Endoscopy for gallstone pancreatitis

1592

GASTROENTEROLOGY Vol. 97, No. 6

SELECTED SUMMARIES

gastroduodenal motility rather than to gallstones (Ann R Co1 Surg Engl 1975;56:69-80). The question of what, if anything, one should do with gallstones in the absence of acute cholecystitis should be decided on the basis of probability of complications in the future of the patient, not symptoms; i.e., the natural history of gallstones. Such data at present are insufficient in quantity and quality to reach a firm conclusion, although what we have suggests much less in the way of complications than we have previously believed (Ann Surg 1985;305:59-63, Sem Liver Dis 1983;3:87-96). J. L. ACHORD, M.D.

Reply. It was with interest that I read the comments by Dr. Achord concerning my recent article on gallstones and abdominal symptoms. There are a number of points I wish to comment on. [a) The strict ultrasonic criteria used in my investigation for stones in the gallbladder have a predictive value of 100% (AJR 1978; 131:227-g), which hardly gives rise to 20% false-positive cases as postulated. (b) Data are stratified according to age and sex and this stratification is accounted for by use of weighted mean values and Mantel-Haenzsel summary ,$ test. (c) The figures in Table 3 are correct (Am J Epidemiol 1987;126:912-21). Dr. Achord seems convinced that gallstones in the absence of acute cholecystitis do not cause pain. The present investigation certainly suggests that this is true, but neither this nor other cross-sectional studies can rule out the possibility of pain caused

by gallstones in the absence of complications of gallstone disease. Cross-sectional studies suffer one serious drawback as pointed out in the discussion. If the time between the occurrence of symptoms caused by gallstones and adequate treatment is short-which could be so in countries with highly developed health servicesprevious cases may have all been treated and future cases not have developed in such a magnitude as to influence the figures. We therefore have to wait for the results from follow-up studies of randomly selected samples, where pain development is assessed in participants with gallstone, those who develop gallstones, and those who do not. To be sure of an unbiased result the participants should not be aware of the gallbladder status. These data are forthcoming. It is tempting to draw conclusions on the basis of incomplete data, but it is important to distinguish between advancing a hypothesis and testing it. T. JORGENSEN, M.D.

ENDOSCOPY FOR GALLSTONE PANCREATITIS Neoptolemos JP, Carr-Locke DL, London NJ, et al. (Departments of Surgery, Gastroenterology and Radiology, Leicester Royal Infirmary, Leicester, U.K.) Controlled trial of urgent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. Lancet 1988; ii:979-83 (October). Over a 4-yr period, 121 patients judged to have gallstone-induced acute pancreatitis were randomized to endoscopic retrograde cholangiopancreatography (ERCP) within 72 h of hospital admission or to conventional treatment. Endoscopic sphincterotomy (ES) was carried out if common duct stones were identified by ERCP. After

the first five hospital days, all patients were offerred ERCP ‘- ES if indicated. Fifty-nine patients were randomized to early ERCP, which was successfully carried out in 52. Among patients with confirmed gallstones, common duct stones were found in 19 of 47 patients (40%). In 9 patients, gallstones were not confirmed. Sixty-two patients were randomized to early noninterventional management. In 9 patients, gallstones were not demonstrated. Fourteen patients underwent later ERCP between day 6 and day 30. Common duct stones were demonstrated in 3 patients (21%]. In the early ERCP * ES group, overall complications were significantly less common (17% vs. 34%). Hospital mortality was also reduced (2% vs. 8%) but this difference was not statistically significant. The patients were divided into those judged to have mild and severe disease on the basis of early objective criteria. Sixty-eight patients had “mild” disease predicted and, among these patients, there were no deaths and no differences in the incidence of complication between the two treatment groups. However, in those predicted to have severe disease, morbidity was significantly lower [24% vs. 61%) in the ERCP 2 ES group and mortality was also less (4% vs. 18%). In patients with severe pancreatitis, median hospital stay was also lower in the ERCP 2 ES group (9.5 vs. 17.0 days). Eleven patients were reported to have associated acute cholangitis, including 1 patient who did not have confirmed gallstones. Six were in the early ERCP 2 ES group. Four had complications (67%) and 1 died (16.7%). Five were in the control group and 2 of these had complications (49%). If these 11 patients are excluded, complication rates are still lower in the ERCP ‘- ES group than among the control patients. The authors conclude that in the hands of skilled endoscopists, ERCP and ES are safe in patients with acute pancreatitis. Furthermore, morbidity was reduced in patients with severe pancreatitis if early treatment included ERCP 2 ES. Comment. In 1978 Acosta (Surgery 1978;83:367-70) reported that in a group of 46 patients with a diagnosis of gallstone pancreatitis, who were treated by operative correction of their biliary tract disease within 48 h of the onset of symptoms, the mortality was 2%. This mortality was significantly better than the 16% mortality noted in an historical control group managed by nonoperative methods. In the group undergoing early operation, 72% had a stone impacted in the ampulla of Vater. This led to the hypothesis that the severity of gallstone-associated pancreatitis was related to persistence of obstruction of the ampulla of Vater. In evaluating Acosta’s report it must be noted that “marked elevation of bilirubin” was one of the criteria used to diagnose acute gallstone pancreatitis. Stone (Ann Surg 1981;194:305-11) evaluated the role of early biliary surgery in gallstone pancreatitis by a controlled clinical study. Common bile duct stones were identified in 64% of patients operated on within 73 h of hospital admission, compared with 18% of those operated on at a later period. Jaundice was not used as a diagnostic criterion in this study and only 5.6% of those operated on early had a stone impacted in the ampulla of Vater. In this study, the morbidity of the episode of pancreatitis was greater in those treated by early biliary surgery. However, an extraordi-

December 1989

narily high morbidity after late elective biliary surgery led Stone to conclude that early operation should be recommended. More recently, Kelly (Surgery 1988;104:600-5) reported a randomized study including 165 patients judged to have gallstone pancreatitis. Eighty-three underwent biliary operation within 48 h with a 30% morbidity and 15% mortality. If biliary surgery was undertaken later in the patient’s course, morbidity fell to 5% and mortality was 2.4%. In those who had “severe” pancreatitis on the basis of objective criteria, the incidence of morbidity was 83% and mortality 48% after early intervention, compared with 18% and 11.8% if early treatment avoided surgery. Impacted ampullary stones were present in 26% of the early surgery group and only 5% of the late surgery patients, Impacted stones were present in only 3 of 15 patients who died. Two were in the early surgery group, and two of these three deaths involved edematous pancreatitis. Kelly’s data suggests that the presence of persistent calculous obstruction of the ampulla is not an important determinant of the severity of pancreatic inflammation. If persistent ampullary obstruction is a significant factor, the benefits of early operative relief are clearly outweighed by the adverse effects of this intervention on the course of this disease. The present report suggests that early identification of those patients who have persistent common bile duct stones and removal of those stones by endoscopic sphincterotomy ameliorates the course of patients judged to have severe gallstone pancreatitis. In evaluating the results of this study it should be noted that 18 (15%)of the 121 patients studied did not have confirmed cholelithiasis and that three of the six deaths occurred in this group. Even if those patients without stones were excluded, complication rates were still reported to be significantly lower in patients with severe pancreatitis treated by early ERCP 2 ES. There were 5 patients with severe pancreatitis who were randomized for ERCP +- ES but in whom the study could not be completed. Although this group is small, it would be of interest to know their morbidity compared to that in the remaining 20 similar patients in whom ERCP f ES was successful. If their morbidity rate was Sl%, as reported for control patients with severe pancreatitis, these 5 patients would account for half of the complicated cases reported in the ERCP f ES group. A major difficulty that plagues studies of the management of gallstone pancreatitis remains difficulty in separating those components of the clinical illness that are due to pancreatic inflammation from those that are due to biliary disease. In the majority of patients, acute biliary disease and acute pancreatitis both subside without interventional measures. The present study finds no benefit from ERCP +- ES in patients judged to have mild pancreatitis. The incidence of severe pancreatitis in the present study was 44%, which is unusually high. In patients who are severely ill, knowledge of the anatomic status of the biliary tree may be essential (Ann Surg 1981;193:393-8). We have preferred to use percutaneous transhepatic cholangiography for this purpose because it avoids the possibility of exacerbation of pancreatitis. In the present study it is clear that the same information can be gained by a highly skilled endoscopist without significant pancreatic risk. Patients with calculous obstruction of the ampulla of Vater or the cystic duct may require urgent biliary intervention. In our experience, persistent ampullary obstruction may be associated with life-threatening biliary sepsis but is rarely associated with severe pancreatitis. Severe gallstone-associated pancreatitis has usually not been associated with persistent calculous obstruction of the ampulla. It is of particular interest, therefore, that in the present study, the incidence of the specifically pancreatic complication of pseudocysts was 12% in patients with confirmed gallstones in the ERCP 2 ES group compared with 19% in similar patients in the control treatment group. This study, therefore, presents convincing evidence that ERCP with the addition of ES,

SELECTED SUMMARIES

1593

if common duct stones are present, benefits patients judged to have severe gallstone-associated pancreatitis. It is, however, important to note that all of the endoscopic procedures were carried out by one very highly skilled and experienced endoscopist. As ERCP and ES carry a risk of inducing pancreatic inflammation and Pancreas pancreatic sepsis (Gastroenterology 1976;70:314-20, 1986;1:160-3), this approach should be applied with caution. J. H. C.

EFFECT OF CHOLECYSTECTOMY ACID KINETICS

RANSON, M.D.

ON BILE

Berr F, Stelloard F, Pratschke E, et al. (Departments of Medicine II and Surgery, Klinikum Grosshadern, University of Munich, Munich, Federal Republic of Germany) Effects of cholecystectomy on the kinetics of primary and secondary bile acids. J Clin Invest 1989;83:1541-50. The early clinical effects of cholecystectomy are surprisingly minimal. In spite of the loss of the reservoir function of the gallbladder, concentrations of bile acids in the jejunum are normal after a meal. This is apparently due to the sequestration of bile acids in the small intestine and the enhanced enterohepatic circulation that occurs after cholecystectomy. Absorption of all dietary constituents is normal. The major concern has been that cholecystectomy might increase the pool of secondary bile acids which, in turn, might increase the risk of colonic neoplasia. There are articles both affirming (Lancet 1981;ii:379-81) and denying (Gastroenterology 1983;85:859-65) the latter possibility. Studies of postcholecystectomy bile acid kinetics have been controversial, in part due to a lack of information based on preoperative and postoperative studies on the same group of patients. It appears that there is an enhanced cycling of the primary bile acids, cholic acid (CA) and chenodeoxycholic acid, through the enterohepatic circulation, but whether there is a significant shift to the main secondary bile acid, deoxycholic acid (DCA), has been uncertain. The present study reports on preoperative and postoperative studies in 9 women who underwent elective cholecystectomy. The selection criteria were stringent and eliminated all males, women > 50 yr of age, and those with obesity, hyperlipidemia, diabetes, gastrointestinal or liver disease, or recent use of antibiotics, steroids, or lipid-lowering drugs. The patients all had functioning gallbladders, small stones relative to gallbladder size, and minimal gallbladder inflammation at the time of surgery. Although probably necessary for this type of study, the strict entrance requirements raise a question of whether the findings are truly representative of all patients with gallstones. While on a standard, moderate cholesterol diet, the 9 subjects were studied within 10 days before surgery and at 6 wk and 3 mo postoperatively. Six of the 9 subjects were also studied at 9-12 mo after surgery. Samples of CA, chenodeoxycholic acid, and DCA labeled with 13C or ‘H were simultaneously administered orally and serum samples were obtained on 4 successive days, 1.5-3 h after the