Useful technique for draining a large cystic tumor through the round ligament in laparoscopic left hemihepatectomy.

INTRODUCTION: Some cystic liver tumors are huge when the diagnosis is made or surgery is needed. Although reducing tumor size by preoperative aspiration or drainage of the contents of the cystic tumor is helpful for liver resection, such procedures have a risk of tumor dissemination. MATERIALS AND SURGICAL TECHNIQUE: After the round ligament was dissected, a 12-Fr drainage catheter was inserted into the tumor via the round ligament under ultrasonography. At that time, close attention was paid to avoid having the catheter deviate outside the round ligament. Through the inserted catheter, fluid was drained from the cystic lesion, and the stump of the round ligament was clipped to avoid fluid leakage. The left Glissonian pedicle was then taped. Laparoscopic left hemihepatectomy was performed under a good operative field because of tumor shrinkage. DISCUSSION: Three cases underwent these procedures without any spillage of the contents of the cystic tumor. This method is useful for the reduction of tumor size and has a low risk of intra-abdominal leakage of the contents, resulting in a secure and good operative field.

Safety and feasibility of liver resection with continued antiplatelet therapy using aspirin.

BACKGROUND: Aspirin is widely used for the secondary prevention of ischemic stroke and cardiovascular disease. Perioperative aspirin may decrease thrombotic morbidity, but may also increase hemorrhagic morbidity. In particular, liver resection carries risks of bleeding, leading to higher risks of hemorrhagic morbidity. Our institution has continued aspirin therapy perioperatively in patients undergoing liver resection. This study examined the safety and feasibility of liver resection while continuing aspirin. METHODS: We retrospectively evaluated 378 patients who underwent liver resection between January 2010 and January 2016. Patients were grouped according to preoperative aspirin prescription: patients with aspirin therapy (aspirin users, n = 31); and patients without use of aspirin (aspirin non-users, n = 347). RESULTS: Aspirin users were significantly older (P < 0.001), with a higher proportion of males (P < 0.001) and higher frequencies of hypertension (P = 0.004) and diabetes mellitus (P < 0.001). No significant differences were observed in intraoperative parameters. Although the frequency of major morbidity tended to be higher among aspirin users than among aspirin non-users, no significant difference was identified. No postoperative hemorrhage was seen among aspirin users. CONCLUSIONS: Liver resection can be safely performed while continuing aspirin therapy without increasing hemorrhagic morbidity. Our results suggest that interruption of aspirin therapy is unnecessary for patients undergoing liver resection.

Amino acid substitutions in core and NS5A regions of the HCV genome can predict virological decrease with pegylated interferon plus ribavirin therapy.

BACKGROUND: The current standard therapy for chronic hepatitis C is pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, it has been reported that amino acid (aa) substitutions in the core region, as well as the IFN-sensitivity-determining region (ISDR), were predictive of non-virological response (NVR), sustained virological response (SVR) and early virological response. Despite the importance of these two predictive factors for combination therapy, their interaction is poorly understood. METHODS: A total of 117 patients who were treated with PEG-IFN-α2b plus RBV combination therapy were selected for participation in this study. We determined the aa sequences in the core region and ISDR by direct sequencing and analysed them along with clinical data to identify predictive factors for therapeutic response. RESULTS: The aa sequences in the core region and γ-glutamyl transpeptidase (GTP) levels were associated with SVR and NVR, but aa sequences in the ISDR were not. However, substitutions at both aa 70 and aa 91 in the core region without substitutions in the ISDR and higher levels of γ-GTP were independent predictive factors for NVR. Wild-type aa 70 and aa 91 in the core region, higher platelet counts and lower levels of γ-GTP were independent predictive factors for SVR. CONCLUSIONS: These results indicate that analyses of aa substitutions in both the core region and the ISDR are useful for predicting the effectiveness of combination therapy, and could help to avoid therapy exposure for patients who have a low probability of SVR.

Importance of serum concentration of adefovir for Lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B.

Lamivudine (LMV)-adefovir pivoxil (ADV) combination therapy suppresses the replication of LMV-resistant hepatitis B virus (HBV), although its efficacy in suppressing HBV varies among patients. This study analyzed the clinical, virological, and pharmaceutical factors that influence the effect of the combination therapy. Patients negative for hepatitis B virus e antigen (HBeAg) and with low HBV DNA titers immediately prior to the combination therapy effectively cleared serum HBV DNA (P=0.0348 and P=0.0310, respectively). The maximum concentration of ADV in serum (ADV Cmax) was higher in patients who showed HBV DNA clearance (P=0.0392), and the cumulative clearance rates of HBV DNA were significantly higher in patients with ADV Cmax equal to or greater than 24 ng/ml (P=0.0284). HBeAg negativity and lower HBV DNA at the start of the combination therapy and higher ADV Cmax were found to be independent factors for serum HBV DNA clearance. Serum creatinine increased significantly during the combination therapy, and the ADV Cmax was higher in patients with low creatinine clearance rates. In conclusion, higher serum concentrations of ADV are associated with a good response to therapy based on clearance of HBV DNA in serum. However, care should be taken to prevent worsening of renal function due to high ADV serum concentrations.

The first Japanese case of COACH syndrome.

COACH syndrome is a disorder characterized by hypoplasia of cerebellar vermis, oligophrenia, congenital ataxia, coloboma and hepatic fibrosis, and 21 cases have been reported to date. Here we describe the first Japanese case of COACH syndrome, who was diagnosed at the age of 37 years and never progressed to liver failure. The patient was found to have delayed developmental milestones at the age of 5 months and mental retardation at the age of 7 years. She had been treated for hepatopathy of unknown origin from the age of 22 years. She was admitted to Hiroshima University Hospital at the age of 37 years after the identification of esophageal varices on a routine upper endoscopy. Computed tomography of the abdomen revealed portal hypertension and splenomegaly, and liver biopsy showed liver fibrosis. In addition, she had coordination disorder and dysarthria. Brain magnetic resonance images revealed hypoplasia of cerebellar vermis. The final diagnosis was COACH syndrome. She underwent endoscopic injection sclerotherapy for esophageal varices. From that point until her death from ovarian cancer at the age of 41 years, the liver function tests were stable without an episode of hematemesis. Physicians should be aware of COACH syndrome when they examine young patients who present with hepatopathy, portal hypertension of unknown origin and cerebellar ataxia.

FDG positron emission tomography/computed tomography for the detection of extrahepatic metastases from hepatocellular carcinoma.

AIMS: To compare the efficacy of positron emission tomography (PET) computed tomography (CT), multi-detector helical computed tomography (MDCT) and bone scintigraphy for the detection of extrahepatic metastases in patients with hepatocellular carcinoma (HCC). METHODS: Thirty-four patients diagnosed with metastatic HCC were enrolled in this study. The lesions included lung (n = 18), bone (n = 12) and lymph node (n = 16) metastases. For receiver operating characteristic (ROC) analysis, lesions were diagnosed as metastatic HCC by two experienced abdominal radiologists. Another three physicians independently reviewed both positive and negative images. Each physician read three sets of images of MDCT, PET-CT and bone scintigraphy for bone metastasis. RESULTS: The mean sensitivity and specificity for diagnosis of lung metastasis were 85.2 and 88.9% for MDCT, and 59.2 and 92.6% for PET-CT, respectively. For lymph node metastasis, these values were 62.5 and 79.2% for MDCT, and 66.7 and 91.7% for PET-CT, respectively; and for bone metastasis 41.6 and 94.5% for MDCT, 83.3 and 86.1% for PET-CT, and 52.7 and 83.3% for bone scintigraphy, respectively. The mean Az values were 0.95 and 0.77 for MDCT and PET-CT in lung metastasis, respectively, 0.75 and 0.80 for MDCT and PET-CT for lymph node metastasis, respectively, and 0.59, 0.88 and 0.62 for MDCT, PET-CT and bone scintigraphy for bone metastasis, respectively. CONCLUSION: PET-CT has high sensitivity and is more suitable for the detection of bone metastases from primary HCC, relative to MDCT and bone scintigraphy.

Effectiveness of combination therapy of splenectomy and long-term interferon in patients with hepatitis C virus-related cirrhosis and thrombocytopenia.

AIM: To elucidate the effectiveness of combination therapy of splenectomy and long-term interferon (IFN) on survival and hepatocarcinogenesis, we retrospectively analyzed 180 patients with hepatitis C virus (HCV)-related cirrhosis and thrombocytopenia. METHODS: Group A consisted of 121 patients who received neither splenectomy nor IFN therapy. Group B consisted of 11 patients who underwent splenectomy only. Group C consisted of 32 patients who underwent IFN therapy only. Group D consisted of 16 patients who received the combination therapy splenectomy followed by IFN therapy. RESULTS: The viral response in group D estimated at least 6 months after IFN therapy showed sustained viral response in four patients, biochemical response in one and no response in six. Multivariate analysis using time-dependent variables showed significant improvement of survival rate in patients on the combination therapy,but no effect on the appearance rate of hepatocarcinogenesis relative to the findings in group A. CONCLUSIONS: In this study, the splenectomy did not directly improve the prognosis, but increased the ability for patients to undergo IFN. As a result, we considered that the combination therapy of splenectomy and long-term IFN significantly improved survival rate in patients with advanced HCV-related cirrhosis and thrombocytopenia.

Randomized trial of high-dose interferon-alpha-2b combined with ribavirin in patients with chronic hepatitis C: Correlation between amino acid substitutions in the core/NS5A region and virological response to interferon therapy.

The aim of this study was to compare the efficacy of high-dose interferon (IFN)-alpha-2b with standard dose of IFN-alpha-2b in combination with ribavirin (RBV) for patients with chronic hepatitis C virus (HCV) infection, and to investigate the predictive factors associated with virological response. Two hundred Japanese patients with high HCV viral load (>100 KIU/ml) were randomized to 6 or 10 mega units (MU) of 24-week IFN-alpha-2b with RBV. Predictive factors were investigated; including pretreatment amino acid (aa) sequences of the core region and the IFN-sensitive determining region (ISDR). The sustained virological response rate was not different in the two groups (24% vs. 30%) but the incidence of depression was significantly higher in the 10 MU group than 6 MU group (7% vs. 0%, P = 0.02). Younger age (<60) and HCV genotype (2a/b) were significant predictors of sustained virological response. In patients infected with genotype 1b, substitutions of core aa 70 and/or 91 were predictive for non-virological response (P < 0.001), and substitutions in the ISDR was observed frequently in virological responders. Early viral kinetics study showed that serum HCV core antigen decreased more slowly in both patients with aa 70 and/or 91 substitutions in the core and with absence of substitutions in the ISDR. In conclusion, the use of a higher dose of IFN-alpha-2b in combination with RBV did not improve virological response but resulted in higher incidence of depression. Amino acid substitutions in the core and ISDR are predictive of virological response to the therapy in patients with genotype 1b and high viral load.

Clinicopathological features, background liver disease, and survival analysis of HCV-positive patients with hepatocellular carcinoma: differences between young and elderly patients.

BACKGROUND: The aim of this retrospective study was to determine the incidence and characteristics of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) antibody-positive elderly patients with chronic hepatitis without cirrhosis. METHODS: The study included 65 patients who developed HCC at >or=75 years of age and who received their first HCC therapy at Toranomon Hospital between 1985 and 2005. Their clinicopathological and laboratory data were analyzed and compared with those of 33 patients who developed HCC at

Beneficial effects of living-donor liver transplantation on esophageal varices.

BACKGROUND: Liver transplantation (LT) is known to improve bleeding esophageal varices (EVs) and portal hypertension. However, many issues related to EVs after LT remain unresolved, such as whether LT reduces blood supply to EVs, improves the diameter of unruptured EVs, or improves or worsens EVs. The aim of this retrospective study was to determine the effects of living-donor liver transplantation (LDLT) in patients with hepatic failure on EVs and inflow vessels to EVs and the factors associated with deterioration of EVs after LDLT. METHODS: The study subjects were 35 patients with cirrhosis who underwent LDLT. Endoscopy and multidetector helical computed tomography (MDCT) were performed before and after LDLT. The diameter of the inflow vessel of EVs was measured by MDCT before and after LDLT, together with the LDLT-related reduction rate of the diameter of the gastric vein (RRGV). RESULTS: Endoscopic examination showed improvement of EVs in 30 of 35 (86%) patients. RRGV improved in 17/35 (49%) patients, did not change in 13/35 (37%), and deteriorated in 5/35 (14%). The cause of RRGV deterioration seemed to be either the complication of portal vein or graft failure. In patients examined endoscopically at >1 year after LDLT, improvement of EVs was associated with significant changes in the rate of reduction of the major inflow vessel diameter and Child-Pugh score, compared with those who showed no improvement. CONCLUSIONS: LDLT results in improvement of EVs. EVs improved in 86% of the patients. Measurement of RRGV with MDCT is a good tool for prediction of EV improvement after LDLT.

Clinicopathological features of elderly patients with hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND: It is well known that the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) correlates with progression of liver fibrosis. However, there is little information on the impact of aging on hepatocarcinogenesis. The aim of this study was to elucidate the clinicopathological features of elderly patients with HCV-related HCC. METHODS: The study subjects were 693 consecutive patients newly diagnosed with HCC with anti-HCV. First, we divided them into a younger group (<70 years) and an elderly group (> or =70 years) and compared clinicopathological features between the two groups. Next, we selected pure HCV-related HCC patients by excluding the patients with other probable factors for hepatocarcinogenesis (anti-HBc, interferon therapy, and alcohol) and compared the two groups again. RESULTS: Higher platelet count, lower male/female ratio, lower rate of habitual alcohol consumption, and better Child-Pugh class were recognized in the elderly group thant the younger group, statistically. In 133 cases of hepatic resection, fibrosis stage was lower in the elderly than the younger group. After selection of pure HCV-related HCC patients, in a stepwise multi variate analysis, male sex and platelet count <10 x 10(4)/mm3 were significant variables associated with age <70. Regarding the latency period to HCC development, the patients who received a blood transfusion at an older age developed HCC sooner despite their lower grade of fibrosis. CONCLUSIONS: The elderly patients developed HCC more often, despite their lower grade of fibrosis, compared with the younger patients. In addition to fibrosis, aging could be a factor affecting HCV-related hepatocarcinogenesis.

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: seven cases.

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC). Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP). Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port. Gemcitabine at 1000 mg/m(2) was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients), and progressive disease (no patients). The median survival period was 8 mo (range, 5-55). With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%), seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non-resectable advanced HCC, but it has severe hematologic toxicity.

Low-dose intermittent interferon-alpha therapy for HCV-related liver cirrhosis after curative treatment of hepatocellular carcinoma.

AIM: To assess the efficacy of low-dose intermittent interferon (IFN) therapy in patients with hepatitis C virus (HCV)-related compensated cirrhosis who had received curative treatment for primary hepatocellular carcinoma (HCC). METHODS: We performed a prospective case controlled study. Sixteen patients received 3 MIU of natural IFN-alpha intramuscularly 3 times weekly for at least 48 wk (IFN group). They were compared with 16 matched historical controls (non-IFN group). RESULTS: The cumulative rate of first recurrence of HCC was not significantly different between the IFN group and the non-IFN group (0% vs 6.7% and 68.6% vs 80% at 1- and 3-year, P = 0.157, respectively). The cumulative rate of second recurrence was not also significantly different between the IFN group and the non-IFN group (0% vs 6.7% and 35.9% vs 67% at 1- and 3-year, P = 0.056, respectively). Although the difference in the Child-Pugh classification score between the groups at initial treatment of HCC was not significant, the score was significantly worse at the time of data analysis in the non-IFN group than IFN group (7.19 +/- 1.42 vs 5.81 +/- 0.75, P = 0.0008). The cumulative rate of deviation from objects of any treatment for recurrent HCC was also higher in the non-IFN group than IFN group (6.7% and 27% vs 0 and 0% at 1- and 3-year, P = 0.048, respectively). CONCLUSION: Low-dose intermittent IFN-alpha therapy for patients with HCV-related compensated cirrhosis after curative HCC treatment was effective by making patients tolerant to medical or surgical treatment for recurrent HCC in the later period of observation.

Effects of a 24-week course of interferon-alpha therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma.

AIM: To assess whether a 24-wk course of interferon (IFN) could prevent hepatocellular carcinoma (HCC) recurrence and worsening of liver function in patients with hepatitis C virus (HCV)-infected patients after receiving curative treatment for primary HCC. METHODS: Outcomes in 42 patients with HCV infection treated with IFN-alpha, after curative treatment for primary HCC (IFN group), were compared with 42 matched curatively treated historical controls not given IFN (non-IFN group). RESULTS: Although the rate of initial recurrence did not differ significantly between IFN group and non-IFN group (0%, 44%, 61%, and 67% vs 4.8%, 53%, 81%, and 87% at 1, 3, 5, and 7 years, P = 0.153, respectively), IFN group showed a lower rate than the non-IFN group for second recurrence (0%, 10.4%, 28%, and 35% vs 0%, 30%, 59%, and 66% at 1, 3, 5 and 7 years, P = 0.022, respectively). Among the IFN group, patients with sustained virologic response (SVR) were less likely to have a second HCC recurrence than IFN patients without an SVR, or non-IFN patients. Multivariate analysis identified the lack of SVR as the only independent risk factor for a second recurrence, while SVR and Child-Pugh class A independently favored overall survival. CONCLUSION: Most intrahepatic recurrences of HCV-related HCC occurred during persistent viral infection. Eradication of HCV is essential for the prevention of HCC recurrence and improvement of survival.