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Gastric cancer (GC) is the fifth most common cancer among all cancer fields and currently the third most common cause of cancer-related deaths both in men and women worldwide. Additionally, the incidence and mortality of GC significantly varies due to different eating habits and environmental and genetic factors in different areas. Remarkably, with the development of techniques and surgical equipment along with newly emerging drugs and therapeutics, the 5-year survival for GC patients has increased and the death rate has decreased. In this perspective, based on current therapies in GC field around the world, we present a systematic discussion about the state of advanced clinical treatments including surgical resection, systemic chemotherapy, targeted therapy, radiotherapy and enhanced recovery after surgery. Although challenges remain which require further study and investigation, in this review, we mainly focus on the promising clinical treatment strategies in GC to date.

Background Currently, there is no formal consensus regarding a standard classification for gastric cancer (GC) patients with Methods All patients in this study underwent R0 gastrectomy. The overall survival (OS) difference between the Limited and Adequate set from a large Chinese multicenter dataset was analyzed. Using the 8th American Joint Committee on Cancer (AJCC) pathological nodal classification (pN) for GC as base, a modified nodal classification (N’) resembling similar analogy as the 8th AJCC pN classification was developed. The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance, Epidemiology, and End Results (SEER) dataset comprising of 10,208 multi-ethnic GC cases. Results Significant difference in OS between the Limited and Adequate set (corresponding N0–N3a) using the 8th AJCC system was observed but the OS of N0limited vs. N1adequate, N1limited vs. N2adequate, N2limited vs. N3aadequate, and N3alimited vs. N3badequate subgroups was almost similar in the Chinese dataset. Therefore, we formulated an N’ classification whereby only the nodal subgroups of the Limited set, except for pT1N0M0 cases as they underwent less extensive surgeries (D1 or D1 + gastrectomy), were re-classified to one higher nodal subgroup, while those of the Adequate set remained unchanged (N’0 = N0adequate + pT1N0M0limited, N’1 = N1adequate + N0limited (excluding pT1N0M0limited), N’2 = N2adequate + N1limited, N’3a = N3aadequate + N2limited, and N’3b = N3badequate + N3alimited). This N’ classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups. Further analyses demonstrated superior statistical performance of the pTN’M system over the 8th AJCC edition and was successfully validated using the SEER dataset. Conclusion The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with

Background: Gastric cancer (GC) is among the malignant tumors of highest morbidity and mortality in the world, and has a profile of high lymph node metastasis rate. Lymph node clearance is a critical part of gastric cancer surgery, however, the extent of lymph node clearance, for example, whether to perform abdominal aortic lymph node dissection, remains considerably controversial. In this study, we performed a systematic review and meta-analysis to assess the effects of D2 plus para-aortic lymphadenectomy (PALD) on survival and postoperative complications in patients with GC.Methods: An electronic search was conducted through PubMed, Embase and cochrane library. The Q test and I2 were used to assess heterogeneity. The publication bias was evaluated via funnel plots. All statistical analyses were performed using STATA 14.0 (STATA, College Station, TX).Results: 908 studies were retrieved via literature search and eight studies were finally included. There was no significant difference between D2 and D2+PALD in the 5-year survival rate after surgery (HR: 1.00, 95% CI: 0.97-1.03, P = 0.897; I2 = 64.9%). Besides, the 30-day mortality (RR: 1.17, 95% CI: 0.66-2.10, P = 0.590; I2 = 0.0%) and the overall risk of postoperative complications (RR: 1.15, 95% CI: 0.83-1.59, P = 0.411; I2 = 35.5%) were comparable between D2 and D2+PALD.Conclusion: Based on current literature body, compared with D2, D2+PALD does not prevail in terms of long-term survival or perioperative outcomes.

Background The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) pathological tumor-node-metastasis (pTNM) staging system may have increased accuracy in predicting prognosis of gastric cancer due to its important modifications from previous editions. However, the homogeneity in prognosis within each subgroup classified according to the 8th edition may still exist. This study aimed to compare and analyze the prognosis prediction abilities of the 8th and 7th editions of AJCC/UICC pTNM staging system for gastric cancer and propose a modified pTNM staging system with external validation. Methods In total, clinical data of 7911 patients from three high-capacity institutions in China and 10,208 cases from the Surveillance, Epidemiology, and End Results (SEER) Program Registry were analyzed. The homogeneity, discriminatory ability, and monotonicity of the gradient assessments of the 8th and 7th editions of AJCC/UICC pTNM staging system were compared using log-rank χ2, linear-trend χ2, likelihood-ratio χ2 statistics and Akaike information criterion (AIC) calculations, on which a modified pTNM classification with external validation using the SEER database was proposed. Results Considerable stage migration, mainly for stage III, between the 8th and 7th editions was observed in both cohorts. The survival rates of subgroups of patients within stage IIIA, IIIB, or IIIC classified according to both editions were significantly different, demonstrating poor homogeneity for patient stratification. A modified pTNM staging system using data from the Chinese cohort was then formulated and demonstrated an improved homogeneity in these abovementioned subgroups. This staging system was further validated using data from the SEER cohort, and similar promising results were obtained. Compared with the 8th and 7th editions, the modified pTNM staging system displayed the highest log-rank χ2, linear-trend χ2, likelihood-ratio χ2, and lowest AIC values, indicating its superior discriminatory ability, monotonicity, homogeneity and prognosis prediction ability in both populations. Conclusions The 8th edition of AJCC/UICC pTNM staging system is superior to the 7th edition, but still results in homogeneity in prognosis prediction. Our modified pTNM staging system demonstrated the optimal stratification and prognosis prediction ability in two large cohorts of different gastric cancer populations.

Figure S1. meta-regression based on percentage of adenocarcinoma (P = 0.279). Figure S2. meta-regression based on sample size (P = 0.671). Figure S3. meta-regression based on mean age (P = 0.112). Figure S4. meta-regression based on percentage male (P = 0.275). Figure S5. meta-regression based on percentage smokers (P = 0.196). Figure S6. meta-regression based on percentage of patients receiving TKI (P = 0.015). (DOCX 2864 kb)

Supplemental 1. Meta-regression analyses for the sex difference of the association between current or former smokers and gastric cancer based on follow-up duration. (DOC 6972 kb)

Background Few studies have shown nomograms that may predict disease-specific survival (DSS) probability after curative D2 gastrectomy for advanced gastric cancer (AGC), particularly among Chinese patients. This study sought to develop an elaborative nomogram that predicts long-term DSS for AGC in Chinese patients. Methods A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1, 2000 and December 31, 2012 from three large medical hospitals in China. We assigned patients from Sun Yat-sen University Cancer Center to the training set, and patients from the First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital to two separate external validation sets. A multivariate survival analysis was performed using Cox proportional hazards regression model in a training set, and a nomogram was constructed. Harrell’s C-index was used to evaluate discrimination and calibration plots were used to validate similarities between survival probabilities predicted by the nomogram model and actual survival rates in two validation sets. Results The multivariate Cox regression model identified age, tumor size, location, Lauren classification, lymphatic/venous invasion, depth of invasion, and metastatic lymph node ratio as covariates associated with survival. In the training set, the nomogram exhibited superior discrimination power compared with the 8th American Joint Committee on Cancer TNM classification (Harrell’s C-index, 0.82 vs. 0.74; P

Baseline characteristics of included studies. (DOCX 29 kb)

Newcastleâ Ottawa Scale (NOS) Table: methodological quality of cohort studies included in the meta-analysis*. (DOC 95 kb)

ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. To clarify the roles of ING5 in gastric tumorigenesis and progression, its expression was examined by immunohistochemistry on a tissue microarray containing gastric nonneoplastic mucosa (n = 119), dysplasia (n = 50), and carcinomas (n = 429), with its comparison with clinicopathologic parameters of the carcinomas. ING5 expression was analyzed in gastric carcinoma tissues and cell lines (MKN28, MKN45, AGS, GT-3 TKB, and KATO-III) by Western blot and reverse transcriptase-polymerase chain reaction. ING5 protein was found to distribute to the nuclei of gastric carcinoma cells with similar messenger RNA levels. An increased expression of ING5 messenger RNA was observed in gastric carcinoma in comparison with paired mucosa (P < .05). Lower expression of nuclear ING5 was detected in gastric dysplasia and carcinoma than that in nonneoplastic mucosa (P < .05). Gastric nonneoplastic mucosa and metastatic carcinoma showed more expression of cytoplasmic ING5 than did gastric carcinoma and dysplasia (P < .05). Nuclear ING5 expression was negatively correlated with tumor size, depth of invasion, lymph node metastasis, and clinicopathologic staging (P < .05), whereas cytoplasmic ING5 was positively associated with depth of invasion, venous invasion, lymph node metastasis, and clinicopathologic staging (P < .05). Nuclear ING5 was more expressed in older than younger carcinoma patients (P < .05). There was a higher expression of nuclear ING5 in intestinal-type than diffuse-type carcinoma (P < .05), whereas it was the converse for cytoplasmic ING5 (P < .05). Survival analysis indicated that nuclear ING5 was closely linked to favorable prognosis of carcinoma patients (P < .05), albeit not independent. It was suggested that aberrant ING5 expression may contribute to pathogenesis, growth, and invasion of gastric carcinomas and could be considered as a promising marker to gauge aggressiveness and prognosis of gastric carcinoma.

Background: Macroscopic serosal classification of gastric cancer has been reported in previous studies, but rarely reported about it of colorectal cancer. The purpose of this study was to propose a macroscopic serosal classification of colorectal cancer and to investigate clinical significance of this classification. Materials and methods: Morphologic features of colorectal cancer were analyzed according to the macroscopic serosal appearance and clinicopathologic characteristics of these patients were retrospectively reviewed. Microscopic serosal structure was compared between different types under light microscope and transmission electron microscope. Results: Macroscopic serosal classification was divided into normal type, reactive type, nodular type and colloid type according to the macroscopic serosal appearance and microscopic structure. There were significant differences in tumor size, tumor gross type, histological type, histological grade, tumor necrosis, pT stage, number of nodes metastasis, lymph node metastasis ratio, pN stage, M stage and peritoneal metastasis between patients with different serosal types. Univariate analysis of prognosis revealed macroscopic serosal classification as one of factors significantly correlated with patient survival. However, multivariate analysis only revealed TNM stage significantly correlated with patient survival, while macroscopic serosal classification did not, maybe due to insufficient samples. Conclusions: Macroscopic serosal classification of colorectal cancer is preliminarily defined and divided into four types. Different macroscopic serosal types indicate different clinicopathologic features and correlate with prognosis of patients with colorectal cancer, but still cannot be proven as an independent factor.

Objective To study the inhibition of adhesion and invasion of SGC7901 cells into the ECM by integrinsl antisense oligodeoxynucleotide asODN.

Canstatin, the non-collagenous domain of collagen type IV α-chains, belongs to a series of collagen-derived angiogenic inhibitors. In this study, the inhibitory effect of recombinant canstatin on tumour growth was investigated using a gastric cancer xenograft model. The volume and weight of tumours in mice treated with canstatin were lower than that in mice treated with PBS. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumours treated with PBS. Moreover, valuable insight into the mechanisms mediated by canstatin was obtained.

Peritoneal dissemination is the most common cause of death in gastric cancer patients. The hypoxic microenvironment plays a major role in controlling the tumor stem cell phenotype and is associated with patients’ prognosis through hypoxia-inducible factor-1α (HIF-1α), a key transcriptional factor that responds to hypoxic stimuli. During the peritoneal dissemination process, gastric cancer stem/progenitor cells (GCSPCs) are thought to enter into and maintained in peritoneal milky spots (PMSs), which have hypoxic microenvironments. However, the mechanism through which the hypoxic environment of PMSs regulated GCSPC maintenance is still poorly understood. Here, we investigated whether hypoxic PMSs were an ideal cancer stem cell niche suitable for GCSPC engraftment. We also evaluated the mechanisms through which the HIF-1α-mediated hypoxic microenvironment regulated GCSPC fate. We observed a positive correlation between HIF-1α expression and gastric cancer peritoneal dissemination (GCPD) in gastric cancer patients. Furthermore, the GCSPC population expanded in primary gastric cancer cells under hypoxic condition in vitro, and hypoxic GCSPCs showed enhanced self-renewal ability, but reduced differentiation capacity, mediated by HIF-1α. In an animal model, GCSPCs preferentially resided in the hypoxic zone of PMSs; moreover, when the hypoxic microenvironment in PMSs was destroyed, GCPD was significantly alleviated. In conclusion, our results demonstrated that PMSs served as a hypoxic niche and favored GCSPCs peritoneal dissemination through HIF-1α both in vitro and in vivo. These results provided new insights into the GCPD process and may lead to advancements in the clinical treatment of gastric cancer. Stem Cells 2014;32:3062–3074

To study the molecular mechanism of epidermal growth factor receptor (EGFR) signaling pathway in mediating paclitaxel-resistance and improving paclitaxel sensitivity in human melanoma A375 cells.Human melanoma cell line A375 cells were treated with different concentrations of paclitaxel with or without 20 µmol/L AG1478 (EGFR inhibitor), 40 µmol/L PD98059 (extracellular signal conditioning kinase (ERK) 1/2 blockers) or 10 µmol/L LY294002 (PI3K inhibitor). MTT method was used to measure the proliferation of A375 cells. Flow cytometry was used to detect cell cycle and apoptosis in the A375 cells. The expressions of P-EGFR, P-ERK and P-AKT proteins were determined by Western blot analysis.Paclitaxel (0.001 µmol/L to 0.1 µmol/L) inhibited the growth of A375 cells (P0.01) and induced apoptosis (P0.05) in a dose- and time-dependent manner. AG1478 (20 µmol/L) increased the 0.01 µmol/L paclitaxel-induced inhibition rate from 38.5% to 62.6% at 72 h. Different doses of paclitaxel induced apoptosis in A375 cells by different ways, in which G0/G1 phase cells were decreased and mitotic phase was prolonged at 0.01 µmol/L, and cell cycle arrest at G2/M phase by 0.1 µmol/L paclitaxel. When DNA damage occurred in A375 cells exposed to paclitaxel, expression of P-EGFR, P-ERK and P-AKT proteins was increased. When EGFR signaling pathway was blocked, paclitaxel did not activate MAPK signaling pathway or PI3K/AKT signaling pathway and did not change its effect on cell cycle in vitro. When EGFR was inhibited by 20 µmol/L tyrophostin AG1478, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 1.73- and 1.80-fold, respectively. When the ERK signaling was blocked by 40 µmol/L PD98059, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 2.73- and 2.25-fold, respectively. When the AKT signaling was blocked by 10 µmol/L LY294002, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 2.02- and 1.46-fold, respectively.Human melanoma A375 cells produce resistance to paclitaxel (0.001 to 0.1 µmol/L) by activating MAPK signaling and PI3K/AKT signaling pathways. Targeting EGFR, ERK and AKT signaling pathways significantly enhances the cytotoxic effect of paclitaxel on human melanoma cells.

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.

To elucidate the effect of transforming growth factor-beta 1 (TGF-β1) on peritoneal fibrosis and the regulation of gastric cancer adhering to mesothelial cells.The peritoneal mesothelial cell line of HMrSV5 was used to determine the role of TGF-β1 in the regulation of gastric cancer cell adhering to mesothelial cells. And the mRNA and protein expressions of collagen III and fibronectin were detected by adhesion assay, Western blot, immunofluorescent staining and reverse transcription-polymerase chain reaction (RT-PCR).(1) The treatment of 5 ng/ml TGF-β1 could induce the expressions of collagen III and fibronectin in mesothelial cells at 24, 48 and 72 h (P0.01). (2) As compared with the controls, the percentages of adhered HGC-27 and HSC-39 gastric cancer cells significantly increased under the treatment of TGF-β1 for 24 and 72 h. The increased adhesion percentages of HGC-27 were 65% ± 5% and 124% ± 11% (P0.05) while those of HSC-39 85% ± 9% and 146% ± 17% respectively (P0.05). (3) Arginyl-glycyl-aspartic acid (RGD) (knockdown of minimal sites for cell-binding domain of extracellular matrix) decreased the number of cancer cells adhering to mesothelial cells under the stimulation of TGF-β1. And the decreased adhesion percentage of HGC-27 was 65% ± 8% (P0.05).TGF-β1 significantly stimulates the expressions of collagen III and fibronectin in mesothelial cells. And it is associated with the increased adhesion of gastric cancer cell and offers a favorable environment for the dissemination of gastric cancer.

The International Union Against Cancer tumor node metastasis classification is routinely applied for evaluating the prognosis of patients with gastric cancer. However, results are still heterogeneous. This study was therefore carried out to evaluate the prognostic significance of the metastatic lymph node (LN) ratio in T3 gastric cancer patients undergoing gastrectomy.Clinical data of 109 LN- positive cases were retrospectively analyzed. Spearman correlation analysis was used to determine the correlation coefficiency. Survival time was determined by Kaplan-Meier and Log-rank test. Multivariate analysis was performed using the Cox model. ROC curves were used to compare the accuracy of the number of metastatic LN and metastatic LN ratio.The metastatic LN ratio did not correlate with the number of LN when at least 15 nodes were dissected, whereas the number of metastatic LN did. Univariate analysis showed that the metastatic LN ratio influenced significantly the survival time, while multivariate analysis revealed it to be a major independent prognostic factor.The metastatic LN ratio can be used as a major independent prognostic factor for the patients with T3 gastric cancer.

To investigate the clinicopathological characteristics and prognostic factors of stage III gastric cancer.A retrospectively study of 1007 patients with Stage III gastric cancer in a single institute in China was performed. The patients underwent surgical resection from January 1991 to December 2005. Univariate and multivariate analyses were performed using log-rank test and Cox proportional hazards model to access the prognostic factors in stage III gastric cancer patients who received curative (R0) gastric resection.The mean age of the 1007 patients was 58.7 years and the male-to-female ratio was 2.6:1.0. There were 242 patients with stage IIIA disease, 403 patients with stage IIIB, and 362 patients with stage IIIC. R0, R1, and R2 resection were performed in 754 patients (74.9%), 56 patients (5.5%), and 197 patients (19.6%), respectively. The 5-year survival rate (37.8%) of patients who received R0 resection was significant higher than that of patients who received R1(21.2%) and R2(8.9%) resection (P0.05). Multivariate analysis revealed that pN stage, pT stage, and Borrmann type were independent prognostic factors (all P0.01).Stage III gastric cancer patients have certain clinicopathological characteristics and R0 resection should be performed if possible. Lymph node count, depth of tumor invasion, and Borrmann type are independent prognostic factors in stage III gastric cancer patients undergoing R0 resection.

To evaluate the value of the metastatic to examined lymph nodes (rN) ratio in gastric cancer patients who underwent radical resection.In this retrospective study, data were collected from the medical records of 710 patients who underwent radical gastrectomy (R0) for gastric cancer from 1980 to 2006 in the Department of Surgical Oncology at the First Affiliated Hospital of China Medical University. The patients were divided into 2 groups according to the number of examined lymph nodes: Group 1 consisted of 327 patients with15 examined lymph nodes and Group 2 consisted of 383 patients with ≥15 lymph nodes. rN categories staging and pN categories were divided separately according to the metastatic lymph node ratio and the examined lymph nodes. The prognostic factors were analyzed by univariate (Log-rank) and multivariate (Cox model) analysis methods.The median survival time was 74 months (95% CI:55.6-92.4 months) in Group 1 and 96 months (95% CI:77.8-119.2 months) in Group 2, and the difference was not statistically significant (P0.05). On multivariate analysis, the N ratio remained as an independent prognostic factor in both Group 1 (P0.01, RR=1.225, 95% CI:1.102-1.362) and Group 2 (P0.01, RR=1.421, 95% CI:1.269-1.592). However, pN stage was an independent prognostic factor only in Group 1. When the rN ratio classification was applied, there were no significant differences between each categories (P0.05). However, the overall survival of patients with pN1 disease in Group 1 was significantly shorter than that in Group 2 according to the pN stage classification (P0.01).The metastatic lymph node ratio is an independent prognostic factor of the prognosis of gastric cancer. The staging system based on metastatic lymph node ratio (rN) is more reliable than the system based on the number of metastatic lymph nodes in the prediction of the prognosis of gastric cancer.

Colorectal cancer is the third most common malignancy and the third-leading cause of cancer-related deaths worldwide. In the last several years, recombinant DNA technology has made cancer gene therapy feasible in the clinic. In our studies, we used both exogenous and endogenous canstatin, a type IV collagen genetically distinct product. We detected the effects of canstatin on colorectal cancer cells HCT-15 and HCT-116. DAPI staining, FCM and migration analyse were used to detect the apoptotic cells, cell cycle and mobility. As shown in the results, the apoptotic cell numbers (p0.05) and G1 arrest cell numbers (p0.05) were higher than in the non- treatment case. The mobility of the cells was also decreased obviously (p0.05). Simultaneously, combination effects of exogenous and endogenous canstatin were identified.

Effectiveness of splenectomy for advanced gastric cancers occupying the upper and/or the middle third of the stomach is still in debate. The aim of the present study is to elucidate the impact of splenectomy on patient survival by investigating the pathological characteristics and prognostic significance of splenic hilar lymph node metastasis.Clinicopathologic and prognostic data of 265 patients with gastric cancer in the upper and/or the middle third of the stomach who underwent the operation of en bloc resection of primary cancer and D2/D3 lymphadenectomy combined with splenectomy were retrospectively reviewed.Multivariate analysis revealed pT category, pN category, and distant lymph node metastasis independently correlated with the presence of splenic hilar lymph node metastasis. Prognoses of patients with positive splenic hilar lymph nodes were significantly poorer than that of patients with negative splenic hilar lymph nodes for the entire study population and for those who underwent R0 resection, but not for those who underwent R1-2 resection. There was no significant difference in survival between patients who underwent R0 resection with positive splenic hilar lymph nodes and those who underwent R1-2 resection. Splenic hilar lymph node metastasis was one of independent indicators predicting worse prognosis and the presence of distant metastasis after surgery. Subset analysis according to the TNM stage revealed there were significant differences in survival between patients with and without splenic hilar lymph node metastasis.Splenic hilar lymph node metastasis should be considered as one of incurable factors. Consequently, the efficiency of splenectomy aiming at prolonging survival for patients with high risk of splenic hilar lymph nodes metastasis should be questioned, although resection of invasive organs form gastric cancers has been recommended if R0 surgery could be achieved.

To investigate the validity of gastric cancers with nodes metastasis at Level II stations limited to No. 7 being classified as level-based n1 stage disease and the impact of this revision on lymph node staging.Clinicopathologic features and prognosis of 1,606 node positive gastric cancers were retrospectively reviewed. Four patient groups were classified according to the status of node involvement: Group A, 734 patients with node metastasis at Level I stations; Group B, 317 patients with nodes metastasis at Level II stations limited to No. 7; Group C, 501 patients with nodes metastasis at Level II stations besides No. 7; and Group D, 54 patients with nodes metastasis at Level III stations.Although the extent of node metastasis for patients in Group B was more severe than that for patients in Group A, clinicopathologic features (especially pT stage) were not significantly different. Although overall survival for patients in Group B was significantly worse than that for patients in Group A, no significant differences in prognosis could be observed when stratified by pN or rN category. A revised level-based n category was established by considering cancers in Group B as level-based n1 stage disease. Multivariate analysis confirmed rN category and the revised level-based n category independently predicted patients' survival. A novel N category was established by combining rN category and the revised level-based n category. Further analysis revealed the novel N category had better homogeneity, discriminatory ability, and monotonicity of gradients than the other node categories, indicating the novel N system might be the most valuable node staging system for prognostic assessment.It might be more suitable for cancers in Group B being classified as level-based n1 stage disease. And we recommend the anatomical location of metastatic lymph nodes also being considered in the categorization of lymph node metastasis.

The clinicopathologic characteristics and prognosis for gastric cancer invading subserosa (SS) are still not clear.A retrospective analysis was under taken of 1,201 patients with advanced gastric cancer (pT2, pT3, and pT4a) who had undergone gastrectomy from 1980 to 2001. Clinicopathologic characteristics and prognosis of gastric cancer invading SS were compared with those of cancers invading muscularis propria (MP) and serosa (Se).Patients with cancers invading SS had larger tumors and more frequent lymphovascular invasion, lymph node and peritoneal metastasis than those with cancers invading MP. Yet, they had smaller tumors and less frequent lymphovascular invasion, lymph node and peritoneal metastasis than those with cancers invading Se. Postoperative survival with cancers invading SS was intermediate between that with cancers invading MP and Se at pN0, pN1, pN2, and pN3 stages. Multivariate analysis indicated lymph node metastasis, type of resection, curability, peritoneal metastasis, and hepatic metastasis were independent prognostic factors for patients with cancers invading SS.Clinicopathologic characteristics and prognosis of gastric cancer invading SS are intermediate between those of gastric cancers invading MP and Se.

Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related deaths after lung carcinoma. The aim of this study was to understand the difference in clinicopathological behaviours and prognosis of gastric cancer in patients from China and Japan.Paraffin-fixed tissue samples of gastric cancer were collected retrospectively from two hospitals between 1993 to 2006 in Japan (n=2063) and during 1980-2003 in China (n=2496) respectively, and staging was done by TNM system and typing by Japanese Endoscopy Society criteria or Borrmann's classification. The histological architecture of the tumours was expressed according to Lauren's classification.Compared to Japan, the occurrence of gastric cancer was more common in younger Chinese population and prone to invasion and metastasis in muscularis propia, lymphatic, lymph node, liver, peritoneal parts, and exhibited large tumour size and high TNM staging in both the sexes and in different age groups (P0.05). Intestinal and mixed types of carcinomas were more frequently observed in Japanese patients compared to Chinese and the difference was significant (P0.05). It was observed that the commonly reported types in early gastric cancers (EGC) in Japanese patients were IIc, IIa+IIc or IIa while those of Chinese patients were IIc, III or IIb. In the case of advanced gastric cancers (AGC), type II and III were most common in both the countries. The cumulative survival rate of Chinese patients was significantly (P0.05) higher compared to Japanese in different stratified groups via depth of invasion, TNM staging or Lauren's classification.Gastric cancers in Chinese patients had more aggressive pathological characteristics and poorer prognosis than those from Japan. To reduce incidence and to improve treatment facilities, it is necessary to have a systematic screening system.

Signet ring cell carcinoma (SRC) of the stomach is a histological type based on microscopic characteristics, and its clinicopathologic characteristics and prognosis are still controversial.A retrospective analysis was under taken for 2,315 patients with gastric cancer who had undergone gastrectomy from 1980 to 2004. Among them, 211 patients had SRC and were compared with 2,104 patients with non-signet ring cell carcinoma (NSRC).Significant differences were noted in age, gender, and depth of tumor invasion between patients with SRC and NSRC of early gastric carcinoma. There were statistically significant differences in age, gender, macroscopic appearance, tumor size, depth of tumor invasion, peritoneal dissemination, and curability between patients with SRC and NSRC of advanced gastric carcinoma. In early gastric carcinoma, patients with SRC had a significantly better survival rate than those with NSRC, and the signet ring cell histology was an independent predictive factor. In advanced gastric carcinoma, there was no significant difference of survival rate between SRC and NSRC, and the signet ring cell histology was not an independent predictive factor.SRC is a distinct type of gastric carcinoma in terms of clinicopathologic characteristics and prognosis.

Human peritoneal mesothelial cells (HPMCs) in intact mesothelium have been demonstrated to protect against tumor peritoneal metastasis. We have previously reported that gastric cancer cells can induce peritoneal apoptosis, lead to damage of peritoneum integrity, and therefore promote peritoneal metastasis. In this study, we investigated the effects of TGF-beta1 on tumor-mesothelial interaction. Briefly, the levels of various soluble factors, in particular TGF-beta1, were measured. HMrSV5 cells, a human peritoneal mesothelial cell line, were co-incubated with TGF-beta1, gastric cancer cells, or gastric cancer cells and TGF-beta1 receptor inhibitor SB431542. The expressions of smad 2/3 and phosphorylated smad 2/3, indicator of TGF-beta/Smads pathway activation, were evaluated. Then the morphological changes of HPMCs were observed. The cell damage was quantitatively determined by fluorescent microscopy and flow cytometry. Tumor-mesothelial cell adhesion was also examined. Results showed a significant elevation of TGF-beta1 expression, which is companied by dramatically increased phosphorylated-smad 2/3 levels, after mesothelial cell co-culture with the gastric cancer cell line. In addition, mesothelial cells exposed to gastric cancer cells or TGF-beta1 became exfoliated and exhibited signs of injury, while blocking TGF-beta1 can partially inhibit these effects. These results indicate that soluble factors, such as TGF-beta1, produced in autocrine/paracrine manner in the peritoneal cavity, affect the morphology and function of mesothelial cells so that the resulting environment becomes favorable for peritoneal metastases.