Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer

AIM:To investigate feasibility,morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric cancer.METHODS:Patients suffering from locally-advanced(T3-4 any N M0 or any T N1-3 M0)gastric carcinoma,staged with endoscopic ultrasound,bone scan,computed tomography,and laparoscopy,were assigned to receive four 21 d/cycles of TCF(docetaxel 75 mg/m 2 day 1,cisplatin 75 mg/m 2 day 1,and flu...     

Neoadjuvant chemotherapy for advanced gastric cancer: a meta-analysis

AIM:To study the value of neoadjuvant chemotherapy (NAC) for advanced gastric cancer by performing a meta-analysis of the published studies.METHODS:All published controlled trials of NAC for advanced gastric cancer vs no therapy before surgery were searched.Studies that included patients with metastases at enrollment were excluded.Databases included Cochrane Library of Clinical Comparative Trials,MEDLINE,Embase,and American Society of Clinical Oncology meeting abstracts from 1978 to 2010.The censor date was...     

Timing of surgery after neoadjuvant chemotherapy for gastric cancer: Impact on outcomes

AIM To evaluate whether the neoadjuvant chemotherapy(NAc T)-surgery interval time significantly impacts the pathological complete response(pc R) rate and longterm survival.METHODS One hundred and seventy-six patients with gastric cancer undergoing NAc T and a planned gastrectomy at the chinese p LA General hospital were selected from January 2011 to January 2017. Univariate and multivariable analyses were used to investigate the impact of NAc T-surgery interval time( 4 wk, 4-6 wk, and 6 wk) on pc R rate and overall survival(OS).RESULTS The NAc T-surgery interval time and clinician T stage were independent predictors of pc R. The interval time 6 wk was associated with a 74% higher odds of pc R as compared with an interval time of 4-6 wk(p = 0.044), while the odds ratio(OR) of clinical T3 vs clinical T4 stage for pc R was 2.90(95%c I: 1.04-8.01, p = 0.041). In cox regression analysis of long-term survival, postneoadjuvant therapy pathological N(yp N) stage significantly impacted OS(N0 vs N3: h R = 0.16, 95%c I: 0.37-0.70, p = 0.015; N1 vs N3: h R = 0.14, 95%c I: 0.02-0.81, p = 0.029) and disease-free survival(DFS)(N0 vs N3: h R = 0.11, 95%c I: 0.24-0.52, p = 0.005; N1 vs N3: h R = 0.17, 95%c I: 0.02-0.71, p = 0.020). The surgical procedure also had a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total gastrectomy was 0.12(95%c I: 0.33-0.42, p = 0.001) for OS, and 0.13(95%c I: 0.36-0.44, p = 0.001) for DFS.CONCLUSION The NAc T-surgery interval time is associated with pc R but has no impact on survival, and an interval time 6 wk has a relatively high odds of pc R.     

Current strategies in systemic treatment of gastric cancer and cancer of the gastroesophageal junction

Gastric cancer is a major health issue and a leading cause of death worldwide. The results of standard therapy remain unsatisfactory mainly because of diagnosis at the late stage of disease. Innovative strategies such as neoadjuvant chemotherapy in locally advanced cancer have improved the outcome even in operable cases. Whether an adjuvant radiochemotherapy is of benefit after curative resection including systematic lymphadenectomy remains yet unclear. Some progress has been made in the palliative setting by introducing new substances. This review examines recent advances in the systemic treatment of gastric and gastroesophageal junction cancer.     

Pancreaticoduodenectomy after neoadjuvant chemotherapy for gastric cancer invading the pancreatic head: A case report

BACKGROUND Pancreaticoduodenectomy(PD)for advanced gastric cancer is rarely performed because of the high morbidity and mortality rates and low survival rate.However,neoadjuvant chemotherapy for advanced gastric cancer has improved,and chemotherapy combined with trastuzumab may have a preoperative tumorreducing effect,especially for human epidermal growth factor receptor 2(HER2)-positive cases.CASE SUMMARY We report a case of successful radical resection with PD after neoadjuvant S-1 plus oxaliplatin(SOX)and trastuzumab in a patient(66-year-old male)with advanced gastric cancer invading the pancreatic head.Initial esophagogastroduodenoscopy detected a type 3 advanced lesion located on the lower part of the stomach obstructing the pyloric ring.Computed tomography detected lymph node metastasis and tumor invasion to the pancreatic head without distant metastasis.Pathological findings revealed adenocarcinoma and HER2 positivity(immunohistochemical score of 3+).We performed staging laparoscopy and confirmed no liver metastasis,no dissemination,negative lavage cytological findings,and immobility of the distal side of the stomach due to invasion to the pancreas.Laparoscopic gastrojejunostomy was performed at that time.One course of SOX and three courses of SOX plus trastuzumab were administered.Preoperative computed tomography showed partial response;therefore,PD was performed after neoadjuvant chemotherapy,and pathological radical resection was achieved.CONCLUSION We suggest that radical resection with PD after neoadjuvant chemotherapy plus trastuzumab is an option for locally advanced HER2-positive gastric cancer invading the pancreatic head in the absence of non-curative factors.     

Role of imaging in predicting response to neoadjuvant chemotherapy in gastric cancer

With the proven overall benefit of neoadjuvant chemotherapy in patients with locally advanced gastric cancer,there has come a need to discriminate responders from non-responders.In this article,the current role of anatomical and molecular imaging in the prediction of response to neoadjuvant therapy in gastric cancer is outlined and future prospects are discussed.     

Current concepts and future potential in neoadjuvant chemotherapy for esophageal cancer

Many trials have evaluated preoperative chemotherapy for the treatment of locally advanced esophageal cancer (LAEC). Most studies were small with conflicting results and no clear evidence of survival advantage. However, two large trials that included squamous cell carcinomas and adenocarcinomas of the esophagus produced opposite outcomes with one showing limited benefit and the other showing none. Recent meta-analyses suggest only a modest benefit from induction chemotherapy in the treatment of LAEC. Two factors associated with prolonged survival are: (1) an R0 resection and (2) pathological complete remission. Preoperative chemotherapy is preferred in Europe for adenocarcinomas; however, chemoradiation has been the treatment of choice in the US. The individualization and optimization of therapy for esophageal cancer patients may come from an in-depth understanding of molecular biology and the development of predictive biomarkers. The use of targeted and immunotherapy agents in the preoperative setting are also promising and warrant further evaluation.     

Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer

Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally advanced gastric cancer (AGC) in the current multidisciplinary treatment model. EORTC trial 40954 has recently reported that NAC plus surgery without postoperative adjuvant chemotherapy could not benefit the locally AGC patients in their overall survival. We performed a meta-analysis of 10 studies including 1518 gastric cancer patients. Stratified subgroups were NAC plus surgery and NAC plus both surgery and adjuvant chemoth...     

Dairy product consumption and gastric cancer risk: A meta-analysis

AIM: To investigate whether dairy product consumption is a risk factor for gastric cancer.METHODS: We searched the PubMed and Web of Science databases for English-language studies on dairy product consumption and gastric cancer risk that were published between October 1980 and September 2013. One author independently extracted data and assessed study quality. Based on the heterogeneity results, we used either the fixed effects model or the random effects model to compute the summary relative risks and 95% confidence intervals (CIs). We also analyzed subgroups according to the study design, geographic region, sex, and whether there were adjustments for confounders (smoking and drinking) with respect to the sources of heterogeneity.RESULTS: We found 39 studies that were potentially eligible for inclusion in this meta-analysis, including 10 cohort studies and 29 case-control studies. The summary relative risk for gastric cancer, comparing the highest and lowest dairy product consumption categories, was 1.06 (95%CI: 0.95-1.18). Specific analyses for milk, butter, and margarine yielded similar results, but the results for cheese and yogurt were different. There was significant heterogeneity for all studies (Q = 112.61; P = 0.000; I² = 67.1%). No publication bias was observed (Egger’s test: P = 0.135; Begg’s test: P = 0.365). There was a nonsignificant association between dairy product consumption and gastric cancer risk in the subgroup analysis for the study design, sex, geographic region, and whether there were adjustments for confounders (smoking and drinking).CONCLUSION: In our meta-analysis, dairy product consumption was associated with a nonsignificantly increased risk of gastric cancer. However, this result should be verified using large, well-designed prospective studies.     

Efficacy of docetaxel combined with oxaliplatin and fluorouracil against stage III/IV gastric cancer

AIM: To investigate the clinical efficacy and toxic effects of neoadjuvant chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for treating stage III/IV gastric cancer.METHODS: A total of 53 stage III/IV gastric cancer patients were enrolled into the study and treated with neoadjuvant chemotherapy. Two of the cases were excluded. The program was as follows: 75 mg/m² docetaxel and 85 mg/m² oxaliplatin on day 1 and 1500 mg/m² fluorouracil on days 1 to 3 for three weeks.RESULTS: The tumour changes, postoperative remission rate, changes in the symptoms and adverse reactions were observed. The overall clinical efficacy (complete remission + partial remission) of the neoadjuvant chemotherapy was 62.7%. R0 radical resection was performed on 60.8% of the patients, with a remission rate (pathological complete response + pathological subtotal response + pathological partial response) of 74.2%. The Karnofksy score improved in 42 cases. The toxicity reactions mostly included myelosuppression, followed by gastrointestinal mucosal lesions, nausea, vomiting and diarrhoea.CONCLUSION: Neoadjuvant chemotherapy consisting of docetaxel combined with oxaliplatin and fluorouracil is effective for stage III/IV gastric cancer. However, the treatment is associated with a high incidence of bone marrow suppression, which should be managed clinically.     

Role of Notch signaling pathway in gastric cancer: A meta-analysis of the literature

AIM: To perform a meta-analysis to quantitatively summarize the evidence for the association between the Notch signaling pathway and gastric cancer (GC).METHODS: An electronic search of the MEDLINE, EMBASE and Chinese National Knowledge Infrastructure, which contain articles published from 1966 onwards, was conducted to select studies for this meta-analysis.RESULTS: Fifteen studies with a total of 1547 gastric cancer cases and 450 controls were included in this meta-analysis. Overall, the expression of Notch1, Notch2, Delta-like 4 and Hes1 was significantly higher in tumor tissues of GC compared to normal tissues. Specifically, stratified analyses showed that significantly increased expression of Notch1 was associated with non-cardia location, > 5 cm size, diffuse type, positive lymphovascular invasion and distal metastasis. Statistically significant higher expression of Notch3 was found in diffuse type GC. Jagged1 was also significantly over-expressed in diffuse type and poor differentiation type of GC. DLL4 was significantly over-expressed in advanced T stage, N stage and TNM stage in GC patients. However, the stratified analysis showed that there was no statistically significant difference in Hes1 expression between different subgroups. Sporadic reports showed that Notch1 and Jagged1 were independent poor prognostic predictors in GC.CONCLUSION: The Notch signaling pathway plays an important role in tumor progression of gastric cancer.     

Effect of gastrectomy with bursectomy on prognosis of gastric cancer: A meta-analysis

AIM: To evaluate the effect of bursectomy on overall survival, recurrence-free survival and safety of patients with gastric cancer by performing a meta-analysis.METHODS: A literature search was performed in PubMed, EMBASE, and the Cochrane Library databases for clinical research that compared bursectomy with non-bursectomy published before October 2013. Inclusion and exclusion criteria were established and applied. Overall survival, recurrence-free survival, complications, hospital stay, operative time and blood loss were compared using hazard ratios (HRs), relative risks and weighted mean differences. Stata 12.0 software was used for statistical analysis.RESULTS: Four studies including 1130 patients were available for the analysis (430 in the bursectomy group, 700 in the non-bursectomy group). No statistically significant difference was observed in the rate of complications between the bursectomy group and the non-bursectomy group. Bursectomy did not have a significant effect (combined HR = 1.14, 95%CI: 0.88-1.47) on overall survival, and it was not a significant factor for recurrence-free survival (combined HR = 1.06, 95%CI: 0.82-1.37).CONCLUSION: Gastrectomy with bursectomy is not superior to non-bursectomy in terms of survival. Bursectomy is not recommended as a routine procedure for the surgical treatment of gastric cancer.     

不同新辅助化疗方案对结直肠癌患者生存质量的前瞻性非随机观察研究

目的探讨OLF和LF不同新辅助化疗方案对结直肠癌患者生存质量的影响。方法收集临沂市罗庄中心医院2009年3月-2012年12月收治的136例结直肠癌患者依据病情和意愿分组,分别采取OLF和LF新辅助化疗方案,以QLQC30生存质量核心问卷比较化疗前、手术前和手术后患者的生存质量。结果手术前,OLF组在总分、恶心呕吐和经济困难指标上与化疗前比较,差异有统计学意义(P0.05);LF组在总分、恶心呕吐症状上与化疗前比较,差异有统计学意义(P0.05);手术后,两组在总分、症状评分上与化疗前和手术前比较,差异有统计学意义(P0.05);两组前手术前恶心呕吐症状、手术后社会功能、腹泻、经济困难比较,差异有统计学意义(P0.05)。结论两种化疗方案均可以改善患者的生存质量,OLF化疗方案对患者功能和症状改善更为明显。     

Prognostic value of Muc5AC in gastric cancer: A meta-analysis

AIM: To assess the correlation between decreased Muc5 AC expression and patients' survival and clinicopathological characteristics by conducting a metaanalysis.METHODS: Literature searches were performed in Pub Med and EMBASE,and 11 studies met our criteria. Summary hazard ratios or odds ratios(ORs) with 95% confidence intervals(CIs) were calculated to estimate the effect. For the pooled analysis of the correlation between decreased Muc5 AC expression and clinicopathological characteristics(tumour invasion depth,lymph node metastasis,tumour-node-metastasis stage,tumour size,venous invasion and lymphatic invasion),ORs and their variance were combined to estimate the effect. RESULTS: Eleven retrospective cohort studies comprising 2135 patients were included to assess the association between Muc5 AC expression and overall survival and/or clinicopathological characteristics. Decreased Muc5 AC expression was significantly correlated with poor overall survival of gastric cancer patients(pooled HR = 1.35,95%CI: 1.08-1.7). Moreover,decreased Muc5 AC expression was also significantly associated with tumour invasion depth(pooled OR =2.12,95%CI: 1.56-2.87) and lymph node metastasis(pooled OR = 1.56,95%CI: 1.00-2.44) in gastric cancer.CONCLUSION: Decreased Muc5 AC expression might be a poor prognostic predictor for gastric cancer.     

Association between cadherin-17 expression and pathological characteristics of gastric cancer:A meta-analysis

AIM: To construct a meta-analysis in order to examine the relationship between cadherin-17(CDH17) andgastric cancer(GC). METHODS: Related articles were selected by searching the following English or Chinese electronic databases: CINAHL, MEDLINE, Science Citation Index, the Chinese Journal Full-Text, and the Weipu Journal. NewcastleOttawa Scale(NOS) criteria were used to ensure consistency in reviewing and reporting results. Statistical analyses were conducted with Version 12.0 STATA statistical software.RESULTS: Ultimately, 11 articles, with a total of 2,120 GC patients, were found to be eligible for study inclusion. In comparisons of GC patients by TNM stage(Ⅲ-Ⅳ vs ?Ⅰ-Ⅱ: OR = 2.35, 95%CI: 1.15-4.825, P = 0.019), histologic grade(3-4 vs 1-2: OR = 3.48, 95%CI: 1.36-8.92, P = 0.009), invasion grade(T3-4 vs T1-2: OR = 2.86; 95%CI: 1.69-4.83; P = 0.000), and lymph node metastasis(positive vs negative: OR = 2.64; 95%CI: 1.33-5.27; P = 0.006), it was found that CDH17 showed more positive expressions in each of the more severe cases. Country-stratified analyses from all four experimental subgroups showed that high CDH17 expression levels may be related to GC among Chinese and Korean populations(all P < 0.05), with the exception of the invasion grade T3-4 vs T1-2 comparison, where the relation only held among the Chinese population(OR = 2.86, 95%CI: 1.69-4.83, P = 0.000). CONCLUSION: Collectively, the data reflects the capacity of CDH17 in tumor proliferation and metastasis among GC patients.     

Acid suppressive drugs and gastric cancer: A meta-analysis of observational studies

AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H 2 RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I2 = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H 2 RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I2 = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I2 = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.     

进展期胃癌新辅助化疗后超声内镜下TN分期准确率及化疗前后TN期变化与术后病理反应程度相关性的研究

目的评估超声内镜判断进展期胃癌患者新辅助化疗后TN,分期的准确率并探讨化疗前后TN分期变化与胃癌根治术后病理反应程度的相关性。方法2007年6月至2009年12月间22例进展期胃癌患者在签署知情同意书后首先接受了新辅助化疗,其中男15例i女7例,年龄36—80岁,平均64岁。采取Folfox6化疗方案治疗3个疗程,治疗结束后3～4周全部接受胃癌根治术（R0切除）治疗,化疗前1—2周和手术前1～2周分别对患者行内镜超声检查术（EUS）,并进行超声内镜下TN分期判断,以手术病理TN分期为金标准,统计胃癌新辅助化疗后超声内镜下TN分期的准确率,同时对化疗前后超声内镜下TN分期变化与手术后病理反应程度（根据瘤床内出现退变或坏死影响的肿瘤细胞的比例分级,分别计作0、1a和lb、2、3,从0到3表示反应程度逐渐变好）行相关性分析。结果胃癌新辅助化疗后超声内镜下T分期的总体准确率为63．6％（14／22）,无一例诊断不足,但存在8例（36．4％,8／22）过度诊断;N分期的总体准确率为54．5％（12／22）,有4例（18．2％,4／22）过度诊断和6例（27．3％,6／22）诊断不足。新辅助化疗后有10例超声内镜下TN分期发生降期（以T期＋N期降期例数进行统计,同时发生T期和N期降期时只计作1例）,包括9例T期（4例T3期降为T2期,5例T4期降为r乃期）和4例N期（4例N1期降为N0期）降期,发生TN期降期的患者手术后病理反应程度大多较好,其中7例降期患者术后病理反应程度为2,l例降期患者术后病理反应程度为3。结论进展期胃癌新辅助化疗后超声内镜下TN分期的准确率并不高,但化疗后出现超声内镜下TN分期降期的患者手术后病理反应程度大多较好。     

Perioperative chemotherapy for resectable gastric cancer: MAGIC and beyond

Over the last 15 years, there have been major advances in the multimodal treatment of gastric cancer, in large part due to several phase III studies showing the treatment benefits of neoadjuvant and adjuvant chemotherapy and chemoradiation protocols. The objective of this editorial is to review the current high-level evidence supporting the use of chemotherapy, chemoradiation and anti-HER2 agents in both the neoadjuvant and adjuvant settings, as well as to provide a clinical framework for use of this data based on our own institutional protocol for gastric cancer. Major studies reviewed include the SWOG/INT 0116, Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC), CLASSIC, ACTS-GC, Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) and Trastuzumab for Gastric Cancer trials. Although these studies have demonstrated that multiple approaches in terms of the timing and therapy for gastric cancer are effective, no standard of care is widely accepted and questions regarding the optimal timing of chemotherapy, the benefit of radiotherapy, the minimum required extent of lymphadenectomy and optimal chemotherapy regimen still exist. Protocols from the upcoming ARTIST II, CRITICS, TOPGEAR, Neo-AEGIS and MAGIC-B studies are outlined, and results from these studies will provide critical information regarding optimal timing and treatment regimen. Additionally, the future directions of gastric cancer research predicated on molecular profiling and tailored therapies based on targetable genetic alterations in individual patient’s tumors are addressed.