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Biliary lithiasis and helminthiasis
Biliary Lithiasis and Helminthiasis Albert E. Yellin, MD, Los Angeles, California Arthur J. Donovan, MD, Los Angeles, California
The syndrome commonly referred to as Oriental cholangiohepatitis [•], recurrent pyogenic cholangitis [2] or biliary obstruction syndrome [3] has been reported primarily from the Orient or in populations where helminthic infestation is very widespread. The purpose of this report is to review the cases of Oriental cholangiohepatitis recently seen at Los Angeles County-University of Southern California Medical Center, to describe the clinical syndrome of Oriental cholangiohepatitis and to indicate what are believed to be the appropriate therapeutic principles in these cases. These unusual biliary syndromes are now seen increasingly in the United States consequent to the trend to intercontinental migration, such as the recent influx of Southeast Asian "boat people." Features of Oriental cholangiohepatitis may include helminthiasis; choledocholithiasis, probably primary and often without cholecystolithiasis; choledochal obstruction by stone; recurrent cholangitis with stones; a propensity for stricture of the !eft hepatic duct; and hepatic abscess, scarring and atrophy of the left hepatic lobe [4-6]. The common duct stone that is typically present is presumed to be primary and is usually darkly pigmented, soft, friable and irregular in shape. Identical stones may also be found in the gallbladder. The contrast between this condition and that usually seen in the cases of cholelithiasis that develop in Western culture is apparent. A parasite may or may not be identified in either the biliary tract or stool in cases of Oriental cholangiohepatitis. The relation, if any, of the parasite t o stone formation is a subject of dispute. Often, past or present helminthic infestation cannot be proven. The clinical syndrome is uncommon in some heavily infested populations, as in India. In the opinion of From the Department of Surgery, University of Southern California School of Medicine and the Los Angeles County-University of Southern California Medical Center, Los Angeles, California. Requests for reprints should be addressed to Albert E. Yellin, MD, Department of Surgery, University of Southern California School of Medicine, 1200 North State Street, Los Angeles, California 90033. Presented at the 52nd Annual Meeting of the Pacific Coast Surgical Ass0ciation, Coronado, California, February 15-18, 1981.
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some, a parasite may act as a nidus for stone formation or provoke the disease in the bile ducts that leads to stones [1,7-9]. Others believe that the relation between choledocholithiasis and parasites is coincidental in a population that is already heavily infested and that stone formation is caused by stasis and infection with Escherichia coli [2,3,6]. The exact etiology that explains all features of the syndrome in all cases has not been established, but the circumstantial evidence implicating helminthiasis is so strong that a brief review of some relevant parasitologic factors is believed appropriate. Parasitology Some parasites, such as the schistosomes, invade the hepatic parenchyma or portal venous radicles but are not associated with biliary lithiasis. A smaller group of parasites are able to directly invade the biliary ducts. These parasites are distributed worldwide and, by conservative estimates, infect at least 500 million persons. Among these various parasites, infestation with Clonorchis sinensis, the Chinese liver fluke, has been extensively studied in relation to biliary lithiasis. These parasites enter humans or other mammals when ingested with raw fish. Eggs, passed in human or mammalian feces, hatch in water and are eaten by freshwater Bithynia snails. The parasite develops in the snail, escapes into the water and burrows between the scales and into the muscle of specifiC freshwater fish, the cyprinidoe. The human is infested upon ingesting the raw fish. The metacercariae form of the parasite ruptures in the duodenum, and the parasite migrates through the ampulla of Vater and swims up the bile duct into the terminal biliary radicles. They mature in 1 month and remain viable for at least 25 years. Larva and adults that measure about 15 mm migrate through the ducts by attaching their suckers to the ductal epithelium and pulling themselves forward. This process causes epithelial desquamation. The parasites burrow into periductal tissue, causing marked fibrosis. This ongoing process ultimately results in crypt and abscess formation. Subsequent ductal The American Journal of Surgery
Biliary Lithiasis and Helminthiasis
hyperplasia and periportal ductal fibroplasia result in stricture formation, stasis and bacterial infection. Additionally, ova or portions of the fluke, in combination with bile stasis, may form the nidus for stone formation and frequently can be identified at the center of a sectioned stone [8,10]. Masses of liver flukes or the stones themselves can cause common duct obstruction [5,11]. Cholangiocarcinoma and hepatocellular carcinoma have been observed in these cases and may be related to the hyperplasia caused by the flukes [12,13]. Clonorchis sinensis in-. festation is a lifelong disease [14]. An effective antihelminthic agent that can eradicate the infestation, has not been identified. This infestation may be manifested by only the presence of viable flukes in the biliary ducts, by stones or by the more advanced disease seen with strictures of the bile duct. Figure 1 shows Clonorchis sinensis retrieved from a common bile duct during surgery. Ascaris lumbricoides, worldwide in distribution and more prevalent than Clonorchis and other flukes, is also associated with cholangiohepatitis. In some cases portions of the ascaris worm can be found as the central nidus of a stone. Cases have been reported from Korea, Africa, South America, the United States and China [9,15-18]. In one series of cases of intestinal ascariasis from South Africa, ascarides : were demonstrated by intravenous cholangiography in the common bile ducts of 40 of the 68 patients [19]. That study demonstrates the frequency of biliary infestation. In Figure 2 an intravenous cholangiogram demonstrates an ascaris in the common bile duct. The ascarides gain entrance to the biliary tree by a complex mechanism that does not require an intermediate host. Adult worms live in the proximal small bowel of the human. Fertilized eggs are passed in the feces and develop in moist soil, where they remain viable for several years. When ingested with food, the eggs hatch in the small intestine. The larvae penetrate the intestinal wall to enter the portal circulation or lymphatics. They migrate through the liver, to the heart, and through the pulmonary artery to the lungs, where they burrow into the alveoli, molt and migrate up the bronchi to the trachea and down the esophagus into the stomach and the proximal small intestine. They molt twice in the intestine before becoming mature adults. The adult form frequently migrates through the ampulla of Vater into the common bile duct. The mature adult is up to 15 cm long and may cause common duct obstruction or become the nidus for formation of stones. The ascarides remain viable for approximately 1 year, but can be readily eradicated by oral therapy with mebendazole. After therapy they do not recur unless additional eggs are ingested. Other helminths that commonly enter the biliary tract are listed in Table I. All of the flukes can produce a syndrome comparable to infestation with Clonorchis sinensis. Strongyloides sterocoralis and Volume 142, July 1981
Figure 1. Viable Clonorchls sinensis, measuring 15 to 16 ram, which were retrieved from the common bile duct. The intraductal flukes were too numerous to count.
Figure 2. a, an ascarls worm in the common bile duct, demonstrafed by Intravenous cholanglography, b, a primary common duct stone. All traces of ascariasis were eliminated preoperatively by oral administration of mebendazole.
hookworm have been known, on rare occasions, to invade the gallbladder or biliary tree. Clinical Data
Patients: Between August 1974 and September 1980, 14 immigrants were admitted to the Los Angeles CountyUniversity of Southern California Medical Center with a syndrome consistent with Oriental cholangiohepatitis. All had biliary lithiasis, 9 had proven helminthiasis, and the remaining 5 patients came from an area of endemic helminthiasis. Eight of these patients were seen in the past 2 years. Nine emigrated from Korea and one each from Thailand, Viet Nam, China (Hong Kong), Mexico and E1 Salvador. There were 10 women and 4 men, aged 22 to 88 years (median 55). Eight patients were admitted with a syndrome characteristic of cholangitis including right
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TABLE I
Parasites That invade the Bile Ducts Parasite
Common Name
Source of Human Infection
Geographic Distribution
Ascaris lumbricoides Clonorchis sinensis Dicrocoelium dendriticum Fasciola gigantica Fasciola hepatica Opisthorchis felineus Opisthorchis viverrini Taenia saginata
Roundworm Chinese liver fluke ... Tropical giant fluke Sheep fluke Cat fluke Cat fluke Beef tapeworm
Fresh fruit, vegetables Raw fish Ants Watercress, lettuce Watercress Raw fish Raw fish Beef
Worldwide Far East Africa, Asia, USSR Africa, Asia, Hawaii Worldwide Eurasia Thailand Worldwide .
upper quadrant pain, fever and jaundice. Four of these eight patients had previously undergone cholecystectomy. In two of the latter a choledochoenterostomy had also been established, choledochoduodenostomy and choledochojejunostomy in one case each. Three patients were admitted with jaundice due to choledocholithiasis, and the final three patients were admitted with acute cholecystitis. Laboratory data: Among patients with cholangitis the total serum bilirubin ranged from 0.9 to 6.8 mg/100 ml (median 2.5), and the alkaline phosphatase level from 3.19 to 8.77 Bessey-Lowry (BL) units with a median of 7.0 BL units (normal 1 to 3). The bilirubin levels in the patients with choledocholithiasis without cholangitis were 6.1, 6.7 and 17 mg/100 ml, with concomitant alkaline phosphatase levels of 7.86, 3.44 and 4.65 BL units, respectively. Eosinophilia, ranging from 3 to 20 percent, was noted in 8 of the 14 patients. Roentgenography: Oral cholecystography was rarely performed because most of the patients had jaundice or had an acute right upper quadrant syndrome. One study in a nonjaundiced patient demonstrated cholecystolithiasis, and the second such study performed did not visualize the gallbladder. Intravenous cholangiography was performed in earlier years in four patients with a total serum bilirubin level below 3 mg/100 ml. Ascariasis and stones were identified in the common bile duct of one patient (Figure 2), and stones only were demonstrated in the
Figure 3. Transverse scan demonstrating a dilated 3 cm left hepatic duct and choledocholithiasis.
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common bile duct of a second patient. The common bile duct was not visualized in the final two patients. Ultrasonography of the biliary tract was performed in eight patients and identified dilated biliary ducts with stones in four (Figure 3) and only a dilated bile duct in one patient in whom choledocholithiasis was subsequently proven. Ultrasonography failed to identify dilated bile ducts that contained calculi in three patients. Cholecystolithiasis was demonstrated by ultrasound in two of the latter three patients. Endoscopic retrograde cholangiography was performed in five patients and identified dilated bile ducts and choledocholithiasis in four. The study was technically unsatisfactory in the fifth patient. An endoscopic retrograde cholangiogram demonstrating a large stone in the common bile duct of a patient with documented ascariasis is shown in Figure 4. Percutaneous transhepatic cholangiography was performed in six patients. Choledocholithiasis was noted in five patients, and stricture of the bile duct was identified in two of the five. Percutaneous transhepatic cholangiography failed to identify choledocholithiasis in one patient in whom the common duct was filled with contrast medium and stones were later proven present. A clinical syndrome consistent with gram-negative bacteremic shock followed percutaneous transhepatic cholangiography in one 88 year old woman. A cholangiogram demonstrated a normal gallbladder but a common
Figure 4, Choledocholithlasis demonstrated by endoscopic retrograde cholangiography. The arrow indicates a stricture of the left hepatic duct.
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Biliary Lithiasis and Helminthiasis
Figure 6. A resected lateral segment of the left hepatic lobe. The hepatic parenchyma is fibrotic and atrophic. The bile ducts are markedly dilated and contained numerous black, friable stones. Figure 5. Calculi are present In the common bile duct ( a ) and the left hepatic duct (b). The gallbladder is free of stones ( c ).
bile duct was filled with stones and showed stricture of the left hepatic duct (Figure 5). These diagnostic radiologic tests, used in varying sequence preoperatively, correctly identified disease in the common duct in all cases. Treatment
Treatment was surgical in 13 of the 14 patients. One patient, in whom oral cholecystography revealed the gallbladder to be free of stones and endoscopic retrograde cholangiography documented one stone in the common duct, underwent endoscopic papillotomy of the sphincter of Oddi with subsequent passage of the common duct stone. (This case is included due to the courtesy of Ian Renner, MD). The remaining 13 patients underwent surgery. The gallbladder was removed in nine patients that had not previously undergone cholecystectomy. Stones were present in the gallbladder of six of these nine patients and absent in three. Stones were present in the common bile duct in the latter three patients. The common bile duct was explored in all 13 surgical patients, and calculi were present in 12. In 1 of the latter 12, the ascaris that had been identified on intravenous cholangiography had passed after preoperative treatment with mebendazole. The final or 13th patient had cholecystolithiasis. When the common bile duct was opened it was found to be packed with viable flukes, identified as Clonorchis sinensis. In the remaining 12 patients, multiple stones that were generally black, soft and friable were present in the common duct with varying amounts of other debris. Stones were specifically documented in the left hepatic duct in 7 of the 12 patients. Hepatic abscesses were present in three, and in two of these there was a stricture of the left hepatic duct. Multiple stones, abscesses and extensive fibrosis were present in the left lateral segment of the left hepatic lobe of these two patients, and a left lateral hepatic segmental resection was performed. The third patient with hepatic abscess underwent drainage of the abscess and removal of stones.
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In one of the two patients with left hepatic duct stricture, who was admitted with cholangitis, the endoprosthetic catheter which was employed for percutaneous transhepatic cholangiography was left in place. The purpose was to attempt decompression of the biliary tree and to control sepsis before surgery. This was unsuccessful, sepsis persisted and emergency surgery was performed. The multiple stones, strictures and abscesses present explain the futility of the attempt at percutaneous decompression. The resected specimen and the removed stones are shown in Figure 6. A biliary enteric anastomosis was established in seven patients. A Roux-Y choledochojejunostomy was fashioned in six patients and choledochoduodenostomy in one. The principal indication was multiple stones in six patients and viable flukes that were diagnosed as Clonorchis sinensis in one. A choledochoenterostomy already existed in two additional patients, both of whom had recurrent cholangitis with left hepatic duct stones. In one of these two patients, a left hepatic duct stricture was present and left lateral hepatic segmental resection was performed; this was the third patient to undergo segmental resection. The other patient with left hepatic stones and previous choledochojejunostomy did not have a stricture and the choledochojejunostomy was revised. The remaining four surgical patients did not have a choledochoenterostomy established. Two had known infestation with ascariasis. The common bile duct was cleared of stones and ascariasis was eliminated by mebendazole therapy. The other two patients, previously discussed, required left lateral segmental hepatic resection for stricture of the biliary ducts and consequent hepatic abscess. Methods of treatment are summarized in Table II. Cultures of bile were positive in 12 of 13 surgical patients. The indication for surgery in the 13th patient was cholangitis, and the negative ctllture probably represents inhibition of bacterial growth by antibiotics administered preoperatively. In 7 of the 12 patients more than one organism was identified. E. coli was identified in nine patients, gamma streptococcus in five, Proteus mirabilis in four, Enterococcus in three, Pseudomonas aeruginosa in two, Klebsiella aerogenes in two and Citrobacter species
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TABLE II
Treatment Patients Procedure
(n) _
Endoscopic papillotomy Surgery Gallbladder present and removed Gallstones present Common bile duct explored Stones removed Flukes removed Left hepatic duct stones Left hepatic duct stricture Biliary enterostomy Choledochojejunostomy Choledochoduodenostomy No biliary enterostomy Previous enterostomy Ascariasis Hepatic resection Left lateral hepatic Iobectomy
1 13 9 6 13 12 1 7 3 7 6 1 6 2 2 2 3
in two. Organisms were monomicrobial in five patients and polymicrobial in seven. One nonsurgical patient had no culture. Parasites were specifically identified in nine patients. Clonorchis sinensis infestation of the common bile duct was documented at surgery in two of the nine patients. An ascaris was seen in the common bile duct in one patient on intravenous cholangiography. In six other patients a total of 15 parasites were identified. Parasites identified in the stool that are known to commonly infect the biliary tract was Ascaris (three), Clonorchis (one) and Fasciola hepatica (one). In four patients, both hookworm and Trichuris were present in the stool. Strongyloides was present in two patients. The five patients without documented parasitic infestation all had a typical syndrome of Oriental cholangiohepatitis with multiple, black, friable stones in the common bile duct. In addition, two patients had bile duct strictures and left hepatic lobe abscess. All patients with proven parasites, other than flukes, were treated with antihelminthic agents such as mebendazole, thiabendazole or piperazine. This therapy effectively eradicates parasites other than liver flukes. As previously noted, an effective agent to eradicate Clonorchis does not yet exist. Results
Seven patients had an uneventful recovery. There were eight major complications in the remaining seven patients. These consisted of intraabdominal hemorrhage in two, myocardial infarction in one, recurrent or persistent sepsis that eventually resolved in three of four patients, and a wound infection in one patient. An 88 year old patient was one of the four with persistent sepsis, and she died after left hepatic lobectomy for multiple hepatic abscesses with left hepatic duct stricture. T hat was the only death in the series. Comments
Digby [4] in 1930 described described a unique clinical syndrome seen primarily in Chinese persons
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in Hong Kong, in which cholangitis occurred in concert with primary choledocholithiasis and often without cholecystolithiasis or disease in the gallbladder. The prevalence of infestation with Clonorchis sinensis in these patients was recognized. Oriental cholangiohepatitis has been reported as the third most common cause of acute abdominal disorders in Hong Kong, exceeded only by acute appendicitis and complications of peptic ulcer [2]. The usual pathologic and clinical manifestations of Oriental cholangiohepatitis and some relevant parasitologic aspects were discussed earlier herein. T he most prominent feature of this " E a s t Asian" disease which differentiates it from the typical cholelithiasis originating in the West is the degree of choledochal and hepatic lithiasis. It is a disease of the bile ducts; the gallbladder is a secondary consideration. In Oriental cholangiohepatitis, the choledochal stones probably originate in the hepatic ducts and pass down into the common duct, where they continue to enlarge. In the West primary common duct stones are rare and may be due to bile stasis secondary to stensosis at the ampulla of Vater or, less often, to metabolic disorders or hemolytic anemias [20,21]. Most common duct stones in the West are secondary stones t hat originated as cholecystolithiasis and migrated into the common duct [21]. The cause of the calculous disease and disease of the bile ducts in Oriental cholangiohepatitis remains a matter of controversy. Helminthiasis or chronic bacterial infection are the most prominent considerations. Those who favor chronic bacteria infection rather than helminthiasis as a cause suggest that the biliary ducts may be colonized by bacteria, particularly E. coli, t hat enter the liver through the portal venous system during bouts of gastroenteritis. Such bouts are frequent in malnourished populations. According to this theory, chronic infection of the biliary ducts themselves ensues, with later formation of stones. Helminthiasis is considered incidental. The likelihood of helminthic infestation is apparent when one recognizes that 65 percent of Chinese in Hong Kong beyond the age of 1 year are infested with liver flukes [11]. T he evidence in favor of a direct relation between helminthiasis and Oriental cholangiohepatitis is strong. Additional evidence in support of a helminthic cause is that the incidence of the syndrome is decreasing in some populations where improved hygiene has reduced infestation by liver flukes [8]. Admittedly, helminthic infestation has not been proven in all reported cases of this syndrome nor in all of the cases described herein. However, if E. coli infection were the cause, it would be surprising th a t the syndrome is not seen in cases of cholelithiasis that develop in the Western world. A majority of the cases of secondary choledocholithiasis treated in the United States have bacterial colonization of the bile ducts, often with E. coll. The pathologic features of
The American Journal of Surgery
Biliary Lithiasis and Helminthiasis
Oriental cholangiohepatitis, particularly development of stricture, is not seen in these cases. Perhaps neither chronic infection nor helminthiasis is the cause of Oriental cholangiohepatitis and the disease is due to an agent and process yet unrecognized. We prefer to accept the evidence directly implicating helminthiasis as the inciting cause. Familiarity with the syndrome of Oriental cholangiohepatitis is important because of the increasing numbers of immigrants to the United States from areas where the disease is frequent and helminthic infestation is epidemic in nature. About three fourths of the Southeast Asians who are immigrants to the United States harbor intestinal parasites. Ascariasis is common not only in this immigrant group [22,23], but also in Koreans. Seven of the nine patients in this series with Oriental cholangiohepatitis and proven helminthiasis had either ascariasis or liver fluke infestation, and most were from Korea. Suspicion of the diagnosis is aroused when a patient from an area with a high incidence of Oriental cholangiohepatitis has cholangitis, previous surgery for cholelithiasis, jaundice, presence of eosinophilia, and identification of parasites or ova in the stool. The absence of eosinophilia or documented parasitic infestation does not preclude the diagnosis in an otherwise typical case. Eight of 14 patients in this series had cholangitis and 4 of these had previous biliary tract surgery. Eosinophilia was documented in seven of nine patients with proven helminthiasis. Radiologic studies can be employed to visualize the nature and extent of the disease. Because of the frequent presence of jaundice, oral cholecystography and intravenous cholangiography are of limited value. Ultrasonography of the liver and biliary tree is quite accurate in identifying the dilated ductal system and may reveal the stones. If dilated intrahepatic bile ducts packed with stones are evident, particularly in association with a gallbladder without stones, the syndrome of Oriental cholangiohepatitis must be suspected. Precise definition of the extent of ductal lithiasis and anatomic localization of strictures can be obtained by either endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography. Such studies can produce or exacerbate an episode of cholangitis if the patient is not concomitantly treated with antibiotics [24]. Recently, indwelling endoprostheses have been employed to temporarily decompress the biliary tree after percutaneous transhepatic cholangiography and to permit sepsis to resolve before undertaking any surgical procedure. Such decompression may not be effective if ductal strictures and multiple abscesses are present. The futility of this procedure was reflected in one such case in this series. Precise anatomic definition of disease, including localization of strictures, is very helpful in preoperative planning and in determination of whether a biliary drainage procedure or hepatic resection will be required. A
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combination of the radiologic studies just discussed indicated the correct preoperative anatomic diagnosis in all of the cases in this series. If Oriental cholangiohepatitis is suspected and time permits, multiple stool specimens should be examined for the presence of parasites, particularly those known to commonly invade the biliary tract. Treatment of helminthic infestation with an appropriate vermifuge can begin as soon as they have been identified. Frequently, the need for surgery to control sepsis associated with cholangitis is urgent and treatment of the infestation must be delayed until after surgery. Cholecystectomy, choledochostomy and extraction of stones are all that are required for eradication of the usual cholecystolithiasis with secondary choledocholithiasis that develops in the West. Ancillary biliary drainage procedures are occasionally performed for patients with countless stones or stones in the hepatic ducts [10,20,21,25,26]. The nature of the disease in Oriental cholangiohepatitis is such that the common bile duct should be explored in all cases. This is dictated by the likelihood of stones or intraductal parasites. There is a frequent need for biliary enteric anastomosis to permit the passage of any residual stones or new stones that form due to the persistent infestation. If Clonorchis sinensis has been diagnosed or is suspected, such recurrent stone formation might be anticipated, and as already stressed, a satisfactory treatment does not exist for Clonorchis infestation. Therefore a biliary enteric shunt is recommended unless infestation of the bile ducts with a parasite such as Ascaris, for which satisfactory treatment is available is proven, and only if a limited number of stones is present in such patients with a treatable parasite. This policy was pursued in the patients reported on herein. At this hospital Roux-Y choledochojejunostomy is preferred. This is apparent from its choice in six of seven cases. Choledochoduodenostomy and transduodenal sphincteroplasty have also been satisfactorily used in patients with Oriental cholangiohepatitis [3,7,15,27]. Cholecystectomy is performed irrespective of the presence of stones and particularly if the sphincter of Oddi is bypassed. In the absence of the sphincter, stasis in the gallbladder is likely to result in the formation of calculi [28]. For that reason, endoscopic papillotomy as performed in one patient in this series is unlikely to be widely adopted for patients with an intact gallbladder. The reason for the propensity for stricture of the left hepatic duct is not known, but the resulting sacculation, fibrosis and abscess formation can only be satisfactorily treated by hepatic resection. The nature of the disease in an advanced case precludes drainage as a satisfactory definitive treatment. The one patient in this series who died had persistent sepsis after biliary drainage and required left lateral segmentectomy in an attempt to eradicate intrahepatic abscess.
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Summary T h e syndrome of Oriental cholangiohepatitis is characterized by helminthiasis, choledocholithiasis often without cholecystolithiasis, biliary duct stricture and hepatic abscess. T h e c o m m o n duct stones are usually multiple, black and friable. F o u r t e e n cases have been seen in recent immigrants to the United States. T h i r t e e n patients h a d choledocholithiasis, a n d 1 had viable flukes in the ducts. Choled o c h o e n t e r o s t o m y is usually required because of multiple stones, including intrahepatic stones, or proven or p r e s u m e d infestation with Clonorchis sinensis. T h e latter, the Chinese liver fluke, is an infestation for which medical t h e r a p y does not exist. Resection, particularly of the lateral segment of the left hepatic lobe, m a y be required in cases of abscess and stones associated with stricture of the left hepatic duct.
References 1. Stock FE, Fung JY. Oriental cholangiohepatitis. Arch Surg 1962;84:409-12. 2. Cook J, Hou PC, Ho HC, McFadzean AJS. Recurrent pyogenic cholangitis. Br J Surg 1954;42:188-203. 3. Harrison-Levy A. The biliary obstruction syndrome of the Chinese. Br J Surg 1961;49:674-85. 4. Digby KH. Common duct stones of liver origin. Br J Surg 1930;17:578-91. 5. Hou PC. The pathology of clonorchis sinensis infestation of the liver. J Pathol Bacteriol 1955;70:53-64. 6. Ong GB. A study of recurrent pyogenic cholangitis. Arch Surg 1962;84:199-225. 7. Fung J. Liver fluke infestation and cholangio-hepatitis. Br J Surg 1961;48:404-15. 8. Maki T. Cholelithiasis in the Japanese. Arch Surg 1961;82: 599-612. 9. Teoh TB. A study of gall-stones and included worms in recurrent pyogenic cholangitis. J Pathol Bacteriol 1963;86:123-9. 10. Baker MS, Baker BH, Woo R. Biliary clonorchiasis. Arch Surg 1979;114:748. 11. Ameres JP, Levine MP, DeBlasi HP. A calculous clonorchiasis obstructing the common bile duct. Am Surg 1976;42: 170-2. 12. Chow CW, Allen PW. Clonorchis sinensis infestation of liver associated with cholangiocarcinoma. Pathology 1978;10: 174-5. 13. Nakashima T', Sakamoto K, Okuda K. A minute hepatocellular carcinoma found in a liver with clonorchis sinensis infection. Cancer 1977;39:1306-11. 14. Attwood HD, Chou ST. The longevity of clonorchis sinensis. Pathology 1978;10:153-6. 15. Cobo A, Hall RC, Torres E, Cuello CJ. Intrahepatic calculi. Arch Surg 1964;89:936-41. 16. Kalejaiye EO, Solanke TF, Adekunle OO, Ogunbiyi O. Biliary lithiasis associated with ascariasis in a Nigerian woman. Arch Surg 1977;112:645-7. 17. Phillips RD, Yune HY. Surgical helminthiasis of the biliary tract. Ann Surg 1960;152:905-10. 18. Raney R, Lilly J, McHardy G. Biliary calculus of roundworm origin. Ann Intern Med 1970;72:405-7. 19. Cremin BJ. Biliary parasites. Br J Radiol 1969;42:506-8. 20. Balasegaram M. Hepatic calculi. Ann Surg 1972;175:14954. 21. Madden JL, Vanderhayden L, Kandalabt S. The nature and surgical significance of common duct stones. Surg Gynecol Obstet 1968;126:3-8. 22. Jones MJ, Thompson JH, Brewer NS. Infectious disease of Indochinese refugees. Mayo Clin Proc 1980;55:482-8. 134
23. Wiesenthal AM, Nickels MK, Hashimoto G, Endo T, Ehrhard HB. Intestinal parasites in Southeast=Asian refugees. JAMA 1980;244:2543-4. 24. Lain SK, Wong KP, Chan PK, Ngan H, Ong GB. Recurrent pyogenic cholangitis: a study by endoscopic retrograde cholangiography. Gastroenterology 1978;74:1196-203. 25. Sato T, Suzuki N, Takashashi W, Uematsu I. Surgical management of intrahepatic gallstones. Ann Surg 1980;192: 28-32. 26. Wen CC, Lee HC. Intrapatic stones. Ann Surg 1972;175: 166-77. 27. Stock FE, Tinckler LF. Choledochoduodenostomy in the treatment of cholangiohepatitis. Surg Gynecol Obstet 1955;101:599-606. 28. Doubilet H, Mulholland JH. The surgical treatment of recurrent acute pancreatitis by endocholedochal sphincterotomy. Surg Gynecol Obstet 1948;86:295-306.
Discussion T h o m a s T. Whelan (Honolulu, HI): The Hawaiian Islands have been a favored site for the immigration of Asians, who have brought with them their endemic diseases as well as their culture. It therefore follows that biliary parasitic infestation and Oriental cholangiohepatitis are seen more often in Hawaii than elsewhere outside the Orient. This study suggests that as migrating populations have widened their final destinations, the diseases endemic to them are being seen for the first time by more physicians in different places. These diseases cause problems in other animals as well as man. Flukey Hawaiian cattle infested with the large liver flukes of cattle, sheep, and swine, Fasciola gigantica and Fasciola hepatica were treated with hexachloroethane. Dr. Alicata, parasitologist at the Hawaii Agricultural Experiment Station, University of Hawaii, proved that this infestation was due to the importation of water buffalo from China in 1880. The parasites had been transferred by snails to taro and watercress leaves that were ingested by the local cattle. These flukes rarely infect humans; 21 cases in Hawaii over a 50 year period, described in 1953, were caused by eating uncooked watercress. In 10 cases of Clonorchis sinensis infestation and 2 cases of Ascaris lumbricoides seen over the past 10 years in hospitals in Honolulu, Hawaii, the Chinese predominance was significant, and Hong Kong was the original home of most of the patients. Essentially, the indications for treatment in our cases were similar to those in the authors' cases. Six patients, including both patients harboring Ascaris in the common duct, presented with abdominal pain, chills, fever and jaundice. Adult Ascaris by its very size causes obstruction and cholangitis. Four patients with Clonorchis, the three presenting as chronic colecystitis and the one designated "asymptomatic," probably harbored Clonorchis as an incidental finding. Certainly many ~ases of Clonorchis infestations are clinically insignificant. Common duct exploration with drainage by T tube or permanent internal drainage into the duodenum or jejunum was necessary in most of our cases of biliary helminthiasis. Most of these patients also had common or hepatic duct stones. Again this experience is similar to that of the authors. In cases of ascariasis, frequently the worm dies in the common duct, becomes fragmented, covered and stained with bile, and resembles pigment stones. This may occur despite adequate vermifuge treatment. The true nature of the "stones" is noted only after piecing together The American Journal of Surgery
Biliary Lithiasis and Helminthiasis
the fragments and demonstrating a black, petrified a d u l t worm form. An interesting observation made on at least two occasions in our series was the apparent toxic effect of Hypaque ® on Clonorchis. After operative or postoperative cholangiography, increased numbers of flukes, all dead, were noted in the tubing. This observation suggests the need for a research effort in t r e a t m e n t of clonorchiasis, which up to now has been essentially untreatable. Oriental cholangiohepatitis is probably a result of a heavy Clonorchis infestation of the common and hepatic ducts. I would agree with the authors in their conclusion on this subject. The absence of the parasite in m a n y cases of Oriental cholangiohepatitis may be the result of the death of the flukes from repeated pyogenic infection in the ducts. Hemobilia may occur secondary to Oriental cholangiohepatitis and biliary helminthiasis and p r o b a b l y is the most common cause of this symptom complex worldwide. One word of caution in resecting the left hepatic lobe or a segment of it for Oriental cholangiohepatitis. The disease may later progress to involve the right hepatic duct. We saw one such case in a young Korean woman and the p l a n n e d left lobectomy was changed to choledochojejunostomy in Roux-Y configuration, which I personally favor over choledochoduodenostomy. Can the authors, from their research, tell us whether Clonorchis sinensis is an etiologic agent in some cases of bile duct carcinoma? P.C. Hou believes that some cases of cholangiocarcinoma are probably secondary to Clonorchis infestation. J o h n F. B a l f o u r (Honolulu, HI): One of the two cases Dr. Whelan mentioned was a 39 year old Filipino m a n referred from Eniwetok because of obstructive jaundice. Ultrasound d e m o n s t r a t e d dilatation of both the common bile and common hepatic ducts without any evidence of filling defects. Endoscopic retrograde cholangiopancreatography was then performed and showed a 10 cm ascaris worm in the stomach. In the duodenum, the ampulla of Vater was friable and had an ascaris worm lying across it. With contrast medium injected into the common bile duct, linear densities representing ascaris worms were seen. There was some question as to whether small stones were seen as well. The duodenum was flooded with ascaris worms. The patient was treated with Vermox ®. Two weeks later endoscopy was repeated. Dead ascaris carcasses could be seen in the common bile duct. These could not be extracted manually. Exploration and cholecystectomy were performed. The common bile duct was explored, removing the stones and ascaris worms. Another case also referred to by Dr. Whelan was a patient with Clonorchis sinensis infestation. At surgery, I spent a good deal of time trying to irrigate and instrument the parasites and stones out of the left hepatic radicles without complete success. Sphincteroplasty was performed and a T tube inserted in the common bile duct. Several sets of cholangiograms were obtained. The parasites were viable after saline irrigation b u t appeared dead after H y p a q u e injections. Unfortunately, it wasn't until some time later that we made this association, and by that time the worms had stopped appearing. I k e p t the T tube in as long as the patient would let me, trying to obtain additional parasites for in vitro testing; however, none were forthcoming. I have asked our bacteriologist to obtain some live Clonorchis for in vitro studies. I talked to him again shortly before coming to this meeting. At the T e n t h International Congress on Volume 142, July 1981
Tropical Disease and Malaria, held in Manila, he said that several studies were presented concerning a new drug Praziquantel, which appears to be the first drug manufactured that can effectively eradicate Clonorchis sinensis. It has been shown to be effective both in vitro a n d in vivo. It is marketed by the Bayer Pharmaceutical Company of West Germany. Although it has not yet been cleared by the Federal Drug Administration, the worldwide d e m a n d at present far exceeds the supply. R. C a m e r o n H a r r i s o n (Vancouver, British Columbia, Canada): I was fortunate to spend some weeks with Professor G.B. Ong recently, and his group sees a great deal of this. We are fortunate to have Dr. Burhenne as head of our Radiology Department. The most difficult common problem is stenosis of the left hepatic duct with stones within that lobe. I agree t h a t a large choledochoduodenostomy is better than Roux-Y anastomosis. Leave a large T t u b e in the common duct. Through this channel the stenosis can be dilated and the intrahepatic stones removed. If the problem returns, as it often does, endoscopic retrograde chol angiography will p e r m i t nonoperative access again to the stenotic duct through the choledochoduodenostomy. Liver resection should be the last resort. Sphincteroplasty is not effective. Koch's postulates have certainly not been satisfied with respect to Chlonorchis sinensus. They are often found in routine gallbladder surgery without the syndrome. E d w a r d P. P a s s a r o , J r . (Los Angeles, CA): Recently I spent a few months in Taiwan, and I would like to review the Taiwanese view of intrahepatic stone disease. In Taiwan Clonorchis is not considered an etiologic factor in most patients with intrahepatic stone disease, and most do not have stones in the gallbladder. In cases reviewed by Dr. Chang TzuMing and I, two thirds of the patients did not have stones in the gallbladder. In the present report, two thirds did have stones in the gallbladder. The Taiwanese consider the disease to be related mostly to socioeconomic factors. Surgeons there point out they do not see this disease in their private patients, b u t almost exclusively among the indigent. Whatever the cause, since 1974, both in Taiwan and in Hong Kong, the incidence of the disease is decreasing. T h e Taiwan surgeons consider t h a t there is no optimal surgical therapy for the disease, having tried a variety of surgical procedures and found each of them wanting. Is there any experimental evidence that infestation with Clonorchis can produce stones? It is quite clear t h a t it can be associated with inflammatory changes in the bile duct, but it is not quite clear to me that the fluke itself can give rise to stone formation. This is, as the authors have pointed out, an increasing problem in such areas as Log Angeles, which is a Pacific city, and I commend the authors for bringing this to our attention. J o h n It. D a w s o n (Seattle, WA): I was chief of surgery in a large civilian Korean hospital from 1963 to 1966. It became evident t h a t the p a t t e r n of biliary tract disease in Korea was not the same as in the United States. Most of the patients had parasites. Many patients had primary stone formation, so we did choledochoduodenostomy almost routinely as p r i m a r y t h e r a p y in patients who presented with large, scarred, thickened common bile ducts. 135
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When I returned to the United States, the first patient I encountered was an elderly Chinese woman who had immigrated to the United States some 25 years before. After I had removed the gallbladder and explored the common duct, I saw a small golden potato chip float by. I retrieved it and put it under the microscope. It was Clonorchis sinensis. I would like to ask the authors what the livers in their patients looked like. Did you do liver biopsies? Almost all of the patients I saw with Clonorchis sinensis plus stone disease had significantly scarred livers. Alex Gerber (Alhambra, CA): During a recent trip to China I was shown an exhibition of hundreds of ascaris gallstones passed in the stool after treatment with acupuncture and herbal medicine. Of special interest to me was the size of these stones. I was amazed that 2 to 3 cm stones could pass through an intact ampulla. The ability of large stones to pass into the duodenum probably explains why those of us who do not perform routine cholangiography during simple cholecystectomy do not see patients returning with missed stones. The "unsuspected" common duct stones evidently pass spontaneously without symptoms. Albert E. Yellin (closing): Dr. Whelan's experience with Oriental cholangiohepatitis and his conclusions parallel ours. His observation that Hypaque is toxic to Clonorchis suggests that intermittent irrigation of the bile ducts with Hypaque through a T tube might reduce the volume of parasitic infestation. We concur with the admonition that
136
hepatic resection be reserved for cases where the functional hepatic tissue has been largely destroyed and replaced by scar or abscess, or in cases where a hepatic duct is strictured, fibrotic and filled with stones. Several pathologists believe that some cases of cholangiocarcinoma are due to the marked ductal irritation, desquamation, epithelial hyperplasia and metaplasia that occurs with Clonorchis infestation. Although logical, this still remains to be proven. Dr. Balfour, ascaris worms seem attracted to tubular structures and have frequently been noted occluding or exiting from T tubes. In response to Dr. Harrison's question regarding biliary diversion, all methods of biliary diversion have been successfully employed. We prefer Roux-Y choledochojejunostomy, which avoids a duodenotomy in an area of marked inflammation. Dr. Passaro's review of !00 cases in Taiwan confirms our impression that this syndrome affects the bile ducts more than the gallbladder. Maki has noted that Oriental chdlangiohepatitis has diminished in Japan, where hygiene has improved and Clonorchis infestation has been reduced. He has repeatedly demonstrated adult Clonorchis or ova in the center of primary stones, where they presumably acted as the nidus for stone formation. Dr. Dawson, we did not routinely biopsy the liver to determine the extent of disease. The three patients with left lateral hepatic segmentectomy had normal right lobes and normal right ductal systems. The left lobes were fibrotic, atrophic and contained strictured ducts or abscesses.
The American Journal of Surgery
The syndrome commonly referred to as Oriental cholangiohepatitis [•], recurrent pyogenic cholangitis [2] or biliary obstruction syndrome [3] has been reported primarily from the Orient or in populations where helminthic infestation is very widespread. The purpose of this report is to review the cases of Oriental cholangiohepatitis recently seen at Los Angeles County-University of Southern California Medical Center, to describe the clinical syndrome of Oriental cholangiohepatitis and to indicate what are believed to be the appropriate therapeutic principles in these cases. These unusual biliary syndromes are now seen increasingly in the United States consequent to the trend to intercontinental migration, such as the recent influx of Southeast Asian "boat people." Features of Oriental cholangiohepatitis may include helminthiasis; choledocholithiasis, probably primary and often without cholecystolithiasis; choledochal obstruction by stone; recurrent cholangitis with stones; a propensity for stricture of the !eft hepatic duct; and hepatic abscess, scarring and atrophy of the left hepatic lobe [4-6]. The common duct stone that is typically present is presumed to be primary and is usually darkly pigmented, soft, friable and irregular in shape. Identical stones may also be found in the gallbladder. The contrast between this condition and that usually seen in the cases of cholelithiasis that develop in Western culture is apparent. A parasite may or may not be identified in either the biliary tract or stool in cases of Oriental cholangiohepatitis. The relation, if any, of the parasite t o stone formation is a subject of dispute. Often, past or present helminthic infestation cannot be proven. The clinical syndrome is uncommon in some heavily infested populations, as in India. In the opinion of From the Department of Surgery, University of Southern California School of Medicine and the Los Angeles County-University of Southern California Medical Center, Los Angeles, California. Requests for reprints should be addressed to Albert E. Yellin, MD, Department of Surgery, University of Southern California School of Medicine, 1200 North State Street, Los Angeles, California 90033. Presented at the 52nd Annual Meeting of the Pacific Coast Surgical Ass0ciation, Coronado, California, February 15-18, 1981.
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some, a parasite may act as a nidus for stone formation or provoke the disease in the bile ducts that leads to stones [1,7-9]. Others believe that the relation between choledocholithiasis and parasites is coincidental in a population that is already heavily infested and that stone formation is caused by stasis and infection with Escherichia coli [2,3,6]. The exact etiology that explains all features of the syndrome in all cases has not been established, but the circumstantial evidence implicating helminthiasis is so strong that a brief review of some relevant parasitologic factors is believed appropriate. Parasitology Some parasites, such as the schistosomes, invade the hepatic parenchyma or portal venous radicles but are not associated with biliary lithiasis. A smaller group of parasites are able to directly invade the biliary ducts. These parasites are distributed worldwide and, by conservative estimates, infect at least 500 million persons. Among these various parasites, infestation with Clonorchis sinensis, the Chinese liver fluke, has been extensively studied in relation to biliary lithiasis. These parasites enter humans or other mammals when ingested with raw fish. Eggs, passed in human or mammalian feces, hatch in water and are eaten by freshwater Bithynia snails. The parasite develops in the snail, escapes into the water and burrows between the scales and into the muscle of specifiC freshwater fish, the cyprinidoe. The human is infested upon ingesting the raw fish. The metacercariae form of the parasite ruptures in the duodenum, and the parasite migrates through the ampulla of Vater and swims up the bile duct into the terminal biliary radicles. They mature in 1 month and remain viable for at least 25 years. Larva and adults that measure about 15 mm migrate through the ducts by attaching their suckers to the ductal epithelium and pulling themselves forward. This process causes epithelial desquamation. The parasites burrow into periductal tissue, causing marked fibrosis. This ongoing process ultimately results in crypt and abscess formation. Subsequent ductal The American Journal of Surgery
Biliary Lithiasis and Helminthiasis
hyperplasia and periportal ductal fibroplasia result in stricture formation, stasis and bacterial infection. Additionally, ova or portions of the fluke, in combination with bile stasis, may form the nidus for stone formation and frequently can be identified at the center of a sectioned stone [8,10]. Masses of liver flukes or the stones themselves can cause common duct obstruction [5,11]. Cholangiocarcinoma and hepatocellular carcinoma have been observed in these cases and may be related to the hyperplasia caused by the flukes [12,13]. Clonorchis sinensis in-. festation is a lifelong disease [14]. An effective antihelminthic agent that can eradicate the infestation, has not been identified. This infestation may be manifested by only the presence of viable flukes in the biliary ducts, by stones or by the more advanced disease seen with strictures of the bile duct. Figure 1 shows Clonorchis sinensis retrieved from a common bile duct during surgery. Ascaris lumbricoides, worldwide in distribution and more prevalent than Clonorchis and other flukes, is also associated with cholangiohepatitis. In some cases portions of the ascaris worm can be found as the central nidus of a stone. Cases have been reported from Korea, Africa, South America, the United States and China [9,15-18]. In one series of cases of intestinal ascariasis from South Africa, ascarides : were demonstrated by intravenous cholangiography in the common bile ducts of 40 of the 68 patients [19]. That study demonstrates the frequency of biliary infestation. In Figure 2 an intravenous cholangiogram demonstrates an ascaris in the common bile duct. The ascarides gain entrance to the biliary tree by a complex mechanism that does not require an intermediate host. Adult worms live in the proximal small bowel of the human. Fertilized eggs are passed in the feces and develop in moist soil, where they remain viable for several years. When ingested with food, the eggs hatch in the small intestine. The larvae penetrate the intestinal wall to enter the portal circulation or lymphatics. They migrate through the liver, to the heart, and through the pulmonary artery to the lungs, where they burrow into the alveoli, molt and migrate up the bronchi to the trachea and down the esophagus into the stomach and the proximal small intestine. They molt twice in the intestine before becoming mature adults. The adult form frequently migrates through the ampulla of Vater into the common bile duct. The mature adult is up to 15 cm long and may cause common duct obstruction or become the nidus for formation of stones. The ascarides remain viable for approximately 1 year, but can be readily eradicated by oral therapy with mebendazole. After therapy they do not recur unless additional eggs are ingested. Other helminths that commonly enter the biliary tract are listed in Table I. All of the flukes can produce a syndrome comparable to infestation with Clonorchis sinensis. Strongyloides sterocoralis and Volume 142, July 1981
Figure 1. Viable Clonorchls sinensis, measuring 15 to 16 ram, which were retrieved from the common bile duct. The intraductal flukes were too numerous to count.
Figure 2. a, an ascarls worm in the common bile duct, demonstrafed by Intravenous cholanglography, b, a primary common duct stone. All traces of ascariasis were eliminated preoperatively by oral administration of mebendazole.
hookworm have been known, on rare occasions, to invade the gallbladder or biliary tree. Clinical Data
Patients: Between August 1974 and September 1980, 14 immigrants were admitted to the Los Angeles CountyUniversity of Southern California Medical Center with a syndrome consistent with Oriental cholangiohepatitis. All had biliary lithiasis, 9 had proven helminthiasis, and the remaining 5 patients came from an area of endemic helminthiasis. Eight of these patients were seen in the past 2 years. Nine emigrated from Korea and one each from Thailand, Viet Nam, China (Hong Kong), Mexico and E1 Salvador. There were 10 women and 4 men, aged 22 to 88 years (median 55). Eight patients were admitted with a syndrome characteristic of cholangitis including right
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Yellin and Donovan
TABLE I
Parasites That invade the Bile Ducts Parasite
Common Name
Source of Human Infection
Geographic Distribution
Ascaris lumbricoides Clonorchis sinensis Dicrocoelium dendriticum Fasciola gigantica Fasciola hepatica Opisthorchis felineus Opisthorchis viverrini Taenia saginata
Roundworm Chinese liver fluke ... Tropical giant fluke Sheep fluke Cat fluke Cat fluke Beef tapeworm
Fresh fruit, vegetables Raw fish Ants Watercress, lettuce Watercress Raw fish Raw fish Beef
Worldwide Far East Africa, Asia, USSR Africa, Asia, Hawaii Worldwide Eurasia Thailand Worldwide .
upper quadrant pain, fever and jaundice. Four of these eight patients had previously undergone cholecystectomy. In two of the latter a choledochoenterostomy had also been established, choledochoduodenostomy and choledochojejunostomy in one case each. Three patients were admitted with jaundice due to choledocholithiasis, and the final three patients were admitted with acute cholecystitis. Laboratory data: Among patients with cholangitis the total serum bilirubin ranged from 0.9 to 6.8 mg/100 ml (median 2.5), and the alkaline phosphatase level from 3.19 to 8.77 Bessey-Lowry (BL) units with a median of 7.0 BL units (normal 1 to 3). The bilirubin levels in the patients with choledocholithiasis without cholangitis were 6.1, 6.7 and 17 mg/100 ml, with concomitant alkaline phosphatase levels of 7.86, 3.44 and 4.65 BL units, respectively. Eosinophilia, ranging from 3 to 20 percent, was noted in 8 of the 14 patients. Roentgenography: Oral cholecystography was rarely performed because most of the patients had jaundice or had an acute right upper quadrant syndrome. One study in a nonjaundiced patient demonstrated cholecystolithiasis, and the second such study performed did not visualize the gallbladder. Intravenous cholangiography was performed in earlier years in four patients with a total serum bilirubin level below 3 mg/100 ml. Ascariasis and stones were identified in the common bile duct of one patient (Figure 2), and stones only were demonstrated in the
Figure 3. Transverse scan demonstrating a dilated 3 cm left hepatic duct and choledocholithiasis.
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common bile duct of a second patient. The common bile duct was not visualized in the final two patients. Ultrasonography of the biliary tract was performed in eight patients and identified dilated biliary ducts with stones in four (Figure 3) and only a dilated bile duct in one patient in whom choledocholithiasis was subsequently proven. Ultrasonography failed to identify dilated bile ducts that contained calculi in three patients. Cholecystolithiasis was demonstrated by ultrasound in two of the latter three patients. Endoscopic retrograde cholangiography was performed in five patients and identified dilated bile ducts and choledocholithiasis in four. The study was technically unsatisfactory in the fifth patient. An endoscopic retrograde cholangiogram demonstrating a large stone in the common bile duct of a patient with documented ascariasis is shown in Figure 4. Percutaneous transhepatic cholangiography was performed in six patients. Choledocholithiasis was noted in five patients, and stricture of the bile duct was identified in two of the five. Percutaneous transhepatic cholangiography failed to identify choledocholithiasis in one patient in whom the common duct was filled with contrast medium and stones were later proven present. A clinical syndrome consistent with gram-negative bacteremic shock followed percutaneous transhepatic cholangiography in one 88 year old woman. A cholangiogram demonstrated a normal gallbladder but a common
Figure 4, Choledocholithlasis demonstrated by endoscopic retrograde cholangiography. The arrow indicates a stricture of the left hepatic duct.
The American Journal of Surgery
Biliary Lithiasis and Helminthiasis
Figure 6. A resected lateral segment of the left hepatic lobe. The hepatic parenchyma is fibrotic and atrophic. The bile ducts are markedly dilated and contained numerous black, friable stones. Figure 5. Calculi are present In the common bile duct ( a ) and the left hepatic duct (b). The gallbladder is free of stones ( c ).
bile duct was filled with stones and showed stricture of the left hepatic duct (Figure 5). These diagnostic radiologic tests, used in varying sequence preoperatively, correctly identified disease in the common duct in all cases. Treatment
Treatment was surgical in 13 of the 14 patients. One patient, in whom oral cholecystography revealed the gallbladder to be free of stones and endoscopic retrograde cholangiography documented one stone in the common duct, underwent endoscopic papillotomy of the sphincter of Oddi with subsequent passage of the common duct stone. (This case is included due to the courtesy of Ian Renner, MD). The remaining 13 patients underwent surgery. The gallbladder was removed in nine patients that had not previously undergone cholecystectomy. Stones were present in the gallbladder of six of these nine patients and absent in three. Stones were present in the common bile duct in the latter three patients. The common bile duct was explored in all 13 surgical patients, and calculi were present in 12. In 1 of the latter 12, the ascaris that had been identified on intravenous cholangiography had passed after preoperative treatment with mebendazole. The final or 13th patient had cholecystolithiasis. When the common bile duct was opened it was found to be packed with viable flukes, identified as Clonorchis sinensis. In the remaining 12 patients, multiple stones that were generally black, soft and friable were present in the common duct with varying amounts of other debris. Stones were specifically documented in the left hepatic duct in 7 of the 12 patients. Hepatic abscesses were present in three, and in two of these there was a stricture of the left hepatic duct. Multiple stones, abscesses and extensive fibrosis were present in the left lateral segment of the left hepatic lobe of these two patients, and a left lateral hepatic segmental resection was performed. The third patient with hepatic abscess underwent drainage of the abscess and removal of stones.
Volume 142, July 1981
In one of the two patients with left hepatic duct stricture, who was admitted with cholangitis, the endoprosthetic catheter which was employed for percutaneous transhepatic cholangiography was left in place. The purpose was to attempt decompression of the biliary tree and to control sepsis before surgery. This was unsuccessful, sepsis persisted and emergency surgery was performed. The multiple stones, strictures and abscesses present explain the futility of the attempt at percutaneous decompression. The resected specimen and the removed stones are shown in Figure 6. A biliary enteric anastomosis was established in seven patients. A Roux-Y choledochojejunostomy was fashioned in six patients and choledochoduodenostomy in one. The principal indication was multiple stones in six patients and viable flukes that were diagnosed as Clonorchis sinensis in one. A choledochoenterostomy already existed in two additional patients, both of whom had recurrent cholangitis with left hepatic duct stones. In one of these two patients, a left hepatic duct stricture was present and left lateral hepatic segmental resection was performed; this was the third patient to undergo segmental resection. The other patient with left hepatic stones and previous choledochojejunostomy did not have a stricture and the choledochojejunostomy was revised. The remaining four surgical patients did not have a choledochoenterostomy established. Two had known infestation with ascariasis. The common bile duct was cleared of stones and ascariasis was eliminated by mebendazole therapy. The other two patients, previously discussed, required left lateral segmental hepatic resection for stricture of the biliary ducts and consequent hepatic abscess. Methods of treatment are summarized in Table II. Cultures of bile were positive in 12 of 13 surgical patients. The indication for surgery in the 13th patient was cholangitis, and the negative ctllture probably represents inhibition of bacterial growth by antibiotics administered preoperatively. In 7 of the 12 patients more than one organism was identified. E. coli was identified in nine patients, gamma streptococcus in five, Proteus mirabilis in four, Enterococcus in three, Pseudomonas aeruginosa in two, Klebsiella aerogenes in two and Citrobacter species
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Y e l l i n and D o n o v a n
TABLE II
Treatment Patients Procedure
(n) _
Endoscopic papillotomy Surgery Gallbladder present and removed Gallstones present Common bile duct explored Stones removed Flukes removed Left hepatic duct stones Left hepatic duct stricture Biliary enterostomy Choledochojejunostomy Choledochoduodenostomy No biliary enterostomy Previous enterostomy Ascariasis Hepatic resection Left lateral hepatic Iobectomy
1 13 9 6 13 12 1 7 3 7 6 1 6 2 2 2 3
in two. Organisms were monomicrobial in five patients and polymicrobial in seven. One nonsurgical patient had no culture. Parasites were specifically identified in nine patients. Clonorchis sinensis infestation of the common bile duct was documented at surgery in two of the nine patients. An ascaris was seen in the common bile duct in one patient on intravenous cholangiography. In six other patients a total of 15 parasites were identified. Parasites identified in the stool that are known to commonly infect the biliary tract was Ascaris (three), Clonorchis (one) and Fasciola hepatica (one). In four patients, both hookworm and Trichuris were present in the stool. Strongyloides was present in two patients. The five patients without documented parasitic infestation all had a typical syndrome of Oriental cholangiohepatitis with multiple, black, friable stones in the common bile duct. In addition, two patients had bile duct strictures and left hepatic lobe abscess. All patients with proven parasites, other than flukes, were treated with antihelminthic agents such as mebendazole, thiabendazole or piperazine. This therapy effectively eradicates parasites other than liver flukes. As previously noted, an effective agent to eradicate Clonorchis does not yet exist. Results
Seven patients had an uneventful recovery. There were eight major complications in the remaining seven patients. These consisted of intraabdominal hemorrhage in two, myocardial infarction in one, recurrent or persistent sepsis that eventually resolved in three of four patients, and a wound infection in one patient. An 88 year old patient was one of the four with persistent sepsis, and she died after left hepatic lobectomy for multiple hepatic abscesses with left hepatic duct stricture. T hat was the only death in the series. Comments
Digby [4] in 1930 described described a unique clinical syndrome seen primarily in Chinese persons
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in Hong Kong, in which cholangitis occurred in concert with primary choledocholithiasis and often without cholecystolithiasis or disease in the gallbladder. The prevalence of infestation with Clonorchis sinensis in these patients was recognized. Oriental cholangiohepatitis has been reported as the third most common cause of acute abdominal disorders in Hong Kong, exceeded only by acute appendicitis and complications of peptic ulcer [2]. The usual pathologic and clinical manifestations of Oriental cholangiohepatitis and some relevant parasitologic aspects were discussed earlier herein. T he most prominent feature of this " E a s t Asian" disease which differentiates it from the typical cholelithiasis originating in the West is the degree of choledochal and hepatic lithiasis. It is a disease of the bile ducts; the gallbladder is a secondary consideration. In Oriental cholangiohepatitis, the choledochal stones probably originate in the hepatic ducts and pass down into the common duct, where they continue to enlarge. In the West primary common duct stones are rare and may be due to bile stasis secondary to stensosis at the ampulla of Vater or, less often, to metabolic disorders or hemolytic anemias [20,21]. Most common duct stones in the West are secondary stones t hat originated as cholecystolithiasis and migrated into the common duct [21]. The cause of the calculous disease and disease of the bile ducts in Oriental cholangiohepatitis remains a matter of controversy. Helminthiasis or chronic bacterial infection are the most prominent considerations. Those who favor chronic bacteria infection rather than helminthiasis as a cause suggest that the biliary ducts may be colonized by bacteria, particularly E. coli, t hat enter the liver through the portal venous system during bouts of gastroenteritis. Such bouts are frequent in malnourished populations. According to this theory, chronic infection of the biliary ducts themselves ensues, with later formation of stones. Helminthiasis is considered incidental. The likelihood of helminthic infestation is apparent when one recognizes that 65 percent of Chinese in Hong Kong beyond the age of 1 year are infested with liver flukes [11]. T he evidence in favor of a direct relation between helminthiasis and Oriental cholangiohepatitis is strong. Additional evidence in support of a helminthic cause is that the incidence of the syndrome is decreasing in some populations where improved hygiene has reduced infestation by liver flukes [8]. Admittedly, helminthic infestation has not been proven in all reported cases of this syndrome nor in all of the cases described herein. However, if E. coli infection were the cause, it would be surprising th a t the syndrome is not seen in cases of cholelithiasis that develop in the Western world. A majority of the cases of secondary choledocholithiasis treated in the United States have bacterial colonization of the bile ducts, often with E. coll. The pathologic features of
The American Journal of Surgery
Biliary Lithiasis and Helminthiasis
Oriental cholangiohepatitis, particularly development of stricture, is not seen in these cases. Perhaps neither chronic infection nor helminthiasis is the cause of Oriental cholangiohepatitis and the disease is due to an agent and process yet unrecognized. We prefer to accept the evidence directly implicating helminthiasis as the inciting cause. Familiarity with the syndrome of Oriental cholangiohepatitis is important because of the increasing numbers of immigrants to the United States from areas where the disease is frequent and helminthic infestation is epidemic in nature. About three fourths of the Southeast Asians who are immigrants to the United States harbor intestinal parasites. Ascariasis is common not only in this immigrant group [22,23], but also in Koreans. Seven of the nine patients in this series with Oriental cholangiohepatitis and proven helminthiasis had either ascariasis or liver fluke infestation, and most were from Korea. Suspicion of the diagnosis is aroused when a patient from an area with a high incidence of Oriental cholangiohepatitis has cholangitis, previous surgery for cholelithiasis, jaundice, presence of eosinophilia, and identification of parasites or ova in the stool. The absence of eosinophilia or documented parasitic infestation does not preclude the diagnosis in an otherwise typical case. Eight of 14 patients in this series had cholangitis and 4 of these had previous biliary tract surgery. Eosinophilia was documented in seven of nine patients with proven helminthiasis. Radiologic studies can be employed to visualize the nature and extent of the disease. Because of the frequent presence of jaundice, oral cholecystography and intravenous cholangiography are of limited value. Ultrasonography of the liver and biliary tree is quite accurate in identifying the dilated ductal system and may reveal the stones. If dilated intrahepatic bile ducts packed with stones are evident, particularly in association with a gallbladder without stones, the syndrome of Oriental cholangiohepatitis must be suspected. Precise definition of the extent of ductal lithiasis and anatomic localization of strictures can be obtained by either endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography. Such studies can produce or exacerbate an episode of cholangitis if the patient is not concomitantly treated with antibiotics [24]. Recently, indwelling endoprostheses have been employed to temporarily decompress the biliary tree after percutaneous transhepatic cholangiography and to permit sepsis to resolve before undertaking any surgical procedure. Such decompression may not be effective if ductal strictures and multiple abscesses are present. The futility of this procedure was reflected in one such case in this series. Precise anatomic definition of disease, including localization of strictures, is very helpful in preoperative planning and in determination of whether a biliary drainage procedure or hepatic resection will be required. A
Volume 142, July 1981
combination of the radiologic studies just discussed indicated the correct preoperative anatomic diagnosis in all of the cases in this series. If Oriental cholangiohepatitis is suspected and time permits, multiple stool specimens should be examined for the presence of parasites, particularly those known to commonly invade the biliary tract. Treatment of helminthic infestation with an appropriate vermifuge can begin as soon as they have been identified. Frequently, the need for surgery to control sepsis associated with cholangitis is urgent and treatment of the infestation must be delayed until after surgery. Cholecystectomy, choledochostomy and extraction of stones are all that are required for eradication of the usual cholecystolithiasis with secondary choledocholithiasis that develops in the West. Ancillary biliary drainage procedures are occasionally performed for patients with countless stones or stones in the hepatic ducts [10,20,21,25,26]. The nature of the disease in Oriental cholangiohepatitis is such that the common bile duct should be explored in all cases. This is dictated by the likelihood of stones or intraductal parasites. There is a frequent need for biliary enteric anastomosis to permit the passage of any residual stones or new stones that form due to the persistent infestation. If Clonorchis sinensis has been diagnosed or is suspected, such recurrent stone formation might be anticipated, and as already stressed, a satisfactory treatment does not exist for Clonorchis infestation. Therefore a biliary enteric shunt is recommended unless infestation of the bile ducts with a parasite such as Ascaris, for which satisfactory treatment is available is proven, and only if a limited number of stones is present in such patients with a treatable parasite. This policy was pursued in the patients reported on herein. At this hospital Roux-Y choledochojejunostomy is preferred. This is apparent from its choice in six of seven cases. Choledochoduodenostomy and transduodenal sphincteroplasty have also been satisfactorily used in patients with Oriental cholangiohepatitis [3,7,15,27]. Cholecystectomy is performed irrespective of the presence of stones and particularly if the sphincter of Oddi is bypassed. In the absence of the sphincter, stasis in the gallbladder is likely to result in the formation of calculi [28]. For that reason, endoscopic papillotomy as performed in one patient in this series is unlikely to be widely adopted for patients with an intact gallbladder. The reason for the propensity for stricture of the left hepatic duct is not known, but the resulting sacculation, fibrosis and abscess formation can only be satisfactorily treated by hepatic resection. The nature of the disease in an advanced case precludes drainage as a satisfactory definitive treatment. The one patient in this series who died had persistent sepsis after biliary drainage and required left lateral segmentectomy in an attempt to eradicate intrahepatic abscess.
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Summary T h e syndrome of Oriental cholangiohepatitis is characterized by helminthiasis, choledocholithiasis often without cholecystolithiasis, biliary duct stricture and hepatic abscess. T h e c o m m o n duct stones are usually multiple, black and friable. F o u r t e e n cases have been seen in recent immigrants to the United States. T h i r t e e n patients h a d choledocholithiasis, a n d 1 had viable flukes in the ducts. Choled o c h o e n t e r o s t o m y is usually required because of multiple stones, including intrahepatic stones, or proven or p r e s u m e d infestation with Clonorchis sinensis. T h e latter, the Chinese liver fluke, is an infestation for which medical t h e r a p y does not exist. Resection, particularly of the lateral segment of the left hepatic lobe, m a y be required in cases of abscess and stones associated with stricture of the left hepatic duct.
References 1. Stock FE, Fung JY. Oriental cholangiohepatitis. Arch Surg 1962;84:409-12. 2. Cook J, Hou PC, Ho HC, McFadzean AJS. Recurrent pyogenic cholangitis. Br J Surg 1954;42:188-203. 3. Harrison-Levy A. The biliary obstruction syndrome of the Chinese. Br J Surg 1961;49:674-85. 4. Digby KH. Common duct stones of liver origin. Br J Surg 1930;17:578-91. 5. Hou PC. The pathology of clonorchis sinensis infestation of the liver. J Pathol Bacteriol 1955;70:53-64. 6. Ong GB. A study of recurrent pyogenic cholangitis. Arch Surg 1962;84:199-225. 7. Fung J. Liver fluke infestation and cholangio-hepatitis. Br J Surg 1961;48:404-15. 8. Maki T. Cholelithiasis in the Japanese. Arch Surg 1961;82: 599-612. 9. Teoh TB. A study of gall-stones and included worms in recurrent pyogenic cholangitis. J Pathol Bacteriol 1963;86:123-9. 10. Baker MS, Baker BH, Woo R. Biliary clonorchiasis. Arch Surg 1979;114:748. 11. Ameres JP, Levine MP, DeBlasi HP. A calculous clonorchiasis obstructing the common bile duct. Am Surg 1976;42: 170-2. 12. Chow CW, Allen PW. Clonorchis sinensis infestation of liver associated with cholangiocarcinoma. Pathology 1978;10: 174-5. 13. Nakashima T', Sakamoto K, Okuda K. A minute hepatocellular carcinoma found in a liver with clonorchis sinensis infection. Cancer 1977;39:1306-11. 14. Attwood HD, Chou ST. The longevity of clonorchis sinensis. Pathology 1978;10:153-6. 15. Cobo A, Hall RC, Torres E, Cuello CJ. Intrahepatic calculi. Arch Surg 1964;89:936-41. 16. Kalejaiye EO, Solanke TF, Adekunle OO, Ogunbiyi O. Biliary lithiasis associated with ascariasis in a Nigerian woman. Arch Surg 1977;112:645-7. 17. Phillips RD, Yune HY. Surgical helminthiasis of the biliary tract. Ann Surg 1960;152:905-10. 18. Raney R, Lilly J, McHardy G. Biliary calculus of roundworm origin. Ann Intern Med 1970;72:405-7. 19. Cremin BJ. Biliary parasites. Br J Radiol 1969;42:506-8. 20. Balasegaram M. Hepatic calculi. Ann Surg 1972;175:14954. 21. Madden JL, Vanderhayden L, Kandalabt S. The nature and surgical significance of common duct stones. Surg Gynecol Obstet 1968;126:3-8. 22. Jones MJ, Thompson JH, Brewer NS. Infectious disease of Indochinese refugees. Mayo Clin Proc 1980;55:482-8. 134
23. Wiesenthal AM, Nickels MK, Hashimoto G, Endo T, Ehrhard HB. Intestinal parasites in Southeast=Asian refugees. JAMA 1980;244:2543-4. 24. Lain SK, Wong KP, Chan PK, Ngan H, Ong GB. Recurrent pyogenic cholangitis: a study by endoscopic retrograde cholangiography. Gastroenterology 1978;74:1196-203. 25. Sato T, Suzuki N, Takashashi W, Uematsu I. Surgical management of intrahepatic gallstones. Ann Surg 1980;192: 28-32. 26. Wen CC, Lee HC. Intrapatic stones. Ann Surg 1972;175: 166-77. 27. Stock FE, Tinckler LF. Choledochoduodenostomy in the treatment of cholangiohepatitis. Surg Gynecol Obstet 1955;101:599-606. 28. Doubilet H, Mulholland JH. The surgical treatment of recurrent acute pancreatitis by endocholedochal sphincterotomy. Surg Gynecol Obstet 1948;86:295-306.
Discussion T h o m a s T. Whelan (Honolulu, HI): The Hawaiian Islands have been a favored site for the immigration of Asians, who have brought with them their endemic diseases as well as their culture. It therefore follows that biliary parasitic infestation and Oriental cholangiohepatitis are seen more often in Hawaii than elsewhere outside the Orient. This study suggests that as migrating populations have widened their final destinations, the diseases endemic to them are being seen for the first time by more physicians in different places. These diseases cause problems in other animals as well as man. Flukey Hawaiian cattle infested with the large liver flukes of cattle, sheep, and swine, Fasciola gigantica and Fasciola hepatica were treated with hexachloroethane. Dr. Alicata, parasitologist at the Hawaii Agricultural Experiment Station, University of Hawaii, proved that this infestation was due to the importation of water buffalo from China in 1880. The parasites had been transferred by snails to taro and watercress leaves that were ingested by the local cattle. These flukes rarely infect humans; 21 cases in Hawaii over a 50 year period, described in 1953, were caused by eating uncooked watercress. In 10 cases of Clonorchis sinensis infestation and 2 cases of Ascaris lumbricoides seen over the past 10 years in hospitals in Honolulu, Hawaii, the Chinese predominance was significant, and Hong Kong was the original home of most of the patients. Essentially, the indications for treatment in our cases were similar to those in the authors' cases. Six patients, including both patients harboring Ascaris in the common duct, presented with abdominal pain, chills, fever and jaundice. Adult Ascaris by its very size causes obstruction and cholangitis. Four patients with Clonorchis, the three presenting as chronic colecystitis and the one designated "asymptomatic," probably harbored Clonorchis as an incidental finding. Certainly many ~ases of Clonorchis infestations are clinically insignificant. Common duct exploration with drainage by T tube or permanent internal drainage into the duodenum or jejunum was necessary in most of our cases of biliary helminthiasis. Most of these patients also had common or hepatic duct stones. Again this experience is similar to that of the authors. In cases of ascariasis, frequently the worm dies in the common duct, becomes fragmented, covered and stained with bile, and resembles pigment stones. This may occur despite adequate vermifuge treatment. The true nature of the "stones" is noted only after piecing together The American Journal of Surgery
Biliary Lithiasis and Helminthiasis
the fragments and demonstrating a black, petrified a d u l t worm form. An interesting observation made on at least two occasions in our series was the apparent toxic effect of Hypaque ® on Clonorchis. After operative or postoperative cholangiography, increased numbers of flukes, all dead, were noted in the tubing. This observation suggests the need for a research effort in t r e a t m e n t of clonorchiasis, which up to now has been essentially untreatable. Oriental cholangiohepatitis is probably a result of a heavy Clonorchis infestation of the common and hepatic ducts. I would agree with the authors in their conclusion on this subject. The absence of the parasite in m a n y cases of Oriental cholangiohepatitis may be the result of the death of the flukes from repeated pyogenic infection in the ducts. Hemobilia may occur secondary to Oriental cholangiohepatitis and biliary helminthiasis and p r o b a b l y is the most common cause of this symptom complex worldwide. One word of caution in resecting the left hepatic lobe or a segment of it for Oriental cholangiohepatitis. The disease may later progress to involve the right hepatic duct. We saw one such case in a young Korean woman and the p l a n n e d left lobectomy was changed to choledochojejunostomy in Roux-Y configuration, which I personally favor over choledochoduodenostomy. Can the authors, from their research, tell us whether Clonorchis sinensis is an etiologic agent in some cases of bile duct carcinoma? P.C. Hou believes that some cases of cholangiocarcinoma are probably secondary to Clonorchis infestation. J o h n F. B a l f o u r (Honolulu, HI): One of the two cases Dr. Whelan mentioned was a 39 year old Filipino m a n referred from Eniwetok because of obstructive jaundice. Ultrasound d e m o n s t r a t e d dilatation of both the common bile and common hepatic ducts without any evidence of filling defects. Endoscopic retrograde cholangiopancreatography was then performed and showed a 10 cm ascaris worm in the stomach. In the duodenum, the ampulla of Vater was friable and had an ascaris worm lying across it. With contrast medium injected into the common bile duct, linear densities representing ascaris worms were seen. There was some question as to whether small stones were seen as well. The duodenum was flooded with ascaris worms. The patient was treated with Vermox ®. Two weeks later endoscopy was repeated. Dead ascaris carcasses could be seen in the common bile duct. These could not be extracted manually. Exploration and cholecystectomy were performed. The common bile duct was explored, removing the stones and ascaris worms. Another case also referred to by Dr. Whelan was a patient with Clonorchis sinensis infestation. At surgery, I spent a good deal of time trying to irrigate and instrument the parasites and stones out of the left hepatic radicles without complete success. Sphincteroplasty was performed and a T tube inserted in the common bile duct. Several sets of cholangiograms were obtained. The parasites were viable after saline irrigation b u t appeared dead after H y p a q u e injections. Unfortunately, it wasn't until some time later that we made this association, and by that time the worms had stopped appearing. I k e p t the T tube in as long as the patient would let me, trying to obtain additional parasites for in vitro testing; however, none were forthcoming. I have asked our bacteriologist to obtain some live Clonorchis for in vitro studies. I talked to him again shortly before coming to this meeting. At the T e n t h International Congress on Volume 142, July 1981
Tropical Disease and Malaria, held in Manila, he said that several studies were presented concerning a new drug Praziquantel, which appears to be the first drug manufactured that can effectively eradicate Clonorchis sinensis. It has been shown to be effective both in vitro a n d in vivo. It is marketed by the Bayer Pharmaceutical Company of West Germany. Although it has not yet been cleared by the Federal Drug Administration, the worldwide d e m a n d at present far exceeds the supply. R. C a m e r o n H a r r i s o n (Vancouver, British Columbia, Canada): I was fortunate to spend some weeks with Professor G.B. Ong recently, and his group sees a great deal of this. We are fortunate to have Dr. Burhenne as head of our Radiology Department. The most difficult common problem is stenosis of the left hepatic duct with stones within that lobe. I agree t h a t a large choledochoduodenostomy is better than Roux-Y anastomosis. Leave a large T t u b e in the common duct. Through this channel the stenosis can be dilated and the intrahepatic stones removed. If the problem returns, as it often does, endoscopic retrograde chol angiography will p e r m i t nonoperative access again to the stenotic duct through the choledochoduodenostomy. Liver resection should be the last resort. Sphincteroplasty is not effective. Koch's postulates have certainly not been satisfied with respect to Chlonorchis sinensus. They are often found in routine gallbladder surgery without the syndrome. E d w a r d P. P a s s a r o , J r . (Los Angeles, CA): Recently I spent a few months in Taiwan, and I would like to review the Taiwanese view of intrahepatic stone disease. In Taiwan Clonorchis is not considered an etiologic factor in most patients with intrahepatic stone disease, and most do not have stones in the gallbladder. In cases reviewed by Dr. Chang TzuMing and I, two thirds of the patients did not have stones in the gallbladder. In the present report, two thirds did have stones in the gallbladder. The Taiwanese consider the disease to be related mostly to socioeconomic factors. Surgeons there point out they do not see this disease in their private patients, b u t almost exclusively among the indigent. Whatever the cause, since 1974, both in Taiwan and in Hong Kong, the incidence of the disease is decreasing. T h e Taiwan surgeons consider t h a t there is no optimal surgical therapy for the disease, having tried a variety of surgical procedures and found each of them wanting. Is there any experimental evidence that infestation with Clonorchis can produce stones? It is quite clear t h a t it can be associated with inflammatory changes in the bile duct, but it is not quite clear to me that the fluke itself can give rise to stone formation. This is, as the authors have pointed out, an increasing problem in such areas as Log Angeles, which is a Pacific city, and I commend the authors for bringing this to our attention. J o h n It. D a w s o n (Seattle, WA): I was chief of surgery in a large civilian Korean hospital from 1963 to 1966. It became evident t h a t the p a t t e r n of biliary tract disease in Korea was not the same as in the United States. Most of the patients had parasites. Many patients had primary stone formation, so we did choledochoduodenostomy almost routinely as p r i m a r y t h e r a p y in patients who presented with large, scarred, thickened common bile ducts. 135
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When I returned to the United States, the first patient I encountered was an elderly Chinese woman who had immigrated to the United States some 25 years before. After I had removed the gallbladder and explored the common duct, I saw a small golden potato chip float by. I retrieved it and put it under the microscope. It was Clonorchis sinensis. I would like to ask the authors what the livers in their patients looked like. Did you do liver biopsies? Almost all of the patients I saw with Clonorchis sinensis plus stone disease had significantly scarred livers. Alex Gerber (Alhambra, CA): During a recent trip to China I was shown an exhibition of hundreds of ascaris gallstones passed in the stool after treatment with acupuncture and herbal medicine. Of special interest to me was the size of these stones. I was amazed that 2 to 3 cm stones could pass through an intact ampulla. The ability of large stones to pass into the duodenum probably explains why those of us who do not perform routine cholangiography during simple cholecystectomy do not see patients returning with missed stones. The "unsuspected" common duct stones evidently pass spontaneously without symptoms. Albert E. Yellin (closing): Dr. Whelan's experience with Oriental cholangiohepatitis and his conclusions parallel ours. His observation that Hypaque is toxic to Clonorchis suggests that intermittent irrigation of the bile ducts with Hypaque through a T tube might reduce the volume of parasitic infestation. We concur with the admonition that
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hepatic resection be reserved for cases where the functional hepatic tissue has been largely destroyed and replaced by scar or abscess, or in cases where a hepatic duct is strictured, fibrotic and filled with stones. Several pathologists believe that some cases of cholangiocarcinoma are due to the marked ductal irritation, desquamation, epithelial hyperplasia and metaplasia that occurs with Clonorchis infestation. Although logical, this still remains to be proven. Dr. Balfour, ascaris worms seem attracted to tubular structures and have frequently been noted occluding or exiting from T tubes. In response to Dr. Harrison's question regarding biliary diversion, all methods of biliary diversion have been successfully employed. We prefer Roux-Y choledochojejunostomy, which avoids a duodenotomy in an area of marked inflammation. Dr. Passaro's review of !00 cases in Taiwan confirms our impression that this syndrome affects the bile ducts more than the gallbladder. Maki has noted that Oriental chdlangiohepatitis has diminished in Japan, where hygiene has improved and Clonorchis infestation has been reduced. He has repeatedly demonstrated adult Clonorchis or ova in the center of primary stones, where they presumably acted as the nidus for stone formation. Dr. Dawson, we did not routinely biopsy the liver to determine the extent of disease. The three patients with left lateral hepatic segmentectomy had normal right lobes and normal right ductal systems. The left lobes were fibrotic, atrophic and contained strictured ducts or abscesses.
The American Journal of Surgery