OBJECTIVETo evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer.

METHODSWe retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups.

RESULTSAccording to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025).

CONCLUSIONIn patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; mortality ; pathology

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Colorectal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Esophageal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Gastrointestinal Tract ; metabolism ; pathology ; Gene Expression ; Humans ; Neoadjuvant Therapy ; methods ; Neoplasm Grading ; Neoplasms, Vascular Tissue ; diagnosis ; drug therapy ; mortality ; secondary ; Prognosis ; SOXB1 Transcription Factors ; genetics ; metabolism ; Stomach Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Survival Analysis

OBJECTIVETo investigate the clinical effect of intraoperative peritoneal hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC).

METHODSA total of 118 AGC patients with serosal invasion were enrolled in this study from 1998 to 2001. Among these cases, 96 patients without macroscopic peritoneal metastases were selected for prophylactic study, including 42 cases with IPHC and 54 cases without IPHC as control. Other 22 patients with macroscopic peritoneal metastases were selected for therapeutic study, including 10 cases with IPHC and 12 without IPHC. Postoperative survival rate and peritoneal recurrence were compared.

RESULTSFor prophylactic study, the 1, 2 and 4 years survival rates were 85.7%, 81.0% and 63.9% respectively in the patients with IPHC,significantly higher than 77.3%, 61.0% and 50.8% in the patients without IPHC. Cox ratio hazard model revealed that IPHC procedure was an independent prognostic factor. More patients in the control group suffered from peritoneal recurrence than those in IPHC group (34.7% vs 10.3%). For therapeutic study,the median survival period of the patients with IPHC was 10 months, higher than 5 months in the patients without IPHC. The overall 1, 2, 4 year survival rates were 76.9%, 69.2%, 55.2% respectively in all cases with IPHC, higher than 66.2%, 49.7%, 41.4% in the cases without IPHC.

CONCLUSIONIPHC procedure can improve the prognosis of AGC patients with serosal invasion, reduce the risk for peritoneal recurrence, and is an independent prognostic factor.

Adult ; Aged ; Chemotherapy, Cancer, Regional Perfusion ; methods ; Female ; Follow-Up Studies ; Humans ; Hyperthermia, Induced ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Peritoneal Neoplasms ; drug therapy ; secondary ; Prognosis ; Stomach Neoplasms ; drug therapy ; mortality ; pathology ; Survival Rate ; Treatment Outcome

PURPOSE: Although neoadjuvant therapy has been accepted as a treatment option in locally-advanced gastric cancer, its prognostic value has been difficult to evaluate. MATERIALS AND METHODS: Seventy-four gastric cancer patients who underwent gastrectomy after neoadjuvant treatment were divided into two groups according to the pathologic response: favorable (ypT0) and others (ypT1-4). The clinicopathologic characteristics, predictive factors for pathologic response, and oncologic outcome were evaluated. RESULTS: Eleven patients (14.8%) demonstrated ypT0 and the remaining 63 patients (85.2%) were ypT1-4. Chemoradiotherapy (CCRTx) rather than chemotherapy (CTx) was the only predictive factor for a favorable pathologic response. Chemotherapeutic factors and tumor marker levels did not predict pathologic response. The 1-, 2-, and 3-year disease-free survivals were 83.4%, 70%, and 52.2%. The 1-, 3-, 5-year overall survivals were 88.5%, 67.5%, and 51.2%, respectively. Although a complete pathologic response (ypT0N0M0) was achieved in 7 patients, 28.6% of them demonstrated recurrence of the tumor within 6 months after curative surgery. CONCLUSION: CCRTx rather than CTx appears to be more effective for achieving good pathologic response. Although favorable pathologic response has been achieved after neoadjuvant treatment, the survival benefit remains controversial.
Aged ; Chemoradiotherapy/*methods ; Disease-Free Survival ; Female ; Gastrectomy ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local/pathology ; Stomach Neoplasms/*drug therapy/mortality/pathology/*radiotherapy/surgery ; Treatment Outcome ; Tumor Markers, Biological

Helicobacter pylori can cause variety of upper gastrointestinal disorders such as peptic ulcer, mucosa associated lymphoid tissue (MALT)-lymphoma, and gastric cancer. The prevalence of H. pylori infection has significantly decreased in Korea since 1998 owing to active eradication of H. pylori. Along with its decrease, the prevalence of peptic ulcer has also decreased. However, the mean age of gastric ulcer increased and this is considered to be due to increase in NSAID prescription. Gastric cancer is one of the leading causes of cancer deaths in Korea and Japan, and IARC/WHO has classified H. pylori as class one carcinogen of gastric cancer. Despite the decreasing prevalence of H. pylori infection, the total number of gastric cancer in Korea has continuously increased from 2006 to 2011. Nevertheless, the 5 year survival rate of gastric cancer patients significantly increased from 42.8% in 1993 to 67% in 2010. This increase in survival rate seems to be mainly due to early detection of gastric cancer and endoscopic mucosal dissection treatment. Based on these findings, the prevalence of peptic ulcer is expected to decrease even more with H. pylori eradication therapy and NSAID will become the main cause of peptic ulcer. Although the prevalence of gastric cancer has not changed along with decreased the prevalence of H. pylori, gastric cancer is expected to decrease in the long run with the help of eradication therapy and endoscopic treatment of precancerous lesions.
Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Gastrointestinal Diseases/complications/*epidemiology ; Helicobacter Infections/complications/drug therapy/epidemiology ; Humans ; Lymphoma, B-Cell, Marginal Zone/epidemiology ; Peptic Ulcer/epidemiology/etiology ; Prevalence ; Stomach Neoplasms/etiology/mortality/pathology

OBJECTIVE: To investigate the prognostic value of tumor deposits(TD)in N0 stage gastric cancer. METHODS: A retrospective case-control study was performed on clinicopathological data of 751 N0 stage gastric cancer patients who underwent subsequent R0 gastrectomy from January 2011 to February 2013 at Zhengzhou University Affiliated Tumor Hospital. Patients were divided into TD-negative group (688 cases) and TD-positive group (63 cases). Propensity score matching was used to balance the covariances between the two groups, such as age, gender, differentiation degree, tumor location, T stage, perineural invasion, lymphovascular invasion, extent of resection, tumor size, surgical procedure,and chemotherapy. Matching was performed by the minimal adjacent method of 1:2 pairing. The survival analysis was carried out using Kaplan-Meier method,and differences between the curves were detected by log-rank test. Cox proportional hazard model was used to perform univariate analysis and multivariate analysis. RESULTS: After matching,56 patients were allocated into the TD-positive group and 112 patients into the TD-negative group, and the baseline of clinicopathological data of 2 groups matched well (all P>0.05). The median follow-up time was 55.2 (12.0-83.2) months, and 3 patients were lost to follow-up (died of other diseases). In TD-positive group, 38 patients died of gastric cancer and 1 died of other disease. In TD-negative group, 52 patients died of gastric cancer and 2 died of other diseases. The TD-positive group had lower 5-year survival rate than TD-negative group (31.0% vs. 52.9%,χ²=6.230, P=0.014). Subgroup analysis showed that the 5-year survival rate of T1-2 stage TD-positive patients was significantly lower than that of T1-2 stage TD-negative patients (47.1% vs. 92.6%, χ²=11.433,P<0.001),while the difference between two groups with T3-4 stage (23.8% vs. 40.0%, χ²=2.995,P=0.084)was not significant. In patients receiving chemotherapy, the 5-year survival rate of TD-positive group was significantly lower than that of TD-negative group(34.1% vs. 54.8%, χ²=4.122, P=0.042). Further subgroup analysis showed that patients receiving postoperative chemotherapy of TD-positive group both in T1-2 stage (63.6% vs. 100%, χ²=3.830,P=0.048) and in T3-4 stage (24.2% vs. 48.4%, χ²=4.740,P=0.029) had significantly lower 5-year survival rates than those of TD-negative group. However,T1-2 stage TD-positive patients receiving chemotherapy had significantly higher 5-year survival rate as compared to those without receiving chemotherapy(63.6% vs. 16.7%, χ²=5.474,P=0.019).Univariate analysis revealed T stage (HR=1.829, 95%CI:1.490-2.245, P<0.001),perineural invasion (HR=2.620, 95%CI:1.617-4.246,P<0.001),tumor size (HR=1.646, 95%CI:1.078-2.512, P=0.021),TD(HR=1.691,95%CI:1.112-2.572,P=0.014) were associated with the prognosis of patients with gastric cancer. Multivariate analysis showed TD-positive (HR=2.035, 95%CI:1.325-3.126, P=0.001), later T stage (HR=1.812, 95%CI: 1.419-2.313,P<0.001), perineural invasion (HR=1.782,95%CI:1.058-3.002,P=0.030) were independent risk factors for the prognosis of gastric cancer. CONCLUSIONS TD is an independent risk factor for N0 stage gastric cancer,and may be closely related to T stage. Patients with TD-positive stage T1-2 should receive chemotherapy, but the prognosis of TD-positive patients undergoing adjuvant chemotherapy is poorer as compared to TD-negative patients. Therefore, more individualized treatments should be administrated.
Antineoplastic Agents ; therapeutic use ; Case-Control Studies ; Chemotherapy, Adjuvant ; Gastrectomy ; Humans ; Neoplasm Staging ; Prognosis ; Propensity Score ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; mortality ; pathology ; surgery ; Survival Analysis ; Survival Rate

OBJECTIVETo observe the efficacy and safety of chemotherapy regimens oxaliplatin combined with capecitabine (CAPOX) or oxaliplatin combined with tegafur, gimeracil and oteracil potassium capsules (S-1)(SOX), and to investigate the value of expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) proteins in tumor tissue for predicting the efficacy of CAPOX and SOX regimens in advanced gastric cancer patients.

METHODSA total of 107 newly-diagnosed, stage Ⅲc/Ⅳ gastric cancer patients (no surgical indication, ECOG performance scores 0-2 and expected survival time ≥3 months) were recruited with 101 patients evaluated. The patients were randomly divided into two groups. One was study group in which the patients received CAPOX regimen. The other was control group received SOX regimen. Each patient received four cycles, at least two cycles chemotherapy every three weeks and followed up until death or lost. Tumor biopsies were obtained by gastroscopy for immunohistochemical examination of the expression of TP and DPD proteins before chemotherapy. Response rate (ORR), overall survival (OS) and time to tumor progression (TTP) of the patients were assessed.

RESULTSThe objective response rate (ORR) of the study and control groups was 49.0% (5/51) vs. 46.0% (23/50), respectively (P>0.05). The overall survival (OS) was 357.36±24.69 days in the study group and 349.87±22.63 days in the control group, and the time-to-progression (TTP) was 216.75±19.32 days in the study group and 220.54±18.47 days in the control group (P>0.05 for both). Stratified analysis showed that the ORR of TP-positive patients in the study group was significantly higher than that in the control group (72.0 % vs. 41.7 %, P=0.032). There was no significant difference in ORR between the TP-negative patients in the study and control groups (26.9% vs. 50.0%, P=0.087), while the ORR of DPD-positive patients in the control group was significantly higher than that of the study group (51.9% vs. 34.6%, P=0.046). There was no significant difference in the ORR between DPD-negative patients in the study and control groups (64.0% vs. 39.1%, P=0.084). The follow-up showed that the OS (378.42±22.56 days) and TTP (271.77±24.92 days) in the TP-positive patients of the study group were significantly longer than those of the control group (OS: 326.57±19.84 days, and TTP: 229.13±22.68 days)( P<0.05). The OS was 371.25±23.97 days and TTP was 264.66±21.36 days in the DPD-positive patients of control group, significantly longer than those of the study group (OS: 334.73±21.47days, and TTP: 208.58±20.70 days) (P<0.05). But there was no significant difference in the OS and TTP between the TP- and DPD-negative patients in the two groups (P>0.05). In respect of adverse events, both the rates of hematological and non-hematological toxicities were low and similar between the two groups (P>0.05), and well-tolerated by the patients.

CONCLUSIONSBoth CAPOX and SOX regimens are effective chemotherapeutic protocols in treatment of patients with advanced gastric cancer. The expression levels of TP and DPD in tumor tissue can be used as a predictive factor for the efficacy of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin regimens. CAPOX chemotherapy regimen is more suitable for the TP-positive gastric cancer patients, and SOX regimen is more suitable for the DPS-positive gastric cancer patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; administration & dosage ; adverse effects ; Capsules ; Dihydrouracil Dehydrogenase (NADP) ; metabolism ; Disease Progression ; Humans ; Neoplasm Proteins ; metabolism ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pyridines ; administration & dosage ; adverse effects ; Stomach Neoplasms ; drug therapy ; metabolism ; mortality ; pathology ; Tegafur ; administration & dosage ; adverse effects ; Thymidine Phosphorylase ; metabolism

BACKGROUND/AIMS: The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer. METHODS: Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0. RESULTS: Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP. CONCLUSIONS: FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.
Adult ; Aged ; Anemia/etiology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Camptothecin/adverse effects/*analogs & derivatives/therapeutic use ; Disease Progression ; Female ; Fluorouracil/adverse effects/therapeutic use ; Humans ; Kaplan-Meier Estimate ; Leucovorin/adverse effects/therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds/adverse effects/therapeutic use ; Retrospective Studies ; Stomach Neoplasms/*drug therapy/mortality/pathology ; Treatment Outcome