Long-Long Cao

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.

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.

A Scoring System to Predict the Risk of Postoperative Complications After Laparoscopic Gastrectomy for Gastric Cancer Based on a Large-Scale Retrospective Study

AbstractTo investigate the risk factors for postoperative complications following laparoscopic gastrectomy (LG) for gastric cancer and to use the risk factors to develop a predictive scoring system.Few studies have been designed to develop scoring systems to predict complications after LG for gastric cancer.We analyzed records of 2170 patients who underwent a LG for gastric cancer. A logistic regression model was used to identify the determinant variables and develop a predictive score.There were 2170 patients, of whom 299 (13.8%) developed overall complications and 78 (3.6%) developed major complications. A multivariate analysis showed the following adverse risk factors for overall complications: age ≥65 years, body mass index (BMI) ≥ 28 kg/m2, tumor with pyloric obstruction, tumor with bleeding, and intraoperative blood loss ≥75 mL; age ≥65 years, a Charlson comorbidity score ≥3, tumor with bleeding and intraoperative blood loss ≥75 mL were identified as independent risk factors for major complications. Based on these factors, the authors developed the following predictive score: low risk (no risk factors), intermediate risk (1 risk factor), and high risk (≥2 risk factors). The overall complication rates were 8.3%, 15.6%, and 29.9% for the low-, intermediate-, and high-risk categories, respectively (P < 0.001); the major complication rates in the 3 respective groups were 1.2%, 4.7%, and 10.0% (P < 0.001).This simple scoring system could accurately predict the risk of postoperative complications after LG for gastric cancer. The score might be helpful in the selection of risk-adapted interventions to improve surgical safety.

A novel predictive model based on preoperative blood neutrophil-to-lymphocyte ratio for survival prognosis in patients with gastric neuroendocrine neoplasms

Purpose Evaluate the predictive value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) on the clinical outcomes of patients with gastric neuroendocrine neoplasms (g-NENs) after radical surgery. Results The NLR was significantly higher in patients with g-NENs than in matched normal volunteers (P < 0.05). A higher blood NLR was not significantly associated with clinical characteristics (all P > 0.05). According to the multivariate analysis, the NLR was an independent prognostic factor of RFS and OS. Nomograms, including the NLR, Ki-67 index and lymph node ratio, had superior discriminative abilities to predict clinical outcomes. The recurrence rate was 37% (55/147). The median time to recurrence was 9 months; 48 (87%) patients experienced recurrence within the first 2 years. Both the NLR and Ki-67 index were correlated with liver metastases (both P < 0.05) and were also negatively correlated with recurrence time (both P < 0.05). Materials And Methods We enrolled 147 patients who were diagnosed with g-NENs and underwent radical surgery. Receiver operating characteristic curve analysis was used to identify the optimal value for blood NLR. Univariate and multivariate survival analysis were used to identify prognostic factors for g-NENs. A nomogram was adopted to predict RFS and OS after surgery. Conclusions As an independent prognostic factor for g-NENs, blood NLR can improve the predictability of RFS and OS. We recommend that g-NEN patients with a high blood NLR or high Ki-67 index undergo surveillance during the first month and then every 3 months for 2 years post-surgery.

Prognostic Value of Tumor Size in Patients with Remnant Gastric Cancer: Is the Seventh UICC Stage Sufficient for Predicting Prognosis?

Background The 7th UICC N stage may be unsuitable for remnant gastric cancer (RGC) because the original disease and previous operation usually cause abnormal lymphatic drainage. However, the prognostic significance of the current TNM staging system in RGC has not been studied. Methods Prospective data from 153 RGC patients who underwent curative gastrectomy from Jan 1995 to Aug 2009 were reviewed. All patients were classified according to tumor size (<3 cm as N0;>3&≤5 cm as N1;>5&≤7 cm as N2; and>7 cm as N3). The overall survival was estimated using the Kaplan-Meier method, and hazard ratios (HRs) were calculated using the Cox proportional hazard model. Results Tumor sizes ranged from 1.0 to 15.0 cm (median 5.0 cm). Tumor size, depth of invasion and lymph node (LN) metastasis were significant prognostic factors based on both the univariate and multivariate analyses (P<0.05). In the survival analysis, the seventh edition UICC-TNM classification provided a detailed classification; however, some subgroups of the UICC-TNM classification did not have significantly different survival rates. The combination of the seventh edition T classification and the suggested N classification, with ideal relative risk (RR) results and P value, was distinctive for subgrouping the survival rates except for the IA versus IB and II A versus IIB. A modified staging system based on tumor size, predicted survival more accurately than the conventional TNM staging system. Conclusions In RGCs, tumor size is an independent prognostic factor and a modified TNM system based on tumor size accurately predicts survival.

Preoperative lymphocyte-to-monocyte ratio as a strong predictor of survival and recurrence for gastric cancer after radical-intent surgery

Objectives To evaluate the predictive value of the preoperative lymphocyte-to-monocyte ratio (LMR) for the prognosis of patients with gastric cancer (GC) after radical-intent surgery. Methods We retrospectively analyzed 1,810 patients who underwent radical-intent gastrectomy for primary GC from December 2008 to December 2013. X-tile software was used to identify the optimal value for blood LMR. Nomograms were developed to predict overall survival (OS) and recurrence-free survival (RFS) after surgery. Results LMR was significantly lower in patients with GC than in matched normal volunteers (P<0.001). As shown by forest plots, the long-term outcomes were poorer in the low LMR group than in the high LMR group when considering subgroups separated by clinical characteristics. Cox regression analysis showed that LMR was an independent prognostic factor for OS (P<0.001) and RFS (P=0.001). Nomograms, combining LMR with age, T stage, and N stage, showed better discriminative abilities than the AJCC staging system did in predicting 5-year survival and recurrence from the time of surgery. The recurrence rate was 30.4% (550/1810) and was significantly higher in the low LMR group than in the high LMR group (P<0.05). The LMR was also closely correlated with liver and lymph node metastases (both P<0.05). Conclusion As an independent prognostic factor for GC, preoperative LMR can improve the predictability of individual survival and recurrence. Furthermore, because liver and lymph node metastases were more commonly observed in patients with low blood LMR before surgery, these patients should be closely followed after the operation.OBJECTIVES To evaluate the predictive value of the preoperative lymphocyte-to-monocyte ratio (LMR) for the prognosis of patients with gastric cancer (GC) after radical-intent surgery. METHODS We retrospectively analyzed 1,810 patients who underwent radical-intent gastrectomy for primary GC from December 2008 to December 2013. X-tile software was used to identify the optimal value for blood LMR. Nomograms were developed to predict overall survival (OS) and recurrence-free survival (RFS) after surgery. RESULTS LMR was significantly lower in patients with GC than in matched normal volunteers (P<0.001). As shown by forest plots, the long-term outcomes were poorer in the low LMR group than in the high LMR group when considering subgroups separated by clinical characteristics. Cox regression analysis showed that LMR was an independent prognostic factor for OS (P<0.001) and RFS (P=0.001). Nomograms, combining LMR with age, T stage, and N stage, showed better discriminative abilities than the AJCC staging system did in predicting 5-year survival and recurrence from the time of surgery. The recurrence rate was 30.4% (550/1810) and was significantly higher in the low LMR group than in the high LMR group (P<0.05). The LMR was also closely correlated with liver and lymph node metastases (both P<0.05). CONCLUSION As an independent prognostic factor for GC, preoperative LMR can improve the predictability of individual survival and recurrence. Furthermore, because liver and lymph node metastases were more commonly observed in patients with low blood LMR before surgery, these patients should be closely followed after the operation.

CDK5RAP3 acts as a tumor suppressor in gastric cancer through inhibition of β-catenin signaling.

CDK5RAP3 was isolated as a binding protein of the Cdk5 activator p35. Although CDK5RAP3 has been implicated in cancer progression, its expression and function have not been investigated in gastric cancer. Our study demonstrated that the mRNA and protein levels of CDK5RAP3 were markedly decreased in gastric tumor tissues when compared with respective adjacent non-tumor tissues. CDK5RAP3 in gastric cancer cells significantly reduced cell proliferation, migration, invasion and tumor xenograft growth through inhibition of β-catenin. Secondly, CDK5RAP3 was found to suppress the phosphorylation of GSK-3β (Ser9), leading to the phosphorylation (Ser37/Thr41) and subsequent degradation of β-catenin. Lastly, the prognostic value of CDK5RAP3 for overall survival was found to be dependent on β-catenin cytoplasm/nucleus localization in human gastric cancer samples. Collectively, our results demonstrated that CDK5RAP3 negatively regulates the β-catenin signaling pathway by repressing GSK-3β phosphorylation and could be a potential therapeutic target for gastric cancer.

Anatomy and influence of the splenic artery in laparoscopic spleen-preserving splenic lymphadenectomy

AIM To investigate the splenic hilar vascular anatomy and the influence of splenic artery (SpA) type in laparoscopic total gastrectomy with spleen-preserving splenic lymphadenectomy (LTGSPL). METHODS The clinical anatomy data of 317 patients with upper- or middle-third gastric cancer who underwent LTGSPL in our hospital from January 2011 to December 2013 were collected. The patients were divided into two groups (concentrated group vs distributed group) according to the distance between the splenic arterys furcation and the splenic hilar region. Then, the anatomical layout, clinicopathologic characteristics, intraoperative variables, and postoperative variables were compared between the two groups. RESULTS There were 205 patients with a concentrated type (64.7%) and 112 patients with a distributed type (35.3%) SpA. There were 22 patients (6.9%) with a single branch of the splenic lobar vessels, 250 (78.9%) with 2 branches, 43 (13.6%) with 3 branches, and 2 patients (0.6%) with multiple branches. Eighty seven patients (27.4%) had type I splenic artery trunk, 211 (66.6%) had type II, 13 (4.1%) had type III, and 6 (1.9%) had type IV. The mean splenic hilar lymphadenectomy time (23.15 ± 8.02 vs 26.21 ± 8.84 min; P = 0.002), mean blood loss resulting from splenic hilar lymphadenectomy (14.78 ± 11.09 vs 17.37 ± 10.62 mL; P = 0.044), and number of vascular clamps used at the splenic hilum (9.64 ± 2.88 vs 10.40 ± 3.57; P = 0.040) were significantly lower in the concentrated group than in the distributed group. However, the mean total surgical time, mean total blood loss, and the mean number of harvested splenic hilar lymph nodes were similar in both groups (P > 0.05 for each comparison). There were also no significant differences in clinicopathological and postoperative characteristics between the groups (P > 0.05). CONCLUSION It is of value for surgeons to know the splenic hilar vascular anatomy when performing LTGSPL. Patients with concentrated type SpA may be optimal patients for training new surgeons.

The Impact of Confluence Types of the Right Gastroepiploic Vein on No. 6 Lymphadenectomy During Laparoscopic Radical Gastrectomy

AbstractThis study investigated anatomical variations in the confluence types of the right gastroepiploic vein (RGEV) to improve knowledge regarding no. 6 lymphadenectomy for laparoscopic gastrectomy.The RGEV drainage patterns of 144 patients who were diagnosed with gastric cancer and underwent laparoscopic distal gastrectomy at our department from July 2010 to June 2011 were prospectively collected and retrospectively analyzed, and we compared the impact of different drainage patterns on no. 6 lymphadenectomy.The RGEV confluence types were classified into 6 categories in this study. Types I, II, and III, which were observed in 53 (36.8%), 27 (18.8%), and 21 (14.6%) cases, respectively, were the most frequently found during gastrectomy. All 3 of these types included a gastropancreatic trunk and were defined as the gastropancreatic group (GP group). In addition, 15 cases (10.4%) were categorized as type IV, 19 (13.2%) were categorized as type V, and 9 (6.3%) were categorized as type VI. These 3 types, which could form a gastrocolic trunk, were defined as the gastrocolic group (GC group). No significant differences were found with respect to the clinicopathological characteristics, postoperative morbidity, perioperative mortality, and 3-year overall survival rates after surgery between the 2 groups (all P > 0.05). However, the mean no. 6 lymph node (No. 6 LN) dissection time, the mean blood loss due to No. 6 LN dissection and the rate of infrapyloric vascular injury were significantly increased in the GC group compared with the GP group (all P < 0.05).The RGEV exhibits 6 types of drainage patterns, and the division points of this vein during laparoscopic gastrectomy depend on the different drainage patterns. For types IV, V, and VI, the surgeon should carefully vascularize and divide the RGEV above its confluences during surgery.

The effectiveness of the 8th American Joint Committee on Cancer TNM classification in the prognosis evaluation of gastric cancer patients: A comparative study between the 7th and 8th editions

BACKGROUND The 8th edition of the AJCC TNM staging system for gastric cancer was released in 2016 and included major revisions, especially of stage III. PATIENTS AND METHODS Data from 3281 patients with GC who underwent R0 resection between December 2006 and November 2014 were reviewed. Of them, 1579 patients with stage III according to the seventh edition were analyzed and the 7th and 8th TNM classifications were compared. RESULTS The most important tumor stages change observed in stage III GC. For stage III patients, the median number of lymph nodes (LNs) resected in stage III patients was 33 (range 5-112), and the optimal cut-off value for the number of LNs resected was 30. Although the 7th edition classification had higher c-index, linear trend and likelihood ratio χ2 scores, and smaller AIC values compared with those for the 8th edition, which represented the optimum prognostic stratification, however, the differences between 7th and 8th edition seems to be not statistically significant, and AIC demonstrates similar trend as well. Further subgroup analysis found that the 8th staging system generated the marginally better prognostic stratification only when LNs removed ≥30. CONCLUSION The 8th TNM classification may provide better accuracy than 7th edition in predicting the prognosis of stage III GC after R0 resection with LNs harvested ≥30. However, further research in an external validation setting is warranted.