recurrent cholangitis after biliary surgery

Recurrent Cholangitis After Biliary Surgery

Leon D. Goldman, MD, Boston, Massachusetts

Michael L. Steer, MD, Boston, Massachusetts

William Silen, MD, Boston, Massachusetts

It is widely accepted that so long as the biliary tree empties freely into the intestine, symptomatic infection will not supervene [l-4]. This basic tenet has been repeatedly applied to conditions after biliary- intestinal bypass operations [1-g], although an oc- casional case of cholangitis in the absence of stoma1 obstruction has been recorded [8,9]. Huang et al [Z] showed that elevated intraductal pressures were necessary for the development of bacteremia from contaminated bile. Madden et al [4] demonstrated in dogs that despite overwhelming biliary contamination, symptomatic infection did not supervene if the biliary-enteric anastomosis was widely patent.

We have recently encountered six patients without biliary calculi who suffered repeated episodes of cholangitis despite proved widely patent drainage into the intestine. These cases form the basis of this report.

Case Reports

Case 1. A 75 year old man underwent an uneventful cholecystectomy in 1959. He was well until 1961, at which time recurrent pain in the right upper quadrant developed. These episodes continued intermittently until February 1979 when fever and jaundice began to accompany the pain. In March 1979 exploration of the common duct re- vealed a large cystic duct stump and a stone tightly im- pacted in a benign stricture of the common duct. The stump was shortened and a side-to-side choledochojejunostomy (Roux-Y) was carried out. Four weeks after an uneventful postoperative course fever, chills, and jaundice developed. The patient had repeated 36 to 48 hour bouts of these symptoms, each of which was treated with a course of antibiotics. At reexploration in November 1979 a patent

From the Departments of Surgery, Harvard Medical School and Seth Israel Hospital, and the Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts.

Requests for reprints should be addressed to William Silen, MD, Depart- ment of Surgery, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215.

Presented at the 63rd Annual Meeting of the New England Surgical So- ciety, Bretton Woods, New Hampshire, October 15-17, 1982.

450

anastomosis without intraluminal suture material was found. The cul-de-sac in the common duct distal to the anastomosis was clean, but multiple, nonobstructing, small (1 mm) pigment stones were present throughout his small hepatic biliary radicles. An intraoperative transhepatic cholangiogram showed no dilated ducts. A liver biopsy showed inflammatory infiltrate in the mononuclear cells. Cultures of the bile grew Escherichia coli, enterococci, and a-streptococci.

During the first year after operation, the patient had four episodes of fever, chills, and pain in the right upper quadrant. Each episode was treated with a short course of antibiotics. There has been no evidence of liver abscess. In June 1980 the patient was placed on an appropriate long- term antibiotic regimen (4 weeks intravenous and 4 weeks oral). Following 8 weeks of the regimen he became and has remained completely asymptomatic.

Case 2. In 1975, epigastric pain and vomitting developed in a 69 year old woman who had had pernicious anemia since 1971. She underwent cholecystectomy for cholelithiasis, at which time a dilated common bile duct (15 to 16 mm) and stenosis of the sphincter of Oddi were found. There were no stones in the common bile duct and a sphincteroplasty was performed. On the third postoperative day she became febrile (temperature 102.4F). T tube bile was noted to be murky and foul-smelling. E. coli was found in the bile and no other source for the fever was found. A T tube cholangiogram showed a completely patent biliary system. The fever promptly disappeared after treatment with ampicillin.

Since operation the patient has had repeated episodes of fever, with and without mild pain in the right upper quadrant. Upper gastrointestinal studies have always shown a patent biliary system, with reflux of barium into the biliary tree but without dilatation. The patient treats her episodes with short courses of self-administered antibiotics but refuses further study or long-term antibiotic therapy.

Case 3. A 75 year old man began having episodes of fever, chills, jaundice, and right upper quadrant pain in November 1976. In February 1977 he underwent cholecystectomy and sphincteroplasty. His gallbladder contained multiple pigment stones, and the common duct was 11 mm in diameter and free of stones. The sphincteroplasty

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was carried out because the papilla was markedly stenotic. Culture specimens of his bile grew E. coli and Clostridia. He was well for 6 months, but then began having episodes of right upper quadrant and epigastric pain which radiated into his back. In October 1977 he was hospitalized because of rigor and fever (temperature 101.6F). The serum amylase and alkaline phosphatase levels were normal but transient elevations of transaminase and bilirubin were noted. He was treated with intravenous ampicillin and his condition improved. An upper gastrointestinal series at that time showed a duodenal diverticulum and free reflux of barium into his biliary system.

In January 1978 he had an episode of fever and pain and was hospitalized elsewhere. His biliary tree was again shown to be patent. He has remained well since treatment of the last attack with antibiotics.

Case 4. A 67 year old woman had a cholecystectomy and common duct exploration at another hospital in 1963. One week postoperatively, an episode of severe sepsis followed a cholangiographic examination that did not demonstrate the presence of calculi. In 1969 and in April 1973 she was hospitalized with jaundice, fever, and an elevated alkaline phosphatase level. At operation in June of 1973 the common duct was found to be dilated and contained many small pigmented stones. The sphincter easily accepted a no. 5 Bakes dilator. A sphincteroplasty was performed because multiple calculi were present.

The patient was well until July 1979 when fever, chills, and fatigue developed. Preoperative endoscopic retrograde cholangiopancreatography demonstrated a completely patent biliary system. At operation she was found to have an abscess in the left lobe of the liver which was successfully treated with incision and drainage. Postoperatively, she was given a long course of appropriate antibiotic therapy and has had no further symptoms. In March of 1982 liver function test results were normal.

Case 5. A 72 year old man underwent cholecystectomy and common duct exploration for calculi in the gallbladder in 1968, at which time a great deal of detritus was present in the common duct. From January 1968 to March 1969 he was admitted repeatedly for chills, fever, jaundice, elevated serum glutamic oxalacetic transaminase @GOT), serum glutamic pyruvic transaminase (SGPT), bilirubin, and alkaline phosphatase levels. In April 1969 a sphincteroplasty was performed because of stenosis of the papilla of Vater. The bile was free of stones and sludge at this time but liver biopsy showed bile stasis and acute inflammatory changes. The patient was well until September 1972 when he was hospitalized with epigastric pain, fever, and jaundice, and elevated bilirubin, SGOT, SGPT, and alkaline phosphatase levels. A subsequent upper gastrointestinal series showed a patent sphincteroplasty with air in the biliary tree and reflux of barium. In December 1975 he was hospitalized with chest pain. The diagnosis of myocardial infarction was excluded, but results of liver function tests were all abnormal. In September 1976 a liver biopsy showed cirrhosis. An upper gastrointestinal series showed a patent sphincteroplasty. Hepatitis-associated antigen was negative. In May 1977 he died from progressive liver failure. An autopsy was not obtained.

Case 6. A 52 year old man received an injury to his am- pulla of Vater while undergoing a vagotomy and antrec- tomy for ulcer disease in 1975. Reconstruction was by sphincteroplasty and choledochojejunostomy (Roux-Y).

He had no gallstones. Postoperatively a transient fistula developed which drained pancreatic juice. The T tube was removed 6 weeks postoperatively, after which he was treated for a week with tetracycline. In November 1976 he was hospitalized with fever and rigor. His bilirubin level was mildly elevated, as were his SGOT and alkaline phosphatase levels. A liver biopsy and liver scan did not reveal abnormalities. His illness resolved with antibiotic therapy. He became ill with fever, chills, and elevated bilirubin and alkaline phosphatase levels in January, April, and September 1978. Each time he responded to antibiotic therapy. In November 1978 he underwent operation, at which time an encrusted silk suture found on the luminal side of the choledochojejunostomy, was removed. The stoma was widely patent. Bile culture grew a-streptococci and Clostridia. No other abnormality of the biliary tree was found. He has been asymptomatic since removal of the silk suture.

Comments

Cholangitis occurring after biliary bypass is always assumed to be due to obstruction of the anastomosis [I ,3], and studies by Huang et al [2] and Madden et al [4] support this view. The six patients described herein are enigmatic because in each the extrahepatic ductal system was patent and free of calculi large enough to obstruct the anastomosis. The literature contains only sporadic accounts of the syndrome we report. Thomas et al [8] mentioned two patients who had cholangitis despite freely draining biliary systems. Delbene et al [9] also described a patient with recurrent cholangitis and no demonstrable obstruction to the extrahepatic biliary tree. Cases of the sump syndrome [5] occurring after side-to-side choledochoduodenostomy also appear to be examples of cholangitis in the presence of a patent biliary- enteric anastomosis.

The mere presence of bactobilia does not explain the clinical symptoms in the patients presented herein since bactobilia frequently occurs without clinical signs. Morgenstern and Shore [IO] showed that construction of a biliary-enteric anastomosis almost always results in biliary contamination. Musgrove et al [II] studied dogs before and 6 to 24 months after biliary-enteric bypass. All dogs had sterile bile at the outset of the study but bactobilia developed after bypass. Both Flemma et al [12] and Thomas et al [13] have shown asymptomatic bactobilia in 67 to 80 percent of patients with biliary-enteric anastomoses.

The sump syndrome suggests that the degree of bacterial contamination may play a role in the development of symptoms because the stagnant, de- bris-filled distal segment of the common duct would be a fertile field for bacteria to grow in large numbers. That massive bacterial contamination is not the sole answer is supported by the observation of Madden et al [4] that symptomatic infections did not occur in dogs in which the dilated common duct was anasto- mosed to the colon in the absence of stenoses of the

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Goldman et al

anastomosis, although the criteria for the presence or absence of symptomatic infection was not clearly enunciated.

Four of our six patients had abnormalities which predisposed to an abnormal,flora in the stomach or duodenum and which could account for high bacterial concentrations near the biliary-enteric stoma. One patient had pernicious anemia, two had duodenal diverticula, which are associated with abnormal upper gastrointestinal flora [14], and one had an exposed silk suture in the anastomosis of the bile duct to the defunctionated Roux-Y limb of jejunum. Chronic infections of silk sutures are common in abdominal wounds, and Akiyama et al [15] have described ulceration and mucosal inflammation in as- sociation with exposed silk sutures in choledocho- duodenostomies. The remaining two of the six patients had long-standing biliary tract disease which could have resulted in high concentrations of bacteria in the bile.

The effects of persistent bactobilia have been presumed to be negligible because patients are usually asymptomatic. However, a study in 1952 by Musgrove et al [II] casts doubt on this viewpoint. These researchers studied the biliary flora and hepatic histopathologic findings in dogs 6 to 24 months after biliary bypass. All dogs had sterile bile at the initiation of the study, but infected bile was univer- sally present after bypass. Slight to moderate cirrhosis developed in most of the animals, even though the stomas were widely patent. Large [16] also found significant hepatic inflammatory changes after bypass, even though the anastomoses were patent. Persistent bactobilia may therefore not be as innoc- uous as has usually been assumed.

Could the duration of preexistent biliary tract disease play a role? Most patients who undergo biliary-enteric anastomoses have had long-standing biliary tract disease, and preoperative episodes of recurrent obstruction, infection, or both, are common. Prolonged intrahepatic biliary obstruction does not leave the liver and intrahepatic biliary system unscathed. Soon after its occurrence there is dilation and sacculation of the biliary canaliculi, which is followed by ductular proliferation, the development of bile thrombi, and extravasation of bile which cause inflammation and fibrosis. Proliferating ductules need not communicate directly with the biliary tree, and a labyrinthine network that slows the flow of bile produces some degree of functional obstruction [I 71. At first, the process is centrilobular, but with time it extends to the portal areas. Concomitantly, the hepatocytes are injured and necrosis occurs with further release of biliary constituents into the pa- renchyma. This extravasation of bile, associated with the increased ductal pressures, stimulates periductal fibrosis and collagen formation [18] as does bacterial infection. Secondary obstruction can be caused by this progressive fibrosis, and a vicious circle of pro-

gressive obstruction is thus produced. Many of these changes are reversible if the obstruction is relieved early, but the longer the duration of the obstruction the slower the resolution of these abnormalities. Lygidakis [19] has shown that even 1 year after choledochoduodenostomy, morphologic changes in the intrahepatic biliary tree persist. Extensive peri- portal fibrosis and secondary biliary cirrhosis are not reversible [17]. Given the irregular distribution of the damage, resolution of the above described changes in patients with long-standing extrahepatic disease probably occurs at different rates throughout the liver, and some areas of irreversible damage probably persist.

The changes in extrahepatic biliary atresia in children closely reflect those in long-standing extrahepatic biliary disease in adults [20]. As a model, extrahepatic biliary atresia represents the most severe form of adult extrahepatic biliary disease; therefore, the results of bypass in these children might provide some insight into this problem. Cholangitis is an almost universal complication of the successful operative treatment of extrahepatic biliary atresia [21]. In the first 6 to 12 months after operation, the cholangitis is not associated with mechanical problems of the biliary-enteric conduit and is thought to be due to ascending infection in partially obstructed intrahepatic bile ducts [22]. Such an infection is usually resolved when the infant is 9 to 12 months old. If cholangitis does develop after 9 to 12 months, mechanical problems in the conduit are usually present. Because the occurrence of cholangitis is unusual when found after portocholecystostomy, which would interpose a functioning sphincter of Oddi between the gastrointestinal tract and the biliary tree [23], an ascending pathway for the bacteria is likely. The long-term control of early cholangitis in children with biliary atresia and in two of our patients (Cases 1 and 4) with long-term antibiotic therapy suggests that such treatment might be of value until reversal of the intrahepatic abnormalities occurs.

Intrahepatic abnormalities, then, can result in persistent or recurrent symptoms despite adequate decompression of the biliary tree. Lilly [23] has pointed out that when there is an intrahepatic com- ponent to the entity of a choledochal cyst, cholangitis may persist, despite the provision of excellent extrahepatic bile drainage.

Our findings indicate that cholangitis can occur after biliary-enteric bypass, despite a widely patent anastomosis, whether it be a sphincteroplasty, choledochoduodenostomy, or choledochojejunostomy. The cause is multifactorial but includes a combina- tion of persistent moderate to marked bacterial contamination and morphologic changes which promote intrahepatic biliary stasis. These changes may have their beginnings in repeated infections and episodes of obstruction. To some extent the persis-

452 The American Journal of Surgery


tent bactobilia that follows a biliary bypass operation may contribute to or aggravate the intrahepatic changes. Long-term therapy with antibiotics may be the only effective treatment. If possible, the cause of the high bacterial count should be eliminated. Al- though anastomotic stenosis remains the most common cause of cholangitis after biliary-enteric anastomoses, when none can be found long-term antibiotic treatment is sometimes curative.

Summary

After a biliary-enteric anastomosis, the development of cholangitis is usually assumed to be due to obstruction of the stoma. Six patients in whom this was not the case are described. Achlorhydria, duodenal diverticula, and foreign bodies are important predisposing factors. When bacterial contamination is severe in an abnormal intrahepatic biliary tree, especially that which follows long-standing inter- mittent common duct obstruction, symptomatic biliary infection may occur in the absence of extrahepatic biliary obstruction.

References

1. Degenshein GA. Choledochoduodenostomy: an 18 year study of 175 cases. Surgery 1974;76:319-24.

2. Huang T, Bass JA, Williams RD. The significance of biliary pressure in cholangitis. Arch Surg 1969;98:629-32.

3. Madden JL, Gruwez JA, Tan PY. Obstructive (surgical) jaundice: consideration of choledochoduodenostomy in its treatment. Am J Surg 1965;109:89-99.

4. Madden JL, Chun JY, Kandalaft S, Parekh M. Choledochoduo- denostomy, an unjustly maligned surgical procedure. Am J Surg 1970;119:45-52.

5. Jones SA. The prevention and treatment of recurrent bile duct stones by transduodenal sphincteroplasty. World J Surg 1978;2:473-85.

6. Stefanini P, Carbone M, Patrassi N, DeBernardinis G, Negro P. Transduodenal sphincteroplasty, its use in the treatment of lithiasis and benign obstruction of the common duct. Am J Surg 1974;128:872-7.

7. White TT. Indications for sphincteroplasty as opposed to choledochoduodenostomy. Am J Surg 1973;126:165-8.

8. Thomas CG Jr, Nicholson CP, Owen J. Effectiveness of choledochoduodenostomy and transduodenal sphincterotomy in the treatment of benign obstruction of the common duct. Ann Surg 1971;173:845-56.

9. Delbene R. Bogliaccini G, Proderi R. Colangitis septica grave por reflujo postcoledocoduodenostomia. Cir del Uruguay 1980;50:574-7.

10. Morgenstern L, Shore JM. Selection of an optional procedure for decompression of the obstructed common bile duct. Am J Surg 1970;119:38-44.

11. Musgrove JE, Grindlay JH, Karlson AG. Intestinal biliary reflex after anastomosis of common duct to duodenum or jejunum. Arch Surg 1952;64:579-89.

12. Flemma RJ, Flint LM, Osterhout S. Shingleton WW. Bacterio- logic studies of biliary tract infection. Ann Surg 1967;166: 563-72.

13. Thomas E, Grant AK, Holford M, Ringwood D, Derrington AW. Magarey JR. Bacterial flora in the duodenum of patients after biliary fenestration. Br J Surg 1973;60:107-11.

14. Effert A, Kirschner J, Teichmann W. Bakteriologische befunde bei patienten mit cholelithiasis und duodenaldivertikelia. Chirurg 1979;50:441-4.

15. Akiyama H, lkezawa H, Kameya S, lwasaki M, Kuroda Y, Tak-

eshita T. Unexpected problems of external choledochoduodenostomy, fiberscopic examination in 15 patients. Am J Surg 1980;140:660-5.

16. Large AM. Effect of direct anastomosis of common bile duct to the duodenum. Arch Surg 1952;65:522.

17. Desmet VJ. Cholestasis; extrahepatic obstruction and secondary biliary cirrhosis. In: MacSween RN, ed. Pathology of the liver. Edinburgh: Churchill-Livingstone. 1979:252-305.

18. Carlson E, Zukoski CF, Campbell J, Chapil M. Morphologic, biophysical, and biochemical consequences of ligation of the common biliary duct in the dog. Am J Pathol 1977;86: 301-21.

19. Lygidakis NJ. Histologic changes and intrahepatic biliary abnormalities in extrahepatic biliaty tract obstruction. Surg Gynecol Obstet 1981;153:532-8.

20. lshak KG, Sharp HL. Developmental abnormalities and liver disease in childhood. In: MacSween RN, Anthony PP. Scheuer PJ, eds. Pathology of the liver. Edinburgh: Chur- chill-Livingstone, 1979:68-87.

21. Lilly JR, Hitch DC. Postoperative ascending cholangitis following portoenterostomy for biliary atresia: measures for control. World J Surg 1978;2:581-7.

22. Lilly JR. Hepatic portocholecystostomy for biliary atresia. J Pediatr Surg 1979;14:301-4.

23. Lilly JR. The surgical treatment of choledochal cyst. Surg Gy- necol Obstet 1979;149:36-42.

Discussion

C. Elton Cahow (New Haven, CT): It is important for clinical surgeons to periodically review the procedures which we have come to accept over the years as being both effective and safe. Many years ago, biliary-enteric anastomosis was carried out frequently in Europe, but it was not accepted in this country because of the high incidence of cholangitis and biliary fistula. It was not until after World War II that first Saunders and then Madden proved that choledochoduodenostomy was a safe procedure both in the laboratory and in patients. All researchers have emphasized that biliary-enteric anastomoses and sphincteroplasties must be as widely patent as the diameter of the common bile duct. Boydens beautiful anatomic descrip- tions of the choledochal sphincter were utilized by Jones when he defined the technique by which we now perform sphincteroplasty; that is, that both the inferior and supe- rior choledochal sphincters must be transsected in order to perform a complete sphincterotomy, and that sphincteroplasty should be carried out by excising a wedge of that sphincter, suturing the mucosa of the duodenum to the common duct in such a way that, in effect, we are per- forming an internal choledochoduodenostomy. The incidence of cholangitis after any of these procedures should be less than 3 percent. When cholangitis develops, it is usually due to stenosis of the anastomosis.

In reviewing the manuscript, I noted that the patency of the sphincter was judged by noting whether or not barium refluxed into the common duct. Reflux can occur with stenosis. It is important to remember that three things must be looked for: (1) ingress of barium, (2) the size of the sphincter and the anastomosis, and (3) free egress of barium. The administration of antibiotics over a period of 4 to 6 weeks in these patients may result in recovery from cholangitis with no further attacks.

John Braasch (Boston, MA): We are indebted to Drs. Goldman, Steer, and Silen for very astutely culling out these very interesting cases from their experience with obstructive biliary tract problems. We agree that chronic

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liver changes can result from infection, as exemplified by some of our patients in whom the strictures progressed proximally. In addition, abscess may form in the liver when proximal segmental ducts become obstructed. Almost all of our patients with biliary-enteric anastomoses for benign strictures have elevated alkaline phosphatase levels for years and years afterwards, presumably because of infections in the livers.

I would exert a note of caution here, though, in that we have found it very difficult to ascertain the degrees of obstruction of anastomoses in patients with cholangitis. Barium may reflux into a duct and contrast material may empty after percutaneous cholangiography, yet functional obstruction may exist even with an anastomosis that is 2 mm in diameter. We believe that all patients with a history of damage to the biliary tract or of a previous anastomosis deserve reexploration, especially if they have cholangitis.

In some of those patients who had sphincteroplasties or side-to-side biliary-enteric anastomoses, might not it have been better if the duct had been cut off and an end-to-end anastomosis performed? This would obliterate any sump effect and give, perhaps, better drainage to the proximal biliary system.

Jack Parker (Newton, MA): The study cases suggest to me a disease that was described by Caroli back in 1958. It was characterized by intrahepatic saccular dilatation of the bile ducts and a marked predisposition to cholangitis, liver abscess, stone formation in the intrahepatic system, and absence of cirrhosis and portal hypertension. These patients may have a lifetime of intrahepatic stone formation, extrahepatic problems similar to those described, and persistent cholangitis and fever which often progresses to

finite abscesses that may require drainage. The cases must be distinguished from polycystic disease of the liver as well as from congenital hepatic fibrosis. Perhaps there is a spectrum of familial diseases in which afflicted patients will continue to get cholangitis despite very free drainage of their intrahepatic and extrahepatic biliary systems.

Leon Goldman (closing): In terms of Dr. Cahows comments, two of the patients could not be studied by endoscopic retrograde cholangiopancreatography because they had Roux-Y loops. Their ducts were calibrated at the time of their reoperation. Two patients have been studied and have patent anastomoses and normal biliary trees as demonstrated by endoscopic retrograde cholangiopancreatography, despite the fact that they are still having recurrent cholangitis. One patient has refused duct studies, so we have had to accept the evidence of barium reflux during an upper gastrointestinal series. One patient died before we were able to perform the endoscopic retrograde cholangiopancreatography. We agree that 4 to 6 weeks of antibiotic therapy in some of these patients may be very useful and may be curative.

We agree with Dr. Braasch that if there has been a previous anastomosis, stenosis is most often present. In fact, the patients who were not amenable to study any other way were explored for that presumption. Our point is, however, that not all patients with cholangitis need have obstruction.

In regard to Carolis disease, our patients who have been studied with endoscopic retrograde cholangiopancreatography have been shown to have normal intrahepatic ducts without gross dilatation. So, as near as we can tell, there is no evidence in any of our patients that they have congenital intrahepatic cystic changes.

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recurrent cholangitis after biliary surgery

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