Jian-Wei Xie

Consideration of tumor size improves the accuracy of TNM predictions in patients with gastric cancer after curative gastrectomy

OBJECTIVE To investigate whether addition of tumor size improves the prognostic accuracy of the UICC 7th TNM staging system in gastric cancer patients who underwent radical surgery (R0 resection). METHODS The clinical and pathological data and postoperative 5-year survival rate of 507 patients with gastric cancer who underwent radical surgery (R0 resection) in our department from January 2004 to June 2006 were evaluated retrospectively. The prognostic accuracy of conventional UICC 7th TNM staging was compared with that of UICC 7th TNM staging plus tumor size. The ability of tumor size to improve the 95% confidence interval (CI) of postoperative 5-year survival rate in gastric cancer patients was assessed. RESULTS Of the 507 patients, 470 (92.7%) were followed up. The five-year survival rate of these patients was 50.4%. The survival rates of patients with pT1, pT2, pT3, and pT4 stage tumors were 89.3%, 72.4%, 36.9%, and 23.7%, respectively (P < 0.05), and the survival rates of patients with pN0, pN1, pN2, and pN3 stage tumors were 75.2%, 68.8%, 46.7%, and 21.3% (P < 0.05). Depth of invasion, lymph node metastasis stage, metastatic lymph node ratio (MLR), lymphatic invasion and tumor size were independent predictors of patient prognosis. The accuracy of UICC 7th TNM staging in predicting 5-year survival was 75.4% and the accuracy of tumor size plus the UICC 7th TNM staging was 77.9% (P < 0.05). This combination improved the 95% CI of postoperative 5-year survival rate in gastric cancer patients. CONCLUSION Tumor size can improve the accuracy of UICC 7th TNM staging in predicting survival in gastric cancer patients following radical surgery (R0 resection). Tumor size is likely to be another important indicator in future UICC-TNM staging systems for gastric cancer patients.

Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach

AIM To explore the impact of tumor size on outcomes in patients with advanced gastric cancer in the lower third of the stomach. METHODS We retrospectively analyzed the clinical records of 430 patients with advanced gastric cancer in the lower third of the stomach who underwent distal subtotal gastrectomy and D2 lymphadenectomy in our hospital from January 1998 to June 2004. Receiver-operating characteristic (ROC) curve analysis was used to determine the appropriate cutoff value for tumor size, which was measured as maximum tumor diameter. Based on this cutoff value, patients were divided into two groups: those with large-sized tumors (LSTs) and those with small-sized tumors (SSTs). The correlations between other clinicopathologic factors and tumor size were investigated, and the 5-year overall survival (OS) rate was compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis and multivariate Coxs proportional hazard model analysis. The 5-year OS rates in the two groups were compared according to pT stage and pN stage. RESULTS The 5-year OS rate in the 430 patients with advanced gastric cancer in the lower third of the stomach was 53.7%. The mean ± SD tumor size was 4.9 ± 1.9 cm, and the median tumor size was 5.0 cm. ROC analysis indicated that the sensitivity and specificity results for the appropriate tumor size cutoff value of 4.8 cm were 80.0% and 68.2%, respectively (AUC = 0.795, 95%CI: 0.751-0.839, P = 0.000). Using this cutoff value, 222 patients (51.6%) had LSTs (tumor size ≥ 4.8 cm) and 208 (48.4%) had SSTs (tumor size < 4.8 cm). Tumor size was significantly correlated with histological type (P = 0.039), Borrmann type (P = 0.000), depth of tumor invasion (P = 0.000), lymph node metastasis (P = 0.000), tumor-nodes metastasis stage (P = 0.000), mean number of metastatic lymph nodes (P = 0.000) and metastatic lymph node ratio (P = 0.000). Patients with LSTs had a significantly lower 5-year OS rate than those with SSTs (37.1% vs 63.3%, P = 0.000). Univariate analysis showed that depth of tumor invasion (χ² = 69.581, P = 0.000), lymph node metastasis (χ² = 138.815, P = 0.000), tumor size (χ² = 78.184, P = 0.000) and metastatic lymph node ratio (χ² = 139.034, P = 0.000) were significantly associated with 5-year OS rate. Multivariate analysis revealed that depth of tumor invasion (P = 0.000), lymph node metastasis (P = 0.019) and tumor size (P = 0.000) were independent prognostic factors. Gastric cancers were divided into 12 subgroups: pT2N0; pT2N1; pT2N2; pT2N3; pT3N0; pT3N1; pT3N2; pT3N3; pT4aN0; pT4aN1; pT4aN2; and pT4aN3. In patients with pT2-3N3 stage tumors and patients with pT4a stage tumors, 5-year OS rates were significantly lower for LSTs than for SSTs (P < 0.05 each), but there were no significant differences in the 5-year OS rates in LST and SST patients with pT2-3N0-2 stage tumors (P > 0.05). CONCLUSION Using a tumor size cutoff value of 4.8 cm, tumor size is a prognostic factor in patients with pN3 stage or pT4a stage advanced gastric cancer located in the lower third of the stomach.

Laparoscopy-assisted gastrectomy with D2 lymph node dissection for advanced gastric cancer without serosa invasion: a matched cohort study from South China

BackgroundGastric cancer is a common malignancy worldwide and a common cause of death from cancer. Despite recent advances in multimodality treatment and targeted therapy, complete resection remains the only treatment that can lead to cure. This study was devised to investigate the technical feasibility, safety and oncologic efficacy of laparoscopy-assisted gastrectomy for advanced gastric cancer without serosa invasion.MethodsA retrospective matched cohort study was performed in south China comparing laparoscopy-assisted gastrectomy and open gastrectomy for advanced gastric cancer without serosa invasion. Eighty-three patients with advanced gastric cancer undergoing laparoscopy-assisted gastrectomy between January 2008 and December 2010 were enrolled. These patients were compared with 83 patients with advanced gastric cancer undergoing open gastrectomy during the same period.ResultsThere was no significant difference in clinicopathologic characteristics between the two groups. Regarding perioperative characteristics, the operation time and time to ground activities did not differ between the two groups, whereas the blood loss, transfused patient number, time to first flatus, time to resumption of diet, and postoperative hospital stay were significantly less in laparoscopy-assisted gastrectomy than in open gastrectomy (P <0.05). There was no statistically significant difference in postoperative morbidity and mortality. No significant difference in the number of lymph nodes dissected was observed between these two groups. There was no significant difference in the cumulative survival rate between the two groups.ConclusionLaparoscopy-assisted gastrectomy with D2 lymphadenectomy is a safe and feasible procedure for advanced gastric cancer without serosa invasion. To be accepted as a choice treatment for advanced gastric cancer, well-designed randomized controlled trials comparing short-term and long-term outcomes between laparoscopy-assisted gastrectomy and open gastrectomy in a larger number of patients are necessary.

Surgical Outcomes of 2041 Consecutive Laparoscopic Gastrectomy Procedures for Gastric Cancer: A Large-Scale Case Control Study

Background Laparoscopic gastrectomy (LG) for gastric cancer has increased in popularity due to advances in surgical techniques. The aim of this study is to validate the efficacy and safety of laparoscopic gastrectomy for gastric cancer compared with open gastrectomy (OG). Methods The study comprised 3,580 patients who were treated with curative intent either by laparoscopic gastrectomy (2,041 patients) or open gastrectomy (1,539 patents) between January 2005 and October 2013. The surgical outcomes were compared between the two groups. Results Laparoscopic gastrectomy was associated with significantly less blood loss, transfused patient number, time to ground activities, and post-operative hospital stay, but with similar operation time, time to first flatus, and time to resumption of diet, compared with the open gastrectomy. No significant difference in the number of lymph nodes dissected was observed between these two groups. The morbidity and mortality rates of the LG group were comparable to those of the OG group (13.6% vs. 14.4%, P = 0.526, and 0.3% vs. 0.2%, P = 0.740). The 3-year disease-free and overall survival rates between the two groups were statistically significant (P<0.05). According to the UICC TNM classification of gastric cancer, the 3-year disease-free and overall survival rates were not statistically different at each stage. Conclusions Our single-center study of a large patient series revealed that LG for gastric cancer yields comparable surgical outcomes. This result was also true of local advanced gastric cancer (AGC). A well-designed randomized controlled trial comparing surgical outcomes between LG and OG in a larger number of patients for AGC can be carried out.

Evaluation of laparoscopic total gastrectomy for advanced gastric cancer: results of a comparison with laparoscopic distal gastrectomy

AbstractObjectiveTo validate the efficacy and safety of laparoscopic total gastrectomy (LTG) for advanced gastric cancer (AGC). BackgroundLaparoscopic distal gastrectomy (LDG) in the treatment of patients with local AGC is becoming increasingly popular, and there have been several multicenter randomized controlled trials focused on this treatment. However, few reports on the procedure of LTG for AGC exist.MethodsThe data of 976 patients who underwent LTG for AGC were retrieved from a prospectively constructed database of 2170 patients who underwent laparoscopic gastrectomy between 2007 and 2013. Surgical outcomes of LTG were investigated and compared with those of patients who underwent LDG.ResultsLTG was associated with significantly longer operation time, number of dissected lymph nodes, and time of resume soft diet compared with the LDG group. According to Clavien–Dindo classification, the morbidity and mortality rates of the LTG group were comparable to those of the LDG group. Multivariate analyses revealed that elderly patients, more comorbidities, and longer operation time were the significant independent risk factors for determining postoperative complications. The difference in overall survival rates between the two groups was statistically significant. However, a comparative analysis of overall survival showed no statistical significance for any of the stages of cancer between the LTG and LDG groups.ConclusionsThe study findings suggest that LTG is an oncologically safe procedure for AGC yields comparable surgical outcomes. A well-designed phase III trial can be carried out to provide valuable evidence for the oncologic safety of LTG for the treatment of AGC.

Cyclin-Dependent Kinase 5 Decreases in Gastric Cancer and Its Nuclear Accumulation Suppresses Gastric Tumorigenesis

Purpose: As a cyclin-independent atypical CDK, the role of CDK5 in regulating cell proliferation in gastric cancer remains unknown. Experimental Design: Expression of CDK5 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was measured by Western blotting, immunohistochemistry, and real-time PCR. The subcellular translocation of CDK5 was monitored during gastric cancer cell proliferation. The role of nuclear CDK5 in gastric cancer tumorigenic proliferation and ex vivo xenografts was explored. Furthermore, by screening for compounds in the PubChem database that disrupt CDK5 association with its nuclear export facilitator, we identified a small molecular (NS-0011) that inhibits gastric cancer cell growth. Results: CDK5 level was significantly decreased in the majority of gastric tumor tissues, and the reduction of CDK5 correlated with the severity of gastric cancer based on tumor and lymph node metastasis and patient 5-year fatality rate. Nuclear localization of CDK5 was found to be significantly decreased in tumor tissues and gastric cancer cell lines, whereas exogenously expression of nucleus-targeted CDK5 inhibited the proliferation and xenograft implantation of gastric cancer cells. Treatment with the small molecule NS-0011, which increases CDK5 accumulation in the nucleus, suppressed both cancer cell proliferation and xenograft tumorigenesis. Conclusions: Our results suggest that low CDK5 expression is associated with poor overall survival in patients with gastric cancer, and nuclear accumulation of CDK5 inhibits the proliferation and tumorigenicity of human gastric cancer cells. Clin Cancer Res; 21(6); 1419–28. ©2015 AACR.

Laparoscopic spleen-preserving splenic hilar lymphadenectomy in 108 consecutive patients with upper gastric cancer.

AIM To evaluate the feasibility and short-term efficacy of laparoscopic spleen-preserving splenic hilar (No. 10) lymphadenectomy to treat advanced upper gastric cancer (AUGC). METHODS Between January and December 2012, 108 laparoscopic spleen-preserving No. 10 lymphadenectomy along with total gastrectomy with routine D2 lymphadenectomy were performed consecutively at our hospital to treat clinical T2-3 (cT2-3) upper gastric cancers. The preoperative clinical T stage was cT2 in 36 patients and cT3 in 72 patients. A prospectively designed database tracked the 108 patients, including the completeness of their medical records and the adequacy of follow-up. Patient clinicopathological characteristics, intraoperative and postoperative surgical outcomes, morbidity and mortality, lymph node (LN) dissection, and postoperative follow-up were analysed retrospectively. RESULTS Laparoscopic spleen-preserving No. 10 lymphadenectomy was successful in all 108 patients. The mean operation time was 169.3 ± 27.1 min, and the mean No. 10 lymphadenectomy time was 20.0 ± 5.7 min. The mean total blood loss was 46.2 ± 11.3 mL, and the mean blood loss from No. 10 lymphadenectomy was 14.3 ± 3.8 mL. The mean postoperative hospital stay was 11.9 ± 6.0 d. The intraoperative and postoperative morbidity rates were 3.7% and 12.0%, respectively; however, there was no postoperative mortality. A mean of 44.4 ± 17.6 LNs were retrieved from each specimen, including 3.0 ± 2.4 No. 10 LNs. Three patients (2.8%) with cT3 cancer had LN metastasis of the splenic hilus, including two patients with pathological T3 (pT3) and one patient with pathological T4a (pT4a) tumours, all located in the greater curvature. No splenic hilar LNs metastasis was evident in the patients with pT1 and pT2 tumours. At a median follow-up time of 18 mo (range, 12 to 23 mo), all patients were alive and none had experienced recurrent or metastatic disease. CONCLUSION Laparoscopic spleen-preserving No. 10 lymphadenectomy is feasible and effective to treat AUGC. Routine No. 10 lymphadenectomy may be unnecessary for AUGC without serosa invasion, unless T3 tumours are located in the greater curvature.

Prognostic analysis of gastric gastrointestinal stromal tumor with synchronous gastric cancer.

BackgroundMany patients with gastric gastrointestinal stromal tumor (GIST) and synchronous gastric cancer have been described, most in single case studies. We retrospectively investigated the clinicopathologic features and prognostic effects of gastric GIST in patients with synchronous gastric cancer.MethodsThe study enrolled 170 patients with gastric GIST, who had undergone complete surgical resection (R0) from January 2000 to December 2011. Forty-two patients had synchronous gastric cancer (CA Group), whereas 128 did not (Non-CA Group). The clinicopathologic features and potential prognostic factors in the two groups were compared.ResultsPatients in the CA Group had more obvious symptoms, but a lower rate of preoperative diagnosis of gastric GIST (P <0.05). The two groups differed significantly in gender, age, greatest tumor diameter, risk stratification, tumor-associated ulcers, and CD117 and CD34 expression (P <0.05 each). Univariate analysis showed that age, risk stratification, postoperative oral imatinib and synchronous gastric cancer were predictive factors of survival (P <0.05). Cox regression analysis showed that risk stratification, postoperative oral imatinib and synchronous gastric cancer were independent predictors of survival (P <0.05). Stratified analysis showed that the 5-year overall survival rate was lower in patients with synchronous gastric cancer than in those without synchronous gastric cancer.ConclusionsGastric GIST with synchronous gastric cancer had a lower rate of preoperative diagnosis, with correct diagnosis often missed. Survival, however, depended primarily on the gastric cancer.

A Modified Delta-Shaped Gastroduodenostomy in Totally Laparoscopic Distal Gastrectomy for Gastric Cancer: A Safe and Feasible Technique

Background The present study introduced a modified delta-shaped gastroduodenostomy (DSG) technique and assessed the safety, feasibility and clinical results of this procedure in patients undergoing totally laparoscopic distal gastrectomy (TLDG) for gastric cancer (GC). Materials and Methods A total of 102 patients with distal GC undergoing TLDG with modified DSG between January 2013 and December 2013 were enrolled. A retrospective study was performed using a prospectively maintained comprehensive database to evaluate the results of the procedure. Univariate and multivariate analyses were performed to estimate the predictive factors for postoperative morbidity. Results The mean operation time was 150.6±30.2 min, the mean anastomosis time was 12.2±4.2 min, the mean blood loss was 48.2±33.2 ml, and the mean times to first flatus, fluid diet, soft diet and postoperative hospital stay were 3.8±1.3 days, 5.0±1.0 days, 7.4±2.1 days and 12.0±6.5 days, respectively. Two patients with minor anastomotic leakage after surgery were managed conservatively; no patient experienced any complications around the anastomosis, such as anastomotic stricture or anastomotic hemorrhage. Univariate analysis showed that age, gastric cancer with hemorrhage and cardiovascular disease combined were significant factors that affected postoperative morbidity (P<0.05). Multivariate analysis found that gastric cancer with hemorrhage was the independent risk factor for the postoperative morbidity (P = 0.042). At a median follow-up of 7 months, no patients had died or experienced recurrent or metastatic disease. Conclusions The modified DSG was technically safe and feasible, with acceptable surgical outcomes, in patients undergoing TLDG for GC, and this procedure may be promising in these patients.

Impact of the number of dissected lymph nodes on survival for gastric cancer after distal subtotal gastrectomy.

Objectives. To investigate the prognostic impact of the number of dissected lymph nodes (LNs) in gastric cancer after curative distal gastrectomy. Methods. The survival of 634 patients who underwent curative distal gastrectomy from 1995 to 2004 was retrieved. Long-term surgical outcomes and associations between the number of dissected LNs and the 5-year survival rate were investigated. Results. The number of dissected LNs was one of the most important prognostic indicators. Among patients with comparable T category, the larger the number of dissected LNs was, the better the survival would be (P < 0.05). The linear regression showed that a significant survival improvement based on increasing retrieved LNs for stage II, III and IV (P < 0.05). A cut-point analysis yields the greatest variance of survival rate difference at the levels of 15 LNs (stage I), 25 LNs (stage II) and 30 LNs (stage III). Conclusion. The number of dissected LNs is an independent prognostic factor for gastric cancer. To improve the long-term survival of patients with gastric cancer, removing at least 15 LNs for stage I, 25 LNs for stage II, and 30 LNs for stage III patients during curative distal gastrectomy is recommended.