Laparoscopic sentinel node navigation surgery versus laparoscopic gastrectomy with lymph node dissection for early gastric cancer: short-term outcomes of a multicentre randomized controlled trial (SENORITA).

BACKGROUND: Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection. METHODS: The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study. RESULTS: A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647). CONCLUSION: The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND). MÉTODOS: El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio. RESULTADOS: Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien-Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647). CONCLUSIÓN: El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.

Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy.

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions.

The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others. (ii) Control arms for chemotherapy: for advanced stage ovarian cancer the standard is intravenous 3-weekly carboplatin and paclitaxel. Acceptable alternatives, which should be stratified variables in trials when more than one regimen is offered, include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal therapy. (iii) Trial Endpoints: overall survival is the preferred primary endpoint for first-line clinical trials with or without a maintenance component. Progression-free survival (PFS) is an alternative primary endpoint, but if PFS is chosen overall survival must be measured as a secondary endpoint and PFS must be supported by additional endpoints, including predefined patient reported outcomes and time to first or second subsequent therapy. For neoadjuvant therapy, additional 'window of opportunity' endpoints should be included.

Correlation between lymph node count and survival and a reappraisal of lymph node ratio as a predictor of survival in gastric cancer: A multi-institutional cohort study.

PURPOSE: The purpose of this study is to evaluate the correlation between lymph node count (LNC) and survival and to evaluate whether lymph node ratio (LNR) which is related to LNC is a better predictor of survival for gastric cancer than the N category of UICC/AJCC through a multi-institutional cohort study. METHODS: The study cohort included 3284 patients from eight institutions. Lower and upper quartiles of LNC were used for comparisons. The cut-off values (0, 0.06, 0.27, and 0.49) for the LNR categories were based on Classification and Regression Trees techniques. Akaike information criteria (AIC) for Cox regression models was used to evaluate goodness of fit between competing predictor variables (LNR vs. N category). RESULTS: The 5-year disease-specific survival (DSS) rates of lower and upper quartiles of LNC were 82.2% and 84.8%. In the subgroup analysis of pN category, the upper quartile of LNC showed better survival than the lower quartile in pN2, pN3a, and pN3b subgroups. Regarding LNR, 5-year DSS of LNR 0, 0-0.06, 0.06-0.27, 0.27-0.49, and >0.49 was 95.3%, 88.7%, 70.6%, 42.7%, and 17.2% respectively. Multivariate analysis showed that pT, pN, LNR, residual tumor status, distant metastasis, and tumor differentiation significantly affected survival. The analysis also confirmed superiority of LNR compared with N category in the AIC analysis. CONCLUSION: Higher LNC correlated with better survival in patients with pN2, pN3a, and pN3b gastric cancer. Our data indicate that LNR is a better predictor of survival than N category of UICC/AJCC.

Comparison of outcomes after laparoscopy-assisted and open total gastrectomy for early gastric cancer.

BACKGROUND: The aim of this study was to compare the results of laparoscopy-assisted total gastrectomy with those of open total gastrectomy for early gastric cancer. METHODS: Patients with gastric cancer who underwent total gastrectomy with curative intent in three Korean tertiary hospitals between January 2003 and December 2010 were included in this multicentre, retrospective, propensity score-matched cohort study. Cox proportional hazards regression models were used to evaluate the association between operation method and survival. RESULTS: A total of 753 patients with early gastric cancer were included in the study. There were no significant differences in the matched cohort for overall survival (hazard ratio (HR) for laparoscopy-assisted versus open total gastrectomy 0.96, 95 per cent c.i. 0.57 to 1.65) or recurrence-free survival (HR 2.20, 0.51 to 9.52). The patterns of recurrence were no different between the two groups. The severity of complications, according to the Clavien-Dindo classification, was similar in both groups. The most common complications were anastomosis-related in the laparoscopy-assisted group (8.0 per cent versus 4.2 per cent in the open group; P = 0.015) and wound-related in the open group (1.6 versus 5.6 per cent respectively; P = 0.003). Postoperative death was more common in the laparoscopy-assisted group (1.6 versus 0.2 per cent; P = 0.045). CONCLUSION: Laparoscopy-assisted total gastrectomy for early gastric cancer is feasible in terms of long-term results, including survival and recurrence. However, a higher postoperative mortality rate and an increased risk of anastomotic leakage after laparoscopic-assisted total gastrectomy are of concern.

Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS).

BACKGROUND: Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). RESULTS: Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3. CONCLUSIONS: SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.

Characterization of novel microsatellite markers derived from Korean rose bitterling (Rhodeus uyekii) genomic library.

Korean rose bitterling (Rhodeus uyekii) is a freshwater fish endemic to Korea. Natural populations of this species have experienced severe declines as a result of habitat fragmentation and water pollution. To conserve and restore R. uyekii, the genetic diversity of this species needs to be assessed at the population level. Eighteen novel polymorphic microsatellite loci for R. uyekii were developed using an enriched partial genomic library. Polymorphisms at these loci were studied in 150 individuals collected from three populations. The number of alleles at each locus ranged from 3 to 47 (mean = 17.1). Within the populations, the observed heterozygosity ranged from 0.032 to 1.000, expected heterozygosity from 0.082 to 0.967, and polymorphism information content from 0.078 to 0.950. Six loci showed significant deviation from Hardy-Weinberg equilibrium after Bonferroni's correction, and no significant linkage disequilibrium was detected between most locus pairs, except in three cases. These highly informative microsatellite markers should be useful for genetic population structure analyses of R. uyekii.

Tumor differentiation is not a risk factor for lymph node metastasis in elderly patients with early gastric cancer.

BACKGROUND: The aim of this study was to identify risk factors for lymph node metastasis in elderly patients (70 years or more) with early gastric cancer. METHODS: We reviewed the prospectively collected database of 6893 patients with early gastric cancer who had undergone curative gastrectomy in 3 tertiary cancer centers between January 2003 and December 2009 in Korea. Patients were sorted into 4 groups according to age: less than 50, fifties, sixties, and 70 years or more. Risk factors for lymph node metastasis in early gastric cancer were analyzed. RESULTS: One thousand and thirty five patients (15.0%) were 70 years or more. As age increased, the frequency of large differentiated tumor, lymphatic and submucosa invasion increased. Old age was associated with a lower risk for lymph node metastasis in patients with early gastric cancer (Odds ratio [OR], OR, 0.622; 95% CI, 0.5466-0.830, P = 0.010). Ulceration or differentiation of tumor was not associated with lymph node metastasis in elderly patients with early gastric cancer. CONCLUSIONS: Elderly patients with undifferentiated type histology early gastric cancer without other risk factors for lymph node metastasis may be candidates for endoscopic resection.

Efficacy and safety of micafungin for the prophylaxis of invasive fungal infection during neutropenia in children and adolescents undergoing allogeneic hematopoietic SCT.

The objective of this study was to evaluate the efficacy and safety of micafungin for the prevention of invasive fungal infection (IFI) during the neutropenic phase of allogeneic hematopoietic SCT (allo-HSCT) in children and adolescents. This was a prospective, multicenter, open-label, single-arm study. Micafungin was administered i.v. at a dose of 1 mg/kg/day (max 50 mg) from the beginning of conditioning until neutrophil engraftment. Treatment success was defined as the absence of proven, probable, possible or suspected IFI through to 4 weeks after therapy. From April 2010 to December 2011, 155 patients were enrolled from 11 institutions in Korea, and 147 patients were analyzed. Of the 147 patients, 121 (82.3%) completed the protocol without premature interruption. Of the 132 patients in whom micafungin efficacy could be evaluated, treatment success was achieved in 119 patients (90.2%). There was no proven fungal infection in any patient. The number of patients with probable, possible and suspected IFI was two, two and nine, respectively. Thirty-five patients (23.8%) experienced 109 adverse events (AEs) possibly related to micafungin. No patients experienced grade IV AEs. Two patients (1.4%) discontinued micafungin administration due to adverse effects. None of the deaths were related to the study drug.

Intermediate-risk grouping of cervical cancer patients treated with radical hysterectomy: a Korean Gynecologic Oncology Group study.

BACKGROUND: In this study, we sought to identify a criterion for the intermediate-risk grouping of patients with cervical cancer who exhibit any intermediate-risk factor after radical hysterectomy. METHODS: In total, 2158 patients with pathologically proven stage IB-IIA cervical cancer with any intermediate-risk factor after radical hysterectomy were randomly assigned to two groups, a development group and a validation group, at a ratio of 3 : 1 (1620 patients:538 patients). To predict recurrence, multivariate models were developed using the development group. The ability of the models to discriminate between groups was validated using the log-rank test and receiver operating characteristic (ROC) analysis. RESULTS: Four factors (histology, tumour size, deep stromal invasion (DSI), and lymphovascular space involvement (LVSI)) were significantly associated with disease recurrence and included in the models. Among the nine possible combinations of the four variables, models consisting of any two of the four intermediate-risk factors (tumour size ≥3 cm, DSI of the outer third of the cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology) demonstrated the best performance for predicting recurrence. CONCLUSION: This study identified a 'four-factor model' in which the presence of any two factors may be useful for predicting recurrence in patients with cervical cancer treated with radical hysterectomy.

Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems.

BACKGROUND: Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. AIM: To validate the OLGA and OLGIM staging systems in a region with high risk of GC. METHODS: This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. RESULTS: More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P < 0.001), particularly among patients with intestinal-type GCs (62.2%) compared with diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. CONCLUSION: As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer.

Second-line chemotherapy versus supportive cancer treatment in advanced gastric cancer: a meta-analysis.

BACKGROUND: Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care. PATIENTS AND METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980-2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013. RESULTS: The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis. A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death [HR = 0.64, 95% confidence interval (CI) 0.52-0.79, P < 0.0001] was observed with salvage chemotherapy. When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40-0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56-0.90, P = 0.004) for docetaxel. CONCLUSION: This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.

Surgical stress after robot-assisted distal gastrectomy and its economic implications.

BACKGROUND: There is a lack of reports evaluating the outcomes of robotic gastrectomy and conventional laparoscopic surgery. The aim of this study was to compare the surgical stress response and costs of robot-assisted distal gastrectomy (RADG) with those of laparoscopy-assisted distal gastrectomy (LADG). METHODS: This prospective study compared a cohort of patients who had RADG with a cohort that underwent conventional LADG for early gastric cancer between March 2010 and May 2011. The surgical outcomes including Eastern Cooperative Oncology Group performance status and complications, surgical stress response and overall costs were compared between the two groups. RESULTS: Thirty patients were enrolled in the RADG group and 120 in the LADG group. There were no conversions. Median duration of operation was longer in the RADG group (218 (interquartile range 200-254) versus 140 (118-175) min; P < 0·001). Postoperative abdominal drain production was less (P = 0·001) and postoperative performance status was worse (P < 0·001) in the RADG group. C-reactive protein (CRP) levels on postoperative days 1 and 3, and interleukin (IL) 6 level on the third postoperative day, were lower in the LADG compared with the RADG group (CRP: P = 0·002 and P = 0·014 respectively; IL-6: P < 0·001). Costs for robotic surgery were much higher than for laparoscopic surgery (difference €3189). CONCLUSION: RADG did not reduce surgical stress compared with LADG. The substantial RADG costs due to robotic system expenses may not be justified.

International models of investigator-initiated trials: implications for Japan.

BACKGROUND: Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. MATERIALS: In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. RESULTS: In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. CONCLUSIONS: To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval.

A randomized phase II study of irinotecan plus cisplatin versus irinotecan plus capecitabine with or without isosorbide-5-mononitrate in advanced non-small-cell lung cancer.

BACKGROUND: We investigated the efficacy of irinotecan/cisplatin (IP) versus irinotecan/capecitabine (IX) with or without isosorbide-5-mononitrate (ISMN) in chemo-naïve advanced non-small-cell lung cancer. PATIENTS AND METHODS: Initially, 74 patients were randomly assigned to either IP or IX. Given the potential benefits of ISMN on chemotherapy, the protocol was amended during the study. Subsequently, 72 patients were randomly assigned to either IP + ISMN or IX + ISMN. Patients were treated with predefined second-line therapies (docetaxel/capecitabine for IP or IP + ISMN, docetaxel/cisplatin for IX or IX + ISMN) when disease progressed. RESULTS: A total of 146 received treatment. Response rate (RR), median progression-free survival (PFS) and overall survival (OS) were 49%, 5.5 months, 14.5 months in IP; 33%, 3.3 months, 13.0 months in IP + ISMN; 30%, 4.3 months, 16.1 months in IX; and 25%, 3.4 months, 13.6 months in IX + ISMN, respectively. While IP arm showed a trend toward higher RR and longer PFS than IX arm, IX arm showed a trend toward longer OS than IP arm. No significant differences were observed between IP + ISMN and IX + ISMN. CONCLUSION: IP showed better RR and PFS but no OS benefit when compared with IX. The addition of ISMN to IP or IX chemotherapy did not seem to improve the treatment outcome.

Effect of chemotherapy on the outcome of self-expandable metallic stents in gastric cancer patients with malignant outlet obstruction.

BACKGROUND AND STUDY AIM: Chemotherapy has been suggested to affect the outcome of pyloric stent placement. This study aimed to investigate the association between the response to chemotherapy and pyloric stent outcome. PATIENTS AND METHODS: Data from 113 patients with inoperable gastric cancer who received chemotherapy after pyloric stent placement at the National Cancer Center hospital were analyzed retrospectively. Chemotherapy response was assessed using the Response Evaluation Criteria in Solid Tumors. A Cox proportional hazards model was used to evaluate the effect of chemotherapy response on the complications of stents. RESULTS: The stent migration rate was 15.9% (18/113) and the re-stenosis rate was 30.1% (34/113). The response rates to chemotherapy were higher in the first-line group than in the salvage chemotherapy group (second-line or more) (44.8% [26/58] vs. 3.6% [2/55], respectively; P < 0.001). The proportion of patients with long time-to-progression (> 8 weeks) was also higher in the first-line than the salvage chemotherapy group (81.0% [47 /58] vs. 61.8% [34 /55], respectively; P = 0.036). Although, the response to chemotherapy was not associated with stent migration or re-stenosis, a long time-to-progression (adjusted hazard ratio [aHR] = 0.29, 95% confidence interval [CI] 0.13-0.67) and first-line chemotherapy (aHR = 0.45, 95%CI 0.22-0.93) were protective factors against re-stenosis in the multivariate analysis. In patients who received first-line chemotherapy, the median duration of patency of covered and uncovered stents was 20 weeks (95%CI 11-29) and 33 weeks (95 %CI 18-48), respectively (P = 0.317). CONCLUSIONS: A long time-to-progression and first-line chemotherapy were significant protective factors against re-stenosis. In chemotherapy-naïve gastric cancer patients with pyloric obstruction, placement of an uncovered stent followed by chemotherapy can be considered to increase stent patency.

Aspirin use and bleeding risk after endoscopic submucosal dissection in patients with gastric neoplasms.

BACKGROUND AND STUDY AIM: The risk of bleeding after endoscopic submucosal dissection (ESD) in patients with early gastric neoplasms who do not discontinue aspirin for the procedure has not been established. We aimed to investigate whether post-ESD gastric bleeding is increased in patients who take aspirin. PATIENTS AND METHODS: Patients who underwent ESD for early gastric neoplasms at the National Cancer Center Hospital, Korea, between November 2008 and January 2011 were enrolled. The risk of post-ESD bleeding was evaluated using Poisson regression analysis. RESULTS: We categorized 514 patients into three groups according to aspirin intake at the time of the procedure: patients who never used aspirin (n=439), patients who interrupted aspirin use for 7 days or more (n=56), and patients who continuously used aspirin (n=19). Post-ESD bleeding occurred in 4.1% (21/514) overall, and was more frequent in continuous aspirin users (4/19 [21.1%]) than in those who never used aspirin (15/439 [3.4%]) (P=0.006) and those with interrupted aspirin use (2/56 [3.6%]) (P=0.033). Multivariate analysis showed that use of aspirin by itself was associated with post-ESD bleeding (relative risk [RR] 4.49; 95% confidence interval [95%CI] 1.09-18.38). The resumption of clopidogrel combined with aspirin use (RR 26.71, 95%CI 7.09-100.53), and increased iatrogenic ulcer size (RR 1.52, 95%CI 1.14-2.02), were significantly associated with post-ESD bleeding. CONCLUSIONS: Continuous aspirin use increases the risk of bleeding after gastric ESD. Aspirin use should be stopped in patients with a low risk for thromboembolic disease to minimize bleeding complications.

CYP2A6 and ERCC1 polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients.

BACKGROUND: We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin. METHODS: Among MGC patients (n=108), who received S-1 (40 mg m(-2) b.i.d., days 1-14) and cisplatin (60 mg m(-2), day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487). RESULTS: Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3%; P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death. CONCLUSION: Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.

Population structure of the olive flounder (Paralichthys olivaceus) in Korea inferred from microsatellite marker analysis.

The population structure of olive flounder Paralichthys olivaceus was estimated using nine polymorphic microsatellite (MS) loci in 459 individuals collected from eight populations, including five wild and three hatchery populations in Korea. Genetic variation in hatchery (mean number of alleles per locus, A = 10.2-12.1; allelic richness, A(R) = 9.3-10.1; observed heterozygosity, H(O) = 0.766-0.805) and wild (mean number of alleles per locus, A = 11.8-19.6; allelic richness, A(R) = 10.9-16.1; observed heterozygosity, H(O) = 0.820-0.888) samples did not differ significantly, suggesting a sufficient level of genetic variation in these well-managed hatchery populations, which have not lost a substantial amount of genetic diversity. Neighbour-joining tree and principal component analyses showed that genetic separation between eastern and pooled western and southern wild populations in Korea was probably influenced by restricted gene flow between regional populations due to the barrier effects of sea currents. The pooled western and southern populations are genetically close, perhaps because larval dispersal may depend on warm currents. One wild population (sample from Wando) was genetically divergent from the main distribution, but it was genetically close to hatchery populations, indicating that the genetic composition of the studied populations may be affected by hydrographic conditions and the release of fish stocks. The estimated genetic population structure and potential applications of MS markers may aid in the proper management of P. olivaceus populations.

Risk factors for lymph node metastasis in patients with early gastric cancer and signet ring cell histology.

BACKGROUND: Early gastric cancer with signet ring cell histology has been reported as a favourable histological type. The aim of this study was to identify risk factors associated with lymph node metastasis in patients with this type of early gastric cancer. METHODS: A cross-sectional study of patients with early gastric cancer with differentiated and signet ring cell histology undergoing surgery was conducted. Risk factors were evaluated using multiple logistic regression analysis with odds ratios and 95 per cent confidence intervals. RESULTS: In 1362 patients undergoing gastrectomy for early gastric cancer, the rate of lymph node metastasis was similar for tumours with signet ring cell and differentiated histological findings (10.7 versus 9.0 per cent respectively; P = 0.307). Logistic regression analysis showed that depth of tumour invasion was predictive of lymph node metastasis in patients with signet ring cell histology (P < 0.001). Tumour size was not associated with lymph node metastasis in either univariable or multivariable analysis. Lesions smaller than 2 cm were not uncommon in patients with signet ring cell gastric tumours and lymph node metastases (six of 48; 13 per cent). CONCLUSION: Patients with early gastric cancer with signet ring cell-type histology are probably best treated by gastrectomy with lymph node dissection.