Current status of extended 'D2 plus' lymphadenectomy in advanced gastric cancer.

The extent of lymph node (LN) dissection has been a topic of interest in gastric cancer (GC) surgery. D2 lymphadenectomy is considered the standard surgical procedure for most resectable advanced GC cases. The value and indications of more extended lymphadenectomy than D2 remain unclear. Currently, the controversial stations beyond the D2 range are mainly focused on no. 14v, no. 16a2/b1 and no. 13 LN stations. The metastatic rate of no. 14v LN is relatively high in advanced distal GC, particularly in patients with suspicious no. 6 LN metastasis. D2 plus no. 14v LN dissection may be attributed to improved survival outcomes for patients with obvious no. 6 LN metastasis. Although GC with para-aortic lymph node (PALN) metastases is considered an M1 disease beyond surgical cure, patients with limited PALN metastases may benefit from the treatment strategy of adjuvant chemotherapy followed by D2 plus no. 16a2-b1 LN dissection. In addition, D2 plus no. 13 LN dissection may be an option in a potentially curative gastrectomy for GC with duodenal invasion. The present review discusses the current status and future perspectives of D2 plus lymphadenectomy.

Effect of complication grade on survival following curative gastrectomy for carcinoma.

AIM: To elucidate the potential impact of the grade of complications on long-term survival of gastric cancer patients after curative surgery. METHODS: A total of 751 gastric cancer patients who underwent curative gastrectomy between January 2002 and December 2006 in our center were enrolled in this study. Patients were divided into four groups: no complications, Grade I, Grade II and Grade III complications, according to the following classification systems: T92 (Toronto 1992 or Clavien), Accordion Classification, and Revised Accordion Classification. Clinicopathological features were compared among the four groups and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified using the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of complications of each grade on survival. RESULTS: Significant differences were found among the four groups in age, sex, other diseases (including hypertension, diabetes and chronic obstructive pulmonary disease), body mass index (BMI), intraoperative blood loss, tumor location, extranodal metastasis, lymph node metastasis, tumor-node-metastasis (TNM) stage, and chemotherapy. Overall survival (OS) was significantly influenced by the complication grade. The 5-year OS rates were 43.0%, 42.5%, 25.5% and 9.6% for no complications, and Grade I, Grade II and Grade III complications, respectively (P < 0.001). Age, tumor size, intraoperative blood loss, lymph node metastasis, TNM stage and complication grade were independent prognostic factors in multivariate analysis. With stratified analysis, lymph node metastasis, tumor size, and intraoperative blood loss were independent prognostic factors for Grade I complications (P < 0.001, P = 0.031, P = 0.030). Age and lymph node metastasis were found to be independent prognostic factors for OS of gastric cancer patients with Grade II complications (P = 0.034, P = 0.001). Intraoperative blood loss, TNM stage, and chemotherapy were independent prognostic factors for OS of gastric cancer patients with Grade III complications (P = 0.003, P = 0.005, P < 0.001). There were significant differences among patients with Grade I, Grade II and Grade III complications in TNM stage II and III cancer (P < 0.001, P = 0.001). CONCLUSION: Complication grade may be an independent prognostic factor for gastric cancer following curative resection. Treatment of complications can improve the long-term outcome of gastric cancer patients.

Characteristics and prognosis of gastric cancer in patients aged ≥ 70 years.

AIM: To elucidate the prognostic value of age for gastric cancer and identify the optimal treatment for elderly gastric cancer patients. METHODS: We enrolled 920 patients with gastric cancer who underwent gastrectomy between January 2003 and December 2007 in our center. Patients were categorized into three groups: younger group (age < 50 years), middle-aged group (50-69 years), and elderly group (≥ 70 years). Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed. The log-rank test was used to assess statistical differences between curves. Independent prognostic factors were identified by the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of age on survival at each stage. Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer. We analyzed the potential prognostic factors for patients aged ≥ 70 years. Finally, the impact of extent of lymphadenectomy and postoperative chemotherapy on survival for each age group was evaluated. RESULTS: In the elderly group, there was a male predominance. At the same time, cancers of the upper third of the stomach, differentiated type, and less-invasive surgery were more common than in the younger or middle-aged groups. Elderly patients were more likely to have advanced tumor-node-metastasis (TNM) stage and larger tumors, but less likely to have distant metastasis. Although 5-year overall survival (OS) rate specific to gastric cancer was not significantly different among the three groups, elderly patients demonstrated a significantly lower 5-year OS rate than the younger and middle-aged patients (elderly vs middle-aged vs younger patients = 22.0% vs 36.6% vs 38.0%, respectively). In the TNM-stratified analysis, the differences in OS were only observed in patients with II and III tumors. In multivariate analysis, only surgical margin status, pT4, lymph node metastasis, M1 and sex were independent prognostic factors for elderly patients. The 5-year OS rate did not differ between elderly patients undergoing D1 and D2 lymph node resection, and these patients benefited little from chemotherapy. CONCLUSION: Age ≥ 70 years was an independent prognostic factor for gastric cancer after gastrectomy. D1 resection is appropriate and postoperative chemotherapy is possibly unnecessary for elderly patients with gastric cancer.

Impact of intraoperative blood loss on survival after curative resection for gastric cancer.

AIM: To elucidate the potential impact of intraoperative blood loss (IBL) on long-term survival of gastric cancer patients after curative surgery. METHODS: A total of 845 stage I-III gastric cancer patients who underwent curative gastrectomy between January 2003 and December 2007 in our center were enrolled in this study. Patients were divided into 3 groups according to the amount of IBL: group 1 (< 200 mL), group 2 (200-400 mL) and group 3 (> 400 mL). Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified by the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of IBL on survival in each stage. Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer. Finally, we explored the possible factors associated with IBL and identified the independent risk factors for IBL ≥ 200 mL. RESULTS: Overall survival was significantly influenced by the amount of IBL. The 5-year overall survival rates were 51.2%, 39.4% and 23.4% for IBL less than 200 mL, 200 to 400 mL and more than 400 mL, respectively (< 200 mL vs 200-400 mL, P < 0.001; 200-400 mL vs > 400 mL, P = 0.003). Age, tumor size, Borrmann type, extranodal metastasis, tumour-node-metastasis (TNM) stage, chemotherapy, extent of lymphadenectomy, IBL and postoperative complications were found to be independent prognostic factors in multivariable analysis. Following stratified analysis, patients staged TNM I-II and those with IBL less than 200 mL tended to have better survival than those with IBL not less than 200 mL, while patients staged TNM III, whose IBL was less than 400 mL had better survival. Tumor location, tumor size, TNM stage, type of gastrectomy, combined organ resection, extent of lymphadenectomy and year of surgery were found to be factors associated with the amount of IBL, while tumor location, type of gastrectomy, combined organ resection and year of surgery were independently associated with IBL ≥ 200 mL. CONCLUSION: IBL is an independent prognostic factor for gastric cancer after curative resection. Reducing IBL can improve the long-term outcome of gastric cancer patients following curative gastrectomy.

[Significance of No.14v lymph node dissection for advanced gastric cancer undergoing D2 lymphadenectomy].

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

[The prognostic analysis of tumor size in T4a stage gastric cancer].

OBJECTIVE: To investigate the impact of tumor size in the prognosis of T4a stage gastric cancer. METHODS: The best cut-off point depending on tumor size was selected by Kaplan-Meier. Compare cliniclópathological characteristics between small size gastric cancer (SSG) and large size gastric cancer (LSG). Univariate analysis was done by Log-rank test and multivariate analysis was performed using the Cox proportional hazard regression model. The independent prognostic factors of patients were performed subgroup analysis. RESULTS: Eight centimetre was the optimal cut-off of tumor size for T4a stage gastric cancer. There were significantly differences between SSG and LSG in tumor location (χ² = 15.695), histological grade (χ² = 4.393), macroscopic type (χ² = 5.629) and early recurrence (χ² = 4.292). Univariate analysis showed age (χ² = 4.463), tumor size (χ² = 9.057), macroscopic type (χ² = 6.679), histological grade (χ² = 5.122), location of tumor (χ² = 8.707) and N stage (χ² = 132.954) are related to survival (P < 0.05). Among them, tumor size (HR = 1.339), histological grade (HR = 1.169) and N stage (HR = 1.876) were independent risk factor for survival (P = 0.05). For SSG, N stage (HR = 2.014) and histological grade (HR = 1.192) were independent risk factor for survival (P = 0.05), and for LSG, N stage (HR = 1.876) was independent risk factor for survival (P = 0.000). Further stratified analysis indicated that the 5-year survival rate of LSG is significantly lower than that of SSG in T4a stage patients of gastric cancer without lymph nodes metastasis or poorly differentiated (HR = 0.182 and 0.653, P < 0.01). CONCLUSIONS: Tumor size is an independent prognostic factor in patients of T4a stage gastric cancer. Tumor size cut-off point of 8 cm can exert significant impact on the prognosis of T4a stage gastric cancer without lymph nodes metastasis or poorly differentiated.

[The significance of No.13 lymph node dissection in D2 gastrectomy for lower-third advanced gastric cancer].

OBJECTIVE: To evaluate the feasibility and necessity of No.13 lymph node dissection in D2 radical gastrectomy for lower-third advanced gastric cancer (AGC). METHODS: Data of 379 cases who were diagnosed as TNM II-III stage AGC were collected from January 2001 to June 2007. One hundred cases who undergone No.13 lymph node dissection during D2 gastrectomy for lower-third AGC were selected as study group. Other 279 cases (control group) received only D2 gastrectomy. The differences in clinicopathologic and intraoperative and postoperative parameters and 5-years survival rate were compared using the SPSS 17.0 software. RESULTS: There were no significant differences between the two groups in patients' gender, age, tumor size, histologic type, Borrmann type, duodenum invasion, tumor depth, lymph node metastasis, TNM classification, operative time, blood loss and the incidence of postoperative complications (P > 0.05). In the study group, there were 9 patients with positive No. 13 lymph node, and its 5-year survival rate (46.0%) was higher than the control group (36.5%, χ² = 4.452, P < 0.05). The Univariate analysis showed that age (χ² = 7.539), No.13 lymph node dissection (χ² = 4.452), tumor size (χ² = 7.100), duodenum invasion (χ² = 9.106), tumor depth (χ² = 7.428), lymph node metastasis (χ² = 45.046), TNM classification (χ² = 57.008) are associated with prognosis of lower-third AGC (P < 0.05). Multivariate analysis identified age (HR = 0.500, 95% CI: 0.343 - 0.730), tumor size (HR = 0.545, 95%CI: 0.339 - 0.876), duodenum invasion (HR = 5.821, 95%CI: 2.326 - 14.572), and tumor depth (T4: HR = 2.087, 95% CI: 1.283 - 3.394) as independent prognostic factors (P < 0.05). CONCLUSION: No. 13 lymph node dissection for TNM II-III stage lower-third advanced gastric cancer is feasible and necessary.

[The value of negative lymph node count in prediction of prognosis of advanced gastric cancer].

OBJECTIVE: To evaluate the value of negative lymph node count (NLNC) in prediction of prognosis of advanced gastric cancer after radical resection. METHODS: The 544 cases of radical gastrectomy patients with complete clinical and follow-up data between January 2011 and July 2007 were collected. Survival was determined by the Kaplan-Merier method and univariate analysis was done by Log-rank test, Multivariate analysis was performed using the Cox proportional hazard regression model. RESULTS: Univariate analysis showed age (χ(2) = 4.449), T stage (χ(2) = 30.482), N stage (χ(2) = 205.452), location of tumor (χ(2) = 16.649), tumor size (χ(2) = 35.117), macroscopic type (χ(2) = 4.750), histological grade (χ(2) = 6.130), NLNC stage (χ(2) = 150.369) and type of gastrectomy (χ(2) = 25.605) were related to survival. Among them, T stage, N stage, tumor size and NLNC stage were independent risk factors for survival (P < 0.05). The prognostic factors of patients were performed subgroup analysis, NLNC > 15 group can prolong the survival than NLNC ≤ 15 group in the T2 stage (HR = 0.315), T4 stage (HR = 0.401), the same classification of location of tumor (HR = 0.286-0.493), tumor size (HR = 0.336, 0.465), macroscopic type (HR = 0.306, 0.418), histological grade (HR = 0.411, 0.365) and type of gastrectomy (HR = 0.444, 0.358 and 0.356, all P < 0.05). More NLNC can prolong Disease-Free Survival for patient of early recurrence (χ(2) = 8.648, P = 0.003). CONCLUSIONS: Sufficient negative lymph node count can prolong the survival and decrease the risk of early recurrence.

[Prognostic value of metastatic lymph node ratio for gastric cancer patients with less than 15 lymph nodes dissection].

OBJECTIVE: To evaluate the prognostic value of metastatic lymph node ratio (MLR) for gastric cancer patients with less than 15 lymph nodes dissected. METHODS: Clinical data of 610 gastric cancer patients undergoing operation in Tianjin Cancer Hospictal from January 2003 to July 2007 were analyzed retrospectively. Patients were divided into two groups: <15 lymph nodes dissected group (n=320) and ≥ 15 lymph nodes dissected group (n=290). MLR was classified based on the following intervals: rN1 ≤ 10%, rN2 10%-30%, rN3 30%-60% and rN4 >60%. Survival was determined by Kaplan-Meier method and difference was assessed by Log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model. Survival rates were compared between two groups in pN and rN stages respectively. RESULTS: In <15 nodes group, all the survival differences among various rN stages were not significant (all P>0.05), while in same rN stage, all the survival differences among various pN stages were not significant (all P>0.05). Significant differences of 5-year cumulative survival rates were found between the two groups in pN2 and pN3a stage patients (both P<0.05) while no significant differences were found among different rN stages (all P>0.05). Multivariate analysis demonstrated rN stage was an independent prognostic factor for gastric cancer patients with <15 lymph nodes dissected (P=0.012, RR=1.617, 95%CI:1.111-2.354). CONCLUSION: The rN staging system based on MLR can predict the prognosis of gastric cancer patients with less than 15 lymph nodes dissected.

[Analysis of clinicopathologic characteristics and prognosis on mixed histology type of gastric cancer].

OBJECTIVE: To evaluate the clinicopathologic characteristics and prognosis of mixed histological type (MHT) gastric cancer. METHODS: Clinical and follow-up data of 1108 gastric cancer patients undergoing radical operation in Tianjin Cancer Hospital between 2003 and 2006 were analyzed retrospectively. Clinicopathologic characteristics of MHT gastric cancer were summarized and the prognosis was analyzed by Kaplan-Meier analysis and COX regression. RESULTS: Among the 1108 patients, 144 (13.0%) had mixed histology type of gastric cancer. Compared to the unitary histological type (UHT), MHT gastric cancer had bigger tumor size, higher proportion of T4 tumor, and was easier for lymph node and distant metastasis (all P<0.05). The 3- and 5-year survival rates of patients with MHT were 26.5% and 10.8% respectively, which were lower than those with UHT (58.8% and 35.0%, P<0.01). Univariate and multivariate analyses showed TNM classification was an independent prognostic factor (P<0.01). CONCLUSIONS: MHT gastric cancer shows worse prognosis than UHT gastric cancer. There is no difference in prognosis among various combination of MHT gastric cancer. TNM classification is an independent prognostic factor of MHT gastric cancer.

[The prognostic influence of D2 lymphadenectomy with para-aortic lymph nodal dissection for gastric cancer in N3 stage].

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