Liver resection in advanced hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to assess the results of major liver resection in patients with advanced hepatocellular carcinoma in terms of safety and survival. METHODOLOGY: The subjects of this study are 19 patients that underwent 24 resections for advanced (stage IV) hepatocellular carcinoma. Eighteen of these resections were performed for primary tumor and 6 were repeat resections. Nine patients presented without cirrhosis, 5 with cirrhosis, and 5 patients had the fibrolamellar variant of hepatocellular carcinoma. RESULTS: Hospital mortality was recorded in 1 case (5%). Morbidity was noted in 7(37%) cases. All patients with fibrolamellar variant of hepatocellular carcinoma are alive at 78, 41, 24, 12 and 9 months (P = 0.008), compared with a median survival of 18 and 9 months for the noncirrhotic hepatocellular carcinoma and cirrhotic hepatocellular carcinoma groups, respectively (P = 0.24). CONCLUSIONS: We conclude that an aggressive policy of major liver resection with vascular reconstruction was justifiable in patients with advanced fibrolamellar variant of hepatocellular carcinoma and in selected patients with noncirrhotic hepatocellular carcinoma, and of doubtful value in patients with cirrhosis.     

Fibrolamellar carcinoma: a review with focus on genetics and comparison to other malignant primary liver tumors

Fibrolamellar carcinoma is a rare primary malignant liver neoplasm that usually affects adolescents and young adults with no underlying liver disease. Morphologically, the tumor cells resemble oncocytic hepatocytes arranged in cords with a stroma of lamellated collagen fibers. Immunohistochemical studies have found that fibrolamellar carcinomas express markers associated with both biliary (CK7 and epithelial membrane antigen) and hepatocytic (heppar-1and glypican-3) differentiation, as well as markers associated with hepatic progenitor cells (CK19 and EpCAM) and stem cells (CD133 and CD44). Genetic studies show fewer alterations compared with classic hepatocellular carcinoma. Pooled data from comparative genomic hybridization studies show that fibrolamellar carcinomas have fewer and less frequent genomic alterations when compared with classic hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma. Of the alterations seen in fibrolamellar carcinoma, the most frequent are gains in 1q and 8q (also frequently seen in other hepatic tumors) and loss of 18q. Fibrolamellar carcinoma also has less frequent methylation of tumor suppressor promoters compared with hepatocellular carcinoma and minimal alterations in mitochondrial DNA. Fibrolamellar carcinoma is associated with better survival than hepatocellular carcinoma and cholangiocarcinoma, presumably due to the young age of the patients and the lack of cirrhosis. These features make more aggressive surgical therapy possible. There is currently very little information on the effectiveness of chemotherapy for fibrolamellar carcinoma.     

Fibrolamellar hepatocellular carcinoma: report of a case

We report a case of fibrolamellar hepatocellular carcinoma, which occurred in a 58-year-old man with normal liver function. Preoperative ultrasonography, computed tomography and magnetic resonance imaging depicted a large tumor in the left lateral segment, which was compatible with the typical radiological features of fibrolamellar hepatocellular carcinoma. He underwent left lobectomy and no lymphadenopathy or distant metastasis was demonstrated. Macroscopic findings of the resected liver demonstrated a well-defined whitish-yellow tumor with a central scar. Microscopic findings of the tumor showed cords of tumor cells, which were surrounded by abundant collagenous fibrous tissue arranged in a lamellar distribution. He has been doing well for approximately one year since the surgery without any signs of recurrence. In addition, we discuss the clinicopathological features of fibrolamellar hepatocellular carcinoma based on a review of 22 Japanese patients who have been previously reported.     

Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy. Identification of two groups of patients with prospects for prolonged survival

Among 37 patients with hepatocellular carcinoma given systemic chemotherapy, 12 (32 percent) lived 14 to 37 months from initiation of treatment whereas the remainder died within five months. Individual factors associated with improved survival included fully ambulatory performance status, lack of jaundice, response to chemotherapy, the fibrolamellar carcinoma pathologic variant, absence of cirrhosis, and normal serum alpha-fetoprotein levels. Patients living longer than 12 months fell into two groups. Seven patients with fibrolamellar carcinoma lacked evidence of hepatitis B serum markers or cirrhosis and had normal alpha-fetoprotein levels and surprisingly frequent extrahepatic metastases. All but one were Caucasians aged 25 years or less. The other five "long-term" survivors were all fully ambulatory without jaundice, and the majority were older non-Caucasians with tumor confined to the liver at the time of diagnosis and with hepatitis B markers, elevated alpha-fetoprotein levels, or cirrhosis. All patients without fibrolamellar carcinoma who were less than fully ambulatory or who had jaundice died quickly. Patients with fibrolamellar carcinoma have homogeneous clinical features, and their disease follows a relatively indolent course. In other patients with hepatocellular carcinoma, assessment of ambulatory status and serum bilirubin determination can identify those with some prospect of prolonged survival.     

Recurrent obstructive jaundice caused by fibrolamellar hepatocellular carcinoma

Summary A 24-year-old man with hepatocellular carcinoma presented with recurrent obstructive jaundice caused by bile duct invasion and distal migration of necrotic tumor fragments. After resection of an isolated left lobe tumor, he was well for 2 years until he again presented with obstructive jaundice caused by necrotic tumor and clot in the common bile duct. Analysis of his tumor revealed the fibrolamellar histologic variant of hepatocellular carcinoma. This case is unique in that the hepatocellular carcinoma was of the fibrolamellar variant and presented both intially and when recurrent 2 years later with obstructive jaundice caused by invasion of the common bile duct.     

Recurrent fibrolamellar hepatocellular carcinoma with biliary invasion: Successful resection

A jaundiced 17-year-old man was diagnosed as having a local recurrence of fibrolamellar hepatocellular carcinoma 2 years and 4 months after left hepatic trisegmentectomy with total caudate lobectomy had been performed. The patient had a tumor occupying the upper part of the extrahepatic and intrahepatic bile ducts. Complete resection of the recurrent tumor was carried out. The patient remains well 3 years after the second surgery. Fibrolamellar hepatocellular carcinoma, a rare type of liver cancer, is a well defined disease entity with distinct clinical and histopathological features and a favorable prognosis. The good prognosis seems to warrant aggressive surgical intervention in patients with recurrences. Therefore, additional surgery for tumor recurrence should be considered. To our knowledge, this is the first report of a case in which a recurrent tumor of fibrolamellar hepatocellular carcinoma invaded the entire bile duct wall was successfully resected.     

Fibrolamellar carcinoma of the liver: hepatocellular carcinoma with favourable prognosis

The authors report a case of fibrolamellar carcinoma of the liver in a young woman with bilateral lung metastases. This tumour was surgically unremovable. Presently, after a chemotherapy with adriamycin and mitomycin, this patient is in good health, two years after initial diagnosis. Review of the literature shows that fibrolamellar carcinoma of the liver occurs mainly in young patients. This tumor is characterised by large polygonal eosinophilic hepatocytes and an abundant fibrous stroma. It can be confused with focal nodular hyperplasia. Resection of the tumor and the methodical, repeated resections of metastases must be performed when possible. Prognosis of this tumor is better than that of the other variants of hepatocellular carcinoma.     

Fibrolamellar liver cell cancer. A case report

Fibrolamellar hepatocellular carcinoma of the liver is a rare variant of hepatocellular carcinoma with characteristic morphological patterns and a good prognosis. Preoperatively the tumor is rarely diagnosed. Surgical treatment is resection, hemihepatectomy or transplantation of the liver. We report a case of a 51 years old patient with fibrolamellar hepatocellular carcinoma of the liver.     

Fibrolamellar hepatocellular carcinoma in pregnancy

BackgroundHepatocellular carcinoma (HCC) is rare in pregnancy but can enlarge rapidly under these circumstances.Case outlineA 25-year-old woman was diagnosed with HCC of fibrolamellar type immediately post-partum. One year after liver resection the patient remains well.DiscussionThis is only the second report of fibrolamellar carcinoma occurring in pregnancy. Other types of hepatocellular carcinoma in pregnancy have generally demonstrated a poor outcome, probably secondary to hormonal changes and increased liver vascularity.     

Liver transplantation for malignant disease

For many patients with malignant disease of the liver, liver transplantation offers the only opportunity for clinical cure or prolonged palliation. As a result of organ scarcity, patients are increasingly selected on the basis of tumour stage and with the predictable likelihood of prolonged survival in mind. Consequently, 3- and 5-year survival rates of 72% and 68% respectively have been described for patients transplanted with hepatocellular carcinoma for tumours measuring less than 5 cm in diameter or up to three in number. Moreover, many centres are developing adjuvant and neo-adjuvant therapeutic protocols to minimize the risks of disease recurrence following transplantation for malignancy. In this chapter, we review the current knowledge in relation to transplantation for hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, cholangiocarcinoma, metastatic neuroendocrine tumours, secondary solid tumours and other rarer malignancies.     

Fibrolamellar hepatocellular carcinoma with a recurrence of classic hepatocellular carcinoma: a case report and review of Oriental cases

A 72-year-old Chinese male, hepatitis B carrier, received a right hepatic trisegmentectomy in 1997 for fibrolamellar hepatocellular carcinoma. Serum alpha-fetoprotein was in the normal range until two years after the operation, a rapid increase to 241 ng/mL occurred and computed tomography showed a 2-cm-sized recurrent nodule in the caudate lobe. Because computed tomography arterioportography showed additional multifocal nodules in the residual liver, transarterial embolization was performed. Four months after the first transarterial embolization, the caudate tumor grew to 6 cm and serum alpha-fetoprotein increased to 6090 ng/mL. Prior to the second transarterial embolization, this new hepatic lesion received a biopsy and showed a characteristic feature of classic hepatocellular carcinoma, which was different from the previous one. Four months after the second transarterial embolization, computed tomography showed no recurrent tumor and serum alpha-fetoprotein subsequently normalized. Twenty-two months after the first transarterial embolization, a 2.5-cm-sized tumor recurred again at the lateral segment. At this time, serum alpha-fetoprotein (3.6 ng/mL) was not elevated. He received the third transarterial embolization and is still alive. Recurrence of fibrolamellar hepatocellular carcinoma after hepatic resection has been reported to be high, but a case report with a character of muticentric, multifocal, and metachronous recurrences of fibrolamellar and classic type hepatocellular carcinoma is very rare. This is the second case report in the literature.     

Fibrolamellar hepatocellular carcinoma complicating ulcerative colitis with primary sclerosing cholangitis.

This case report describes the previously undocumented association between fibrolamellar hepatocellular carcinoma and ulcerative colitis complicated by primary sclerosing cholangitis.     

Current status of surgery and transplantation in the management of hepatocellular carcinoma: an overview

Despite many therapeutic advances in the field of hepatocellular carcinoma over the past two decades, this disease continues to be a major cause of cancer‐related mortality worldwide. This review focuses on the recent advances in surgical technique, perioperative management, and transplantation of cirrhotic and noncirrhotic patients with hepatocellular carcinoma. Liver resection continues to be the mainstay of curative treatment in noncirrhotic patients and selected cirrhotic patients with small tumors and preserved liver function. Transplantation should be advocated for patients with poor liver function and localized lesions or for patients with large fibrolamellar carcinomas that are otherwise unresectable. Surgery has a definite role in the management of hepatic recurrences in the absence of systemic dissemination. Newer advances in the therapeutic armamentarium, such as cryotherapy, radiofrequency ablation, microwave coagulation, and ethanol injections are discussed, and their overall efficacy assessed.     

A resected case of fibrolamellar hepatocellular carcinoma with chronic hepatitis (type B)]

We report a case of a 34-year-old woman who tested positive for HBs Ag with fibrolamellar hepatocellular carcinoma of the liver. The sister of this patient, who was also positive for HBs Ag, died of hepatocellular carcinoma (HCC). The patient showed elevation of alpha-fetoprotein. Abdominal CT scan showed a tumor in the posterior segment of the liver and hepatic angiography revealed marked neovascularity in the tumor. Partial resection of the liver was performed, and the histological diagnosis was fibrolamellar hepatocellular carcinoma. The patient is now tumor free and doing well 20 months after the operation.     

Hepatocellular carcinoma in women: probable lack of etiologic association with oral contraceptive steroids

To investigate the possibility of an association between oral contraceptive steroids (CS) and hepatocellular carcinoma (HCC), we reviewed 128 cases of HCC in women collected between 1953 and 1980. There were 48 cases under the age of 40, and 13 of these (27%) had used CS. However, 62% of HCC associated with CS and 58% of HCC in women under 40 not using CS were classified histologically as "fibrolamellar" carcinoma. This subtype of HCC occurs predominantly in young people, both male and female. The apparent increase in HCC in young women can be explained by the presence of cases of fibrolamellar carcinoma in this age group, an the apparent association with CS is probably coincidental.     

Fibrolamellar Hepatoma

Primary hepatocellular carcinoma (HCC) has a high incidence rate worldwide with an extremely grave prognosis, but, fortunately, accounts for only 2% of all cancers in the United States. Yet, a unique subset of HCC fibrolamellar hepatocellular carcinoma (FLHC) is reported only from the United States. Five cases of FLHC from the University of Minnesota's 17 years of experience are reported and compared with the literature reports for FLHC, as well as contrasted to reports of HCC. The review of the literature is addressed for data evaluating FLHC as a distinct entity from HCC.     

Budd-Chiari syndrome as the primary manifestation of a fibrolamellar hepatocellular carcinoma.

An 18-year-old female patient was admitted with ascites, right upper abdominal tenderness and peripheral edema. Angiography showed complete occlusion of the vena cava inferior up to the level of the right atrium. By open heart surgery, masses of thrombotic material were pulled out of the v. cava inferior/vv. iliacae which histologically contained tumor cell populations consistent with a hepatocellular carcinoma. Celiacography showed a highly vascularized tumor in the right hepatic lobe. Histologically, it proved to be fibrolamellar subtype hepatocellular carcinoma.     

Hepatic neoplasms: computed tomography and magnetic resonance features

Over the last decade, major advances in computed tomography and magnetic resonance technology have occurred. These advances enable accurate, noninvasive detection and characterization of many hepatic neoplasms. This article illustrates the role of imaging in the evaluation of hepatic neoplasms and reviews the typical imaging features of both benign and malignant hepatic tumors. Benign tumors discussed include hemangiomas, focal nodular hyperplasia, hepatocellular adenoma, and simple cysts, as well as cysts associated with polycystic liver disease. Malignant neoplasms reviewed include metastases and conventional hepatocellular carcinoma as well as less common tumors such as fibrolamellar hepatocellular carcinoma, intrahepatic cholangiocarcinoma, angiosarcoma, and epithelioid hemangioendothelioma.     

Expresion of cell adhesion molecule CD44 in primary tumors of the liver: an immunohistochemical study

Abstract: CD44, a widely distributed integral membrane protein, has been implicated in tumor invasion and metastatic spread in some human carcinomas and lymphomas. In this study, 35 cases of hepatocellular carcinoma from 32 patients (11 cholangiocarcinomas, 9 hepatic adenomas, and 5 cases of focal nodular hyperplasia, a non-neoplastic lesion) were examined by imunohistochemical methods for expression of CD44. The mouse monoclonal antibody A3D8 was used on formalin-fixed, paraffin-embedded tissue; this antibody does not distinguish between standard CD44 and splice variants. Positive membrane staining was seen in 13 of 35 cases of hepatocellular carcinoma (12 of 32 patients), 8 of 11 cases of cholangiocarcinoma, and 1 of 9 cases of hepatic adenoma. The strongest staining for CD44 was seen in two cases of fibrolamellar carcinoma, but CD44 expression was otherwise not related to degree of tumor differentiation. All five cases of focal nodular hyperplasia were negative for CD44. In non-neoplastic liver, hepatocytes were negative; sinusoidal lining cells and portal lymphocytes were positive; bile ducts and proliferating bile ductules were focally positive in some cases. Anatomic stage at time of presentation was similar in both groups of patients, with most patients presenting with stage III or IV disease. A trend towards slightly longer survival in patients whose hepatocellular carcinomas were CD44 negative was noted. These results show that aberrant CD44 expression is present in a subset of hepatocellular carcinomas and in most cholangiocarcinomas. The relationship between CD44 expression and tumor spread is unclear in this group of tumors, but is unlikely to be a simple association between CD44 expression and metastatic potential.     

Lack of increase in heterozygous alpha 1-antitrypsin deficiency phenotypes among patients with hepatocellular and bile duct carcinoma.

Homozygous alpha 1-antitrypsin deficiency (PiZZ phenotype) is known to be associated with increased risk of cirrhosis and primary liver cancer. Although a relationship between heterozygous alpha 1-antitrypsin deficiency and chronic liver disease was suggested recently, it is still a matter of controversy whether such patients are at increased risk of liver cancer. The goal of this study was to determine the prevalence of heterozygous alpha 1-antitrypsin deficiency of different phenotypes among patients with primary hepatobiliary cancers. We studied 82 patients with primary hepatobiliary cancer; 59 had hepatocellular carcinoma and 23 had bile duct carcinoma. alpha 1-Antitrypsin quantitation and phenotyping were performed in each patient using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds-ratio and chi 2 tests were used to measure the relative risk and the significance of association, respectively, between primary hepatobiliary cancers and heterozygous alpha 1-antitrypsin deficiency. Four patients in each of the cancer groups were heterozygous. Among the hepatocellular carcinoma patients, three had the PiMS phenotype and one had the PiMZ phenotype. Of these four heterozygous patients, only two had cirrhosis; one had cryptogenic cirrhosis and the other had hepatitis B virus-related cirrhosis. One noncirrhotic patient with a PiMZ phenotype had a fibrolamellar carcinoma. Of the four patients with bile duct carcinoma, three had the PiMS phenotype and one had the PiMZ phenotype. Of the four heterozygous patients, two had primary sclerosing cholangitis without associated inflammatory bowel disease and one patient had had previous biliary operations.(ABSTRACT TRUNCATED AT 250 WORDS)