Background This study was conducted to investigate whether human epidermal growth factor receptor 2 (HER2) status, epidermal growth factor receptor (EGFR) status, and c-MET status are independent prognostic factors for advanced gastric cancer patients who received standard chemotherapy. Method Unresectable or recurrent gastric or gastroesophageal junction cancer patients with histologically confirmed adenocarcinoma treated with S-1 plus cisplatin as first-line chemotherapy were eligible. Formalin-fixed paraffin-embedded tumor samples were examined for HER2, EGFR, and c-MET status using immunohistochemistry (IHC). Additionally, gene amplification was examined using fluorescent in situ hybridization (FISH) for HER2. Positivity was defined as an IHC score of 3? or an IHC score of 2?/ FISH positive for HER2, and an IHC score of 2? or 3? for both EGFR and c-MET. Results Of the 293 patients from nine institutions, 43 (15 %) were HER2 positive, 79 (27 %) were EGFR positive, and 120 (41 %) were c-MET positive. Ten patients (3 %) showed positive co-expression of HER2, EGFR, and c-MET. After a median follow-up time of 58.4 months with 280 deaths, there was no significant difference in overall survival (OS) in terms of HER2 and EGFR status. However, there was a significant difference in OS between c-MET-positive and c-MET-negative patients [median, 11.9 months vs 14.2 months; hazard ratio, 1.31 (95 % confidence interval, 1.03-1.67); log-rank P = 0.024]. 123Gastric Cancer (2016( ) 19:183-191 DOI 10.1007 Multivariate analysis also showed that c-MET positivity was still a prognostic factor for OS [hazard ratio, 1.30 (95 % confidence interval, 1.02-1.67); P = 0.037]. Conclusions The study suggested that c-MET-positive status had poor prognostic value. These data could be used as the basis for future clinical trials for targeting agents for advanced gastric cancer patients.

BackgroundRetrospective analyses in the West suggest that mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA are negative predictive factors for cetuximab treatment in colorectal cancer patients. We developed a novel multiplex kit detecting 36 mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA using Luminex (xMAP) assay in a single reaction.MethodsTumor samples and clinical data from Asian colorectal cancer patients treated with cetuximab were collected. We investigated KRAS, BRAF, NRAS, and PIK3CA mutations using both the multiplex kit and direct sequencing methods, and evaluated the concordance between the 2 methods. Objective response, progression-free survival (PFS), and overall survival (OS) were also evaluated according to mutational status.ResultsIn total, 82 of 83 samples (78 surgically resected specimens and 5 biopsy specimens) were analyzed using both methods. All multiplex assays were performed using 50 ng of template DNA. The concordance rate between the methods was 100%. Overall, 49 (59.8%) patients had all wild-type tumors, 21 (25.6%) had tumors harboring KRAS codon 12 or 13 mutations, and 12 (14.6%) had tumors harboring KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA mutations. The response rates in these patient groups were 38.8%, 4.8%, and 0%, respectively. Median PFS in these groups was 6.1 months (95% confidence interval (CI): 3.1–9.2), 2.7 months (1.2–4.2), and 1.6 months (1.5–1.7); median OS was 13.8 months (9.2–18.4), 8.2 months (5.7–10.7), and 6.3 months (1.3–11.3), respectively. Statistically significant differences in both PFS and OS were found between patients with all wild-type tumors and those with KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA mutations (PFS: 95% CI, 0.11–0.44; P < 0.0001; OS: 95% CI, 0.15–0.61; P < 0.0001).ConclusionsOur newly developed multiplex kit is practical and feasible for investigation of a range of sample types. Moreover, mutations in KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA detected in Asian patients were not predictive of clinical benefits from cetuximab treatment, similar to the result obtained in European studies.

This randomized clinical trial assesses whether etoposide plus cisplatin or irinotecan plus cisplatin is a more effective treatment regimen in terms of overall survival in patients with advanced neuroendocrine carcinoma of the digestive system.

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Background: It has been reported that morphologic response to preoperative chemotherapy is an independent prognostic factor in patients who undergo hepatic resection of colorectal liver metastases (CLM). The aim of this study was to evaluate the predictive value of morphologic response to first-line chemotherapy in patients with CLM. Methods: We assessed 41 patients with CLM who received fluorouracil-based chemotherapy with or without bevacizumab as the first-line chemotherapy between April 2006 and June 2012. Three blinded radiologists evaluated computed tomography images and classified them as optimal, incomplete or no response according to the morphologic criteria. Response to systemic chemotherapy was also evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Predictive factors associated with progression-free survival (PFS) were identified in multivariate analysis. Results: Twenty-three patients (56%) received chemotherapy with bevacizumab, while 18 patients (44%) received chemotherapy without bevacizumab. Optimal morphologic response was observed in 11 patients (48%) treated with bevacizumab and in 5 patients (28%) treated without bevacizumab (p = 0.19). Eight patients (20%) underwent hepatic resection after chemotherapy. The median follow-up period was 31.3 months. The median PFS was 13.3 months for patients with optical morphologic response and 8.7 months in those with incomplete/no morphologic response (p = 0.0026). On multivariate analysis, performance status and morphologic response were significant independent predictors of PFS. Conclusion: Optimal morphologic response was significantly associated with PFS in patients with CLM who were treated with fluorouracil-based chemotherapy as the first-line chemotherapy.

Endoscopic submucosal dissection (ESD) is an accepted standard treatment for early gastric cancer but is not widely used in the esophagus because of technical difficulties. To increase the safety of esophageal ESD, we used a scissors-type device called the stag beetle (SB) knife. The aim of this study was to determine the efficacy and safety of ESD using the SB knife. We performed a single-center retrospective, uncontrolled trial. A total of 38 lesions were excised by ESD from 35 consecutive patients who were retrospectively divided into the following two groups according to the type of knife used to perform ESD: the hook knife (hook group) was used in 20 patients (21 lesions), and the SB knife (SB group) was used in 15 patients (17 lesions). We evaluated and compared the operative time, lesion size, en bloc resection rate, pathological margins free rate, and complication rate in both groups. The operative time was shorter in the SB group (median 70.0 minutes [interquartile range, 47.5-87.0]) than in the hook group (92.0 minutes [interquartile range, 63.0-114.0]) (P = 0.019), and the rate of complications in the SB group was 0% compared with 45.0% in the hook group (P = 0.004). However, the lesion size, en bloc resection rate, and pathological margins free rate did not differ significantly between the two groups. In conclusion, ESD using the SB knife was safer than that using a conventional knife for superficial esophageal neoplasms.

Object: To examine the clinical outcomes of a project to enhance the awareness of community-based palliative care (awareness-enhancing project), focusing on home death and care rates in communities.Methods: A single-center study on community-based intervention was conducted. The awareness-enhancing project, consisting of three intervention approaches (outreach, palliative care education for community-based medical professionals, and information-sharing tool use), was executed, and changes in the home death rate in the community were examined.Results: The home death rate markedly exceeded the national mean from 2010. In 2012–2013, it was as high as 19.9%, greater than the previous 5.9% (p = 0.001). Through multivariate analysis, the participation of home care physicians and visiting nurses in a palliative care education program, and patients' Palliative Prognostic Index values were identified as factors significantly influencing the home death rate.Conclusion: The three intervention approaches time dependently increased the home death rate as a clinical outcome in the community, although they targeted limited areas. These approaches may aid in increasing the number of individuals who die in their homes.

Weekly paclitaxel was modestly active in patients with gastric cancer refractory to docetaxel-based chemotherapy.