April 1995 Biliary Disorders A403

• REG GENE EXPRESSION IS INHIBITED DURING DIFFERENTIATION OF CULTURED RAT ACINAR CELLS M_EE Zenilman, TH Magnuson, R Perfetti, K Swinson, and AR Shuldiner. Dept of Surgery, Albert Einstein College of Medicine, Bronx, NY, and Johns Hopkins University, Baltimore, MD Factors which control pancreatic regenerating (reg) gene expression are unknown. It is induced during cellular de-differentiation following pancreatic resection and is involved in islet regeration. We recently demonstrated that reg is expressed in the rat acinar cell line AR42J, and used this line to study reg expression during cellular differentiation. 2-10XI05 AR42J cells were treated with 10nM dexamethasone (DEX), gastrin, CCK, or secretin for 48hr. Cellular proliferation was assayed by thymidine incorporation; differentiation by expression of elastase. Cellular RNA was subjected to slot blot analysis with a cDNA probe to rat elastase constructed by PCR. Blots were stripped and re- probed with a rat reg I cDNA probe. Loading was normalized by hybridization with oligo-dT. Data is expressed as percent control (Mean ± SEM, n=5 per experiment).

zero dexa 3H-ineorp i00± 6% 8± i* elastase 100±20% 200±24* reg 100±16% 40±18"

*p<0.05 compared to zero, unpaired t-test. DEX treatment caused AR42J cells to differentiate: proliferation ceased and elastase gene expression increased. Associated with differentiation was inhibition of reg gene expression. Gastrin and secretin stimulated AR42J.proliferation, but had no significant effect on either elastase or reg gene expression. CCK had no effect on proliferation, elastase or reg gene expression. We conclude that reg gene expression inversely correlates with the level of cellular differentiation, is unaffected by GI hormone stimulation, but is modulated via the glucocorticoid receptor.

Extracorporeal Shock Wave Lithotripsy of Non-accessible Stones in Chronic Pancreatitis

A. Zipf, T. Wehrmann, W.F. Caspary, M.Jung Med. Klinik ll, University Hospital, Frankfurt/Main, Germany

Introduction:In chronic pancrcatitis w~ith obstruction and severe pain, the ondoscopist has to face nonextractable stones in the pancreatic duct. In a prospective study in 26 consecutive patients, we have been evaluating the technical feasibility, fragmentation rate, side effects and outcome of extracorporeal shock wave lithotripsy (ESWL). Methods: ESWL was performed in sedoanalgesia using Midazolam (5mg) and Nalbuphni (10mg) using an eleclromagnctical lithotriptor with indine-nitrasoand (SL 20, Storz Medical. Switzcrland). Fluoroscopic control was not necessary. ESWL was followed by repeated ERCP the following day. Results: From 1/1993- 10/1994 we treated 26 patients ( 9 female, 17 male) with a medium age of 46 years. Chronic pancreatitis was demonstrated by laboratory testing, nilrasound, partially CT scans and ERCP prior to ESWL in all patients. The medium diameter of the obstmcted pancreatic duct in its prestenotic part was 9 mm (r=4-25), the medium number of impacted stones was 4 (I=1->10), the diameter of the concrements was 6 mm (r = 3-12 mm). 2312 impulses were administered (1"= 1400 - 4500) in one to three sessions of abont one hour each, using energies of 15 kV (13- 16kV). Fragmentation of concrements was achieved in 20/26 patients (76%). In another five patients . there was no fragmentation according to the ultrasound after ESWL or fluoroscopic imaging at ERCP, but the formerly impacted stone could be cnduscopically extracted. In 7/26 patients, there was spontaneous clearance of fragments after ESWL, mostly in patients with a nasopancreatic drainage, inserted after the first ERCP. In another 18/26 patients, the stones oder fragments could endoscopicany be extracted.In one patient fragmentation and repeated attempt of stone removal failed. One patient experienced severe pain after ESWL, that could be managed by oral analgetics, obviously due to stone passage, No pancreatitis and no bleeding complications were noticed. 5 patients complained of orthostatic problems after sedoanalgesia. In die follow-up 15/26 (58%) patients were given a short-term nasopancreaiic drainage after ESWL and stone exlraction for prevention of papillary edema after pancreatic sphincterotomy. In 11/26 palicuts (42%) a pancreatic cndoprusthesis was inserted for coexisting stenosis of the pancreatic duct. Conclusion: In chronic pancreatitis with obstruction and pain, ESWL is an adjuvant, rather painless method of conditioning concremcnts within the pancreatic duct for endoscopic extraction. There are no severe complications of pancreatic ESWL. ESWL is not recommended for patients in whom surgical procedures are needed for ductal decompression or due to duodenal stenosis and also in patients with pseudocysts within the application area.

Biliary Disorders

• PREDICTING COMMON BILE DUCT STONES BEFORE CHOLECYSTECTOMY: A META-ANALYSIS. P.C. Abboud. P.F. Malet, J.A. Berlin, M.D. Cabana, R. Staroscik, J.R. Clarke, J.A. Shea, J.S. Schwartz, and S.V. Williams. Divisions of General Internal Medicine and Gastroenterology, Dept. of Medicine and Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA.

Approximately 10% of patients with uncomplicated gallbladder stones have associated common bile duct stones (CBDS). Because of questions regarding the risk, efficacy, and cost of present techniques for diagnosing CBDS before or during elective cholecystectomy, it is important to identify patients at highest risk, in order to decide whether or not to investigate for CBDS. The aim of this meta-analysis was to identify individual predictors of CBDS in pre-cholecystectomy patients.

2221 citations identified from MEDLINE and a bibliographic review were reviewed by trained readers using predefined criteria. 1814 of these citations were excluded after review of the abstract; another 352 were excluded after review of the full article. Readers, including physicians, screened and abstracted data from the remaining 55 studies, and included 21 studies in the final meta-analysis. Pooled proportion algorithms were used to determine weighted average values for indicator characteristics. Sensitivity (sons) describes the probability that a patient with CBDS will manifest an indicator; specificity (spec) describes the probability that a patient.without CBDS will not manifest an indicator. Likelihood ratios describe how much the odds of CBDS increase when the indicator is present (LR+), and how much the odds decrease when the indicator is absent (LR-). Indicator sens soec LR+ 9 5 % C 1 LR- 9 5 % C I #s tds # p ! s CBDSonUS 0.39 1.00 58.9(24.8-139.5) 1.5 (1.3-1.6) 5 1438 Cholangltis 0.11 0.99 18.3 (9.0-37.1) 1.1 (1.0-1.1) 4 2288 Dilated CBD on US 0.40 0.97 9.2 (7.3-11.6) 1.3 (1.2-1.4) 10 3462 Bilirubin 0.69 0.88 5.6 (5.1-6.2) 1.9 (1.7-2.1) 8 4539 Jaundice 0.41 0.93 4.3 (3.7-5.0) 1.3 (1.2-1.3) 10 4157 AlkalinePhosphatase 0.54 0.87 3.2 (2.9-3.7) 1.4 (1.2-1.6) 9 3179 Amylase 0.09 0.96 2.4 (1.7-3.5) 1.0 (1.0-1.0) 5 3623 Pancreatitis 0.10 0.95 2.1 (1.6-2.7) 1.0 (1.0-1.0) 11 6896 Cholecvstitis 0.50 0.76 1.6 (1.4-1.9) 1.1 (1.0-1.2) 3 1349 US = ultrasound; CI = confidence interval; stds = studies; pts = patients

While 6 of the 9 indicators exhibited a specificity greater than 92%, none of the indicators had good sensitivity. The LRs indicate that a negative result on any of the indicators provides only weak diagnostic information. In contrast, the isolated presence of cholangitis or ultrasound evidence of CBDS or duct dilation makes the diagnosis of CBDS much more likely. Because cholangitis and ultrasound evidence of CBDS are uncommon in this population, clinicians must also consider the second tier of indicators. The isolated presence of elevated bilirubin, clinical jaundice, or elevated alkaline phosphatase has marginal diagnostic value, which can only be assessed in the context of a clinician's own threshold for undertaking diagnostic procedures. Since no single indicator is both clinically conclusive and highly prevalent, we conclude that a strategy to identify patients at risk for CBDS will depend on the development of a multivariable prediction instrument.

Q BILE ALKALINE PHOSPHATASE ACTIVITY IN CHOLESTATIC DISORDERS, A. Abu-Hammour R.P. Venu, K.P. Etzkom, D.E. McGuire, R.D. Brown, I. Alum, and J.L. Watkins, Depamnent of Medicine, Universi ty o f Illinois at Chicago, Chicago, Illinois 60612.

I N T R O D U C T I O N . Serum alkaline phosphatase (AP) is a commonly used laboratory test for the diagnosis of cholestatic liver disease. However , it fails to distinguish between intrahepatic and extrahepatic cholestasis. AIM. The a im of our study was to evaluate if AP levels in the bile would differentiate be tween intrahepatic cholestasis (IHC) and extrahepatic cholestasis (EHC). M A T E R I A L S AND METHODS. Patients referred with cholestatic l iver dysfunction were appropriately evaluated and bile samples were collected during ERCP. Bile was analysed for AP, GGPT. Bile samples were also collected from a control group of patients who had normal LFT's and referred for ERCP for non- biliary problems. Liver biopsy was performed when indicated. RESULTS. Of 31 patients (12 males and 19 females, ages 32 to 56 years), evaluated, bile collection was successful in 28. Fifteen patients had EHC and 7 patients had IHC. Mean bile AP levels for controls, IHC, and EHC were 120 IU/L, 151 IU/L, and 654 IU/L, respectively (with highest levels noted in patients with EHC and cholangitis). Mean serum AP for controls, IHC, and EHC, were 104 IU[L, 517 IU[L and 206 IU/L, respectively.

Patients Grou t (N) Bile A P mean ± SD Serum AP mean ± SD

EHC (15) 654 ± 60* 207 ± 51 IHC (7) 151 ± 40 509 ± 80 Control (6) 120 ± 12 103 ± 18

*p <0.001 S U M M A R Y A N D C O N C L U S I O N . Bile A P levels were significantly higher in patients with EHC than IHC and controls. Bile A P levels may help to differentiate be tween patients with IHC and EHC. Possible mechanisms for the marked bile AP elevation in EHC include a varying degree of cannalicular membrane dissolution or tight junction disruption. In addition, A P m a y have a bacteriostatic effect and hence its enhanced synthesis may be beneficial in patients with EHC and infected bile.