Vascular Functional and Morphological Alterations in Smokers during Varenicline Therapy.

BACKGROUND: Varenicline has been reported to achieve high rates of smoking cessation. It remains undetermined whether varenicline therapy improves vascular function in smokers. METHODS: Consecutive Seventy-two smokers (age 57 ± 12 years) who succeeded in complete smoking cessation and 46 normal healthy volunteers (age 24 ± 3 years) with no cardiovascular risk factors were enrolled into this study. Vascular function and structure were assessed by flow-mediated dilation (FMD), nitroglycerin-induced vasodilation, and brachial artery intima-media thickness (baIMT) at baseline and 20 weeks after the initiation of varenicline therapy in smokers. FMD and baIMT were measured simultaneously using a semi-automatic vessel wall-tracking software program. 75 µg dose of a nitroglycerin tablet were sublingually administered for the nitroglycerin-induced vasodilation measurement. RESULTS: Exhaled-carbon monoxide concentration decreased significantly (20.0 ± 11.1 ppm at baseline vs 1.9 ± 1.5 ppm after 20 weeks, p < 0.001). FMD was significantly improved after 20 weeks (4.09% ± 1.83% at baseline vs 4.77% ± 2.33% after 20 weeks, p = 0.010), whereas nitroglycerin-induced vasodilation and baIMT were not significantly changed. CONCLUSIONS: Smoking cessation with varenicline therapy significantly increased FMD without significant changes of nitroglycerin-induced vasodilation or baIMT from baseline to 20 weeks. It appears to improve vascular function in smokers, which depends on endothelial function rather than on vascular smooth muscle function or changes in vascular structure.

Fibrosing cholestatic hepatitis after successful interferon and ribavirin therapy for recurrent hepatitis C post living related liver transplantation: a case report.

A 33-year-old Japanese man who had suffered from liver cirrhosis due to hepatitis C virus (HCV) underwent living related liver transplantation (LRLT). The allograft was given by his brother, who was healthy with no history of hepatitis or hepatic virus infection. After LRLT, the patient's hepatitis C recurred. Liver biopsy revealed chronic viral hepatitis and no allograft rejection such as shown by portal lymphocytic infiltration or mild bridging fibrosis. Interferon and ribavirin were administered, and sustained viral response (SVR) was obtained. Although serum hepatitis B virus (HBV)-DNA/HCV-RNA polymerase chain reaction found no presence of hepatic virus, the serum examination demonstrated liver dysfunction seven months after SVR. Liver biopsies histopathologically showed portal fibrosis invading to the sinusoids, cholestasis, mild hyperplasia of the cholangioles, and no features of allograft rejection. Fibrosing cholestatic hepatitis (FCH) was diagnosed. The FCH was resistant to treatment and advanced, and the patient died 17 months post-LRLT. Several serum examinations failed to demonstrate the existence of HBV/HCV during the patient's course. FCH is a type of viral hepatitis that is characterized by recurrent viral hepatitis after allograft transplantation. Because SVR obtained by anti-viral therapy commonly resolves FCH, we believe that this patient represented a rare case of FCH. The present case suggests that not only direct viral cytotoxicity, but other factors as well, promote the development of fibrosis and cholestasis. FCH sometimes progresses irreversibly despite the absence of serum viral load. The present case informed us that immediate anti-viral therapy should be initiated when recurrent allograft viral hepatitis is diagnosed.

Colorectal cancer metastasis to the thyroid.

A 69-year-old Japanese woman underwent a curative operation for rectal cancer (T2, N0, M0, Dukes B, R0, and stage IIA of American Joint Committee on Cancer) 3 years ago. On subsequent routine follow-up, a right-side thyroid nodule and a regional lymph node of up to 1.5 cm in diameter was palpated. FDG-PET demonstrated high FDG accumulation in the right lobe of the thyroid gland, neck lymph nodes, and sacral periosteum. We diagnosed a local recurrence of rectal cancer and a primary thyroid cancer. We chose radiotherapy for the periosteal recurrence, and then right hemithyroidectomy with regional lymph node dissection for the thyroid tumor was performed. Pathological examination demonstrated mucinous carcinoma, the same as the previous surgical specimen from the rectum. She had been treated with postoperative chemotherapy and had been alive and well for 26 months with lung metastases. Although thyroid gland metastasis from colorectal cancer is rarely reported, physicians should consider the possibility of thyroid gland metastasis when performing routine follow-up examinations for recurrence of colorectal cancer.

Huge liver abscess radiologically mimicking cystadenocarcinoma.

A 72-old-year Japanese man was incidentally found to have out liver dysfunction on serum examination and a cystic tumor in the liver. Dynamic computed tomography revealed a solitary cystic tumor 14 cm in diameter with multiple septa. The cyst wall was occasionally irregular with hyperarterial inflow. After admission, he suffered from fever and right upper abdominal pain. We suspected cystadenocarcinoma with intraluminal infection. Percutaneous transhepatic drainage was performed. However, neither cytologic examination nor culture test was positive. The cystic tumor had been decreasing in size, and hepatic resection performed. Macroscopically, the tumor was a gray-yellow solid tumor with a fine boundary between tumor and liver parenchyma, and the cystic lesion collapsed. Microscopically, the tumor consisted of hepatic infarction, degenerated Glisson's sheath, and chronic inflammation, and chronic liver abscess was diagnosed. Most cases of bacterial liver abscess can be diagnosed because progression is accompanied by typical signs. However, it is difficult to diagnose liver abscess in the chronic phase because chronic liver abscesses exhibit various features on imaging series without typical signs or symptoms. When atypical liver cyst is found, the possibility of liver abscess in chronic phase should be considered.

A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma.

BACKGROUND: A novel index, the serum aspartate aminotransferase activity/platelet count ratio index (APRI), has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. We evaluated the ability of preoperative APRI to predict hepatic failure following liver resection for hepatocellular carcinoma. METHODS: Potential preoperative risk factors for postoperative hepatic failure (hepatic coma with hyperbilirubinemia, four patients; intractable pleural effusion or ascites, 30 patients; and variceal bleeding, one patient) as well as APRI were evaluated in 366 patients undergoing liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses. RESULTS: Hepatic failure developed postoperatively in 30 patients, causing death in four. APRI correlated with histological intensity of hepatitis activity and degree of hepatic fibrosis, and was significantly higher in patients who developed postoperative hepatic failure than in others without failure. Risk of postoperative hepatic failure increased as the serum albumin concentration and platelet count decreased and as indocyanine green retention rate at 15 min, aspartate and alanine aminotransferase activities, and APRI increased. Only APRI was an independent preoperative factor on multivariate analysis. Of the four patients who died of postoperative hepatic failure, three had an APRI of at least 10. CONCLUSIONS: Preoperative APRI independently predicted hepatic failure following liver resection for hepatocellular carcinoma. Patients with an APRI of 10 or more have a high risk of postoperative hepatic failure.

Hepatocellular carcinoma (HCC) recurring 10 years after clearance of hepatitis B surface antigen and 20 years after resection of hepatitis B virus-related HCC.

A 62-year-old man had been followed up for chronic hepatitis B (HB) since 1973. Hepatocellular carcinoma (HCC) was detected in 1985, at the age of 42 years. Serum HB surface antigen and anti-HB envelope antibody were positive at that time. A right hepatic lobectomy was performed. In 1995, serum HB surface antigen had cleared spontaneously and liver function had normalized. In March 2005, at the age of 62 years, a 1.5-cm diameter hepatic mass was detected in the left lateral segment. At that time, he was seropositive only for anti-HB core antibody. A diagnosis of recurrent HCC was made, and partial hepatectomy was performed. Covalently closed circular HBV DNA was detected in both cancerous and noncancerous tissues by nested polymerase chain reaction (PCR). Cassette-ligation-mediated PCR showed that HBV DNA was integrated into the telomerase reverse transcriptase gene located on chromosome 5p15.

Convenience of a tape-guiding technique in different types of hepatectomy.

BACKGROUND/AIMS: The liver hanging maneuver is widely used in right lobectomy to resect huge tumors and harvest living donors. The convenience of tape assistance in other types of hepatectomy is not well known. METHODOLOGY: Tape-guiding technique (TGT) was applied in 30 hepatectomies of different type between April 2003 and April 2006. The indications were liver carcinoma in 22 and living-donor in 8. Hepatectomies included right lobectomy, 14; left lobectomy with caudate lobectomy, 8; left lobectomy without caudate lobectomy, 2; lateral segmentectomy, 3; central bisegmentectomy, posterior segmentectomy, and superior dorsal partial resection, 1 each. A tape was placed in front of the inferior vena cava for right hepatectomy and left hepatectomy with caudate lobectomy. In other hepatectomies, the tape was positioned to be the target of parenchymal dissection. RESULTS: TGT was successfully performed in all 30 cases. Tape facilitated dissection by helping the surgeon maintain orientation, and traction on the tape flattened the parenchyma, making it easier to identify and manage vessels and ducts. With an assistant holding the tape, the surgeon's left hand was free, and ligation and suturing was easier and more secure. CONCLUSIONS: The TGT is a convenient technique that is applicable to different types of liver resection.

Risk factors for massive blood loss during liver resection for hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND/AIMS: Liver resection for hepatocellular carcinoma in patients with cirrhosis carries risk of major hemorrhage and sometimes requires blood transfusion. We investigated risk factors for massive blood loss during liver resection and indications for storing blood for autologous intraoperative transfusion. METHODOLOGY: We analyzed clinical records of 100 patients with cirrhosis who underwent liver resection for hepatocellular carcinoma. Autologous blood was stored preoperatively for 19 patients. RESULTS: Intraoperative blood loss ranged from 5 to 3000 mL (mean, 640). Liver resection was performed without transfusion in 67 patients and with autologous blood storage in 17 patients not receiving homologous blood. In the other 16 patients, homologous blood was transfused. Univariate analysis identified youth, large tumors (> 4cm), major hepatectomy, portal tumor involvement, hepatic vein involvement, and prolonged operation time as risk factors for massive blood loss; multivariate analysis identified portal involvement and hepatic vein involvement as independent risk factors. Blood loss exceeded 1000 mL in the 4 transfused group B patients and 3 of the 4 patients had hepatic vein involvement. CONCLUSIONS: Portal involvement and hepatic vein involvement were risk factors for massive blood loss during liver resection for hepatocellular carcinoma in patients with cirrhosis. Autologous blood storage is indicated in patients with such risk factors.

A histopathological study on combined hepatocellular and cholangiocarcinoma: cholangiocarcinoma component is originated from hepatocellular carcinoma.

BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma of the liver is relatively infrequent, and its pathogenesis remains obscure. The aim of this study is to investigate its clinical and pathological features and proliferative activity. METHODOLOGY: In this study, we investigated the histopathological features, Ki-67 labeling index, and p53 immunohistochemistry of 18 surgically resected cases of combined hepatocellular and cholangiocarcinoma among 1102 consecutive cases of surgically resected primary liver cancers. All tumors were compatible with the WHO definition of this tumor. Microscopically, we classified the cases into the following three categories according to the arrangement of the hepatocellular carcinoma and cholangiocarcinoma components; (1) Type I in which hepatocellular carcinoma and cholangiocarcinoma formed nodules that could easily be distinguished from each other, (2) Type II in which the both components were finely mixed, so that the two components were almost indistinguishable, and (3) Type III in which the tumors had lobular structures with hepatocellular carcinomas existing centrally and cholangiocarcinomas existing peripherally. RESULTS: Microscopically, the tumors were classified into type I 7 tumors, type II 5 tumors, and type III 6 tumors. In one case of type I, well differentiated hepatocellular carcinoma demonstrated cholangiocarcinoma in "nodules-in-nodules" fashion. The average of Ki-67 labeling index of hepatocellular carcinoma component of combined hepatocellular and cholangiocarcinoma was 4.4 +/- 3.4% and the index of cholangiocarcinoma component was 11.0 +/- 8.5%, which is significantly higher than that of the hepatocellular carcinoma component. On p53 immunohistochemistry, 5 of 18 cases (29.4%) were positive. In one case, the cholangiocarcinoma component was positive for p53, but the hepatocellular carcinoma component was negative. In the other 4 cases, both the hepatocellular carcinoma and cholangiocarcinoma components were positive. CONCLUSIONS: Microscopically, type III seems to be a feature of metaplasia or proliferation of bipotential progenitor cells. Metaplasia of hepatocellular carcinoma to intrahepatic cholangiocarcinoma is assumed to be one of the pathogenic pathways of combined hepatocellular and cholangiocarcinoma.

S-allyl cysteine prevents CCl(4)-induced acute liver injury in rats.

Aged garlic extract (AGE) possesses multiple biological activities. We evaluated the protective effect of S-allyl cysteine (SAC), one of the organosulfur compounds of AGE, against carbon tetrachloride (CCl(4))-induced acute liver injury in rats. SAC was administrated intraperitoneally (50-200 mg/kg). SAC significantly suppressed the increases of plasma ALT and LDH levels. SAC also attenuated histological liver damage. CCl(4) administration induced lipid peroxidation accompanied by increases in the plasma malondialdehyde and hepatic 4-hydroxy-2-nonenal levels, and SAC dose-dependently attenuated these increases. The hepatic total level of hydroxyoctadecadienoic acid (HODE), a new oxidative stress biomarker, was closely correlated with the amount of liver damage. These results suggest that SAC decreased CCl(4)-induced liver injury by attenuation of oxidative stress, and may be a better therapeutic tool for chronic liver disease.

Pseudotumor of the omentum with a fishbone nucleus.

A 23-year-old Japanese man was admitted with a chief complaint of abdominal pain. He was previously healthy, and his past medical history was unremarkable. Local tenderness and rebound tenderness at McBurney's point were elicited. Abdominal roentgenography was non-diagnostic. Ultrasonography and computed tomography showed a tumor with a central core. Based on a diagnosis of appendicitis with omental inflammation or an omental tumor, laparotomy performed. Intraoperatively, no site of gastrointestinal perforation was detected; however, a 5-cm omental granuloma was identified that proved to have a fishbone nucleus on pathological examination. The postoperative course was uneventful, and upper gastrointestinal endoscopy and barium enema were unremarkable. A large solitary omental pseudotumor is rare, and the clinical course in this case was atypical compared with the usual course of intestinal perforation by a foreign body and formation of an intra-abdominal granuloma.

Surgical treatment for hepatocellular carcinoma detected after successful interferon therapy.

PURPOSE: Interferon therapy suppresses the development of hepatocellular carcinoma (HCC) and tumor recurrence after a resection of HCC in patients with chronic hepatitis C. However, the value of a liver resection and which method is best for the treatment of HCC detected after successful interferon therapy remains to be clarified. The risk factors for tumor recurrence after a liver resection for HCC detected after successful interferon therapy were investigated to determine the appropriate operative method for such HCC. METHODS: Risk factors including the clinicopathologic findings and the operative methods for tumor recurrence were evaluated by univariate and multivariate analyses in 24 patients who underwent liver resection for HCC detected after successful interferon therapy (sustained viral response or biochemical response). RESULTS: According to a univariate analysis, large tumor (> 2 cm, P = 0.0326), multiple tumors (P = 0.0372), nonanatomic resection (P = 0.0103), and positive surgical margin (< 5 mm of a free surgical margin, P = 0.0245) were possible risk factors for short tumor-free survival time after surgery. A multivariate analysis showed that large tumor (P = 0.0407), nonanatomic resection (P = 0.0215), and positive surgical margin (P = 0.0253) were independent risk factors for a short tumor-free survival time after surgery. CONCLUSION: An anatomic resection with an appropriate surgical margin (> or = 5 mm of a free surgical margin) is recommended for patients with HCC detected after successful interferon therapy.

Bowel injury associated with liver surgery for hepatocellular carcinoma.

BACKGROUND/AIMS: Bowel injury associated liver surgery is rare but can be fatal if not adequately treated. The contribution of underlying liver disease and previous hepatectomy to bowel injury in hepatectomy for hepatocellular carcinoma is unknown. METHODOLOGY: Clinical records of 531 patients who underwent hepatic resection without combined resection of the biliary tract or intestine for hepatocellular carcinoma during 13 years were reviewed. Differences in incidence of bowel injury according to presence or absence of liver cirrhosis, technique of hepatectomy, and history of hepatectomy were investigated. Outcome after treatment also was reviewed. RESULTS: Bowel injury occurred in 5 patients (0.9%). Previous hepatectomy history was associated with an increased incidence of bowel injury [repeat hepatectomy, 3/91 (3.3%), and first hepatectomy, 2/440 (0.5%), p = 0.038]. Injury was recognized intraoperatively in two patients and postoperatively in three. In the former two patients, the injured bowel was repaired immediately but a fistula still developed in one patient. One patient with a fistula eventually required temporary fecal diversion and eventually limited colectomy. The other three patients were treated by continuous external drainage, but two of them required debridement or colic sleeve resection. CONCLUSIONS: Previous hepatectomy increases the risk for bowel injury during hepatectomy. Care must be taken to prevent adhesion to the hepatic cut surface. Careful use of electrocautery to prevent burn injury also should be taken.

Influence of interferon therapy on outcome after surgery for hepatitis C virus-related hepatocellular carcinoma.

Influence of interferon (IFN) therapy on postoperative outcomes in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is still inconclusive. Of 518 patients who underwent hepatic resection for HCV-related HCC, 312 patients with Japan integrated staging score 0-2 were included in this study. Of 50 patients underwent IFN therapy, 29 patients who obtained a normalized alanine aminotransferase (ALT) activity irrespective of disappearance of serum HCV RNA were classified as the response group, while 21 patients were classified as the non-response group because their ALT activities were not normalized and serum HCV RNA persisted. The non-IFN group included 262 patients who had not received IFN therapy. The tumor-free and the overall survival rates for patients in the response group were significantly higher than those in other groups. Only one patient in the response group died of HCC recurrence, and the proportion of deaths associated with liver disease (HCC recurrence or cirrhosis) was significantly lower in the response group than other two groups. IFN therapy can improve postoperative outcomes in patients with HCV-related HCC because of suppression of recurrence and preventing progress of cirrhosis, especially when IFN therapy has controlled their active hepatitis.

Immunohistochemical demonstration of c-Kit protooncogene product in gallbladder cancer.

BACKGROUND/PURPOSE: Although some gallbladder carcinomas are immunoreactive for c-Kit, the reasons for the c-Kit expression and its clinicopathologic implications are unknown. METHODS: We investigated the prevalence of c-Kit immunoreactivity, its clinicopathologic correlates (including microvessel density and postoperative outcome), and the possible mechanisms of c-Kit expression. We reviewed retrospectively, the clinicopathologic records of 47 patients who had undergone macroscopically complete gallbladder carcinoma resection. The numbers of patients at pathologic stages I to IV, according to current TNM-based staging, were 10, 5, 18, and 14, respectively. For immunohistochemical examination, we used monoclonal antibodies against c-Kit and CD 34 (progenitor cell markers), cytokeratin 7 and cytokeratin 19 (cholangiocyte markers), and OCH1E5 (a hepatocyte marker). Control tissue samples were from five gallbladder specimens each with chronic cholecystitis, polyp, and adenoma. RESULTS: Cytoplasmic immunostaining for c-Kit was detected in 21 of the 47 gallbladder carcinomas (45%), and in 1 of the 15 control specimens (diagnosis, chronic cholecystitis). Young age was significantly associated with c-Kit positivity; however, there were no significant differences in the incidence of c-Kit positivity among other variables, including tumor stage and outcome. However, microvessel density was significantly higher in c-Kit-positive gallbladder carcinoma compared with c-Kit-negative gallbladder carcinoma. None of the 47 cancer specimens or the 15 control specimens were stained for CD34 and OCH1E5, but all 47 cancer specimens were stained for cytokeratins 7 and 19. CONCLUSIONS: Gallbladder carcinomas positive for c-Kit are unlikely to arise from immature cells, but may be associated with neovascularization. Angiogenesis inhibitors, such as tyrosine kinase inhibitors, therefore, may suppress the growth of some gallbladder cancers.

Clinical significance of serum cytokeratin-19 fragment (CYFRA 21-1) in hepatocellular carcinoma.

BACKGROUND/PURPOSE: CYFRA 21-1, a soluble fragment of cytokeratin 19, is increased in serum in some patients with hepatocellular carcinoma, but the clinical significance of this increase is still unknown. METHODS: Serum concentrations of CYFRA 21-1 were measured in 240 patients with hepatocellular carcinoma prior to hepatic resection. The relationships between serum CYFRA 21-1 concentrations and clinicopathologic features were analyzed. RESULTS: The sensitivity of CYFRA 21-1 as a test for hepatocellular carcinoma was 18.8%. Serum CYFRA 21-1 was significantly higher in patients with portal vein tumor thrombus, and serum CYFRA 21-1 increased with the progression of portal vein tumor thrombus. Tumor size was related to serum CYFRA 21-1, but there were no significant correlations between serum CYFRA 21-1 concentrations and tumor differentiation or number of tumors. Although patients with stage IV tumor had significantly higher CYFRA 21-1 concentrations than those with stages I, II, and III, CYFRA 21-1 was not associated with postoperative prognosis. CONCLUSIONS: Although high concentrations of CYFRA 21-1 were often detected in patients with a tumor diameter greater than 5 cm or tumor thrombus in the major portal vein, CYFRA 21-1 is not a useful diagnostic tool for hepatocellular carcinoma because of its low sensitivity.

Clinicopathological implications of immunohistochemically demonstrated mucin core protein expression in hepatocellular carcinoma.

METHODS: We examined the expression of mucin core protein 1 (MUC1) immunohistochemically in 186 surgical specimens of histopathologically nonmucinous hepatocellular carcinoma (HCC) and compared the clinicopathological features in patients with MUC1-positive HCC (MUC1-positive group) with those in patients with MUC1-negative HCC (MUC1-negative group). RESULTS: MUC1 immunoreactively was present in 85 of the 186 HCCs. Of the clinicopathological variables examined, the serum concentration of alpha-fetoprotein, tumor differentiation, bile duct invasion, lymph node metastasis, and cytokeratin 19 expression exhibited significant associations with MUC1 expression. Although cumulative and tumor-free survival rates were not different between the two groups, the percentage of patients with first recurrence of HCC in distant organs (distant metastasis) within 2 years after surgery was significantly higher in the MUC1-positive group than in the MUC1-negative group (P = 0.0104). The risk ratio of MUC1 positivity for this type of distant metastasis was 3.156 (95% confidence interval, 1.064-9.358). CONCLUSIONS: In patients with MUC1-positive HCC, careful follow-up is necessary, not only for intrahepatic recurrence but also for distant metastasis, after the resection of primary HCC.

Hepatocellular carcinoma arising from nonalcoholic steatohepatitis: report of two cases.

Sporadic cases of hepatocellular carcinoma (HCC) originating from nonalcoholic steatohepatitis (NASH) have recently been reported. Thus, we investigated the prevalence of NASH in patients with HCC. A review of the clinical records of 481 patients who underwent liver resection for HCC in our department between January 1991 and December 2003 revealed only two (0.4%) patients with HCC associated with NASH. Both of these patients had noninsulin-dependent diabetes mellitus, and neither had a history of alcohol consumption or blood transfusion. All serologic markers for hepatitis B and C viruses were negative. Histological examination of the noncancerous hepatic tissue revealed NASH with moderate hepatic fibrosis in one patient and cirrhosis in the other. Thus, clinical follow-up and screening for HCC should be done for patients with hepatic fibrosis caused by NASH, even though this form of hepatitis is an uncommon cause of HCC.

Splenic metastasis of hepatocellular carcinoma.

A 76-year-old man, who underwent central bisegmentectomy of the liver, transcatheter arterial chemoembolization, and radiofrequency ablation for chronic hepatitis C virus-related hepatocellular carcinoma (HCC), was found to have a 3 cm mass in the spleen and a 2 cm mass in the liver by computed tomography in January 2003. As both tumors were adjacent, a diagnosis of HCC with splenic infiltration was made. In February 2003, transcatheter arterial chemoembolization and splenic arterial chemo-infusion were performed. However, the splenic tumor increased to 5 cm with slight enhancement on contrast-enhanced computed tomography performed 6 months later, while the hepatic tumor had no enhancement. Limited resection of the liver with splenectomy was performed in October 2003. Macroscopically, the splenic tumor showed infiltrative growth without a capsule while the hepatic tumor showed complete necrosis within its capsule. The splenic tumor was limited to the splenic parenchyma. Histologic examination revealed that the splenic tumor was poorly differentiated HCC, leading to the diagnosis of splenic metastasis. The patient is doing well 17 months after surgery without recurrence. One should perform surgery for splenic metastasis of HCC without hesitation whenever possible.

Two cases of intrahepatic cholangiocarcinoma detected after interferon therapy for chronic hepatitis C.

Recently, it has been suggested that hepatitis C virus infection plays a role in the pathogenesis of some intrahepatic cholangiocarcinomas (ICC). We describe two patients with small ICC detected after interferon therapy for chronic hepatitis C. Case 1 was diagnosed with ICC by preoperative biopsy and underwent anterior segmentectomy of the liver, while Case 2 was diagnosed with hepatocellular carcinoma preoperatively and the tumor was diagnosed as ICC after biopsy and microwave coagulonecrotic therapy. Both patients are in good health six months and five months, respectively, after operation. It is important to monitor carefully for ICC as well as hepatocellular carcinoma in patients with chronic hepatitis C, even when interferon therapy has been carried out, since the outcome of treatment for small ICC is favorable.