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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. 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. 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. Our study suggests that AL can be early diagnosed after gastric cancer surgery by measuring drainage IFs.

Neoadjuvant chemotherapy (NACT) and laparoscopic surgery have been increasingly used in the treatment of gastric cancer, however, the feasibility and safety of totally laparoscopic gastrectomy after NACT still remain unknown.At the Gastrointestinal cancer center of Peking university cancer hospital and institute in Beijing, clinical and pathological data of patients who has received NACT, followed by radical laparoscopic gastrectomy was retrospectively reviewed between March 2011 and November 2019. Patients were divided into 2 groups according to whether intracorporeal anastomosis or extracorporeal anastomosis had been performed, short-term outcomes (post-operative recovery index and complications) and economic cost were compared between 2 groups.All of 139 patients underwent laparoscopic gastrectomy. 87 [62.6%] patients had totally laparoscopic gastrectomy (TLG) and 52 [37.4%] patients had laparoscopic-assisted gastrectomy (LAG). Overall complication rate was 28.8% in all patients. TLG group was significantly associated with lower overall complication rate (21.8% VS 40.4%; p = 0.019) and major complication rate (3.4% VS 13.5%; p = 0.001) compared with LAG group. Overall cost was similar (p = 0.077). In subgroup analysis, totally laparoscopic total gastrectomy (TLTG) group showed lower overall postoperative complication rate (19.0% VS 56.5%; p = 0.011), as well as marginal significant differences in major complication (0% VS 21.7%; p = 0.05) than laparoscopic-assisted total gastrectomy (LATG) group. Earlier first liquid diet (4 [3.5-5] day VS 6 [4-6.5] day; p = 0.047), earlier first aerofluxus (3 [3-4] day VS 4 [3-4.5] day; p = 0.02) and a shorter hospital stay (9 [8-12] day VS 12 [10-15] day; p = 0.004) were observed in TLTG group. Overall and major complication rate were similar in totally laparoscopic distal gastrectomy (TLDG) and laparoscopic assisted distal gastrectomy (LADG) group (22.7% VS 27.6%; p = 0.611; 4.5% VS 6.9%; p = 0.639; respectively). Significant differences were found between TLDG and LADG groups regarding time to first liquid diet (4 [3-5] day VS 6 [3.75-6] day; p = 0.006), time to first aerofluxus (3 [3-3] day VS 4 [3-6] day; p 0.001), time to first defecation (4 [4-5] day VS 5 [4-6] day; p = 0.045), time to remove all drainage (7 [6-8] day VS 8 [6-9] day; p = 0.021), white blood cell count on postoperative Day 1 (9.54 ± 2.49 10For patients with Locally advanced gastric cancer who received NACT, totally laparoscopic gastrectomy, including TLTG and TLDG, doesn't increase complications and overall cost compared with LAG, and has advantages in gastrointestinal function recovery, incision length and postoperative hospital stay.

Summary Background The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. Methods We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40–60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40–60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. Findings Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5–56·3) in the adjuvant-CapOx group, 56·5% (51·0–61·7) in the adjuvant-SOX group, and 59·4% (53·8–64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61–0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68–1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3–4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. Interpretation Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. Funding National Key Research and Development Program of China, Beijing Scholars Program 2018–2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Background The prognostic values of preoperative tumor markers (TMs) remain elusive in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy treatment (NACT). This study aimed to assess and establish a novel scoring system incorporating carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4) to enhance prognostic accuracy for progression-free survival (PFS) and pathological response (pCR). Methods Patients' data were retrospectively analyzed from December 2006 to December 2017 in our center. The cutoff value of TMs was determined using the time-dependent receiver operating test characteristics method. These three TMs were allocated 1 point each for the post neoadjuvant chemotherapy combination of tumor markers (post-NACT CTM) scores. The training group comprised 533 patients, responsible for full analysis, and the validation group comprised 137 patients based on the selection protocol. Results Of 533 enrolled patients, 138, 233, 117, and 45 patients scored 0, 1, 2, 3 respectively. The 3-year PFS rate Multivariate analysis revealed that post-NACT CTM score was an independent predictor of PFS (0 vs. 1, HR: 1.34, 95% CI: 0.92–1.96, P = 0.128; 0 vs. 2, HR: 2.03, 95% CI: 1.35–3.05, P = 0.001; 0 vs. 3, HR: 2.98, 95% CI: 1.83–4.86, P P = 0.077; 2/3 vs. 0, OR: 4.33, 95% CI: 1.38–13.61, P = 0.012). A nomogram was formed with both internal and external validation. Conclusions The post-NACT CTM score system served as a strong independent predictor for PFS and pCR in LAGC patients who received NACT. Further population-based studies are required to confirm our results.

BACKGROUND: Until now, little is known about the benefit of laparoscopic total gastrectomy (LTG) after neoadjuvant chemotherapy (NACT). This study was designed to compare the safety and efficacy of the LTG versus the open total gastrectomy (OTG) approach after NACT treatment in patients with advanced gastric cancer (AGC). METHODS: This study involved a cohort of 145 patients with AGC who underwent total gastrectomy after NACT at our centre between April 2013 and August 2018 including 24 cases of LTG and 121 OTG. The baseline characteristics were matched based on 1:2 balanced propensity score-matching method. RESULTS: Sixty-nine marched cases were finally analysed (23 LTG vs. 46 OTG). All patients underwent R0 resection. Compared to the OTG group, the LTG group had a longer surgery duration (P0.05). CONCLUSIONS: LTG had comparable safety and histological findings to OTG after NACT in the perioperative period; however, LTG is less invasive and patients can benefit from less IV-PCA use. Further research is needed to investigate long-term effects. KEYWORDS: Gastric cancer (GC); neoadjuvant chemotherapy (NACT); safety; laparoscopic technique

Background Evidence suggests that the anatomic extent of metastatic lymph nodes (MLNs) affects prognosis, as proposed by alternative staging systems. The aim of this study was to establish a new staging system based on the number of perigastric (PMLN) and extra-perigastric (EMLN) MLNs. Methods Data from a Chinese cohort of 1090 patients who had undergone curative gastrectomy with D2 or D2 plus lymphadenectomy for gastric cancer were retrospectively analysed. A Japanese validation cohort (n = 826) was included. Based on the Cox proportional hazards model, the regression coefficients of PMLN and EMLN were used to calculate modified MLN (MMLN). Prognostic performance of the staging systems was evaluated. Results PMLN and EMLN were independent prognostic factors in multivariate analysis (coefficients: 0.044, 0.115; all P MMLN = PMLN + 2.6 × EMLN. The MMLN staging system showed superior prognostic performance (C-index: 0.751 in the Chinese cohort; 0.748 in the Japanese cohort) compared with the five published LN staging systems when MMLN numbers were grouped as follows: MMLN0 (0), MMLN1 (1–4), MMLN2 (5–8), MMLN3 (9–20), and MMLN4 (>20). Discussion The MMLN staging system is suitable for assessing overall survival among patients undergoing curative gastrectomy with D2 or D2 plus lymphadenectomy.

Background Recently, artificial neural network (ANN) methods have also been adopted to deal with the complex multidimensional nonlinear relationship between clinicopathologic variables and survival for patients with gastric cancer. Using a multinational cohort, this study aimed to develop and validate an ANN‐based survival prediction model for patients with gastric cancer. Methods Patients with gastric cancer who underwent gastrectomy in a Chinese center, a Japanese center, and recorded in the Surveillance, Epidemiology, and End Results database, respectively, were included in this study. Multilayer perceptron neural network was used to develop the prediction model. Time‐dependent receiver operating characteristic (ROC) curves, area under the curves (AUCs), and decision curve analysis (DCA) were used to compare the ANN model with previous prediction models. Results An ANN model with nine input nodes, nine hidden nodes, and two output nodes was constructed. These three cohort's data showed that the AUC of the model was 0.795, 0.836, and 0.850 for 5‐year survival prediction, respectively. In the calibration curve analysis, the ANN‐predicted survival had a high consistency with the actual survival. Comparison of the DCA and time‐dependent ROC between the ANN model and previous prediction models showed that the ANN model had good and stable prediction capability compared to the previous models in all cohorts. Conclusions The ANN model has significantly better discriminative capability and allows an individualized survival prediction. This model has good versatility in Eastern and Western data and has high clinical application value., Using a multinational cohort, this study developed and externally validated an artificial neural network‐based survival prediction model for patients with gastric cancer after gastrectomy.

Background: With the rapid aging of global population, the number of elderly patients with gastric cancer is increasing. This study aimed to evaluate short- and long-term outcomes after laparoscopi...

Background The clinical values of inflammatory and nutritional markers remained unclear for gastric cancer with neoadjuvant chemotherapy (NACT). Methods The inflammatory, nutritional markers and their changes were analyzed for locally advanced gastric cancer with NACT. The predictive value was evaluated by the Cox proportional hazards regressions under three hypothesized scenarios. The nomograms including independent prognostic factors were plotted for survival prediction. Results A total of 225 patients were included in the study. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index, and hemoglobin (Hgb) were significantly reduced, and the body mass index was significantly increased after NACT (all P P = 0.059] showed a trend to correlate with the overall survival (OS) when only pre-NACT markers available; The post-NACT Hgb (HR = 0.982, P = 0.015) was the independent prognostic factor when only post-NACT markers available; The post-NACT Hgb (HR = 0.984, P = 0.025) and the change value of LMR (HR = 1.183, P = 0.036) were the independent prognostic factors when both pre- and post-NACT markers available. The nomogram had a similar Harrell’s C-statistic compared to ypTNM stage (0.719 vs. 0.706). Conclusion For locally advanced gastric cancer, the NACT could significantly decrease some inflammatory markers. The pre-NACT NLR, the post-NACT Hgb and the change value of LMR had some values in survival prediction combined with age, sex, tumor location and the clinical stages under different clinical scenarios. The elevated initial NLR, the preoperative anemia and the greater change value of LMR implied a poor prognosis.

H-ferritin (HFn) nanocarrier is emerging as a promising theranostic platform for tumor diagnosis and therapy, which can specifically target tumor cells via binding transferrin receptor 1 (TfR1). This led us to investigate the therapeutic function of TfR1 in GC. The clinical significance of TfR1 was assessed in 178 GC tissues by using a magneto-HFn nanoparticle-based immunohistochemistry method. The therapeutic effects of doxorubicin-loaded HFn nanocarriers (HFn-Dox) were evaluated on TfR1-positive GC patient-derived xenograft (GC-PDX) models. The biological function of TfR1 was investigated through in vitro and in vivo assays. TfR1 was upregulated (73.03%) in GC tissues, and reversely correlated with patient outcome. TfR1-negative sorted cells exhibited tumor-initiating features, which enhanced tumor formation and migration/invasion, whereas TfR1-positive sorted cells showed significant proliferation ability. Knockout of TfR1 in GC cells also enhanced cell invasion. TfR1-deficient cells displayed immune escape by upregulating PD-L1, CXCL9, and CXCL10, when disposed with IFN-γ. Western blot results demonstrated that TfR1-knockout GC cells upregulated Akt and STAT3 signaling. Moreover, in TfR1-positive GC-PDX models, the HFn-Dox group significantly inhibited tumor growth, and increased mouse survival, compared with that of free-Dox group. TfR1 could be a potential prognostic and therapeutic biomarker for GC: (i) TfR1 reversely correlated with patient outcome, and its negative cells possessed tumor-aggressive features; (ii) TfR1-positive cells can be killed by HFn drug nanocarrier. Given the heterogeneity of GC, HFn drug nanocarrier combined with other therapies toward TfR1-negative cells (such as small molecules or immunotherapy) will be a new option for GC treatment.

Gastric cancer (GC) is a global health problem, with more than 1 million people newly diagnosed with GC worldwide each year. GC is more prevalent in less developed countries than in more developed countries. About half of all GC cases worldwide occur in East Asia, notably China. Globally, overall incidence rates of GC are declining, which is potentially attributed to a decrease in Helicobacter pylori (H. pylori) infection and the use of refrigeration to preserve foods rather than salt. GC is a multifactorial disease, and its occurrence and development were impacted by environmental and genetic factors. H. pylori infection is the primary risk factor for GC, especially for non-cardia. The prognosis of GC is poor due to stages at the first diagnosis. The 5-year survival rate is less than 10% when patients are diagnosed at an advanced stage, but the rate is as high as 85% if patients are detected at an earlier stage. Endoscopic screening can potentially prevent GC by early diagnosis and early treatment and has been widely adopted in screening programs in East Asian countries, such as Japan and Korea. This review summarizes updated epidemiological aspects, risk factors, and prevention strategies of GC in recent years to help researchers determine the most effective intervention strategies for reducing risk of GC.

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.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 IWe 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).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.

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)-1β, 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.

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.

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

Background Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. Patients and methods A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients’ PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. Results RS1, RS2, and Lauren type were significant predictors of occult PM (all P

Background Among locally advanced gastric cancer (LAGC) patients, poor response to initial neoadjuvant chemotherapy (NAC) is associated with unfavorable outcomes; however, changing the postoperative therapy regimen in this group of patients is unclear. We compared the poor responders who continued the original protocols with that of patients who switched treatment after NAC plus D2 gastrectomy. Methods Our study included LAGC patients who achieved tumor regression grade 3 according to the American Joint Committee on Cancer/College of American Pathologists system, after NAC, between December 2006 and December 2017 at our institution. Outcomes were overall survival (OS), progression-free survival (PFS), and adverse events during postoperative treatment. The propensity score matching method was used to match patients. Results Overall, 160 patients were enrolled in the final analysis set, including 21 switched cases and 139 non-switched cases. A 1:2 matched cohort (21 switching vs. 42 non-switching) was generated to eliminate all confounding factors. No statistical differences were observed in OS and PFS, either in the whole patients (OS: log-rank p = 0.804; PFS: log-rank p = 0.943) or in the matched cohort (OS: log-rank p = 0.907; PFS: log-rank p = 0.670) between the two groups. Patients with changed regimens had a significantly higher rate of peripheral neurotoxicity (p = 0.045). Contrarily, a lower rate of overall adverse events was observed in the non-switching group with marginal significance (p = 0.069). Conclusion Adjusting to a non-cross-resistant regimen only by post-NAC pathological evaluation may not be sufficient for designing an effective treatment route for LAGC poor responders. Treatment change required a more scrutinized clinical track, which involved a multifaceted assessment.

BackgroundThe relationship between time to surgery (TTS) and survival benefit is not sufficiently demonstrated by previous studies in locally advanced gastric cancer (LAGC). This study aims to assess the impact of TTS after neoadjuvant chemotherapy (NACT) on long-term and short-term outcomes in LAGC patients.MethodsData were collected from patients with LAGC who underwent NACT between January 2007 and January 2018 at our institution. Outcomes assessed were long-term survival, pathologic complete response (pCR) rate, and postoperative complications.ResultsThis cohort of 426 patients was divided into five groups by weeks of TTS. Under cox regression, compared to other groups, the 22–28 days and 29–35 days groups revealed a better OS (≤21 vs. 22–28 days: HR 1.54, 95% CI = 0.81–2.93, P = 0.185; 36–42 vs. 22–28 days: HR 2.20, 95% CI = 1.28−3.79, P = 0.004; 43–84 vs. 22–28 days: HR 1.83, 95% CI = 1.09–3.06, P = 0.022) and PFS (≤21 vs. 22–28 days: HR 1.54, 95% CI = 0.81–2.93, P = 0.256; 36–42 vs. 22–28 days: HR 2.20, 95% CI = 1.28−3.79, P = 0.111; 43–84 vs. 22–28 days: HR 1.83, 95% CI = 1.09–3.06, P = 0.047). Further analysis revealed a better prognosis in patients with TTS within 22–35 days (OS: HR 1.78 95% CI = 1.25−2.54, P = 0.001; PFS: HR 1.49, 95% CI = 1.07−2.08, P = 0.017). Postoperative stay was significantly higher in the ≤21 days group, while other parameters revealed no statistical significance (P > 0.05). Restricted cubic spline depicted the nonlinear relationship between TTS and OS/PFS.ConclusionPatients who received surgery within 3−5 weeks experienced the maximal survival benefit without an increase in postoperative complications or lowering the rate of pCR. Further investigations are warranted.

Background: With the popularization of Enhanced Recovery After Surgery (ERAS), identifying patients with complications before discharging becomes important. This study aimed to explore the efficacy of C-reactive protein (CRP) in predicting infectious complications after gastrectomy. Methods: Patients with gastric cancer who underwent gastrectomy at Beijing Cancer Hospital from March 2017 to April 2018 were enrolled in the training set. Complications were prospectively registered. Receiver operating characteristic analysis was performed to assess the diagnostic accuracy of CRP via evaluating the area under the curve (AUC). Patients who had CRP tested on postoperative day (POD) 5 and accepted gastrectomy from April to December 2018 were included in the validation set to validate the cut-off value of CRP obtained from the training set. Results: A total of 350 patients were included (263 patients in the training set and 87 patients in the validation set). Out of these, 24 patients were diagnosed with infectious complications and 17 patients had anastomotic leakage in the training set. The CRP level on POD5 had superior diagnostic accuracy for infectious complications with an AUC of 0.81. The cut-off value of CRP on POD5 at 166.65 mg/L yielded 93% specificity and 97.2% negative predict value (NPV); For anastomotic leakage, the AUC of CRP on POD5 was 0.81. Using the cut-off value of CRP at 166.65 mg/L on POD5 achieved 92% specificity and 98.6% NPV. The optimal cut-off value (CRP 166.65 mg/L on POD5) was validated in the validation set. It achieved 97.5% specificity and 94.0% NPV for infectious complications, and 97.6% specificity and 96.4% NPV for anastomotic leakage. Conclusion: CRP is a reliable predictive marker for the diagnosis of inflammatory complications following gastric surgery. However, this study was based on preliminary data. The validity of this data needs confirmation by a larger number of cases.

Several patient-derived tumor models emerged recently as robust preclinical drug-testing platforms. However, their potential to guide clinical therapy remained unclear. Here, we report a model called patient-derived tumor-like cell clusters (PTCs). PTCs result from the self-assembly and proliferation of primary epithelial, fibroblast, and immune cells, which structurally and functionally recapitulate original tumors. PTCs enabled us to accomplish personalized drug testing within 2 weeks after obtaining the tumor samples. The defined culture conditions and drug concentrations in the PTC model facilitate its clinical application in precision oncology. PTC tests of 59 patients with gastric, colorectal, or breast cancers revealed an overall accuracy of 93% in predicting their clinical outcomes. We implemented PTC to guide chemotherapy selection for a patient with mucinous rectal adenocarcinoma who experienced recurrence with metastases after conventional therapy. After three cycles of a nonconventional therapy identified by the PTC, the patient showed a positive response. These findings need to be validated in larger clinical trials, but they suggest that the PTC model could be prospectively implemented in clinical decision-making for therapy selection.

Supplemental material, Supplementary_material for Clinical predictive efficacy of C-reactive protein for diagnosing infectious complications after gastric surgery by Jinyao Shi, Zhouqiao Wu, Qi Wang, Yan Zhang, Fei Shan, Shiyang Hou, Xiangji Ying, Longtao Huangfu, Ziyu Li and Jiafu Ji in Therapeutic Advances in Gastroenterology

This study aims to evaluate the new ypTNM staging system in Chinese gastric cancer patients. We conducted retrospective survival and regression analyses using a database of gastric cancer patients who underwent neoadjuvant chemotherapy at the Peking University Cancer Hospital and Institute from January 2007 to January 2015. A total of 473 patients were included in the study with 28 pathological complete response (pCR) cases, 3 ypT0N1 cases, 65 stage I cases, 126 stage II cases, and 251 stage III cases. The pCR cases had similar survival to stage I patients (p > 0.05). The 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates of stage I, II and III patients were significantly different (3-year DFS: 89.0, 75.5, and 39.6%, p

Objective To compare the effect of neoadjuvant chemotherapy (NACT) with adjuvant chemotherapy (ACT) using oxaliplatin plus S-1 (SOX) or capecitabine (CapeOX) on gastric cancer patients with D2 lymphadenectomy. Methods This was a two-by-two factorial randomized phase II-III trial, and registered on ISRCTN registry (No. ISRCTN12206108). Locally advanced gastric cancer patients were randomized to neoadjuvant SOX, neoadjuvant CapeOX, adjuvant SOX, or adjuvant CapeOX arms. Primary analysis was performed on an intention-to-treat (ITT) basis using overall survival (OS) as primary endpoint. Results This trial started in September 2011 and closed in December 2012 with 100 patients enrolled. Treatment completion rate was 56%, 52%, 38% and 30% in the four arms, respectively. NACT group had fewer dropouts due to unacceptable toxicity (P=0.042). Surgical complication rate did not differ by the four groups (P=0.986). No survival significant difference was found comparing NACT with ACT (P=0.664; 5-year-OS: 70% vs. 74% respectively), nor between the SOX and CapeOX groups (P=0.252; 5-year-OS: 78% vs. 66% respectively). Subgroup analysis showed SOX significantly improved survival in patients with diffuse type (P=0.048). Conclusions No significant survival difference was found between NACT and ACT. SOX and CapeOX had good safety and efficacy as neoadjuvant regimens. Diffuse type patients may survive longer due to SOX.

In order to describe and examine differences in social support and care needs among disabled Chinese elderly, the current study used stratified sampling to survey local residents of Beijing age 60 or over in the districts of Xicheng, Chaoyang, and Tongzhou in 2016. Structured in-person interviews were conducted with a 7-domain questionnaire. Multiple logistic regressions were used to compare social support and care needs among functioning, partially disabled, and completely disabled elderly. All statistical analyses were performed using SPSS 19.0 with a significance level of 0.05 (two-sided). One thousand and eighty-three residents completed the survey. Based on Activities of Daily Living (ADL) scores, 736 (68.0%) respondents were functioning (ADL score = 14), 167 (15.4%) were partially disabled (14 < ADL score < 22), and 180 (16.6%) were fully disabled (ADL score ≥ 22). Most of the disabled had formal financial support, they received daily care at home, and they received modest emotional support. After controlling for confounding factors, fully disabled respondents were 2.35 times (p = 0.018) more likely to receive financial support and 3.65 times (p = 0.003) more likely to receive emotional support than functioning respondents. However, the fully functioning and partially disabled did not differ significantly in terms of financial or emotional support. Compared to fully functioning respondents, partially disabled respondents were 0.49 (p < 0.001) times less likely to be fully satisfied with their daily care while fully disabled respondents were 0.37 (p < 0.001) times less likely to be fully satisfied with that care. The current study provided a thorough depiction of the current status of social support and care needs of disabled Chinese elderly. More attention should be paid to social support for the partially disabled and daily care for both the partially and fully disabled.

Background: The objective of this study is to identify independent risks and protective factors and to construct a mortality prediction model for gastrectomy in the Chinese population. Study design: This is a population-based prospective cohort at an institutional level. Seventy-two participating hospitals reported their annual gastrectomy data between 2014 and 2016, while 44 variables covering the institution and surgical information were included in the analysis. We used R software to encode and complete data pre-processing. The first difference model was applied to build the risk model. Data from 2014 and 2015 were assigned to risk model development, while data from 2016 was used for validation. Results: In the included centers with 94,277 gastric cancer cases, the in-hospital mortality rate was 0.32%. The regression model revealed that provinces with low-middle GDP, hospitals with annual gastrectomy volume between 100 and 500, greater volume of urgent surgeries performed, larger proportion of males, and a higher proportion of liver metastasis were independent risk factors for mortality following gastric surgeries, while higher laparoscopic resection volume, greater volume of distal gastrectomy with B2 reconstruction, and larger proportion of palliative surgery were independent protective factors (p < 0.05, respectively). In the prediction test, the mean square error of the training set was 0.948, while that of the test set was 0.728, demonstrating the effectiveness of this model. Conclusions: We constructed the first mortality risk prediction model for gastric cancer surgery in the Chinese population. The identified risk factors will help with the therapy selection, while further informing Chinese medical policy decision-makers.

Background: Understanding the contextual factors that influence the dissemination and implementation of evidence-based chronic disease prevention (EBCDP) interventions in public health settings across countries could inform strategies to support the dissemination and implementation of EBCDP interventions globally and more effectively prevent chronic diseases. A survey tool to use across diverse countries is lacking. This study describes the development and reliability testing of a survey tool to assess the stageof dissemination, multi-level contextual factors, and individual and agency characteristicsthat influence the dissemination and implementation of EBCDP interventions in Australia, Brazil, China, and the United States. Methods: Development of the 26-question survey included, a narrative literature review of extant measures in EBCDP; qualitative interviews with 50 chronic disease prevention practitioners in Australia, Brazil, China, and the United States; review by an expert panel of researchers in EBCDP; and test-retest reliability assessment. Results: A convenience sample of practitioners working in chronic disease prevention in each country completed the survey twice (N = 165). Overall, this tool produced good to moderately reliable responses. Generally, reliability of responses was higher among practitioners from Australia and the United States than China and Brazil. Conclusions: Reliability findings inform the adaptation and further development of this tool. Revisions to four questions are recommended before use in China and revisions to two questions before use in Brazil. This survey tool can contribute toward an improved understanding of the contextual factors that public health practitioners in Australia, Brazil, China, and the United States face in their daily chronic disease prevention work related to the dissemination and implementation of EBCDP interventions. This understanding is necessary for the creation of multi-level strategies and policies that promote evidence-based decision-making and effective prevention of chronic diseases on a more global scale. Refereed/Peer-reviewed

Table S1. Univariate analysis of clinical and pathological characteristics associated with using ypTNM stage and patient survival. Figure S1. Adjusted comparative prognosis implication of ypTNM vs yTNM on overall survival in unmatched cohorts of patients with gastric cancer, stratified by detailed TNM stage (DOCX 1083 kb)

Background Pathological stage is considered as the best prognosis indicator for gastric cancer. With the increasing use of neoadjuvant chemotherapy (NACT), the latest TNM staging included a new pathological stage of ypTNM for patients with NACT. However, no study has investigated if ypTNM stage has the same prognostic implication as pTNM stage for gastric cancer. Methods We retrospectively selected eligible patients within a prospectively maintained database containing all patients treated with gastric cancer in Peking University Cancer Hospital from 2007 to 2015 using overall survival as the outcome. Patients using ypTNM and pTNM were 1:1 matched by propensity scores (PS) calculated from a model containing variables associated with ypTNM use or survival. Overall survival was compared by unconditional Cox regression. Conventional multivariate analysis was conducted to corroborate PS matching results. Results 1441 patients were included in the analysis with a median follow-up of 37 months (range = 2–106). The matched sample contained 756 patients. After PS matching, patients with specific ypTNM stage were 1.34 (95%CI = 1.05–1.72, P = 0.019) times more likely to die than patients with the same pTNM stage. Similar to the results of PS matching, multivariate Cox regression yielded a hazard ratio (HR) of 1.35 (95%CI = 1.09–1.67, P = 0.006). Subgroup analysis indicated this survival difference between ypTNM and pTNM stage varied by the specific TNM stage of patients. The HR was 3.44 (95%CI = 1.06–11.18, P = 0.040) and 1.28 (95%CI = 1.00–1.62, P = 0.048) for patients in stage I and III, respectively; whereas for stage II patients, no significant difference was observed (HR = 1.37, 95%CI = 0.78–2.38, P = 0.27). Conclusion Gastric cancer patients with specific ypTNM stage had worse prognosis compared to those at the same stage defined by pTNM. Electronic supplementary material The online version of this article (10.1186/s12885-019-5283-3) contains supplementary material, which is available to authorized users.

Background Preoperative diagnosis of peritoneal metastasis with gastric cancer remains challenging. This study explored the abnormal computed tomography (CT) signs of occult peritoneal metastasis (OPM) and evaluated it by region-to-region comparison using staging laparoscopy, from which a 4-point CT score system was developed. Methods Patients with advanced gastric cancer (stage cT ≥ 2M0) diagnosed by CT were enrolled in the study. Occult peritoneal metastasis detected during staging laparoscopy was compared with preoperative CT to investigate the presence of abnormal signs by a region-to-region comparison. A 4-point CT score system was developed to define the radiologic characteristics. Subsequently, the diagnostic efficacy of the CT score system was prospectively verified. Results In this study, 57 OPM regions were detected by staging laparoscopy in 33 of the 385 enrolled patients. The greater omentum was the most frequent site of OPM (38.60%, 22/57), which usually exhibited a smudge-like ground-glass opacity (S-GGO) (90.91%, 20/22) with a mean CT score of 2.14. The parietal and perihepatic peritoneum was the second most common site (22.81%, 13/57). A 4-point CT score system was developed based on the results. A cutoff CT score of 2 or higher was associated with a false-negative rate of 2% (2/99). This CT score system had a sensitivity of 87.5% and a specificity of 76.4% for an OPM-positive diagnosis (area under the curve, 0.848). The agreement between two radiologists on the assigned final score was 76.2% (kappa, 0.5). Conclusions Patients with OPM mostly exhibited S-GGO on CT, which should be interpreted cautiously. The 4-point CT score system may improve the pretreatment evaluation of occult peritoneal metastasis, and staging laparoscopy might not be necessary for patients with a score lower than 2.