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Background: The aim of this study was to compare the outcome of patients with hepatocellular carcinoma (HCC), Barcelona Clinic Liver Cancer (BCLC) stages 0 and A, and portal hypertension (PHT) who underwent liver resection (LR) or radiofrequency ablation (RFA). Methods: The study population consisted of 121 patients with PHT and HCC of BCLC stage 0 and A who underwent LR ( n = 81) or RFA ( n = 40). To reduce bias in patient selection, the different covariate distributions in two groups were adjusted using inverse probability treatment weighting (IPTW). The prognostic outcomes of LR- and RFA-treated patients were then analyzed. Results: Before IPTW adjustment, the 5-year overall survival (OS) of LR and RFA patients was comparable. Five-year recurrence-free survival (RFS) was significantly better in the LR group than in the RFA group ( P < 0.0001). Multivariate analysis showed that RFA was an independent predictor of worse RFS ( P = 0.0004). The local recurrence rate was higher in the RFA than in the LR group, with recurrences in each group tending to be treated with the same modality as initially. After IPTW adjustment, the OS of patients in the LR and RFA groups did not significantly differ, whereas the RFS of the LR group remained significantly better than that of the RFA group ( P = 0.00014). However, the RFA group had fewer postoperative complication rates and a shortened length of hospital stay. Conclusions: By reducing postoperative complications, LR may be a treatment option for patients with BCLC stage 0 or A HCC and PHT. [ABSTRACT FROM AUTHOR]

Background: Undifferentiated carcinoma (UC) of the liver is extremely rare, and its clinicopathological characteristics have not been fully elucidated. Case presentation: The present study reports the case of a 56-year-old male with UC of the liver. At 16 days post-admission, the patient suddenly succumbed due to intra-abdominal bleeding resulting from a ruptured liver. Macroscopic examination revealed that the hepatic parenchyma was almost completely replaced by innumerable minute nodules. Microscopically, the tumor demonstrated a diffuse proliferation of anaplastic cells that were positive for epithelial membrane antigen and neuron-specific enolase, suggesting neuroendocrine differentiation. Grimelius and Fontana-Masson staining were negative. Neuroendocrine markers were also negative, including chromogranin A, synaptophysin, and S-100 protein. Cytokeratin markers and mesenchymal markers were all negative. Tumor markers, such as α-fetoprotein and carcinoembryonic antigen, were also negative. Conclusions: Although larger studies involving more patients are required to establish a therapeutic strategy, appropriate chemotherapy following an early diagnosis may be important to UC of the liver because the tumor behaves in an aggressive way. [ABSTRACT FROM AUTHOR]

Background: The management of hepatocellular carcinoma (HCC) in patients with concomitant esophageal varices (EV) remains controversial. We assessed the surgical outcome of hepatectomy and aimed to clarify the indications and management of HCC in patients with concomitant EV. Methods: We retrospectively enrolled 502 patients with HCC (100 with and 402 without EV), who underwent curative hepatectomy. We analyzed the prognostic outcomes and risk factors for EV bleeding after hepatectomy. Results: Overall survival (OS) was significantly lower in HCC patients with EV than in those without EV ( p = 0.003), although recurrence-free survival was similar in both groups. Multivariate analysis showed that indocyanine green retention test at 15 min (ICGR) >17 % ( p = 0.007) and α-fetoprotein >12.5 ng/ml ( p = 0.003) was independent predictors of poorer OS. Among patients with EV who underwent hepatectomy, multivariate analysis identified ICGR >17 % ( p = 0.03) as the only independent predictor of poorer OS. There was no significant difference in OS between HCC patients with EV and ICGR ≤17.0 % and HCC patients without EV. Ten patients experienced EV bleeding after hepatectomy. Multivariate analysis showed that preoperative endoscopic findings of blue color EV ( p = 0.008) and red color sign ( p = 0.0005) were independent predictors of EV bleeding in patients with HCC after hepatectomy. Conclusions: These results suggest that HCC patients with EV and ICGR ≤17 % may be suitable for surgery, but patients with preoperative endoscopic blue color EV and red color sign need to be managed appropriately. [ABSTRACT FROM AUTHOR]

Introduction: Previous reports have indicated an association between blood transfusion and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. However, clinicopathological biases were not adjusted in these studies. We aimed to clarify the effect of blood transfusions in patients with HCC and Child-Pugh class A after hepatectomy by using inverse probability of treatment weighting (IPTW) analysis for selection bias control. Materials and methods: We enrolled 479 patients with primary HCC and Child-Pugh class A retrospectively (91 transfused and 388 nontransfused patients) who underwent curative hepatectomy. After adjusting for different covariate distributions for both groups by IPTW, we analyzed the prognostic outcomes. Results: In the unweighted analyses, overall survival (OS) rate of transfused patients was significantly lower than in nontransfused patients ( P < 0.0001). Recurrence-free survival (RFS) rate of transfused patients was significantly lower than that of nontransfused patients ( P = 0.0024). Multivariate analysis showed that blood transfusion was an independent prognostic factor of OS and RFS. The different distributive covariates between the two groups were age, presence of liver cirrhosis, serum level of alpha-fetoprotein, maximum tumor diameter, and amount of intraoperative blood loss. After IPTW by these covariates, OS rate of transfused patients was not significantly lower than those of nontransfused patients, whereas RFS rate of transfused patients remained significantly lower than those of nontransfused patients ( P = 0.038, adjusted HR 1.45; 95 % CI 1.0-2.1). Conclusions: These results suggest that blood transfusion was associated with recurrence of HCC after hepatectomy in patients with HCC and Child-Pugh class A. [ABSTRACT FROM AUTHOR]

Background. Measurement of thymidine phosphorylase (TP) activity in normal liver tissue adjacent to hepatocellular carcinoma (HCC) may predict multicentric recurrence a long time after an operation. The authors investigated this activity in 92 patients with HCC who had a single HCC equal to or less than 5cm. Methods. Fresh samples (tumors with adjacent normal tissues) were collected from 92 patients with HCC who underwent curative hepatic resection. The levels of TP activity in nonfixed, fresh, and frozen HCC specimens with adjacent noncancerous liver tissue were biochemically measured by using an enzyme-linked immunosorbent assay method. Results. Patients who had a high TP level in normal liver tissue had significantly earlier recurrence (median disease-free survival, 819 days; 95% confidence interval [95% CI], 478-1044 days) compared with patients who had a low TP level (median disease-free survival, 1376 days; lower limit of 95% CI, 921 days; P = 0.0171). Multivariate analysis showed that patients who had a low TP level in adjacent liver tissue had a 0.387-fold higher risk of postoperative recurrence compared with patients who had a high TP level (P = 0.0067). Conclusion. TP activity in normal liver tissue adjacent to HCC is related to tumor occurrence and may predict postoperative tumor recurrence. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the results of a thoracoabdominal hepatectomy and a transdiaphragmatic hepatectomy for hepatocellular carcinoma in patients with impaired liver function. Design: Retrospective study. Setting: A university hospital in Japan. Patients: Twenty-seven patients who from 1991 to 1996 underwent a thoracoabdominal hepatectomy for hepatocellular carcinoma located mainly in the superior portion of the liver and 20 patients who underwent a transdiaphragmatic hepatectomy for hepatocellular carcinoma located near the diaphragm. Main Outcome Measures: Morbidity, survival, and disease-free survival after each operation. Comparisons were then made with 183 patients who had undergone an ordinary transabdominal hepatectomy during the same period. Results: In the thoracoabdominal hepatectomy group, 17 patients underwent a partial resection, 4 patients underwent a subsegmentectomy, and another 6 patients underwent either a segmentectomy or a procedure that was greater in size than a segmentectomy, whereas all of the patients in the transdiaphragmatic group underwent a partial resection. The morbidities in the thoracoabdominal group included pleural effusion in 6 patients (22%); intra-abdominal infection in 5 patients (19%); and hepatic failure in 3 patients (11%), of whom 1 died (mortality rate, 4%). In the transdiaphragmatic group, only 2 patients (10%) had non–life-threatening complications. The cumulative survival rates and the disease-free survival rates of the patients at 3 years were 51% and 24% in the thoracoabdominal hepatectomy group and 62% and 30% in the transdiaphragmatic hepatectomy group; no significant differences were observed when these findings were compared with those of patients who had undergone a transabdominal hepatectomy. Conclusion: The outcomes of the patients undergoing thoracoabdominal hepatectomy and those undergoing a transdiaphragmatic hepatectomy were generally satisfactory in spite of the fact that these procedures... [ABSTRACT FROM AUTHOR]

Background A retrospective study was performed at some high-volume institutions to clarify the prognostic significance of postoperative complications in patients who had undergone hepatectomy for hepatocellular carcinoma (HCC). No published studies have investigated the relationship between postoperative complications of Clavien–Dindo grade III or more and prognosis in patients who have undergone hepatic resection. Methods Patient data were retrospectively collected for 966 consecutive patients who had undergone hepatectomy for HCC with curative intent between January 2004 and December 2012. The patients were assigned to two groups according to the presence of postoperative complications. Clinicopathologic, surgical outcome, and long-term survival data were analyzed. Results Hospital deaths occurred in nine patients (0.9%). Postoperative complications were identified in 165 patients (17.1%). Compared with patients without complications, patients with complications had significantly larger tumors, more advanced-stage tumors, more poorly differentiated tumors, more intrahepatic metastasis, longer operation time, greater blood loss, more blood transfusion, and more anatomic resection and combined resection. The overall 5-y survival rates were 48.6% in patients with postoperative complications and 73.2% in patients without them. The 5-y recurrence-free survival rates were 23.7% in patients with postoperative complications and 36.7% in patients without them. Multivariate analysis revealed that longer operation time and lower serum albumin level of albumin were independent predictive factors for occurrence of postoperative complications. Conclusions In patients with HCC, posthepatectomy complications are predictive of a worse overall survival, even when adjustments have been made for other known predictors. [ABSTRACT FROM AUTHOR]

Background/Aims: We measured aspartyl (asparaginyl)-β-hydroxylase (AAH) gene expression in human hepatocelluar carcinoma and surrounding uninvolved liver at both the mRNA and protein level and examined the regulation and function of this enzyme. Methods: Since growth of HCC is mediated by signaling through the insulin-receptor substrate, type 1 (IRS-1), we examined—if AAH is a downstream gene regulated by insulin and IGF-1 in HCC cells. In addition, IRS-1 regulation of AAH was examined in a transgenic (Tg) mouse model in which the human (h) IRS-1 gene was over-expressed in the liver, and an in vitro model in which a C-terminus truncated dominant-negative hIRS-1 cDNA (hIRS-ΔC) was over-expressed in FOCUS HCC cells. The direct effects of AAH on motility and invasiveness were examined in AAH-transfected HepG2 cells. Results: Insulin and IGF-1 stimulation increased AAH mRNA and protein expression and motility in FOCUS and Hep-G2 cells. These effects were mediated by signaling through the Erk MAPK and PI3 kinase-Akt pathways. Over-expression of hIRS-1 resulted in high levels of AAH in Tg mouse livers, while over-expression of hIRS-ΔC reduced AAH expression, motility, and invasiveness in FOCUS cells. Finally, over-expression of AAH significantly increased motility and invasiveness in HepG2 cells, whereas siRNA inhibition of AAH expression significantly reduced directional motility in FOCUS cells. Conclusions: The results suggest that enhanced AAH gene activity is a common feature of human HCC and growth factor signaling through IRS-1 regulates AAH expression and increases motility and invasion of HCC cells. Therefore, AAH may represent an important target for regulating tumor growth in vivo. [Copyright &y& Elsevier]