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Aims: Overweight/obesity is currently a common health issue that may cause many diseases, even malignancies. The influence of steatosis on long-term results of surgical treatment for hepatocellular carcinoma (HCC) is not well known. The aim of this study is to analyze the results of hepatectomy for HCC patients with steatosis., Methods: The study included 1048 patients who underwent hepatectomy for HCC from 1999 to 2005. The patients were divided into two groups; group A patients without steatosis (n = 693) and group B patients with steatosis (n = 355). The clinicopathological data and long-term survival were analyzed., Results: Mean tumor size in group B patients was smaller than that in group A patients (4.61 ± 3.40 vs. 5.91 ± 4.36 cm, p < 0.01). Group B patients showed lower tumor differentiation grade, lower vascular invasion rate and better 5-year overall survival compared to group A patients (61.2% vs. 50.1%, p = 0.001). By multivariate analysis, steatosis was found to be associated with well-differentiated, small-sized, and less α-fetoprotein productive tumors. When focusing on the tumors >5 cm in diameter, group B patients had better survival rate than group A patients (p = 0.041). Vascular invasion and steatosis were independent prognostic factors for the overall survival., Conclusion: HCC in steatotic liver was less aggressive than that in non-steatotic liver. HCC patients with steatosis have better surgical outcomes than those without steatosis. Vascular invasion and steatosis were independent prognostic factors for the overall survival if tumors were >5 cm in diameter., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Backgrounds/aims: Intrahepatic cholangiocarcinoma and colorectal cancer liver metastasis are the most primary and secondary adenocarcinoma of the liver, respectively. A large-scale long-term comparative study of these two cohort patient is lacking., Methods: A total of 166 colorectal cancer liver metastasis patients and 206 intrahepatic cholangiocarcinoma patients who had undergone curative liver resection were retrospectively analysed. Among 206 intrahepatic cholangiocarcinoma, there were 47 intraductal growth type-intrahepatic cholangiocarcinoma and 159 non-intraductal growth type-intrahepatic cholangiocarcinoma. The demographics, clinicopathological data, immunohistochemical study and survival were analysed., Results: The intrahepatic cholangiocarcinoma patients were more female-predominated, associated with hepatolithiasis, symptomatic, jaundiced, and with larger tumour size compared with those of colorectal cancer liver metastasis. Prognostic factors of intrahepatic cholangiocarcinoma were pathologic staging, histologic pattern and section margin; whereas prognostic factors of colorectal cancer liver metastasis were rectal origin, differentiation, section margin and bilobar distribution. CK7 and CK20 differentiated majority of intrahepatic cholangiocarcinoma from colorectal cancer liver metastasis, while CDX2 and MUC5AC helped to differentiate inconclusive cases. The 1-, 3-, 5- and 10-year survival rates of colorectal cancer liver metastasis were 77%, 31%, 20% and 14%, compared to 53%, 21%, 13% and 7% of intrahepatic cholangiocarcinoma (p=.0001). Furthermore, the survival of colorectal cancer liver metastasis was comparable to staged II intrahepatic cholangiocarcinoma (p=.8866) and intraductal growth type-intrahepatic cholangiocarcinoma (p=.1915)., Conclusions: Demographics, precipitating factor, clinical manifestations, and prognostic factors of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma differed remarkably. High incidence of CDX2 and MUC2 expression in colorectal cancer liver metastasis and intraductal growth type-intrahepatic cholangiocarcinoma might explain their similar cytoarchitecture and survival.

Biliary papillary neoplasia of the liver characterized by intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk has been sporadically reported, and includes intraductal growing cholangiocarcinoma and biliary papillomatosis. In addition, biliary papillary dysplasia and in situ and microinvasive carcinoma with papillary configuration reported in hepatolithiasis and in other chronic biliary diseases, could be included in this category. Usually, they arise in the intrahepatic large bile ducts, and the neoplastic and non-neoplastic parts of the intrahepatic biliary tree show saccular and segmental dilatation with mucin hypersecretion. This neoplasia frequently shows intraductal spreading and peribiliary glandular involvement. Acute repeated episodes of cholangitis or obstructive jaundice are a frequent clinical manifestation. Gastroenteric metaplasia with aberrant expression of cytokeratin 20, MUC2, MUC5AC, and/or MUC6, is frequent in the neoplastic parts, and biliary epithelial dysplasia with such metaplasia may give rise to in situ and then invasive carcinoma in hepatolithiasis. Interestingly, this type tends to contain foci of mucinous carcinoma elements, and this element may be predominant (mucinous carcinoma). Some may progress to "mucinous biliary cystadenocarcinoma" without ovarian mesenchymal stroma and with intraluminal continuous growth into the neighboring bile duct lumens. Interestingly, the biliary papillary neoplasm resembles histologically, phenotypically and clinically intraductal papillary mucinous neoplasm of the pancreas which is now being established as an infrequent, slow-growing pancreatic neoplasm. Recognition of such biliary papillary neoplasm with respect to the pancreatic equivalent may lead to a better understanding and further studies of the intrahepatic biliary neoplasm.

Intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling intraductal papillary mucinous neoplasm of pancreas is occasionally associated with hepatolithiasis. In this study, 136 cases of hepatolithiasis in Taiwan, between January 1998 and March 2000, and an additional 21 cases of IPN-L before December 1998, were examined histologically. IPN-L was found in 41 of 136 hepatolithiasis cases (30.1%). Sixty-two IPN-L cases (42 women and 20 men; age range, 59.8 +/- 10 years) were divided into 4 types (type 1, IPN-L with low-grade dysplasia, 23 cases; type 2, IPN-L with high grade dysplasia, 11 cases; type 3, IPN-L with in situ and microinvasive carcinoma, 13 cases; and type 4, IPN-L of types 2 and 3 with distinct invasive carcinoma, 15 cases). Intraductal spreading and glandular involvement were commonly observed in all types. About half of types 3 and 4 cases had mucobilia, and mucinous carcinoma was variably found in two thirds of group 4 patients. IPN-L frequently showed variable gastroenteric differentiation such as goblet cells and foveolar and colon-like metaplasia. IPN-L with goblet cells and colon-like metaplasia was frequently associated with overproduction of mucin and mucobilia (P <.01). In Japan, IPN-L was not frequent in hepatolithiasis (12 of 135 cases). In conclusion, IPN-L forms a spectrum of biliary neoplasm in hepatolithiasis. It often displays variable gastroenteric metaplasia and significant intraductal spread. IPN-L tends to progress to mucinous carcinoma. Formerly reported "mucin-producing intrahepatic cholangiocarcinoma" with a favorable prognosis is included in IPN-L.

Background and Objectives: Angiomyolipoma is a rare benign tumor that occurs in the liver and other organs. We provide data on eight cases of hepatic angiomyolipoma, regarding clinical presentations, diagnoses, management, and prognosis., Methods: A retrospective review of medical records of the eight patients with hepatic angiomyolipoma treated at the Chang Gung Memorial Hospital-Taipei between October 1988 and October 1999., Results: Eight female patients with hepatic angiomyolipoma were identified, with ages ranging from 30 to 66 years (mean, 45.3 years). Abdominal pain was the most common symptom, occurring in six of eight patients (75%). Hepatocellular carcinoma was the most common preoperative diagnosis, occurring in three of eight patients (37.5%). Laparotomy was performed in seven of eight patients (87.5%). Among these seven patients, three patients (43%) received hepatic resection with 100% cure rate to date. One of the eight patients (12.5%) was closely follow up after diagnosis made by echo-guided needle biopsy., Conclusions: Hepatic angiomyolipoma is a rare and benign entity. It has a wide variation and poses a diagnostic challenge clinically, radiologically, and pathologically. Its prognosis is good regardless of management, including hepatic resection or conservative treatment after tissue biopsy by echo-guided needle. To alleviate the mass effect, surgical resection may be needed for hepatic angiomyolipoma in selected cases., (Copyright 2001 Wiley-Liss, Inc.)

Aberrant genome-wide hypomethylation has been thought to be related to tumorigenesis. However, its mechanism and implications in hepatocellular carcinogenesis remain to be elucidated. Samples of hepatoma (hepatocellular carcinoma, HCC) and paired non-HCC liver tissues were obtained from 17 HCC patients. Normal liver tissues obtained from three individuals were used as controls. Compared with the paired non-HCC liver tissues, genome-wide 5-methylcytosine content in HCC was reduced in all of the tested HCC samples (P < 0.001). Conversely, genome-wide 5-methylcytosine content did not significantly differ among normal, noncirrhotic, and cirrhotic liver tissues. Moreover, the degree of reduced DNA methylation was related to late histopathological HCC grade (P = 0.005) and large tumor size (P = 0.079). Compared with the paired non-HCC liver tissues, expression of DNA methyltransferases DNMT-1, DNMT-3A, and DNMT-3B and the DNA methyltransferase-like gene, DNMT-2, was up-regulated in 53, 41, 59, and 47% of the HCC samples, respectively. Surprisingly, small amounts of LINE-1 retrotransposon transcripts were detected in HCC and non-HCC as well as normal liver tissues, and the expression levels were not significantly different in HCC compared with the paired non-HCC or normal liver tissues. Of interest, the 3' ends of these LINE-1 transcripts were truncated. Our findings suggest that genome-wide hypomethylation in HCC is a continuing process that persists throughout the lifetime of the tumor cells rather than a historical event occurring in precancer stages or in cell origins for HCC. Up-regulation of DNA methyltransferases might simply be a result of increased cell proliferation in cancer. In addition, our results did not support the hypothesis of activation of transposable elements in HCC via genome-wide hypomethylation.

Hepatic angiomyolipoma is a rare benign mesenchymal tumor of the liver. Most multiple hepatic angiomyolipomas have appeared in patients with renal angiomyolipoma and tuberous sclerosis. A 38-year-old female patient without chronic hepatitis B or C was hospitalized because of epigastric fullness for 2 months. Radiologic studies showed a large solid tumor with a small daughter nodule in the right hepatic lobe. Upon intravenous bolus injection of contrast medium, both tumors showed weak heterogeneous enhancement in the delayed phase. Although hepatocellular carcinoma was suspected by the findings of computed tomography, percutaneous transhepatic ultrasound-guided biopsy was performed for the large tumor. The histopathology showed many mature fat cells intermingled with thick-walled blood vessels, and epithelioid cells with eosinophilic cytoplasm; the epithelioid cells stained positively for HMB-45 and smooth muscle actin. Angiomyolipoma of the liver was confirmed. The main tumor enlarged considerably during a follow-up period of 3 years. Surgical resection was performed due to persistent symptoms. She had an uneventful postoperative recovery and was well when followed up 10 months after surgery. We should be aware that a hepatic angiomyolipoma can change in size during its natural course, and this finding does not necessarily indicate malignancy.

Two cases of hepatic follicular dendritic cell (FDC) tumor are described. Both patients were female, aged 57 and 51 years. They presented with epigastralgia or abdominal fullness and weight loss. The first patient refused surgical resection. She developed progressive polyclonal gammopathy and then bilateral purpura over the legs. Skin biopsy revealed leukocytoclastic vasculitis with granular vascular deposits of IgA and C3. The second patient had marked peripheral blood and tissue eosinophilia. The histological diagnosis was confirmed by positive staining for CD21 and CD23. The stromal lymphocytes were predominantly composed of CD3(+)and CD8(+) cells. In situ hybridization for EBER showed a positive nuclear signal in tumor cells but not in inflammatory cells. Polymerase chain reaction amplification for Exon 3 of the latent membrane protein-1 (LMP-1) gene showed a characteristic 30-bp deletion between nucleotides 168282 and 168253, corresponding to the B95-8 sequence. The unique clinicopathological features of our cases have not been reported for FDC tumors before. The clinical significance of the 30-bp deletion in Exon 3 of the LMP-1 gene in FDC tumor of the liver warrants further investigation.

We describe a hepatocellular carcinoma partially surrounded by focal nodular hyperplasia in a 65-year-old female patient. In order to clarify the relationship of the hepatocellular carcinoma and the adjacent focal nodular hyperplasia, clonal analysis was conducted. The clonal analysis was based on the methylation pattern of the polymorphic X-chromosome-linked androgen receptor gene (HUMARA). The allelic bands from the amplification of the focal nodular hyperplasia and of the hepatocellular carcinoma showed a significant reduction in the intensity of one of the two alleles as compared with two alleles of equal intensity in the buff coat after HhaI digestion, which indicated that these two parts were monoclonal. However, the inactivated allele in the focal nodular hyperplasia and that in the hepatocellular carcinoma were not identical. Therefore, the focal nodular hyperplasia and hepatocellular carcinoma probably derived from the clonal expansion of two different clones.

Background: Nuclear factor kappaB (NF-kappaB) is a transcription factor that plays important roles in cell proliferation and in immunity against viral infections. NF-kappaB is a dimer of Rel proteins that is sequestered in the cytoplasm as an inactive form through interaction with an inhibitory kappaB (IkappaB) protein. When IkappaB is degraded, the NF-kappaB dimer will enter the nucleus to activate the target genes. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may activate NF-kappaB and, thus, may modulate cell apoptosis and may be associated with oncogenesis. The role of NF-kappaB in hepatocellular carcinoma (HCC) has not yet been explored., Methods: Immunohistochemical staining to search for active nuclear RelA and nuclear IkappaBalpha proteins were done on formalin fixed liver tissues from 65 patients with HCC and from 9 normal control participants. Nuclear extracts of fresh-frozen tumor and nontumor liver tissues from 37 patients with HCC and from 7 normal controls were tested for NF-kappaB-DNA binding activity by electrophoretic mobility shift assay. The RelA and IkappaBalpha protein expressions were studied by Western blot analysis., Results: Nuclear NF-kappaB stainings were significantly more abundant in HBV-infected or HCV-infected tumors as well as nontumor parts of HCC compared with normal controls. Nuclear NF-kappaB DNA binding activity and nuclear RelA protein expression were greater in tumor tissue compared with nontumor tissue, whereas cytosolic IkappaBalphs protein expression was generally greater in nontumor tissue compared with tumor tissue., Conclusions: Constitutive activation of NF-kappaB was found more frequently in tumor tissue compared with nontumor tissue. It is possible that NF-kappaB overexpression accompanied by dysregulation of IkappaBalpha may play a role in the hepatocarcinogenesis of HBV or HCV infection.

Hypothesis: Dedifferentiation of human hepatocellular carcinoma (HCC) may influence telomerase activation and Ki-67 expression., Design: Laboratory study using human HCC specimens., Setting: University hospital., Patients: Twelve patients with HCC with specific morphologic patterns (nodule-in-nodule [n = 4] or confluent multinodular [n = 8] type) and histological heterogeneity and who had undergone curative hepatectomy were studied. Of these, 8 patients had 2 different histological grades of HCC cells distributed at various nodules but within the same tumor; 3 patients, 3 different histological grades; and 1 patient, all 4 different histological grades., Intervention: Tissue samples were retrieved from each nodule of the tumor and not mixed with one another. A total of 42 cancerous tissues from different distinctive nodules of the 12 patients were taken for telomerase and Ki-67 study, and corresponding noncancerous counterparts (n = 12) served as healthy control samples. Telomerase activity was assayed by the telomerase repeat amplification protocol. Expression of messenger RNA (mRNA) by the human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) was determined using reverse transcription polymerase chain reaction. The relative telomerase activity and hTERT mRNA in each tissue sample was quantified using densitometry and expressed as a percentage of the standardized HeLa cell line. Immunostaining with anti-Ki-67 antibody was used to detect Ki-67 and was expressed as Ki-67 labeling index., Main Outcome Measures: Telomerase activity, hTERT mRNA, and Ki-67 labeling index stratified by different histological gradings in each patient was analyzed. The correlations between telomerase activity and hTERT mRNA and between telomerase activity and expression of Ki-67 were plotted., Results: Telomerase activity increased from more to less differentiated foci of HCC cells in each case (generalized linear model, P<.001). Mean +/- SD expression of hTERT mRNA in 43 cancerous tissue samples, even those 4 with negative telomerase activity, was distinguishable from that of the noncancerous controls (0.84 + 0.23 vs 0.41 + 0.11; t test, P =.008). Telomerase activity was correlated to hTERT mRNA expression (Pearson correlation, r(2) = 0.56; P<.001). The Ki-67 labeling index increased from more to less differentiated foci of HCC in each case (generalized linear model, P<.001). Expression of Ki-67 correlated with telomerase activity within differently graded areas within individual tumors (Pearson correlation, r(2) = 0.38; P<. 001)., Conclusion: Using the model of human HCC with histological heterogeneity, we determined that dedifferentiation of human HCC induces telomerase activation and Ki-67 expression.

The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner. To investigate whether mutations of this enzyme occur in hepatocellular carcinoma (HCC), KAP mRNA was analyzed by reverse transcription-PCR (RT-PCR), followed by cloning and sequencing. Eight of 14 biopsy tissues obtained from advanced HCC, 6 of 13 surgically removed HCC tissues, and 2 of the adjacent noncancerous tissues contained aberrant KAP transcripts. Using the yeast two-hybrid system, five of seven representative KAP mutants were shown to be defective in interacting with Cdk2. These data suggest a possible role of KAP mutations in multiple-step hepatocarcinogenesis.

Inflammatory pseudotumor (IPT) is a rare lesion of the liver that can be clinically indistinguishable from a malignant tumor. A 51-year-old woman was hospitalized for upper abdominal pain and a weight loss of 5 Kg in 2 months. Radiological examination showed a large heterogenous hypervascular mass in the left lobe of her liver, strongly in favor of hepatocellular carcinoma. However, an ultrasound-guided liver biopsy revealed the typical characteristics of IPT, which consist of plump spindle cells with dense inflammatory cell infiltration. A left lobectomy was performed. No microorganisms were found on stained sections. The markedly elevated eosinophil count reverted to normal postoperatively and she remained well on follow-up examination 8 months after discharge. This case exemplifies the difficulty in radiological diagnosis of hepatic IPT and underscores the importance of its histological differentiation from malignancy before laparotomy.

p27(Kip1) is an inhibitor of cyclin-dependent kinase. It has been reported that reduced p27(Kip1) expression is present in human hepatocellular carcinoma. To determine the role of p27(Kip1) in hepatocarcinogenesis, 46 cases with hepatocellular carcinomas were studied. p27(Kip1) mutation was first screened by single strand conformation polymorphism, and direct DNA sequencing was then performed on those cases with mobility shifts. Two polymorphism sites were found. One is a previously described polymorphism at codon 109 (GTC-->GGC) which was found in two cases. The second polymorphism was identified at codon 55 (GCG-->GCA) in six of the 46 cases. However, the polymorphism at codon 55 was also present in seven of 93 healthy controls (7.5%), indicating that it is not associated with a predisposition for development of hepatocellular carcinoma (Fisher's exact test, 0.05). These results show that p27(Kip1) mutation is not a frequent event in human hepatocellular carcinoma, and suggest that it may be inactivated predominantly by transcriptional and/or posttranscriptional regulation rather than genomic aberrations.

Background: The p16INK4 (MTS1/CDNK2A) gene, located on chromosome 9p21, is an inhibitor of cyclin-dependent kinase 4. Various data have shown that it is frequently inactivated in several types of cell lines and primary human cancers., Materials and Methods: Thirty cases with hepatocellular carcinoma were studied for possible p16INK4 gene mutation in Taiwan. Homozygous deletion was determined using polymerase chain reaction (PCR). The p16INK4 gene mutation was first screened by single strand conformation polymorphism, then direct DNA sequencing was performed on the cases with mobility shifts. Deletion mapping of chromosome 9p21-22 was also carried out with two polymorphic microsatellite markers (D9S925 and D9S168) using PCR., Results: One of the 30 cases had homozygous deletion at exon 3 of the p16INK4 gene. Another tumor had altered electrophoresed mobility in exon 2 with G to T transversion in the first nucleotide of codon 61 by direct sequencing causing a stop codon (GAG-->TAG). At the D9S925 and D9S168 loci, six out of 24 (25%) and three out of 19 (16%) informative cases showed loss of heterozygosity, respectively., Conclusion: Point mutation and homozygous deletion of the p16INK4 gene are present in a subset of hepatocellular carcinomas in Taiwan. The patterns of the p16INK4 gene alteration are, however, different from those from other regions. In addition, allelic loss on chromosome 9p21-22 is not an uncommon event in hepatocellular carcinomas. Therefore, the significance of chromosome 9p loss deserves to be extensively investigated.

p73, a structural homologue of the tumor suppressor gene, p53, has recently been identified and mapped to chromosome 1p36, where genomic loss of heterozygosity (LOH) often occurs in human hepatocellular carcinoma (HCC). To determine whether p73 is involved in the development of HCC and whether there is an inverse correlation between the mutations of p73 and p53, we examined 22 paired tumors/noncancerous liver tissues for allelic expression, LOH and mutation of p73 and for mutation of p53. p73 was biallelically expressed in noncancerous liver tissues and in 7 out of the 8 informative tumors. One tumor tissue expressed only a single allele. LOH of p73 was found in 2 out of the 11 (18%) informative cases. A tumor-specific five-nucleotide deletion mutation causing a reading frameshift/early truncation of p73 DNA-binding domain was found, in which case no concomitant mutation in the DNA-binding domain of p53 was identified. Nine out of the 22 cases (41%) contained tumor-specific mutations in the DNA-binding domain of p53. Two of the three cases with p73 genetic alternations had a tumor size of less than 2 centimeters. These results suggest that p73 is a biallelically expressed gene in the liver and that allelic loss and mutation of p73 is infrequent and may occur early in HCC. p73 is unlikely to be the putative tumor suppressor gene located at chromosome 1p36 in HCC.

Hepatic epithelioid hemangioendothelioma (HEH) is a very rare vascular tumor of the liver. It usually affects adult women and presents as multiple hepatic nodules with mainly peripheral distribution. It poses special difficulties for clinicians in its diagnosis and treatment because of its non-specific clinical manifestations and findings on imaging, and it is easy to be misdiagnosed pathologically. Its clinical course and prognosis are variable but supposed to be intermediate between hemangioma and angiosarcoma. The primary treatments of choice are radical resection or liver transplantation. We report a 62-year-old man with right upper quadrant abdominal pain of several days' duration, who was initially misdiagnosed as having a liver abscess. Finally, HEH was diagnosed on the basis of positive immunohistochemical staining for factor VIII-related antigen in tumor cells. This case could serve to highlight the pitfalls in diagnosing this rare tumor. Increasing the index of suspicion and familiarity with the radiological and histological characteristics of this tumor would facilitate the accurate diagnosis and thus avoid unnecessary interventions.

APC gene mutations have been demonstrated not only in colorectal carcinoma but also in a variety of human cancers. To define the possible role of mutations of the APC gene in hepatocarcinogenesis, we examined 46 pairs of hepatocellular carcinomas and corresponding non-tumorous liver tissue by polymerase chain reaction and single strand conformation polymorphism. All 46 hepatocellular carcinomas had no altered electrophoretic mobility to suggest the presence of APC gene mutation in the mutation cluster region. We also examined the possible loss of heterozygosity of APC and MCC gene loci by fragment length polymorphism analysis and by polymerase chain reaction. None of the cases showed a loss of heterozygosity at the APC and MCC gene loci. The results suggested that the possibility of APC and MCC as the gene defect in the genesis of human hepatocellular carcinoma may be very rare.

Hepatic angiosarcoma is a rare malignant tumor with a rapidly fatal course. It has become a subject of interest because of its intimate relationship with environmental carcinogens, such as thorium dioxide (Thorotrast), vinyl chloride monomer, and arsenic. We describe a case of a chronic hepatitis B surface antigen carrier, with a 20-year history of environmental exposure to arsenical-containing agricultural herbicides and bactericides, who developed a hepatic angiosarcoma. He died due to rupture of the hepatic angiosarcoma with acute hemoperitoneum 9 weeks after initial diagnosis. This is a rare case of primary hepatic sarcoma, especially in Taiwan where hepatocellular carcinoma is endemic. This case not only serves to give more evidence of the relationship between hepatic angiosarcoma and arsenical exposure, but also demonstrates the key point in the differential diagnosis of liver tumors. Increased familiarity with this disease will facilitate correct diagnosis and help to improve management of the condition in the future.

Nineteen patients with hepatocellular carcinoma associated with hepatolithiasis were retrospectively analyzed. Eleven of the 19 patients presented with hepatolithiasis-related biliary infection. Diagnosis was erroneously assumed to be hepatolithiasis alone, liver abscess, or cholangiocarcinoma in five of 11 patients before surgery was attempted. Middle-age, male sex, liver cirrhosis, hepatitis B or C infection, abnormal alpha-fetoprotein, and negative carcinoembryonic antigen raised the suspicion of associated hepatocellular carcinoma rather than cholangiocarcinoma in patients with hepatolithiasis. Antibiotics and nonoperative methods to resolve biliary infection first, followed by hepatectomy, in selected cases, to eradicate hepatocellular carcinoma and hepatolithiasis simultaneously provides the best chance for long-term survival. Otherwise, patients often died of hepatolithiasis-related biliary sepsis rather than hepatocellular carcinoma per se in the long run.

A 48-year-old asymptomatic male hepatitis B virus carrier presented with a 2-day history of fever, chills, right upper quadrant abdominal pain, and jaundice. Shock was detected on admission. Emergency abdominal computed tomography (CT) scanning without contrast enhancement showed the features of acute pancreatitis. Hemobilia, edematous pancreatitis, cholestasis and cholecystitis were found on exploratory laparotomy. Neither stone nor active bleeding were detected on intraoperative choledochoscopic examination. Postoperative T-tube cholangiography one month later revealed non-opacification of the left intrahepatic duct. The patient's abdominal pain and hemobilia recurred. Celiac angiography and CT scanning with contrast showed two hepatocellular carcinomas (HCC) in the left lobe of the liver. This is the first case report in the English literature of HCC presenting as jaundice, hemobilia, and acute pancreatitis.

We performed a 17-year retrospective analysis of 10 cases of hepatocellular carcinoma presenting as pyogenic liver abscess. Spontaneous tumor necrosis and biliary obstruction caused by tumor thrombi, superimposed with bacterial infection, were the two major pathogeneses. Exact diagnosis of the underlying hepatocellular carcinoma was made for five of the 10 patients before management was attempted. Main clinical manifestations included fever, chills, right-upper-quadrant pain, malaise, anorexia, jaundice, and hepatomegaly. Characteristics such as middle age and male sex, seropositivity for hepatitis B and/or hepatitis C, chronic liver disease, unexplained anemia, marked weight loss, and a severely inversed albumin/globulin ratio raise suspicions about the underlying hepatocellular carcinoma. Management strategies included percutaneous drainage (n = 3), surgical drainage (n = 4), and hepatectomy (n = 3) in addition to administration of parenteral antibiotics in all cases. The prognosis was dismal, with a mean survival of 3.5 months (range, 8 days to 6 months).

Background: The purpose of our study was to report on the surgical outcomes of patients with hepatocellular carcinoma (HCC) with dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and to assess the differences in the surgical results between those patients and the patients with hepatitis B- or hepatitis C-related HCC., Methods: The operative outcomes of 13 patients with hepatitis B surface antigen (HBsAg)-positive and hepatitis C antibody (HCV Ab)-positive (the BC-HCC group) results, 57 patients with HBsAg-positive and HCV Ab-negative (the B-HCC group) results, and 34 patients with HBsAg-negative and HCV Ab-positive (the C-HCC group) results, who had undergone hepatic resection from 1991 to 1995, were compared., Results: The operative mortality rate within 1 month after operation for patients with BC-HCC was 7.7%. No statistically significant difference was found compared with the patients with B-HCC and C-HCC (5.3% and 5.9%, respectively). The postoperative course of patients with BC-HCC was complicated by liver failure, postoperative ascites, and wound infection in one patient each. Also, no statistically significant difference was found among the groups (23.1%, 22.8%, and 20.5% for patients with BC-HCC, B-HCC, and C-HCC, respectively). The overall 1-, 3-, and 5-year survival rates of patients with BC-HCC in this series were 75%, 50%, and 40%, respectively. The postoperative recurrence rate was 66.7%. No statistically significant differences were found between the various groups of the virus-related HCC on the overall survival rate and disease-free survival rate., Conclusions: Hepatic resection for HCC in patients with dual HBV and HCV infections was associated with slightly higher operative morbidity and mortality rates, but there were no statistical differences compared with hepatitis B- or C-related HCC regarding the survival and recurrence rates.

To define the critical region of liver-specific tumor suppressor genes in human hepatocellular carcinoma (HCC), we analyzed 30 cases of hepatocellular carcinoma using nine 4q and six 16q microsatellite polymorphic DNA markers. We observed one major common deleted region which was flanked by D4S175-D4S1625 and there may be two tumor suppressor genes on chromosome 16q associated with HCC. An extensive study of allelotyping of human HCC was therefore carried out in the candidate region on arms of chromosome 4q with additional tumor tissues and more informative microsatellite DNA markers. These data imply that at least one putative tumor suppressor gene is located in the human chromosome 4q26-q27 region and provides very useful information for further construction of a long-range physical restriction map and thereafter cloning of the putative tumor suppressor gene.

Most small hepatocellular carcinomas are asymptomatic. While small hepatocellular carcinomas do have symptoms, these symptoms are usually related to the underlying liver disease, not to the tumor itself. We encountered a 63-year-old male patient with a small hepatocellular carcinoma, 2.5 cm in diameter, presenting with fever, abdominal pain and sensation of abdominal fullness. These were unusual clinical manifestations related to the small hepatocellular carcinoma itself and challenged the diagnosis.

Ten cases of hepatoblastoma were studied for overexpression of p53 protein by immunohistochemistry and for possible p53 gene mutation by single strand conformation polymorphism (SSCP) analysis and direct DNA sequencing of the polymerase chain reaction products. Only one case of the macrotrabecular type at stage IV showed overexpression of p53 protein. No DNA mobility shift was found in any of these cases studied by SSCP analysis. DNA sequencing performed on the case showing overexpression of p53 protein revealed no mutation within exons 5 to 8. The associated adrenal cortical carcinoma of the same case also showed overexpression of p53 protein, but no mutation of the p53 gene. These results indicate that mutation of the p53 gene is infrequent in hepatoblastoma. This observation supports the view that mutation of the p53 gene is not as important in the oncogenesis of childhood neoplasms as in adult cancers.

Neurofibromatosis (NF) is a hereditary autosomal dominant disorder. Von Recklinghausen first described NF in 1882, which is now classified as Neurofibromatosis 1 (NF-1). NF-1 is the most commonly encountered NF which affects 1 in 4000 persons. Clinical manifestations of NF-1 include: generalized cutaneous neurofibroma, pigmented skin patches (cafe-au-lait spots), pigmented iris hamartoma (Lisch nodules), skeletal abnormally, CNS tumors, etc. The subject of this case study is a young adult male with a huge plexiform neurofibroma involving both the liver and head regions. The head tumor measured 10 x 8 x 3.5 cm3 in size, weighted approximately 180g with overlying hyperpigmented skin and an underlying congenital skull defect. A CT scan and MRI of the head and neck revealed a well defined lobulated tumor and deformed external ear. A abdominal sonogram, CT scan and MRI showed a huge plexiform neurofibroma with liver invasion. Lisch nodules and multiple cafe-au-lait spots were also found. Surgical removal of the head tumor along with an external ear reconstruction was performed. Satisfactory cosmetic results and improved hearing were achieved.

The sera of apparently healthy carriers of hepatitis B virus surface antigen enrolled in the Taiwan Prospective Study were tested retrospectively for anti-HBc IgM, to determine whether this test would be useful in predicting the development of hepatocellular carcinoma (HCC) and/or cirrhosis. In comparison with men who did not develop HCC or cirrhosis, the relative risk of those with anti-HBc IgM elevations was 3.4 and 5.6, respectively. Each of these factors was highly statistically significant, although the difference between them was not. Demonstration of anti-HBc IgM titers of greater than 1:1000 in serum probably reflects ongoing low level viral replication but not recent infection. Anti-HBc IgM appears to be a useful prognostic indicator for the future development of HCC and/or cirrhosis.