Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer / 中华胃肠外科杂志

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

Mode of lymph node metastasis in early gastric cancer and risk factors / 中华胃肠外科杂志

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

Prognosis analysis of 310 patients with pathological stage pN3 gastric cancer / 中华胃肠外科杂志

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

Significance of No.14v lymph node dissection for advanced gastric cancer undergoing D2 lymphadenectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To elucidate the necessity of No.14v lymph node dissection in D2 lymphadenectomy for advanced gastric cancer.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

The prognostic influence of D2 lymphadenectomy with para-aortic lymph nodal dissection for gastric cancer in N3 stage / 中华外科杂志

<p><b>OBJECTIVE</b>To elucidate the necessity of para-aortic lymph nodal dissection in D2 lymphadenectomy for gastric cancer in N3 stage.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Changes of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the change of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients.</p><p><b>METHODS</b>Twenty-one peripheral blood lymphocyte subsets from 62 colorectal carcinoma patients before and after FOLFOX4(including oxaliplatin, 5-fluorouracil and leucovorin) , FOLFRI(including irinotecan, 5-fluorouracil and leucovorin) , or XELOX(including oxaliplatin and capecitabine) regimen chemotherapy were examined by flow cytometry.The differences of these lymphocyte subsets were analyzed.</p><p><b>RESULTS</b>After chemotherapy, the percentages of CD3(+), CD3(+)CD8(+), CD29(+), CD4(+)CD29(+), and CD4(+)CD25(+) cells in peripheral blood of colorectal carcinoma patients increased significantly, while the percentages of CD19(+) and human leukocyte antigen(locus) DR(HLA-DR) (+) cells decreased significantly(P<0.05) .The results of subgroup analysis showed that the patients' CD3(+)CD8(+) and CD4(+)CD25(+) cells increased significantly, CD19(+) and HLA-DR(+) cells decreased significantly after FOLFOX4 regimen chemotherapy(P<0.05) ;CD3(+)CD8(+) cells increased significantly and CD19(+) cells decreased significantly after XELOX regimen chemotherapy(P<0.05) ;while after FOLFRI regimen chemotherapy, there were no significant changes in all 21 lymphocyte subsets(P>0.05) . CD3(+), CD3(+)CD8(+), memory T lymphoctye(45RO(+)) , and CD4(+)CD45RO(+) cells increased significantly(P<0.05) in patients who received no more than 4 cycles of chemotherapy. However, in patients that received 5 to 8 cycles and more than 9 cycles chemotherapy, we only found significant decrease of HLADR(+) cells and significant increase of CD29(+) cells, respectively(P<0.05) .</p><p><b>CONCLUSIONS</b>The humoral immunity is attenuated after chemotherapy in colorectal carcinoma patients. FOLFOX4 may suppress the cellular immunity.Chemotherapy that is less than 4 cycles will strengthens the cellular immunity by modulating body immunity arrangement;however, along with the increase of chemotherapy cycles, the cellular immunity gradually declines in these patients.</p>

Clinical analysis of combined organ resection for T4b gastric cancer / 中华胃肠外科杂志

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

The reasonable surgery for gastric body cancer and prognostic analysis / 中华外科杂志

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

Detection of T lymphocyte subsets in the peripheral blood of patients with advanced lung adenocarcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the CD4+CD25+ regulatory T cells (Treg) and other lymphocyte subsets in the peripheral blood of patients with advanced lung adenocarcinoma.</p><p><b>METHODS</b>Peripheral blood samples were obtained from 64 patients with advanced lung adenocarcinoma (case group) and analyzed by flow cytometry. The ratios of CD4+CD25+Treg T cells and other T lymphocyte subsets in peripheral blood were compared with those from 33 healthy controls (control group).</p><p><b>RESULTS</b>The percentages of CD3+ and CD3+CD4+ were (66.5±11.0)% and (37.7±10.6)% respectively in the peripheral blood of the case group, which were significantly lower than those [(72.0±6.0)% and (42.0±6.4)%] in the control group (t=-3.2,-2.4; P=0.020, 0.015, respectively). The ratio of CD4+ CD25+ Treg cells in case group (10.5±4.0)% was significantly higher than that [(8.4±3.5)%] in the control group (t=-2.2, P=0.013). CD4+/CD8+ value of case group (1.4±0.8) was significantly lower than that (1.8±0.7) in control group(t=-2.2, P=0.029). CD3+CD8+, CD8+CD28-, and CD8+CD28+ showed no significant differences (all P>0.05). Smoking, differentiation grade, and size of the tumor showed no association with the function damage of T lymphocyte subsets, while the carcino-embryonic antigen level did.</p><p><b>CONCLUSIONS</b>In patients with advanced lung adenocarcinoma, Treg increases and CD4+/CD8+ decreases, suggesting remarkably suppressed immune functions. However, more research is warranted to validate the association of T cells subset dysfunction with smoking, differentiation grade, and size of tumor.</p>

Prognostic factors in 138 patients with node-negative gastric cancer / 中华胃肠外科杂志

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

Comparative study on four different reconstruction procedures after total gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the optimal reconstruction technique after total gastrectomy.</p><p><b>METHODS</b>A total of 159 patients with gastric cancer undergoing total gastrectomy in Tianjin Cancer Hospital between January 2005 and December 2007 were divided into 4 groups according to the reconstruction technique: group A(functional jejunal interposition with a pouch, n=46), group B(modified Braun type II(, n=38), group C (P pouch with Roux-en-Y esophagojejunostomy, n=25), group D(Roux-en-Y esophagojejunostomy, n=50). Quality of life(QOL), nutritional status 1 year after surgery, and perioperative complications were analyzed.</p><p><b>RESULTS</b>There were no significant differences in perioperative complications(P>0.05). One year after operation, QOL(Visick index) was better in group A than that in group B, C and D(P<0.05), and group D was inferior to group A, B and C(P<0.05). The increase in food intake, weight gain, hemoglobin and total protein were better in group A than those in group B, C and D(P<0.05) and group D was inferior to group A, B and C(P<0.05). The prognostic nutrition index ratio of the four groups were 1.21±0.15, 1.14±0.97, 1.15±0.16, and 1.10±0.16, respectively. Group A was better than that in group B, C and D (P<0.05) and group D was inferior to group A, B and C(P<0.05). The incidences of dumping syndrome, reflux esophagitis, Roux-en-Y stasis syndrome in group A were 4.3%(2/46), 2.2%(1/46) and 2.2%(1/46), respectively, which were significantly lower than those in other groups (P<0.05).</p><p><b>CONCLUSIONS</b>Functional jejunal interposition with a pouch is associated with improved nutritional condition and quality of life, and less perioperative complications. It is a reasonable reconstruction method after total gastrectomy.</p>

Clinical characteristics of 103 lymph node metastasis in advanced proximal gastric cancer / 中华胃肠外科杂志

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

Risk factors of early recurrence in patients with gastric cancer after curative resection / 中华外科杂志

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