CLINICAL CONFERENCE CHOLEDOCHOLITHIASIS. Introduction. Case Presentation. I. DODD WILSON, M.D. Moderator I. DODD WILSON, M.D.

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1 /78/ $02.00/0 GASTROENTEROLOGY 75: , 1978 Copyright 1978 by the American Gastroenterological Association Vol. 75, No.1 Printed in U.S A. CLINICAL CONFERENCE CHOLEDOCHOLITHIASIS Introduction I. DODD WILSON, M.D. Moderator DISCUSSANTS: JOHN P. DELANEY, M.D., PH.D., WILLIAM C. DUANE, M.D., JAMES M. PRIES, M.D., STEPHEN E. SILVIS, M.D., AND JACK A. VENNES, M.D. Section of Gastroenterology, Department of Medicine and Department of Surgery, University of Minnesota, Minneapolis I. DODD WILSON, M.D. Biliary tract surgery is the most frequently performed type of abdominal operation with about 500,000 such procedures being done yearly. 1 Approximately 15% of patients operated upon for cholelithiasis also have concomitant choledocholithiasis. Most common duct stones are adequately treated during the primary procedure. More than 1% of patients having a cholecystectomy, however, will be found to have a retained gallstone in the common bile duct during the immediate postoperative period. l About 2% of those having undergone cholecystectomy will eventually require further surgery for choledocholithiasis_ Continued efforts to reduce the incidence of choledocholithiasis are important because complications, such as cholangitis, hepatic abscess, secondary biliary cirrhosis, and pancreatitis, have serious morbidity. Several recent advances improve both our understanding of gallstone formation and ability to detect and manage gallstone disease. This clinical conference will examine recent developments as well as time-honored concepts and relate them to a patient who had complications of choledocholithiasis. Case Presentation JAMES M. PRIES, M.D. A 52-year-old white male was transferred to the Minneapolis Veterans Administration Hospital for evaluation of recurrent pancreatitis. Twenty-five years earlier he had had a cholecystectomy for gallstones which were found during an evaluation for episodes of abdominal pain. There was no history of jaundice and the common bile duct was not explored at surgery. Six years ago, acute abdominal pain and vomiting occurred associated with obstructive jaundice. Laparotomy findings at the time included a firm, nodular pancreas showing fibrosis on biopsy, a fibrotic cystic duct stump that was removed, and a dilated common bile duct. Gallstones were not palpated in the duct. Neither an operative cholangiogram nor an exploration of the duct was performed. His jaundice, Received December 5, Accepted February 15, Address requests for reprints to: I. Dodd Wilson, M.D., Box 172, Mayo Building, University of Minnesota Hospitals, Minneapolis, Minnesota which cleared postoperatively, was thought to be secondary to pancreatitis. In the subsequent 6 years he had four episodes of abdominal pain during which he noticed dark urine and light-colored stools. Five weeks before transfer he developed nausea and abdominal pain radiating to the back. The following laboratory values were obtained at that time: serum amylase, 1,300 U (normal 20 to 170); total bilirubin, 10.5 mg per 100 ml; serum glutamic oxaloacetic transaminase, 177 U (normal <50); alkaline phosphatase, 321 U (normal <115); and white blood count, 17,600. Coagulation studies, hemoglobin, several fasting blood glucoses, and serum protein and lipoprotein electrophoreses were normal. His symptoms resolved with fluids, antibiotics, and nasogastric suction. Within 2 days all laboratory values had returned almost to normal except for the alkaline phosphatase. One week after discharge he again developed pancreatitis and was transferred to the Minneapolis Veterans Administration Hospital when his symptoms did not resolve.

2 July 1978 CLINICAL CONFERENCE 121 FIG. 1. The retrograde pancreatogram demonstrates a cavity (arrow) beginning to fill with the contrast material. The pancreatic duct proximal to this pseudocyst is normal. The patient occasionally drank up to 6 ounces of whiskey per day on weekends and was a bartender. He had no history of hepatitis, diabetes, diarrhea, itching, or weight loss. He was taking no medications and there was no family history of gallstones or hyperlipidemia. Physical findings included dullness to percussion and decreased breath sounds at the left chest base. The abdomen was not tender but there was a left epigastric mass. There was no hepatosplenomegaly. A chest X-ray showed left lower lobe atelectasis and left pleural effusion. On upper gastrointestinal X-ray, the stomach was displaced by a posterior mass. Ultra/ sound and computed tomography (CT) scans demonstrated a complex mass in the region of the tail of the pancreas. Endoscopic retrograde cholangiopancreatography confirmed a pseudocyst in the tail of the pancreas. The main pancreatic duct was otherwise normal (fig. 1). The common bile duct was dilated above the intrapancreatic portion and contained at least two gallstones (fig. 2). At operation, a 10-cm pseudocyst containing 800 ml of FIG. 2. Endoscopic retrograde cholangiogram showing a dilated common bile duct above a narrowed intrapancreatic and/or intramural segment (arrow). Two gallstones were demonstrated but only one (arrow) can be seen in this photograph. A possible intrahepatic stone was also noted (arrow). gray, necrotic material was drained into the stomach. Soft, friable gallstones were removed, an operative cholangiogram was performed, and, because dilators could not be passed into the duodenum, a choledochoduodenostomy was constructed. Bile obtained at surgery grew Escherichia coli. The postoperative period was uneventful. Comments 1. DODD WILSON, M.D. This patient had recurrent attacks of pancreatitis which led to surgery on two occasions, 19 and 25 years after cholecystectomy. Choledocholithiasis, the topic of this conference and one cause of pancreatitis, was found during the most recent hospitalization. Whether stones were present in the common bile duct at the laparotomy done 6 years ago is not certain because neither operative cholangiography nor exploration of the common duct was performed. How do gallstones cause pancreatitis? Despite a vast

3 122 CLINICAL CONFERENCE Vol. 75, No.1 literature of experiments, the precise pathogenesis of gallstone pancreatitis remains in doubt. Opie's observations dominate the literature beginning just after the. turn of the century. They include: (1) recognition that the combination of obstruction of the pancreatic duct and active pancreatic secretion leads to pancreatitis, (2) emphasis on the frequency of the association between gallstones and pancreatitis, and (3) development of the common channel theory.2, 3 The common channel theory states that a common channel exists between pancreatic and common bile ducts near the ampulla of Vater, that the duct can be occluded distally by a stone without blocking this common channel, and that bile will then enter the pancreatic duct causing pancreatitis. Most people (over 80%) have a common channel. In over half of these people, however, the common channel is too short to allow distal obstruction by a stone without blocking the entire common channel. 4 That bile does not induce pancreatitis unless injected into the pancreatic duct under excessive pressure is further evidence against the common channel theory.5 Numerous other pathogenetic mechanisms, such as effects of trypsin, 5 toxicity of lysolecithin,6 and spasm of the sphincter of Oddi,7 have been postulated, but none is generally accepted as having primary importance in gallstone pancreatitis. Opie also stated that "lodgement of a stone near the orifice of the bile duct, where it may at the same time compress and occlude the duct ofwirsung, is not uncommonly a cause of pancreatic lesions and disseminated fat necrosis."2 Indeed, obstruction of the pancreatic duct has been a common pathophysiological explanation for gallstone pancreatitis. One of the most perplexing observations regarding gallstone pancreatitis, then, has been the fact that only 5 to 10% of patients have a stone at the ampulla at operation and only about 20% have demonstrable choledocholithiasis. Two recent articles present data which suggest that this low incidence of choledocholithiasis is explained by the fact that stones which cause pancreatitis have already passed into the duodenum when the X-ray studies are performed. 8, H Both articles describe studies on patients with gallstone pancreatitis and a control group with only gallstones. Gallstones were found in the feces of almost 90% of patients with pancreatitis after the attack had subsided. Those patients having only one attack often had one stone found, whereas individuals having more than one attack tended to have multiple stones in their feces. The authors suggest that acute pancreatitis associated with gallstone disease is often the result of transient obstruction of the ampulla of Vater by migrating gallstones. This is compatible with the generally accepted observation that, under some experimental circumstances, obstruction of the pancreatic duct will produce pancreatitis. Because 10% of control patients also had gallstones in their feces, not all gallstones that were passed resulted in clinical pancreatitis. The case under discussion is confused somewhat by the suggestion of alcoholism, an important cause of pancreatitis. Usually, differentiation of alcoholic from gallstone pancreatitis is relatively easy. This distinction is important because gallstone pancreatitis is cured in over 95% of cases by appropriate surgery. In contrast, when alcoholism is thought to be the cause, the pancreatitis may continue unabated after gallstones are removed. A comparison of the two diseases shows some distinctive pathological and clinical differences. 1O Gallstone pancreatitis, although on occasion severe or even fatal, rarely produces chronic pancreatitis. In contrast, acute alcoholic pancreatitis occurs in a gland already involved by chronic disease and complications are common. Gallstone pancreatitis is characterized by attacks which resolve completely, whereas the alcoholic patient, who is likely to have chronic pancreatitis, often experiences pain between acute episodes. Pseudocysts are far more common in the alcoholic patient. Laboratory tests help little in this differentiation. Finally, whether gallstones or alcoholism caused this patient's pancreatitis is uncertain. Some in the audience will favor alcoholism because of the patient's occupation as a bartender, the presence of chronic pancreatitis and a pseudocyst, and the unlikely possibility that the large stones found could pass through the narrow stricture in the common duct (fig. 2). Others will be influenced toward gallstone pancreatitis by the presence of friable gallstones which could conceivably fragment into smaller pieces in vivo, the pattern of attacks, and the absence of a clear history of alcoholism. Indeed, both alcoholism and gallstones may have contributed to the development of pancreatitis in this patient. Comparison of the Invasive and Noninvasive Diagnostic Techniques in Biliary Tract and Pancreatic Disease STEPHEN E. SILVIS, M.D. One of the major problems in interpretation of tests designed to study the pathological anatomy of the pancreas and biliary tract relates to the marked normal variation in these structures. In an analysis of 100 normal pancreatic ducts, Varley et al. 11 found that the general position and shape of the pancreas varied widely. For instance, the tail of the pancreas may be directed up at the spleen or swing down toward the left lower quadrant. Moreover, the position of the main pancreatic duct, relative to the spine, varies from the body of T-l1 to the body of L-2. Similarly, marked variation is found in the level ofthe papilla. In addition,

4 July 1978 CLINICAL CONFERENCE 123 a number of variations occur in branching of the major duct and in the side branches. Normal anatomy of the pancreas is also difficult to define with sonographyl2 and computeriz~d axial tomography. 13 Several comparisons have been made of some of the tests used in the diagnosis of pancreatic and biliary tract disease. Elias et al. 14 studied 60 patients that were randomly allocated to percutaneous transhepatic cholangiogram or endoscopic retrograde cholangiopancreatogram (ERCP). Cases in which the first procedure failed had the second procedure performed. The combined success rate was approximately 90%, using both procedures. With ERCP, the success rate was essentially the same (65%) in extrahepatic obstruction or intrahepatic cholestasis. With percutaneous transhepatic cholangiogram, the success rate was very high (95%) with extrahepatic obstruction and quite low (25%) with intrahepatic cholestasis. Complications were essentially the same. These authors concluded that transhepatic cholangiogram required less skill and probably should be the first procedure performed. where the suspicion of extrahepatic obstruction.was high. When the ducts are probably of normal caliber, ERCP should be the first procedure. DiMagno et al. I;j asked the question as to which procedures best diagnose pancreatic carcinoma. They found that ERCP was a valid way to diagnose pancreatic carcinoma; however, the rate of resectability remained the same. The tumor was not found at an earlier stage for surgical therapy. This corresponds to our experience on the diagnosis of pancreatic carcinoma. 16 Bradley and Clements, 17 using ultrasound, studied 25 patients with a clinical diagnosis of pseudocyst. Of the 13 patients who were positive, 10 were explored and all had a pseudocyst. Two other studies comparing ERCP and ultrasonography have demonstrated similar good results Conclusions from our studies of ERCP and pseudocyst are as follows. (1) Filling of an extraductal cavity is diagnostic. (2) Pancreatography, when the cavity fills, allows the precise localization of the cyst in relation to other structures. (3) Definitive diagnosis can be made in about three-fourths of the patients. (4) Ductal obstruction is a nonspecific finding. (5) A normal pancreatogram is good evidence against a pseudocyst. Serious septic complications occur only when surgery is delayed. 20 Although some gastroenterologists think that ERCP should not be done in the presence of suspected pseudocyst, we continue to believe that it is valuable as an immediate preoperative study. Studies of Stanley et al. 21 address CT scanning of the abdomen. The problem of dilated ducts seems to be well handled by CT scan when the interpreter is experienced. Of 22 patients with dilated ducts on CT scan, dilatation was confirmed in all 17 patients in whom confirmation was sought. When the pancreas was studied by the same group, only four pseudocysts were seen, but all four were correctly diagnosed. In an additional article by Levitt et al., of 39 patients with confirmed surgical jaundice were correctly diagnosed by CT scan, whereas 1 patient was incorrectly diagnosed. In 26 patients with confirmed medical jaundice, 21 patients were correctly diagnosed, and 5 were incorrectly diagnosed. In summary, the data are not yet available as to which of the diagnostic tests recently developed will be most useful in evaluating various pancreatic and biliary diseases. The following generalizations can be made. (1) Ultrasound has the advantage of being noninvasive, gives no radiation exposure, and uses modestly priced equipment, but appears to require a high degree of interpretative skill. (2) CT scanning has radiation exposure, requires expensive equipment, and data are insufficient to evaluate its value in comparison to the other tests. (3) Percutaneous transhepatic cholangiography and ERCP both require some radiation exposure, and are invasive procedures with about equal morbidity. In the patient where obstructive jaundice is likely, percutaneous transhepatic cholangiography appears to be the preferred procedure to study the common duct. ERCP requires considerably more experience and is more expensive. It, however, provides more information than percutaneous transhepatic cholangiography from both the endoscopy of the upper gastrointestinal tract and the X-rays obtained of the pancreas. As illustrated in the patient today, information with regard to both systems frequently is valuable. Pathogenesis of Common Bile Duct Stones WILLIAM C. DUANE, M.D. Our patient, who presented with stones in his common bile duct, had a cholecystectomy for gallstones 25 years previously. This extended period of time raises a fundamental general question regarding pathogenesis of common duct stones: are these stones formed in the gallbladder and left behind at cholecystectomy or are they formed in the duct sometime after surgery? Judging from textbooks and review articles, the consensus of opinion is that the great majority of common duct stones formed in the gallbladder and were simply overlooked at cholecystectomy. Indeed, there are reasons for favoring this retention hypothesis. First, removal of the gallbladder cures gallstone disease in the great majority of patients. Also, in spite of a good operative cholangiogram and thorough common duct exploration, the postoperative cholangiogram will show

5 124 CLINICAL CONFERENCE Vol. 75, No.1 stones in 2 to 5% of cases. 1, 23 Because the intervening few days is not enough time to form new stones, it is clear that some common duct stones are overlooked. In addition, at the time of cholecystectomy, only about 10% of patients with demonstrable stones in the duct have no stones in the gallbladder. 24 These observations tend to strengthen our prejudice that the duct is not a good place for stone formation. From a pathogenetic viewpoint, removal of the gallbladder reduces the lithogenic potential of ductal bile. A prerequisite for the formation of cholesterol stones is the presence of more cholesterol in bile than can be held in solution by the two micellar lipids, bile salt and lecithin.25 Hepatic secretion of bile salt occurs largely because of enterohepatic cycling of the bile salt pool. Secretion of lecithin is directly linked to the secretion of bile salt. Cholesterol secretion is similarly, but less tightly, linked. In man there is a large component of cholesterol secretion which is independent of bile salt secretion. 26 During brief overnight fasts, as more and more of the bile salt pool is sidetracked in the gallbladder, bile salt and lecithin secretion decrease. Because there is not a proportionate reduction in cholesterol secretion, the lithogenic potential of hepatic bile rises during such fasts, and cholesterol solubility limits are exceeded in almost everyone. 27 Removal of the gallbladder prevents these swings toward excess cholesterol content. Nevertheless, in many postcholecystectomy patients the relative cholesterol content of hepatic bile remains above the limits of cholesterol solubility, so the possibility of cholesterol stone formation in the duct cannot be completely excluded. 28 Moreover, these considerations obviously have little if anything to do with the question of pigment stone formation in the duct. Unfortunately, all of the above evidence favoring retention versus new formation of postcholecystectomy stones is circumstantial. Furthermore, there is no question that stones can and do form in the common bile duct. In cholecystectomized animal models, formation of stones can be induced by a stricture in the distal duct. 29 More relevant to the situation in man is the observation that more than 20% of reported cases of agenesis of the gallbladder (but without other abnormalities and without a cystic duct remnant) have had gallstones. 30 What might be the mechanism for stone formation in the duct? As already stated, cholecystectomy shifts the lipid composition of hepatic bile away from the imbalance which favors cholesterol precipitation. The mechanism for formation of stones other than cholesterol stones remains speculative. In some patients with ductal stones there appears to be a degree of obstruction to bile flow at the ampullary area. 31 The resulting bile stasis presumably favors bacterial growth. It has been suggested that elaboration of,b-glucuronidase by some bacterial species could cause deconjugation ofbilirubin. 32 The unconjugated bilirubin, which has little aqueous solubility, could then precipitate forming pigment stones or perhaps a nidus for cholesterol stones. If such events really do take place, the patient presented would typify them. A small dilator would not pass through his distal duct, and cultures of his bile were positive for E. coli. It should be noted, however, that the majority of patients with ductal stones do not have any indication of partial biliary obstruction other than from the stone itself. A more definitive answer to the question of retained versus newly formed stones could be obtained along two lines: the composition of ductal stones versus gallbladder stones and the incidence of ductal stones after cholecystectomy. What little data there are along these lines tend to support the notion that many ductal stones form de novo rather than being simply left behind by the surgeon. To my knowledge there has been only one attempt to document the composition of common duct stones. Madden et al. 33 examined ductal stones from 107 patients. Of these patients 56% had soft, dark stones. Such stones are termed "earthy stones" and are thought by some to form only in the duct. However, even if these are regarded as ordinary pigment stones, this percentage is much higher than would be expected for gallbladder stones. Unfortunately, this study is far from conclusive. Stone composition was determined by gross inspection only, gallbladder stone composition was not simultaneously determined, and little information about the patients themselves was offered. The one study of the incidence of ductal stones after cholecystectomy is a retrospective analysis of 91 patients presenting with common duct stones over a 10- year period. 34 If the great majority of ductal stones actually formed in the gallbladder, then the incidence of symptomatic stones versus time after cholecystectomy should have defined a simple exponential curve. Rather than such a curve, an exponential decline in incidence was found during the 1st year postoperatively, followed by a rise in incidence which peaked at the 3rd postoperative year. Ofthe 91 patients, 26% presented 10 or more years after cholecystectomy. Although this study is not conclusive, it suggests that an appreciable number of stones form after removal of the gallbladder. Additional studies of ductal stone composition and incidence are needed. In the absence of further data we presume that some stones presenting after cholecystectomy formed in the gallbladder and some formed in the duct. At present the fraction in each category is unknown.

6 July 1978 CLINICAL CONFERENCE 125 Surgical Aspects of Common Duct Stones and Biliary Stasis JOHN P. DELANEY, M.D., PH.D. This case touches on many of the major issues in surgery of the biliary tract. I will confine my remarks to two of the questions raised. First, what is the best approach to identification of common bile duct stones at the time of operation? Second, when should sphincter of Oddi function be interrupted, and by what operative means? Certainly a major goal of a biliary tract operation is to ensure removal of common bile duct stones in order to avert later obstructive complications. The general policy among our surgery staff is to carry out an operative cholangiogram in association with every cholecystectomy, even when we intend to explore the common duct. Important abnormalities identified by cholangiogram may include filling defects, dilation of the extrahepatic biliary tree, and narrowing of the duct, particularly distally. Most series in which operative cholangiography has been employed in a systematic fashion have shown totally unsuspected common bile duct stones in 4 or 5% of instances. 35 Failure of the contrast agent to enter the duodenum may be attributed to an impacted calculus, stenosis of the sphincter, or, frequently, functional sphincter spasm. An approach to identifying spasm is to give amyl nitrate, an agent that relaxes the sphincter. If the radiographic contrast material still does not enter the duodenum, the duct must be explored and the cause of the holdup determined and corrected. Simple palpation of the duct to determine the presence or absence of stones can be misleading. The major problem is that the distal 3 or 4 cm pass through the substance of the pancreas. Small stones are not readily appreciated because the duct cannot be compressed between the fingers in this region. On a number of occasions I have been unable to feel stones even though the cholangiogram had demonstrated their presence. Why not routinely open the bile duct in search of stones? One obvious disadvantage is that postoperatively the patient has an annoying T-tube. Hospital stay is prolonged. Rarely, the removal of the T-tube is followed by bile peritonitis or localized abscess. Common bile duct exploration is associated with a slightly increased mortality but only if abnormalities are present. As a rule, patients who require such exploration have more serious problems. 36 It is generally accepted that bile duct exploration is best avoided if not required. This avoidance is one major benefit of operative cholangiography. In Zollinger's experience the so called "nonproductive choledochotomies" were reduced from over 70% in the early 1950's to 38% in the mid 1970's by the routine use of operative cholangiography. 35 How often does the cholangiogram fail to detect stones which are, in fact, present in the duct? An accurate figure is impossible to state. A negative cholangiogram followed some time later by discovery of common bile duct stones might be accounted for by primary formation of new stones in the duct or by retained stones not appreciated at the original X-ray study. In addition, calculi not readily identified on cholangiography are often small enough to pass spontaneously into the duodenum and, therefore, are never discovered. If common bile duct stones are found at the time of the initial cholecystectomy, they need only be removed and a T-tube placed, unless there is reason to suspect biliary stasis by virtue of a dilated duct and distal narrowing. More often, the issue of operative interference with sphincter function arises when bile duct stones are found some time after cholecystectomy. The question discussed by Dr. Duane is whether the calculi were left at the time of cholecystectomy, having come from the gallbladder, or whether they developed later in the common bile duct. Sludge, sand, and gravel-like concretions in the bile duct strongly suggest the presence of stasis and the need for bypassing the sphincter. Round, soft nonfaceted stones also suggest primary ductal origin. When in doubt, the most conservative plan is to create a large opening from the duct to the intestine, which corrects potential bile duct stasis and allows either retained or newly formed stones to pass. One corrective procedure is to divide the sphincter mechanism directly from within the duodenum. To be certain that all sphincter fibers are divided may require an incision in excess of 2 cm. Because there is a potential for extending this long opening into the peritoneal cavity, it is essential that the mucosa of the duct and mucosa of the duodenum be approximated with sutures. This is termed sphincteroplasty and should be contrasted with sphincterotomy in which a relatively shorter cut is made with no effort to suture mucosa. Sphincterotomy may leave residual circular muscle fibers intact that could result in continued stasis. In addition, stenosis caused by scar formation at the site of the incision is an occasional late development. A sphincterotomy may be necessary to remove a stone impacted at the ampulla. When there is a long narrowing, either idiopathic or caused by pancreatic fibrosis, a sphincteroplasty is inappropriate because the fibrosing process continues and eventually may cause restenosis. Dr. Vennes will discuss the impressive results that can be obtained with endoscopic sphincterotomy with particular regard to extraction of stones. Proof that this procedure will provide permanent sphincter incompetence awaits late follow-up studies. It should be noted that sphincterotomy under direct vision at operation has had inconsistent long term results. The most commonly employed alternative procedure is a side-to-side choledochoduodenal anastomosis. This operation is somewhat simpler than sphincteroplasty. It has the theoretical disadvantage of a distal pouch be-

7 126 CLINICAL CONFERENCE Vol. 75, No. 1 tween the stoma and the ampulla in which debris may accumulate and obstruct the pancreatic orifice. This event rarely occurs. A choledochoduodenal anastomosis does not allow enlargement of the pancreatic duct orifice, but, on the other hand, has no potential to induce postoperative pancreatitis as does sphincteroplasty. Long term results of both procedures are comparable, with similar operative morbidity and mortalityy,38 The choledochoduodenal anastomosis requires that the duct be dilated enough to allow an anastomosis at least 2 cm in length. Another important and common indication for carrying out choledochoduodenostomy or sphincteroplasty is uncertainty that the duct has been completely emptied of stones. Calculi in the hepatic ducts are best dealt with by means of these operations. The hepatic ducts are notoriously difficult to clear and imprudent attempts to do so may merely impact the stones high in the hepatic radicals. Similarly, when the duct contains numerous concretions of varying sizes, complete removal is difficult and long term freedom from ductal obstruction is best assured by one of these two procedures. Medical Treatment of Common Duct Stones WILLIAM C. DUANE, M.D. First-line treatment for common duct stones is almost never medical. In the patient without a T-tube, the only medical alternative is oral administration of chenodeoxycholic acid. Such therapy has frequently resulted in dissolution of radiolucent gallbladder stones; however, complete dissolution has required at least 6 months of chenodeoxycholic acid therapy.:l9,40 Obviously, when stones are located in the common duct, a delay of 6 months or more is rarely justified. It is conceivable, of course, that chenodeoxycholic acid feeding might result in fragmentation and early passage of ductal stones. In the patient with a T-tube, an attempt at extraction of the stone with a Dormia basket is the treatment of choice when feasible. 4 I Nevertheless, there have been many attempts to dissolve or fragment ductal stones by infusion of solutions into an indwelling T-tube. Earliest efforts were with organic solvents, often combined with nitrates intended to relax the sphincter By and large, both chloroform and ether were surprisingly well tolerated by patients. Some authors, however, recount disastrous consequences in occasional patients, especially with chloroform Enthusiasm for the use of ether was tempered by the fact that its boiling point is about 2 C below body temperature. Therefore, when instilled into the ducts, the ether rapidly vaporized causing distension of the biliary tree and pain. Heparin infusions have been touted by some authors as effective treatment for ductal stones. The rationale for using heparin is that it increases the ~ potential of bile, meaning that it increases the electrostatic repulsive forces between charged particles in bile. 45 Because bile salt micelles are charged, it is theorized that an increased ~ potential will decrease micele aggregation and enhance cholesterol solubility. However, there is no evidence that micelle size is affected by heparin. Moreover, cholesterol precipitation in bile is probably not a function of micelle aggregation, and an effect of heparin on cholesterol solubility has not been demonstrated. There is a report that heparin increases the tendency for stones to fragment in vitro;46 however, other reports do not confirm this finding Clinical trials of heparin infusion for common duct stones show about a 70% success rate. 49, 50 This observation must be tempered with the fact that infusion of saline alone results in disappearance of ductal stones in about 50% of cases. 5 1 The most physiological solution for T-tube infusion is bile salt, the natural cholesterol-solubilizing agent in bile. Almost all experience with bile salt infusion has been with cholic acid, which until recently was the only bile salt available in large quantities. In vitro, the rate of cholesterol dissolution is a function of both cholic acid concentration and NaCI concentration. 52 This may account in part for the disagreement regarding the success rate of cholate infusion variously reported at 50 to 80%.23. 5:l, 54 Unfortunately, no controlled comparison of cholate solutions versus saline is available. During T-tube infusions patients may experience right upper quadrant pain and occasionally fever. Mild episodes of pancreatitis have been reported. 54 Moreover, such infusions require from 1 to 6 weeks of hospitalization to achieve the desired effect. This delay and expense may be justified by the cost and potential mortality of reoperation. On the other hand, this approach is unsatisfactory enough to warrant investigations of other alternatives such as sphincterotomy discussed in the following section.

8 July 1978 CLINICAL CONFERENCE 127 Endoscopic Retrograde Sphincterotomy (ERS) JACK A. VENNES, M.D. The recurrent jaundice experienced by this patient could have been caused by compression of the common duct by pancreatitis or, alternatively, the result of recurrent ductal obstruction by calculi with complicating pancreatitis. A discussion of ERS is relevant only to the latter possibility, choledocholithiasis. Morbidity and mortality in biliary surgery rise when choledochotomy is necessary. Moreover, the risks increase with age, and those patients requiring surgery for common duct calculi are frequently elderly. 55 As in this patient, a precise diagnosis can be made without operation, reserving surgery for definitive management of disease. Acknowledging these factors, the Germans and Japanese developed slightly different methods of performing an ERS.56,57 We have proceeded rather cautiously because of the possibility of subsequent sphincter stenosis, Trials in dogs revealed that sphincterotomy can be safely accomplished with several American electrosurgical units. One unit produced by Cameron-Miller resulted in consistent sphincter stenosis. 58 The technique that we and others are using is now satisfactory. The procedure introduced in Erlangen, West Germany, is the one most frequently used in this country. 59 Very briefly, an endoscopic cholangiogram is done with sufficient detail to outline the pathology, be it stones or papillary stenosis, The pancreatic duct is also visualized because it must be avoided during sphincterotomy. The sphincterotome consists of a wire which is controllably bent across a terminal length of cannula as the string on a bow (fig. 3). A radiofrequency current passed along the wire results in cutting of ampullary tissue and sphincter fibers. Calculi may immediately pass into the duodenum, but more usually this occurs over the next few days. Subsequent cholangiography 5 or more days later usually confirms that the calculi have quietly evacuated the duct. In the collective European experience of over 1000 ERS procedures, morbidity and mortality are 7 and 1.8%, respectively.60 Restenosis has occurred only rarely in patients followed 1 to 2 years. 61 The procedure is FIG. 3. Schematic demonstration of endoscopic sphincterotomy. First, the wire cannula is passed up the papillary and intramural common bile duct. Next, as radiofrequency current is applied to the wire, all sphincter fibers are transected. successful in a reported 92% of patients. An unpublished survey of experience in this country with 250 procedures, including our own, recently revealed very similar data, with 12 complications and three deaths (4.8 and 1.2%, respectively). This compares very favorably with surgical experience. Indications and contraindications for ERS are still evolving. The clearest indication for ERS is in the postcholecystectomy patient with choledocholithiasis who is at increased risk for surgical choledochotomy. As experience and confidence in the safety and effectiveness of the endoscopic approach has accumulated, this risk proviso is gradually being relaxed. Some patients with common duct stones, but without prior cholecystectomy, are candidates for ERS because of high surgical risk from severe associated disease; gallbladder surgery may be considered at a later time. In the rare instances in which short papillary stenoses occur, ERS is providing a safe and effective method of relieving the obstruction. ERS is contraindicated in the presence of acute pancreatitis or a significantly abnormal clotting mechanism. Ductal stenosis extending proximal to the papilla should be managed surgically, as should problems involving very large calculi. The presence of a juxtaampullary diverticulum may prevent a safe sphincterotomy. Lastly, a retained common duct stone should be removed when possible through a T-tube tract rather than by ERS. Endoscopic sphincterotomy will probably become a safe, expeditious alternative to surgical management of choledocholithiasis and papillary stenosis. The economic advantages are evident. Careful, continuing long term appraisal of this technique will be necessary to evaluate the incidence of late complications such as stricture formation or recurrence of symptomatic choledocholithiasis. REFERENCES 1. Glenn F: Retained calculi within the biliary ductal system. Ann Surg 179: , Opie EL: The relation of cholelithiasis to disease of the pancreas and to fat necrosis. 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