Journal of Surgical Oncology 47:131-135 (1991)
lntrahepatic Cholangiocarcinoma in Hepatolithiasis: A Frequently Overlooked Disease SHYR-MING SHEEN-CHEN, MD, FONG-FU CHOU, MD, AND HOCK-LIEW ENG, MD From the Division of General Surgery, Department of Surgery and Pathology, Chang-Cung Memorial Hospital at Kaohsiung, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan, Republic of China
Five cases of intrahepatic cholangiocarcinoma were found among 101 cases of hepatolithiasis. There was no definite sign of cholangiocarcinoma in ERCP and image studies of four cases. The possibility of the existence of occult cholangiocarcinoma should be kept in mind, especially when unusual presentations, such as body weight loss, anemia, palpable abdominal mass, and intractable pain, appear. An intraoperative frozensection examination should be considered under the following circumstances: (1) whitish nodular mass over liver, (2) mucinous substance within bile duct, and (3) enlarged, firm lymph nodes clustered along the hepatic arteries and/or celiac arteries, KEYWORDS:choledochotomy, abdominal ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP)
INTRODUCTION Hepatolithiasis, rarely encountered in the Western world, has a high incidence in Taiwan, Japan, and other countries of East Asia [ 1 4 1 . Cholangiocarcinoma is said to be rarely found in hepatolithiasis. However, this phenomenon does exist [5-10]. Recently, five patients with cholangiocarcinoma among 101 cases of hepatolithiasis (5%) between December 1987 and December 1988 were treated at Chang-Gung Memorial Hospital at Kaohsiung in southern Taiwan. The retrospective study of these cases notes the existence of this rare entity and provides some diagnostic clues to this frequently overlooked disease.
intrahepatic stones without definite sign of cholangiocarcinoma (Fig. 1). Choledocholithotomy , operative choledochofiberoscopy, and left lateral segmentectomy of the liver were performed with the diagnosis of hepatolithiasis. The resected liver showed thickened bile duct with stones. Fibrosis and several whitish nodular masses were noted over the left liver. The histological diagnosis was cholangiocarcinoma (Fig. 2).
Case 2 A 58-year-old woman suffered from body weight loss of 5 kg, right upper quadrant pain, and a palpable abdominal mass for six months. Abdominal utrasonography and aspiration cytology were performed by outside clinics. Laparotomy was performed at this hospital under CASE REPORTS the impression of hepatolithiasis associated with maligCase 1 nant tumor. Enlarged firm lymph nodes were found A 48-year-old man suffered from left flank pain for one clustered along the celiac and hepatic arteries. Choleweek prior to admission. Laboratory data after admission dochotomy and left lobectomy were performed. Stones showed total bilirubin, 13.4 mgldl; SGOT, 54 IU; and a mucinous substance were found within the thickSGOT, 146 IU; alkaline phosphatase, 218 IU; hemoglobin, 9.1 /dl; and white blood cell (WBC) count, 15,600 cells/mm5 . Abdominal ultrasonography and endoscopic Accepted for publication September 13, 1990. reprint requests to Dr. Shyr-Ming Sheen-Chen, Division of retrograde cholangiopancreatography (ERCP) showed Address General Surgery, Department of Surgery, Chang-Gung Memorial bilateral dilated intrahepatic ducts with stones. Ab- Hospital at Kaohsiung, 123 Ta-Pei Road, Niao Sung Hsiang, Kaohsidominal computed tomography also showed bilateral ung Hsien, Taiwan, Republic of China. 0 1991 Wiley-Liss, Inc.
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Sheen-Chen et al.
Fig. 1. Computed tomography showed dilated intrahepatic ducts with stones
ened duct. The histological diagnosis was stones and cholangiocarcinoma.
Case 3 A 53-year-old man was admitted with complaints of body weight loss of 12 kg, chills, fever for two weeks, and jaundice for 10 days. Laboratory data showed elevated total bilirubin 14.10 mgidl and alkaline phosphatase, 453 IU. He underwent laparotomy with the diagnosis of hepatolithiasis after abdominal ultrasonography and ERCP examination. Fibrosis, whitish nodular masses over the left lateral liver, and enlarged firm lymph nodes clustered along the choledochal duct, were found. Frozen section of these enlarged lymph nodes revealed metastatic adenocarcinoma. The whole abdomen was examined, and no other abnormality was found. Cholangiocarcinoma with lymph node metastasis was the impression. Choledochotomy and left lateral segmentectomy were performed. Stones and a mucinous substance were found within the thickened duct. Histological examination confirmed the diagnosis of hepatolithiasis associated with cholangiocarcinoma. Case 4 A 30-year-old woman was admitted with complaints of intermittent fever, chills, and right upper quadrant pain for 3 months. Laboratory data showed mild elevated SGOT, 166 IU, and alkaline phosphatase, 235 IU.
Hepatolithiasis was diagnosed, but an operation was refused by patient. She agreed to undergo laparotomy six months later because of intractable pain. Fibrosis, whitish nodular masses over the left lateral liver, and enlarged firm lymph nodes clustered along the celiac and hepatic arteries were found. Choledochotomy , left lateral segmentectomy, and lymph node biopsy were performed. Stones and a mucinous substance were found within the thickened duct. Histological examination revealed cholangiocarcinoma with metastasis to lymph nodes.
Case 5 A 68-year-old man was admitted with complaints of body weight loss of 5 kg, fever, chills, right upper quadrant pain, and yellowish discoloration of skin for 1 week. Laboratory data showed total bilirubin, 9.8 mgidl, SGOT, 79 IU, hemoglobin, 7.2 gidl, and 16,900 WBCi mm’. The patient underwent operation with the impression of left intrahepatic stones with abscess after evaluation by abdominal ultrasonography , ERCP, and 99m Tc-phytate liver scan. Left lobectomy was performed. Stones, and a mucinous substance were found within the duct. Frozen section examination confirmed the diagnosis of cholangiocarcinoma. Choledochal bile culture taken during operation was positive for gram-negative micro-organisms in all five cases, the most common being Eschevichia coli and Klebsiella pneurnoniae. No evidence of parasite infection was found in these patients.
Cholangiocarcinoma
Fig. 2. Microscopy of adenocarcinoma of bile duct. (Hematoxylin and eosin.
DISCUSSION In 1942, Sanes and MacCallum [5] first reported two cases of cholangiocarcinoma associated with hepatolithiasis. Other authors later have reported the same phenomenon. The incidence of this rare entity ranges from 2.36% to 10% [&lo]. In this series, five cases of cholangiocarcinoma were found among 101 cases of hepatolithiasis ( 5 % ) between December 1987 and December 1988. Most hepatolithiases are located in the left intrahepatic duct [2,3, lo]; this type of cholangiocarcinoma also usually occurs in the left intrahepatic duct [8,9]. Among the five cases of this series, stones were located in the left duct in four patients and in bilateral ducts in one patient. All the cholangiocarcinomas in this series occurred in the left intrahepatic duct. This may reflect the close relationship between hepatolithiasis and cholangiocarcinoma. Multiple factors are probably responsible for the development of bile duct cancer. Although there is no conclusive evidence that stones can cause the development of cholangiocarcinoma, bile stasis and bacterial infection seem to be the most important causative factor [6,12]. Hou [ 131, in animal experiments, discovered that prolonged severe infection resulted in adenomatous hyperplasia and bile duct cancer. Congenital dilatation of the intrahepatic duct, choledochal cyst, polycystic liver disease, and Clonorchis sinensis infection have also been reported in association with cholangiocarcinoma [ 13-
133
X25.)
161. In this series, stricture of the left intrahepatic duct with peripheral cystic dilatation and gram-negative bacterial infection of choledochal bile were demonstrated in all five cases. Although it is not clear whether these strictures and dilatations are congenital or acquired, the pathological changes of the bile duct and the bacterial infection of bile associated with hepatolithiasis seem closely related to this rare entity. Because hepatolithiasis is rarely encountered in the Western world but is not uncommon in Taiwan, Japan, and other countries of East Asia [ 1-41, there is usually no difficulty in establishing the diagnosis of hepatolithiasis [ 11,17-191. However, the diagnosis of intrahepatic cholangiocarcinoma in hepatolithiasis is very difficult. Although ERCP or image studies may show a suspicious filling defect or hyperechoic mass in some patients at a more advanced stage, most cases of this rare phenomenon were frequently overlooked because: ( I ) cholangiocarcinoma usually infiltrates the bile duct without mass formation; ( 2 ) cholangiography is insufficient to demonstrate the intraluminal changes of cholangiocarcinoma due to the coexistence of stones; and (3) stricture or stenosis caused by cholangiocarcinoma is not easy to differentiate from that caused by stones [7-91. In this series, excluding case 2 (advanced stage proved by outside clinics), there was no definite sign of cholangiocarcinoma in the preoperative endoscopic retrograde cholangiopancreatography and image studies (sonograDhv. ,, liver scan and comDuterized tomograuhv) (Table I). I
"
I
-
134
Sheen-Chen et a].
TABLE I. Unusual Clinical Presentations, Operative Findings, and Initial Impressions of ERCP and Image Studies*
Age (years)/sex Body weight loss Anemia Abdominal mass Intractable pain Ultrasonography ERCP Liver scan CT scan Whitish nodular mass over liver Mucinous substance within duct Enlarged, firm lymph nodes
Case 1
Case 2
Case 3
Case 4
Case 5
48/male A P A A Stones Stones NP Stones P A A
58lfemale P A P A Stones and hyperechoic lesion Nonvisualization of left IHD NP NP A P P
53/male P A A A Stones Stones NP NP P P P
30lfemale A A A P Stones Stones NP NP P P P
68/male P P A A Stones Stones Abscess NP A
P A
*Abbreviations: A, absent; P, present; NP, not performed; ERCP, endoscopic retrograde cholangiopancreaticography; IHD, intrahepatic duct.
Therefore, an initial “negative” ERCP or image study does not rule out the possibility of this frequently overlooked disease [7-91. The possibility of existence of intrahepatic cholangiocarcinoma should still be kept in mind even if the preoperative workup of hepatolithiasis is “negative” for associated neoplasm. Aside from the classical cholangitis of hepatolithiasis, there were some unusual presentations, including body weight loss (cases 2, 3, 3, anemia (cases 1, 5 ) , palpable abdominal mass (case 2), and intractable pain (case 4) in this series (Table I). We believe that the possibility of occult cholangiocarcinoma in hepatolithiasis should be considered when these unusual presentations appear. Repeated cholangitis and abscess formation attributable to hepatolithiasis usually leads to chronic fibrosis, contracture and adhesion of the liver to adjacent organs. Cholangiocarcinoma in hepatolithiasis may have the same pathological changes, making the differential diagnosis rather difficult, even during operation. Operative choledochofiberoscopy was said to be useful in the diagnosis of biliary tract neoplasms [20]. However, the situation seems somewhat difficult in the peripheral type cholangiocarcinoma with hepatolithiasis. The biliary tree usually can not be well visualized due to the stenosis of duct and firm impaction of hepatolithiasis. Intrahepatic stones should be first removed, as many as possible through both choledochotomy and partial hepatectomy (or hepatotomy) for exposing the post-stenotic intrahepatic duct, and well visualization of the whole biliary tree should be obtained later by thorough choledochofiberoscopy. An infiltrating lesion or mucinous substance can sometimes be detected. Several gross findings were noted in this series which may be unique to cholangiocarcinoma (Table I). These unusual gross findings included: (1) whitish nodular masses over liver (cases 1, 3, 4); (2) mucinous substance within the bile duct (cases 2-5); and (3) enlarged firm lymph nodes clustered along hepatic
arteries and/or celiac arteries (cases 2-4). Histological examinations finally confirmed the diagnosis. For a thorough therapeutic plan, frozen-section examination of enlarged lymph nodes, suspicious whitish nodular masses, and/or resected liver should be considered under these circumstances.
SUMMARY Intrahepatic cholangiocarcinoma in hepatolithiasis, although rare, does exist. With knowledge of its existence, careful survey of clinical presentations, proper preoperative ERCP andlor image studies, thorough intraoperative choledochofiberoscopy , and detailed intraoperative examination, the diagnosis of this frequently overlooked disease should be obtained earlier. REFERENCES 1. Wen CC, Lee HC: Intrahepatic stones: A clinical study. Ann Surg
175:166-1 77. 1972. 2 . Galasegaram M: Hepatic calculi. Ann Surg 175:149-154, 1972. 3. Sheen PC, Ker CG: lntrahepatic stones. 11. Clinical study. J Formosan Med Assoc 80:1217-1225, 1981 [in Chinese]. 4. Nakayma Y, Soloway RD, Nakamat: Hepatolithiasis in East Asia: Retrospective study. Dig Dis Sci 3 I :21-26, 1986. 5. Sanes S, MacCallum JD: Primary carcinoma of the liver. Cholangioma in hepatolithiasis. Am J Pathol 18:675-683, 1942. 6. Koga A, Ichimiya H, Yamaguchi K, Miyazaki K, Nakayama F: Hepatolithiasis associated with cholangiocarcinoma possible etiology significance. Cancer 55:2826-2829, 1985. 7. YoshiMoto H, Ikeda S, Tanaka M, Matsuomto S: lntrahepatic cholangiocarcinoma associated with hepatolithiasis. Gastrointest Endosc 31:26@263, 1985. 8. Chen PH, Lo HW, Wane CS, Tsai KR, Chen YC, Lin KY, Siauw CP, Hwang RR, Liu MH, KOHC, Chen TY: Cholangiocarcinoma in hepatolithiasis. J Clin Gastroenterol 6539-547, 1984. 9. Yi-Yin J , Miin Fu C, Chia-Siu W, Long-Bin .I,Liaw YF, Chen TJ: Intrahepatic stones in association with cholangiocarcinoma J Surg Assoc ROC 21:181-187, 1988 [in Chinese]. 10. Ohta G , Nakayama Y, Terada T: “Pathology of Hepatolithiasis: Cholangitis and Cholangiocarcinoma. Intrahepatic Calculi.” New York: Alan R Liss, 1984, pp 91-1 13. 11. Chen PC: Diagnosis of intrahepatic stones by ERCP. Gastroenterol Endosc 21:1190-1200, 1979.
Cholangiocarcinoma 12. Falchuk KR, Lesser PB, Galdabini J, Isselbacher KJ: Cholangiocarcinoma as related to chronic intrahepatic chlangitis and hepatolithiasis. Am J Gastroenterol 66:57-61, 1976. 13. Hou PC: Pathological changes in the intrahepatic bile ducts of cats infected with clonorchis sinensis. J Pathol 89:357-364, 1975. 14. Belamaric J: Intrahepatic bile duct carcinoma and C. sinensis infection in Hong Kong. Cancer 31:468473, 1972. 15. Gallagher PJ. Millis RR, Mitchinson MJ: Congenital dilatation of the i6ahepatic bile ducts with cholangiocarcinoma. J Clin Pathol 25:804808. 1972. 16. Willis RA: Carcinoma arising in congenital cysts of the liver. J Pathol 55:492495, 1943. 17. Huong MF, Liaw YF, Wu CS: Comparison of intravenous
135
radionuclide cholescintigraphy and endoscopic retrograde cholangiography in the diagnosis of intrahepatic gall stones. Br J Radio1 54:302-306, 1981. 18. Chang-Chien CS, Wu CS, Chen PC, Liaw YF: Clinical study of primary intraheptic stones. J Formosan Med Assoc 82:936940, 1983. 19. Pan S, Liao CH: Intrahepatic stones probable factors, clinical manifestation and recent advances in diagnosis. J Formosan Med Assoc 82:226-238, 1983. 20. Tompkins RK, Johnson J, Storm FK, Longmire WP: Operative endoscopy in the management of biliary tract neoplasms. Am J Surg 132:174-182, 1976.
lntrahepatic Cholangiocarcinoma in Hepatolithiasis: A Frequently Overlooked Disease SHYR-MING SHEEN-CHEN, MD, FONG-FU CHOU, MD, AND HOCK-LIEW ENG, MD From the Division of General Surgery, Department of Surgery and Pathology, Chang-Cung Memorial Hospital at Kaohsiung, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan, Republic of China
Five cases of intrahepatic cholangiocarcinoma were found among 101 cases of hepatolithiasis. There was no definite sign of cholangiocarcinoma in ERCP and image studies of four cases. The possibility of the existence of occult cholangiocarcinoma should be kept in mind, especially when unusual presentations, such as body weight loss, anemia, palpable abdominal mass, and intractable pain, appear. An intraoperative frozensection examination should be considered under the following circumstances: (1) whitish nodular mass over liver, (2) mucinous substance within bile duct, and (3) enlarged, firm lymph nodes clustered along the hepatic arteries and/or celiac arteries, KEYWORDS:choledochotomy, abdominal ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP)
INTRODUCTION Hepatolithiasis, rarely encountered in the Western world, has a high incidence in Taiwan, Japan, and other countries of East Asia [ 1 4 1 . Cholangiocarcinoma is said to be rarely found in hepatolithiasis. However, this phenomenon does exist [5-10]. Recently, five patients with cholangiocarcinoma among 101 cases of hepatolithiasis (5%) between December 1987 and December 1988 were treated at Chang-Gung Memorial Hospital at Kaohsiung in southern Taiwan. The retrospective study of these cases notes the existence of this rare entity and provides some diagnostic clues to this frequently overlooked disease.
intrahepatic stones without definite sign of cholangiocarcinoma (Fig. 1). Choledocholithotomy , operative choledochofiberoscopy, and left lateral segmentectomy of the liver were performed with the diagnosis of hepatolithiasis. The resected liver showed thickened bile duct with stones. Fibrosis and several whitish nodular masses were noted over the left liver. The histological diagnosis was cholangiocarcinoma (Fig. 2).
Case 2 A 58-year-old woman suffered from body weight loss of 5 kg, right upper quadrant pain, and a palpable abdominal mass for six months. Abdominal utrasonography and aspiration cytology were performed by outside clinics. Laparotomy was performed at this hospital under CASE REPORTS the impression of hepatolithiasis associated with maligCase 1 nant tumor. Enlarged firm lymph nodes were found A 48-year-old man suffered from left flank pain for one clustered along the celiac and hepatic arteries. Choleweek prior to admission. Laboratory data after admission dochotomy and left lobectomy were performed. Stones showed total bilirubin, 13.4 mgldl; SGOT, 54 IU; and a mucinous substance were found within the thickSGOT, 146 IU; alkaline phosphatase, 218 IU; hemoglobin, 9.1 /dl; and white blood cell (WBC) count, 15,600 cells/mm5 . Abdominal ultrasonography and endoscopic Accepted for publication September 13, 1990. reprint requests to Dr. Shyr-Ming Sheen-Chen, Division of retrograde cholangiopancreatography (ERCP) showed Address General Surgery, Department of Surgery, Chang-Gung Memorial bilateral dilated intrahepatic ducts with stones. Ab- Hospital at Kaohsiung, 123 Ta-Pei Road, Niao Sung Hsiang, Kaohsidominal computed tomography also showed bilateral ung Hsien, Taiwan, Republic of China. 0 1991 Wiley-Liss, Inc.
132
Sheen-Chen et al.
Fig. 1. Computed tomography showed dilated intrahepatic ducts with stones
ened duct. The histological diagnosis was stones and cholangiocarcinoma.
Case 3 A 53-year-old man was admitted with complaints of body weight loss of 12 kg, chills, fever for two weeks, and jaundice for 10 days. Laboratory data showed elevated total bilirubin 14.10 mgidl and alkaline phosphatase, 453 IU. He underwent laparotomy with the diagnosis of hepatolithiasis after abdominal ultrasonography and ERCP examination. Fibrosis, whitish nodular masses over the left lateral liver, and enlarged firm lymph nodes clustered along the choledochal duct, were found. Frozen section of these enlarged lymph nodes revealed metastatic adenocarcinoma. The whole abdomen was examined, and no other abnormality was found. Cholangiocarcinoma with lymph node metastasis was the impression. Choledochotomy and left lateral segmentectomy were performed. Stones and a mucinous substance were found within the thickened duct. Histological examination confirmed the diagnosis of hepatolithiasis associated with cholangiocarcinoma. Case 4 A 30-year-old woman was admitted with complaints of intermittent fever, chills, and right upper quadrant pain for 3 months. Laboratory data showed mild elevated SGOT, 166 IU, and alkaline phosphatase, 235 IU.
Hepatolithiasis was diagnosed, but an operation was refused by patient. She agreed to undergo laparotomy six months later because of intractable pain. Fibrosis, whitish nodular masses over the left lateral liver, and enlarged firm lymph nodes clustered along the celiac and hepatic arteries were found. Choledochotomy , left lateral segmentectomy, and lymph node biopsy were performed. Stones and a mucinous substance were found within the thickened duct. Histological examination revealed cholangiocarcinoma with metastasis to lymph nodes.
Case 5 A 68-year-old man was admitted with complaints of body weight loss of 5 kg, fever, chills, right upper quadrant pain, and yellowish discoloration of skin for 1 week. Laboratory data showed total bilirubin, 9.8 mgidl, SGOT, 79 IU, hemoglobin, 7.2 gidl, and 16,900 WBCi mm’. The patient underwent operation with the impression of left intrahepatic stones with abscess after evaluation by abdominal ultrasonography , ERCP, and 99m Tc-phytate liver scan. Left lobectomy was performed. Stones, and a mucinous substance were found within the duct. Frozen section examination confirmed the diagnosis of cholangiocarcinoma. Choledochal bile culture taken during operation was positive for gram-negative micro-organisms in all five cases, the most common being Eschevichia coli and Klebsiella pneurnoniae. No evidence of parasite infection was found in these patients.
Cholangiocarcinoma
Fig. 2. Microscopy of adenocarcinoma of bile duct. (Hematoxylin and eosin.
DISCUSSION In 1942, Sanes and MacCallum [5] first reported two cases of cholangiocarcinoma associated with hepatolithiasis. Other authors later have reported the same phenomenon. The incidence of this rare entity ranges from 2.36% to 10% [&lo]. In this series, five cases of cholangiocarcinoma were found among 101 cases of hepatolithiasis ( 5 % ) between December 1987 and December 1988. Most hepatolithiases are located in the left intrahepatic duct [2,3, lo]; this type of cholangiocarcinoma also usually occurs in the left intrahepatic duct [8,9]. Among the five cases of this series, stones were located in the left duct in four patients and in bilateral ducts in one patient. All the cholangiocarcinomas in this series occurred in the left intrahepatic duct. This may reflect the close relationship between hepatolithiasis and cholangiocarcinoma. Multiple factors are probably responsible for the development of bile duct cancer. Although there is no conclusive evidence that stones can cause the development of cholangiocarcinoma, bile stasis and bacterial infection seem to be the most important causative factor [6,12]. Hou [ 131, in animal experiments, discovered that prolonged severe infection resulted in adenomatous hyperplasia and bile duct cancer. Congenital dilatation of the intrahepatic duct, choledochal cyst, polycystic liver disease, and Clonorchis sinensis infection have also been reported in association with cholangiocarcinoma [ 13-
133
X25.)
161. In this series, stricture of the left intrahepatic duct with peripheral cystic dilatation and gram-negative bacterial infection of choledochal bile were demonstrated in all five cases. Although it is not clear whether these strictures and dilatations are congenital or acquired, the pathological changes of the bile duct and the bacterial infection of bile associated with hepatolithiasis seem closely related to this rare entity. Because hepatolithiasis is rarely encountered in the Western world but is not uncommon in Taiwan, Japan, and other countries of East Asia [ 1-41, there is usually no difficulty in establishing the diagnosis of hepatolithiasis [ 11,17-191. However, the diagnosis of intrahepatic cholangiocarcinoma in hepatolithiasis is very difficult. Although ERCP or image studies may show a suspicious filling defect or hyperechoic mass in some patients at a more advanced stage, most cases of this rare phenomenon were frequently overlooked because: ( I ) cholangiocarcinoma usually infiltrates the bile duct without mass formation; ( 2 ) cholangiography is insufficient to demonstrate the intraluminal changes of cholangiocarcinoma due to the coexistence of stones; and (3) stricture or stenosis caused by cholangiocarcinoma is not easy to differentiate from that caused by stones [7-91. In this series, excluding case 2 (advanced stage proved by outside clinics), there was no definite sign of cholangiocarcinoma in the preoperative endoscopic retrograde cholangiopancreatography and image studies (sonograDhv. ,, liver scan and comDuterized tomograuhv) (Table I). I
"
I
-
134
Sheen-Chen et a].
TABLE I. Unusual Clinical Presentations, Operative Findings, and Initial Impressions of ERCP and Image Studies*
Age (years)/sex Body weight loss Anemia Abdominal mass Intractable pain Ultrasonography ERCP Liver scan CT scan Whitish nodular mass over liver Mucinous substance within duct Enlarged, firm lymph nodes
Case 1
Case 2
Case 3
Case 4
Case 5
48/male A P A A Stones Stones NP Stones P A A
58lfemale P A P A Stones and hyperechoic lesion Nonvisualization of left IHD NP NP A P P
53/male P A A A Stones Stones NP NP P P P
30lfemale A A A P Stones Stones NP NP P P P
68/male P P A A Stones Stones Abscess NP A
P A
*Abbreviations: A, absent; P, present; NP, not performed; ERCP, endoscopic retrograde cholangiopancreaticography; IHD, intrahepatic duct.
Therefore, an initial “negative” ERCP or image study does not rule out the possibility of this frequently overlooked disease [7-91. The possibility of existence of intrahepatic cholangiocarcinoma should still be kept in mind even if the preoperative workup of hepatolithiasis is “negative” for associated neoplasm. Aside from the classical cholangitis of hepatolithiasis, there were some unusual presentations, including body weight loss (cases 2, 3, 3, anemia (cases 1, 5 ) , palpable abdominal mass (case 2), and intractable pain (case 4) in this series (Table I). We believe that the possibility of occult cholangiocarcinoma in hepatolithiasis should be considered when these unusual presentations appear. Repeated cholangitis and abscess formation attributable to hepatolithiasis usually leads to chronic fibrosis, contracture and adhesion of the liver to adjacent organs. Cholangiocarcinoma in hepatolithiasis may have the same pathological changes, making the differential diagnosis rather difficult, even during operation. Operative choledochofiberoscopy was said to be useful in the diagnosis of biliary tract neoplasms [20]. However, the situation seems somewhat difficult in the peripheral type cholangiocarcinoma with hepatolithiasis. The biliary tree usually can not be well visualized due to the stenosis of duct and firm impaction of hepatolithiasis. Intrahepatic stones should be first removed, as many as possible through both choledochotomy and partial hepatectomy (or hepatotomy) for exposing the post-stenotic intrahepatic duct, and well visualization of the whole biliary tree should be obtained later by thorough choledochofiberoscopy. An infiltrating lesion or mucinous substance can sometimes be detected. Several gross findings were noted in this series which may be unique to cholangiocarcinoma (Table I). These unusual gross findings included: (1) whitish nodular masses over liver (cases 1, 3, 4); (2) mucinous substance within the bile duct (cases 2-5); and (3) enlarged firm lymph nodes clustered along hepatic
arteries and/or celiac arteries (cases 2-4). Histological examinations finally confirmed the diagnosis. For a thorough therapeutic plan, frozen-section examination of enlarged lymph nodes, suspicious whitish nodular masses, and/or resected liver should be considered under these circumstances.
SUMMARY Intrahepatic cholangiocarcinoma in hepatolithiasis, although rare, does exist. With knowledge of its existence, careful survey of clinical presentations, proper preoperative ERCP andlor image studies, thorough intraoperative choledochofiberoscopy , and detailed intraoperative examination, the diagnosis of this frequently overlooked disease should be obtained earlier. REFERENCES 1. Wen CC, Lee HC: Intrahepatic stones: A clinical study. Ann Surg
175:166-1 77. 1972. 2 . Galasegaram M: Hepatic calculi. Ann Surg 175:149-154, 1972. 3. Sheen PC, Ker CG: lntrahepatic stones. 11. Clinical study. J Formosan Med Assoc 80:1217-1225, 1981 [in Chinese]. 4. Nakayma Y, Soloway RD, Nakamat: Hepatolithiasis in East Asia: Retrospective study. Dig Dis Sci 3 I :21-26, 1986. 5. Sanes S, MacCallum JD: Primary carcinoma of the liver. Cholangioma in hepatolithiasis. Am J Pathol 18:675-683, 1942. 6. Koga A, Ichimiya H, Yamaguchi K, Miyazaki K, Nakayama F: Hepatolithiasis associated with cholangiocarcinoma possible etiology significance. Cancer 55:2826-2829, 1985. 7. YoshiMoto H, Ikeda S, Tanaka M, Matsuomto S: lntrahepatic cholangiocarcinoma associated with hepatolithiasis. Gastrointest Endosc 31:26@263, 1985. 8. Chen PH, Lo HW, Wane CS, Tsai KR, Chen YC, Lin KY, Siauw CP, Hwang RR, Liu MH, KOHC, Chen TY: Cholangiocarcinoma in hepatolithiasis. J Clin Gastroenterol 6539-547, 1984. 9. Yi-Yin J , Miin Fu C, Chia-Siu W, Long-Bin .I,Liaw YF, Chen TJ: Intrahepatic stones in association with cholangiocarcinoma J Surg Assoc ROC 21:181-187, 1988 [in Chinese]. 10. Ohta G , Nakayama Y, Terada T: “Pathology of Hepatolithiasis: Cholangitis and Cholangiocarcinoma. Intrahepatic Calculi.” New York: Alan R Liss, 1984, pp 91-1 13. 11. Chen PC: Diagnosis of intrahepatic stones by ERCP. Gastroenterol Endosc 21:1190-1200, 1979.
Cholangiocarcinoma 12. Falchuk KR, Lesser PB, Galdabini J, Isselbacher KJ: Cholangiocarcinoma as related to chronic intrahepatic chlangitis and hepatolithiasis. Am J Gastroenterol 66:57-61, 1976. 13. Hou PC: Pathological changes in the intrahepatic bile ducts of cats infected with clonorchis sinensis. J Pathol 89:357-364, 1975. 14. Belamaric J: Intrahepatic bile duct carcinoma and C. sinensis infection in Hong Kong. Cancer 31:468473, 1972. 15. Gallagher PJ. Millis RR, Mitchinson MJ: Congenital dilatation of the i6ahepatic bile ducts with cholangiocarcinoma. J Clin Pathol 25:804808. 1972. 16. Willis RA: Carcinoma arising in congenital cysts of the liver. J Pathol 55:492495, 1943. 17. Huong MF, Liaw YF, Wu CS: Comparison of intravenous
135
radionuclide cholescintigraphy and endoscopic retrograde cholangiography in the diagnosis of intrahepatic gall stones. Br J Radio1 54:302-306, 1981. 18. Chang-Chien CS, Wu CS, Chen PC, Liaw YF: Clinical study of primary intraheptic stones. J Formosan Med Assoc 82:936940, 1983. 19. Pan S, Liao CH: Intrahepatic stones probable factors, clinical manifestation and recent advances in diagnosis. J Formosan Med Assoc 82:226-238, 1983. 20. Tompkins RK, Johnson J, Storm FK, Longmire WP: Operative endoscopy in the management of biliary tract neoplasms. Am J Surg 132:174-182, 1976.
