The Efficacy of Adjuvant FOLFOX6 for Patients With Gastric Cancer after D2 Lymphadenectomy: A Propensity Score-matched Analysis.

Adjuvant 5-fluorouracil, folinic acid, and oxaliplatin (FOLFOX6) are widely used for treating resected gastric cancer in clinics in China, but only few clinical trials have investigated its efficacy. Using propensity score matching, we evaluated the efficacy of adjuvant FOLFOX6 following D2 lymphadenectomy. Patients who received adjuvant FOLFOX6 following D2 lymphadenectomy (FOLFOX6, n = 113) or D2 lymphadenectomy only (surgery-only, n = 512) between 1998 and 2007 at our center were propensity score-matched; we identified a balanced 1:2 cohort, with 96 patients in the FOLFOX6 group and 192 patients in the surgery-only group. The overall survival (OS) was estimated using the Kaplan-Meier method; factors affecting survival were identified by Cox regression models. A nomogram incorporating independent prognosticators was constructed for predicting the 3-, 5-, and 7-year OS, and bootstrap validation was performed. The median follow-up was 9.3 years, and the 7-year OS was 52.1% in the FOLFOX6 group and 43.8% in the surgery-only group (P = 0.04), with an adjusted hazard ratio of 0.69 (95% confidence interval = 0.49-0.98). A prognostic nomogram was generated with the identified significant prognosticators (adjuvant FOLFOX6, number of total harvested nodes, the interaction effect between these two variables, tumor size, T and N stage). Internal validation of the nomogram revealed good predictive abilities, with a bootstrap-corrected concordance index of 0.70. Adjuvant FOLFOX6 following D2 lymphadenectomy is associated with survival benefit in resected gastric cancer. Receiving adjuvant FOLFOX6 can be developed into a nomogram with other independent prognosticators to refine OS prediction and estimation of benefit from adjuvant FOLFOX6 for resected gastric cancer.

Comparison of endoscopic ultrasonography and multislice spiral computed tomography for the preoperative staging of gastric cancer - results of a single institution study of 610 Chinese patients.

BACKGROUND: This study compared the performance of endoscopic ultrasonography (EUS) and multislice spiral computed tomography (MSCT) in the preoperative staging of gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: A total of 610 patients participated in this study, all of whom had undergone surgical resection, had confirmed gastric cancer and were evaluated with EUS and MSCT. Tumor staging was evaluated using the Tumor-Node-Metastasis (TNM) staging and Japanese classification. The results from the imaging modalities were compared with the postoperative histopathological outcomes. The overall accuracies of EUS and MSCT for the T staging category were 76.7% and 78.2% (P=0.537), respectively. Stratified analysis revealed that the accuracy of EUS for T1 and T2 staging was significantly higher than that of MSCT (P<0.001 for both) and that the accuracy of MSCT in T3 and T4 staging was significantly higher than that of EUS (P<0.001 and 0.037, respectively). The overall accuracy of MSCT was 67.2% when using the 13th edition Japanese classification, and this percentage was significantly higher than the accuracy of EUS (49.3%) and MSCT (44.6%) when using the 6th edition UICC classification (P<0.001 for both values). CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that the overall accuracies of EUS and MSCT for preoperative staging were not significantly different. We suggest that a combination of EUS and MSCT is required for preoperative evaluation of TNM staging.

Time-varying pattern of recurrence risk for gastric cancer patients.

This study analyzed the time-varying pattern of the recurrence risk for gastric cancer after surgery. A total of 1,222 gastric patients undergoing D2 resection surgery were studied retrospectively. The annual recurrence hazard curve for all of the populations showed one early peak and a late rise within 10 years after the surgery. The first major recurrence peak covers the first 3 years after the surgery, rising to a maximum at 1.5 years after surgery, followed by a decline until 7.5 years after the surgery, at which point the curve began to rise again. A subgroup analysis of this pattern also revealed that the curves of the patients with bigger tumors, poorly differentiated/undifferentiated adenocarcinomas, lymphatic/venous invasion, T3 and T4, node positive or with fewer lymph nodes retrieved were steeper. Chemotherapy can reduce the hazard rate for recurrence of gastric cancer. Our study confirms the time-varying pattern of the recurrence risk for gastric cancer, and it further supports the hypothesis of tumor dormancy after surgery. To effectively reduce the recurrence risk, new adjuvant therapies beyond chemotherapy may be needed.

The prognostic value of harvested lymph nodes and the metastatic lymph node ratio for gastric cancer patients: results of a study of 1,101 patients.

AIM: To investigate whether the recommendation to remove 15 lymph nodes that is used in the staging system is necessary to assess gastric cancer progression and to evaluate whether our metastatic lymph node ratio dividing method, adapted from the AJCC's (American Joint Committee on Cancer) 7(th) TNM staging system, is helpful for the patients with fewer than 15 harvested lymph nodes. METHODS: We performed a retrospective study of 1101 patients with histologically diagnosed gastric cancer who underwent a D2 gastrectomy at the Sun Yat-sen University Cancer Center between January 2001 and December 2010. The Kappa and Chi-squared tests were employed to compare the clinicopathological variables. The Kaplan-Meier method and Cox regression were employed for the univariate and multivariate survival analyses. RESULTS: In the trial, 346, 601 and 154 patients had 0-14, 15-30 and more than 30 lymph nodes harvested, respectively. The median survival times of patients with different lymph nodes harvested in N0, N1, N2 and N3a groups were 45.43, 54.28 and 66.95 months (p=0.068); 49.22, 44.25 and 56.72 months (p<0.001), 43.94, 47.97 and 35.19 months (p=0.042); 32.88, 42.76 and 23.50 months (p=0.016). Dividing the patients who had fewer than 15 lymph nodes harvested by the metastatic lymph node ratio at 0, 0.13 and 0.40, the median survival times of these 4 groups were 70.6, 50.5, 53.5 and 30.7 months (p<0.001). After re-categorising these 4 groups into the N0, N1, N2, N3a groups, the histological grade, T staging, premier N staging, and restaged N staging were the independent prognostic factors. CONCLUSIONS: Large numbers of lymph nodes harvested in radical gastrectomy do not cause stage migration. For those patients with a small number of harvested lymph nodes, their stage should be divided by the metastatic lymph node ratio, referred to in the TNM staging system, to assign them an accurate stage.

Beclin-1 expression is a significant predictor of survival in patients with lymph node-positive gastric cancer.

BACKGROUND: Beclin 1 is a main actor of autophagy. The expression of Beclin 1 and its prognostic role in gastric cancer is largely unexplored. The purpose of the present study is to investigate the expression of beclin 1 in gastric cancer cells, tissues and its relationship with prognosis. METHODS: The expression of Beclin 1 was detected in 271 specimens of lymph-node positive gastric cancer patients by immunohistochemistry. The correlation of Beclin 1 expression to clinicopathologic features and survival of gastric cancer was studied. Beclin-1 expression in gastric cancer cell lines and clinical specimens is also detected using reverse transcription-PCR and Western blotting. RESULTS: Beclin 1 is up-regulated at both mRNA and protein levels in six gastric cancer cell lines compared with those in normal gastric mucosa cell line (GES-1). The expression of Beclin-1 in gastric clinical specimens is also higher than those in the adjacent noncancerous tissues. Of the 271 patients, 229 (84.5%) were Beclin 1 high expression tumors by immunohistochemistry. Beclin 1 expression is closely associated with intravascular embolus. Kaplan-Meier analysis showed high beclin 1 expression was associated with longer overall survival. Both univariate analysis and multivariate analysis revealed that Beclin 1 expression were independent prognostic factors in the patients with node-positive gastric cancer. CONCLUSIONS: Our findings strongly suggest that Beclin 1 has a potential role in tumorigenesis of gastric cancer and could be a promising biomarker for predicting the prognosis of patients with lymph node-positive gastric cancer. It might also serve as a novel therapeutic target for gastric cancer treatment.

[Comparison of two types of digestive tract reconstruction after total gastrectomy in patients with gastric carcinoma].

OBJECTIVE: To evaluate the influence of two different types of digestive tract reconstruction on the life quality, nutritional status and tolerance to adjuvant chemotherapy after total gastrectomy in patients with gastric carcinoma. METHODS: The clinical data of a total of 107 patients treated in our department from January 2005 to december 2008 were analyzed retrospectively. Among them, 49 patients underwent digestive tract reconstruction with functional jejunal interposition (FJI group) and 58 patients underwent Roux en-Y jejunal P-type anastomosis (PR group) after total gastrectomy. 79 of 107 (73.8%) patients received postoperative adjuvant chemotherapy with XELOX regimen. The digestive complications and tolerance to chemotherapy were assessed respectively. RESULTS: Neither severe complications nor surgery-related or chemotherapy-related death were observed among the 107 patients. There were statistical differences in the incidence rate of emaciation, dumping syndrome and retention syndrome between the FJI and PR groups (P < 0.05), but no significant statistical difference in incidence rate of reflux esophagitis (P > 0.05). 28 of 40 (70.0%) patients in the FJI group completed all six cycles of chemotherapy, while 12 (30.0%) patients interrupted the treatment due to chemotherapy-related toxicity. 39 patients in the PR group received chemotherapy, 19 (48.7%) of them completed 6 cycles of chemotherapy but 20 (51.3%) patients interrupted. There was a significant difference in the incidence rate of grade III/IV chemotherapeutic toxicity and completion rate of chemotherapy (P < 0.05). CONCLUSIONS: Both functional jejunal interposition and Roux-Y operation are reasonable and safe procedures of digestive tract reconstruction. The incidence rates of emaciation, dumping syndrome and retention syndrome are lower in the patients with FJI, showing a better tolerance to adjuvant chemotherapy than Roux en-Y jejunal p type anastomosis.

Comparison of the 6th and 7th editions of the UICC TNM staging system for gastric cancer: results of a Chinese single-institution study of 1,503 patients.

AIM: To evaluate the prognostic efficacy of the 7th edition tumor-node-metastasis (TNM) classification compared with the 6th edition in gastric cancer patients. METHODS: A total of 1,503 gastric cancer patients undergoing surgical resection were staged using the 6th and 7th edition staging systems. Homogeneity, discriminatory ability, and monotonicity of gradients of the two systems were compared using linear trend χ(2), likelihood ratio χ(2) statistics, and Akaike information criterion (AIC) calculations. RESULTS: Significant differences in 5-year survival rates were observed for the T, N, and M subgroups using the 7th edition system, except for stage N2 and N3 patients in the 6th edition system. There were no significant differences in survival between IB and IIA in the 7th edition system. Patients with stage IV disease due to T4/N3 in the 6th edition system who were downstaged to stage III in the 7th edition system had significantly better survival than those who remained at stage IV. The 7th edition system had higher linear trend and likelihood ratio χ(2) scores, and smaller AIC values compared with those for the 6th edition, which represented the optimum prognostic stratification. CONCLUSIONS: Our study suggests that the 7th edition system performs better than the 6th edition in several aspects.

No survival benefit from postoperative adjuvant chemotherapy after D2 radical resection for the patients with stage II gastric cancer.

OBJECTIVE: To evaluate the effect of 2 regimens of postoperative combination chemotherapies on the prognosis of early stage gastric cancer patients. METHODS: A total of 268 patients with stage II gastric cancer underwent D2 resection in our Cancer Center between January 1990 and December 2006 were recruited. Among them, 34 patients received the FAM regimen (5-fluorouracil [5-FU] 600 mg/m(2) intravenous [IV] drip on days 1, 8, 29, and 36; doxorubicin 30 mg/m(2) IV bolus injection on days 1 and 29; and mitomycin-C 10 mg/m(2) IV bolus injection on day 1; repeated every 8 weeks) and 81 patients received the FOLFOX regimen (oxaliplatin 100 mg/m(2) IV drip on days 1 and 15; leucovorin 400 mg/m(2) IV drip on days 1 and 15; 5-FU 400 mg/m(2) IV bolus injection; 5-FU 2.4/3.0 mg/m(2) continuous IV infusion for 48 hours on day 1, 2, 15, and 16; repeated every 4 weeks for at least 4 cycles). Patients were followed-up until December 2008. The Kaplan-Meier method was used to compare survival rates between treatment groups. RESULTS: The 1-, 3-, 5-, and 10-year survival rates for the patients who received postoperative chemotherapy versus the patients who underwent surgery only were 98%, 84%, 58%, 18% versus 96%, 78%, 59%, 22%, respectively (P > 0.05). Furthermore, the survival rates for patients who received the FAM and FOLFOX regimens were not significantly different (P > 0.05). CONCLUSIONS: Postoperative adjuvant chemotherapy did not produce survival benefits for the patients with stage II gastric cancer. Randomized controlled clinical trials are demanded to confirm the finding from this study.

[Surgical approach for upper gastric cancer].

OBJECTIVE: To investigate the reasonable surgical approach for upper gastric cancer, surgical technique, and indications for combined resection of the spleen. METHODS: Eight hundred and three patients with upper gastric cancer were operated in the Cancer Center of Sun Yat-Sen from December 1964 to December 2004, including 341 cases undergoing abdominal incision and 462 thoracotomy or abdomino-thoracic incision. Clinical data were analyzed retrospectively. RESULTS: The operative time was significantly shorter in the abdominal incision group (170 vs. 220 min, P<0.01), as was the transfusion volume (200 vs. 650 ml, P<0.05). Positive resection margin was similar between the two groups (5.6% vs. 6.7%, P>0.05). There was no difference in overall postoperative complication rate (3.2% vs. 5.0%, P>0.05). Length of hospital stay was shorter in the abdominal incision group (21 vs. 26.6 days, P<0.05). CONCLUSION: Selection of surgical approach should be based on the tumor characteristics. Abdominal incision should be the approach of choice where possible.

Prognostic values of chromosome 18q microsatellite alterations in stage II colonic carcinoma.

AIM: To investigate the prognostic value of chromosome 18q microsatellite alterations (MA) in stage II colon cancer. METHODS: One hundred and six patients with sporadic stage II colon cancer were enrolled in this study. DNA was extracted from formalin-fixed, paraffin-embedded tumor and adjacent normal mucosal tissue samples. MA, including loss of heterozygosity (LOH) and microsatellite instability (MSI), was analyzed by polymerase chain reaction, polyacrylamide gel-electrophoresis and DNA sequencing at 5 microsatellite loci on chromosome 18q (D18S474, D18S55, D18S58, D18S61 and D18S64). RESULTS: Among the 102 patients eligible for MA information, the overall frequencies of LOH, high and low frequency MSI/microsatellite stable were 49.0%, 17.6% and 82.4%, respectively. The high frequency of 18q-LOH was significantly associated with the poor 5-year overall survival (OS) (P = 0.008) and disease free survival (P = 0.006). High levels of MSI were significantly associated with a longer 5-year OS (P = 0.045) while the higher frequency of 18q-LOH at the loci of D18S474 and D18S61 was significantly associated with a poorer 5-year OS (P = 0.010 and 0.005, respectively). But multivariate analysis showed that only the frequency of 18q-LOH was significantly associated with the prognosis of the disease. CONCLUSION: High frequency of 18q-LOH is an independent prognostic factor indicating poor prognosis of the patients with stage II colon cancer.

Prognosis of 980 patients with gastric cancer after surgical resection.

BACKGROUND AND OBJECTIVE: Although surgery is the only possible means to cure gastric cancer, the prognosis is often discrepant. The American Joint Committee on Cancer / International Union against Cancer (AJCC/UICC) published the TNM classification of Malignant Tumors (seventh edition) for gastric cancer recently. This study aimed to use this new edition staging system to investigate the prognostic factors for gastric cancer. METHODS: The clinicopathologic data of 980 patients with gastric cancer treated by surgical resection in our hospital between January 2000 and December 2006 were analyzed retrospectively. The overall survival rate was determined by using Kaplan-Meier method and log-rank test was used to determine significance. The prognosis was analyzed using univariate analysis and multivariate analysis with the Cox proportional hazards model. The 6th and 7th edition AJCC/UICC TNM staging systems were used to compare the survival outcomes for the cohort of patients. RESULTS: The overall 1-, 3-, 5-year survival rates for the whole group were 82.5%, 58.7%, and 52.6%. The 5-year survival rates for patients with pTNM stage I, II, III, and IV disease classified by the 7th edition staging system were 93.2%, 72.4%, 39.1%, and 5.2%, respectively. In both univariate analysis and Cox multivariate analysis, age, tumor site, tumor size, histological type, resection type, radical resection, lymphatic/venous invasion, depth of invasion, nodal status, metastasis, retrieved lymph nodes, metastatic lymph node ratio, and adjuvant chemotherapy were prognostic factors with these patients. CONCLUSION: Compared with the 6th edition system, the new edition of TNM staging system for gastric cancer can accurately predict the survival after operation.

Activated mammalian target of rapamycin is a potential therapeutic target in gastric cancer.

BACKGROUND: The mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis. The purpose of our present study is to investigate the expression of activated mTOR (p-mTOR) in gastric cancer patients, their prognostic significance and the inhibition effect of RAD001 on tumor growth and to determine whether targeted inhibition of mTOR could be a potential therapeutic strategy for gastric cancer. METHODS: The expression of p-mTOR was detected in specimens of 181 gastric cancers who underwent radical resection (R0) by immunohistochemistry. The correlation of p-mTOR expression to clinicopathologic features and survival of gastric cancer was studied. We also determined the inhibition effect of RAD001 on tumor growth using BGC823 and AGS human gastric cancer cell lines. RESULTS: Immunostaining for p-mTOR was positive in 93 of 181 (51.4%) gastric cancers, closely correlated with lymph node status and pTNM stage. Patients with p-mTOR positive showed significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those with p-mTOR-negative tumors in univariable analyses, and there was a trend toward a correlation between p-mTOR expression and survival in multivariable analyses. RAD001 markedly inhibited dose-dependently proliferation of human gastric carcinoma cells by down-regulating expression of p70s6k, p-p70s6k, C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53. CONCLUSIONS: In gastric cancer, p-mTOR is a potential therapeutic target and RAD001 was a promising treatment agent with inducing cell cycle arrest and apoptosis by down-regulating expression of C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53.

Correlation analysis between loss of heterozygosity at chromosome 18q and prognosis in the stage-II colon cancer patients.

BACKGROUND AND OBJECTIVE: Colorectal cancer is one of the most common malignant cancers in the world. Although the clinicopathologic staging is the golden criterion for the prognosis at present, the optimum prognostic criteria for colorectal cancer should be a combination of the clinicopathologic staging and the molecular markers. However, there are currently no molecular markers available for the prognosis of colorectal cancer. Several tumor-suppressor genes associated with colorectal cancer have been mapped at the 18q21-23 region. In this study we detected the frequency of loss of heterozygosity (LOH) at chromosome 18q and investigated the relationship between LOH and clinicopathologic features and its prognostic value for patients with stage II colon cancer. METHODS: A total of 106 samples of tumor tissues and corresponding normal mucosa from patients with sporadic stage-II colon cancer were included in this study. All the samples were formalin-fixed and paraffin-embedded. DNA was extracted from tumor tissues and LOH of D18S474, D18S55, D18S58, D18S61 and D18S64 at chromosome 18q was analyzed using polymerase chain reaction (PCR), polyacrylamide gel-electrophoresis, and DNA sequencing method. Multivariate analysis for association between LOH and prognosis in colon cancer patients was performed with Cox proportional hazards regression model. RESULTS: The median follow-up time was 68 months. For 106 patients, 5-year survival rate was 83.6%, which was associated with age and gross tumor type (P = 0.011 and 0.034, respectively). Among 102 patients who were eligible for LOH information, the overall frequency of LOH is 49.0% (50/102), and that of LOH at 5 microsatellite loci of D18S474, D18S55, D18S58, D18S61, and D18S64 was 30.2% (26/86), 23.4% (18/77), 28.6% (20/70), 35.0% (28/80), and 20.8%(15/72), respectively. The occurrence of LOH was significantly associated with tumor location and histopathologic grade (P = 0.023, 0.016 and 0.005, respectively). LOH was more frequent on the left-side, poorly-differentiated adenocarcinoma, and nonmucinous colon cancers. The occurrence of 18q-LOH was significantly associated with 5-year overall survival rate and disease free survival rate (P = 0.008 and 0.006, respectively). The occurrence of 18q-LOH at the loci of D18S474 and D18S61 was significantly associated with 5-year overall survival rate (P = 0.010 and 0.005, respectively). The multivariate analysis showed that only the occurrence of 18q-LOH was significantly associated with prognosis (P = 0.021). CONCLUSIONS: There is a high occurrence of LOH at the loci of 18q. The expression of LOH is significantly associated with tumor location and histopathologic grade. The occurrence of 18q-LOH is an independent poor prognostic factor for the patients with stage-II colon cancer.

[Relationship between the number of lymph node detection and prognosis in stage II gastric cancer after D(2) dissection].

OBJECTIVE: To explore the relationship between the lymph node count and prognosis in stage II gastric cancer. METHODS: Retrospective analysis was performed for the 268 cases with gastric cancer who underwent parallel D(2) dissection between January 1990 and December 2006 in the Sun Yat-Sen Cancer Center. The Japanese Gastric Cancer Association(JGCA) 13th edition of pathological staging system was used to define stage II gastric cancer. Patients were followed up until December 2008. The Kaplan-Meier method and chi-square test were used for data analysis. All the data were analyzed using SPSS16.0 for Windows. RESULTS: The average number of detected lymph nodes was 17.3+/-1.2. There were 109 patients with detected lymph node <15. The 1-, 3-, and 5-year survival rates were 92.7%, 67.8%, and 50.9%, respectively. The number of detected lymph node was > or =15 in 159 cases, and the 1-, 3-, and 5-year survival rates were 96.9 %, 81.0%, and 66.4%, respectively. The difference between two groups was statistically significant (P=0.003). Further analysis of the 199 cases with no lymph node metastasis (pN(0) group) showed that there were 95 cases with lymph nodes <15, and the 1-, 3-, and 5-year survival rates were 92.6%, 70.4%, and 55.9%, respectively. There were 104 patients with > or =15 lymph nodes, and the 1-, 3-, and 5-year survival rates were 97.1%, 84.4%, and 66.8%, respectively. The difference was also statistically significant (P=0.049). There were 69 cases with lymph node metastasis (PN(1) group), and the 1-, 3-, and 5-year survival rates of 14 patients with lymph nodes <15 were 92.9%,57.1%, and 34.3%, respectively. Comparing two groups, the survival rate was significantly different (P=0.034). There were 55 patients with > or =15 lymph nodes, and the 1-, 3-, and 5-year survival rates were 96.4%, 73.4%, and 63.8%. The difference was statistically significant (P=0.036). CONCLUSION: In patients with stage II gastric cancer as defined by the JGCA 13th edition, the survival rate is better in patients with more than 15 detected lymph nodes as compared to those with less than 15.

[Pathologic characteristics of residual carcinoma at incisal edge after gastrectomy for gastric cancer].

OBJECTIVE: To explore the reason, features and preventive measures of residual carcinoma at incisal edge after gastric cancer operation. METHODS: Clinical data of 108 cases with positive incisal margin(6.47%) from December 1964 to December 2004 in Cancer Center of Sun Yat-sen were summarized and analyzed retrospectively. RESULTS: Positive incisal margin patients accounted for 6.5%(108/1670) of total gastric carcinoma cases during above period. There were 62 men and 46 women with median age of 54 years(ranged from 23 to 82). The residual carcinoma rates of incisal edge were 3.6%(48/1333) in radical resection group and 17.8%(60/337) in palliative resection group respectively(P=0.000). Also, the residual carcinoma rates were 2.3%(3/129) in early group, 6.8(105/1541) in advanced group(P=0.046), 4.5%(37/815) in distal gastrectomy group and 8.0%(55/689) in proximal group respectively(P=0.000). Residual carcinomas were related with pTNM stage, Borrmann type, tumor size, differentiation and invasion depth(P<0.05). CONCLUSIONS: Superior gastric carcinoma, Borrmann III(, IIII( type advanced cancer, tumor diameter > or =5 cm, poor differentiation or undifferentiated type and serosa invaded easily result in residual carcinoma at incisal edge. The radical preventive measure is to ensure that incisal edge ought to exceed 5 cm apart from the tumor.

Positive lymph node ratio is an independent prognostic factor in gastric cancer after d2 resection regardless of the examined number of lymph nodes.

The purpose of this study was to clarify the outcome of the ratio between metastatic and examined lymph nodes (N ratio) in gastric cancer patients with < or =15 examined lymph nodes after D2 lymphadenectomy. A retrospective study was performed in 906 patients with gastric cancer who had undergone D2 resection. Patients with < or =15 examined lymph nodes (group 1, n = 729) and those with >15 lymph nodes (group 2, n = 177) were analyzed separately. N ratio categories were identified as follows: N ratio 0, 0%; N ratio 1, 1% to 9%; N ratio 2, 10% to 25%; N ratio 3, >25%. Univariate analysis found that both the tumor, node, metastasis system (N staging system) and N ratio system well classified patients with significantly different prognosis. By multivariate analysis, only the N ratio classification was retained as an independent prognostic factor in both group 1 and 2 compared with the N stage system. Furthermore, when patients were divided into four groups according to the number of lymph nodes examined (1 to 3, 4 to 7, 8 to 11, and 12 to 15), the 5-year survival rates remained similar between groups according to the same N ratio (p > .05). Positive N ratio classification is a better prognostic tool compared with N staging system after D2 resection in patients with gastric cancer. It can prevent stage migration and can be used regardless of the examined number of lymph nodes.

[Comparative study on clinical characteristics of gastric carcinoma between young and elderly patients].

OBJECTIVE: To compare the clinical characteristics of gastric cancer between young and elderly patients,and bring forward corresponding countermeasures. METHODS: Clinical characteristics, treatment and prognosis between 79 young (or= 65 years old) patients were compared. RESULTS: The constituent ratio of gender between young and elderly group was not significantly different (P=0.226). There was no particularity of early symptom in young patients, but they had shorter course of disease (165 d vs 400 d, P=0.029) and more frequent inferior part of cancer (49.4% vs 41.7%, P=0.038) as compared to elderly patients. There was significant difference between two groups in pathological stage ratio (P=0.027). The median total survival time of young and elderly patients was 1006 d and 530 d respectively, which was not significantly different (P=0.108). Furthermore, median survival time of young and elderly patients after radical resection were 1197 d and 919 d respectively, and the difference was not significant as well (P=0.242). CONCLUSIONS: Characteristics of young patients with gastric cancer are lower incidence, larvaceous symptoms, more malignancy and quick development, which still remain general features of gastric cancer. By correct therapy, the efficacy of above young patients is similar to elderly patients. The key to improve prognosis is to further fortify cognition for gastric cancer and elevate early diagnostic rate.

[Influence of neoadjuvant chemotherapy on microsatellite instability in gastric carcinoma].

BACKGROUND & OBJECTIVE: Most results from clinical trials of neoadjuvant chemotherapy for gastric carcinoma are certain. Meanwhile, microsatellite instability (MSI) is thought to be a new mechanism of cell canceration. This study was to investigate the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma. METHODS: Two microsatellite loci D2S123 and D3S1298 in tumor samples from 48 patients with gastric carcinoma, received preoperative chemotherapy of 5-fluorouracil (5-FU) and leucovorin (CF), were analyzed by polymerase chain reaction (PCR), electrophoresis on 8% denatured polyacrylamide gel, and silver staining. The microsatellite statuses of preoperative and postoperative specimens were compared. Chi-square test was used to analyze the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma. RESULTS: The detection rate of MSI was significantly higher in preoperative samples than in postoperative samples (31.3% vs. 12.5%, P=0.026). After neoadjuvant chemotherapy, 9 cases changed from MSI-positive to MSI-negative, while no MSI-negative cases became MSI-positive. CONCLUSION: The neoadjuvant chemotherapy regimen of 5-FU/CF can induce some MSI-positive gastric carcinoma change to MSI-negative, but has no effect on MSI-negative cases.

Loss of heterozygosity analysis of a candidate gastric carcinoma tumor suppressor locus at 7q31.

Gastric carcinoma is one of the most common malignancies in Asia. Although the allelic deletion of 7q has been reportedly associated with primary gastric carcinoma tumorigenesis, no predisposing genes in this region have been identified so far. Here, we report the results of genotype and loss of heterozygosity (LOH) analysis on 7q in this tumor. A panel of nine microsatellite markers distributed over the whole chromosome 7q was used for genotyping primary gastric carcinomas. Of 72 primary tumors LOH of D7S486 occurred in 24.0% (12/50) of cases. Fine mapping with 12 additional markers flanking D7S486 resulted in LOH of 30.36% (17/56) and defined one minimal deleted region in primary gastric carcinomas, a 90-kilobase region bounded by D7S2543 and D7S486 at 7q31.2. The allelic deletion correlates statistically with clinicopathologic variables. Our data suggest a possible link between putative tumor suppressor genes and gastric carcinoma in the 7q31 region.

[Long-term results of surgical treatment of stomach cancer: clinical experience of forty years from Sun Yat-sen University Cancer Center].

OBJECTIVE: To investigate the approaches to improve therapeutic effect of stomach cancer by analysis of the long-term results of surgical treatment of this disease. METHODS: Prognostic factors of stomach cancer were analyzed by Cox multivariate regression model based on clinical data of 2561 stomach cancer cases who underwent surgical treatment from 1964 to 2004 at Sun Yat-sen University Cancer Center. Survival rates were calculated by life table method. RESULTS: Gastrectomy was performed for 1950 cases with resectability of 76.1%, among which there were 1192 cases of curative resection (46.5%) and 758 cases of non-curative resection (29.6%). The other 611 cases of palliative operation included bypass procedures and laparotomy. Operative mortality of all cases was 0.8% and morbidity was 5.1%. For all cases the 1-, 3- and 5-year survival rate was 52.4%, 38.6% and 35.5%, respectively. The stage-specific 5-year survival rate was 86.8% (Stage I), 58.7% (Stage II), 28.4% (Stage III) and 7.6% (Stage IV), respectively. The 5-year survival after curative resection in the period of 40 years was 45.5%, and increased to 52.7% in the last two decades and 61.8% in recent decade. Stage-specific case proportion during the earlier two decades was 1.4% (Stage I), 10.6% (Stage II), 23.1% (Stage III) and 64.9% (Stage IV), respectively, and that during the recent two decades was 9.3%, 18.5%, 35.3% and 36.8%, respectively. The 5-year survival rate of cases during the earlier two decades was 18.0% and increased to 37.5% during the recent two decades. Multivariate analysis indicated that main prognostic factors of stomach cancer included TNM staging, curative resection and multidisciplinary treatment. CONCLUSIONS: Early detection and curative resection were the most important measures to improve therapeutic effect of stomach cancer. A surgery-predominant multidisciplinary treatment individualizing biological characteristics of tumor, staging of disease and tumor site will contribute to improvement of therapeutic effect of stomach cancer.