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Introduction: Patients with the head and neck squamous cell carcinoma (SCC) are often treated with immune checkpoint inhibitors (ICIs). Recently, antibiotic intake was reported to lower the efficacy of ICIs in patients with several types of cancers. However, it is unclear if antibiotics affect the efficacy of ICIs in patients with head and neck SCC. We retrospectively assessed the influence of antibiotics on the treatment efficacy of nivolumab, an ICI, in patients with head and neck SCC. Methods: We reviewed the medical records of patients with head and neck SCC treated with nivolumab at the Department of Medical Oncology, Tohoku University Hospital, between 2017 and 2021. Patients who received oral or intravenous antibiotics from a month before the day of nivolumab initiation to the day of the first imaging evaluation of ICI efficacy were assigned to the antibiotic-treated group. The remaining patients were assigned to the antibiotic-untreated group. The response rate (RR), progression-free survival (PFS), and overall survival time (OS) of both groups were compared. Results: Forty-five patients were assigned to the antibiotic-treated group and 19 to the antibiotic-untreated group. The RR, median PFS, and median OS of the antibiotic-treated group were 23.7%, 3.2 months (95% confidential interval [CI]: 2.0–4.1), and 8.4 months (95% CI: 5.3–15.1) and those of the antibiotic-untreated group were 42.1%, 5.8 months (95% CI: 2.3–16.7), and 18.4 months (95% CI: 6.2–23.1), respectively. The PFS of the antibiotic-untreated group was significantly longer than that of the antibiotic-treated group. Conclusion: Our findings indicate that antibiotic treatment significantly shortens the PFS with nivolumab therapy in patients with head and neck SCC. [ABSTRACT FROM AUTHOR]

Introduction: Robotic surgery is regarded as an evolved type of laparoscopic surgery. Few studies have undertaken detailed analysis of complications following robotic gastrectomy for gastric cancer. Methods: This is a single-center retrospective study of 149 consecutive patients with gastric cancer who underwent robotic gastrectomy. It examines in detail the postoperative complications in robotic gastrectomy for gastric cancer, focusing on intra-abdominal infectious complications including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess. We also aim to identify the related risk factors. Results: The median operation time was 299 min and the median bleeding was 25 mL. The incidence of overall complications higher than grade II was 8.7%. Clinically serious complications higher than grade IIIa occurred in 6.7% of cases. The incidence of intra-abdominal infectious complications that were higher than grade II was 4.0%. Mortality in our consecutive series was zero. Multivariate logistic regression analysis indicated that postoperative intra-abdominal infectious complications were significantly associated with history of abdominal surgery (p = 0.043), with odds ratios of 17.890 (95% confidence interval 1.092–293.150) and with non-curative resection (p = 0.025), with odds ratios of 58.629 (95% confidence interval 1.687–2,037.450). Discussion/Conclusion: Robotic gastrectomy was shown to be a safe and effective treatment for gastric cancer when performed by experienced surgeons. Attention should be paid to the risk of developing postoperative complications when performing robotic gastrectomy in gastric cancer patients with a history of abdominal surgery and in patients with advanced gastric cancer in whom there is expected to be difficulty in curative resection. [ABSTRACT FROM AUTHOR]

Background: The present study sought to evaluate host-related factors as predictors in patients receiving chemotherapy for recurrent advanced gastric cancer. Methods: Sixty-three patients were enrolled in the study and received chemotherapy for recurrent gastric cancer at the Kochi Medical School from 2008 to 2015. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes. Results: The median survival time was significantly higher for patients with a Glasgow prognostic score (GPS) of 0 compared to a GPS of 1 or 2 (18.2 vs. 7.1 months; p = 0.006), and for patients in the normal range for carbohydrate antigen-125 (CA125) compared to higher levels (17.9 vs. 4.1 months; p = 0.003). There was no significant influence on overall survival by age, gender, disease status, metastatic site, time to recurrence, carcinoembryonic antigen level, CA19–9 level, prognostic nutrition index, or neutrophil to lymphocyte ratio according to the results of the univariate log-rank tests. Multivariate survival analysis identified a GPS of 1 or 2 (hazard ratio, 3.520; 95% confidence interval, 1.343–9.227; p = 0.010) and a high CA125 level (hazard ratio, 3.135; 95% confidence interval, 1.276–7.697; p = 0.013) as significant independent predictors associated with a poorer prognosis in the studied group of cancer patients. Conclusions: A GPS of 1 or 2 and a high level of CA125 are independent predictors of a poorer prognosis in patients receiving chemotherapy for recurrent gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: Transarterial chemoembolization (TACE) is recommended as a first-line therapy for hepatocellular carcinoma (HCC) patients ineligible for curative therapy and without portal invasion. The Assessment for Retreatment with TACE (ART) scoring system was recently proposed for identifying patients who would not show sufficient survival benefit from repeated TACE. We reevaluated the performance of ART in HCC patients treated in Japan, where selective TACE is commonly used. Methods: Between 2000 and 2013, 988 patients with HCC underwent TACE at Kinki University Hospital, and 627 received ≥2 sessions of TACE. Seventy-six patients who underwent ≥2 TACE sessions within 90 days were investigated for their performance of the ART score in the context of overall survival (OS). Results: Only 12% (76/627) of patients underwent ≥2 TACE sessions within 90 days. Of those, 52 patients showed a low ART score (0-1.5), and 24 had a high ART score (≥2.5); the median OS was 20.2 and 37.6 months, respectively (p = 0.8207). Conclusion: The ART scoring system did not demonstrate a sufficiently predictive impact on OS among the patients who underwent ≥2 TACE sessions within 90 days. Application of the ART score should be carefully considered because differences in TACE procedures and post-TACE treatment can affect the results while evaluating OS. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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]

Background: Gefitinib treatment has come to be recognized as the standard therapy for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. However, resistance to gefitinib has been observed in certain subpopulations of these patients. The purpose of this study was to evaluate the impact of smoking status on the efficacy of gefitinib in patients with NSCLC harboring EGFR mutations. Methods: The records of NSCLC patients harboring EGFR mutations who were treated with gefitinib at Kitasato University Hospital were retrospectively reviewed, and the treatment outcomes were evaluated. Results: In 153 patients with NSCLC harboring EGFR mutations, the overall response rate and progression-free survival (PFS) were 66.7% and 9.0 months, respectively. PFS differed significantly among the current smokers and never-smokers/former light smokers (10.7 vs. 5.4 months, p = 0.0002), and the response rate was significantly higher in the never-smokers/former light smokers than in the current smokers (72.3 vs. 55.8%, p = 0.04). Multivariate analysis identified smoking status as an independent predictor of PFS. Conclusion: The clinical data obtained in this study provide a valuable rationale for considering smoking status as a predictor of the efficacy of gefitinib in patients with NSCLC harboring activating EGFR mutations. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Protracted low-dose infusion of irinotecan has been suggested to enhance antitumor activity. A phase II study was conducted to evaluate the safety and efficacy of oral S-1 combined with 24-hour infusion of irinotecan and intravenous bevacizumab for metastatic colorectal cancer (MCRC). Methods: The subjects were 79 patients with MCRC; 57 were chemotherapy naïve. Irinotecan (125 mg/m2) was administered as a 24-hour infusion on days 1 and 15, S-1 (80 mg/m2) was administered orally on days 1-14, and bevacizumab (5.0 mg/kg) was given on days 1 and 15. The treatment was repeated every 4 weeks. Results: Median follow-up was 20.0 months, and the mean number of cycles was 7. The overall response rate was 79.7% (95% CI, 69.2-88.0), 86.0% (95% CI, 74.2-93.7) for first-line and 63.6% (95% CI, 40.7-82.8) for second-line treatment. The median progression-free survival was 16.4 months (95% CI, 13.9-21.0) for first-line and 9.4 months (95% CI, 4.9-16.5) for second-line treatment. The median overall survival was not reached. Grade 3-4 toxicities were neutropenia (43%), leukopenia (20.3%), anorexia (19.0%), and diarrhea (10.1%). Toxicity was tolerable. Conclusions: Combination chemotherapy with oral S-1 and biweekly 24-hour infusions of irinotecan plus bevacizumab appears to be highly active and well tolerated both as first-line and second-line chemotherapy for MCRC. © 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]

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: 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]

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]

Objective: A combination of weekly cisplatin plus gemcitabine is a new standard regimen for patients with advanced biliary tract cancer (BTC). This regimen does not require prolonged hydration schedules; however, the long-time safety profile has not been evaluated so far. In particular, the aim of this study was to evaluate the renal function during this regimen. Methods: We reviewed 79 consecutive patients with BTC who received the weekly cisplatin plus gemcitabine regimen. The incidence of adverse events was evaluated by CTCAE v4.0. Results: A total of 402 courses were administered. The median cumulative dose of cisplatin was 250 mg (range: 25-825). The renal function was exacerbated gradually throughout the treatment course. The incidence of a decreased glomerular filtration rate (GFR) at <50 ml/min was significantly related to a pretreatment GFR at <80 ml/min and a total dose of cisplatin >400 mg [p = 0.011, odds ratio (OR) 58.2, 95% confidence interval (CI): 2.5-1334.0 and p = 0.021, OR 18.3, 95% CI: 1.6-215.5]. Conclusions: The combination of weekly cisplatin and gemcitabine for advanced BTC gradually affected the renal function, and it was highly recommended to focus on both the change of GFR and total dose of cisplatin during this regimen. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The overexpression of Arf6 and GEP100 is responsible for the invasive activity that is crucial for the activation of the epidermal growth factor receptor (EGFR) signaling pathways in human cancer. However, whether or not the expression of the EGFR-GEP100-Arf6 axis can be used as a biomarker for the prognosis of lung cancer has yet to be fully determined. Tumor specimens were collected from 182 patients who underwent a complete resection for lung adenocarcinoma. We analyzed phospho-EGFR (p-EGFR), GEP100, and Arf6 expression levels in the primary tumor by immunohistochemical analysis. The expression of p-EGFR, GEP100, and Arf6 was observed in 65 (35.7%), 95 (52.2%), and 20 (11.0%) patients, respectively. Significant associations between p-EGFR and GEP100 expression and vessel invasion were identified. The expression of these individual molecules was not associated with any statistically significant differences in survival. However, triple positive expression of p-EGFR, GEP100, and Arf6 was significantly associated with an increased risk of death based on the multivariate analysis. The EGFR-GEP100-Arf6 axis affected the prognosis of patients with primary lung adenocarcinoma. The combination of p-EGFR, GEP100, and Arf6 staining can predict the prognosis of patients after surgery. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: C-reactive protein (CRP) is a practical prognostic marker in patients with hepatocellular carcinoma (HCC). We investigated the prognostic value of adding the CRP level to other validated staging systems (Cancer Liver Italian Program, Japan Integrated Staging, Barcelona Clinic Liver Cancer classification system, Tokyo score and tumor node metastasis classification) in HCC patients. Methods: One hundred and eighty-six newly diagnosed HCC patients were retrospectively evaluated. A multivariate analysis identified the clinicopathological variables associated with overall survival; the variables identified were then added to each staging system and compared to those without the additional variable. Results: In multivariate analysis, an elevated serum CRP level was independently associated with a poor prognosis (hazard ratio 3.792, p < 0.0001). The addition of the CRP level to each of the established staging systems provided a higher linear χ2 valueand a lower -2 log likelihood than those without the addition of the term. Moreover, the area under the receiver-operating characteristic curve (AUC) analysis showed that the addition of CRP improved the AUC of each staging system. Conclusions: This study demonstrates that an elevated serum CRP level is independently associated with a poor prognosis in HCC patients, and the addition of the CRP level to the validated staging systems could improve the prognostic ability of each staging system. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: A dose escalation study of biweekly irinotecan (CPT-11) combined with capecitabine was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) for metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Methods: Escalating doses of CPT-11 (80-120 mg/m2) were administered on days 1 and 15. Capecitabine was administered at a fixed dose of 1,657 mg/m2/day for 21 consecutive days, followed by 7 days of rest. We treated 3-6 patients at a particular dose level until the MTD was determined. Results: Twenty patients were treated. The MTD was determined to be 100 mg/m2, as 3 of 6 patients developed dose-limiting toxicities, grade 3 leukopenia, neutropenia, photophobia, fatigue and diarrhea. The RD for the phase II study was thus determined to be 90 mg/m2. The response rate was 41.7%. Conclusions: Combination therapy with CPT-11 and capecitabine was well tolerated with a promising response rate for MBC that had been treated previously with anthracyclines and taxanes. A multi-center phase II study is warranted to evaluate the efficacy and safety of this combination therapy with pharmacokinetic assessment. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Lymph node (LN) metastasis is one of the most important prognostic factors for undifferentiated-type early gastric cancer (EGC). The aim of this study was to examine expansion of micrometastasis in regional LNs to clarify the importance of lymphadenectomy for undifferentiated-type EGC. Methods: Clinicopathological features of 307 patients with undifferentiated-type EGC who underwent gastrectomy with lymphadenectomy between 1997 and 2010 at the Department of Surgical Oncology, Osaka City University, were retrospectively reviewed. Micrometastasis in LNs was detected by immunohistochemistry using anticytokeratin antibody. Results: The incidence of LN metastasis was 1.8% in patients with mucosal (pT1a) tumors and 17.3% in those with submucosal (pT1b) tumors. Multivariate analysis revealed that lymphatic invasion and tumor depth were independently related to LN metastasis. Micrometastasis was found in 41 (13.3%) patients. Twenty-two patients with pN0 had micrometastasis in the perigastric region. Micrometastasis had spread to the area along the left gastric or common hepatic artery in 12 patients. Patients with an upgraded stage by micrometastasis had significantly worse disease-free survival. Conclusions: LN micrometastasis was observed beyond the perigastric LNs and correlated with poor outcomes in patients with undifferentiated-type EGC. These data underscore the importance of adequate lymphadenectomy for patients with undifferentiated-type EGC. © 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]

Objectives: Recent reports indicated that reduced SLC22A7 (a gene-encoding organic anion transporter 2) expression in noncancerous liver tissue predicts hepatocellular carcinoma (HCC) recurrence after curative resection. Our study aimed to elucidate the association between SLC22A7 expression and HCC development in chronic hepatitis C patients. Methods: HCC recurrence after local ablation therapy and SLC22A7 expression in noncancerous liver tissue were analyzed in 20 patients. Subsequently, the association between de novo HCC development and SLC22A7 expression was examined at baseline in 38 hepatitis C patients without HCC who subsequently developed HCC as well as in 76 hepatitis C patients who did not develop HCC and were matched for age, gender and stage of fibrosis. Results: In the patients whose HCC had been cured, reduced SLC22A7 expression in noncancerous liver tissue was significantly associated with a high incidence of multifocal HCC recurrence. In patients without HCC at baseline, cumulative incidence of de novo HCC development was significantly higher with a reduced SLC22A7 expression than with a normal expression (p = 0.01). This difference remained significant among patients without known risk factors for HCC like age and advanced fibrosis. Conclusion: Reduced SLC22A7 expression in the liver indicates a significant risk for HCC development in chronic hepatitis C, independently of other risk factors. © 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: To explore the possibility of nonsurgical treatment of primary breast cancers by a sequential treatment of chemotherapy and radiotherapy. Methods: We conducted a safety and efficacy trial of chemotherapy and radiation therapy sequentially as primary therapy in patients with stage I-IIIA breast cancer. All patients underwent mastectomy or lumpectomy 12-16 weeks after the completion of radiation therapy to maximize the effect of radiation therapy. The primary endpoint was the pathological complete response (pCR) rate. Results: Between June 2004 and April 2005, one hundred eight patients were enrolled. Thirty six percent of the entire population achieved a pCR, which could not reject the null hypothesis. The pCR rate was 57% in patients with hormone receptor (HR)-negative/HER-2-positive tumors and 52% in patients with triple-negative tumors. While 7% of the HR-negative/HER2-positive patients recurred, a higher incidence of recurrence (24%) was observed in triple-negative tumors in a follow-up of 4.5 years. The rate of breast-conserving surgery was 88.9% (96/108). Conclusion: The pCR rate was not high enough, even though preoperative sequential chemoradiation therapy did not increase the risk of operative complications and could achieve a high rate of breast-conserving surgery. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: We reported that the KDIGO (Kidney Disease: Improving Global Outcomes) criteria could stratify the risk of mortality in acute kidney injury (AKI) caused by cisplatin. The purpose of this study was to investigate risk factors of severe cisplatin-induced AKI (CIA). Methods: From January 2006 to December 2012, we identified Japanese cancer patients who were treated with cisplatin as a first-line chemotherapy at Nagoya University Hospital. Serum creatinine levels were used to define CIA. Results: We evaluated 1,721 patients treated with cisplatin. In multivariable analysis, cisplatin dosages/m2 [odds ratio (OR) 1.019] or diagnosis of cancer stage 4 (OR 1.797) were risk factors of moderate CIA. History of diabetes mellitus (OR 3.454), history of cardiovascular disease (OR 3.612) or diagnosis of cancer stage 4 (OR 2.610) were risk factors of severe CIA. Conclusions: Diabetes mellitus, cardiovascular disease and advanced cancer increased the risk of severe CIA. As severe CIA shortens the survival period, we should consider whether the use of cisplatin benefits these patients. © 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]

Background: Breast cancer is associated with a relatively good prognosis. Prognostic factors examined to date are related to early recurrence while those related to late recurrence and their countermeasures remain unclear. Therefore, we examined the factors related to late recurrence. Patients and Methods: From January 1980 to August 2012, 4,774 patients who underwent primary treatment and estrogen (ER) and progesterone receptor (PgR) assessment were enrolled in this study. The patients were divided into two groups, those with a follow-up period <10 years and those without any recurrence at 10 years but who continued follow-up examinations. Recurrence occurred in 711 patients followed up for <10 years and in 51 patients for ≥10 years. Results: The overall 10-year cumulative disease-free survival rate was 79.5%, and the recurrence rate at ≥10 years was 5.8%. A multivariate analysis revealed that the factors related to late recurrence were PgR positivity and positive nodes. This result differed from that for early recurrence in terms of ER/PgR, Ki-67 index and p53 overexpression. Conclusion: PgR positivity and lymph node metastases significantly correlated with late recurrence. Therefore, it is important to evaluate appropriate measures such as treatment period and treatment regimen for hormone-sensitive patients. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: A phase II study was performed to investigate the safety and efficacy of concurrent chemoradiotherapy (CCRT) combined with an orally active fluoropyrimidine, S-1, plus cisplatin for locally advanced esophageal cancer (LAEC). Methods: CCRT comprised 2 courses, a 30-Gy radiotherapy over 3 weeks plus daily oral S-1 (80 mg/m2/day) for 2 weeks and a 24-hour cisplatin infusion (70 mg/m2) on day 8, and an identical course administered after a 2-week break. Results: One hundred and sixteen patients, 12 with stage II, 71 with stage III, and 33 with stage IVa LAEC participated, and 106 of them (91.4%) completed the CCRT course. The most serious toxicity was myelosuppression: grade 3 and 4 neutropenia occurred in 28.4 and 9.5% of patients, respectively. Nonhematologic toxicity was moderate. Complete response rates in patients with stage II, III, and IVa LAEC were 91.7, 67.6, and 36.4%, respectively. The overall median survival time was 2.3 years and that of patients with stage II, III, and IVa cancer was 7.0, 2.6, and 1.3 years, respectively. Conclusions: CCRT combined with S-1 plus cisplatin showed promising safety and efficacy. Potentially, this combination therapy could become a baseline medication for patients with LAEC. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical significance of the serum inflammatory cytokines and the blood granulocytes/lymphocytes (G/L) ratio in patients with colorectal cancer. Methods: Forty-six patients underwent surgery for colorectal cancer. The G/L ratio and serum inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor-α (TNF-α), granulocyte colony-stimulating factor and macrophage colony-stimulating factor (M-CSF) were measured before surgery and correlated with the Tumour Node Metastasis classification and overall survival. Results: Serum IL-6 in T3-4, N1-2, M1 cases and cancer stages III-IV sub-groups was significantly higher than in Tis-2, N0, M0 and cancer stages 0-II sub-groups. The G/L ratio, serum M-CSF and TNF-α in T3-4 cases were significantly higher than in Tis-2 cases. Furthermore, the G/L ratio and serum IL-6 showed a significant inverse correlation with the overall survival, while the G/L ratio showed a significant positive correlation with serum IL-6, TNF-α and M-CSF. Multivariate analysis showed that the serum IL-6 level and G/L ratio were independent risk factors for poor prognosis. Conclusions: In this investigation, a pre-operative high level of serum IL-6 and the G/L ratio appeared to be significant predictive factors for cancer progression and poor prognosis. Accordingly, these variables might be clinically relevant biomarkers in patients with colorectal cancer. Copyright © 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]

Objective: This phase II study examined the efficacy and safety of alternating regimens of mFOLFOX6 and FOLFIRI as a first-line treatment for unresectable or metastatic colorectal cancer. Patients and Methods: Forty-eight patients were enrolled in this study. Patients received an alternating regimen of 4 cycles of mFOLFOX6 followed by 4 cycles of FOLFIRI. Results: The characteristics of the study population were as follows: males/females 34/12, median age 66 years (range 43-75) and Eastern Cooperative Oncology Group performance status 0/1/2 in 37/9/0 patients. The overall response rate was 58.7% [95% confidence interval (CI) 43.9-73.5]. The median progression-free survival was 10.3 months (95% CI 7.5-11.9), and the median overall survival was 28.4 months (95% CI 22.5-35.7). Among the 47 patients evaluated for toxicity, the most common grade 3-4 adverse events were leukopenia (26%), neutropenia (55%), anemia (4%), neurotoxicity (0%), diarrhea (2%), febrile neutropenia (4%), nausea (4%), vomiting (2%), and hypersensitivity (0%). Conclusions: The results of this phase II study indicate that this alternating schedule is effective and well tolerated as a first-line treatment for unresectable or metastatic colorectal cancer. The low rate of grade 3 neurotoxicity is also promising. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]