Management of silent gallstones: A clinical decision analysis to assess survival and costs

A522 AGA ABSTRACTS • G2126 GALLSTONES AND THE DEVELOPMENT OF GALLBLADDER CANCER. U. Gustafsson1, C. Einarsson2, L. Eriksson3, S. Sahlin 1, B. Tribukait4, V. Gadaleanu~. IDept of Surgery, Danderyd Hospital, 2Center for Gastroenterology and 3Dept of Pathology, Huddinge University Hospital, 4Dept of Medical Radiobiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden. Background: An increasing frequency of gallbladder cancer has been observed in Sweden since 1960, during the same period of time as the frequency of cholecystectomies has decreased. Gallstones have been suggested as a risk factor in the development of gallbladder cancer. DNA aneuploidy is a marker of genetic instability and can induce neoplastic transformation and is regarded to correlate with histopathology and prognosis in a variety of malignant tumors. Purpose of the study: Determine a) DNA aneuploidy in the gallbladder mucosa of gallstone patients, b) DNA ploidy pattern in gallbladder carcinomas and c) prognostic significance of the ploidy pattern. Methods: The present study included gallbladders from 81 consecutive gallstone patients, undergoing laparoscopic cholecystectomy, and archival material from paraffin embedded samples of 49 gall bladder carcinomas. Three biopsies were sampled from the gallbladder mucosa in a standardized fashion. All specimens were examined by one pathologist. The cells obtained from the samples were analyzed by DNA flow cytometry. Results: One gallbladder s a m p l e from the gallstone group showed anenploidy, all the others had a normal diploid cell population without any signs of morphological dysplasia. 73% of the gallbladder carcinomas displayed an anaeuploid cell population; 27% were diploid. The median survival time for the patients with anaeuploid and diploid cell population were 4 and 14 months respectively. The median survival time for the patients with low and medium/high level of cell differentiation were 2 and 10 months respectively. These differences were statistically significant. Conclusions: If one compares the high prevalence of gallstones with the low incidence of gallbladder cancer, the expected frequency of premalignant changes in gallstone patients should be low. One of the gallstone patients showed aneuploidy in the gallbladder mucosa which indicates that gallstones may contribute to the development of gallbladder cancer. The morphological level of cell differentiation and DNA ploidy analyzed by flow cytometry was a prognostic indicator in the gallbladder cancer patients. G2127 THE PRESENCE OF STONES BUT NOT OF COLICKY PAIN IS ASSOCIATED WITH SPHINCTER OF ODDI DYSFUNCTION IN GALLSTONE PATIENTS. FI Habib, M Cicala*, N Pallotta, F Fiocca§, E Corazziari. Cattedra di Gastroenterologia I, II Clinica Medica, §II Clinica Chirurgica, Universit~t 'La Sapienza', *LIU Campus Biomedico, Roma, Italy In a previous study (1) we have reported an increased SO pressure in patients with gallstone disease presenting with a history of biliary colicky pain. Aim of this study was to evaluate whether the increased SO pressure in gallstone patients may contribute to the pathogenesis of biliary colicky pain or it is related to the presence of gallstones per se. Twenty one patients (mean age 51 ± 14years) with gallstones and recurrent biliary colicky pain (colicky), fifteen patients (mean age 49 ± 18 years) with gallstones and no colicky pain (no colicky) and 25 control patients (mean age 49,2 -+ 15yrs) with acalcolons gallbladder (controls) were submitted to ERCP and SO manometry No patient had choledochal stones. Perendoscopic SO manometry was performed according to previous published method. SO mean and maximal resting pressures as well as frequency, amplitude and duration of phasic waves were considered. Maximal resting SO pressure >40 mmHg was considered evidence of SO dysfunction. Results: SO resting pressures (mmHg) are shown in the table: Colicky No colicky Controls Mean basal pressure 21.9 ± 14.5# 18.8 ± 8.4§ 14.4 ± 5 Maximal basal pressure 45.2 ± 30.7** 36.2 ± 17" 21.5 ± 8 **p < 0.001; *p < 0.005; #p < 0.04; §ns vs Controls Frequency, amplitude and duration of phasic activity did not differ among the three groups of patients. SO dysfunction was detected in 9 out of the 21 colicky pain patients, in 7 out of the 15 non colicky pain patients and in no control patient (p<0.0004 vs both groups of gallstone patients). Laboratory evidence of biliary stasis was detected only in 12 patients with colicky pain. Conclusions: Data of the present study indicate that the increase of SO pressure is associated with the presence of gallstones which may affect sphincter of Oddi contractility through a gallbladder-SO reflex (2). Although it cannot be excluded that SO dysfunction may contribute to the finding of biliary stasis and colicky pain in some colicky patients, the increased SO pressure does not appear to be associated with the presence of cholicky pain in gallstone patients. [1] Habib FI et al., Gastroenterology 1996; 110:456 [2] Thune A e t al, Gut 1991;32:690.

GASTROENTEROLOGY Vol. 114, No. 4 G2128

MANAGEMENT OF SILENT GALLSTONES: A CLINICAL DECISION ANALYSIS TO ASSESS SURVIVAL AND COSTS. Y, Habu, *M. Kobayashi, Y. Sugano, K. Ko, S. Waki, K. Kiyota, H. Inokuchi, *K. Kawai. Dept. of Gastroenterology, Saiseikai-Noe Hospital, Osaka., *Dept. of Gastroenterology, Yukawa Gastrointestinal Hospital, Osaka., *Dept. of Gastroenterology, General Railway Hospital of Osaka, Osaka, Japan. The aim of this study was to assess available different strategies for the management of asymptomatic gallstone patients. Methods: Using a decision tree-based state transition model (Markov approach), patient's life expectancy and expected life time medical costs under five possible different strategies were compared. These strategies were: expectant management without followup (EX), expectant management with periodical (once a year) follow-up using abdominal ultrasonography (US), oral dissolution therapy (OD), extracorporeal shock wave lithotripsy (ESWL), and laparoscopic cholecystectomy (LC). The transition probabilities and costs were estimated from published literature and official charges under the Japanese health insurance system. Results; (ex. in 45-year-old female with one radiolucent stone<2cm)

EX US OD ESWL LC

Life expectancy gained relative to EX (Days) 0 8 10 16 8

Expected life time direct costs (Yen) 143,790 272,173 456,901 919,010 428,604

Four strategies except EX were effective in prolonging life expectancy. US was the least costly among these 4 strategies. The effectiveness and costs of Oral dissolution and ESWL were dependent upon the efficacy of treatments and age of patients. LC was less cost-effective than US. Conclusions: Expectant management with periodical follow-up using abdominal ultrasonography was effective in prolonging life expectancy and economically cost-effective, and therefore, should be the standard strategy for the management of silent gallstones. ESWL and oral dissolution therapy should not be routinely recommended, but might be acceptable on the basis of their optimal indications. Laparoscopic cholecystectomy should be avoided in patients with silent stones. G2129 ENDOSCOPIC PAPILLARY BALOON DILATATION (EPBD) AND ENDOSCOPIC SPHINCTECTOMY (EST) FOR COMMON BILE DUCT STONES (CBDS). K. Hanada, F. Hino, H. Amano, S. Murakami, S. Yamasaki, M. Obayashi. Department of Internal Medicine, Onomichi General Hospital, Hiroshima, JAPAN. Backgrounds. Recently, the techniques of endoscopic sphinctectomy (EST) and endoscopic papillary balloon dilatation (EPBD) have been widely accepted for the treatment of common bile duct stones (CBDS). However, there have been few reports about clinical data of EST and EPBD for CBDS. Methods. We performed EPBD or EST in 70 cases of CBDS from 1995 to 1997 (EST: 39, EPBD: 31). EST was carded out according to standard techniques. EPBD was carded out using a hydrostatic balloon (MAXFORCE, Microvasive, Boston) to dilate the papilla with a diameter of 8 mm. After the dilatation of papilla, CBDS were removed. The number of examination, the success rate of stone cleaning, the number of CBDS, the maximum size of CBDS, the rate of complication, the period of hospital treatment, and the change of serum amylase in two groups were evaluated. Results. Median number of exam. Success rate of cleaning (%) Median number of CBDS Median max. size of CBDS (mm) Median changes of serum amylase (IU/I) Median period of hospital treatment (day) Number of complication

EST 1.67 100 2.87 11.4 37.8 44.8 4/39

EPBD 1.83 96 2.38 12.3 306.9 (p < 0.05) 27.5 (p < o.os) 2/28

Condnsions. These results suggest that EPBD seems to be a safe and effective technique for CBDS, and that it may contribute reduce the period of hospital treatment of patients with CBDS. • G2130 U T P STIMULATES ELECTROGENIC BICARBONATE SECRETION ACROSS CFTR KNOCKOUT MOUSE GALLBLADDER. M.C. Harline 1, N. M. Walker 1, G. A. Weisman2 and LL. Clarke 1. Dalton Cardiovasc. Research Ctr., Depts. of Vet. Biomed. Sci. 1 & Biochemistry2, Univ. of Missouri-Columbia, MO, 65211. Abnormal regulation of transepithelial pH in cystic fibrosis (CF) patients results from the loss of bicarbonate secretion mediated by the CF transmembrane conductance regulator protein (CFTR), a cAMP-activated anion channel. However, some epithelial tissues express alternate C1- channels (i.e., Cal2+-regulated), that may also be involved in bicarbonate secretion and,