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Objectives: Radiofrequency ablation plays a key role in the treatment of early-stage hepatocellular carcinoma. However, it is not recommended for intermediate-stage hepatocellular carcinoma. The objective of this study was to clarify the efficacy and safety of radiofrequency ablation for treating intermediate-stage hepatocellular carcinoma. Methods: We examined the outcome of 65 consecutive patients who were treated with radiofrequency ablation with or without transarterial chemoembolization for intermediate-stage hepatocellular carcinoma. Results: With a median follow-up of 37 months, overall survival rates of 65 cases at 1, 3, 5, and 7 years were 90, 70, 51, and 36%, respectively. Multivariate analysis of clinical parameters revealed that the multicentric occurrence (MC)/intrahepatic metastasis (IM) was the only significant prognostic factor for overall survival (hazard ratio, 4.9; 95% confidence intervals, 2.1-11.4). Tumor size and tumor number were not significant factors for survival. The overall survival rates of patients with MC (n = 33) at 1, 3, 5, and 7 years were 97, 90, 80, and 59%, respectively; those for patients with IM (n = 32) were 86, 55, 14, and 8%, respectively (p < 0.0001). Two cases (4.9%) had complications of hemothorax and diaphragmatic burn; however, no major complications were observed. Conclusion: Radiofrequency ablation is safe and effective for the treatment of intermediate-stage hepatocellular carcinoma, especially for patients with MC. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Barcelona Clinic Liver Cancer (BCLC) stage B, an intermediate stage, includes various conditions of hepatocellular carcinoma (HCC). This heterogeneity of the patients with intermediate-stage HCC makes it difficult to predict their survival rates. In the present study, we examined the validity of the modified Bolondi classification (Kinki criteria) as a subclassification of patients with BCLC stage B HCC. Methods: Of 906 patients who underwent conventional transarterial chemoembolization at Kinki University Hospital, 753, who met the inclusion criteria, were examined. Of these 753 patients, 425 (56.4%) with BCLC stage B were subclassified using the Kinki criteria to examine the survival rate. Results: According to the Kinki criteria, 158 (37.2%) were subclassified into subclass B1, 236 (55.5%) into B2, and 31 (7.3%) into B3. The comparison of the survival rates showed that the median overall survival was 3.9 years (95% CI, 3.2-4.6) in the BCLC subclass B1 group, 2.5 years (95% CI, 2.2-3.1) in the B2 group, and 1.1 years (95% CI, 0.6-1.5) in the B3 group (p < 0.001). Conclusion: When the BCLC stage B patients were subclassified according to the Kinki criteria, survival curves were stratified with significant differences, suggesting that the Kinki criteria were suitable for the subclassification of the intermediate-stage HCC patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objecitive: Fucosyltransferase 8 (FUT8), the only enzyme responsible for the core α1,6-fucosylation of asparagine-linked oligosaccharides of glycoproteins, is a vital enzyme in cancer development and progression. We examined FUT8 expression in non-small cell lung cancers (NSCLCs) to analyze its clinical significance. We also examined the expression of guanosine diphosphate-mannose-4,6-dehydratase (GMD), which is imperative for the synthesis of fucosylated oligosaccharides. Methods: Using immunohistochemistry, we evaluated the expression of FUT8 and GMD in relation to patient survival and prognosis in potentially curatively resected NSCLCs. Results: High expression of FUT8 was found in 67 of 129 NSCLCs (51.9%) and was significantly found in non-squamous cell carcinomas (p = 0.008). High expression of FUT8 was associated with poor survival (p = 0.03) and was also a significant and independent unfavorable prognostic factor in patients with potentially curatively resected NSCLCs (p = 0.047). High expression of GMD was significantly associated with high FUT8 expression (p = 0.04). Conclusions: High expression of FUT8 is associated with an unfavorable clinical outcome in patients with potentially curatively resected NSCLCs, suggesting that FUT8 can be a prognostic factor. The analysis of FUT8 expression and its core fucosylated products may provide new insights for the therapeutic targets of NSCLCs. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify the prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who are refractory or intolerant to sorafenib and to exclude unsuitable candidates from subsequent therapy. Methods: The study cohort consisted of 111 patients who had discontinued sorafenib therapy. Uni- and multivariate analyses were conducted to identify the prognostic factors for survival after discontinuation of sorafenib therapy. Results: The median age of the patients was 70 years, and 96 of them (86%) were male. The Eastern Cooperative Oncology Group performance status was 0-1 in 94 patients (85%). Forty patients (36%) were classified as Child-Pugh class A and 57 (51%) as Child-Pugh class B. The median survival time after discontinuation of sorafenib therapy was 146 days. Hepatitis C viral antibody negativity, presence of ascites, absence of a history of previous treatment excluding sorafenib, elevated serum total bilirubin level, and elevated serum α-fetoprotein level were identified as the independent unfavorable prognostic factors by multivariate analysis. The median survival time of the patients with 4 or 5 unfavorable prognostic factors was 59 days. Conclusions: We should judge the indication of any subsequent therapy carefully in patients with 4 or 5 of the aforementioned factors. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Exon 19 deletion and L858R point mutation of the epidermal growth factor receptor (EGFR) are the most commonly encountered EGFR mutations in non-small cell lung cancer (NSCLC), and predict higher clinical outcomes following treatment with gefitinib. The objective of this study was to evaluate the differential clinical outcomes of gefitinib in patients with NSCLC according to the type of active EGFR mutation, i.e. exon 19 deletion or L858R point mutation. Methods: We identified patients with advanced NSCLC harboring the exon 19 deletion or the L858R point mutation of EGFR who were on gefitinib treatment. The clinical outcomes were evaluated. Results: Of the 124 patients with NSCLC harboring active EGFR mutations, the overall response rate, progression-free survival and overall survival were 60.5%, 11.3 and 27.3 months, respectively, and did not differ significantly between patients with the exon 19 deletion (61.8%, 11.3 and 32.2 months, respectively) and those with the L858R point mutation (58.9%, 9.0 and 27.7 months, respectively). Conclusion: It may be considered that there is no difference in the clinical efficacy of gefitinib between NSCLC patients who harbor the exon 19 deletion and those with the L858R point mutation. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to evaluate the superiority of the high-sensitivity modified Glasgow prognostic score (HS-mGPS) before surgery in patients with gastric cancer. Patients and Methods: The participants of this retrospective study comprised 552 patients with gastric cancer who underwent gastrectomy at the Fukuoka University Hospital. The HS-mGPS was calculated before surgery based on cutoff values of 0.3 mg/dl for C-reactive protein and 3.5 g/dl for albumin, and correlations between the HS-mGPS and the clinicopathological parameters and prognosis were evaluated. In addition, the superiority of the HS-mGPS to the mGPS as a prognostic indicator was examined in detail. Results: The mGPS was 0 in 494 patients, 1 in 24 patients and 2 in 34 patients. In contrast, the HS-mGPS was 0 in 411 patients, 1 in 75 patients and 2 in 66 patients. Both the mGPS (p < 0.0001) and HS-mGPS (p < 0.0001) were good prognostic predictors in gastric cancer patients who underwent gastrectomy. Of the 494 patients with an mGPS of 0 before surgery, 51 and 32 exhibited an HS-mGPS of 1 and 2, respectively. The patients who exhibited migration in the HS-mGPS demonstrated a significantly more unfavorable prognosis than the patients with an HS-mGPS of 0 (p < 0.0001). The prognostic impact of the HS-mGPS was especially clear in stage I and IV patients (p = 0.0027, p = 0.017). The HS-mGPS was found to be a superior prognostic predictor compared to the mGPS in a multivariate analysis (p = 0.0002). Conclusions: The HS-mGPS before surgery is a superior prognostic predictor in patients with gastric cancer. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) have risen steadily in the USA and in northern Europe. These increases are thought to be a consequence of persistent infection with high-risk human papillomavirus (HPV) in OPSCC patients. HPV is an emerging etiologic factor in OPSCC. In Japan, the incidence of OPSCC has significantly increased over the last three decades. However, the population of HPV-positive OPSCC patients is currently unknown. We examined the nationwide trends with regard to HPV incidence in OPSCC patients at 21 specific sites, and examined the relationship between the presence of HPV and survival in OPSCC patients in Japan. Methods: Tumor samples were obtained from patients with OPSCC prior to treatment, and HPV infection was investigated by polymerase chain reaction (PCR). Hybrid Capture 2 (HC2) was also adopted for swab examination on the surface of fresh tumors. Results: HPV was detected by PCR in 79 (50.3%) out of 157 OPSCC patients. The clinical features of HPV-positive OPSCC were low differentiation, a tendency to involve the lateral wall, and high nodal staging. The sensitivity and specificity of HC2 were 93.7 and 96.2%, respectively, indicating its utility as a screening test. HPV-positive patients had significantly better overall survival and disease-free survival than HPV-negative patients. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Mutations in the KRAS gene have been identified as negative predictors of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy by patients with metastatic colorectal cancer (mCRC). However, it has been based on the study of mainly Caucasian mCRC patients. This prospective study investigated the relationship between the mutation status of EGFR-related genes including KRAS and the response rate (RR) to cetuximab plus irinotecan therapy in Japanese mCRC patients. Methods: Samples taken from 43 chemotherapy-refractory mCRC patients who had undergone cetuximab plus irinotecan therapy at 11 medical centers in Japan were subjected to direct DNA sequencing to determine the KRAS, BRAF, PIK3CA, NRAS, and AKT1 mutation status. The clinical outcome after the treatment was evaluated for each mutation status. Results:KRAS mutations were detected in 31.7% of 41 eligible patients. The RR to cetuximab plus irinotecan therapy was found to be 17.9 and 0% in the KRAS wild-type and mutant subgroups, respectively. Conclusion: Despite the identification of a lower-than-expected RR to treatment by the KRAS wild-type subgroup, KRAS mutation status appears to be a useful predictive marker of response to cetuximab plus irinotecan therapy in Japanese mCRC patients. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Epithelioid tumors with aggressive behavior have been reported; however, the epithelioid type of malignant pleural mesothelioma (MPM) has a less aggressive behavior. Few studies have evaluated the prognostic value of epithelial-mesenchymal transition (EMT) markers in MPM. We hypothesized that mesenchymal characteristics might predominate in the tumors. Tumor specimens were collected from 33 consecutive patients. We analyzed the EMT expression levels in tumor samples by an immunohistochemical analysis. Positive expression of E-cadherin, γ-catenin, vimentin, fibronectin, Twist and YB-1 was observed in 25, 14, 21, 1, 19 and 18 patients, respectively. No significant association between these markers and the clinicopathological characteristics was found. γ-Catenin demonstrated a trend towards decreased expression in sarcomatoid tumors compared to epithelioid tumors. On the other hand, a trend was noted towards higher expression of vimentin, Twist and YB-1 in sarcomatoid tumors. The survival curves demonstrated that the patients with negative γ-catenin and positive Twist staining had a tendency to have a worse prognosis. Although the individual proteins might not significantly affect the progression of MPM, the combination of γ-catenin and Twist staining can predict the prognosis of patients with MPM. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Combined chemotherapy with S-1 and irinotecan (IRIS) for metastatic colorectal cancer has been reported to be effective and safe. However, there are only a few studies on the effects of adding bevacizumab to IRIS. We conducted a clinical study to evaluate the efficacy and safety of IRIS plus bevacizumab as first-line therapy for metastatic colorectal cancer. Methods: Forty metastatic colorectal cancer patients were enrolled in this phase II study. All patients received irinotecan (80 mg/m2) and bevacizumab (7 mg/kg) on days 1 and 15 and S-1 (40-60 mg twice daily) on days 1-21 of a 5-week repeated cycle. Results: The response rate was 47.4% [95% confidence interval (CI) 31.5-63.2], progression-free survival was 11.9 months (95% CI 9.4-16.8), and overall survival was 23.4 months (95% CI 19.0-inf). The only grade 3 hematological toxicity was neutropenia (16%) and the incidences of grade 3 nonhematological toxicity were low at <10%, other than diarrhea (10.9%). Conclusion: In this clinical study, we revealed IRIS plus bevacizumab to be a promising first-line regimen for metastatic colorectal cancer with a low incidence of serious toxicities, in which favorable response rates and extension of survival time can be expected. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The study aimed to evaluate the efficacy of surgery after preoperative chemotherapy for unresectable advanced gastric cancer. Method: Twenty patients with disappeared peritoneal dissemination or decreased lymph node metastasis by systemic chemotherapy underwent surgery (group S), while 14 with peritoneal dissemination or lymph nodes >N2 (group C) received continuous systemic chemotherapy. Among group S patients, 15 underwent a curative resection (group R0), while the other 5 did not microscopically undergo a curative resection (group R1). Results: The median survival time for all patients was 535 days. Survival time was significantly dependent on the chemotherapy response (p < 0.002). The survival period in group S was significantly longer than that in group C (median survival time 747 vs. 476 days; p < 0.02). The relapse-free survival was 299 days in group S. In particular, the survival period of patients who underwent R0 surgery by preoperative chemotherapy was significantly longer than that of group R1 patients (median survival time 794 vs. 485 days; p < 0.02). Multivariate analysis revealed that R0 surgery was a significant and independent prognostic factor. Conclusion: Surgery was effective for advanced gastric cancer patients when performed as R0 resection following the disappearance of non-curative factors by preoperative chemotherapy. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the association between BCL2 single-nucleotide polymorphisms and survival outcome in advanced non-small cell lung cancer (NSCLC). Methods: One hundred and sixty-eight patients with advanced NSCLC who were treated with anti-cancer drugs and could be evaluated for therapeutic response between April 2005 and March 2010 at Kyoto University Hospital were enrolled. DNA was extracted from peripheral blood samples. The BCL2 polymorphisms -938 C→A (rs2279115) and +21 A→G (rs1801018) were genotyped using the 5′-nuclease assay. The univariate relationship between each independent clinicopathologic variable and BCL2 genotype was examined using Fisher's exact test. To evaluate risk factors associated with prognosis, a Cox proportional hazards regression model with a step-down procedure was used. Results: The median survival time of patients with the -938 AA and AC genotypes were significantly shorter than those with the -938 CC genotype (p = 0.027 by log-rank test). Based on multivariate analysis, poor performance status [hazard ratio (HR) 2.424, 95% confidence interval (CI) 1.727-3.262; p < 0.0001], non-adenocarcinoma histology (HR 1.512, 95% CI 1.167-1.938; p = 0.0048) and the BCL2 -938 AA + AC genotype (HR 1.219, 95% CI, 1.024-1.456; p = 0.0256) were significant independent prognostic factors for survival. Conclusions: Polymorphisms in BCL2 may be associated with survival in advanced-stage NSCLC patients who received chemotherapy. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]