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Purpose: To investigate the potential of intravoxel incoherent motion diffusion-weighted imaging (IVIM) for preoperative prediction of lymphovascular invasion (LVI) in gastric cancer (GC)., Methods: This study prospectively enrolled 90 patients (62 males, 28 females, 60.79 ± 9.99 years old) who received radical gastrostomy. Abdominal MRI examinations including IVIM were performed within 1 week before surgery. Patients were divided into LVI-positive and -negative group according to pathological diagnosis after surgery. The apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D*), and pseudodiffusion fraction (f), were compared between the two groups. The relationship between MRI parameters and LVI was studied by Spearman's correlation analysis. Multivariable logistic regression analysis was used to screen independent predictors of LVI. Receiver-operating characteristic curve analyses were applied to evaluate the efficacy., Results: The ADC, D in LVI-positive group were lower, whereas tumor thickness and f parameter in LVI-positive group were higher than those in LVI-negative group, and they were statistically correlated with LVI (p < 0.05). D, f and tumor thickness were independent risk factors of LVI. The area under the curve of ADC, D, f, thickness, and the combined parameter (D + f + thickness) were 0.667, 0.754, 0.695, 0.792, and 0.876, respectively. The combined parameter demonstrated higher efficacy than any other parameters (p < 0.05)., Conclusion: The ADC, D, and f can effectively distinguish LVI status of GC. The D, f and thickness were independent predictors. The combination of the three predictors further improved the efficacy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Metabolic syndrome (MetS) and gastric cancer are age-related diseases, and their incidence rates have risen in past decades. However, few studies have examined the relationship between MetS and the prognosis of elderly patients who underwent radical gastrectomy, and the conclusions remain controversial., Methods: We conducted a prospective study of elderly patients who underwent radical gastrectomy for gastric cancer from August 2014 to February 2018. MetS was defined based on visceral fat area (VFA) instead of BMI or waist circumference. Receiver operating characteristic curve analysis was used to determine the cutoff values for VFA., Results: A total of 585 patients were included in this study. The optimal cutoff values for VFA were 96.1 cm 2 for men and 105.2 cm 2 for women, and 212 patients were diagnosed with MetS. The patients with MetS suffered significantly more postoperative complications than those without MetS (37.3% versus 21.4%, P < 0.001). The multivariable logistic regression analysis demonstrated that MetS (OR 2.923, P < 0.001), BMI < 18.5 kg/m 2 (OR 2.086, P = 0.045), cardiac tumor (OR 1.865, P = 0.013), and Nutritional Risk Screening 2002 scores ≥ 3 (OR 1.654, P = 0.015) were independent risk factors for postoperative complications. During a median follow-up period of 56.4 months, the MetS group and the non-MetS group had comparable overall survival and disease-specific survival., Conclusions: MetS was an independent risk factor for complications of the elderly patients after radical gastrectomy, but had no influence on long-term survival., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Purpose: To investigate the efficacy of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the early prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC)., Methods: Fifty patients with LAGC who were treated with NAC followed by radical gastrectomy were enrolled. Uncontrasted and DCE-MRI were performed within 1 week before NAC. According to tumor regression grading (TRG), patients were labeled as responders (TRG = 0 + 1) and non-responders (TRG = 2 + 3). Apparent diffusion coefficients (ADC) and DCE-MRI kinetics (K trans , V e , and K ep ) were compared between the two groups. Logistic regression analysis was performed to screen independent factors to predict the NAC efficacy. The relationship between MRI parameters and TRG was studied by Spearman's correlation analysis. Receiver-operating characteristic curve analyses were applied to evaluate the efficacy., Results: ADC, K trans , and K ep values were higher in responders than in non-responders (p < 0.05) and correlated with TRG (p < 0.05). The ADC and K ep values were independent markers for predicting TRG. The area under the curve, sensitivities, specificities of ADC, K trans , K ep , and ADC + K ep were 0.813, 0.699, 0.709, 0.886;73.64%, 65.54%, 63.21%, 70.37%; 86.47%, 54.97%, 79.47%, 95.65%; respectively. ADC + K ep demonstrated a higher efficacy than K trans and K ep (p = 0.012, 0.011), but without improvement compared with ADC (p > 0.05)., Conclusion: Both DWI and DCE-MRI can effectively predict the pathologic response to NAC in LAGC. A combination of ADC and K ep increased the efficacy, and ADC is the most valuable imaging parameter., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Increasing evidence has suggested that sarcopenia is linked with cancer prognosis, but only limited data have focused on the impact of myosteatosis on cancer outcomes. This study evaluates the influence of myosteatosis on postoperative complications and survival in those patients who underwent radical resection of gastric carcinoma., Methods: Patients who underwent elective radical gastrectomy for gastric cancer and had computed tomographic images available were identified from a prospectively collected database between 2008 and 2013. Myosteatosis was diagnosed by the cutoff values obtained from the method of optimum stratification. To obtain 2 well-balanced cohorts for available variables influencing clinical outcomes, the myosteatosis group was matched 1:1 with nonmyosteatosis group by using a propensity score match., Results: Of 973 patients, 584 were matched for analyses. Compared with the nonmyosteatosis group, the myosteatosis group manifested significantly higher severe postoperative complications rates, shorter overall survival, and disease-free survival. Before matching, multivariate analyses identified that myosteatosis was an independent risk factor for severe postoperative complications, and Cox proportions hazards model showed that myosteatosis was an independent predictor for shorter overall survival and disease-free survival. In addition, subgroup analyses of each muscle phenotype showed that patients with both sarcopenia and myosteatosis had a poorer overall survival and disease-free survival than other patients., Conclusion: Myosteatosis in gastric cancer is associated with poor prognosis. Classifying the skeletal muscle into subranges of radio density is a promising strategy to understand the impact of skeletal muscle on unfavorable surgical outcomes in gastric cancer patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background/objectives: The aim of this study was to examine the impact of visceral fat on surgical complications and long-term survival for patients undergoing radical gastrectomy., Subjects/methods: From 2009 to 2013, 859 patients who underwent curative resection for gastric cancer were enrolled from a prospectively maintained database. Visceral fat area (VFA) was assessed by preoperative CT scans. Patients were divided into two groups by VFA. Perioperative variables and postoperative outcomes were compared between the high VFA group and low VFA group. Univariable and multivariable analysis were performed to investigate independent risk factors of postoperative complications and survival., Results: Some 859 patients were included in the study, 308 of whom were classified as high VFA. High VFA was correlated with advance age (P = 0.020), higher albumin levels (P = 0.001), hemoglobin levels (P < 0.05), ASA grade (P = 0.043) and Charlson Comorbidity Index (P = 0.004). Relative to patients with low VFA, those with high VFA had longer surgical durations (P = 0.004), higher rate of postoperative complications (P = 0.004), and longer hospital stays (P = 0.004). High VFA was identified as the only determinant for surgical complications by logistic regression analysis (OR, 2.236, 95% CI, 1.537-3.254; P < 0.001). Cox proportional hazards regression revealed no correlation between VFA and overall survival (OS) or disease-free survival (DFS)., Conclusions: Increased VFA independently predicts surgical complications in patients after gastrectomy. However, VFA is not a prognostic biomarker of OS or DFS in patients with gastric cancer.

Gastric cancer (GC) is among the most malignant cancers with high incidence and poor prognoses worldwide as well as in China. dCTP pyrophosphatase 1 (DCTPP1) is overexpressed in GC with a poor prognosis. Given chemotherapeutic drugs share similar structures with pyrimidine nucleotides, the role of DCTPP1 in affecting the drug sensitivity in GC remains unclear and is worthy of investigation. In the present study, we reported that DCTPP1-knockdown GC cell line BGC-823 exhibited more sensitivity to 5-fluorouracil (5-FU), demonstrated by the retardation of cell proliferation, the increase in cell apoptosis, cell cycle arrest at S phase and more DNA damages. Multidrug resistance 1 (MDR1) expression was unexpectedly down-regulated in DCTPP1-knockdown BGC-823 cells together with more intracellular 5-FU accumulation. This was in large achieved by the elevated methylation in promoter region of MDR1 gene. The intracellular 5-methyl-dCTP level increased in DCTPP1-knockdown BGC-823 cells as well. More significantly, the strong correlation of DCTPP1 and MDR1 expression was detectable in clinical GC samples. Our results thus imply a novel mechanism of chemoresistance mediated by the overexpression of DCTPP1 in GC. It is achieved partially through decreasing the concentration of intracellular 5-methyl-dCTP, which in turn results in promoter hypomethylation and hyper-expression of drug resistant gene MDR1. Our study suggests DCTPP1 as a potential indicative biomarker for the predication of chemoresistance in GC.

Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm²/m² for women and 40.8 cm²/m² for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P < 0.001), but not for total complications. However, sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR = 1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage, sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia is independently associated with overall and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I., Competing Interests: The authors have no conflicts of interest to disclose.

Our previous study suggests that heme oxygenase-1 (HO-1) may play an important role in the metastasis of gastric cancer. Zinc protoporphyrin IX (ZnPPIX) is a special HO-1 inhibitor that inhibits the angiogenesis of pancreatic and lung cancer. In this study, we employed ZnPPIX to investigate the role of HO-1 in peritoneal metastasis of gastric cancer (PMGC) and explored the potential mechanism. We established animal model of PMGC by orthotopic implantation into nude mice of human gastric cancer cell line GC9811-P with high peritoneal metastasis potential. The mice were injected intraperitoneally with saline, CTX or ZnPPIX. Tumor microvessel density (MVD) in peritoneal metastatic nodules was determined by immunohistochemistry, and vascular endothelial growth factor (VEGF) level was determined by ELISA. We found that the number, volume, weight of peritoneal metastatic nodules and volume of seroperitoneum in ZnPPIX (4 mg/kg) group decreased remarkably compared with control group. MVD value and VEGF level of peritoneal metastatic tumor in ZnPPIX (4 mg/kg) group also decreased significantly, while the survival rate and survival time of the mice were higher than control group. ZnPPIX dose-dependently suppressed VEGF and GC9811-P induced angiogenesis. Furthermore, ZnPPIX suppressed VEGF induced reactive oxygen species production and ERK phosphorylation in human umbilical vein endothelial cells. In conclusion, our results suggest that HO-1 plays an important role in PMGC and ZnPPIX is an effective antitumor and antiangiogenic agent for PMGC., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Aim: To assess the efficacy of immunotherapy with expanded activated autologous lymphocytes (EAALs) in gastric cancer., Methods: An observational study was designed to retrospectively analyze the clinical data of 84 gastric cancer patients, of whom 42 were treated by EAAL immunotherapy plus conventional treatment and another 42 only received conventional treatment (control group). EAALs were obtained by proliferation of peripheral blood mononuclear cells from patients followed by phenotype determination. Clinical data including age, gender, clinical stage, chemotherapeutic regimens, hospitalization, surgical, radiotherapy, and survival data were collected along with EAAL therapy details and side effects. Patients were followed and the relationship between treatment and overall survival (OS) data obtained for the immunotherapy and control groups were compared retrospectively. The safety of EAAL immunotherapy was also evaluated., Results: After in vitro culture and proliferation, the percentages of CD3+, CD3+CD8+, CD8+CD27+, CD8+CD28+, and CD3+CD16+/CD56+ cells increased remarkably (P < 0.05), while the percentages of CD3+CD4+, CD4+CD25+, and CD3-CD16+/CD56+ (natural killer cells) were overtly decreased (P < 0.05); no significant change was observed in CD4+CD25+CD127- cells (P = 0.448). Interestingly, OS in the immunotherapy group was significantly higher than that in the control group, with 27.0 and 13.9 mo obtained for the two groups, respectively (P = 0.028, HR = 0.573, 95%CI: 0.347-0.945). These findings indicated a 42.7% decrease in the risk of death. In addition, we found that clinical stage and application of EAAL immunotherapy were independent prognostic factors for gastric cancer patients. Indeed, the OS in stage IIIc and IV patients that had received surgery was prolonged after EAAL immunotherapy (P < 0.05). Importantly, in vitro induction and proliferation of EAAL were easy and biologically safe., Conclusion: Overall, EAAL adoptive immunotherapy might prolong the OS in gastric cancer patients.

Objective: The aim of this study was to evaluate the efficacy and safety of adjuvant chemoradiotherapy (CRT) versus chemotherapy (CT) for patients with gastric cancer., Methods: Electronic databases including PUBMED, EMBASE, and Cochrane Library were retrieved for original studies from their inception to April 2014. Two reviewers independently evaluated the quality of the included studies and extracted the data. All Statistical analyses were performed using RevMan Version 5.2 software., Results: Six randomized controlled trials involving 1,171 patients were included. The meta-analysis showed that there were statistical significances between chemoradiotherapy group and chemotherapy group in 5-year disease free survival rate (OR = 1.56, 95% CI: 1.09-2.24), local-regional recurrence rate (OR = 0.46, 95% CI: 0.32-0.67) and neutropenia (OR = 1.47, 95% CI: 1.11-1.96). While treatment efficacy did not differ significantly by the 5-year overall survival rate (OR = 1.32, 95% CI: 0.92-1.88), 3-year disease free survival rate (OR = 1.28, 95% CI: 0.92-1.80), and new metastases (OR = 0.76, 95% CI: 0.57-1.03). Toxicities were not significantly different between two groups for nausea/vomiting, diarrhea, anemia, and thrombocytopenia., Conclusions: For patients with gastric cancer, adjuvant chemoradiotherapy could significantly improve 5-year disease free survival rate and reduce local-regional recurrence rate compared with chemotherapy and, can be well accepted and tolerated., (© 2014 Wiley Periodicals, Inc.)

Aim: To elucidate the potential impact of examined lymph nodes (eLNs) on long-term survival of node-negative gastric cancer patients after curative surgery., Methods: A total of 497 node-negative gastric cancer patients who underwent curative gastrectomy between January 2000 and December 2008 in our center were enrolled in this study. Patients were divided into 4 groups according to eLNs through cut-point analysis. Clinicopathological features were compared between ≤ 15 eLNs group and > 15 eLNs group and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified using the Cox proportional hazards regression model. Stratified analysis was performed to investigate the impact of eLNs on patient survival in each stage. Overall survival was also compared among the four groups. Finally, we explored the recurrent sites associated with eLNs., Results: Patients with eLNs > 15 had a better survival compared with those with eLNs ≤ 15 for the entire cohort. By the multivariate survival analysis, we found that the depth of invasion and the number of eLNs were the independent predictors of overall survival (OS) of patients with node-negative gastric cancer. According to the cut-point analysis, T2-T4 patients with 11-15 eLNs had a significantly longer mean OS than those with 4-10 eLNs or 1-3 eLNs. Patients with ≤ 15 eLNs were more likely to experience locoregional and peritoneal recurrence than those with > 15 eLNs., Conclusion: Number of eLNs could predict the prognosis of node-negative gastric cancer, and dissection of > 15 eLNs is recommended during lymphadenectomy so as to improve the long-term survival.

Background: Cyclooxygenase-2 (COX-2) is believed to be involved in gastric carcinogenesis. However, it is still controversial whether COX-2 expression can be regarded as a prognostic factor for gastric cancer patients., Aim: To obtain a more accurate relationship between COX-2 overexpression and prognosis in gastric cancer by meta-analysis., Method: Relevant articles published up to May 2013 were searched by use of several keywords in electronic databases. Separate hazard ratio (HR) estimates and 95 % confidence intervals (95 % CI) for COX-2 overexpression and overall survival (OS) and disease-free survival (DFS) with gastric cancer were extracted. Combined HR with 95 % CI was calculated by use of Stata11.0 software to estimate the size of the effect. Publication bias testing and sensitivity analysis were also performed., Results: A total of 27 studies which included 3,891 gastric cancer patients were combined in the final analysis. Combined results suggested that COX-2 overexpression was associated with an unfavorable OS (HR 1.58, 95 % CI 1.36-1.84) but not DFS (HR 1.15, 95 % CI 0.93-1.43) among patients with gastric cancer. Publication bias was absent. Sensitivity analysis suggested that the results of this meta-analysis were robust., Conclusions: The results of this meta-analysis suggest that high COX-2 expression may be an independent risk factor for poor OS of patients with gastric cancer. More large prospective studies are now needed to further clarify the prognostic value of COX-2 expression for DFS in gastric cancer.

Objective: To elucidate the necessity of para-aortic lymph nodal dissection in D2 lymphadenectomy for gastric cancer in N3 stage., Methods: A total of 278 gastric cancer patients staged N3 who underwent gastrectomy between January 2003 and December 2007 were enrolled. There were 180 male and 98 female patients, and the patients' age were 26-93 years (median was 61 years). All patients had undergone surgical treatment. There were R0 resection in 246 cases and R1 resection in 32 cases. Lymph node dissection included D1 lymphadenectomy with 125 cases, D2 lymphadenectomy with 109 cases and D2+para-aortic lymph nodal dissection(PAND) with 44 cases. The surgical approach were total gastrectomy (98 cases) and subtotal gastrectomy (180 cases). Potential prognostic factors were analyzed., Results: The lymph node metastasis of each station was high in gastric cancer patients staged N3 and 34.1% patients had the para-aortic lymph nodal metastasis. Borrmann type (HR = 1.350, 95%CI: 1.018-1.790, P = 0.037), curability (HR = 1.580, 95%CI: 1.076-2.322, P = 0.020), depth of invasion (HR = 1.697, 95%CI: 1.005-2.864, P = 0.048), metastatic lymph node ratio (HR = 1.631, 95%CI: 1.261-2.111, P = 0.000), extranodal metastasis (HR = 1.336, 95%CI: 1.027-1.738, P = 0.031), postoperative adjuvant chemotherapy (HR = 1.312, 95%CI: 1.015-1.696, P = 0.038), extent of lymphadenectomy (HR = 1.488 and 2.114, P = 0.054 and 0.000) and number of retrieved lymph node (HR = 1.503 and 2.112, P = 0.025 and 0.000) were found to be factors correlated to overall survival. In multivariate analysis, only Borrmann type (HR = 1.399, 95%CI: 1.050-1.863, P = 0.022), metastatic lymph node ratio (HR = 1.353, 95%CI: 1.016-1.802, P = 0.039) and extent of lymphadenectomy (HR = 1.725, 95%CI: 1.111-2.678, P = 0.015) were independent prognostic factors for gastric cancer patients in N3 stage., Conclusions: Patients in N3 stage should at least have 30 lymph node examined. D2 lymph node dissection plus PAND may improve the overall survival for gastric cancer patients in N3 stage.

Recently, stathmin 1 has been proposed to function as an oncogene based on some relevant studies in multiple types of human cancers. However, the role of stathmin 1 in gastric cancer carcinogenesis has not been elucidated yet. The aim of this study was to investigate the expression of stathmin 1 as well as its association with overall survival of gastric cancer patients. The expression of stathmin 1 was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, stathmin 1 expression was analyzed by immunohistochemistry in paraffin samples from 210 primary gastric cancer patients. The expression levels of stathmin 1 mRNA and protein in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of stathmin 1 is correlated with Lauren's classification, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (all P < 0.05). Univariate analysis showed that high stathmin 1 expression was associated with poor prognosis in gastric cancer patients (P = 0.040). Multivariate analysis demonstrated that only lymph node metastasis and TNM stage were the independent prognostic indicators for gastric cancer. Stathmin 1 expression status is not an independent prognostic factor for patients with gastric cancer. Further subgroup analysis revealed that stathmin 1 expression was significantly correlated with prognosis in diffuse type gastric cancer. This research showed that the stathmin 1 overexpression might play an important role in the pathogenesis and subsequent progression of gastric cancer. Stathmin 1 could also be a potential therapeutic target in gastric cancer, especially for diffuse type gastric cancer.

Objective: To elucidate the necessity of No.14v lymph node dissection in D2 lymphadenectomy for advanced gastric cancer., Methods: Clinicopathological data of 131 cases of advanced gastric cancer receiving D2 or D2+ plus No.14v lymph node dissection were reviewed retrospectively. Clinicopathological factors associated with No.14v lymph node metastasis were analyzed and prognostic value of No.14v lymph node metastasis was evaluated., Results: Of the 131 patients, 24 (18.3%) had positive No.14v lymph node. The incidence of 14v metastasis was associated with tumor location, tumor size, depth of invasion, N staging, TNM staging, No.1, No.6, and No.8a lymph nodes metastasis. Tumor location and N staging were independent risk factors for No.14v metastasis (all P<0.05). The 5-year survival rate was 8.3% and 37.8% in patients with and without No.14v metastasis respectively. The difference was statistically significant (P<0.01). Multivariate analysis revealed that metastasis of No.14v was an independent prognostic factor for advanced gastric cancer after D2 lymphadenectomy (P=0.029, RR=1.807, 95%CI:1.064-3.070)., Conclusions: For advanced middle and lower gastric cancers, especially those with larger size, serosa invasion and possibility of No.6 lymph node metastasis, it is necessary and feasible to remove the No.14v lymph node.

Objective: To investigate the clinicopathological characteristics and prognostic factors of patients with pathological stage pN3 gastric cancer., Methods: A retrospective study of 310 patients with histologically confirmed pN3 stage gastric cancer undergoing radical gastrectomy from January 2000 to December 2006 in our department was performed. The Kaplan-Meier method was used to analyze the survival. Log-rank test and Cox regression model were carried out for univariate and multivariate analyses., Results: All the patients were followed up for 2 to 103 (mean 35.7) months. The overall 5-year survival rate was 14.6%. There were 201 cases with stage pN3a and 109 cases with stage pN3b, and the 5-year survival rates were 16.8% and 10.3% respectively (P=0.013). Univariate analysis showed that tumor location, Borrmann type, depth of tumor invasion, surgical method, metastatic lymph node ratio, and pN stage were associated with postoperative survival (all P<0.05). The multivariate analysis revealed that depth of tumor invasion, surgical method and metastatic lymph node ratio were independent prognostic factors, while the pN stage was not. The difference of 5-year survival rate between pN3a and pN3b subgroups was significant in pT4a patients (16.1% vs. 12.8%, P=0.001), while such difference was not significant in pT4b patients (8.6% vs. 3.1%, P=0.137)., Conclusions: Prognosis of patients with pN3 stage gastric cancer after radical resection is poor. Depth of tumor invasion and surgical method are independent prognostic factors for pN3 stage gastric cancer. Metastatic lymph node ratio is valuable to predict the prognosis of pN3 stage patients. The pN3 staging of the 7th UICC provides a more accurate prediction of prognosis.

Objective: To investigate the status of lymph node metastasis (LNM) and to discuss reasonable lymphadenectomy in early gastric cancer (EGC)., Methods: Between January 1991 and December 2010, 242 EGC patients underwent surgery in the Tianjin Cancer Hospital. Their clinical characteristics, pathologic features, and lymph node metastasis were analyzed retrospectively., Results: LNM was observed in 22 of 242 patients (9.1%), and 10 (5.5%) in 182 mucosal lesions and 12 (20.0%) in 60 submueosal lesions. There were 14 patients had LNM in the first tier alone, 4 patients had skipped metastasis, and 4 patients had LNM in the first, second, and third ties. The LNM was identified in 18 patients at the first tier with groups 7 and 3 being the most common (8 patients in each group), 7 patients at the second tier (4 patients in group 8a and 3 in group 9), and 2 patients at the third tier (one 16b, and one 4sa). Multivariable analysis showed that the depth of invasion (P=0.003, OR=4.386, 95%CI:1.656-11.617), and lymphatic vessel involvement(P=0.002, OR=13.621, 95%CI:2.711-68.447) were independent risk factors for LNM., Conclusions: LNM in EGC is mainly correlated with depth of invasion, and lymphatic vessel involvement. Precise evaluation of LNM pre- and intra-operatively is very important for the reasonable surgery.

Objective: To discuss the reasonable surgery for gastric body cancer., Methods: From January 2001 to December 2006, the clinicopathological data of 145 patients with a tumor in the middle third of the stomach underwent radical gastric resection were analyzed retrospectively. We conducted comparative analysis for the differences in clinicopathological characteristics and prognosis between total gastrectomy (TG) and subtotal gastrectomy (STG)., Results: The 98 patients underwent TG, 47 received STG. There were significant differences in aspects of tumor size, depth of tumor, nodal status and TNM stage between the 2 groups. Patients with more advanced cancer were more likely to receive TG. The 5-year survival rate for TG was lower (25.5%) than STG (63.8%) (χ(2) = 11.707, P = 0.000). However, if tumor stages were stratified, there was no significant difference in the 5-year survival rate. TNM stage (P = 0.044) and histologic type (HR = 1.834, 95%CI: 1.073 - 3.135, P = 0.027) were independent prognostic factors., Conclusions: The overall survival rate of STG for gastric cancer in the middle third of the stomach is better than that of TG. If the radical resection margin can be obtained for gastric body carcinoma, STG is considered instead of TG.

Objective: To evaluate the outcomes of combined organ resection for T4b gastric cancer, and determine the operative indication and prognostic factors., Methods: Clinical data of 96 cases with T4bN0-3bM0 gastric cancer treated with combined organ resection in Tianjin Cancer Hospital from 2001 to 2005 were analyzed retrospectively., Results: Twelve patients developed postoperative complications, including pancreatic fistula (n=4), abdominal infection(n=5), pulmonary infection(n=3), all of which were managed with conservative treatment. There were no perioperative deaths. All the patients had postoperative follow up with a median of 73 months. The 1-, 3-, 5-year overall survival rates were 70.5%, 42.1%, and 23.5%, respectively. Univariate analysis showed that Borrmann type, histologic type, lymph node staging, and pancreatic invasion were associated with the survival in patients with T4b gastric cancer(both P<0.05). Multivariable analysis showed that lymph node staging and histologic type were independent prognostic factors(all P<0.05)., Conclusion: For well differentiated gastric cancer with lymph node staging of pN0 or pN1, combined organ resection may offer survival benefit.

Gastric cancer remains one of the major health problems worldwide. Chemotherapy is an important therapeutic modality for gastric cancer, but the success rate of this treatment is limited because of chemoresistance. The ubiquitously expressed transcription factor NF-κB has been suggested to be associated with chemoresistance of gastric cancer. Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance to chemotherapeutics are needed for the treatment of gastric cancer. Curcumin, a component of turmeric, is one such agent that has been shown to suppress NF-κB and increase the efficacy of chemotherapy. In this study, we investigated whether curcumin can reverse chemoresistance by downregulating NF-κB in human gastric cancer cells. SGC-7901 human gastric cancer cells was treated with chemotherapeutics (etoposide and doxorubicin) or by combined application of curcumin and chemotherapeutics. The viability of SGC-7901 cells was measured by MTT assay. Apoptosis of SGC-7901 cells was detected using the TUNEL and Annexin V/PI methods. The protein levels of NF-κB were analyzed by immunocytochemical staining. EMSA was used to confirm the increased nuclear translocation of RelA. The protein levels of p-IκBα, Bcl-2 and Bcl-xL were analyzed by Western blotting. The chemotherapeutics (etoposide and doxorubicin) suppressed the growth of SGC-7901 cells, in a time-dose-dependent manner. Use of curcumin in addition to these agents can suppress cell growth further (inhibitory rate: doxorubicin vs. doxorubicin + curcumin, 33% vs. 45%, p<0.05; etoposide vs. etoposide + curcumin, 35% vs. 48%, p<0.05). Furthermore, chemotherapeutics induced apoptosis of SGC-7901 cells and activated NF-κB. The combination of curcumin and chemotherapeutics induced apoptosis of SGC-7901 cells further, attenuated the activation of NF-κB, and reduced expression of the NF-κB-regulated anti-apoptotic gene products Bcl-2 and Bcl-xL. Curcumin potentiates the antitumor effects of chemotherapeutics in gastric cancer by suppressing NF-κB and NF-κB-regulated anti-apoptotic genes.

Objective: To investigate the risk factors for the prognosis in patients with node-negative gastric cancer., Methods: Clinicopathological characteristics of 138 patients with node-negative gastric carcinoma undergoing curative gastrectomy from January 2000 to December 2005 were retrospectively analyzed., Results: The overall 5-year survival rate was 62.4%. The univariate analysis revealed that tumor size, tumor location, cell differentiation, invasive depth, operative type and Lauren histologic type had significant effects on the survival. The independent prognostic factors of these patients were tumor size, cell differentiation, and serosal involvement in multivariate analyses., Conclusion: For node-negative gastric cancer patients, tumor size, poor differentiation and serosal involvement are important markers to evaluate prognosis.

Objective: To analyze the clinical and pathologic influencing factors of early recurrence in patents with gastric cancer after radical gastrectomy., Methods: Clinicopathological data of 141 patients with recurrence after curative gastrectomy for gastric cancer from January 2001 to December 2004 were analyzed retrospectively. Risk factors correlated with tumor early recurrence and survival difference between early recurrence group (< 1 year, 82 cases) and control group (1 year after, 59 cases) were assessed., Results: The 1- and 3-year survival rates of in early recurrence group and control group were 36.6%, 2.4% and 100%, 45.8%, respectively (P < 0.05). The median survival time after recurrence in the two groups was 3, 5 months, respectively (P < 0.05). Univariate analysis showed that the age, tumor Borrmann type, tumor site, invasive depth, lymph node metastasis, pTNM stage, metastatic lymph node ratio, surgical procedure and intraperitoneal hyperthermic perfusion chemotherapy (IHPC) were significant factors associated with early recurrence after curative gastrectomy for gastric cancer (P < 0.05). Lymph node metastasis, metastatic lymph node ratio and IHPC were independent factors associate with early recurrence after curative gastrectomy on multivariate analysis (P < 0.05)., Conclusions: The patients with early recurrence after the radical gastrectomy have a poorer survival compared with cases recur later. Lymph node metastasis, metastatic lymph node ratio and IHPC are independent factors associate with early recurrence after curative gastrectomy for gastric cancer.

Objective: To explore the pattern of lymph node metastasis(LNM) in advanced proximal gastric cancer in order to guide lymphadenectomy., Methods: Between September 2001 and December 2005, a total of 103 patients with advanced proximal gastric cancer underwent radical gastrectomy with D2 or>D2 lymphadenectomy. The clinical characteristics, pathologic features, and LNM were analyzed by univariate and multivariate analysis., Results: LNM was observed in 81 of 103 cases(78.6%). The LNM was identified in 70.8% at N1, 38.3% at N2, 22.3% at N3. LNM frequency was found in groups No.3,No.1,No.2 and No.4Sa,4Sb (from the highest to the lowest) at N1, groups No.7, No.10, No.9, No.11, No.8a and No.4d at N2, and groups No.5, No.6, No.16 and No.12 at N3. Ordinal Logistic regression analysis showed that histopathological type, tumor size, depth of invasion, and distant metastasis were independent factors for lymph node metastasis in advanced proximal gastric cancer., Conclusions: The number of lymph node metastasis in advanced proximal gastric cancer is mainly associated with differentiation, tumor size, depth of invasion, and distant metastasis. It is essential to dissect the lymph nodes according to the risk of lymph node metastasis.

The ubiquitously expressed serine-threonine kinase Akt and the transcription factor NF-kappaB both are involved in cell proliferation and apoptosis. Furthermore, the activation of Akt or NF-kappaB has been suggested to associate with chemo-resistance of human tumors. The exact mechanism and interreaction of Akt and NF-kappaB pathway on chemoresistance in gastric cancer is still unknown. We explored the function of Akt and NF-kappaB pathway on chemoresistance in human gastric cancer cells. MTT method was used to analyze the influence of chemotherapeutics and the combined use of wortmannin or MG-132 on the growth of SGC-7901 cells. Apoptosis of SGC-7901 was detected by TUNEL and Annexin V/PI methods. The protein level of NF-kappaB was analyzed by immunocytochemical staining. EMSA was used to confirm the increased nuclear translocation of RelA. The protein level of p-Akt and p-IkappaBalpha were analyzed by Western blotting. Etoposide and doxorubicin suppressed the growth of SGC-7901 time and dose-dependently. Combined use of wortmannin or MG-132 can suppress growth further. Chemotherapeutics induced apoptosis of SGC-7901 and activated Akt and NF-kappaB, combined use of wortmannin or MG-132 induced apoptosis further and attenuated the activation of NF-kappaB. The combined use of wortmannin attenuated the activation of Akt, but combined use of MG-132 did not attenuate the activation of Akt. The activation of NF-kappaB is a branch mechanism of Akt anti-apoptosis effects. The chemotherapeutics induced apoptosis and induced the activation of Akt and NF-kappaB in SGC-7901 cell, suppression the activation of Akt or NF-kappaB can increase the effects of chemotherapeutics. NF-kappaB is a downstream target of Akt.

The major obstacle to successful treatment of gastric cancer is chemotherapy resistance. Our study was designed to investigate the role of phosphoinositide 3-kinase (PI3K)/Akt pathway in the development of chemoresistance in gastric cancer. In the present study, elevated Akt expression and Akt phosphorylation (Ser 473), as well as decreased PTEN expression were observed in 28 cases of gastric cancer tissues. Etoposide and doxorubicin stimulated Akt and PI3K activities in 2 gastric cancer cell lines (BGC-823 and SGC-7901), and the activities were concentration and time-dependent. Up-regulation of PTEN expression in BGC-823 cells by PEAK8-PTEN transient transfection obviously decreased the basal and anticancer drugs induced Akt activities, then sensitized BGC-823 cells to etoposide and doxorubicin. Pretreatment of BGC-823 and SGC-7901 cells with wortmannin, a PI3K inhibitor, attenuated cells's resistance to etoposide and doxorubicin. In addition, pretreatment of wortmannin blocked etoposide and doxorubicin induced IkappaB-alpha degradation, NFkappaB activation, phosphorylation of Akt, MDM-2 and forkhead transcription factors. Wortmannin pretreatment also promoted the accumulation of p27/Kip, but inhibited the Mcl-1 expression. Furthermore, wortmannin promoted etoposide and doxorubicin induced caspase-3, caspase-9 activation and poly ADP-ribose polymerase cleavage. Taken together, the observations indicate the PI3K/Akt pathway plays an important role in the chemoresistance of gastric cancer cells. A new strategy for combined chemotherapy of gastric cancer should be designed to more specifically block PI3K/Akt pathway and then decrease the amount of resistant cells., (Copyright 2007 Wiley-Liss, Inc.)