Clinicopathological significance of survivin expression in patients with hepatocellular carcinoma.

AIMS: Survivin, a newly discovered member of the inhibitor of apoptosis protein family, is suggested to be involved in liver carcinogenesis. The aim was to investigate the clinical significance of survivin expression in resected hepatocellular carcinoma (HCC) and paired adjacent non-tumour tissue. METHODS AND RESULTS: Immunohistochemistry, reverse transcriptase-polymerase chain reaction and Western blots were used to examine survivin mRNA and protein levels in 94 specimens of HCC tissues at different TNM stages and the data were correlated with the clinicopathological profiles. Patients were categorized into those with high tumour survivin protein levels (T-N >or= -1) and those with low levels (T-N < -1). Follow-up data were collected prospectively. mRNA levels of survivin and its splice variants in tumour tissue were significantly higher than in paired non-tumour tissue. However, survivin protein levels in paired non-tumour tissue were significantly higher than in tumour tissue from all three TNM stages. Additionally, high tumour survivin protein levels (T-N >or= -1) correlated with a better prognosis and low levels (T-N < -1) with a worse survival rate. CONCLUSIONS: High cytoplasmic survivin protein levels in HCC tissues seem to be an indicator of better prognosis in HCC patients after resection.

Recurrent hepatocellular carcinoma after hepatic resection: prognostic factors and long-term outcome.

AIM: The prognosis of patients with recurrent hepatocellular carcinoma (HCC) after hepatic resection varies widely. This study analyzed long-term survival and prognostic factors of patients with recurrent HCC after hepatectomy. METHODS: From July 1991 to December 2000, 623 patients underwent hepatic resection for HCC. Of those, 347 (56.5%) patients had tumour recurrence, and 286 patients with follow-up time more than 24 months after recurrence were enrolled. Twenty-seven clinicopathologic factors underwent both univariate and multivariate analysis. RESULTS: Of these 286 patients, survival times after tumour recurrence were mean 672+/-619 days; median 468 days; and, range 10-3753 days. The overall 1-, 3-, 5-, and 10-year post-recurrence survival rates were 61.5, 33.4, 18.2, and 9.0%, respectively. Seventy (24.5%) patients were alive at the time of study, and 10 of the 34 patients who underwent re-resection were disease-free. By Cox regression analysis, multiple initial tumours (relative risk (RR) 1.428), recurrent multiple (RR 1.372), extrahepatic recurrence (RR 2.434), recurrent tumour size >2 cm (RR 1.926), post-hepatectomy period until recurrence <1 year (RR 1.769), and non-resectional treatment of recurrent tumours (RR 3.527) were independent prognostic factors for post-recurrent survival rates. CONCLUSIONS: In patients with recurrent HCC after hepatectomy, both initial and recurrent tumour factors influenced their prognosis. Early detection of recurrent tumours is important. Re-resection correlated with better post-recurrent survival rates.

Reliability of contemporary radiology to measure tumour size of hepatocellular carcinoma in patients undergoing resection: limitations and clinical implications.

BACKGROUND: Preoperative radiology has been widely used to detect and measure hepatocellular carcinoma (HCC). However, its accuracy and reliability are unclear. This study aimed to assess the ability of current radiology to measure tumour size in patients undergoing resection. METHODS: We evaluated 212 HCC patients undergoing curative resection. Tumour size measured in the pathological examination was correlated with that obtained in preoperative ultrasound (US) and contrast-enhanced dynamic computed tomography (CT). Accuracy and association with tumour recurrence were investigated. RESULTS: The mean size of the tumour was 4.5 +/- 2.6 cm and was accurate in both US and CT in only 6 (3%) patients. Cirrhosis (P = 0.015), absence of tumour stain (P = 0.002) and small (< or = 4 cm) tumour (P < 0.001) were the significant factors associated with size deviation using both US and CT. Ninety-four (44%) patients developed tumour recurrence within 17 +/- 11 months of resection. Recurrence rate was 52%, 52% and 67% in patients with underestimation in US (relative risk [RR]: 2.0, 95% confidence interval [CI]: 1.2-3.4, P = 0.01), CT (RR: 2.1, 95% CI: 1.1-4, P = 0.022) and both modalities (RR: 2.5, 95% CI: 1.4-4.2, P = 0.001), respectively, compared to 30% recurrence in patients with accurate estimation of tumour size. CONCLUSION: The accuracy of radiology in measuring tumour size was poor, and may lead to inappropriate treatment. The finding that underestimation of tumour size was associated with a higher tumour recurrence rate is consistent with the hypothesis that HCC may recur from pre-existing tumour foci which could not be identified from the current imaging modalities.

Long-term evaluation of recombinant interferon alpha2b in the treatment of patients with hepatitis B e antigen-negative chronic hepatitis B in Taiwan.

The effect of interferon (IFN) on hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) has not been fully investigated in Chinese patients. We enrolled 58 HBeAg-negative CHB Chinese patients with hepatitis B viremia in Taiwan to evaluate the response to IFN. 30 patients received recombinant IFN 5 million units 3 times weekly for 6-10 months, and 28 patients who refused IFN treatment served as controls. Rates of virological response and biochemical response were higher in the treated group at the end of treatment (57% vs 18%, P = 0.006, and 73% vs 29%, P = 0.002, respectively). Both effects were superior in the treated group at 6 months after IFN withdrawal (virological: 30% vs 7%, P = 0.06; biochemical: 47% vs 7%, P = 0.002). Improvement of liver histological activities with persistently biochemical response was found in 65% of the treated patients. After a mean of 32 months' follow-up, virological response was rarely maintained (17% vs 4%, P = 0.228) but biochemical response was better in the treated group (27% vs 4%, P = 0.039). None of the treated patients but five controls developed severe complications of CHB during the follow-up period. A larger total IFN dosage or a younger age (< or = 40 years) were associated with 'sustained' virological response. Younger age and higher baseline alanine transaminase values (> or = 120 Ul(-1)) were related to 'sustained' biochemical response.

Clinicopathologic and prognostic differences between patients with hepatitis B- and C-related resectable hepatocellular carcinoma.

BACKGROUND AND PURPOSE: Hepatitis B and C viral infections are important factors in the development of hepatocellular carcinoma (HCC). This study examined the clinicopathologic and prognostic differences in patients with hepatitis B- and C-related resectable HCC. METHODS: A total of 270 HCC patients who underwent hepatic resection were enrolled. Among these patients, 211 were positive for hepatitis B surface antigen (HBsAg) and 59 were positive for anti-hepatitis C virus antibody (anti-HCV). The clinical manifestations, pathologic features, and treatment outcomes were compared between the HBsAg-positive and anti-HCV-positive groups. RESULTS: Compared to anti-HCV-positive patients, HBsAg-positive patients were significantly younger, had a higher familial incidence of HCC, larger tumor size, and a higher incidence of multiple tumors. HCC patients who were anti-HCV positive had worse liver function and a higher incidence of history of blood transfusion. DNA flow cytometric analysis revealed significantly more proliferative activity in the non-tumor part of the liver in HBsAg-positive HCC patients. The 1-, 3-, and 5-year overall survival rates of HBsAg-positive patients were 79%, 57%, and 48%, respectively, and for anti-HCV-positive patients were 91%, 75%, and 62%, respectively. HBsAg-positive patients had a significantly lower overall survival rate than anti-HCV-positive patients (p = 0.018). CONCLUSIONS: HBsAg-positive patients with resectable HCC had a less favorable survival rate after tumor resection than anti-HCV-positive HCC patients. This survival difference might have been related to the relatively advanced stage of disease and the higher proliferative activity of the non-tumor part of the liver in HBsAg-positive HCC patients.

Malignant melanoma of the eustachian tube.

The case report describes the diagnosis and the management of malignant melanoma of the eustachian tube. This is an exceedingly rare condition that was treated with endoscopic surgery and post-operative radiotherapy. During a 15-month follow-up, there was no evidence of recurrence.

An unusual cutaneous metastasis from hepatocellular carcinoma.

Cutaneous metastases from hepatocellular carcinoma are rare. In this report we detail a case of hepatocellular carcinoma with the unusual manifestations of multiple skin metastases. A 49-year-old male, who had received surgical resection of hepatocellular carcinoma one year prior, presented with multiple reddish-blue, firm, painless and nonulcerative cutaneous papules and nodules over the fingers, palms, toes, soles and back. Pathology of the cutaneous nodules showed characteristic hepatocellular carcinoma with trabecular gland formation. These lesions grew very rapidly and developed to cauliflower appearances which had not been described previously in the literature. The patient died of respiratory failure secondary to lung metastasis two months after the first appearance of the skin lesions.

Clinical, virological, and pathological significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C.

PURPOSE: Hepatic bile duct injuries are characteristic histological findings in patients with chronic hepatitis C virus (HCV) infection. However, the pathogenesis and clinical significance of this phenomenon remain unclear. The aims of this study were to evaluate the prevalence and clinical significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C. METHODS: One hundred and seventeen Chinese patients with chronic hepatitis C were enrolled. Clinical, biochemical, immunological (serum autoantibodies and cryoglobulinemia), histological, and virological data (serum HCV RNA titer and HCV genotype) were compared between patients with and without hepatic bile duct injuries. RESULTS: Eighty-three (71%) of the 117 patients with chronic hepatitis C had hepatic bile duct injuries. Patients with hepatic bile duct injuries had a significantly higher frequency of HCV genotype 1b; a higher mean serum globulin level; significantly higher mean scores for histological periportal necro-inflammation, portal inflammation, and fibrosis; and more severe portal lymphoid aggregation/follicles when compared with patients without hepatic bile duct injuries (P < 0.05, all). No significant differences in the presence of serum autoantibodies, cryoglobulinemia, mean serum HCV RNA titer, or response to interferon treatment were noted between the two groups. Multivariate logistic regression analysis showed that HCV genotype 1b infection, portal inflammation, and lymphoid aggregation/follicles were significant independent predictors associated with hepatic bile duct injuries. CONCLUSIONS: The presence of hepatic bile duct injuries in Chinese patients with chronic hepatitis C was significantly correlated with HCV genotype 1b infection, and the patients with these injuries had more severe portal inflammation and formation of lymphoid aggregates/follicles.

Clinical, virological, immunological, and pathological significance of GB virus C/hepatitis G infection in patients with chronic hepatitis C.

GB virus-C (GBV-C)/hepatitis G virus (HGV), a single-strand RNA virus, has been identified as a transfusion transmissible virus and categorized as a member of the Flaviridiae family. GBV-C/HGV superinfection in patients with chronic hepatitis C is not seen uncommonly, most likely because of the similar transmission routes. This study aimed to investigate the prevalence of GBV-C/HGV infection in 100 Chinese patients with histologically proven chronic hepatitis C, and to clarify the clinical, virological, immunological, and histopathological impact of GBV-C/HGV infection on chronic hepatitis C patients. Serum GBV-C/HGV RNA was positive in 22 (22%) of the 100 chronic hepatitis C patients. There were no significant differences in mean age, gender, and serum liver biochemical tests between GBV-C/HGV infected and non-infected chronic hepatitis C patients. The HCV genotype distribution and mean serum HCV RNA level were not significantly different between patients with and without GBV-C/HGV co-infection. The presence of serum autoantibodies (anti-nuclear antibody and anti-smooth muscle antibody) and cryoglobulinemia showed no significant difference between the two groups. Liver histopathological analysis revealed no significant difference in the grade of periportal, portal, and intralobular necro-inflammation, in the stage of fibrosis/cirrhosis, or in the presence of steatosis and lymphoid aggregation/follicle formation between patients with and without GBV-C/HGV infection. However, a higher degree of bile duct damage was noted in chronic hepatitis C patients co-infected with GBV-C/HGV infection than in those without infection (P=0.036). In conclusion, GBV-C/HGV infection had no apparent influence on the clinical, immunological, or virologic features of patients with chronic hepatitis C. However, the clinical significance of a higher degree of bile duct damage in patients with HCV and GBV-C/HGV co-infection deserves further investigation.

Clinical, virologic, and pathologic significance of elevated serum alpha-fetoprotein levels in patients with chronic hepatitis C.

Elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C is not uncommonly seen, but the pathogenesis of this phenomenon remains unclear. The aims of this study were to assess the prevalence of elevated serum AFP in patients with chronic hepatitis C and to evaluate the clinical, virologic, and histopathologic significance of this phenomenon. One hundred and fifteen Chinese patients with a histologic diagnosis of chronic hepatitis C were enrolled. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 2 years' follow-up. Of the 115 patients, 33 (29%) had elevated serum AFP (more than 12 ng/mL). There was a significantly lower mean serum albumin (4.0 +/- 0.1 vs. 4.3 +/- 0.1 gm/dL, p <0.001) and higher mean scores for periportal necroinflammation (3.3 +/- 0.3 vs. 2.3 +/- 0.2, p = 0.007) and fibrosis (2.3 +/- 0.2 vs. 1.1 +/- 0.1, p < 0.001) in patients with elevated serum AFP when compared with patients without elevated serum AFP. Patients with elevated serum AFP had significantly more incidences of genotype 1b infection when compared with patients without elevated serum AFP (77% vs. 51%, p = 0.021). Mean serum hepatitis C virus (HCV) RNA titer showed no significant difference between the two groups. Multivariate logistic regression analysis showed that as serum albumin of less than 4.2 gm/dL, a histology fibrotic score of more than 3, and HCV genotype 1b infection were significantly independent predictors associated with elevated serum AFP. In conclusion, elevated serum AFP levels were significantly correlated with lower serum albumin levels, advanced fibrosis/cirrhosis, and genotype 1b infection in patients with chronic hepatitis C.

Amyloidosis-induced gastrointestinal bleeding in a patient with multiple myeloma.

We present a case of multiple myeloma (MM) complicated by recurrent amyloidosis-induced gastrointestinal bleeding. The patient presented with episodes of coffee-ground vomitus or massive hematochezia. No bleeding focus could be identified using endoscopy, a red blood cell scan, or angiography. Finally, a tissue biopsy taken at the irregular mucosa beside protruding vessels in the duodenum confirmed the diagnosis of gastrointestinal amyloidosis. As this case illustrates, the absence of systemic symptoms of amyloidosis and nonspecific endoscopic findings in gastrointestinal amyloidosis may make diagnosis difficult. Therefore, we recommend that a diagnosis of amyloidosis-induced gastrointestinal bleeding should be considered in patients with MM with an obscure hemorrhage.

Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation.

BACKGROUND AND AIMS: Hepatic steatosis is a histological characteristic in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to evaluate the prevalence of hepatic steatosis in Chinese patients with chronic hepatitis C, and to look for possible correlation with various histopathological changes and to look for possible correlation with various clinical and pathologic variables. METHODS: One hundred and six patients were enrolled, and patients with alcoholism or diabetes mellitus were excluded. Clinical, biochemical and virologic data, including HCV genotype and serum HCV-RNA titer and histological findings, were compared between patients with and without hepatic steatosis. RESULTS: Fifty-five (52%) of the 106 patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis had significantly higher mean serum levels of triglyceride and gamma-glutamyl transpeptidase, higher body mass index, and a higher incidence of obesity compared with patients without hepatic steatosis. No significant differences in serum HCV-RNA titer and HCV genotype or the response to interferon therapy were noted between the two groups. Histological analysis showed patients with hepatic steatosis had a significantly higher mean fibrotic score than patients without hepatic steatosis (1.9 +/- 1.2 vs 1.3 +/- 1.0; P = 0.016). There were no significant differences in the severity of necroinflammation, the presence of lymphoid aggregation/follicle or bile duct damage between the two groups. Multivariate logistic regression analysis showed that independent predictors associated with hepatic steatosis were obesity or a histology fibrotic score of > or = 2. CONCLUSION: It was found that 52% of Chinese patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis were more frequently obese and had more severe hepatic fibrosis.

Comparison of clinical, virologic and pathologic features in patients with acute hepatitis B and C.

BACKGROUND AND AIMS: The clinical outcomes of adult-acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. In order to compare the clinical, biochemical, virologic and pathologic pictures in these two groups of patients, we enrolled 22 adult patients with acute hepatitis C and 16 adult patients with acute hepatitis B, on whom liver biopsies were performed within 3 months of acute onset of the illness. RESULTS: The results showed that a significantly younger age, a higher ratio of the clinical symptoms of jaundice, nausea, vomiting, and poor appetite, a higher mean serum level of alanine transaminase, aspartate transaminase, and total bilirubin were present in patients with acute hepatitis B patients than in those with acute hepatitis C (P < 0.05). There was a significantly higher degree of periportal inflammation and total necro-inflammatory activity in the acute hepatitis B patients (P = 0.002 and 0.049, respectively). Fifteen (68.2%) of the 22 patients with acute hepatitis C had detectable serum HCV-RNA, but only two (14.3%) of the 14 tested patients with acute hepatitis B had detectable serum HBV-DNA, detected by using the branched DNA signal amplification assay. Eighteen (82%) of the 22 acute hepatitis C patients and none of the 16 acute hepatitis B patients progressed into a chronic hepatitis stage (P < 0.001). CONCLUSION: The manifestations of mild clinical symptoms, lower mean serum transaminases and bilirubin levels, a lesser degree of histological periportal necroinflammation, and more patients with a high circulatory viral load among the acute hepatitis C patients, may lead to more of that group developing chronicity than patients with acute hepatitis B.

A progressive growing inflammatory pseudotumor of the liver.

Inflammatory pseudotumors of the liver are very rare, and their etiology and pathogenesis remain unclear. The diagnosis is often difficult to make because these masses often mimic other lesions such as primary neoplasms, metastases or liver abscesses. Herein, we report a rare case of progressive growing hepatic pseudotumor in a 47-year-old man. The patient presented with body weight loss and general malaise. A series of radiological examinations showed the progressive growth of the hepatic tumor from 3.5 cm to 10.0 cm in diameter within 8 months. He underwent a right lobectomy of the liver, and the final diagnosis was proven by pathology. There were no complications in the post-operative course.

Cholestatic hepatitis caused by acute gold potassium cyanide poisoning.

INTRODUCTION: Poisoning after oral ingestion of gold potassium cyanide is rarely reported. A case of suicidal ingestion of gold potassium cyanide (potassium dicyanoaurate; CAS# 13967-50-5) is described. CASE REPORT: A 27-year-old man attempted suicide by ingesting 5 mL gold potassium cyanide solution. He developed vomiting, hyperamylasemia, and hepatic dysfunction. Cyanide poisoning was not detected but acute gold toxicity was noted. Pathologic findings of the liver showed centrilobular cholestasis with eosinophilic degeneration. The whole blood and serum gold were 4361 and 6011 microg/L, respectively, and the 24-hour urine gold was 429 microg/d in samples obtained on day 4. CONCLUSION: Gold-induced hepatotoxicity has been seen infrequently in patients receiving gold therapy. Reported agents include sodium aurothiomalate, sodium aurothiopropranol sulfonate, aurothioglucose, aurothiopolypeptide (Auro-detoxin), auric sulfide, and gold thiosulfate, our report adds gold potassium cyanide.

Resection of triple synchronous tumors--gastric adenocarcinoma, gallbladder adenocarcinoma and stromal tumor of the stomach.

We herein report a rare case of triple synchronous tumors: gastric adenocarcinoma, gallbladder adenocarcinoma and stromal cell tumor of stomach, which were resected in the same operation. A 72-year-old male patient suffered from poor appetite and epigastric pain that radiated to his back for one month. Upper gastrointestinal endoscopy showed a gastric ulcer measuring 1.5 cm at the prepyloric area, which was proven to be adenocarcinoma by biopsy. A second tumor was found in the gallbladder, measuring 3 cm, by ultrasonography. On computed tomography, a third tumor about 2.5 cm in size was recognized posterior to the gastric high body and anterior to the pancreas. Given the presence of three tumors, he underwent a radical subtotal gastrectomy with Billroth-II gastrojejunostomy and simultaneous cholecystectomy. Pathological findings revealed gastric adenocarcinoma, gallbladder adenocarcinoma and stromal cell tumor of the stomach. The postoperative course was smooth.