Publication of Results of Registered Trials With Published Study Protocols, 2011-2022.

Importance: Publishing study protocols might reduce research waste because of unclear methods or incomplete reporting; on the other hand, there might be few additional benefits of publishing protocols for registered trials that are never completed or published. No study has investigated the proportion of published protocols associated with published results. Objective: To estimate the proportion of published trial protocols for which there are not associated published results. Design, Setting, and Participants: This cross-sectional study used stratified random sampling to identify registered clinical trials with protocols published between January 2011 and August 2022 and indexed in PubMed Central. Ongoing studies and those within 1 year of the primary completion date on ClinicalTrials.gov were excluded. Published results were sought from August 2022 to March 2023 by searching ClinicalTrials.gov, emailing authors, and using an automated tool, as well as through incidental discovery. Main Outcomes and Measures: The primary outcome was a weighted estimate of the proportion of registered trials with published protocols that also had published main results. The proportion of trials with unpublished results was estimated using a weighted mean. Results: From 1500 citations that were screened, 308 clinical trial protocols were included, and it was found that 87 trials had not published their main results. Most included trials were investigator-initiated evaluations of nonregulated products. When published, results appeared a mean (SD) of 3.4 (2.0) years after protocol publications. With the use of a weighted mean, an estimated 4754 (95% CI, 4296-5226) eligible clinical trial protocols were published and indexed in PubMed Central between 2011 and 2022. In the weighted analysis, 1708 of those protocols (36%; 95% CI, 31%-41%) were not associated with publication of main results. In a sensitivity analysis excluding protocols published after 2019, an estimated 25% (95% CI, 20%-30%) of 3670 (95% CI, 3310-4032) protocol publications were not associated with publication of main results. Conclusions and Relevance: This cross-sectional study of clinical trial protocols published on PubMed Central between 2011 and 2022 suggests that many protocols were not associated with subsequent publication of results. The overall benefits of publishing study protocols might outweigh the research waste caused by unnecessary protocol publications.

Pre- and Post-treatment Double-Sequential-Point Dynamic Radiomic Model in the Response Prediction of Gastric Cancer to Neoadjuvant Chemotherapy: 3-Year Survival Analysis.

BACKGROUND: Prognosis prediction of patients with gastric cancer after neoadjuvant chemotherapy is suboptimal. This study aims to develop and validate a dynamic radiomic model for prognosis prediction of patients with gastric cancer on the basis of baseline and posttreatment features. PATIENTS AND METHODS: This single-center cohort study included patients with gastric adenocarcinoma treated with neoadjuvant chemotherapy from June 2009 to July 2015 in the Gastrointestinal Cancer Center of Peking University Cancer Hospital. Their clinicopathological data, pre-treatment and post-treatment computed tomography (CT) images, and pathological reports were retrieved and analyzed. Four prediction models were developed and validated using tenfold cross-validation, with death within 3 years as the outcome. Model discrimination was compared by the area under the curve (AUC). The final radiomic model was evaluated for calibration and clinical utility using Hosmer-Lemeshow tests and decision curve analysis. RESULTS: The study included 205 patients with gastric adenocarcinoma [166 (81%) male; mean age 59.9 (SD 10.3) years], with 71 (34.6%) deaths occurring within 3 years. The radiomic model alone demonstrated better discrimination than the pathological T stage (ypT) stage model alone (cross-validated AUC 0.598 versus 0.516, P = 0.009). The final radiomic model, which incorporated both radiomic and clinicopathological characteristics, had a significantly higher cross-validated AUC (0.769) than the ypT stage model (0.516), the radiomics alone model (0.598), and the ypT plus other clinicopathological characteristics model (0.738; all P < 0.05). Decision curve analysis confirmed the clinical utility of the final radiomic model. CONCLUSIONS: The developed radiomic model had good accuracy and could be used as a decision aid tool in clinical practice to differentiate prognosis of patients with gastric cancer.

Pilot Trial Characteristics, Postpilot Design Modifications, and Feasibility of Full-Scale Trials.

Importance: Pilot trials often lead to study design changes in subsequent full-scale trials. Yet, it remains unclear whether these modifications improve the feasibility of the larger trial. Objective: To compare feasibility estimates between pilot and full-scale trials and identify pilot trial characteristics and modifications associated with equivalent or improved feasibility in the full-scale trial. Design, Setting, and Participants: This cohort study used pilot trials published between January 2005 and December 2018 and their corresponding full-scale trials. PubMed was searched for trials on February 19, 2022. Exposures: Pilot trial characteristics and postpilot trial design modifications. Main Outcomes and Measures: The outcome of interest was difference in 3 feasibility parameters: successful screening probability, enrollment rate, and retention probability. These metrics were defined as equivalent or improved if the full-scale trial's estimate was within or exceeding 10% of the pilot trial's estimate. Results: A total of 249 pairs of pilot and full-scale trials were analyzed, with 43%, 77%, and 82% of full-scale trials having equivalent or improved successful screening probabilities, enrollment rates, and retention probabilities, respectively. When pilot trials used feasibility progression criteria (relative risk [RR], 1.94; 95% CI, 1.02-5.97) and maintained masking for participants (RR, 1.82; 95% CI, 1.04-4.33) or health care practitioners (RR, 1.81; 95% CI, 1.03-3.97) consistent with the full-scale trial, the likelihood of achieving equivalent or improved screening success in full-scale trials increased. Increasing study sites after the pilot was associated with higher likelihood of equivalent or improved enrollment rates (RR, 1.03; 95% CI, 1.01-1.08). Adding extra content to the intervention (RR, 0.82; 95% CI, 0.66-0.98), changing to active control (RR, 0.74; 95% CI, 0.48-0.99), administrating the control treatment more frequently (RR, 0.60; 95% CI, 0.29-0.93), different follow-up lengths (RR, 0.85; 95% CI, 0.73-0.97), and more follow-up visits (RR, 0.86; 95% CI, 0.75-0.98) were associated with lower likelihood of equivalent or improved retention probability in the full-scale trial. Conclusions and relevance: In this cohort study of pilot and full-scale trial pairs, pilot trial characteristics and postpilot modifications had varying associations with full-scale trial's feasibility. If full-scale trials planned for masking, it was desirable to use it in the pilot. Modifications increasing participant burden might decrease full-scale trial feasibility. Trialists and funders should consider both pilot trial data and proposed design changes when assessing full-scale trials.

Re-evaluating the role of pilot trials in informing effect and sample size estimates for full-scale trials: a meta-epidemiological study.

BACKGROUND: Some have argued that pilot trials have little value for informing the expected effect size of a subsequent large trial. This study aims to empirically evaluate the roles of pilot trials in informing the effect and sample size estimates of a full-scale trial. METHODS: We conducted a search in PubMed on 19 February 2022, for all pilot trials published between 2005 and 2018 and their subsequent full-scale trials. We analysed the agreement in results by comparing the direction and magnitude of the effect size in the pilot trial and full-scale trial. Logistic regression was used to explore whether a significant pilot trial and other characteristics were associated with a significant full-scale trial. RESULTS: A total of 248 pairs of pilot and full-scale trials were analysed. Full-scale trials with a significant pilot trial were 2.72 times more likely to find a significant result for the primary efficacy outcome than those with a non-significant pilot trial (95% CI 1.52 to 4.86, p=0.001). The association remained significant irrespective of changes made to the trial design. In 73% of the pairs, the pilot trial produced a larger point estimate than the subsequent full-scale trial, but 87% of pairs had a 95% CI estimated by the pilot trial that covered the full-scale trial point estimate. Full-scale trials with a sample size estimated using the SD from the pilot trial were less likely to yield a significant result (OR=0.26, 95% CI 0.10 to 0.65, p=0.004). CONCLUSION: Pilot trials can provide strong signals on intervention efficacy. When determining the sample size for full-scale trials, using the CI bounds from the pilot trials instead of the point estimate may improve power estimation.

Efficacy of chemotherapy versus surgery as initial treatment for gastric cancer with positive peritoneal cytology.

BACKGROUND: The prognosis of gastric cancer (GC) patients with positive peritoneal cytology (CY1) without other distant metastasis is poor, and there are no standard treatment strategies. Our study aimed to compare the survival outcomes of CY1 GC patients receiving chemotherapy or surgery as initial treatment. METHODS: From February 2017 to January 2020, clinical and pathological data of patients diagnosed with CY1 GC without other distant metastasis in the Peking University Cancer Hospital was reviewed. Patients were divided into two groups: chemotherapy-initial group and surgery-initial group. In chemotherapy-initial group, patients received preoperative chemotherapy initially. According to the treatment response, the patients were divided into three subgroups: conversion gastrectomy group, palliative gastrectomy group, and further systematic chemotherapy group. In surgery-initial group, patients underwent gastrectomy followed by postoperative chemotherapy. RESULTS: A total of 96 CY1 GC patients were included with 48 patients in each group. In chemotherapy-initial group, preoperative chemotherapy yielded an objective response rate of 20.8% and disease control rate of 87.5%. Conversion to CY0 after preoperative chemotherapy was obtained in 24 (50%) patients. The median overall survival was 36.1 months in chemotherapy-initial group and 29.7 months in surgery-initial group (p = 0.367). The median progression-free survival was 18.1 months in chemotherapy-initial group and 16.1 months in surgery-initial group (p = 0.861). The 3-year overall survival rates were 50.0% and 47.9%, respectively. In chemotherapy-initial group, twenty-four patients who converted to CY0 by preoperative chemotherapy and received surgery obtained a significantly better prognosis. The median overall survival was still not reached in these patients. CONCLUSION: There was no significant difference in survival outcomes between chemotherapy-initial group and surgery-initial group. CY1 GC patients who converted to CY0 by preoperative chemotherapy and received radical surgery could obtain a favorable long-term prognosis. Further investigation should focus on preoperative chemotherapy to eliminate peritoneal cancer cell. TRIAL REGISTRATION: This study is retrospectively registered.

Pilot trials may improve the quality of full-scale trials: a meta-research study.

OBJECTIVES: Evidence on the value of pilot trials for subsequent trial's quality is scarce. This study aims to determine if a pilot trial improves the quality of the full-scale trial. STUDY DESIGN AND SETTING: We searched PubMed for pilot trials and their subsequent full-scale trials. The meta-analysis of the full-scale trials was used to identify other full-scale trials on the same research topic but without a pilot trial. Markers of trial quality included publication outcomes and Cochrane Risk of Bias (RoB) assessment. RESULTS: Fifty-eight full-scale trials with a pilot trial and 151 full-scale trials without were identified from 47 meta-analyses. Trials with a pilot trial were published 0.9 years sooner (mean ± standard deviation: 1.7 ± 1.0 vs. 2.6 ± 2.0, P = 0.005) and in peer-reviewed journals with higher impact factors (60.9 ± 75.0 vs. 24.8 ± 50.3, P < 0.001). A pilot trial's presence was associated with lower risk of bias in full-scale trial random sequence generation (OR [95% CI]: 4.05 [1.27-12.91]), allocation concealment (2.89 [1.07-7.83]), and participants/researchers masking (4.31 [1.37-13.50]), but not outcome assessment masking (1.03 [0.49-2.18]), incomplete outcome data (1.27 [0.47-3.42]), and selective reporting (1.23 [0.44-3.46]). CONCLUSION: Conducting a pilot trial may enhance the quality of the subsequent full-scale trial.

Global burden prediction of gastric cancer during demographic transition from 2020 to 2040.

BACKGROUND: Despite the decline in the incidence and mortality rates of gastric cancer (GC), the impact of demographic transition on the global burden of GC remains unclear. The current study aimed to estimate the global disease burden through 2040 by age, sex, and region. METHODS: GC data for incident cases and deaths by age group and sex were taken from The Global Cancer Observatory (GLOBOCAN) 2020. The incidence and mortality rates were predicted through 2040 by fitting a linear regression model over the most recent trend period with the Cancer Incidence in Five Continents (CI5) data. RESULTS: The global population will grow to 9.19 billion by 2040, accompanied by increasing population ageing. The incidence and mortality rates of GC will show a persistent decrease, with an annual percent change of -0.57% for males and -0.65% for females. East Asia and North America will have the highest and lowest age standardized rates, respectively. A slowdown in the growth of incident cases and deaths will be observed worldwide. The proportion of young and middle-aged individuals will decline, while the percentage of the elderly will increase, and the number of males will be almost twice the number of females. East Asia and high human development index (HDI) regions will be heavily burdened by GC. East Asia had 59.85% of the new cases and 56.23% of deaths in 2020; these will increase to 66.93% and 64.37% by 2040, respectively. The interaction between population growth, the change in ageing structure and the decline in incidence and mortality rates will lead to an increased burden of GC. CONCLUSIONS: Ageing and population growth will offset the decline in the incidence and mortality rate of GC, resulting in a substantial increase in the number of new cases and deaths. The age structure will continue to change, especially in high HDI regions, requiring more targeted prevention strategies in the future.

Risk factors associated with peritoneal carcinomatosis of gastric cancer in staging laparoscopy: A systematic review and meta-analysis.

Background: The optimal indications of staging laparoscopy in gastric cancer to detect peritoneal carcinomatosis are still controversial. We performed this systematic review and meta-analysis to quantify the relevance of the preoperative factors with peritoneal carcinomatosis to explore the indications of staging laparoscopy. Materials and methods: Systematic searches were conducted using Medline, Embase, and the Cochrane Library in December 2021. On the basis of calculating the odds ratio (OR) of each factor, we quantified the association between the risk factors and peritoneal carcinomatosis such as clinical T/N stage, Borrmann type, and tumor markers, using meta-analysis with a random-effects model. Results: A total of 21 case-control studies and one cohort study were obtained. T stage, N stage, and differentiation degree were most widely studied, with OR values of 2.96 (95% CI: 1.87-4.69), 1.22 (95% CI: 0.86-1.73), and 1.91 (95% CI: 1.42-2.56), respectively. Among all the factors, elevated CA125 (OR = 19.45, 95% CI: 4.71-80.30), Borrmann type IV (OR = 7.68, 95% CI: 3.62-16.27), and large tumor diameter (OR = 5.12, 95% CI: 2.55-10.31) had the highest OR. In particular, CA125 had the best predictability for peritoneal carcinomatosis but was only mentioned by three articles. Conclusions: There was a cognitive gap between the awareness and importance of risk factors for peritoneal carcinomatosis. In addition to T4 stage, patients with factors with high OR, such as Borrmann type IV, large tumor diameter, and elevated CA125, should undergo staging laparoscopy.

Laparoscopic vs. open lower mediastinal lymphadenectomy for Siewert type II/III adenocarcinoma of esophagogastric junction: An exploratory, observational, prospective, IDEAL stage 2b cohort study (CLASS-10 study).

Objective: This study aims to verify the feasibility and efficacy of laparoscopic lower mediastinal lymphadenectomy for Siewert type II/III adenocarcinoma of esophagogastric junction (AEG). Setting: An exploratory, observational, prospective, cohort study will be carried out under the Idea, Development, Exploration, Assessment and Long-term Follow-up (IDEAL) framework (stage 2b). Participants: The study will recruit 1,036 patients with cases of locally advanced AEG (Siewert type II/III, clinical stage cT2-4aN0-3M0), and 518 will be assigned to either the laparoscopy group or the open group. Interventions: Patients will receive lower mediastinal lymphadenectomy along with either total or proximal gastrectomy. Primary and secondary outcome measures: The primary endpoint is the number of lower mediastinal lymph nodes retrieved, and the secondary endpoints are the surgical safety and prognosis, including intraoperative and postoperative lower-mediastinal-lymphadenectomy-related morbidity and mortality, rate of rehospitalization, R0 resection rate, 3-year local recurrence rate, and 3-year overall survival. Conclusions: The study will provide data for the guidance and development of surgical treatment strategies for AEG. Trial registration number: The study has been registered in ClinicalTrials.gov (No. NCT04443478).

Associations of Annual Hospital and Surgeon Volume with Patient Outcomes After Gastrectomy: A Systematic Review and Meta-analysis.

BACKGROUND: Procedural volume is an important determinant of outcomes in cancer surgery. There is a lack of a comprehensive and updated assessment of hospital and surgeon volumes in relation to short- and long-term outcomes after gastrectomy for cancer. METHODS: The PubMed and Embase databases were searched on January 2021. We conducted meta-analyses and meta-regressions assuming a random effects model to assess the associations of procedural volumes with outcomes after gastrectomy. Effect sizes included hazard ratios (HRs), odds ratios (ORs), and standardized mean differences (SMDs). Heterogeneity was evaluated with the I2 statistic and explored by subgroup analyses. The risk of publication bias, risk of bias, and certainty of evidence were also assessed. RESULTS: We identified 53 primary publications on the effect of hospital (n = 48) or surgeon (n = 11) volume on 11 gastrectomy outcomes. Patients operated on in high-volume centers had better overall survival (HR 0.82, 95% confidence interval [CI] 0.75-0.90), lower short-term mortality (OR 0.66, 95% CI 0.58-0.75), more adequate lymphadenectomy (OR 2.14, 95% CI 1.76-2.59), and shorter length of stay (SMD - 0.08, 95% CI - 0.12 to - 0.04). The meta-analysis showed no significant associations of hospital volume with surgical complications, R0 or negative margin resection, or disease-free survival (all p > 0.05). A higher surgeon volume was associated with lower 30-day mortality (OR 0.94, 95% CI 0.90-0.97). CONCLUSIONS: The current study suggested with high confidence that gastric cancer patients operated on in high-volume centers had better overall survival. Centralization of gastrectomy in high-volume centers might lead to an overall improvement in other outcomes, but more studies, especially on surgeon volume, are needed.

Predicting peritoneal carcinomatosis of gastric cancer: A simple model to exempt low-risk patients from unnecessary staging laparoscopy.

Background: Peritoneal carcinomatosis (PC) of gastric cancer indicates a poor outcome and is mainly diagnosed by staging laparoscopy (SL). This study was designed to develop a risk stratification model based on the number of risk factors to exempt low-risk patients from unnecessary SL. Methods: This was a retrospective cohort study based on a single institution between January 2015 and December 2019. SL is indicated for patients of advanced locoregional stage, and clinicopathologic characteristics of 535 consecutive patients were included. PC-associated variables were identified by logistic regression analysis. A risk stratification model based on the number of risk factors was constructed, and we defined its predictive value with a receiver operating characteristic (ROC) curve and negative predictive value. Results: In total, 15.9% of included patients were found to have PC during SL. Borrmann type IV, elevated CA125, and tumour diameter ≥5 cm were independent risk factors of PC. These three factors combined with cT4 were selected as predictive factors, and the number of predictive variables was significantly related to the possibility of PC (2.0%, 12.8%, 20.0%, 54.2%, and 100%, respectively). When the cutoff value is more than one predictive factor, the negative predictive value is 98.0%, with an area under the curve of 0.780. This model could exempt 29.8% of unnecessary SL compared to the indication of the current NCCN guideline. Conclusions: We constructed a simple model to predict the probability of PC using the number of predictive factors. It is recommended that patients without any of these factors should be exempt from SL.

Early diagnosis of anastomotic leakage after colorectal cancer surgery using an inflammatory factors-based score system.

BACKGROUND: Anastomotic leakage (AL) is a severe complication after colorectal surgery. This study aimed to investigate a method for the early diagnosis of AL after surgical resection by analysing inflammatory factors (IFs) in peritoneal drainage fluid. METHODS: Abdominal drainage fluid of patients with colorectal cancer who underwent resection between April 2017 and April 2018, were prospectively collected in the postoperative interval. Six IFs, including interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor (TNF)-α, matrix metalloproteinase (MMP)2, and MMP9, in drainage were determined by multiplex immunoassay to investigate AL (in patients undergoing resection and anastomosis) and pelvic collection (in patients undergoing abdominoperineal resection). Sparreboom and colleagues' prediction model was first evaluated for AL/pelvic collection, followed by a new IF-based score system (AScore) that was developed by a least absolute shrinkage and selection operator (LASSO) regression, for the same outcomes. The model performance was tested for the area under the curve (AUC), sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). RESULTS: Out of 123 patients eligible, 119 patients were selected, including 12 patients with AL/pelvic collection. Sparreboom and colleagues' prediction model was documented with the best diagnostic efficacy on postoperative day 3 (POD3), with an AUC of 0.77. After optimization, AScore on POD3 increased the AUC to 0.83 and on POD1 showed the best diagnostic efficiency, with an AUC of 0.88. Based on the Youden index, the cut-off value of AScore on POD1 was set as -2.46 to stratify patients into low-risk and high-risk groups for AL/pelvic collection. The model showed 90.0 per cent sensitivity, 69.7 per cent specificity, 98.4 per cent NPV, and 25.0 per cent PPV. CONCLUSIONS: The early determination of IFs in abdominal drainage fluid of patients undergoing colorectal surgery could be useful to predict AL or pelvic collection.

Preventive Antenatal Educational Program on Allergic Diseases (PAEPAD) versus standard antenatal care for prevention of atopic dermatitis: study protocol for a single-centre, investigator-blinded randomised controlled trial.

INTRODUCTION: Patient education serves an essential purpose in the long-term management of allergic diseases as a secondary prevention approach. However, evidence on using education for primary prevention is limited. This study aims to evaluate the effect of an educational intervention, that is, the Preventive Antenatal Educational Program on Allergic Diseases (PAEPAD), on infantile allergic disease incidences compared with the standard care. METHODS AND ANALYSIS: This is a single-centre randomised controlled trial of expecting mother-children dyads in Daxing Teaching Hospital of Beijing, China. A total of 2266 expecting mothers will be recruited. Expecting mothers enlisted in the birth registry of Daxing Teaching Hospital of Capital Medical University and intend to give birth at this location will be screened for eligibility. Women aged≥18 years with less than 14+6 weeks of pregnancy who intends to remain resident in Daxing district for at least 2 years postpartum will be entered into the run-in phase. Randomisation will take place at 30 weeks of gestation. Women at high risk for miscarriage or intend to have abortions will be excluded. The participants will be allocated into two groups (ie, the PAEPAD and the standard care group) by random allocation (1:1). The PAEPAD group will receive a multidisciplinary education of neonatal care, including standard education as the control group and additional information on skincare of infants, sun protection, topical corticosteroids and an overview of atopic dermatitis (AD), whereas the standard care group will receive the standard neonatal care education carried out by obstetricians. Participants will be followed for 2 years. The primary outcome will be infantile AD cumulative incidence at 2 years postpartum. Secondary outcomes will include other AD outcomes, atopic march outcomes, knowledge outcomes and other maternal and neonatal outcomes. Data collection will be carried out using both electronic and paper questionnaires. Biological samples will also be collected longitudinally. ETHICS AND DISSEMINATION: The study design was approved by the ethical committee of Capital Medical University Daxing Teaching Hospital, Beijing, China. The trial results will be published in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: ChiCTR registry (Trial ID: ChiCTR2000040463).

Early Diagnosis of Anastomotic Leakage After Gastric Cancer Surgery Via Analysis of Inflammatory Factors in Abdominal Drainage.

BACKGROUND: Anastomotic leakage (AL) is the most serious postoperative complication for patients with gastric cancer. We aim to develop clinically tools to detect AL in the early phase by analysis of the inflammatory factors (IFs) in abdominal drainage. METHODS: We prospectively included 326 patients to establish two independent cohorts, and the concentration of IFs within abdominal drainage was detected. In the primary cohort, an IF-based AL prediction model was constructed using the least absolute shrinkage and selection operator (LASSO) regression. The predictive value of the model was later validated via the validation cohort. RESULTS: Analyzing the IFs with LASSO regression, we developed an Anastomotic Score system on postoperative Day 3 (AScore-POD3), which yielded high diagnostic efficacy in the primary cohort (the area under the curve (AUC) = 0.87). The predictive value of AScore-POD3 was validated in the validation cohort, and its AUC was 0.83. We further built an AScore-POD3 based nomogram by combining the AScore-POD3 system with other clinical risk factors of AL. The C-index of the nomogram was 0.93 in the primary cohort and 0.82 in the validation cohort. CONCLUSIONS: Our study suggests that AL can be early diagnosed after gastric cancer surgery by measuring drainage IFs.

The significance of time interval between perioperative SOX/XELOX chemotherapy and clinical decision model in gastric cancer.

Introduction: To investigate the influences of time interval between multimodality therapies on survival for locally advanced gastric cancer (LAGC) patients, 627 patients were included in a retrospective study, and 350 who received neoadjuvant chemotherapy (NACT) based on SOX (S-1 plus Oxaliplatin)/XELOX (Capecitabine plus Oxaliplatin) treatment, radical surgery, and adjuvant chemotherapy (AC) from 2005.01 to 2018.06 were eligible for analyses. Methods: Three factors were used to assess influences, including time interval from NACT accomplishment to AC initiation (PECTI), time to surgery after NACT accomplishment (TTS), and time to adjuvant chemotherapy after surgery (TAC). Results: Concerning PECTIs, 99 (28.29%) experienced it within 9 weeks, 188 (53.71%) within 9-13 weeks, 63 (18.00%) over 13 weeks. Patients' 5-year overall survival (OS) significantly decreased as trichotomous PECTI increased (78.6% vs 66.7% vs 55.7%, P = .02). Analogously, there was a significant decrease for dichotomous TTS (within vs over 5 weeks) in OS (P = .03) and progression free survival (PFS) (P = .01) but not for dichotomous TAC (within vs over 6 weeks) in OS and PFS (P = .40). Through multivariate Cox analyses, patients with PECTI over 13 weeks had significantly worse OS (P = .03) and PFS (P = .02). Furthermore, extended TTS had significantly worse OS and PFS but insignificantly worse OS and PFS than extended TAC. Therefore, gastric patients receiving perioperative SOX/XELOX chemotherapy and surgery with extended PECTI over 9 weeks or TTS over 5 weeks would have a negative correlation with PFS and OS, and worse when PECTI over 13 weeks. Nomograms (including PECTI, ypT, ypN, Area Under Curve (AUC) = 0.81) could predict patient survival probability and guide intervention with net benefit. Discussion: In control of PECTI, TTS could be extended appropriately, and shortened TAC might make a remedy, and delayed TAC might be allowed when TTS was shortened.

Duration of Perioperative Chemotherapy in Locally Advanced Gastric Cancer: A "Less Is More" Question When ypN0 Is Achieved.

BACKGROUNDS: Perioperative chemotherapy (PEC) and neoadjuvant chemotherapy (NAC) have become a vital part of locally advanced gastric cancer (LAGC) treatment, but the optimal duration of PEC has not been studied. The aim of this study was to demonstrate the possibility of duration reduction in PEC in the adjuvant chemotherapy (AC) phase for ypN0 patients. METHODS: We included LAGC patients who achieved ypN0 after NAC in our institution from 2005 to 2018. The risk/benefit of AC and other covariates were majorly measured by overall survival (OS) and progression-free survival (PFS). We developed a survival-tree-based model to determine the optimal PEC duration for ypN0 patients in different classes. RESULTS: A total of 267 R0 resection patients were included. There were 55 patients who did not receive AC. The 5-year OS was 74.34% in the non-AC group and 83.64% in the AC group with a significant difference (p = 0.012). Multivariate Cox regression revealed that both AC (AC vs. non-AC: HR, 0.49; 95%CI, 0.27-0.88; p = 0.018) and ypT stages (ypT3-4 vs. ypT0-2: HR, 2.00; 95%CI, 1.11-3.59; p = 0.021) were significant protective/risk factors on patients OS and PFS. A decision tree model for OS indicated an optimal four to six cycles of PEC, which was recommended for ypT0-2N0 patients, while a minimum of five PEC cycles was recommended for ypT3-4N0 patients. CONCLUSION: AC treatment is still necessary for ypN0. The duration reduction could be applied for the ypT0-2N0 stage patients but may not be suitable for higher ypT stages and beyond. A multicenter-based study is required.

Correlative Analysis Between Adverse Events of Preoperative Chemotherapy and Postoperative Complications of Gastric Cancer.

Background and Objectives: This study aims to explore the safety of preoperative chemotherapy and clarify whether preoperative chemotherapy with oxaliplatin + S-1 (SOX) regimen and its adverse events are associated with higher risks of postoperative complications. Methods: We included consecutive patients with gastric cancer who underwent gastrectomy in our department between July 1 2018, and January 31 2020. Patients with preoperative SOX regimen chemotherapy were included in the analysis. Results: In the 343 included patients, 77 cases underwent preoperative chemotherapy. In total, surgical complications were found in 117 patients (34.1%), and there was no significant difference between the patients with and without preoperative chemotherapy before and after propensity score matching (p > 0.05, respectively). Multivariate analysis showed that preoperative comorbidities (p = 0.026) and the preoperative cT4b (p = 0.028) were independent risk factors in postoperative complications. In patients with preoperative chemotherapy, neither the occurrence of adverse events nor their severity was associated with postoperative complications (p > 0.05). However, the patients who received five to six cycles were more prone to postoperative complications than those who received three to four cycles (62.5 vs. 27.9%, OR = 4.306, 95% Cl = 1.282-14.464, p = 0.018). Conclusions: Occurrence of postoperative complications was not influenced by preoperative SOX chemotherapy. However, increased cycles of chemotherapy may lead to higher incidence of postoperative complications.

Prognostic and predictive value of mismatch repair deficiency in gastric and gastroesophageal junction adenocarcinoma patients receiving neoadjuvant or adjuvant chemotherapy.

BACKGROUND AND OBJECTIVES: Evidence is inconclusive regarding the prognostic significance of deficient DNA mismatch repair (dMMR) in gastric and gastroesophageal junction (GEJ) adenocarcinoma patients receiving chemotherapy. We aim to explore such associations with a large cohort. METHODS: We retrospectively identified a consecutive cohort of patients who had histology proven gastric or GEJ adenocarcinoma and received neoadjuvant chemotherapy plus surgery or upfront surgery plus adjuvant chemotherapy. MMR status was assessed by immunohistochemistry staining on surgical specimen. The association of MMR status with tumor regression grade (TRG), overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: In total, 1568 patients received neoadjuvant or adjuvant chemotherapy, of which 128 (8.2%) had dMMR tumors. No significant difference was found in the frequencies of TRG categories between proficient MMR (pMMR) and dMMR tumors (p = .62). Among patients receiving neoadjuvant chemotherapy, dMMR status was associated with better OS (log-rank p = .044) and DFS (log-rank p = .022) in the univariate analysis; this association became nonsignificant after adjusting for pathologic stages and other prognostic factors. Similar results were found for patients receiving adjuvant chemotherapy. CONCLUSIONS: dMMR status was not significantly associated with OS and DFS among gastric and GEJ adenocarcinoma patients with neoadjuvant and adjuvant platinum and fluorouracil-based chemotherapy.

Short-term outcomes after totally laparoscopic total gastrectomy with esophagojejunostomy constructed by π-shaped method versus overlap method.

BACKGROUND: Regarding the overlap anastomosis and recently introduced π-shaped anastomosis, there is no consensus on which intracorporeal esophagojejunostomy (EJS) methods are preferred using linear stapler in totally laparoscopic total gastrectomy (TLTG). This study aims to evaluate the short-term outcomes using two methods. METHODS: Patients with upper gastric cancer underwent TLTG with either π-shaped (n = 48) or the modified overlap method using knotless barbed sutures (MOBS) (n = 37) were included in our study. Intraoperative and perioperative outcomes were compared. RESULTS: All patients achieved R0 resection margin. The overall esophagojejunal (E-J)-related complications rate was 7.06%. There was no significant difference between the two groups in terms of postoperative complications, margin distance, numbers of lymph nodes (LNs), length of stay. In the π-shaped group, anastomosis time (19.61 ± 7.17 min vs. 27.09 ± 3.59 min, p < 0.001) was significantly lower. The consumable costs for surgery were similar (44 507.74¥ [42 933.03-46 937.29] vs. 43 718.36¥ [42 743.25-47 256.06], p = 0.825). The first defection time was significantly longer in π-shaped group (131.00 h [93.75-171.25] vs. 100.00 h [85.00-120.00], p = 0.026), whereas the other postoperative recovery parameters were similar. No mortality was observed. CONCLUSIONS: Both methods showed similar short-term postoperative outcomes. The π-shaped technique was faster than the MOBS method without significantly increasing the supplies costs. Large prospective studies are warranted.