Indications for Adjuvant Chemotherapy in Stage II Gastric Cancer After D2 Gastrectomy-A Chinese Multicenter Study.

BACKGROUND: The benefit of adjuvant chemotherapy (AC) for patients with stage II gastric cancer remains controversial. This study aimed to explore the indications for adjuvant chemotherapy in patients with stage II gastric cancer by constructing an individual prediction model. PATIENTS AND METHODS: In this Chinese multicenter study, a total of 1012 patients with stage II gastric cancer after D2 radical gastrectomy were retrospectively analyzed. All patients were randomly assigned to a training cohort (n = 674) or a validation cohort (n = 338). A nomogram was constructed according to the training cohort. Concordance index (C-index), the area under the receiver operating characteristic (ROC) curves (AUC), calibration curves, and decision curve analysis (DCA) were applied to evaluate the performance of the nomogram. ROC curves and stratified survival were used to determine the patients' cutoff score for a benefit from adjuvant chemotherapy. An additional 338 patients were used as a validation cohort to validate the feasibility of using this nomogram to guide individualized therapy for patients with stage II gastric cancer. RESULTS: Univariate and multivariate analyses illustrated that age, sex, tumor location, size, carcinoembryonic antigen (CEA), hemoglobin (HB), and T stage were independent prognostic factors for overall survival (OS), and they were used to establish a nomogram. The cutoff value was determined by ROC curve analysis, and patients were divided into a high-risk group (< 239 points) and a low-risk group (≥ 239 points). There was no significant difference in the OS of low-risk patients in either the training cohort or the validation cohort. However, the OS of high-risk patients in the AC group was better than that of patients in the surgery-only group. CONCLUSIONS: This prediction model can be applied to guide treatment of patients with stage II gastric cancer. High-risk patients (< 239 points) are likely to benefit from AC after D2 radical gastrectomy.

Compliance with Oral Nutritional Supplementation among Gastric Cancer Patients at Nutritional Risk: A Cross-Sectional Study.

AIMS: To explore compliance with oral nutritional supplementation (ONS) and to identify the risk factors for noncompliance among gastric cancer patients based on the health belief model (HBM). METHODS: This prospective, observational study included gastric cancer patients at nutritional risk who were prescribed ONS from July to September 2020. Demographic factors, clinical factors, ONS-related factors, social factors and variables derived from the HBM were collected. The outcome of interest was compliance with ONS, which was measured by self-reported intake of ONS. Uni- and multivariate analyses of potential risk factors for noncompliance were performed. RESULTS: A total of 162 gastric cancer patients in the preoperative and adjuvant chemotherapy periods were analyzed. The compliance rate with ONS was 24.7%. Univariate analysis identified thirteen variables as risk factors for decreased compliance. Multivariate logistic analysis indicated that ONS compliance was independently associated with the treatment period, perceived barriers to ONS, the motivation to take ONS, and the timing of taking ONS. CONCLUSION: This study showed that overall ONS compliance among gastric cancer patients was notably low. Patients in the chemotherapy treatment period who took ONS at random times each day perceived more barriers to taking ONS and had a lower level of motivation were associated with lower compliance with ONS.

Optimal Nutrition Formulas for Patients Undergoing Surgery for Colorectal Cancer: A Bayesian Network Analysis.

Optimal nutrition formulas for colorectal cancer patients underwent surgery remains uncertainty. We constructed an indirect comparison study to assess comparative efficacy of different immunonutrition formulas and standard nutrition in colorectal cancer patients underwent surgery. PubMed, the Cochrane Library, EMBASE, ClinicalTrials.gov and Web of Science databases were searched to identify RCTs that compared immunonutrition with standard nutrition or different immunonutrition formulas. Data on length of hospital stays (LOS), infectious complications (IC), noninfectious complications (NIC) and anastomotic leakage (AL) were extracted from the included RCTs for Bayesian network analysis using a random-effect model. Twelve articles that included 1032 individuals were incorporated into this study. The indirect comparison confirmed the potential improvement of arginine-based immunonutrition on IC (odds ratios [OR] = 0.43, 95%confidence interval [CI]: 0.17 to 0.95), glutamine on NIC (OR = 0.07 CI: 0.00 to 0.78) and LOS (MD=-3.91 CI: -6.33 to -1.69) and omega-3 polyunsaturated fatty acids on LOS (OR=-3.49 CI: -5.46 to -1.00). Results indicated that glutamine had the highest probability of reducing complications and hospital stays. As for colorectal cancer patients underwent surgery, this indirect comparison suggested some superiority of glutamine. Future more RCTs with larger scale are required to provide evidence for the optimal immunonutrition formulas.

Survival analysis of stage II gastric cancer patients after D2 gastrectomy: a Chinese people-based research.

OBJECTIVE: The benefit of adjuvant chemotherapy is still controversial for stage II gastric cancer patients. This study aims to identify prognostic factors to guide individualized treatment for stage II gastric cancer patients. METHODS: We retrospectively reviewed 1121 stage II gastric cancer patients who underwent D2 radical gastrectomy from 2007 to 2017 in the Sixth Affiliated Hospital of Sun Yat-sen University, FuJian Medical School Affiliated Union Hospital and Sun Yat-sen University Cancer Center. Propensity score matching was used to ensure that the baseline data were balanced between the adjuvant chemotherapy group and surgery-only group. Kaplan-Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. RESULTS: In univariate analysis, after propensity score matching, age, tumor location, tumor size, CEA, T stage and N stage were associated with overall survival (OS). Multivariate analysis illustrated that age ≥ 60 years old, linitis plastica and T4 were independent risk factors for OS, but lower location and adjuvant chemotherapy were protective factors. CONCLUSION: Stage II gastric cancer patients with adverse prognostic factors (age ≥ 60, linitis plastica and T4) have poor prognosis. Adjuvant chemotherapy may be more beneficial for these patients.

Effects of art therapy in cancer care: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of art therapy on cancer patients' quality of life and physical and psychological symptoms. METHODS: The databases PubMed, Embase, Web of Science, The Cochrane Library, Clinical Trial.gov, the China National Knowledge Infrastructure (CNKI), Wanfang and the Chinese Biomedical Literature Database (CBM) were searched from their inception up to 20 August 2019. Trials examining the effects of art therapy on physical and psychological symptoms and quality of life versus a control group were included. The methodological quality of the included randomised controlled trials was assessed using the risk of bias tool of Cochrane Handbook. Meanwhile, the Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate the methodological quality of the non-randomised studies. RESULTS: Twelve studies involving 587 cancer patients were included. The results revealed that art therapy significantly reduced anxiety symptoms (standard mean difference [SMD] = -0.46, 95% confidence interval [CI] [-0.90, 0.02], p = .04), depression symptoms (SMD = -0.47, 95% CI [-0.72, 0.21], p < .01), and fatigue (SMD = -0.38, 95% CI [-0.68, -0.09], p = .01) in cancer patients. Art therapy also significantly improved the quality of life of cancer patients (SMD = 0.43, 95% CI [0.18, 0.68], p < .01). CONCLUSIONS: Art therapy had a positive effect on quality of life and symptoms in cancer patients and can be used as a complementary treatment for cancer patients.

Prognosis of Young Survivors of Gastric Cancer in China and the U.S.: Determining Long-Term Outcomes Based on Conditional Survival.

BACKGROUND: Young survivors of gastric cancer (GC) have better prognoses than elderly patients, yet their disease-specific survival (DSS) has received little attention. PATIENTS AND METHODS: Data on young patients (aged ≤40 years) with GC undergoing resections at three Chinese institutions (n = 542) and from the SEER database (n = 533) were retrospectively analyzed. Three-year conditional disease-specific survival (CS3) was assessed. The effects of well-known prognostic factors over time were analyzed by time-dependent Cox regression. RESULTS: Overall, young Chinese patients with GC had a better 5-year DSS than U.S. patients (62.8% vs. 54.1%; p < .05). The disease-specific mortality likelihood of the entire cohort was not constant over time, with most deaths occurring during the first 3 years after surgery but peaking at 1 and 2 years in China and the U.S., respectively. Based on 5-year survivorship, the CS3 rates of both groups were similar (90.9% [U.S.] vs. 91.5% [China]; p > .05). Cox regression showed that for Chinese patients, site, size, T stage, and N stage were independent prognostic factors at baseline (p < .05). For U.S. patients, grade, T stage. and N stage significantly affected DSS at baseline (p < .05). In both groups, only T stage continuously affected DSS within 3 years after gastrectomy. However, for both groups, the initial well-known prognostic factors lost prognostic significance after 5 years of survival (all p > .05). Although the 5-year DSS rates of young Chinese patients with T3 and T4a disease were significantly better than those of young U.S. patients, in each T stage, the CS3 of both regions trended toward consistency over time. CONCLUSION: For young patients with GC, the factors that predict survival at baseline vary over time. Although the initial 5-year DSS is heterogeneous, insight into conditional survival will help clinicians evaluate the long-term prognoses of survivors while ignoring population differences. IMPLICATIONS FOR PRACTICE: With the increasing number of young survivors of gastric cancer (GC), it is essential for clinicians to understand the dynamic prognosis of these patients. Based on large data sets from China and the U.S., this study found that the prognostic factors that predict survival for young patients with GC at baseline vary over time. Although the initial 5-year disease-specific survival is heterogeneous, insight into conditional survival will help clinicians evaluate the long-term prognoses of survivors while ignoring population differences. This knowledge may be more effective in helping young patients with GC to manage future uncertainties, especially when they need to make important life plans.

Postoperative dynamic survival of gastric cancer patients: A multi-institutional, international analysis of 22 265 patients.

BACKGROUND: How to best evaluate the disease-specific survival (DSS) of gastric cancer (GC) survivors over time is unclear. METHODS: Clinicopathological data from 22 265 patients who underwent curative intend resection for GC were retrospectively analyzed. Changes in the patients' 3-year conditional disease-specific survival (CS3) were analyzed. We used time-dependent Cox regression to analyze which variables had long-term effects on DSS and devised a dynamic predictive model based on the length of survival. RESULTS: Based on 1-, 3-, and 5-year survivorships, the CS3 of the population increased gradually from 62% to 68.1%, 83.7%, and 90.6%, respectively. Subgroup analysis showed that the CS3 of patients who had poor prognostic factors initially demonstrated the greatest increase in postoperative survival time (eg, N3b: 26.6%-84.1%, Δ57.5% vs N0: 84.1%-93.3%, Δ9.2%). Time-dependent Cox regression analysis showed the following predictor variables constantly affecting DSS: age, the number of examined lymph nodes (LNs), T stage, N stage, and site (P < .05). These variables served as the basis for a dynamic prediction model. CONCLUSIONS: The influence of prognostic factors on DSS and CS3 changed dramatically over time. We developed an effective model for predicting the DSS of patients with GC based on the length of survival time.

Significant Role of Palliative Gastrectomy in Selective Gastric Cancer Patients with Peritoneal Dissemination: A Propensity Score Matching Analysis.

OBJECTIVE: The aim of this study was to explore whether palliative gastrectomy is suitable for gastric cancer patients with peritoneal metastasis, and for patients in whom the type of peritoneal metastasis should be selected to receive palliative gastrectomy. METHODS: A total of 747 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis at our centers between January 2000 and April 2014 were retrospectively analyzed. After propensity score matching, the clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. RESULTS: After propensity score matching, the median overall survival (OS) of patients in the gastrectomy group was longer than that for patients in the non-gastrectomy group (11.87 vs. 9.27 months; p = 0.020). Patients who received first-line chemotherapy had a significantly longer median OS than those who did not (11.97 vs. 7.03 months; p < 0.001); among these patients, those undergoing more than eight periods of first-line chemotherapy benefited the most (p < 0.001). Subgroup analyses revealed that patients classified as P1 who were undergoing chemotherapy benefited from gastrectomy (p = 0.024), and patients without multisite metastasis also benefited from gastrectomy with regard to OS (p = 0.007). In the multivariate survival analysis, multisite distant metastasis was the independent poor prognostic factor (p < 0.001), while palliative gastrectomy (p = 0.006) and a period of first-line chemotherapy (p < 0.001) were good prognostic factors. Morbidity rates in the gastrectomy and non-gastrectomy groups were 10.4 and 1.0 %, respectively (p = 0.003); however, no difference in mortality was noted between the two groups (p = 0.590). CONCLUSIONS: Palliative gastrectomy can prolong the survival of P1 patients without multisite distant metastasis when combined with more than five periods, and particularly more than eight periods, of first-line chemotherapy.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

Neoadjuvant chemotherapy for gastric cancer: a meta-analysis of randomized, controlled trials.

BACKGROUND AND AIM: Although the effect of neoadjuvant chemotherapy in gastric cancer has been extensively studied, the data of survival benefit are still controversial. The purpose of this work was to assess the effectiveness of neoadjuvant chemotherapy followed by surgery in patients with gastric cancer. METHODS: We searched systematically electronic through the databases of PUBMED, EMBASE, China Biological Medicine, and China National Knowledge Infrastructure Whole Article for studies published from 1975. Two reviewers independently evaluated the relevant reports and searched manually reference from these reports for additional trials. Outcomes assessed by meta-analysis included overall survival rate, progression-free survival rate, R0 resection rate, downstaging effect, postoperative complications, and perioperative mortality. RESULTS: Six randomized, controlled trials with 781 patients were included in the meta-analysis. Odds ratio (95% confidence interval; P-value), expressed as neoadjuvant chemotherapy and surgery versus surgery alone, was 1.16 (0.85-1.58; P = 0.36) for overall survival, 1.24 (0.78-1.96; P = 0.36) for R0 resection, 1.25 (0.75-2.09; P = 0.39) for postoperative complications, and 3.60 (0.59-22.45; P = 0.17) for perioperative mortality. CONCLUSIONS: Compared with surgery alone, neoadjuvant chemotherapy followed by surgery was not associated with a higher rate of overall survival or complete resection (R0 resection). It does not increase treatment-related morbidity and mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.

Features of synchronous and metachronous dual primary gastric and colorectal cancer.

BACKGROUND: Studies evaluating the characteristics of dual primary gastric and colorectal cancer (CRC) (DPGCC) are limited. AIM: To analyze the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with DPGCC. METHODS: From October 2010 to August 2021, patients with DPGCC were retrospectively reviewed. The patients with DPGCC were divided into two groups (synchronous and metachronous). We compared the overall survival (OS) between the groups using Kaplan-Meier survival methods. Univariate and multivariate analyses were performed using Cox's proportional hazards model to identify the independent prognostic factors for OS. RESULTS: Of the 76 patients with DPGCC, 46 and 30 had synchronous and metachronous cancers, respectively. The proportion of unresectable CRC in patients with synchronous cancers was higher than that in patients with metachronous cancers (28.3% vs 3.3%, P = 0.015). The majority of the second primary cancers had occurred within 5 years. Kaplan-Meier survival analysis showed that the patients with metachronous cancers had a better prognosis than patients with synchronous cancers (P = 0.010). The patients who had undergone gastrectomy (P < 0.001) or CRC resection (P < 0.001) had a better prognosis than those who had not. In the multivariate analysis, synchronous cancer [hazard ratio (HR) = 6.8, 95% confidence interval (95%CI): 2.0-22.7, P = 0.002)] and stage III-IV gastric cancer (GC) [HR = 10.0, 95%CI: 3.4-29.5, P < 0.001)] were risk prognostic factor for OS, while patients who underwent gastrectomy was a protective prognostic factor for OS [HR = 0.2, 95%CI: 0.1-0.6, P = 0.002]. CONCLUSION: Regular surveillance for metachronous cancer is necessary during postoperative follow-up. Surgical resection is the mainstay of therapy to improve the prognosis of DPGCC. The prognosis appears to be influenced by the stage of GC rather than the stage of CRC. Patients with synchronous cancer have a worse prognosis, and its treatment strategy is worth further exploration.

Laparoscopy-assisted versus open distal gastrectomy for early gastric cancer: evidence from randomized and nonrandomized clinical trials.

OBJECTIVE: To evaluate the safety and efficacy of laparoscopy-assisted distal gastrectomy (LADG) in patients with early gastric cancer (EGC) to determine whether LADG is an acceptable alternative to open distal gastrectomy (ODG). BACKGROUND: LADG combined with less than D2 or D2 lymphadenectomy for EGC is still a controversial surgical intervention for its uncertain oncological safety and economic benefit. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) and non-RCTs of LADG versus ODG to evaluate whether the safety and efficacy of LADG in patients with EGC are equivalent to those of ODG. METHODS: A comprehensive search of PubMed, EMBASE, Cochrane Library, and China Knowledge Resource Integrated Database was performed. Eligible trials published between January 1, 1994, and December 31, 2010, were included in the study. Data synthesis and statistical analysis were carried out by RevMan 5.0 software. The quality of evidence was assessed by GRADEpro 3.2.2. RESULTS: Twenty-two studies with 3411 participants were included in this study. The mean number of lymph nodes retrieved in LADG was close to that retrieved in ODG (in the less than D2 resection: weighted mean difference [WMD] = -1.79; 95% confidence interval [95% CI], -5.78 to 2.19; P = 0.38; heterogeneity: P < 0.00001, I = 98%; and in the D2 resection: WMD = -1.53; 95% CI, -3.56 to 0.51; P = 0.14; heterogeneity: P = 0.23, I = 26%). The overall postoperative morbidity was significantly less in LADG than in ODG (relative risk = 0.58; 95% CI, 0.46-0.74; P < 0.00001; heterogeneity: P = 0.94, I = 0%). LADG reduced the intraoperative blood loss, postoperative analgesic consumption, and hospital duration, without increasing the total hospitalization costs and cancer recurrence rate. The long-term survival rate of patients undergoing LADG was similar to that of patients undergoing ODG. However, LADG was still a technically dependent and time-consuming procedure. Conversion rate of LADG was 0% to 2.94%. The reported reasons for conversion were bleeding, adhesion, and safety resection margin requirement. LIMITATIONS: : There were potential biases and significant heterogeneity in some clinical outcome measures in this study. Methodologically high-quality controlled clinical trials were sparse for this new surgical intervention. According to The Grading of Recommendations Assessment, Development and Evaluation approach, when assessing the safety and efficacy of LADG by comparing with those of ODG with the defined clinical outcomes in patients with EGC, the quality of the currently available clinical evidence was very low. CONCLUSIONS: LADG may be a technically feasible alternative for EGC when it is performed in experienced surgical centers in which patients undergoing LADG may benefit from the faster postoperative recovery. However, the currently available evidence cannot exclude the potential clinical benefits or harms, especially in the node-positive cases. Methodologically high-quality comparative studies are needed for further evaluation.

A novel hematological classifier predicting chemotherapy benefit and recurrence hazard for locally advanced gastric cancer A multicenter IPTW analysis.

BACKGROUND: Effective classifiers for the prediction of individual adjuvant chemotherapy (AC) benefits are scarce. PURPOSE: This study aimed to construct a useful classifier to predict the AC benefit and recurrence hazard based on preoperative hematological indices through a multicenter database. METHODS AND RESULTS: Multivariate analysis revealing GCRF (comprehensive deep learning classifier) as an independent prognostic factor associated with overall survival (OS) and disease-free survival (DFS). Locally advanced gastric cancer (LAGC) patients are categorized into the high-risk group (HRG) and low-risk group (LRG). In HRG, OS and DFS of the AC group are significantly higher than those of the non-AC group (all p˂0.05), whereas in LRG, OS and DFS of the AC group are comparable to those of the non-AC group (all p > 0.05). Furthermore, combined GCRF with 8th AJCC TNM staging system, only 650 (51.1%) patients can benefit most from AC among 1273 patients with pStage II-III. From the perspective of recurrence pattern, the recurrence rate of HRG is significantly higher than that of LRG in any recurrence type, including local recurrence, peritoneal recurrence, and distant recurrence (all p˂0.05). Furthermore, the mean time to peritoneal recurrence and lung metastasis in HRG is earlier than that in the LRG (p = 0.028 and 0.011, respectively). CONCLUSION: In summary, our novel classifier based on deep learning preoperative hematological indices can predict not only the AC benefit of LAGC patients, but also the recurrence hazard after surgery. This classifier is expected to be an effective supplement to the 8th AJCC TNM staging system for the prediction of AC benefits and is helpful for clinical decision in AC individual administration. Further large-scale western studies are warranted.

Retrieval of 30 Lymph Nodes Is Mandatory for Selected Stage II Gastric Cancer Patients.

BACKGROUND: According to the 8th edition AJCC staging manual, a least of 16 lymph nodes retrieval (LNRs) is the minimal requirement for lymph nodes (LNs) dissection of gastric cancer surgery. Previous studies have shown that increasing the number of LNRs (≥30) prolongs survival for selected patients. However, the necessity of retrieving 30 or more LN for stage II gastric cancer patients is still under debate. AIM: This study aims to explore the impact of retrieving 30 or more lymph nodes on the survival of stage II cancer patients. METHODS: A total of 1,177 patients diagnosed with stage II gastric cancer were enrolled in this study. The clinicopathological parameters and the impact of different LNRs (<30 or ≥30) and positive lymph node ratio (NR) on overall survival (OS) were retrospectively analyzed. RESULTS: The mean number of LNRs was 34 ± 15. A total of 44% (518/1,177) of patients had an LNRs <30, while 56% (659/1,177) of patients had an LNRs ≥30. The 5-year survival rate was 81% for all patients, 76% for the LNRs <30 group, and 86% for LNRs ≥30 group, respectively (P = 0.003). The survival benefit of retrieving 30 lymph nodes was significant in certain subgroups: age >60 years/male/underwent total gastrectomy/stage IIB. For N+ patients, higher NR was significantly correlated with poor survival. CONCLUSION: The survival benefit of retrieving 30 LNs varies in different subgroups. An LNRs of 30 is mandatory for selected stage II gastric cancer patients.

Meta-analysis of laparoscopy-assisted distal gastrectomy and conventional open distal gastrectomy for early gastric cancer.

BACKGROUND AND OBJECTIVE: With the application of laparoscopy, laparoscopic gastrectomy for the treatment of patients with early gastric cancer has been performed, but the safety and effectiveness of this method need to be explored. This study evaluated the safety and effectiveness of laparoscopy-assisted and conventional open distal gastrectomy for patients with early gastric cancer. METHODS: A search of MEDLINE, EMBASE, the Chinese Biomedical Database (CBM), and Cochrane Central Register of Controlled Trials (CENTRAL) identified all the randomized clinical trials that compared laparoscopy-assisted gastrectomy with open distal gastrectomy for patients with early gastric cancer published in the last 10 years. Quality assessment was done on each trial and relevant data were extracted from qualified trials. Meta-analysis was performed using RevMan 4.2.2 software (Cochrane). RESULTS: Six randomized controlled trials (RCTs) involving 218 patients were included. Comparing laparoscopic resection with open resection, results showed less estimated blood loss (WMD (weighted mean difference): -121.86; 95% CI (confidence interval): -145.61, -98.11; P < 0.001), earlier postoperative first flatus (WMD: -0.95; 95% CI: -1.09, -0.81; P < 0.001), and shorter durations of hospital stays (WMD: -2.27; 95%CI: -3.47, -1.06; P = 0.0002), but longer surgery times (WMD: 58.71; 95% CI: 52.69, 64.74; P < 0.001) and fewer lymph nodes dissected (WMD: -3.64; 95% CI: -5.80,-1.47; P = 0.001). There was no significant difference between the two groups in postoperative complications (OR (odds ratio): 0.57; 95% CI: 0.31,1.03; P = 0.06). CONCLUSIONS: The short-term outcome of laparoscopy-assisted distal gastrectomy for patients with early gastric cancer is superior to the open procedure, but its long-term outcome should be proven by further outcomes of RCTs.

Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer.

BACKGROUND: Survival benefit of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC) is a debatable issue. Studies have shown that the survival benefit of NAC is dependent on the pathological response to chemotherapy drugs. For those who achieve pathological complete response (pCR), NAC significantly prolonged prolapsed-free survival and overall survival. For those with poor response, NAC yielded no survival benefit, only toxicity and increased risk for tumor progression during chemotherapy, which may hinder surgical resection. Thus, predicting pCR to NAC is of great clinical significance and can help achieve individualized treatment in AGC patients. AIM: To establish a nomogram for predicting pCR to NAC for AGC patients. METHODS: Two-hundred and eight patients diagnosed with AGC who received NAC followed by resection surgery from March 2012 to July 2019 were enrolled in this study. Their clinical data were retrospectively analyzed by logistic regression analysis to determine the possible predictors for pCR. Based on these predictors, a nomogram model was developed and internally validated using the bootstrap method. RESULTS: pCR was confirmed in 27 patients (27/208, 13.0%). Multivariate logistic regression analysis showed that higher carcinoembryonic antigen level, lymphocyte ratio, lower monocyte count and tumor differentiation grade were associated with higher pCR. Concordance statistic of the established nomogram was 0.767. CONCLUSION: A nomogram predicting pCR to NAC was established. Since this nomogram exhibited satisfactory predictive power despite utilizing easily available pretreatment parameters, it can be inferred that this nomogram is practical for the development of personalized treatment strategy for AGC patients.

Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model.

BACKGROUND: The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis. METHODS: Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR). The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR. RESULTS: Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (P < 0.05). Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05). Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P < 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (P < 0.05). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups. CONCLUSION: Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.

Postoperative complications and nutritional status between uncut Roux-en-Y anastomosis and Billroth II anastomosis after D2 distal gastrectomy: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Gastric cancer is the fourth most common malignant disease worldwide, with lower one-third gastric cancer the most common type. Distal gastrectomy with D2 lymph node dissection was recommended as a standard surgery for distal gastric cancer patients. However, some controversy remains about the anastomosis of the residual stomach and the intestine. The objectives of this trial are to test the hypothesis that uncut Roux-en-Y anastomosis can reduce postoperative complications and improve nutritional status more effectively than Billroth II anastomosis in gastric cancer patients after D2 gastrectomy. METHODS/DESIGN: This multi-center, prospective, phase III, randomized controlled trial will compare the efficacy of uncut Roux-en-Y anastomosis versus Billroth II anastomosis in phase I-III patients with initial treatment of radical distal gastrectomy. Patients will be randomized to undergo either the intervention (uncut Roux-en-Y anastomosis) or the control (Billroth II anastomosis). We will recruit 832 patients who meet the trial eligibility criteria and will follow the patients after surgery to observe postoperative complications and nutrition status for 5 years. The primary assessment indices of the study are reflux gastritis, esophagitis, bile regurgitation, and anastomotic ulcer. The secondary assessment indices are nutritional status, quality of life, perioperative complications, overall survival rate, and others. When the number of cases reaches 400, an interim analysis will be performed to identify any evidence of definite superiority of the experimental intervention. DISCUSSION: We aim to test the hypothesis that uncut Roux-en-Y anastomosis can reduce postoperative complications and improve nutritional status more than Billroth II anastomosis in gastric cancer patients after D2 gastrectomy. The results of the trial will contribute to the best evidence on which to base the reconstruction of distal gastrectomy. TRIAL REGISTRATION: Chinese Southern Gastric Cancer Conference CSGC002 Trial. ClinicalTrials.gov, NCT02763878 . Registered on 5 May 2016.

The Development and Future of Digestive Tract Reconstruction after Distal Gastrectomy: A Systemic Review and Meta-Analysis.

Background: Billroth I, Billroth II, Roux-en-Y, and Un-cut Roux-en-Y are common reconstruction techniques of distal gastrectomy. Which of these techniques is better has yet to be established. We performed an indirect comparison to evaluate which technique was optimal for preventing reflux symptoms. Methods: The PubMed, Cochrane Collaboration, Embase, ClinicalTrials.gov and Web of Science databases were searched to identify clinical trials that compared at least two of the reconstruction skills among Billroth I, Billroth II, Roux-en-Y, and Un-cut Roux-en-Y. Data on reflux gastritis, intraoperative blood loss, bile reflux and postoperative hospital stays were extracted from the included clinical trials for meta-analysis using a random-effects model. Results: Twenty-four articles that included 5419 individuals were assessed as eligible for meta-analysis. The indirect comparison suggested that Roux-en-Y reconstruction significantly reduces reflux gastritis, and it tended to rank first and had the highest probability of preventing bile reflux. No significant differences were found in intraoperative blood loss and postoperative hospital stays. Conclusion: This indirect comparison suggested some superiority of Roux-en-Y reconstruction after distal gastrectomy. Further perspective clinical trials are required to provide evidence for the optimal reconstruction skill.

Oral exclusive enteral nutrition induces mucosal and transmural healing in patients with Crohn's disease.

BACKGROUND AND AIMS: Mucosal healing is regarded as a clinical endpoint of Crohn's disease (CD), and transmural healing is correlated to the concept of deep remission. Current therapies to induce mucosal and transmural healing in CD are not satisfactory. Exclusive enteral nutrition (EEN) is underestimated therapy and its value has not been fully evaluated. Our aim was to investigate the efficacy of oral EEN for inducing mucosal and transmural healing in CD patients. METHODS: This was a prospective, single-center, open-label study including diagnosed CD children and adults conducted between January 2015 and December 2016 in the Sixth Affiliated Hospital of Sun Yat-sen University. All patients were treated with oral EEN and underwent paired assessment at baseline and completion using C-reaction protein, erythrocyte sedimentation rate, platelets, hemoglobin, body mass index, CD activity index, simple endoscopic score for CD and bowel sonography. Azathioprine was combined to prevent relapse. RESULTS: In this prospective observational study, 29 CD patients with an average age of 28.9 years were identified. After oral EEN treatment, 23 patients (79%) achieved complete mucosal healing, and the mean time to reach mucosal healing was 123 days (ranged from 50 to 212 days). Although only five patients (17%) achieved transmural healing, a significant reduction was observed in bowel-wall thickness (9.41 ± 3.06 vs 4.97 ± 1.76 mm, P < 0.001) and a significant improvement was observed in complications (including fistulas, abscess, ascites, stricture) assessed by bowel sonography (all P < 0.05). CONCLUSIONS: Oral EEN therapy is highly effective for inducing mucosal healing in CD patients. Both CD patients at active stage and those at clinical remission show excellent clinical response to oral EEN.