An updated meta-analysis of adjuvant chemotherapy after curative resection for gastric cancer

Objectives

To investigate whether and how much gastric cancer patients after curative resection could benefit from chemotherapy.

Patients and methods

Meta-analysis was conducted with all the qualified clinical randomized trials which compared adjuvant chemotherapy with surgery alone. The database includes MEDLINE, EMBase and CBM disc, and the censor data were up to November 2007. Primary outcomes were relative risk (RR) on death and disease-free survival (DFS); secondary outcomes include RR of adverse reactions of the two arms. Sub-group analysis and sensitivity analysis were also performed. All the calculations and statistical tests were done with the RevMan 4.2.8 software.

Results

Finally, 23 trials which included 4919 patients (2441 in the adjuvant chemotherapy arm, 2478 in the observation arm) achieved all the criteria. Among them, 19 studies reported the survival rate at the end of follow-up, 60.6% alive among 2286 patients in the adjuvant chemotherapy arm, 53.4% alive among 2313 patients in the observation arm, with the RR on death of 0.85 (95%CI: 0.80–0.90). Eight studies reported the DFS, and the observation arm had a shorter DFS (RR: 0.88, 95%CI: 0.77–0.99). Grade 3/4 of myelosuppression and GI toxicity occurred more frequently in the treatment arm. Nine studies reported the recurrence rate and suggested that the treatment arm had a lower recurrence rate (RR: 0.78, 95%CI: 0.71∼0.86).

Conclusions

Statistically, adjuvant chemotherapy could improve the survival rate and disease-free survival rate in gastric cancer after curative resection and reduce the relapse rate. However, the clinical benefits of adjuvant chemotherapy still need to be improved. Additionally, post-operative chemotherapy could be tolerated.     

Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: An updated meta-analysis of randomized controlled trials

Aims

To assess the efficacy and safety of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC).

Methods

By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC-combined surgery versus surgery alone in AGC were included. All calculations and statistical tests were performed using RevMan 5.0 software.

Results

12 RCTs with a total of 1820 patients were included. All patients had locally advanced but resectable gastric cancer and received NAC. NAC can slightly improve the survival rate (OR = 1.32, 95% confidence interval (CI): 1.07–1.64, P = 0.01), with little or no significant benefits in subgroup analyses between either different population or regimens. NAC can significantly improve the 3-year progression-free survival (PFS) (OR: 1.85, 95% CI: 1.39–2.46, p < 0.0001), tumor down-staging rate (OR: 1.71, 95% CI: 1.26, 2.33, p = 0.0006) and R0 resection rate (OR: 1.38, 95% CI: 1.08–1.78, P = 0.01) of patients with AGC. There was no difference between the two arms, in terms of relapse rates (OR: 1.03, 95% CI: 0.60–1.78, p = 0.92), operative complications (OR: 1.20, 95% CI: 0.90–1.58, p = 0.21), perioperative mortality (OR: 1.14, 95% CI: 0.64–2.05, p = 0.65) and grade 3/4 adverse effects: gastrointestinal problem (OR: 0.57, 95% CI: 0.25–1.30, p = 0.18), leukopenia (OR: 0.88, 95% CI: 0.41–1.91, p = 0.75), thrombocytopenia (OR: 1.27, 95% CI: 0.27–5.93, p = 0.76).

Conclusion

NAC is effective and safe. However, further prospective multi-national and multi-center RCTs are still needed in order to investigate the long-term oncological and functional outcomes to define the clinical benefits of NAC and the most effective strategies for AGC.     

胃差分化腺癌根治术后辅助化疗的临床研究

目的:观察和比较HELF方案和HELF/HPLF交替方案对胃差分化腺癌(低分化腺癌、粘液腺癌、印戒细胞癌)根治术后患者无病生存期(DFS)、总生存期(OS)的影响。方法:经组织学证实为低分化腺癌、粘液腺癌及印戒细胞癌的Ⅱ~Ⅲ期胃癌根治术后患者,随机分配至A组(单独HELF方案化疗)或B组(HELF/HPLF方案交替化疗),术后3~5周开始化疗,化疗4~6周期。结果:共入组80例患者,72例可按要求随访及评价不良反应,A组、B组各36例。全组患者共随访7~98月,A组与B组中位随访期差异无统计学意义(30月vs.33月,P=0.383)。A组患者的DFS为4~97月(中位值20月),B组为5~98月(中位值39月),两组差异有统计学意义(P=0.025)。A组的OS为10~97月(中位值28月),B组为7~98月(中位值48月),以B组生存时间更长(P=0.042)。主要不良反应为骨髓抑制及消化道反应,多为Ⅰ~Ⅱ度。结论:HELF方案与HPLF方案交替用于差分化胃腺癌根治术后的辅助治疗,在推迟肿瘤复发转移及延长生存期方面可能优于单用HELF方案。     

Current status of adjuvant chemotherapy for gastric cancer

Although radical gastrectomy is a standard treatment for advanced gastric cancer, recurrence remains high. After several large-scale controlled studies have shown the beneficial effects of adjuvant chemotherapy, that treatment emerged as a standard option for advanced gastric cancer after gastrectomy. However, various guidelines from different countries have suggested different adjuvant chemotherapies. Understanding the differences between guidelines is very important for investigating further therapeutic strategies. Fortunately, because there are many ongoing studies about new regimens for adjuvant treatment, it is expected that patients with gastric cancer after surgery will have better outcome.     

Adjuvant chemotherapy for gastric cancer in Japan: present status and suggestions for rational clinical trials

A review of the present status of adjuvant chemotherapy for gastric cancer in Japan has been made. The single use of mitomycin C (MMC) after curative gastrectomy, a multidrug combination of MMC, 5-fluorouracil (5FU) and cytosine arabinoside (CA) (MFC therapy), and a combination of inductive MFC followed by maintenance 5FU in an adjuvant setting have proved beneficial in subsets of moderately locally advanced diseases. The advantages of the Japanese trials seem to be attributable to perioperative chemotherapy with MMC and/or 5FU, obviously given in less amounts than in other countries, against minimum residual tumors following surgery. Effort should be directed, however, to improving the quality of data, at present biased by a number of exclusions and drop-outs which should not be considered negligible. The author mentions the beneficial use of a computer-assisted randomization system for avoiding the violation of entry criteria, and of controlling data quality with individual dose intensity (I.D.I.) and relative performance (R.P.) indices. Prerequisites for success in the adjuvant chemotherapy's clinical trial included planning effective regimens, proper selection of subjects and faithful performance of proposed regimens.     

Solitary living worsens the continuation of adjuvant chemotherapy for gastric cancer

BackgroundNo studies have reported the effect of solitary living on adjuvant chemotherapy continuation in patients with gastric cancer. This study aimed to investigate the influence of solitary living on the efficacy of adjuvant chemotherapy after curative gastrectomy.MethodsWe enrolled 155 patients with pathological stage II/III gastric cancer who underwent gastrectomy and adjuvant chemotherapy between January 2013 and March 2020. The patients were divided into two groups according to their living conditions, the solitary group (n = 34) versus the non-solitary group (n = 121). Clinicopathological features, predictive factors for the continuation of adjuvant chemotherapy, and long-term survival were compared between the two groups.ResultsThe median body weight loss (BWL) at one month after surgery (8.9% vs. 7.0%, p = 0.01), and the rates of failure to continue six courses of chemotherapy were higher in the solitary group (41.2% vs. 14.9%, p = 0.002) than in the non-solitary group. Multivariate analysis revealed that solitary living was an independent predictive factor for discontinuing adjuvant chemotherapy (odds ratio 3.36, 95% confidence interval [CI; 1.32–8.58], p = 0.01) as well as 10% BWL at one month after surgery (odds ratio 3.99, 95% CI [1.57–10.2], p = 0.004). The relapse-free survival was significantly worse in the solitary group (p = 0.03).ConclusionsSolitary living may be an independent risk factor for discontinuation of adjuvant chemotherapy in patients with gastric cancer. It is necessary to examine whether social and medical support organized by medical institutes and the government improves the continuation of adjuvant chemotherapy in patients living alone.     

胃癌术后放化疗与单纯化疗随机对照试验结果的荟萃分析

目的 采用偱证医学荟萃分析的方法比较胃癌术后放化疗与单纯化疗的RCT结果差异。 方法 检索中国期刊全文数据库、维普、中国生物医学文献数据库,Cochrane图书馆、PubMed和EMBASE,纳入胃癌术后放化疗及单纯化疗的RCT研究。汇总数据采用RevMan5.2及Stata12软件进行分析。两组间差异采用RR及95%CI描述。 结果 根据纳入和排除标准,最终纳入11个1 143例患者的RCT资料。荟萃分析结果显示胃癌术后放化疗比单纯化疗的1、2、3年OS率高（RR=1.20,95%CI=1.10～1.30,P=0.00;RR=1.34,95%CI=1.16～1.56,P=0.00;RR=2.62,95%CI=1.72～3.97,P=0.00）;3、5年PFS率也高（RR=1.10,95%CI=1.00～1.21,P=0.04;RR=1.27,95%CI=1.02～1.60,P=0.04)。胃肠道反应、肝功能损害、骨髓移植及手足综合征等3~4级发生率低且两组相似（P=0.03~0.78）。结论 胃癌术后放化疗可提高生存时间,且患者对药物的耐受性尚可。     

Trial sequential analysis of randomized controlled trials on neoadjuvant therapy for resectable pancreatic cancer

IntroductionMeta-analyses of randomized controlled trials (RCTs) provide the highest level of evidence but can suffer from type I (false-positive) and II (false-negative) errors, which can be estimated through trial sequential analysis (TSA) demonstrating eventual credibility of results. Aim of the study was to establish through TSA which strategy between neoadjuvant approach or upfront surgery provides best results when treating potentially resectable pancreatic adenocarcinoma.Materials and methodsRCTs were searched until September 2021. Intention-to-treat (ITT) overall survival, resection rate, ITT R0 and N0 rates and per-protocol R0 and N0 rates were the outcomes considered. Fixed-effect model was applied. TSA assumed an alpha = 5% and a power = 80%.ResultsFour RCTs were identified accruing 325 patients for the ITT analyses and 242 for the per-protocol analyses. Neoadjuvant did not improve survival (p = 0.167) and TSA supported that this result was underpowered, requiring additional 1514 patients to prove credibility. Neoadjuvant reduced resection rate (p = 0.044) but type I error was not avoided. Neoadjuvant credibly increased per-protocol R0 and N0 rates (p = 0.003 and p < 0.001), and TSA showed that these were true-positive findings. Neoadjuvant did not increase ITT R0 rate since randomization (p = 0.169) but TSA showed lack of power. Neoadjuvant credibly increased the ITT N0 rate (p < 0.001) and TSA supported that this was a true positive finding.ConclusionsNeoadjuvant strategy credibly demonstrated superiority over upfront surgery in determine per-protocol R0 resection and N0 rates, as well as ITT N0 rate. For the remaining outcomes, TSA suggested the need of larger samples to exclude type I and II errors.     

Multimodality management of resectable gastric cancer: A review

Adenocarcinoma of the stomach carries a poor prognosis and is the second most common cause of cancer death worldwide. It is recommended that surgical resection with a D1 or a modified D2 gastrectomy (with at least 15 lymph nodes removed for examination) be performed in the United States, though D2 lymphadenectomies should be performed at experienced centers. A D2 lymphadenectomy is the recommended procedure in Asia. Although surgical resection is considered the definitive treatment, rates of recurrences are high, necessitating the need for neoadjuvant or adjuvant therapy. This review article aims to outline and summarize some of the pivotal trials that have defined optimal treatment options for non-metastatic non-cardia gastric cancer. Some of the most notable trials include the INT-0116 trial, which established a benefit in concurrent chemoradiation and adjuvant chemotherapy. This was again confirmed in the ARTIST trial, especially in patients with nodal involvement. Later, the Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial provided evidence for the use of perioperative chemotherapy. Targeted agents such as ramucirumab and trastuzumab are also being investigated for use in locally advanced gastric cancers after demonstrating a benefit in the metastatic setting. Given the poor response rate of this difficult disease to various treatment modalities, numerous studies are currently ongoing in an attempt to define a more effective therapy, some of which are briefly introduced in this review as well.     

Efficacy of adjuvant chemotherapy using tegafur-based regimen for curatively resected gastric cancer: update of a meta-analysis

A consensus regarding standard adjuvant chemotherapy for curatively resected gastric cancer has not been obtained between Japan and the Western world. In order to evaluate the effect of a tegafur-based regimen (the most frequently used regimen in Japan) compared with a surgery-alone control, a meta-analysis was performed, investigating four clinical trials. After meticulous examination of each trial, trials with improper noncentralized randomization were excluded from the analysis. A total of 1197 patients were enrolled in the four relevant trials determined to be eligible for the meta-analysis (Nakajima 1984; Japan Clinical Oncology Group [JCOG] 8801, JCOG 9206-2, and National Surgical Adjuvant Study of Gastric Cancer [NSASGC], in which a tegafur-based regimen was used for chemotherapy and central randomization was performed. The endpoint was overall survival, and a common hazard ratio was estimated. The 5-year overall survival rates differed among the trials because of differences in the background disease status. But there was no heterogeneity (P = 0.235) of treatment effect. The estimated common hazard ratio was 0.75, with a 95% confidence interval of 0.58–0.98. The treatment effect of the tegafur-based agent was shown to be statistically significant (P = 0.037) compared with surgery-alone therapy (n = 1179). From the results of the above meta-analysis, it is suggested that chemotherapy with a tegafur-based agent after surgery can improve the survival of patients with curatively resected gastric cancer. The Global Advanced/Adjuvant Stomach Tumor Research through International Collaboration (GASTRIC) group is conducting two individual patient data meta-analyses, testing post-operative adjuvant chemotherapy for resect-able gastric cancer and chemotherapy for advanced gastric cancer. It is expected to determine and quantify the role of adjuvant chemotherapy in detail from the GASTRIC.     

Perioperative chemotherapy versus adjuvant chemotherapy strategies in resectable gastric and gastroesophageal cancer: A Markov decision analysis

BackgroundPerioperative chemotherapy has been shown to improve overall survival (OS) for operable gastric and gastroesophageal cancer. However, optimal sequence of surgery and chemotherapy has not been clearly identified. Markov models are useful for analyzing the outcomes of different treatment strategies in the absence of adequately powered randomized clinical trials. In this study, we use Markov decision analysis models to compare median OS (mOS), quality-adjusted mOS, life expectancy (LE), and quality-adjusted life expectancy (QALE) of perioperative chemotherapy with adjuvant chemotherapy strategies in resectable gastric and gastroesophageal cancer patients.MethodsMarkov models are constructed to compare two strategies: adjuvant chemotherapy after surgery and preoperative chemotherapy followed by cancer resection and postoperative chemotherapy. LE and QALE are calculated analytically, and mOS are obtained by simulation. Parameters used in the models are computed from prospective clinical trial data published in PUBMED from January 2000 to July 2020.ResultsTotal of 8088 patients from 25 prospective studies were included in this analysis. Regardless of R0 resection ratio, the analyses of the models show a higher mOS for patients in the perioperative therapy arm compared to adjuvant chemotherapy. For R0 resected patients, the perioperative therapy arm provided an additional 11.0 mOS months (61.3 months vs. 50.3 months). For R1 resected patients, the perioperative therapy arm had mOS of 17.0 months vs. 10.7 months in adjuvant therapy.ConclusionsThe Markov models indicate that perioperative chemotherapy improves mOS, quality-adjusted mOS, LE, and QALE for resectable gastric and gastroesophageal cancer patients compared to adjuvant chemotherapy strategies.     

Evaluation of effectiveness of chemotherapy in patients with gastric cancer after curative resection

Background. A prospective randomized study involving gastric cancer patients was undertaken to evaluate combined adjuvant chemotherapy and the prognostic value of biologic markers. Methods. One hundred and eighty-five patients under 75 years of age who underwent a curable resection of pathologic stage II or III gastric cancer were randomly assigned to receive adjuvant chemotherapy containing either: mitomycin C (MMC) plus oral 5-fluorouracil (FU) (MF), epirubicin plus oral FU (EF), or oral FU (F). Tumor tissue collected at surgery was immunohistochemically analyzed for p53 and proliferating cell nuclear antigen, and DNA ploidy was determined. Results. All prognostic factors were equally distributed in each arm. There was no significant difference among the groups in the 5-year overall survival. When the relationship between the biologic markers and prognosis was analyzed, the overall survival of all patients and stage III patients was poorer in those with p53 positivity, but the difference did not achieve significance. For patients with positive nodes, irrespective of the treatment regimen, p53-positivity was significantly associated with poorer prognosis (P = 0.05). In stage III patients, the survival of those with p53-positivity and DNA aneuploidy was significantly worse than that for patients with any other combination (P = 0.02). Conclusion. No survival benefit was observed with the combined chemotherapeutic regimens compared with FU alone. p53 positivity was negatively correlated to survival for node-positive and stage III patients. Received: July 3, 2000 / Accepted: September 21, 2000     

A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma

BACKGROUND: The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to update the 1997 meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy of doxorubicin-based chemotherapy with respect to recurrence and survival. METHODS: A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft-tissue sarcoma. Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were local, distant, and overall recurrence and survival calculated through the fixed effect or random effect model. RESULTS: Four new eligible trials were identified allowing for a total of 18 trials representing 1953 patients to be included in the analysis. The odds ratios (OR) for local recurrence was 0.73 (95% confidence interval [CI] 0.56-0.94; P = .02) in favor of chemotherapy. For distant and overall recurrence the OR was 0.67 (95% CI 0.56-0.82; P = .0001) in favor of chemotherapy. In terms of survival, doxorubicin alone had an OR of 0.84 (95% CI, 0.68-1.03; P = .09), which as not statistically significant. However, the OR for doxorubicin combined with ifosfamide was 0.56 (95% CI, 0.36-0.85; P = .01) in favor of chemotherapy. CONCLUSIONS: This updated meta-analysis confirms the marginal efficacy of chemotherapy in localized resectable soft-tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. These benefits are further improved with the addition of ifosfamide to doxorubicin-based regimens, but must be weighed against associated toxicities.     

Neoadjuvant chemotherapy for resectable esophageal carcinoma: a meta-analysis of randomized clinical trials

Neoadjuvant chemotherapy for resectable esophageal carcinoma has been a focus of study, but no agreement has been reached on clinical randomized controlled trials and relevant systematic evaluation. The purpose of this study was to perform a meta-analysis on published randomized controlled trials (RCTs) that compared neoadjuvant chemotherapy and surgery with surgery alone for resectable esophageal carcinoma. Medline and manual searches was conducted in PubMed, ASCO (American Society of Clinical Oncology) meeting summary, Embase, the Cochrane Library (up to October 2010), Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database. The selection contents were to identify all published and unpublished RCTs that compared neoadjuvant chemotherapy and surgery with surgery alone for resectable esophageal carcinoma. Sixteen RCTs which included 2,594 patients were selected. The risk ratio (RR) (95% confidence interval [CI]; P value), expressed as neoadjuvant chemotherapy and surgery versus surgery alone (treatment versus control), was 1.02 (0.95, 1.10; P=0.54) for 1-year survival, 1.29 (1.13, 1.47; P=0.0001) for 3-year survival, 1.31 (1.13, 1.51; P=0.0003) for 5-year survival, 1.00 (0.95, 1.04; P= 0.85) for rate of resection and 0.89 (0.64, 1.23; P=0.48) for operative mortality. The results showed that neoadjuvant chemotherapy for resectable esophageal carcinoma can raise the overall survival rate of patients with esophageal carcinoma, but it does not affect treatment-related mortality.     

胃癌术后辅助放化疗与辅助化疗比较的荟萃分析

目的 采用偱证医学荟萃分析的方法比较胃癌术后辅助放化疗与辅助化疗间的疗效差异。方法 计算机检索PubMed、EMbase、Cochrane图书馆、万方、维普、CNKI及中国生物医学等数据库,搜集有关胃癌术后辅助放化疗和辅助化疗比较的临床对照研究资料,汇总数据采用RevMan 5.2.5和Stata 12.0软件进行分析。两组间差异采用优势比(OR)及95%可信区间(95% CI)描述。结果 根据纳入和排除标准,最终纳入12个包括1674例患者的临床对照研究资料。荟萃分析结果显示,与胃癌术后辅助化疗相比,辅助放化疗的3、5年生存率更高(OR=2.96,95% CI= 1.75~5.03,P=0.000;OR=1.45,95% CI=1.06~1.99,P=0.020),辅助放化疗的局部复发率更低(OR=0.50,95% CI=0.34~0.72,P=0.000),但远处转移率两组相似(OR=0.79,95% CI=0.58~1.07,P=0.130)。结论 现有研究结果的荟萃分析显示,与胃癌术后辅助化疗相比,胃癌术后辅助放化疗是一种较为安全和有效的治疗方法。     

中国淋巴瘤治疗随机对照临床试验文献分析

目的 依据循证医学及医学临床科研设计原则,通过分析中国淋巴瘤治疗领域随机对照临床试验文献,评估临床试验研究质量,为规范治疗试验、提高研究质量提供依据.方法 选择万方数据库（1989年至2012年）、中国知网（1979年至2013年）,以“淋巴瘤”、“随机”、“对照”、“病人”或“病例”或“患者”为检索词,对中国期刊2000年1月至2011年12月间发表的随机对照临床试验文献进行检索.同时以“Chinese／China”、“randomized controlled trials”、“lymphoma”为检索词,在PubMed数据库中进行检索.对文献研究对象的选择标准、样本含量、随机方法的应用、组间均衡性比较、盲法的应用、统计学方法的应用、随访情况等进行描述性分析.结果 在两个中文数据库中共检得有效文献120篇,在PubMed数据库中检索所得文献均包括在这120篇文献中.其中,对具体随机方法进行说明者37篇（30.8％）,有明确纳入、排除标准者33篇（27.5％）,样本数＜ 60例者55篇（45.8％）,对基线资料可比性进行描述者61篇（50.1％）,对随访情况进行描述者43篇（35.8％）,仅1篇文献提及单盲法.结论 研究结果可从一个侧面反映出中国淋巴瘤治疗性随机对照临床试验总体研究质量不高,证据的可信度低,质量与循证医学标准有一定差距.     

Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials

Introduction

An important component of treatment failure in gastric cancer (GC) is cancer dissemination within the peritoneal cavity and nodal metastasis. Intraperitoneal chemotherapy (IPC) is considered to give a fundamental contribute in treating advanced GC. The purpose of the study is to investigate the effects of IPC in patients with advanced GC.

Material and methods

A systematic review with meta-analysis of randomized controlled trials (RCTs) of IPC + surgery vs. control in patients with advanced GC was performed.

Results

Twenty prospective RCTs have been included (2145 patients: 1152 into surgery + IPC arm and 993 into control arm). Surgery + IPC improves: 1, 2 and 3-year mortality (OR = 0.31, 0.27, 0.29 respectively), 2 and 3-year mortality in patients with loco-regional nodal metastasis (OR = 0.28, 0.16 respectively), 1 and 2-year mortality rate in patients with serosal infiltration (OR = 0.33, 0.27 respectively). Morbidity rate was increased by surgery + IPC (OR = 1.82). The overall recurrence and the peritoneal recurrence rates were improved by surgery + IPC (OR = 0.46 and 0.47 respectively). There was no statistically significant difference in lymph-nodal recurrence rate. The rate of haematogenous metastasis was improved by surgery + IPC (OR = 0.63).

Conclusions

1, 2 and 3-year overall survival is incremented by the IPC. No differences have been found at 5-year in overall survival rate. 2 and 3-year mortality rates in patients with nodal invasion and 1 and 2-year mortality rates in patients with serosal infiltration are improved by the use of IPC. IPC has positive effect on peritoneal recurrence and distant metastasis. Morbidity rate is incremented by IPC. Loco-regional lymph-nodes invasion in patients affected by advanced gastric cancer is not a contraindication to IPC.     

Quality control of surgical technique in a multicenter, prospective, randomized, controlled study on the surgical treatment of gastric cancer.

To evaluate the effect of lymph node dissection on gastric cancer patients operated upon with curative intent, we are carrying out a multicenter, prospective, randomized, controlled study in the Netherlands. The trial compares conventional gastrectomy to gastrectomy with extended lymph node dissection. In the first four months, a Japanese supervisor attended all the extended surgery and instructed many Dutch surgeons, including the eight consulting surgeons; since then, all extended gastrectomies have been attended by one of the consulting surgeons. The study coordinator attended all conventional cases. This assured that the quality of the extended surgery was as good as the Japanese standard, of which excellent results have been reported. To achieve this quality control, randomization before surgery was obligatory for practical reasons. Curability assessment at laparotomy, however, is done quite objectively with histological proof, except for the judgement of irresectability. Although this has resulted in many non-curative cases being randomized but subsequently not given the allocated surgery, the sample size should be sufficient to allow analysis according to randomization or the initial "intention to treat." This is the first protocol for a multicenter trial in surgical oncology to have such excellent surgical quality control and to assure a quality as high as that in the original report with uniformity in the level of technique. In studies comparing surgical techniques, it is vital that attention should be given to surgical quality control, otherwise survival rates may show little improvement and fail to make any impact on surgical practice.     

MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy

Objective: To evaluate the impact of the multi-drug resistance 1(MDR1) C3435T polymorphism on clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. Methods: From January 2005 to December 2008, 102 patients with surgically resected gastric cancers were enrolled into this study in the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University. The polymorphism was tested using real time polymerase chain reaction (RT-PCR) cycling probes and the relationship with clinical outcomes after postoperative adjuvant chemotherapy was analyzed by SPSS 17.0. Results: The CT/TT genotype of C3435T was significantly associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with the CC genotype [PFS: adjusted hazard ratio(HR)= 2.01, 95% confidence intervals(CI): 1.17-3.45, P = 0.012; OS: adjusted HR = 2.37, 95% CI: 1.31-4.28, P=0.004]. TNM stage was also associated with PFS (adjusted HR = 2.33, 95% CI: 1.34-4.05, P = 0.003) and OS (adjusted HR = 2.62, 95% CI: 1.44-4.76, P = 0.002) in gastric cancer patients treated with postoperative adjuvant chemotherapy. Conclusion: Our results suggest that the MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. This now needs to be confirmed by a randomized prospectively controlled study.