved in nine patients and the other had multiple stones inthe CBD and we inserted a plastic stent. Mild acute pancreatitis ocurred inone patient after ERCP. In the follow-up period, biliary colic ocurred intwo patients (10.5%) and they underwent cholecystectomy. No ABP,jaundice, acute cholecystitis or biliary colic ocurred in seventeen patients.Not one patient died during the follow-up period. CONCLUSION: Theresults of the present study suggest that ES may be considered a very usefuland safe option for reducing the recurrence of ABP in patients withgallstones. In patients with high anesthesiological risk may be an alterna­tive to cholecystectomy.

AGAA1153

5310

EXPRESSION OF P53 PROTEIN, K·RAS POINT MUTATION, ANDCLINICAL SIGNIFICANCE IN PANCREATIC CANCER ANDCHRONIC PANCREATITIS.Im-Hwan Roe, Myung-In Lee, Jung-Taik Kim, Cheong-Hee Cho, DankookUniv Coli of Medicine, Cheonan, South Korea.

Some progress about pathogenesis of pancreatic carcinoma(PCA)has beenmade in understanding the molecular basis of pancreatic carcinogenesis.Recent molecular studies of PCA have described mutation or overexpres­sion of important oncogenes and deletion of tumor suppressor genes. Theaim of this study was to evaluate the expression of p53 protein and K-rasmutation in PCA and chronic pancreatitis, and to determine their clinicalsignificance. p53 protein was studied by immunohistochemical assay, andK-ras mutation analyzed by PCR-RFLP in the surgically resected pancre­atic tissues from 26 pancreatic ductal adenocarcinoma, 12 chronic pancre­atitis(CP) and 5 normal pancreas. p53 protein was postive in normal ducts,CP, and PCA in 0 of 5,3 of 12(25%), and 6 of 26(61.5%), respectively.K-ras mutation was positive in 0 of 5, 2 of 12(16.7%), and 20 of26(76.9%), respectively. Diagnostic sensitivity for PCA was 96.2%(25/26)by combined analyses of p53 protein and/or K-ras mutation, but thespecificity was relatively low, 25%(3/12), therefore, the diagnostic valueusing combined analyses was insufficient. There were no significant cor­relations between p53 immunoreactivity or K-ras mutation, age, gender,tumor size, histopathological grade, and stage in analyses of PCA. But thep53 positive PCA had a significantly lower survival period than those withp53 negative tumor (p<0.05). In conclusion, the mutation of p53 tumorsuppressor gene might be an important role in carcinogenesis of PCA aswell as K-ras mutation. The detection ofp53 alterations may be beneficialin the prediction of the patients' survival. In addition, the genetic alter­ations are likely to begin since from the stage of chronic pancreatitis.

5311

THE OVEREXPRESSION OF REG GENE IN NON OBESE DIA­BETIC MOUSE PANCREAS DURING ACTIVE DIABETOGEN·ESIS IS RESTRICTED TO EXOCRINE TISSUE.Didier Sanchez, Nathalie Baeza, Richard Blouin, Christiane Devaux, GillesGrondin, Kamel Mabrouk, Odette Guy-Crotte, Catherine Figarella, GroupeRech Gl Exocr, Marseille, France; Dept Bioi , Fac Sci, Sherbrooke,Quebec, Canada; UMR6560, Fac Med Nord, Marseille, France.

The Reg (for regenerating) gene was found to be specifically expressed innormal exocrine pancreas and in regenerating islets but not in normal isletsand has therefore been suggested to be involved in islets regeneration. Inmouse, two reg genes Reg I and Reg II encoding proteins with 76%homology were detected in the normal pancreas and hyperplastic islets ofaurothioglucose-treated mice. It is possible that defence phenomena andparticularly cellular replication may occur during autoimmune agression ofpancreatic beta cells. To test this hypothesis, we studied the expression ofreg gene(s) in a spontaneous model of insulin dependent diabetes mellitus,the Non Obese Diabetic (NOD) mouse, which shows a pattern of thedisease very similar to that of human. Our previous results have shown thata progressive increase in reg genes expression parallels the activity ofdiabetogenic process but it remained to determine in which part of thepancreas (endocrine and/or exocrine) the gene(s) and the protein(s) wereexpressed and if their localization was varying with the presence ofinsulitis and with the progression of the disease. Investigations were carriedout on pancreas of female and male mice which both develop insulitis withinvasion of the islets but diabetes will only develop in females, while malescan develop diabetes when treated by cyclophosphamide. In situ hybrid­ization analysis was performed using sense and specific antisense ribo­probes and immunocytochemical studies were realized using a specificrabbit antiserum prepared against a peptide of 16 aminoacids present in theprotein sequences deduced from the cDNAs of the two mouse reg genes.Our present data shows that whatever the age, sex, presence of insulitis orof diabetes, the expression of reg mRNAs and of the correspondingprotein(s) are restricted to exocrine tissue. Moreover reg mRNA andprotein expression remain localized in acinar cells in the two oppositesituations: 1) the cyclophosphamide treated males in a prediabetic stagepresenting a high level of both insulin and reg mRNAs and 2) the overtlydiabetic females with no insulin and an high level of reg mRNA. Thesepresent findings suggest that the overexpression of the reg gene observedin NOD mouse as well as in experimental models of islets regenerationmay be due to a defence of the acinar cell to pancreatic agression followedby regeneration and do not support the hypothesis of a direct proliferativeeffect of the protein on preexisting beta cells.