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. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Lymph node metastasis and lymphadenectomy of resectable adenocarcinoma of the esophagogastric junction

Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal nodal metastasis than those of type H or III, especially at middle-upper mediastinum. With regard to the necessity of mediastinal lymphadenectomy, theoretically, transthoracic esophagogastrectomy with complete mediastinal lymphadenectomy is suggested for Siewert type I AEGs, while transhiatal total gastrectomy with lower mediastinal and D2 perigastric lymphadenectomy is a standard surgery for type II-III AEGs. Nevertheless, the mediastinal nodal metastasis is an independent factor of poor prognosis for any type of AEG.

Cost-effectiveness analysis of chemotherapy for advancedgastric cancer in China

AIM： To assess the economics of various chemotherapeutic regimens for advanced gastric cancer （AGC）, and to select the best cost-effective regimen for the common Chinese patients. METHODS： Data source used in this study was the Chinese Biomedical Disk Database. Patients were diagnosed as AGC and any regimen was eligible. Outcome measures included median survival time （MST） and percentage of complete and partial response （CR＋PR）. Economic statistics was per capita direct medical cost （DMC） of a single cycle. TreeAge Pro Healthcare 2007 software was used to carry out costeffectiveness and incremental cost-effectiveness analysis. Sensitivity analyses were applied by altering willingness- to-pay and annual discount rate, and also re-analyzed by excluding the studies with apparent heterogeneity. RESULTS： Seven retrospective economics studies on 760 patients were included. S-fluorouracil-based regimens were universal, and also some new agents were involved, such as docetaxel, paclitaxel, andoxaliplatin. By processing analysis, we could recommend etoposide, leucovorin and 5-fluorouracil （ELF） regimen as preference, with a DMC/MST ratio of 2543 RBM/11.7 mo and a DMC/CR＋PR ratio of 2543 RMB/53.3%. Uraciltegafur, etoposide and cisplatin （FEP） or 5-fluorouracil, adrimycin/epirubin and mitomycin （FAM） regimens could be regarded as optional first-line chemotherapy for AGC in common Chinese patients. With no regard for willingness-to-pay, the docetaxel, cisplatin and 5-fluorouracil （DCF） regimen could be chosen as either a first- or a second-line chemotherapy, with a DMC/CR＋PR ratio of 9979 RMB/56.3%. CONCLUSION： 5-fluorouracial regimens are still considered the mainstream for AGC, while new agents such as taxanes are optional. More randomized clinical trials are required before any mandatory recommendation of certain regimens for patients with AGC in China is made.

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 chemotherapy (AC), while control was surgery alone. The results showed that NAC plus surgery did not benefit the patients with locally AGC in their overall survival [odds ratio (OR) = 1.20, 95% CI 0.80-1.80, P = 0.37] and the number needed to treat (NNT) was 74. However, the NAC plus both surgery and AC had a slight overall survival benefit (OR = 1.33, 95% CI 1.03-1.71, P = 0.03) and NNT was 14, which is superior to the NAC plus surgery. Therefore, we recommend that combined NAC and AC should be used to improve the overall survival of the locally AGC patients.

Digestive tract reconstruction pattern as a determining factor in postgastrectomy quality of life

Postgastrectomy quality of life (QoL) is affected by various symptoms, and compared with the preoperative baseline QoL, is typically impaired for the first 6 mo after surgery. Thereafter, improvement to a stable QoL is observed at approximately 12 mo postoperatively. We consider the digestive tract reconstruction pattern to be a determining factor in postgastrectomy QoL among gastric cancer patients, and believe it requires further discussion. Proximal gastrectomy is associated with the worst postoperative QoL among gastrectomy procedures and should be performed cautiously. The trend of better QoL provided by the pouch procedure of total gastrectomy requires further robust support. Whether the use of Billroth-I gastroduodenostomy or Roux-en-Y gastrojejunostomy for distal gastrectomy is optimal remains controversial, but Roux-en-Y gastrojejunostomy is likely to be preferable. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Individualized proximal margin for early gastric cancer patients

There is no robust evidence to define a safe proximal margin by distance for early gastric cancer (EGC). The discussion on resection margin should not only focus on the oncologic safety, but also the postgastrectomy quality of life. The distance 1-10 mm is only acceptable for those endoscopic treatment fit EGC patients. For endoscopic unfit EGC cases, if the borderline of tumor is able to be clearly determined intraoperatively, the distance 1-3 cm is recommended for proximal resection margin. If there is any uncertainty on the tumor borderline, the distance 3-5 cm should be considered for proximal margin. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Role of the gut microbiota in anticancer therapy:from molecular mechanisms to clinical applications

In the past period,due to the rapid development of next-generation sequencing technology,accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response.More importantly,available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible.However,intricate complexities exist,and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment.The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development,and to highlight the relationship between gut microbes and the efficacy of immunotherapy,chemotherapy,radiation therapy and cancer surgery,which may provide insights into the formulation of individualized therapeutic strategies for cancer management.In addition,the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized.Although many challenges remain for now,the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies,and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.