[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

[Establishment of a nomogram prediction model using common preoperative indicators for early weight loss after laparoscopic sleeve gastrectomy].

Objectives: To construct a nomogram prediction model using common preoperative indicators for early weight loss (EWL) 1 year after laparoscopic sleeve gastrectomy (LSG). Methods: Relevant data of obese patients who had undergone LSG from January 2015 to May 2022 in Fujian Medical University Union Hospital and Quanzhou First Hospital Affiliated Fujian Medical University were analyzed. Patients with a history of major abdominal surgery, severe gastroesophageal reflux disease, pregnancy within 1 year after surgery, or who were lost to follow-up were excluded, resulting in a total of 200 patients in the study (190 from Fujian Medical University Union Hospital and 10 from Quanzhou First Hospital Affiliated Fujian Medical University). The participants were 51 men and 149 women of a mean age 29.9±8.2 years and a body mass index (BMI) 38.7±6.5 kg/m2. All patients in this group underwent standardized LSG procedure. Achieving ideal weight (BMI≤25 kg/m2) 1 year after LSG was defined as goal of EWL. Logistic regression analyses were performed to identify factors that independently influenced EWL. These factors were incorporated into the nomogram model. Receiver operating characteristic (ROC) curves (the larger the area under the curve [AUC], the better the predictive ability and accuracy of the model), likelihood ratio test (higher likelihood ratio indicates greater model homogeneity), decision curve analysis (higher net benefit indicates a better model), Akaike information criterion (AIC; smaller AIC indicates a better model), and Bayesian information criterion (BIC; smaller BIC indicates a better model) were used to validate the predictive ability of the column line diagram model. Results: In this study of 200 obese patients who underwent LSG surgery, 136 achieved EWL goal, whereas the remaining 64 did not. The rate of EWL goal achievement of the entire group was 68.0%. Compared with patients who did not achieve EWL goal, those who did had lower BMI, alanine transaminase, aspartate transaminase, triglycerides, and higher cholesterol. Additionally, the proportion of female was higher and the proportions of patients with fatty liver and hypertension lower in those who achieved EWL goal (all P<0.05). Univariate and multivariate logistic regression analysis revealed that preoperative BMI (OR=0.852, 95%CI: 0.796-0.912, P<0.001), alanine transaminase (OR=0.992, 95%CI: 0.985-0.999, P=0.024), presence of fatty liver (OR=0.185, 95%CI: 0.038-0.887, P=0.035) and hypertension (OR=0.374, 95%CI: 0.144-0.969, P=0.043) were independently associated with failure to achieve EWL goal. Cholesterol (OR=1.428, 95%CI: 1.052-1.939, P=0.022) was independently associated with achieving EWL goal. We used the above variables to establish an EWL nomogram model. ROC analysis, the likelihood ratio test, decision curve analysis, and AIC all revealed that the predictive value of the model was better than that of BMI alone (nomogram model vs. BMI: area under the curve 0.840 vs. 0.798, P=0.047; likelihood ratio: 58.785 vs. 36.565, AIC: 193.066 vs. 207.063, BIC: 212.856 vs. 213.660). Conclusion: Our predictive model is more accurate in predicting EWL after LSG compared with using BMI.

[Feasibility of a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection for middle and low rectal cancer].

Objective: To explore the feasibility and value of performing a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection (LLND) for middle and low rectal cancer. Methods: This was a retrospective review. The study cohort comprised patients who met the diagnostic criteria for rectal cancer according to the Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer, had a short lymph node diameter of >5 mm on the lateral side within the 15 days before surgery, were evaluated as feasible candidates for laparoscopic total mesorectal excision+LLND surgery, had been diagnosed with low or intermediate level rectal cancer, and whose tumor was less than 8 cm away from the anal verge according to pathological examination of the operative specimen. Patients with a history of other malignant tumors of the abdomen or with incomplete follow-up data were excluded. Forty-two patients with middle and low rectal cancer who had undergone lateral lymph node dissection in diagnosis and treatment center of Gastrointestinal Cancer of Guangdong Hospital of Chinese Medicine from Jan.2018 to Dec.2022 were enrolled. There were 24 men (57.1%) and 18 women (42.9%) aged 58.4±11.8 years and the median BMI was 22.5 (19.3-24.1) kg/m2. The main point of the three-sided encapsulation procedure is to expand the external side medial to the external iliac artery and vein, narrowing the range of exterior side dissection. The anterior-medial side is designed to expand the vesical fascia to define the range of anterior-medial side extension. The internal side is fully extended to the ureterohypogastric nerve fascia; the distal point of the caudal extension reaches the level of the Alcock canal and the bottom reaches the piriformis, enabling dissection of the obturator nerve and No.283 lymph nodes. No.263D lymph nodes are dissected by exposing the internal iliac artery and its branches, dissecting the group No.263P lymph nodes, and severing the inferior vesical artery. Finally, the lateral lymphatic tissue is completely resected. Relevant variables were recorded, including the number of lateral lymph nodes detected, the rate of lymph node metastasis, operation duration, intraoperative blood loss, postoperative complications, postoperative hospital stay, and 3-year overall survival rate. Results: Laparoscopic surgery was successfully completed in all patients with no conversions to open surgery and no intraoperative complications. Twenty-seven (64.3%) of the study patients underwent left-sided LLND, 10 (23.8%) right-sided LLND, and five (11.9%) bilateral LLND, with lymph nodes cleared on both sides. All patients' lymph nodes were examined pathologically. A median of 17.0 (11.7, 26.0) lymph nodes was detected, the median of lateral lymph nodes being 5.0 (2.0, 10.2). The median operation time was 254.5 (199.0, 325.2) minutes. The median intra-operative blood loss was 50.0 (30.0, 100.0) mL. All patients were diagnosed with adenocarcinoma by pathological examination of the operative specimen. Two patients developed postoperative intestinal obstruction, one lymphatic leakage, and one a perineal incision infection. There were no cases of anastomotic leakage. The median postoperative hospital stay was 6.0 (5.0, 7.0) days and the median follow-up time 23.5 (9.0, 36.7) months. During follow-up, three patients (7.1%) died of tumor recurrence and metastasis. Two (4.8%) experienced mild urinary dysfunction, and one (2.4%) had moderate postoperative erectile dysfunction. One patient (2.4%) was found to have prostate and lung metastases 3 month after surgery. The 3-year overall survival rate was 74.4%. Conclusions: Three sided encapsulation is a safe and feasible procedure for LLND, achieving accurate and complete clearance of lateral lymphatic tissue.

[Effect of splenic hilar lymphadenectomy on locally advanced Siewert type â ¡ and â ¢ adenocarcinoma of esophagogastric junction with a tumor diameter ≥4 cm: a five-year survival analysis].

Objective: To examine the long term outcome of splenic hilar lymphadenectomy (SHL) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) with a tumor diameter ≥4 cm. Methods: A total of 489 locally advanced Siewert type Ⅱ and Ⅲ AEG patients with a tumor diameter ≥4 cm who underwent radical resection from January 2010 to April 2016 were included. There were 383 males and 106 females. There were 225 patients aged≥65 years and 264 patients aged <65 years. SHL was conducted in 270 patients(SHL group). Wilcoxon rank-sum test or χ2 test were conducted for inter-group comparison. Cox proportional hazard regression was used to analyze the long term outcome of SHL and the prognosis factors of overall survival. Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results: Followed-up to April 2021,the median follow-up time was 78.0 months (range: 74.0 to 85.0 months), the follow-up rate was 95.5%(467/489). The splenic hilar lymphnode metastasis rate of the SHL group was 12.6% (34/270). Younger patients (<65 years old), less complications, higher proportion of patients received adjuvant chemotherapy were demonstrated in the SHL group (χ2: 5.644 to 6.744, all P<0.05). Multivariate analysis showed that SHL was the independent prognosis factor of overall survival for patients with Siewert type Ⅱ and Ⅲ AEG and a tumor diameter≥4 cm (HR=0.68, 95%CI: 0.52 to 0.88, P=0.004) along with preoperative CA19-9, pathological T stage, pathological N stage, adjuvant chemotherapy and postoperative complication. Further subgroup analysis demonstrated that the SHL group had better 5-year overall survival than non-SHL group (62.4% vs. 39.2%, χ2=17.983, P=0.006) in Siewert type Ⅲ AEG rather than in Siewert type Ⅱ AEG(57.3% vs. 53.7%, χ2=3.031, P=0.805). Conclusion: In experienced center, splenic hilar lymphadenectomy can improve the prognosis of Siewert type Ⅲ AEG with a tumor diameter ≥4 cm.

[Quality of life after totally laparoscopic versus laparoscopic-assisted total gastrectomy: a retrospective cohort study with propensity score matching].

Objective: To evaluate the postoperative quality of life in patients after totally laparoscopic total gastrectomy (TLTG). Methods: A retrospective cohort study based on propensity score matching was performed. Clinical and follow-up data of patients who underwent laparoscopic radical gastrectomy at Union Hospital of Fujian Medical University from January 2014 to May 2015 were collected. Case indusion criteria: (1) primary gastric cancer confirmed by postoperative pathology; (2) receiving TLTG or laparoscopic-assisted total gastrectomy (LATG);(3) R0 resection; (4) completing follow-up for 12 months and complete follow-up data. Exclusion criteria: (1) gastric stump cancer; (2) concurrent tumor; (3) distal metastasis found during operation; (4) history of upper abdominal operation. According to surgical procedures, patients were divided into the LATG group (1076 cases) and the TLTG group (106 cases). To eliminate potential bias in baseline data between the two groups, the propensity score was calculated using a logistic regression model with the following covariates, including age, sex, body mass index, American Society of Anesthesiologists score, tumor location, tumor size, pathology type, and stage. The two groups were matched using a 1:2 propensity assessment ratio and a caliper width of 0.01 standard deviation was specified. The primary outcomes were the quality of life of the two groups at 3, 6 and 12 months after gastrectomy, including physical symptoms and social function. Higher function score indicated better function, and higher symptom score presented worse symptoms. Quality of life score = (100 - somatic symptom scale score + social function scale score) / 2. The secondary outcomes were postoperative nutritional recovery and food tolerance at 3, 6 and 12 months after gastrectomy. The categorical variables were expressed as n(%), and compared using the χ2 test or Fisher exact test. The continuous variables conforming to the normal distribution were represented by Mean ± SD and compared with the paired t-test. Repeated measurement of variance was used to compare nutrition-related indicators within the group among pre-operation, postoperative 1, 3, 6, 12 months. Results: After PSM, there were no significant differences in clinicopathological baseline data between the TLTG group (n=104) and the LATG group (n=208) (all P>0.05). The physical symptoms scores in the TLTG group before operation and 3, 6 and 12 months after operation were 8.6±5.8, 15.5±8.4, 10.1±5.9 and 6.1±2.4 respectively (F=43.493, P<0.001). In the LATG group, the above mentioned scores were 9.7±6.9, 23.7±10.4, 13.3±8.3 and 8.5±4.2 respectively (F=112.588, P<0.001). Compared with the LATG group, the symptom scores in the TLTG group were lower at 3 and 6 months after operation, and the differences were statistically significant (t=-3.653, P<0.001; t=-2.513, P=0.012). At 12 months after operation, although the physical symptom score in the TLTG group was also lower than that in LATG group, the difference was not statistically significant (t=-1.487, P=0.138). The social function scores in the TLTG group before operation and 3, 6 and 12 months after operation were 90.3±8.9, 77.5±14.3, 87.4±10.3 and 91.7±6.7 respectively (F=28.524, P<0.001). In the LATG group, the above mentioned scores were 92.5±6.3, 68.5±16.8, 79.8±14.7 and 84.7±11.1 respectively (F=57.975, P<0.001). Compared with the LATG group, the social function scores of patients in the LATG group were higher at 3, 6 and 12 months after operation (t=3.543, P<0.001; t=3.216, P=0.001; t=2.235, P=0.026). The total scores of quality of life at 3, 6 and 12 months after operation in the TLTG group were 81.0±15.6, 88.3±8.1 and 93.3±9.1 respectively, and the above mentioned scores in the LATG group were 72.4±13.6, 83.3±11.5 and 88.1±7.7 respectively, whose differences at corresponding time point were all significant between the two groups (all P<0.05). The change of total body mass[(-8.4±1.4)% vs. (-13.2±1.6)%, t=2.273, P=0.024], serum albumin[(-5.1±0.7)% vs. (-7.4±0.8)%,t=2.095, P=0.037], meal quantity [(-15.6±4.7)% vs. (-24.1±6.0)%, t=2.885, P=0.004] and meal times [(20.8±7.1)% vs. (30.6±11.5)%, t=3.043, P<0.001] in the TLTG group were significantly lower than those in the LATG group one year after operation (all P<0.05). At 3, 6 and 12 months after operation, the diet proportions of solid and soft food in the TLTG group were higher than those in the LATG group (all P<0.05). Conclusions: Compared with LATG, patients with gastric cancer undergoing TLTG have better health-related quality of life and faster recovery of nutrition.

[Establishment of a mutation prediction model for evaluating the efficacy of immunotherapy in renal carcinoma].

OBJECTIVE: To establish a mutation prediction model for efficacy assessment, the genomic sequencing data of renal cancer patients from the MSKCC (Memorial Sloan Kettering Cancer Center) pan-cancer immunotherapy cohort was used. METHODS: The genomic sequencing data of 121 clear cell renal cell carcinoma patients treated with immune checkpoint inhibitors (ICI) in the MSKCC pan-cancer immunotherapy cohort were obtained from cBioPortal database (http://www.cbioportal.org/) and they were analyzed by univariate and multivariate Cox regression analysis to identify mutated genes associated with ICI treatment efficacy, and we constructed a comprehensive prediction model for drug efficacy of ICI based on mutated genes using nomogram. Survival analysis and time-dependent receiver operator characteristic curves were performed to assess the prognostic value of the model. Transcriptome and genomic sequencing data of 538 renal cell carcinoma patients were obtained from the TCGA database (https://portal.gdc.cancer.gov/). Gene set enrichment analysis was used to identify the potential functions of the mutated genes enrolled in the nomogram. RESULTS: We used multivariate Cox regression analysis and identified mutations in PBRM1 and ARID1A were associated with treatment outcomes in the patients with renal cancer in the MSKCC pan-cancer immunotherapy cohort. Based on this, we established an efficacy prediction model including age, gender, treatment type, tumor mutational burden (TMB), PBRM1 and ARID1A mutation status (HR=4.33, 95%CI: 1.42-13.23, P=0.01, 1-year survival AUC=0.700, 2-year survival AUC=0.825, 3-year survival AUC=0.776). The validation (HR=2.72, 95%CI: 1.12-6.64, P=0.027, 1-year survival AUC=0.694, 2-year survival AUC=0.709, 3-year survival AUC=0.609) and combination (HR=2.20, 95%CI: 1.14-4.26, P=0.019, 1-year survival AUC=0.613, 2-year survival AUC=0.687, 3-year survival AUC=0.526) sets confirmed these results. Gene set enrichment analysis indicated that PBRM1 was involved in positive regulation of epithelial cell differentiation, regulation of the T cell differentiation and regulation of humoral immune response. In addition, ARID1A was involved in regulation of the T cell activation, positive regulation of T cell mediated cyto-toxicity and positive regulation of immune effector process. CONCLUSION: PBRM1 and ARID1A mutations can be used as potential biomarkers for the evaluation of renal cancer immunotherapy efficacy. The efficacy prediction model established based on the mutation status of the above two genes can be used to screen renal cancer patients who are more suitable for ICI immunotherapy.

[Establishment of artificial neural network model for predicting lymph node metastasis in patients with stage â ¡-â ¢ gastric cancer].

Objective: To establish a neural network model for predicting lymph node metastasis in patients with stage II-III gastric cancer. Methods: Case inclusion criteria: (1) gastric adenocarcinoma diagnosed by pathology as stage II-III (the 8th edition of AJCC staging); (2) no distant metastasis of liver, lung and abdominal cavity in preoperative chest film, abdominal ultrasound and upper abdominal CT; (3) undergoing R0 resection. Case exclusion criteria: (1) receiving preoperative neoadjuvant chemotherapy or radiotherapy; (2) incomplete clinical data; (3) gastric stump cancer.Clinicopathological data of 1231 patients with stage II-III gastric cancer who underwent radical surgery at the Fujian Medical University Union Hospital from January 2010 to August 2014 were retrospectively analyzed. A total of 1035 patients with lymph node metastasis were confirmed after operation, and 196 patients had no lymph node metastasis. According to the postoperative pathologic staging. 416 patients (33.8%) were stage Ⅱ and 815 patients (66.2%) were stage III. Patients were randomly divided into training group (861/1231, 69.9%) and validation group (370/1231, 30.1%) to establish an artificial neural network model (N+-ANN) for the prediction of lymph node metastasis. Firstly, the Logistic univariate analysis method was used to retrospectively analyze the case samples of the training group, screen the variables affecting lymph node metastasis, determine the variable items of the input point of the artificial neural network, and then the multi-layer perceptron (MLP) to train N+-ANN. The input layer of N+-ANN was composed of the variables screened by Logistic univariate analysis. Artificial intelligence analyzed the status of lymph node metastasis according to the input data and compared it with the real value. The accuracy of the model was evaluated by drawing the receiver operating characteristic (ROC) curve and obtaining the area under the curve (AUC). The ability of N+-ANN was evaluated by sensitivity, specificity, positive predictive values, negative predictive values, and AUC values. Results: There were no significant differences in baseline data between the training group and validation group (all P>0.05). Univariate analysis of the training group showed that preoperative platelet to lymphocyte ratio (PLR), preoperative systemic immune inflammation index (SII), tumor size, clinical N (cN) stage were closely related to postoperative lymph node metastasis. The N+-ANN was constructed based on the above variables as the input layer variables. In the training group, the accuracy of N+-ANN for predicting postoperative lymph node metastasis was 88.4% (761/861), the sensitivity was 98.9% (717/725), the specificity was 32.4% (44/136), the positive predictive value was 88.6% (717/809), the negative predictive value was 84.6% (44/52), and the AUC value was 0.748 (95%CI: 0.717-0.776). In the validation group, N+-ANN had a prediction accuracy of 88.4% (327/370) with a sensitivity of 99.7% (309/310), specificity of 30.0% (18/60), positive predictive value of 88.0% (309/351), negative predictive value of 94.7% (18/19), and an AUC of 0.717 (95%CI:0.668-0.763). According to the individualized lymph node metastasis probability output by N+-ANN, the cut-off values of 0-50%, >50%-75%, >75%-90% and >90%-100% were applied and patients were divided into N0 group, N1 group, N2 group and N3 group. The overall prediction accuracy of N+-ANN for pN staging in the training group and the validation group was 53.7% and 54.1% respectively, while the overall prediction accuracy of cN staging for pN staging in the training group and the validation group was 30.1% and 33.2% respectively, indicating that N+-ANN had a better prediction than cN stage. Conclusions: The N+-ANN constructed in this study can accurately predict postoperative lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer. The N+-ANN based on individualized lymph node metastasis probability has better accurate prediction for pN staging as compared to cN staging.

[Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019].

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

[Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019].

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

LncRNA GAS5 induces chondrocyte apoptosis by down-regulating miR-137.

OBJECTIVE: Long non-coding RNA (lncRNA) participates in the pathogenesis of human knee osteoarthritis (KOA). Growth arrest specificity 5 (GAS5) is a member lncRNA, but its role in pathological regulation of KOA is still unknown. This study aims to explore the mechanism of GAS5 in KOA on chondrocyte apoptosis and other pathological processes. PATIENTS AND METHODS: The serum and cartilage tissues were collected from 35 patients with KOA and 30 patients with traumatic amputation admitted to our hospital from April 2016 to April 2020. The expressions of GAS5 and miR-137 were detected and analyzed. Chondrocytes were extracted from cartilage tissues of KOA patients, and the genes were regulated by transfection. Then, the cells were detected, including apoptosis, apoptosis-related proteins (caspase-3, Bax/Bcl-2), and proliferation. The targeting relationship between GAS5 and miR-137 was verified. RESULTS: GAS5 was up-regulated in serum and cartilage tissues of KOA patients, and down-regulation of GAS5 could inhibit the apoptosis process of chondrocytes and promote proliferation. MiR-137 was down-regulated in samples of KOA patients and was negatively regulated by GAS5. GAS5 induced apoptosis of chondrocytes and inhibited its proliferation through targeted down-regulating miR-137. CONCLUSIONS: GAS5 is up-regulated in KOA serum, cartilage tissues and cells, and can induce chondrocyte apoptosis through down-regulating miR-137.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

Development and validation of a staging system for gastric adenocarcinoma after neoadjuvant chemotherapy and gastrectomy with D2 lymphadenectomy.

BACKGROUND: Neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy is commonly used for patients with locally advanced gastric adenocarcinoma. The eighth AJCC ypTNM staging system was validated based on patients undergoing more limited lymphadenectomy (less than D2). The aim of this study was to develop a system for accurate staging of patients with locally advanced gastric adenocarcinoma who receive neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy. METHODS: A modified system of ypTNM was developed, based on overall survival (OS) of patients receiving neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy at Memorial Sloan Kettering Cancer Center, and validated using data from an international cohort of patients who had similar treatment. RESULTS: Of 325 patients in the derivation cohort, 33 (10·2 per cent) had ypT0 N0/+ tumours, which are not classifiable under the AJCC system. The 5-year OS rate for modified ypTNM stages I, II, IIIA and IIIB was 89, 71, 42·3 and 10 per cent respectively, compared with 82, 65·2 and 24·1 for AJCC stages I, II and III respectively. The concordance index (0·730 versus 0·709), estimated area under the curve (0·765 versus 0·740) and time-dependent receiver operating characteristic (ROC) curve throughout the observation period were all superior for modified ypTNM staging. For the validation cohort of 186 patients, the modified system was again better at separating patients into prognostic groups for OS. CONCLUSION: The modified ypTNM staging system improves the accuracy of OS prediction for patients treated with neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy.

Investigation on the properties of borate bonding agents: Ti6Al4V-porcelain bonding, chemical durability and preliminary cytotoxicity.

The purpose of this study was to investigate the properties of the borate bonding agents (BBAS) including chemical durability, biocompatibility and bonding characteristics of porcelain to Ti6Al4V. The bond strength was performed by the three-point bending test. And the chemical durability and ion release of BBAS were tested by chemical soaking and inductively coupled plasma optical emission spectrometry (ICP-OES), respectively. Moreover, cytotoxicity was evaluated by cell viability assay and cell adhesion using human osteosarcoma cells (MG-63) and cell counter kit-8 (CCK-8) assay. To investigate the influences of composition and microstructure changes on all the properties mentioned above, the 11B and 27Al spectra and infrared spectra of BBAS were measured by solid-state nuclear magnetic resonance (SSNMR) and Fourier transform infrared spectroscopy (FTIR), respectively. Combined with all these properties of BBAS, the optimal addition proportion of Al2O3 into BBAS is 20 mol%. The relative contents of [BO3], [BO4], [AlO4], [AlO5] and [AlO6] have great influences on these properties of BBAS. BBAS, possessing excellent chemical durability, good biocompatibility and low ion release and being an effective way to improve the Ti6Al4V-porcelain bond strength, have significant clinical potentials in porcelain fused to metal restorations.

Prognostic significance of preoperative albumin-to-globulin ratio in patients with cholangiocarcinoma.

BACKGROUND: This study aimed to assess the prognostic value of the serum albumin to globulin ratio (AGR) in cholangiocarcinoma patients after surgery. METHODS: We retrospectively enrolled 123 cholangiocarcinoma patients who underwent surgical treatment between June 2003 and September2014 at the Third Affiliated Hospital of Sun Yat-sen University. Univariate and multivariate analyses using the Cox regression model were performed to determine the prognostic value of AGR. RESULTS: Univariate analysis suggested that AGR was a predictive factor for (overall survival) OS but not for recurrence free survival (RFS). After adjustment for other risk factors, multivariate analysis showed that AGR remained independently associated with OS. The optimal cut-off point for AGR was determined to be 1.44. Kaplan-Meier curves showed that there was a significantly lower mean survival time in the low AGR group compared to the high AGR group. A low AGR was found to be significantly associated with high alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin levels and an advanced American Joint Committee on Cancer TNM stage, but a low hemoglobin level. CONCLUSION: In summary, patients with higher AGRs have better outcomes than those with lower AGRs. Preoperative AGR can be a reliable marker for evaluating the prognosis of cholangiocarcinoma patients.

Development of a nomogram for predicting the risk of anastomotic leakage after a gastrectomy for gastric cancer.

AIMS: To investigate the incidence of and factors associated with anastomotic leakage (AL) following gastrectomy for gastric cancer. METHODS: We retrospectively analyzed 3632 patients who underwent a laparoscopic gastrectomy or open gastrectomy for gastric cancer. A logistic regression model was used to identify the determinant variables, and a nomogram for AL was developed. RESULTS: A total of 3632 patients were included in the study, 50 of whom (1.4%) developed AL. Postoperative deaths occurred in 6 (0.2%) patients with AL failure to rescue. Esophagojejunal AL (27/50) and Billroth I AL (20/50) were the most common types of AL. Gastrografin swallow was the main diagnostic method. The diagnosis was made a median of 9 days postoperatively. The median healing time for AL was 34.5 days. Of the 50 AL patients, 56% of patients could be managed nonsurgically, whereas 28% of patients required percutaneous radiologic drainage, 6% of patients were treated by endoscopy, and 10% of patients required a second surgery. A multivariate analysis showed the following adverse risk factors for AL: age ≥65 years, hemoglobin ≤8.0 g/dL and malnourishment. A multivariable model for AL showed a strong optimism-adjusted discrimination (concordance index, 0.675). The 5-year overall survival rates for patients without or with AL were 59.4% and 67.4%, respectively (p = 0.354). CONCLUSIONS: AL was infrequent but was more prevalent in patients with age ≥65 years, hemoglobin ≤8.0 g/dL and malnourishment. We created a novel nomogram that can provide individualized prediction of AL in patients after a gastrectomy for gastric cancer, which may help clinicians in making treatment decisions.

[Surgical outcomes after laparoscopy-assisted distal gastrectomy and open distal gastrectomy for patients with advanced gastric cancer: a case-control study using a propensity score method].

Objective: To investigate the surgical outcomes after the laparoscopy-assisted distal gastrectomy (LADG) for patients with advanced gastric cancer. Methods: The data of 213 patients who underwent LADG and 213 treated by open distal gastrectomy (ODG) were selected using the propensity score matching method from a prospectively constructed database of 641 patients who underwent radical distal gastrectomy between January 2005 and June 2012 in Department of Gastric Surgery, Fujian Medical University Union Hospital. The baseline characteristics and surgical outcomes were compared using a paired t-test or the Wilcoxon signed ranks test for continuous variables. The cumulative survival rates were compared using the Kaplan-Meier method and log-rank test. Results: Among all patients, there were significant differences in tumor location, digestive tract reconstruction, histologic type, pT stage, and pTNM stage between LADG and ODG group (P<0.05). After propensity score matching, patient distributions were closely balanced. There was no significant difference in clinicopathologic characteristics between the two groups (P>0.05). Regarding perioperative characteristics, the time to first flatus, and time to resumption of diet, did not differ between the two groups (P>0.05), while there were significant differences in the operation time (t=-11.28, P=0.000), blood loss (t=-5.674, P=0.000), number of dissected lymph nodes (t=4.727, P=0.000), and post-operative hospital stay (t=-2.193, P=0.038). LADG group has less morbidity than ODG group (χ2=4.777, P=0.029). Multivariate analysis revealed that the laparoscopic surgery (RR=0.392, P=0.009) was the protected factor for determining postoperative complications. There was no significant difference in the cumulative survival rate at total and each UICC stage between the two groups, either (P>0.05). Conclusion: LADG is an oncological safe minimally invasive procedure for advanced gastric cancer yields comparable oncological outcomes with ODG.

Evaluation of clinicopathological factors related to the prognosis of gastric neuroendocrine carcinoma.

BACKGROUND: Research on the clinicopathology and prognosis of gastric neuroendocrine carcinoma (GNEC) is rare, and a uniform standard for treatment has not been established. Therefore, we retrospectively analyzed the clinical data of 132 cases of GNEC to investigate the factors influencing prognosis. METHODS: A total of 132 patients diagnosed with GNEC at Fujian Medical University Union Hospital from January 2006 to December 2013 were enrolled. This study was performed to analyze the factors related to patient prognosis. RESULTS: In total, 58 men and 74 women whose ages ranged from 38 to 83 years old (62 ± 10) were enrolled. The 1- and 3-year survival rates for these patients were 83.9% and 47.6%, respectively. Of these patients, 100 underwent radical resection, 22 underwent palliative resection, and 10 received chemotherapy alone. The median survival times following radical resection, palliative resection and chemotherapy alone were 48, 20 and 12 months, respectively (P < 0.01). Univariate and multivariate survival analyses of patients who underwent radical resection showed that tumor size, N stage, Ki-67 labeling index, mitotic index and the application of postoperative adjuvant chemotherapy were independent factors affecting patient prognosis. The correlation analysis of the Ki-67 labeling index and mitotic index with prognosis showed that patient survival decreased significantly when the Ki-67 labeling index increased (P < 0.05). CONCLUSIONS: Patients who underwent radical resection had the best prognosis among GNEC. For these patients, tumor size, N stage, Ki-67 labeling index, mitotic index and the application of postoperative adjuvant chemotherapy were the clinicopathological factors significantly associated with patient prognosis.

Coadministration of VDR and RXR agonists synergistically alleviates atherosclerosis through inhibition of oxidative stress: An in vivo and in vitro study.

BACKGROUND AND AIMS: Diabetes contributes to atherosclerosis partially through induction of oxidative stress. Both vitamin D receptor (VDR) and retinoid X receptor (RXR) agonists exhibit anti-atherogenic effects. METHODS: We explored the effects of combination treatment with VDR and RXR agonists (represented by calcitriol and bexarotene, respectively) on atherosclerosis progression and the mechanisms involved, using a diabetes model of mice. The animals were intragastrically fed calcitriol (200 ng/kg, twice-a-week), bexarotene (10 mg/kg, once-daily) either alone or in combination for 12 weeks. RESULTS: VDR and RXR agonists delayed atherosclerosis progression independent of serum lipid and glucose levels, and significantly reduced the protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox and nuclear factor-kappa B (NF-κB) subunit p65, as well as plasma biomarkers of oxidative stress and inflammation. Combination therapy alleviated atherosclerosis and inhibited indexes of oxidative stress and inflammation to a greater extent than either monotherapy. In the in vitro study, naturally occurring VDR ligand 1α,25-dihydroxyvitamin D3 (1,25[OH]2D3) and RXR ligand 9-cis retinoic acid (9-cis-RA), both significantly inhibited high-glucose-induced endothelial cell apoptosis. Co-administration of VDR and RXR ligands produced synergistic protection against endothelial apoptosis by antagonizing the protein kinase C /NADPH oxidase/reactive oxygen species pathway. The inhibitory effects of 9-cis-RA on oxidative stress was attenuated when VDR was downregulated by VDR siRNA; however, downregulation of RXR by RXR siRNA imposed no influence on the effects of 1,25(OH)2D3. CONCLUSIONS: Combination treatment with VDR and RXR agonists synergistically alleviated diabetic atherosclerosis through inhibition of oxidative stress, and the preventive effects of RXR agonist may partially depend on VDR activation.

RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells.

An inflammatory response induced by high glucose is a cause of endothelial dysfunction in diabetes and is an important contributing link to atherosclerosis. Diabetes is an independent risk factor of atherosclerosis and activation of retinoid X receptor (RXR) has been shown to exert anti-atherogenic effects. In the present study, we examined the effects of the RXR ligands 9-cis-retinoic acid (9-cis-RA) and SR11237 on high glucose-induced inflammation in human umbilical endothelial vein endothelial cells (HUVECs) and explored the potential mechanism. Our results showed that the inflammation induced by high-glucose in HUVECs was mainly mediated by the activation of nuclear factor-B (NF- κB). High glucose-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were in comparison, significantly decreased by treatment with RXR. The effect of RXR agonists was mainly due to the inhibition of NF-κB activation. Using pharmacological inhibitors and siRNA, we confirmed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was an upstream activator of NF-κB. Furthermore, RXR agonists significantly inhibited high glucose-induced activation of NADPH oxidase and significantly decreased the production of reactive oxygen species (ROS). To explore whether the rapid inhibitory effects of RXR agonists were in fact mediated by RXR, we examined the effect of RXR downregulation by RXR siRNA. Our results showed that RXR siRNA largely abrogated the effects of RXR agonists, suggesting the requirement of RXR expression. Therefore, we have shown that RXR is involved in the regulation of NADPH oxidase- NF-κB signal pathway, as the RXR ligands antagonized the inflammatory response in HUVECs induced by high glucose.

Effect of negative lymph node count on survival for gastric cancer after curative distal gastrectomy.

AIMS: The aim of this study is to evaluate the long-term effect of negative lymph node (LN) counts on the prognosis after curative distal gastrectomy among gastric cancer patients. METHODS: The study enrolled 634 patients with gastric cancer, who had undergone curative resection (R0) with distal gastrectomy from 1995 to 2004. Long-term surgical outcomes and relationships between the negative LN count and the 5-year survival rate were investigated. RESULTS: The 5-year survival rate of the entire cohort was 57.6%. The number of metastasis negative LN was positively associated with the retrieved node according to the Pearson's correlation test (P < 0.001). Cox regression analysis showed the negative LN count was an independent predictor of survival (P < 0.05). Based on the statistical assumption the best fitting linear, linear regression showed a significant survival improvement based on increasing negative LN count for patients with stages I (P = 0.014), II (P = 0.011) and III (P = 0.003). The greatest survival differences were observed at cutoff value 10 negative LN counts for stage I, and 15 for stages II, III and IV. CONCLUSION: Negative LN counts can reflect the extent of lymphadenectomy for gastric cancer after curative distal gastrectomy. The higher the negative LN count, the better the survival would be; the best long-term survival outcome was observed on the negative LN count more than 10 (stage I) or 15 (stages II, III, and IV).