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Objective: To compare the clinicopathological characteristics and the prognosis of gastric adenocarcinoma patients with and without neuroendocrine differentiation (NED) after radical gastrectomy plus D2 lymph node dissection. Methods: A retrospective cohort study was performed. The inclusion criteria were as follows: (1) patients who underwent radical resection of gastric cancer plus D2 lymph node dissection and were confirmed as gastric adenocarcinoma by postoperative pathology and received immunohistochemical examination of neuroendocrine markers Syn and/or CgA; (2) patients aged 20 to 75 years with normal organ function; (3) patients who did not receive neoadjuvant chemotherapy or radiotherapy before operation; (4) patients with postoperative pathological stage I to III according to the 8th edition of tumor staging system of American Joint Committee on Cancer (AJCC); and (5) patients who completed adjuvant chemotherapy according to the postoperative pathological stage. Those who had other malignant tumors in the past 5 years and who could not be followed up according to the required rules were excluded. According to the above criteria, the clinicopathological characteristics of gastric cancer patients who underwent radical resection plus D2 lymph node dissection in Zhongshan Hospital of Fudan University from January 2010 to June 2017 were collected and compared. All patients were followed up till June 2020. The disease-free survival (DFS) and overall survival (OS) between the patients with and without NED were compared, and the effect of NED on the prognosis was corrected by Cox proportional hazards model. The propensity score matching method was used for sensitivity analysis. Results: A total of 539 patients were enrolled in this study, including 35 with NED and 504 without NED. Compared with the patients without NED, the patients with NED were older [(65.0±7.5) years vs. (54.5±11.3) years, t =-7.681, P <0.001], had higher proportion of undergoing proximal gastrectomy [22.9% (8/35) vs. 7.6% (36/504), χ(2)=10.335, P =0.006], higher proportion of intestinal-type based on Lauren classification [77.1% (27/35) vs. 42.5% (214/504), χ(2)=14.553, P <0.001], and higher proportion of pathologic stage III [65.7% (23/35) vs. 27.6% (139/504), χ(2)=25.653, P <0.001]. The 3-year DFS of patients with NED and those without NED was 48.9% (95% CI: 33.8%-70.8%) and 37.4% (95% CI: 32.9%-42.5%) respectively, and no significant difference was found ( P =0.44). The 3-year OS was 56.1% (95% CI: 39.9%-79.1%) and 64.3% (95% CI: 59.3%-69.7%) respectively, and no significant difference was found as well ( P =0.32). Univariate and multivariate analyses showed that NED was not an independent risk factor for DFS and OS (all P >0.05). Sensitivity analysis showed that there was no significant difference in DFS and OS between the two groups after propensity score matching. Conclusion: Compared with patients without NED, patients with NED were older at onset, had a higher proportion of proximal gastrectomy, intestinal-type, and later diagnostic stage, but the survival prognosis had no significant difference with that of patients without NED.

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy in patients with locally advanced gastric cancer, and to analyze the relevant factors of recurrent death of gastric cancer after adjuvant chemotherapy., Methods: Clinical data of 49 patients who underwent neoadjuvant chemotherapy for locally advanced gastric cancer between July 2007 and June 2011 were reviewed. Preoperative staging was determined by endoscopic ultrasonography and abdominal computer tomography (CT) or magnetic resonance imaging (MRI). Chemotherapy was administered for regimen of two or three drugs. Prognostic factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model., Results: The response rate was 33.3% (16/48) and disease control rate was 93.8% (45/48). Forty-four (89.8%, 44/49) patients received curative resection after neoadjuvant chemotherapy, among whom 90.9% (40/44) underwent D2 lymphadenctomy. Thirty-two cases had pathological response and 2 patients had pathological complete response. The average hospital stay was 11.6 days and 2 patients had longer hospitalization because of postoperative pancreatic complications. The toxicities were most in grade 1-2. All the patients were followed up postoperatively and the median follow-up was 21.6 months. Median progression-free survival was 29.6 (95%CI:24.0-35.2) months and median overall survival was 34.6 months (95%CI:29.8-39.4). Imaging response (P=0.038, RR=0.168, 95%CI:0.031-0.904) and pathological response (P=0.007, RR=0.203, 95%CI:0.064-0.642) were identified as independent prognostic factors with COX multivariate analysis., Conclusions: Neoadjuvant chemotherapy has quite high disease control rate and R0 resecting rate for patients with locally advanced gastric cancer. Imaging response and pathological response are most important prognostic factors in those patients.

Objective: To investigate the efficacy and safety of chemotherapy combined with intraperitoneal perfusion of cytokine-induced killer (CIK) cells for advanced gastric cancer patients with ascites., Methods: From January 2008 to December 2010, 42 advanced gastric cancer patients with ascites in Zhongshan Hospital of Fudan University were enrolled in the study. According to personal choice, patients were divided into 2 groups: XELOX chemotherapy alone (Capecitabine and Oxaliplatin) was applied in 22 patients (chemotherapy group) and XELOX combined with intraperitoneal perfusion of CIK cells in 20 patients (combination group). The efficacy, safety, and immunological function, including the time to progression (TTP), overall survival (OS), Karnofsky performance status (KPS) score, immunity index (CD4+/CD8+ ratio), volume of peritoneal fluid, were compared between two groups., Results: Compared with the chemotherapy group after treatment, the combination group had a higher KPS score (78.0±9.8 vs. 70.0±8.9, P=0.009), less volume of 2-cycle peritoneal fluid drainage [(4500±1218) ml vs. (5527±1460) ml, P=0.018 ], longer median TTP (4.0 vs. 2.5 months, P=0.001) and OS (11.0 vs. 6.0 months, P=0.006), higher ratio of CD4+/CD8+ (1.34±0.36 vs. 0.96±0.26, P=0.001). While no significant significances were found between the two groups in disease response rate (35.0% vs. 22.7%, P=0.499) and disease control rate (75.0% vs. 54.5%, P=0.209). There were no serious adverse reactions in the combination group., Conclusions: As compared with XELOX chemotherapy alone, the combination immunological treatment of XELOX chemotherapy and intraperitoneal perfusion of CIK cells possesses better efficacy for the advanced gastric cancer patients with ascites, which can prolong the survival and enhance the immunological function with favorable safety.

Objective: To investigate whether AJCC staging system(2010 edition) for gastric cancer has influence on the adoption of adjuvant chemotherapy., Methods: This was a cohort study and the data were collected from patients who underwent radical surgery and received adjuvant chemotherapy from January 2004 to December 2009. There were 48 patients with stage II( disease and 95 patients with stage III( disease according to TNM staging(2010 edition). Doublets were defined as 5-fluorouracil or capecitabine plus cisplatin or oxaliplatin, while triplets had epirubicin added. Ninety-six patients received doublet chemotherapy and 47 received triplet. All the patients were followed-up in the outpatient clinic until death or the censor time of May 2011., Results: The median follow-up time was 48 months in this cohort of 143 patients. The two groups had similar disease-free survival(DFS)(median, 23 months vs. 30 months, P>0.05). The median overall survival was 48 months in both groups. Subgroup analysis by TNM staging(2010 edition) showed that the median DFS of patients with stage III( gastric cancer was 15 months in the doublet group, significantly shorter than that of patients in the triplet group (18 months, P<0.05). However, the difference in overall survival was not statistically significant between the two groups. Patients with stage II( disease had comparable DFS and OS between the two groups(all P>0.05)., Conclusions: Triplets regimens (epirubicin, platins and fluorouracil) show benefit on disease-free survival for the stage III( gastric cancer patients staged by TNM staging 2010 edition.

The role of chemotherapy has become more and more important in the whole process of gastric cancer. S-1 or XELOX regimen is regarded as the standard treatment option in adjuvant chemotherapy. First-line chemotherapy in advanced gastric cancer has been established to improve survival, and the benefit from second-line chemotherapy is being acknowledged. More studies are needed to assess the neoadjuvant chemotherapy.

Objective: To compare oncologic outcomes between doublet and triplet adjuvant chemotherapy for gastric cancer patients undergoing radical resection., Methods: Patients with gastric cancer receiving adjuvant chemotherapy after radical resection from January 2004 to December 2008 were included. Doublet was defined as 5-FU 750 mg/m² (days 1-5) or capecitabine 1000 mg/m² (days 1-14) plus cisplatin 60 mg/m² (day 1) or oxaliplatin 130 mg/m² (day 1), while triplets had epirubicin 50 mg/m² (day 1) added. Chemotherapy was initiated 4-6 weeks after surgery, repeated every three weeks for 6 cycles. Patients were followed-up in the outpatient clinic until death or the most recent follow up(April 30, 2010). Cox proportional- hazard model and Chi-square test were used to test statistical difference., Results: A total of 316 patients (210 received doublets, 106 received triplets) had a median follow-up time of 47 months. Seventy-seven patients died at the end of the follow-up. Two groups were comparable except for age (median age of 57 in doublets, 51 in triplets, P<0.01). The two groups had similar disease-free survival (16 months vs. 23 months, P=0.656) and 3-year overall survival(59.6% vs. 64.8%, P=0.293). There was no significant difference in severe adverse side effects between the two groups (21.9% vs. 30.2%, P=0.107)., Conclusion: Triplet adjuvant chemotherapy appears not to be associated with superior efficacy than doublet regimen for patients with gastric cancer after radical resection.

Objective: To compare FOLFOX6 and FOLFIRI regimen in the treatment of metastatic colorectal cancer with cost-effective analysis., Methods: Cost-effective analysis was conducted based on the efficacy results of V308 clinical trial of FOLFOX6 and FOLFIRI regimen and the medical system price in Zhongshan hospital., Results: The minimal cost analysis showed FOLFIRI followed by FOLFOX6 had the cost of RMB 206365.78 Yuan for each patient during the whole treatment period, and RMB 170468.89 Yuan for the FOLFOX6 followed by FOLFIRI regimen. Incremental analysis showed FOLFIRI followed by FOLFOX6 regimen could prolong one month of overall survival with additional cost of RMB 39885.44 Yuan in each patient while compared with the regimen of FOLFOX6 followed by FOLFIRI., Conclusions: Both FOLFOX and FOLFIRI regimens are able to prolong the survival time of patients with metastatic colorectal cancer, but cost of such treatments are still quite expensive for Chinese patients. FOLFOX6 regimen suggests better cost-effectiveness than FOLFIRI.

Objective: To evaluate the survival, complication and postoperative mortality after D(1) or D(2) lymph node dissection for gastric cancer., Methods: All the randomized clinical trials about nodal dissection for gastric cancer published within the last 20 years were collected. Quality assessment was done on each trial and relevant data were extracted from qualified trials. Meta-analysis was performed with the use of RevMan 4.2 (Cochrane) for statistic analysis., Results: Three hundred and ninety-four trials were yielded at the initial search. Four trials, recruited 1316 cases of gastric cancer in total, were included after quality assessment. Results of Meta-analysis showed that standard D(2) dissection could effectively improve patients' long-term survival [RR 1.35, 95%CI(1.12-1.62), NNT=9] as compared with D(1) dissection. If splenectomy (or pancreatico-splenectomy) was involved, D(2) dissection only improved the clinical outcome of T(3)-staged cases [RR 1.80,95%CI(1.03-3.15), NNT=13]. D(2) dissection produced higher rates of postoperative complication [RR 1.72,95%CI(1.46-2.03), NNT=6] and mortality [RR 2.12,95%CI(1.39-3.25), NNT=21] than D(1) dissection., Conclusions: Standard D(2) dissection can increase the overall survival rate when compared with D(1) dissection. If splenectomy (or pancreatico-splenectomy) cases are involved,D(2) dissection can only improve the survival rate of T(3)-staged patients. D(2) dissection yields higher postoperative morbidity and mortality than D(1) dissection.

Objective: To investigate the binding activity of activator protein-1 (AP-1) with DNA probe in the colorectal carcinoma (CRC) tissues and surrounding tissues and explore the correlation between the activation of AP-1 signal transduction pathway and metastasis of CRC., Methods: The AP-1 DNA binding activities were investigated by electrophoretic mobility shift assay (EMSA) in CRC specimens (T), surrounding tissues including 2 cm (P(2)), 5 cm(P(5)) far away from primary tumor margin and distal resection margin of the specimens (N). The mRNA expression level of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) were measured by quantitive reverse transcription polymerase chain reaction (Q- RT-PCR)., Results: The AP-1 DNA binding activity in T was significantly higher than those in P(2), P(5) and N (P< 0.05) tissues. There were significantly positive correlations between AP-1 DNA binding activity in tumor and invasive degree, lymphatic metastasis respectively (P< 0.01), but no correlation with histological classification and differentiation (P> 0.05). The transcription levels of VEGF and MMP-9 in CRC were significantly higher than those in P(5) and N (P< 0.01, P< 0.05) tissues. The transcription levels of VEGF and MMP-9 were significantly correlated with increasing AP-1 DNA binding activity (P< 0.01)., Conclusions: AP-1 is significantly correlated to the invasion and metastasis in CRC. The activation of AP-1 signal transduction pathway might be involved in the angiogenesis and of degradation extracellular matrix during tumor metastasis.