Factor In Advanced Gastric Cancer Research Articles

Current prognostic factors of advanced gastric cancer patients treated with chemotherapy: real world data from a Japanese 12 institutions.

Understanding the prognostic factors of advanced gastric cancer before starting chemotherapy is important to determine personalized treatment strategies. However, the details of chemotherapy and the prognosis of advanced gastric cancer patients have changed with the time and environment. The aim of this study was to understand the current reality of chemotherapy and to estimate the prognostic factors of advanced gastric cancer patients before starting chemotherapy at multiple centers. This includes specialized cancer hospitals and community hospitals, with the latest data under the Japanese insurance system. We evaluated the clinical parameters and treatment details of 1025 patients who received systemic chemotherapy for unresectable advanced gastric cancer from 2012 to 2018 at 12 institutions in Japan. Prognostic factors were analyzed using the Cox proportional hazards regression model. As of April 2021, 953 (93%) patients had died, while 72 (7%) patients survived. The median overall survival and progression-free survival of first-line chemotherapy was 11.8months (95% confidence interval, 10.8-12.3months) and 6.3months (95% confidence interval, 5.9-6.9months), respectively. Multivariate analysis revealed eight prognostic factors: age<40years, performance status ≥2, no gastrectomy, diffuse histological type, albumin <3.6, alkaline phosphatase ≥300, creatinine ≥1.0 and neutrophil-to-lymphocyte ratio>3.0. Patients using trastuzumab showed better survival than patients without (16.1months vs. 11.1months; P=0.0005). We identified eight prognostic factors for patients with advanced gastric cancer undergoing Japanese standard chemotherapy. Our results will help clinicians develop treatment strategies for every patient.

ASO Visual Abstract: Evaluation of HLA-E Expression Combined with Natural-Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer

ASO Visual Abstract: Evaluation of HLA-E Expression Combined with Natural-Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer

Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer.

The NKG2A/HLA-E pathway functions as an immune checkpoint with potential for inhibition using therapeutic antibodies. Through this pathway, immune cells lose activity, which allows cancers to progress. We aimed to determine whether HLA-E expression combined with NK cell status serves as a prognostic biomarker for gastric cancer (GC). We enrolled patients (n = 232) with advanced GC who underwent curative gastrectomy. Immunohistochemical analyses of global HLA-E expression, and the expression of CD56 and CD3 to identify NK cells were performed. Survival analysis was performed to evaluate the significance of HLA-E expression and NK status. Patients with HLA-E-positive was 104 (41.3%) and had significantly worse prognosis of relapse-free survival (RFS) compared with those with HLA-E-negative. Moreover, patients with NK Low status had worse prognoses for RFS compared with those with NK High status. Statistical analysis of RFS demonstrated that HLA-E expression was a significant independent factor for poor prognosis (HR 1.57, 95% CI 1.04-2.36, P = 0.031). Furthermore, HLA-E-positive patients with low NK low status experienced the shortest RFS, particularly those in the upper GC group. HLA-E served as a prognostic factor after curative resection of GC, and HLA-E expression combined with NK status served as a sensitive prognostic biomarker for advanced GC.

A Nomogram Combining Neutrophil-to-Lymphocyte Ratio and D-Dimer Predicts Chemosensitivity of Oxaliplatin-Based First-Line Chemotherapy in Patients with Unresectable Advanced Gastric Cancer.

Introduction: No effective peripheral blood predictors have been establoshed for first-line chemotherapy in patients with advanced gastric cancer. In this study, a nomogram combining the neutrophil-to-lymphocyte ratio/D-dimer with gender, number of metastases, and histological grade was established to predict progression-free survival in patients with unresectable advanced gastric cancer. Methods: We retrospectively collected baseline clinical characteristics and blood parameters from 153 patients diagnosed with advanced gastric cancer that underwent oxaliplatin-based first-line chemotherapy. Kaplan–Meier analysis and Cox regression analysis were used to determine the factors associated with progression-free survival. The concordance index (C-index) and calibration curve were used to determine the prediction accuracy and discriminative ability of the nomogram as a visual complement to the prognostic score system. Results: Determined by the X-tile software, the optimal cut-off points for the neutrophil-to-lymphocyte ratio and D-dimer were 3.18 and 0.56 mg/L, respectively. Multivariate analysis identified four independent prognostic factors: two or more metastatic organs (HR: 1.562, 95% CI: 1.009-2.418, P = .046), poor differentiation (HR: 0.308, 95% CI: 0.194-0.487, P < .001), neutrophil-to-lymphocyte ratio >3.18 (HR: 1.427, 95% CI: 1.024-1.989, P = .036), and D-dimer >0.56 mg/L (HR: 1.811, 95% CI: 1.183-2.773, P = .006). Receiver operating characteristic curves showed that the combination of the neutrophil-to-lymphocyte ratio and D-dimer in the prediction model exhibited the highest predictive performance (area under the curve, 0.800). The prognostic nomogram yielded a C-index of 0.800. Decision curve analysis demonstrated that the prognostic nomogram was clinically useful. A nomogram-based risk classification system was also constructed to facilitate risk stratification of advanced gastric cancer for optimal clinical management. Conclusion: We identified the neutrophil-to-lymphocyte ratio and D-dimer level as independent prognostic factors for advanced gastric cancer. The prognostic nomogram combining the neutrophil-to-lymphocyte ratio and D-dimer level can be applied in the individualized prediction of treatment outcome in patients with advanced gastric cancer.

Clinical significance of peripheral blood-derived inflammation markers in advanced gastric cancer after radical resection

BackgroundThe prognostic significance of peripheral blood-derived inflammation markers in patients with gastric cancer (GC) has not been elucidated. This study aimed to investigate the relationship between systemic inflammatory markers and GC prognosis.MethodsA prospective observational cohort study involving 598 patients was conducted to analyze the prognosis of GC based on systemic inflammatory markers. The following peripheral blood-derived inflammation markers were evaluated: the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein/albumin (CRP/Alb) ratio, Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), prognostic nutrition index (PNI), and prognostic index (PI). The receiver operating characteristics (ROC) curve and the Youden index were used to determine the optimal cutoff values. Univariate and multivariate analysis of prognostic factors was conducted accordingly.ResultsThe optimal cutoff values of the PNI, fibrinogen, NLR, PLR, SII, and CRP/Alb were 49.5, 397 ng/dl, 2.5, 154, 556, and 0.05, respectively. Multivariate analysis showed that age, PLR, TNM stage, and chemotherapy were the independent prognostic factors for advanced gastric cancer (AGC). Adjuvant chemotherapy improved the long-term prognosis of patients with PLR ≥154, but chemotherapy had no significant effect on the survival of patients with PLR < 154.ConclusionsOur findings show that higher PLR (≥154) is an independent risk factor for poor prognosis in GC patients. Besides, PLR can predict adjuvant chemotherapy (oxaliplatin/5-fluorouracil combination) response in patients with GC after surgery.

High Endothelial Venule with Concomitant High CD8+ Tumor-Infiltrating Lymphocytes Is Associated with a Favorable Prognosis in Resected Gastric Cancer.

CD8+ tumor-infiltrating lymphocytes (TILs) play a major role in antitumor immunity. High endothelial venules (HEVs) are related to diverse immune cells in solid tumors. We analyzed CD8+ and Foxp3+ TILs in combination with HEVs to determine their prognostic role in advanced gastric cancer (AGC). We enrolled 157 patients with AGC in this study. The densities of CD8+ TILs and Foxp3+ TILs were calculated using immunohistochemical staining. HEVs were evaluated by MECA-79 expression. HEVs were identified in 60 (38.2%) cases and was significantly associated with an increased number of CD8+ TILs (p = 0.027) but not of Foxp3+ TILs (p = 0.455) and CD20+ TILs (p = 0.163). A high CD8+/HEV+ level was significantly associated with nodal metastasis (p = 0.048). In survival analysis, patients with high CD8+/HEV+ levels demonstrated the longest overall survival (OS) (p = 0.015). Furthermore, a high CD8+/HEV+ level was an independent prognostic factor in AGC (p = 0.011; hazard ratio (HR) = 0.435; 95% confidence interval (CI) = 0.245–0.837). HEVs were found to play an important role in antitumor immunity associated with CD8+ TILs in AGC. This analysis of HEVs and CD8+ TILs helps stratify patients with AGC and sheds light on tumor immunity.

Different prognostic significance of signet ring cell histology for early and advanced gastric cancer patients: a systematic review and meta-analysis

ABSTRACT Objective To review relevant studies and perform a meta-analysis to evaluate the prognostic significance of signet ring cell (SRC) histology for gastric cancer (GC) patients. Methods Systematic literature search was performed using PubMed and Embase databases. The relevant data were extracted and the association between SRC histology and survival outcome were evaluated using a fixed-effect or random-effect model. Results A total of 21 studies were included in this meta-analysis. The prevalence of SRC histology varied from 8.7% to 50%. SRC histology type was associated with poorer OS (HR: 1.12, 95%CI: 1.01–1.23, P = 0.034; I2 = 85.1%) and DFS (HR: 1.17, 95%CI: 1.00–1.37, P = 0.040; I2 = 63.6%). The subgroup analysis indicated that SRC type had a better OS than non-SRC type for early GC patients (HR: 0.60, 95%CI: 0.48–0.75, P < 0.001; I2 = 33.7%). However, it was a poor prognostic factor for advanced GC when excluding stage IV patients (HR: 1.18, 95%CI: 1.07–1.29, P < 0.001; I2 = 6.5%). SRC type had a higher risk of peritoneal recurrence than non-SRC type (OR: 1.36, 95%CI: 1.06–1.75, P = 0.017; I2 = 1.3%). Conclusion SRC type had a distinctly different prognostic significance for early and advanced GC patients. SRC type was associated with better survival outcomes in early GC patients, but it was a predictive factor for poor survival in advanced GC patients.

Prognosis factors of advanced gastric cancer according to sex and age.

Gastric cancer has a relatively high prevalence and is one of the most common causes of cancer-related death worldwide. However, the prognosis for gastric cancer remains poor, especially in the advanced stages, despite many improvements in diagnosis and treatment. To evaluate the outcomes regarding advanced gastric cancer development according to sex and age. We retrospectively reviewed 2005 patients who underwent curative gastrectomy for advanced gastric cancer between 2002 and 2007 at a single Korean centre. Prognosis and risk factors for nodal involvement were evaluated according to sex and age. In this retrospective cohort study, we examined the cases of 2005 patients [sex, 1384 men (69%), 621 women (31%)] with advanced gastric cancer. The patients' age range was 22-87 years (mean age: 57.7 ± 12.3 years), with approximately 53.3% of the patients being ≤ 60 years old. Based on a Cox proportional hazards model, overall survival was independently predicted by older age, larger tumour size, lymphovascular invasion, lymph node metastasis, deeper tumour invasion, moderately-to-poorly differentiated tubular adenocarcinoma, and signet ring cell carcinoma. The same model revealed that relapse-free survival was independently predicted by advanced age, larger tumour size, lymphovascular invasion, deeper tumour invasion, poorly differentiated tubular adenocarcinoma, and signet ring cell carcinoma. Among patients with advanced gastric cancer, older age independently predicted poor overall survival and relapse-free survival. However, there were no significant sex-based differences in relapse-free and overall survival.

Immune checkpoint molecule V-set Ig domain-containing 4 (VSIG4) expression is associated with poor prognosis in advanced gastric cancer patients

Abstract Background New therapeutic approaches are needed for the treatment of advanced gastric cancer (AGC). V-set Ig domain-containing 4 (VSIG4) is an immune checkpoint molecule that may have prognostic or predictive utility in the treatment of AGC. The aim of this study was to investigate expression of VSIG4 and its clinical significance in AGC and other major cancers. Methods We analyzed VSIG4 expression and its correlation with survival rate in various carcinomas including 1,034 surgically resected AGCs from two academic hospitals. Patients were divided into a discovery (N = 572), internal validation (N= 230), and external validation (N= 232) sets. Results VSIG4-positive AGC tumors were significantly associated with overall survival (OS) (hazard ratio (HR) = 3.02, 95% confidence interval (CI) = 2.32–3.94, P&amp;lt;0.001,) and event-free survival (HR = 2.8, 95% CI=2.18–3.72, P &amp;lt;0.001). These findings was successfully validated in the independent cohorts. VSIG4-positive status was also significantly correlated with low intratumoral CD8+ T-cell infiltration (P = 0.036) and high FoxP3+/CD8+ intratumoral T-cell infiltration ratios (P = 0.016). VSIG4 expression in other cancers was not associated with higher 5-year OS rates (colon, P = 0.459, lung, P = 0.275, kidney, P = 0.121, breast, P = 0.147). Conclusions VSIG4 is an independent prognostic factor in AGC. Notably, VSIG4 expression was significantly associated with low CD8+ T-cell infiltration and high regulatory T cell/CD8+T cell ratios, implying a cancer tolerating immune environment. Our results may be an important basis for future gastric cancer-specific immunotherapeutic drug development.

Clinical Significance of Jagged-1 Activated by APEX1 as a Chemoresistance Factor in Advanced Gastric Cancer.

We investigated the clinical role of the molecular targets, APEX1 and Jagged-1, and the Apex1 - Jagged-1 cascade in gastric cancer cells. We used 6 human gastric cancer cell lines (SNU-1, SNU-5, SNU-16, NCI-N87, KATO- III and AGS), and demonstrated the chemosensitivity of APEX1 and Jagged-1 through the MTT assay and immunoblotting. Tumor growth was assayed following cisplatin and 5-FU treatment using a xenograft model injected with KATO-III cells. Moreover, gastric tumor samples from 9 patients, divided in 2 groups according to chemotherapy response, were examined by immunocytochemical (IHC) staining, and protein expression levels were scored. Following APEX1 knockdown, the MTT assay revealed that the IC50 of cisplatin and 5-FU in AGS cells was decreased approximately 7% and 15%, respectively, however, their decrease in chemoresistant KATO-III cells was decreased by approximately 21% and 67% for cisplatin and 5-FU, respectively. The tumor volume of KATO-III/sicontrol mice treated with cisplatin and 5-FU was affected less, compared with KATO-III/siAPEX1 mice treated with cisplatin and 5-FU. Also, the expression levels of APEX1, Jagged-1 and CD133, assayed by IHC staining, were higher in the chemorefractory group than in the chemoresponsive group. Jagged-1-activated signaling by APEX1 plays a role in advanced gastric cancer.

Immune checkpoint molecule V-set Ig domain-containing 4 (VSIG4) expression is associated with poor prognosis in advanced gastric cancer patients

Abstract Background New therapeutic approaches are needed for the treatment of advanced gastric cancer (AGC). V-set Ig domain-containing 4 (VSIG4) is an immune checkpoint molecule that may have prognostic or predictive utility in the treatment of AGC. The aim of this study was to investigate expression of VSIG4 and its clinical significance in AGC and other major cancers. Methods We analyzed VSIG4 expression and its correlation with survival rate in various carcinomas including 1,034 surgically resected AGCs. Patients were divided into a discovery (N = 572), internal validation (N = 230), and external validation (N = 232) sets. Tumor microarrays using multiple tumor pieces were made considering intratumoral heterogeneity. A quantitative image analysis was applied. Digital slide images were obtained using the Pannoramic 250 Flash III and analyzed using the CellProfiler v2.2.0. The region of interest was manually selected within the TMA scanned image and extracted as 2 – 10 JPEG images in each case. Single cell segmentation and quantification of staining intensity were performed using a CellProfiler v2.2.0 pipeline. Results VSIG4-positive AGC tumors were significantly associated with overall survival (OS) (hazard ratio (HR) = 3.02, 95% confidence interval (CI) = 2.32-3.94, P Conclusions VSIG4 is an independent prognostic factor in AGC. Notably, VSIG4 expression was significantly associated with low CD8+ T-cell infiltration and high regulatory T cell/CD8+T cell ratios, implying a cancer tolerating immune environment. Our results may be an important basis for future gastric cancer-specific immunotherapeutic drug development. Legal entity responsible for the study The authors. Funding Grant (2019IP0408) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, and grant (NRF-2017R1D1A1B03033660) from the National Research Foundation of Korea. Disclosure All authors have declared no conflicts of interest.

Prognostic value of mismatch repair deficiency in patients with advanced gastric cancer, treated by surgery and adjuvant 5-fluorouracil and leucovorin chemoradiotherapy

ObjectiveThe predictive value of mismatch repair protein deficiency (MMRD) for chemoradiotherapeutic outcome has rarely been reported in gastric cancer. This study investigated the clinical significance of MMRD as a prognostic factor for tumor recurrence, and as a predictor of response to adjuvant chemoradiotherapy in advanced gastric cancer patients. MethodsBetween 1995 and 2008, tissue specimens of 881 patients who underwent radical gastrectomy for stage II and III gastric cancer were analyzed. MMRD was assessed using immunohistochemical stains for MLH1, PMS2, MSH2, and MSH6. Patients were divided into two groups according to adjuvant treatment: a 5-fluorouracil/leucovorin (FL) adjuvant chemoradiotherapy group and a surgery alone group. Disease-free survival (DFS) was compared between the two groups correlated to MMRD. Risk factors for tumor recurrence were analyzed using multivariate analysis. ResultsOf the 881 gastric cancer patients, 88 (10.0%) exhibited MMRD and 398 (45.2%) patients received adjuvant FL chemoradiotherapy. The multivariate analysis revealed that MMRD was a good independent prognostic factor (hazard ratio, 0.572; 95% confidence interval, 0.370–0.883; P = 0.012). For stage III gastric cancer displaying mismatch repair protein proficiency (MMRP), adjuvant FL chemoradiotherapy after surgery resulted in better DFS than surgery alone (P = 0.001). Among the stage II gastric cancer patients, adjuvant FL chemoradiotherapy did not show survival benefit, regardless of MMRD. ConclusionMMRD is a good independent prognostic factor in advanced gastric cancer. Adjuvant FL chemoradiotherapy was beneficial in patients with stage III gastric cancer with MMRP but not in those with MMRD.

Post-therapy pathologic tumor volume predicts survival in gastric cancer patients who underwent neoadjuvant chemotherapy and gastrectomy

BackgroundTo demonstrate that post-therapy pathological tumor volume (ypTV) should be considered as an independent prognostic factor in advanced gastric cancer (GC) patients who underwent neoadjuvant chemotherapy (NAC) and gastrectomy.MethodsA total of 253 GC patients who received gastrectomy between January 2010 and December 2016 in our hospital were enrolled in this study. Clinicopathologic factors were evaluated using univariable and multivariable analysis. ypTV was calculated using π* (tumor diameter/2)2 *tumor invasion depth (cm3).ResultsCut-point survival analysis demonstrated that the appropriate cut-offs for ypTV were 3, 6, 10, and 19 (cm3). Patients with tumor volumes of 0–3.0, 3.1–6.0, 6.1–10.0, 10.1–19.0, ≥19.1 cm3 were defined as ypTV1, 2, 3, 4a and 4b. Using multivariable analysis, the tumor volume (ypTV stage, P < 0.05), ypN stage (P < 0.05), response to NAC (P < 0.05), vascular invasion (P < 0.05) and ypTvNM staging (P < 0.05) were independent prognostic factors. Kaplan-Meier analysis demonstrated that the 8th AJCC/UICC ypTNM staging was not a significant predictor for survival (P > 0.05); however, our newly defined ypTvNM staging was a significant predictor for survival (P < 0.05).ConclusionsypTV should be considered as an independent prognostic factor for GC patients after NAC. ypTvNM staging should be recommended to improve the accuracy of prognostic prediction for GC patients who received NAC plus gastrectomy.

Immunohistochemical Expression of Autophagy-Related Proteins in Advanced Tubular Gastric Adenocarcinomas and Its Implications.

In neoplastic conditions, autophagy may act as a tumor suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumor growth. Although ultrastructural analysis has been considered the traditional method to identify autophagy, some proteins such as microtubule-associated protein 1 light chain 3 (LC3A/B), Beclin-1 and activating molecule in Beclin-1-regulated autophagy protein-1 (AMBRA-1) may be considered as markers of autophagy-assisted cancerogenesis. Herein, we analyzed a cohort of advanced tubular gastric adenocarcinomas by the abovementioned immunohistochemical antisera; through immunohistochemistry, autophagy (A-IHC) is diagnosed when at least two out of the three proteins are positive in the samples. Immunostaining for LC3A/B, Beclin-1, and AMBRA-1 was exclusively found in neoplastic elements, but not in surrounding stromal cells. In detail, LC3A/B and Beclin 1 were expressed both in the cytoplasm and in the nucleus of the cancer cells, while AMBRA-1 was preferentially localized in the nucleus, mainly in high grade cases. LC3A/B, Beclin 1, and AMBRA-1 expression were positive in 18 (56.2%), 17 (53.1%), and 12 (37.5%) cases, respectively. The sensibility and specificity of LC3A/B and Beclin-1 ranged from 81.25% to 93.75%, with high efficiency (90.63%) for Beclin-1. Moreover, the ultrastructural autophagic index (AI) was also available in all cases. All high-grade cases documented a Ki-67 labelling index (LI) ≥ 30%, even if three low-grade cases revealed a high Ki-67 value; p53 positivity was encountered in 21/32 (65.62%) of cases, independently of the tumor grade. A statistically significant correlation among A-IHC and clinicopathological parameters such as grade, stage, clinical course, Ki-67 LI and AI was revealed. Univariate analysis documented a significant p-value for the same autophagic variables. Additionally, multivariate survival analysis identified the grade, AI and A-IHC as independent significant variables. Finally, the overall survival curves of all cases of gastric tubular adenocarcinoma were greatly dependent on A-IHC. Therefore, we suggest that autophagic-related proteins might be considered promising predictive prognostic factors of advanced gastric cancer. Further investigations may be required to determine whether new targeted therapies should be addressed to autophagy-related proteins.

Pathological evaluation of neoadjuvant chemotherapy in advanced gastric cancer

BackgroundAlthough pathological evaluation has been considered an effective evaluation method, some problems still exist in practice. Therefore, we explored whether there are more reasonable and practical pathological evaluation criteria for neoadjuvant chemotherapy in patients with advanced gastric cancer. Here, we aim to determine pathological judgment criteria for neoadjuvant chemotherapy in patients with advanced gastric cancer.MethodsEighty-seven patients with cT2–4 or cN+ were enrolled in this study. Pathological factors for overall survival (OS) were investigated using univariate and multivariate analyses, and the pathological criteria for neoadjuvant chemotherapy were then determined.ResultsA total of 87 patients underwent 3–4 cycles of neoadjuvant chemotherapy, with 67 (77.0%), 15 (17.2%), and 5 (5.8%) receiving Folfox6, Xelox, and SOX regimens, respectively. All patients showed different levels of graded histological regression (GHR) of the primary tumor, with a ≥ 50% regression rate of 50.6%. The univariate analysis showed that GHR ≥ 50% (p = 0.022), 66.7% (p = 0.013), and 90% (p = 0.028) were significantly correlated with OS. The multivariate analysis demonstrated that ypTNM (II/III) stage was significantly associated with OS compared with ypTNM (0+I) stage [HR = 3.553, 95% CI 1.886–6.617; HR = 3.576, 95% CI 1.908–6.703, respectively] and that the Lauren classification of diffuse type was also an independent risk factor for OS compared with the intestinal type (HR = 3.843, 95% CI 1.443–10.237).ConclusionsThe Lauren classification and ypTNM stage after neoadjuvant chemotherapy are independent prognostic factors in advanced gastric cancer. A GHR ≥ 50%/< 50% can be used as the primary criterion for advanced gastric cancer after neoadjuvant chemotherapy to determine postoperative adjuvant chemotherapy regimens.

Clinicopathological differences in signet ring cell adenocarcinoma between early and advanced gastric cancer.

Signet ring cell adenocarcinoma is a histological classification based on the WHO classification. The presence of this specific histological type is associated with a worse pathological appearance. The prognosis of signet ring cell adenocarcinoma in gastric cancer patients after curative surgery is still under debate. From January 1988 to December 2012, a total of 2971 patients, including 819 early and 2152 advanced gastric cancer patients underwent curative resection for gastric cancer. Among them, there were 185 cases of signet ring cell adenocarcinoma in early gastric cancer patients, while there were 570 cases in advanced gastric cancer patients. The overall incidence of signet ring cell adenocarcinoma was 25.4%. Our results showed that the 5-year overall survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 90.7 and 83.2%, respectively (P = 0.001). The 5-year disease-free survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 87.4 and 81.6%, respectively (P = 0.003). The 5-year overall survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 32.1 and 37.9%, respectively (P = 0.041). The 5-year disease-free survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 28.6 and 35.2%, respectively (P = 0.037). Signet ring cell adenocarcinoma was an independent predictor for overall survival in advanced gastric cancer (P = 0.017). The clinical features and prognosis of signet ring cell adenocarcinoma are different between early and advanced gastric cancer. Signet ring cell adenocarcinoma is a poor prognostic factor in advanced gastric cancer after curative resection.

P-085 - The impact of the difference in total diameter of metastatic tumor as a prognostic factor for advanced gastric cancer treated with systemic chemotherapy

P-085 - The impact of the difference in total diameter of metastatic tumor as a prognostic factor for advanced gastric cancer treated with systemic chemotherapy

212P - The impact of the difference in total diameter of metastatic tumor as a prognostic factor for advanced gastric cancer treated with systemic chemotherapy

212P - The impact of the difference in total diameter of metastatic tumor as a prognostic factor for advanced gastric cancer treated with systemic chemotherapy

P-132 - Prognostic factors for node-negative advanced gastric cancer after curative gastrectomy

Introduction: It is well established that the existence of lymph node (LN) metastasis are the most important prognostic factor in advanced gastric cancer. Although the number of patients with node negative advanced gastric cancer is small, the question is: whom of them could benefit of aggressive postoperative treatments. Our purpose is to identify the clinicopathological factors that influence the prognostic in node-negative advanced gastric cancer. Methods: Retrospective analysis of a prospective database (n = 476) with gastric cancer cases submitted to curative intent surgery between January 2010 and December 2015, in an Upper GI Surgery Unit. Selection of 61 patients with negative primary node stage T2-4 gastric cancer. We analyzed the following variables: age, gender, clinical stage, T-stage, tumour size, surgery type, lymphadenectomy type, histological type, venous invasion, lymphatic invasion, neural invasion, Lauren’s and Ming’s classification, tumour location, number of resected LN, perioperative blood transfusions, duration of surgery and macroscopic type of tumour. Results: Of the 61 patients, 25 (41%), 23(38%), 10(16%) and 3(5%) had T2,T3,T4a and T4b tumours, respectively. Our recurrence rate was of 11,5%; none of the T2 tumours recur, the recurrence in T3 tumours was 13% (all distant metastasis), in T4a was 40% (66% locoregional and 34% distant metastasis) and also none of the T4b recurs. In univariate analysis lymphadenectomy type, macroscopic type of tumour, T-stage and perioperative blood transfusion significantly correlated with tumour recurrence; while tumour location, T-stage, age and perioperative blood transfusion significantly correlated with cumulative overall survival. In multivariate logistic regression analysis (stepwise forward) lymphadenectomy type and perioperative blood transfusion were significantly and independently correlated with recurrence; age and perioperative blood transfusions with overall survival. Conclusion: Lymphadenectomy type and blood transfusion reliably predict recurrence, as well age and perioperative blood transfusion reliably predict overall survival. More aggressive postoperative treatments and timely follow-up should be considered in patients with these characteristics.

The prognostic factors for advanced gastric cancer with para-aortic nodal involvement after extended gastrectomy.

158 Background: The prognosis of patients with advanced gastric cancer with para-aortic lymph node (PAN) involvement is poor. We retrospectively investigated the prognostic factors for advanced gastric cancer with PAN involvement. Methods: The patients who underwent radical gastrectomy with PAN dissection for advanced gastric cancer between 1992 and 2014 in our institution included in this study. The clinicopathological features and prognostic factors of the patients who identified pathologically PAN involvement after curative gastrectomy were analyzed. Results: In this period, a total of 704 patients underwent gastrectomy with PAN dissection and 65 patients were identified as pathologically PAN positive and eligible for this study. Total gastrectomy and combined resection of other organs were performed for 48 patients and 51 patients, respectively. Complete PAN dissection (a2/b1) was performed for 32 patients. Postoperative abdominal complication was 20% with no hospital deaths. The 3 year and the 5 year overall survival (OS) were 33.8% and 21.2%, respectively. Multivariate cox regression analysis revealed nodal involvement (any of the station No.8a, No.9 and No.11; hazard ratio, 4.04; 95% confidence interval, 1.55-10.5), tumor diameter (over 120mm; HR, 3.37; 95%CI, 1.18-9.63) and total number of PAN involvement (over 2 nodes; HR, 2.24; 95%CI, 1.21-4.15) were poor prognostic factor. The patients without these poor prognostic factors had survived significantly longer than the patient with any of these factors in Kaplan-meier analysis (the 5 year OS: 87.5% vs 9.4%, P &lt;0.001). Conclusions: Tumor size, nodal involvement of the station No.8a, No.9 and No.11 and total number of PAN involvement were poor prognostic factors for advanced gastric cancer with PAN involvement. The candidates for extensive nodal dissection for advanced gastric cancer should carefully be selected.