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Background: Robotic gastrectomy is increasingly utilized for gastric cancer, but high morbidity remains a concern. Myosteatosis or low skeletal muscle density reflecting fatty infiltration, associates with complications after other cancer surgeries but has not been evaluated for robotic gastrectomy., Methods: This retrospective study analysed 381 patients undergoing robotic gastrectomy for gastric cancer from September 2019 to October 2022. Myosteatosis was quantified on preoperative computed tomography (CT) images at lumbar 3 (L3). Propensity score matching addressed potential confounding between myosteatosis and non-myosteatosis groups. Outcomes were postoperative complications, 30 days mortality, 30 days readmissions and survival., Results: Myosteatosis was present in 33.6% of patients. Myosteatosis associated with increased overall (47.7% vs. 26.5%, p < 0.001) and severe complications (12.4% vs. 4.9%, p < 0.001). After matching, myosteatosis remained associated with increased overall complications, major complications, intensive care unit (ICU) transfer and readmission (all p < 0.05). Myosteatosis independently predicted overall [odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.57-5.20, p = 0.001] and severe complications (OR = 4.81, 95% CI: 1.51-15.27, p = 0.008). Myosteatosis also associated with reduced overall (85.0% vs. 93.2%, p = 0.015) and disease-free survival (80.3% vs. 88.4%, p=0.029). On multivariate analysis, myosteatosis independently predicted poorer survival [hazard ratio (HR) = 2.83, 95% CI: 1.32-6.08, p=0.012] and disease-free survival (HR = 1.83, 95% CI: 1.01-3.30, p=0.032)., Conclusion: Preoperative CT-defined myosteatosis independently predicts increased postoperative complications and reduced long-term survival after robotic gastrectomy for gastric cancer. Assessing myosteatosis on staging CT could optimize preoperative risk stratification., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Choosing an optimal reconstruction method is pivotal for patients with gastric cancer undergoing distal gastrectomy. The uncut Roux-en-Y reconstruction, a variant of the conventional Roux-en-Y approach (or variant of the Billroth II reconstruction), employs uncut devices to occlude the afferent loop of the jejunum. This modification is designed to mitigate postgastrectomy syndrome and enhance long-term functional outcomes. However, the comparative benefits and potential harms of this approach compared to other reconstruction techniques remain a topic of debate., Objectives: To assess the benefits and harms of uncut Roux-en-Y reconstruction after distal gastrectomy in patients with gastric cancer., Search Methods: We searched CENTRAL, PubMed, Embase, WanFang Data, China National Knowledge Infrastructure, and clinical trial registries for published and unpublished trials up to November 2023. We also manually reviewed references from relevant systematic reviews identified by our search. We did not impose any language restrictions., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs comparing uncut Roux-en-Y reconstruction versus other reconstructions after distal gastrectomy for gastric cancer. The comparison groups encompassed other reconstructions such as Billroth I, Billroth II (with or without Braun anastomosis), and Roux-en-Y reconstruction., Data Collection and Analysis: We used standard Cochrane methodological procedures. The critical outcomes included health-related quality of life at least six months after surgery, major postoperative complications within 30 days after surgery according to the Clavien-Dindo Classification (grades III to V), anastomotic leakage within 30 days, changes in body weight (kg) at least six months after surgery, and incidence of bile reflux, remnant gastritis, and oesophagitis at least six months after surgery. We used the GRADE approach to evaluate the certainty of the evidence., Main Results: We identified eight trials, including 1167 participants, which contributed data to our meta-analyses. These trials were exclusively conducted in East Asian countries, predominantly in China. The studies varied in the types of uncut devices used, ranging from 2- to 6-row linear staplers to suture lines. The follow-up periods for long-term outcomes spanned from 3 months to 42 months, with most studies focusing on a 6- to 12-month range. We rated the certainty of evidence from low to very low. Uncut Roux-en-Y reconstruction versus Billroth II reconstruction In the realm of surgical complications, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Billroth II reconstruction may make little to no difference to major postoperative complications (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.24 to 4.05; I² = 0%; risk difference (RD) 0.00, 95% CI -0.04 to 0.04; I² = 0%; 2 studies, 282 participants; very low-certainty evidence) and incidence of anastomotic leakage (RR 0.64, 95% CI 0.29 to 1.44; I² not applicable; RD -0.00, 95% CI -0.03 to 0.02; I² = 32%; 3 studies, 615 participants; very low-certainty evidence). We are very uncertain about these results. Focusing on long-term outcomes, low- to very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Billroth II reconstruction may make little to no difference to changes in body weight (mean difference (MD) 0.04 kg, 95% CI -0.84 to 0.92 kg; I² = 0%; 2 studies, 233 participants; low-certainty evidence), may reduce the incidence of bile reflux into the remnant stomach (RR 0.67, 95% CI 0.55 to 0.83; RD -0.29, 95% CI -0.43 to -0.16; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 3 to 7; 1 study, 141 participants; low-certainty evidence), and may have little or no effect on the incidence of remnant gastritis (RR 0.27, 95% CI 0.01 to 5.06; I 2 = 78%; RD -0.15, 95% CI -0.23 to -0.07; I 2 = 0%; NNTB 7, 95% CI 5 to 15; 2 studies, 265 participants; very low-certainty evidence). No studies reported on quality of life or the incidence of oesophagitis. Uncut Roux-en-Y reconstruction versus Roux-en-Y reconstruction In the realm of surgical complications, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Roux-en-Y reconstruction may make little to no difference to major postoperative complications (RR 4.74, 95% CI 0.23 to 97.08; I² not applicable; RD 0.01, 95% CI -0.02 to 0.04; I² = 0%; 2 studies, 256 participants; very low-certainty evidence) and incidence of anastomotic leakage (RR 0.34, 95% CI 0.05 to 2.08; I² = 0%; RD -0.02, 95% CI -0.06 to 0.02; I² = 0%; 2 studies, 213 participants; very low-certainty evidence). We are very uncertain about these results. Focusing on long-term outcomes, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Roux-en-Y reconstruction may increase the incidence of bile reflux into the remnant stomach (RR 10.74, 95% CI 3.52 to 32.76; RD 0.57, 95% CI 0.43 to 0.71; NNT for an additional harmful outcome (NNTH) 2, 95% CI 2 to 3; 1 study, 108 participants; very low-certainty evidence) and may make little to no difference to the incidence of remnant gastritis (RR 1.18, 95% CI 0.69 to 2.01; I² = 60%; RD 0.03, 95% CI -0.03 to 0.08; I² = 0%; 3 studies, 361 participants; very low-certainty evidence) and incidence of oesophagitis (RR 0.82, 95% CI 0.53 to 1.26; I² = 0%; RD -0.02, 95% CI -0.07 to 0.03; I² = 0%; 3 studies, 361 participants; very low-certainty evidence). We are very uncertain about these results. Data were insufficient to assess the impact on quality of life and changes in body weight., Authors' Conclusions: Given the predominance of low- to very low-certainty evidence, this Cochrane review faces challenges in providing definitive clinical guidance. We found the majority of critical outcomes may be comparable between the uncut Roux-en-Y reconstruction and other methods, but we are very uncertain about most of these results. Nevertheless, it indicates that uncut Roux-en-Y reconstruction may reduce the incidence of bile reflux compared to Billroth-II reconstruction, albeit with low certainty. In contrast, compared to Roux-en-Y reconstruction, uncut Roux-en-Y may increase bile reflux incidence, based on very low-certainty evidence. To strengthen the evidence base, further rigorous and long-term trials are needed. Additionally, these studies should explore variations in surgical procedures, particularly regarding uncut devices and methods to prevent recanalisation. Future research may potentially alter the conclusions of this review., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context., Methods: From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors., Results: Compared with ctDNA-negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37-5.48; P = 0.003], while patients with positive post-ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08-72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival (RFS). Moreover, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index (0.78; 95% CI = 0.71-0.84) than the model without ctDNA (0.71; 95% CI = 0.64-0.79; P = 0.009)., Conclusions: Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue-based and circulating tumor features could achieve better risk prediction., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of SUN YAT-SEN UNIVERSITY CANCER CENTER.)

Background: Gastric cancer is the fifth most frequent cancer globally. The introduction of minimally invasive surgery for gastric cancer aimed at reducing post-operative morbidity and hospital length of stay. Although the role of laparoscopic gastrectomy has been established, robotic gastric surgery has only recently gained popularity. The purpose of this study was to evaluate, with a multidimensional analysis, the learning curve of a single surgeon with extensive experience in laparoscopic gastrectomy., Methods: We prospectively collected data from 104 gastric cancer patients who underwent surgery with a robotic approach from June 2015 to June 2019 by a single surgeon. We performed 21 total gastrectomies (TGs) and 83 subtotal gastrectomies (STGs). A D2 lymphadenectomy was performed in all the patients. Proximal and distal resection margins were tumoour-free in all patients. There were no intraoperative complications, and no conversions occurred., Results: The plateau of the learning curve based on harvesting lymph nodes and operative time was not reached for TG. The learning curve of operative time for STG could be divided into three different phases: an early or learning phase from 1 to 27 cases, an intermediate or proficiency phase from 28 to 48 cases, and a late or mastery phase from 49 to 83 cases. The learning curve for harvesting lymph nodes was achieved after 41 cases in the STG group., Conclusion: This study shows that robotic gastrectomy is a complex procedure with a significant multiphasic learning curve. Nevertheless, the robotic learning curve seems to be more rapid than that of conventional laparoscopy. Most importantly, our results suggest that the robotic technique can provide oncological adequacy in terms of lymph node harvesting even in the very first phase of the learning curve., (© 2023 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons Ltd.)

Background: Although depression is associated with poor treatment outcomes in patients with cancer, little is known about whether lifestyle modifications could help prevent depression. The authors aimed to identify the effect of lifestyle modifications, including smoking cessation, alcohol abstinence, and starting regular physical activity, on new-onset depression in patients with gastric cancer who underwent surgery., Methods: By using the Korean National Health Insurance Service database, patients with gastric cancer who underwent surgery between 2010 and 2017 were identified. Self-reported lifestyle behaviors within 2 years before and after surgery were analyzed using the health examination database. Patients were classified according to changes in lifestyle behaviors, and their risk of new-onset depression was compared., Results: Among 18,902 patients, 2302 (12.19%) developed depression (26.00 per 1000 person-years). Smoking cessation (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66-0.91) and alcohol abstinence (HR, 0.79; 95% CI, 0.69-0.90) were associated with reduced risk of depression development compared with persistent smoking and persistent drinking, respectively. Starting regular physical activity was not associated with risk of depression. When lifestyle behaviors after gastrectomy were scored from 0 to 3 points (1 point each for not smoking, not drinking, and being physically active), the risk of depression tended to decrease as lifestyle scores increased from 0 points (reference) to 1 point (HR, 0.69; 95% CI, 0.55-0.83), 2 points (HR, 0.60; 95% CI, 0.50-0.76), and 3 points (HR, 0.55; 95% CI, 0.45-0.68)., Conclusions: Smoking cessation and alcohol abstinence are associated with reduced risk of developing depression in patients with gastric cancer who undergo surgery., (© 2023 American Cancer Society.)

The most effective option for gastric cancer risk management in individuals with a CDH1 germline pathogenic or likely pathogenic variant (PV) in Australia is prophylactic total gastrectomy (PTG). There is, however, increasing confidence in endoscopic surveillance as a risk management strategy thus affording individuals with a CDH1 PV with challenging decisions regarding their gastric cancer risk management. For young people, this decision-making comes at a complex development stage of emerging and young adulthood. This study aims to explore the factors that influence young people's decision-making about their gastric cancer risk management due to a CDH1 PV. Potential participants were identified and approached through the Parkville Familial Cancer Centre in Melbourne, Australia. Thematic analysis was used to interpret and analyze the data. Qualitative interviews were conducted with 13 people with a CDH1 PV aged 18 to 39 years, inclusive. The interviews found that participants' familial and shared experiences of cancer and risk management, perceived tolerance of uncertainty, and desire for control over their cancer risk were fundamental in their decision-making about their gastric cancer risk management. The participants' young adult life stage was also deemed particularly important in decisions about the timing of PTG. The findings of this study are vital to inform decisional counseling discussions with this unique population., (© 2021 National Society of Genetic Counselors.)

Objective: Our objective is to validate the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) criteria in malnutrition diagnosis compared with Patient-Generated Subjective Global Assessment (PG-SGA) and assess the impact of malnutrition diagnosed using GLIM criteria on the clinical outcomes of patients with GC., Methods: We retrospectively analyzed the data of 895 patients who underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Nutrition assessment was performed on all patients according to the GLIM criteria and PG-SGA. The κ statistic was used to evaluate the agreement between two methods. Multivariate logistic regression and Cox regression based on single-factor analysis were used to predict postoperative complications and overall survival rates., Results: Based on the GLIM criteria, 38.3% of the patients were diagnosed as malnourished, including 21.7% Stage I (moderate malnutrition) and 16.6% Stage II (severe malnutrition). GLIM criteria had a moderate agreement with PG-SGA (κ = 0.548). Patients in the Stage II malnutrition group had a higher incidence of complications, a longer postoperative length of stay, and higher hospitalization costs. Logistic regression showed that Stage II malnutrition was an independent risk predictor of postoperative complications (odds ratio, 3.28; 95% confidence interval [CI], 2.18-4.94). Furthermore, Cox regression analysis showed that both Stage I (hazard ratio [HR], 1.52; 95% CI, 1.11-2.07; P = .009) and Stage II (HR, 1.85; 95% CI, 1.34-2.53; P < .001) malnutrition were independent risk predictors of overall survival., Conclusion: Diagnosis of malnutrition according to the GLIM criteria is useful in predicting the adverse postoperative clinical outcomes of patients with gastric cancer., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background and Aim: Gastrointestinal endoscopy and biopsy-based pathological findings are needed to diagnose early gastric cancer. However, the information of biopsy specimen is limited because of the topical procedure; therefore, pathology doctors sometimes diagnose as gastric indefinite for dysplasia (GIN)., Methods: We compared the accuracy of physician-performed endoscopy (trainee, n = 3; specialists, n = 3), artificial intelligence (AI)-based endoscopy, and/or molecular markers (DNA methylation: BARHL2, MINT31, TET1, miR-148a, miR-124a-3, NKX6-1; mutations: TP53; and microsatellite instability) in diagnosing GIN lesions. We enrolled 24,388 patients who underwent endoscopy, and 71 patients were diagnosed with GIN lesions. Thirty-two cases of endoscopic submucosal dissection (ESD) in 71 GIN lesions and 32 endoscopically resected tissues were assessed by endoscopists, AI, and molecular markers to identify benign or malignant lesions., Results: The board-certified endoscopic physicians group showed the highest accuracy in the receiver operative characteristic curve (area under the curve [AUC]: 0.931), followed by a combination of AI and miR148a DNA methylation (AUC: 0.825), and finally trainee endoscopists (AUC: 0.588)., Conclusion: AI with miR148s DNA methylation-based diagnosis is a potential modality for diagnosing GIN., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Gastric cancer is the fifth most common cancer diagnosed worldwide. Due to improved early detection rates of gastric cancer and technological advances in treatments, a significant improvement in survival rates has been achieved in people with cancer undergoing gastrectomy. Subsequently, there has been increasing emphasis on postgastrectomy syndrome (e.g. fullness, delayed emptying, and cold sweat, amongst others) and quality of life postsurgery. However, it is uncertain which types of reconstruction result in better outcomes postsurgery., Objectives: To assess the evidence on health-related quality of life and safety outcomes of Roux-en-Y and Billroth-I reconstructions after distal gastrectomy for people with gastric cancer., Search Methods: We searched the Cochrane Library and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase on 4 May 2021. We checked the reference lists of the included studies and contacted manufacturers and professionals in the field. There were no language restrictions., Selection Criteria: Randomised controlled trials (RCTs) allocating participants to Roux-en-Y reconstruction or Billroth-I reconstruction after distal gastrectomy for gastric cancer., Data Collection and Analysis: Two review authors independently screened studies identified by the search for eligibility and extracted data. The primary outcomes were health-related quality of life after surgery and incidence of anastomotic leakage. The secondary outcomes included body weight loss, incidence of bile reflux, length of hospital stay, and overall morbidity. We used a random-effects model to conduct meta-analyses. We assessed risk of bias of the included studies in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, and the certainty of the evidence using the GRADE approach., Main Results: We included eight RCTs (942 participants) in the review. One study included both cancer patients and benign disease patients such as stomach ulcers. Two studies compared Roux-en-Y, Billroth-I, and Billroth-II reconstructions, whilst the other studies compared Roux-en-Y and Billroth-I directly.  For the primary outcomes, the evidence suggests that there may be little to no difference in health-related quality of life between Roux-en-Y and Billroth-I reconstruction (standardised mean difference 0.04, 95% confidence interval (CI) -0.11 to 0.18; I² = 0%; 6 studies; 695 participants; low-certainty evidence due to study limitations and imprecision). The evidence for the effect of Roux-en-Y versus Billroth-I reconstruction on the incidence of anastomotic leakage is very uncertain (risk ratio (RR) 0.63, 95% CI 0.16 to 2.53; I² = 0%; 5 studies; 711 participants; very low-certainty evidence). The incidence of anastomotic leakage was 0.6% and 1.4% in the Roux-en-Y and Billroth-I groups, respectively. For the secondary outcomes, the evidence suggests that Billroth-I reconstruction may result in little to no difference in loss of body weight compared to Roux-en-Y reconstruction (mean difference (MD) 0.41, 95% CI -0.77 to 1.59; I² = 0%; 4 studies; 541 participants; low-certainty evidence). Roux-en-Y reconstruction probably reduces the incidence of bile reflux compared to Billroth-I reconstruction (RR 0.40, 95% CI 0.25 to 0.63; I² = 22%; 4 studies; 399 participants; moderate-certainty evidence). Billroth-I reconstruction may shorten postoperative hospital stay, but the evidence for this outcome is very uncertain (MD 0.96, 95% CI 0.16 to 1.76; I² = 56%; 7 studies; 894 participants; very low-certainty evidence). Billroth-I reconstruction may reduce postoperative overall morbidity compared to Roux-en-Y reconstruction (RR 1.47, 95% CI 1.02 to 2.11; I² = 0%; 7 studies; 891 participants; low-certainty evidence)., Authors' Conclusions: The evidence suggests that there is little to no difference between Roux-en-Y and Billroth-I reconstruction for the outcome health-related quality of life. The evidence for the effect of Roux-en-Y versus Billroth-I reconstruction on the incidence of anastomotic leakage is very uncertain as the incidence of this outcome was low. Although the certainty of evidence was low, we found some possibly clinically meaningful differences between Roux-en-Y and Billroth-I reconstruction for short-term outcomes. Roux-en-Y reconstruction probably reduces the incidence of bile reflux into the remnant stomach compared to Billroth-I reconstruction. Billroth-I reconstruction may shorten postoperative hospital stay compared to Roux-en-Y reconstruction, but the evidence is very uncertain. Billroth-I reconstruction may reduce postoperative overall morbidity compared to Roux-en-Y reconstruction. Future trials should include long-term follow-up of health-related quality of life and body weight loss., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell-free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients., Methods: The status of THBS1 methylation was detected by quantitative methylation-specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve., Results: Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p < 0.0001). No THBS1 methylation was found in 40 healthy controls, and partial methylation was detected in 3 of 48 patients with chronic non-atrophic gastritis. The frequency of THBS1 methylation in pairing PPLF and serum from 92 GC patients was 52.2% (48/92) and 58.7% (54/92), respectively. The results of methylated THBS1 in pairing PPLF and serum were similar to those of tumor tissues. Aberrant THBS1 methylation in tumor tissues and pairing PPLF or serum was closely related to peritoneal dissemination, tumor progression, and poor prognosis (all p < 0.0001)., Conclusion: Circulating methylated THBS1 DNAs in PPLF/serum may predict peritoneal dissemination, a potential poor prognostic factor for GC patients., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Introduction: Endoscopic submucosal dissection (ESD) has become the treatment of choice for early gastric malignancies. In recent years, the ESD technique has been implemented in Western countries with increasing use., Objectives: To describe the results of gastric ESD in a Western country with a low incidence of gastric cancer., Patients and Methods: The prospective national registry was conducted over 4 years in 23 hospitals, including 30 endoscopists. Epithelial and subepithelial lesions (SEL) qualified to complete removal with ESD were assessed. The technique, instruments, and solution for submucosal injection varied at the endoscopist's discretion. ESD was defined as difficult when: en-bloc resection was not achieved, had to be converted to a hybrid resection, lasted more than 2 h or an intraprocedural perforation occurred. Additionally, independent risk factors for difficult ESD were analyzed., Results: Two hundred and thirty gastric ESD in 225 patients were performed from January 2016 to December 2019 (196 epithelial and 34 SEL). Most lesions were located in the lower stomach (111; 48.3%). One hundred and twenty-eight (55.6%) ESD were considered difficult. The median procedure time was 105 min (interquartile range [IQR]: 60-150). The procedure time for SEL was shorter than for epithelial lesions (90 min [45-121] vs. 110 min [62-160]; p = 0.038). En-bloc, R0, and curative resection rates were 91.3%, 75.2%, and 70.9%, respectively. Difficult ESD had lower R0 resection rates than ESD that did not meet the difficulty criteria (64.8% and 87.6%; p = 0.000, respectively). Fibrosis and poor maneuverability were independent factors associated with difficult ESD (OR 3.6, 95%CI 1.1-11.74 and OR 5.07, 95%CI 1.6-16.08; respectively)., Conclusions: Although the number of cases is limited, the results of this analysis show acceptable en-bloc and R0 rates in gastric ESD considering the wide variability in experience among the operators. Fibrosis and poor maneuverability were associated with more difficulty in completing ESD., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background: The survival impact of the geriatric nutrition risk index (GNRI) has yet to be investigated in patients undergoing gastric carcinoma (GC) surgery., Methods: In total, 1166 GC patients who underwent radical gastrectomy were retrospectively reviewed. The predictive and discrimination abilities for overall survival (OS) were compared among GNRI, nutrition indices, and systemic inflammatory markers. Patients were dichotomized by GNRI (GNRI <98, low; GNRI ≥98, high), and the impacts of GNRI on OS and cancer-specific survival (CSS) were evaluated using Cox hazards analysis., Results: GNRI showed superior discrimination and predictive ability for OS as compared with other indices. There were 447 (38.3%) and 719 (61.7%) patients in the low- and high-GNRI groups, respectively. Patients with low GNRI were older and had a higher pStage III disease rate than those with high GNRI (P < .001). OS curves were significantly stratified by GNRI in all patients (P < .001) and those with pStage I (P < .001), II (P < .001), and III (P = .02) disease. Multivariate analysis showed low GNRI to be independently associated with poor OS (hazard ratio [HR], 2.15; 95% CI, 1.612.87; P < .001). Furthermore, low GNRI was an independent predictor of poor CSS (HR, 1.61; 95% CI, 1.072.44; P = .02), as were total gastrectomy (P < .001) and pStage III disease (P < .001). Patients who had low GNRI and underwent total gastrectomy showed quite poor 5-year OS (54.8%)., Conclusion: GNRI is useful for predicting survival and oncological outcomes in GC patients., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Objective: This study applied network analyses to illustrate patterns of associations between cancer-related physical and psychological symptoms (CPPS) and quality of life (QOL) before and after surgery., Methods: Participants consisted of 256 gastric cancer patients admitted for curative section surgery at the surgical department in a teaching hospital in Korea between May 2016 and November 2017. Participants completed the survey, including MD Anderson Symptom Inventory, Hospital Anxiety and Depression Scale, and Functional Assessment of Cancer Therapy-Gastric Cancer before surgery (T0), 1 week after surgery (T1), and 3-6 months after surgery (T2)., Results: Three networks featured several salient connections with varying magnitudes between CPPS and QOL across all time points. Particularly, anxiety was tightly connected to emotional wellbeing (EWB) across all time points and physical wellbeing (PWB) at T1. On the other hand, depression was connected to functional wellbeing at T0 and T2, gastric cancer concerns (CS) at T1, and PWB at T2. Distress and sadness were the most central symptoms in the three networks. Other central symptoms included shortness of breath at T0, fatigue at T0 and T1, and PWB and CS at T2. Anxiety, depression, and EWB served as bridges connecting CPPS to QOL across all time points with varying degrees of importance, as did PWB at T1 and T2., Conclusions: Treating psychological distress and enhancing EWB and PWB can be high impact intervention targets throughout the cancer trajectory., (© 2021 John Wiley & Sons Ltd.)

Objectives: Nutrition status is of great significance to the clinical outcome after major abdominal surgery. However, the effect of preoperative short-term parenteral nutrition (PN) support among gastric cancer (GC) patients remains unknown and was evaluated in the current study., Methods: We retrospectively analyzed 455 nutritionally at-risk GC patients after radical resection from 2010 to 2016. We matched patients with 3-7 days of PN support to those without PN support. χ 2 And Mann-Whitney U tests were used to compare differences between the PN and control groups., Results: The propensity-matched sample included 368 GC patients (PN group, n = 184; control group, n = 184). The PN and control groups did not differ regarding postoperative complications (P = .528). The incidence of anastomotic leakage in the PN group was lower than in the control group (P = .011), whereas other complications were not found to differ between the groups. The hospitalization cost of the PN group was significantly higher than that of the control group (P < .001), whereas other outcome indicators were similar. Subgroup analysis showed that short-term PN support may have an improved benefit for patients with serum albumin level <35 g/L, but not at the level of statistical significance (P = .17)., Conclusion: Short-term PN support did not significantly improve the short-term clinical outcomes of nutritionally at-risk GC patients, with the exception of a lower incidence of anastomotic leakage. Considering that short-term PN support increases economic burden, PN should not be the preferred method among these patients., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Introduction: To compare outcomes of robotic gastrectomy (RG) performed during the learning curve (P1) with those after its completion (P2)., Methods: In this retrospective study, all consecutive RG patients (n = 92) performed between 2008 and 2018 were included. Primary outcome was conversion rate., Results: D2 lymphadenectomies were more common in P2 (41, 97.6%) than P1 (41, 82.0%) (p = 0.019). Conversions were 11 (22%) in P1 versus 2 (4.8%) in P2 (p = 0.006). Postoperative morbidity was comparable between the groups. Median hospital stay was significantly shorter in P2. The only factor significantly associated with conversion was P2 (odds ratio = 0.18; 95% confidence interval, 0.04-0.85; p = 0.039). The 5-year overall survival in P1 was 79.6% versus 79.7% in P2 (p = 0.373)., Conclusions: The learning curve affected operative and postoperative outcomes: during the learning curve, conversion to open surgery was significantly more frequent, the number of D2 was higher and patients were discharged earlier., (© 2021 John Wiley & Sons Ltd.)

Purpose: To present the outcomes of gastric gastrointestinal stromal tumour (GIST) resection from five Italian centres, focussing the analysis on the comparison among open (OG), laparoscopic (LG) and robotic (RG) approaches., Methods: All consecutive gastric wedge resections for GIST between 2009 and 2019 were included., Results: In total 101 (OG = 14, LG = 63 and RG = 24) were included. No differences were seen in the preoperative characteristics among the groups. Robotic procedures were longer (RG 180 min vs. LG 100 vs. OG 110; p < 0.0001). Time-to-first flatus and length of hospital stay were significantly longer in the OG group. Complication rates were similar among the groups. A sub-analysis on minimally invasive (RG = 19 vs. LG = 20) wedge resections and hand/robot-sewn suture showed that operative time was longer in the RGs (p = 0.007). No conversions were recorded in the RG group versus three in the LG group (p = 0.231). Safety-related factors were similar., Conclusions: Gastric GIST can be safely treated with a minimally invasive approach which is also associated with improved postoperative outcomes., (© 2020 John Wiley & Sons Ltd.)

Background: Near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) allows intraoperative visualisation of the lymph nodes (LNs) draining the tumour., Methods: We included in our study 20 patients who underwent robotic subtotal gastrectomy + D2 lymphadenectomy for gastric cancer. In 10 cases, intraoperative ICG-guided lymphography has been used (Group A). We compared the number of LNs retrieved with the use of NIR imaging and the number of LNs retrieved without the use of this technique (Group B, historical group)., Results: No complications related to ICG injection or near-infrared imaging were observed. The mean number of overall LNs retrieved was significantly greater in Group A than in group B (40 vs. 24). No statistically significant difference in operative time was observed., Conclusions: ICG-guided fluorescent lymphography can help in performing a more accurate locoregional lymphadenectomy during robotic subtotal gastrectomy for gastric cancer. This technique represents a precious contribution to gastric cancer surgery., (© 2021 John Wiley & Sons Ltd.)

Background: Data regarding the outcomes of pure minimally invasive techniques of radical gastrectomy are scarce. We aimed to compare short-term post-operative outcomes in patients undergoing totally minimally invasive radical gastrectomy with the da Vinci Xi ® robotic system versus straight laparoscopy for gastric adenocarcinoma., Methods: Between December 2013 and March 2018, robotic and laparoscopic radical gastrectomy performed in two centres were included. Both groups were compared with respect to perioperative short-term outcomes., Results: Ninety-four patients were included in the study. Anticoagulant and neoadjuvant chemotherapy use were higher in the robotic group (p = 0.02, p = 0.02). There were conversions in the laparoscopy group whereas no conversions occurred in the robotic group (p = 0.052). Operating time in the robotic group was longer (p = 0.001). The number of harvested lymph nodes in the laparoscopic group was higher (p = 0.047)., Conclusion: Totally robotic technique with the da Vinci Xi ® robotic system provides similar short-term results compared to laparoscopic surgery in radical gastrectomy., (© 2020 John Wiley & Sons Ltd.)

Objective: The aim of the study was to find factors associated with overall survival (OS) and establish a nomogram predicting OS of patients with gastric cancer (GC) after D2R0 resection., Methods: Demographic and clinicopathologic factors of patients with GC underwent D2R0 surgical resection were retrospectively collected from medical records, telephone interview or outpatient follow-up. To find factors significantly associated with OS, univariate and multivariate analyses were conducted. The concordance index (C-index) was used to measure the accuracy of the nomogram. Discrimination and calibration of the nomogram were tested using the patients in the validation set., Results: Overall, patients with 890 GC underwent D2R0 surgical resection were included. Based on the results of univariate analysis and multivariate analysis, T stage, number of metastatic local lymph nodes, lymph node positive rate, adjuvant chemotherapy and diameter of tumour were used to construct a nomogram predicting OS of patients with GC after surgical resection. In the validation cohort, the C-index was 0.73 and the nomogram performed well in predicting OS., Conclusion: The nomogram was able to accurately predict OS of patients with GC underwent curative surgery and performed well in internal validation, which would also be useful for the decision-making of doctors., (© 2020 John Wiley & Sons Ltd.)

Background: To investigate the value of anti-helicobacter pylori (Hp) antibody, serum carbohydrate antigen (CA)-724, CA19-9, and carcinoembryonic antigen (CEA) in the diagnosis and prognosis evaluation of young patients with early gastric cancer., Methods: A total of 200 young patients with gastric cancer from April 2014 to December 2015 were enrolled. A total of 206 patients with gastritis and 204 healthy subjects were also selected. Gastric cancer patients were followed up for 3 years, and the number of recurrences, metastasis, and death was recorded., Results: The positive rate of anti-Hp antibody, CA724, CA19-9, and CEA in young patients with early gastric cancer were significantly higher than those in gastritis and healthy subjects (P < .05), and was positively correlated with tumor stage, tumor size, and lymph node metastasis (P < .05). The predicting model was as follows: Logit (P) = 26.433-3.014(CA724)-3.908(CA19-9)-0.303(CEA)-2.208(anti-Hp antibody, Positive = 1; Negative = 0). This model had a high value in identifying young patients with early gastric cancer with AUC of 0.918, and the estimated probability was .806. Compared to patients with negative anti-Hp antibody and low serum levels of CA724, CA19-9, and CEA, the recurrence rate, metastasis rate, and mortality of patients with positive anti-Hp antibody, high serum levels of CA724, CA19-9, and CEA increased significantly (P < .05)., Conclusion: This study indicated that anti-Hp antibody combined with CA724, CA19-9, and CEA had important value in the identification of young patients with early gastric cancer and were of great value in evaluating the risk of postoperative recurrence, metastasis, and death., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Background: National Comprehensive Cancer Network (NCCN) guidelines recommend accurate clinical staging, perioperative therapy, and complete lymphadenectomy for patients with stage II to III gastric cancer. However, national compliance remains low. It was hypothesized that integrated cancer networks might improve compliance and outcomes within the community., Methods: Patients with stage II to III gastric adenocarcinoma undergoing curative-intent resection (National Cancer Data Base, 2006-2015) were examined. Guideline compliance was defined as any perioperative adjunctive therapy, complete lymphadenectomy, complete clinical staging, and complete compliance (all measures). Univariate comparisons and multivariable regression were used to assess factors associated with compliance, and Kaplan-Meier analysis was used to assess survival., Results: There were 27,210 patients identified: 7235 (26.6%) underwent surgery alone, whereas 19,975 (73.4%) received additional therapy. Half (53.1%) had complete lymphadenectomies, whereas complete clinical staging was available for 65.5%. Overall compliance with all 3 measures was 30.1%. Compliance improved by approximately 20% for each measure across the 10-year study period. Although patients treated at academic programs were most likely to receive concordant care in an adjusted analysis, those treated at integrated care networks were more likely to receive guideline-concordant care (odds ratio [OR], 0.69) than those treated at comprehensive community programs (OR, 0.48) or community programs (OR, 0.45; all P values <.001). The median overall survival was 45.5 months for patients who received guideline-concordant care and 32.0 months for those who did not (P < .001, reference for all ORs: academic programs)., Conclusions: Compliance with guidelines was associated with improved outcomes. Although the rate of compliance with NCCN guidelines is improving, integrated care networks may be an important way of improving the quality of gastric cancer care within the community., (© 2019 American Cancer Society.)

Background: Perioperative chemotherapy (POC) is one standard approach for the treatment of resectable cancers of the stomach and gastroesophageal junction (GEJ), whereas there has been growing interest in preoperative therapies. The objective of the current study was to compare survival between patients treated with preoperative chemoradiotherapy and adjuvant chemotherapy (PCRT) with those receiving POC using a large database., Methods: The National Cancer Data Base was queried for patients diagnosed between 2004 and 2013 with American Joint Committee on Cancer clinical group stage IB to stage IIIC (excluding T2N0 disease) adenocarcinoma of the stomach or GEJ. Patients treated with definitive surgery and POC with or without preoperative radiotherapy of 41 to 54 Gy were included. Overall survival (OS) was defined from the date of definitive surgery and estimated using the Kaplan-Meier method. A total of 14 patient and treatment variables were used for propensity score matching (PSM)., Results: A total of 1048 patients were analyzed: 53.2% received POC and 46.8% received PCRT. The primary tumor site was the GEJ in 69.1% of patients and stomach in 30.9% of patients. The median age of the patients was 60 years, and the median follow-up was 25.8 months. The use of PCRT was associated with a greater pathologic complete response rate of 13.1% versus 8.2% (P = .01). POC was associated with a decreased risk of death in unmatched groups (hazard ratio [HR], 0.83; P = .043). Using PSM cohorts, POC decreased the risk of death with a median OS of 45.1 months versus 31.4 months (HR, 0.70; P = .016). The 2-year OS rate was 72.9% versus 62.5% and the 5-year OS rate was 40.7% versus 33.1% for POC versus PCRT, respectively. Survival favored POC in PSM gastric (HR, 0.41; P = .07) and GEJ (HR, 0.77; P = .08) patient subgroups., Conclusions: The addition of preoperative radiotherapy to POC appears to be associated with an increased risk of death in patients with resectable gastric and GEJ cancers., (© 2019 American Cancer Society.)

Background: The gastric cancer (GC) represents a common malignancy especially in China. Long non-coding RNAs (lncRNAs) are critically involved in various types of cancer. However, the underlying mechanisms of OLC8 in gastric cancer are still largely unknown., Methods: The lncRNA profiling was used to identify novel lncRNAs associated with GC. The expression of OLC8 was quantified using qRT-PCR. Migration and viability assays were performed to evaluate the in vitro effects. Xenograft tumor models were conducted to investigate the in vivo oncogenic potential. RNA-seq was used to identify IL-11 as OLC8 binding partner., Results: In current study, we have identified a novel lncRNA termed OLC8. OLC8 was significantly overexpressed in gastric cancer specimens and cell lines. In vitro experiments showed that OLC8 facilitated migration and viability of MKN1 and AGS cells. As expected, in vivo experiments also confirmed an oncogenic role for OLC8. Mechanistic study indicated that OLC8 associated with IL-11 transcripts. The OLC8-IL-11 binding greatly impaired the degradation of IL-11 mRNAs. Not surprisingly, enhanced expression of IL-11 could increase STAT3 activation to favor gastric cancer development., Conclusions: Our current research has identified OLC8 as a novel oncogenic lncRNA in IL-11/STAT3 signaling, and OLC8 may constitute a potential target for gastric cancer intervention., (© 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Background: The aim of this study was compare short- and long-term outcomes between robotic (RG) and standard open gastrectomy (OG)., Methods: This is a single-center propensity score-matched study including patients who underwent RG or OG for gastric cancer between 2008 and 2018., Results: In total, 191 patients could be included for analysis. Of 60 RG patients, 49 could be matched. After matching, significant differences in baseline characteristics were no longer present. Operative time was significantly longer (451 min, IQR: 392-513) in the RG group than in the OG (262 min, IQR: 225-330) (P < .0001). No significant differences in postoperative complications between RG (n = 15, 30.6%) and OG (n = 15, 30.6%) were seen (P = 1.000). Overall survival was comparable between the groups., Conclusions: RG is feasible and safe. With regard to long-term oncologic outcomes, survivals in the RG group were similar to those in OG group., (© 2019 John Wiley & Sons, Ltd.)

Background: The optimal number of retrieved lymph nodes (LNs) in gastric cancer (GC) is still debatable and previous studies proposing new classification alternatives mostly focused on the number of retrieved LNs without proper consideration on the anatomic nodal groups' location. Here, we assessed the impact of retrieved LNs from different nodal location groups on the survival of GC patients., Methods: Stage I-III gastric cancer patients who had radical gastrectomy were investigated. LN grouping was determined according to the 13th edition of the JCGC. The optimal cut-off values of retrieved LNs in different LN groups (Group 1 and 2) were calculated, based on which a proposed nodal classification (rN) simultaneously accounting the optimal number and location of retrieved LNs was proposed. The performance of rN was then compared to that of LN ratio, log-odds of metastatic LNs (LODDs) and the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) N classification., Results: The optimal cut-off values for Group 1 and 2 were 13 and 9, respectively. The 5-year overall survival (OS) was higher for patients in retrieved Group 1 LNs > 13 (vs. Group 1 LNs ≤ 13, 63.2% vs. 57.9%, P = 0.005) and retrieved Group 2 LNs > 9 (vs. Group 2 LNs ≤ 9, 72.5% vs. 60.7%, P = 0.009). Patients staged as pN0-3b were sub classified using this Group 1 and 2 nodal analogy. The OS of pN0-N2 patients in retrieved Group 1 LNs > 13 or Group 2 LNs > 9 were superior to those in retrieved Group 1 LNs ≤ 13 and Group 2 LNs ≤ 9 (All P < 0.05); except for pN3 patients. The rN classification was formulated and demonstrated better 5-year OS prognostication performance as compared to the LNR, LODDs, and the 8th UICC/AJCC N staging system., Conclusions: The retrieval of > 13 and > 9 LNs for Group 1 and Group 2, respectively, could represent an alternative lymph node retrieval approach in radical gastrectomy for more precise survival prognostication and minimizing staging migration, especially if > 16 LNs is found to be difficult.

Background: Despite its clinical benefits, early oral nutrition after total gastrectomy is not widely implemented because of concerns about tolerability and safety. We investigated the feasibility and safety of early oral nutrition after total gastrectomy in gastric carcinoma patients., Methods: This is a retrospective before-after study. From 2008-2016, 301 patients received conventional oral feeding (COF) before May 2012, and 454 patients, early oral feeding (EOF) after May 2012. The EOF group received oral diet on postoperative day 1, and the COF group was maintained nil-by-mouth until patients demonstrated gas passage. After balancing potential confounders using propensity score matching, 203 patients were selected in each group., Results: Both matched groups demonstrated well-balanced baseline characteristics. The EOF group demonstrated significantly earlier first flatus time (2.9 vs 3.1 days, P = .013) and hospital discharge (8.9 vs 12.6 days, P < .001) than the COF group. No significant differences were observed for overall morbidity and mortality, but the EOF group demonstrated lower incidence of abdominal infection (3.0% vs 7.4%, P = .044) and anastomosis leakage (1.5% vs 4.9%, P = .048). Subgroup analyses by age, sex, operative approach, lymph node dissection, and tumor stage demonstrated no increased risk of morbidity, anastomosis leakage, and short hospital stay in the EOF group., Conclusion: Early oral nutrition may be feasible and safe after total gastrectomy, with no increase in postoperative complications. Large, randomized, controlled trials are warranted to further investigate the clinical benefits of early oral nutrition after total gastrectomy., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Objective: The main objective was to test the indirect effects of emotional competence (EC) after diagnosis (T1) on the health-related quality of life (HRQoL) after surgery (T2) of esogastric cancer patients via fewer anxiety and depression symptoms (T2)., Methods: Data were collected from 30 French centers via the clinicobiological database French EsoGastric Tumors (FREGAT). Two hundred and twenty-eight participants completed a self-reported questionnaire at T1 and T2, assessing their EC (Profile of Emotional Competence (PEC)), HRQoL (EORTC Quality of Life Questionnaire-Core (QLQ-C30)), and anxiety and depression symptoms (Hospital Anxiety and Depression Scale (HADS)). Regression analyses were used to test the direct effects of intrapersonal and interpersonal EC on their anxiety/depression symptoms and HRQoL at T1 and T2. The PROCESS Macro in SPPS v.22 with bootstrap methods was used to test the indirect effects of intrapersonal and interpersonal EC at T1 on HRQoL at T2 via anxiety and depression symptoms., Results: EC predicted fewer anxiety and depression symptoms of patients at T1 and T2 and better HRQoL at T1. EC at T1 also predicted a better HRQoL at T2 via fewer anxiety and depression symptoms at T2., Conclusions: Patients who tended to use their EC in daily life could be more effective in regulating the emotional impact of the cancer diagnosis and surgery. This explains why they reported fewer anxiety and depression symptoms, which in turn enabled a better perceived HRQoL after surgery. Therefore, reinforcing the use of patients' EC in daily life following their diagnosis could decrease their emotional distress and, in this way, improve their HRQoL in the preoperative and postoperative stages., (© 2019 John Wiley & Sons, Ltd.)

Background: Endoscopic submucosal dissection (ESD) for early esophageal and stomach cancer is usually performed under general anesthesia. However, propofol sedation without endotracheal intubation has been suggested as a viable alternative., Objective: The objective of this study was to evaluate the safety of propofol sedation without endotracheal intubation during ESD in the upper gastrointestinal tract., Methods: We performed a retrospective cohort study of patients who underwent ESD for upper gastrointestinal tumors with propofol-remifentanil analgosedation in a tertiary referral center in the Netherlands between October 2013 and February 2018. Primary endpoints were the rates of intraprocedural endoscopy- and anesthesia-related complications. Secondary endpoints were the postprocedural complication rates within 30 days and endotracheal intubation conversion rates., Results: Of 88 patients, intraprocedural ESD-related complications occurred in three patients (3.4%). Intraprocedural anesthesia-related complications occurred in two patients (2.3%), one of whom required conversion to endotracheal intubation. Postprocedural ESD-related complications occurred in 14 patients (15.9%), and minor postprocedural complications occurred in two patients (2.3%). Eighty-two (93.2%) patients were discharged within one day after ESD. No patient was readmitted for anesthesia-related complications., Conclusion: Propofol-based sedation without endotracheal intubation is safe for ESD procedures in the esophagus and stomach with low anesthesia-related complication rates and short hospital stay.

The Japan Clinical Oncology Group has recently conducted large scale clinical trials with findings that have revealed pivotal strategies for the treatment of resectable gastric cancer surgery. These findings include the fact that D3 lymphadenectomy does not improve survival rates when compared to D2 lymphadenectomy, and it is not recommended for resectable gastric cancer. Also, a transhiatal approach is recommended, instead of the left thoraco-abdominal approach, for the treatment of adenocarcinoma of the esophago-gastric junction or gastric cardia which has invaded ≤ 3 cm of the esophagus. Gastrectomy with splenectomy and bursectomy had been recommended as a part of the D2 lymphadenectomy. However, the results of the recent clinical trials revealed that splenectomy should be avoided in total gastrectomy with D2 lymphadenectomy for proximal gastric cancer and that bursectomy should be avoided in gastrectomy with D2 lymphadenectomy for resectable gastric cancer. Both splenectomy and bursectomy were found to be unable to improve survival, but instead increased operative morbidity. These trials revealed that the above-mentioned invasive and aggressive procedures did not provide sufficient survival benefits and that gastric cancer surgery may be trending from an "invasive to less invasive" and "aggressive to more conservative" approach.

A simple and rapid ultra-high-performance liquid chromatographic (UHPLC) for the simultaneous determination of meropenem and ciprofloxacin in human plasma was developed and validated. All of the analytes were separated in <5 min. A solid-phase extraction method was applied from sample preparation. Analytical separation was performed on a Poroshell SB C 18 column (50 × 2.1 mm, 2.7 μm particle size) with photodiode array (PDA) detection. Meropenem and ciprofloxacin were determined at wavelengths of 300 and 277 nm, respectively. The mobile phase was a mixture of acetonitrile-10 mm ammonium acetate-methanol in gradient elution. The method has been validated for both drugs in gastric surgery for cancer patients. The method showed good linearity with correlation coefficients, r 2  = 0.994 for the two drugs, as well as high precision (RSD < 10.5% in each case); accuracy ranged from -5.8 to +6.0%. The limit of quantitation of the two drugs was established at 0.02 and 0.01 μg/mL, respectively. Meropenem, ciprofloxacin and the internal standard were extracted from human plasma with a mean recovery ranging from 92.5 to 98.6%. The method was applied to quantify the drugs dosage in complicated gastric surgery patients., (© 2018 John Wiley & Sons, Ltd.)

Background: Little is known about the correlation between the clinicopathological features, postoperative treatment, and prognosis of multiple gastric cancers (MGCs). In this study, we aimed to investigate the correlation between these features and the impact of postoperative adjuvant chemotherapy on the long-term survival of patients with MGC., Methods: The clinical and pathological data of patients diagnosed with gastric adenocarcinoma who had radical gastrectomy from January 2007 to December 2016 were analyzed. Using propensity score matching, the prognostic differences, and the impact of postoperative adjuvant chemotherapy between those with MGC and solitary gastric cancers (SGC) were compared., Results: Among the 4107 patients investigated, the incidence of MGC was 3.2% (133/4107). Before matching, patients with MGC and SGC had disparities in the type of gastrectomy, pathological tumor stage (pT), pathological node stage (pN), and pathological tumor-node-metastasis stage (pTNM). After a 1:4 ratio matching, the clinical data of 133 cases of MGC and 532 cases of SGC were found to be comparable. The 5-year overall survival (OS) rate was 56.6% in the entire matched cohort, 48.1% in the MGC group, and 58.7% in the SGC group (P = 0.013). Multivariate analysis revealed that MGC, age, pT stage, pN stage, and adjuvant chemotherapy were independent predictors of OS (all P < 0.05). Stratified analyses demonstrated that for the cohort of advanced gastric cancer (AGC) patients who did not had adjuvant chemotherapy, the 5-year OS rate of advanced cases of MGC was inferior than that of SGC patients (34.0% vs. 46.1%, respectively; P = 0.025) but there were no significant difference in the 5-year OS rate between advanced MGC and SGC patients who had adjuvant chemotherapy (48.0% vs. 53.3%, respectively; P = 0.292). Further, we found that the 5-year OS rate of advanced MGC who had adjuvant chemotherapy was significantly higher than those who did not had adjuvant chemotherapy (48.0% vs. 34.0%, P = 0.026)., Conclusions: Patients with advanced MGC was identified as having a poorer survival as to SGC patients, but the implementation of postoperative adjuvant chemotherapy showed that it had the potential to significantly improve the long-term prognoses of MGC patients.

Background: Gastric cancer (GC) is a disease associated with a higher incidence and mortality, and some host genetic polymorphisms have been reported as potential factors contributing to the development of GC. In view of this, the study was conducted to investigate the effects of HLA-DQB1 gene polymorphisms and perioperative blood transfusion on prognosis of patients with gastric cancer (GC)., Methods: A total of 142 patients with GC (case group) and 150 healthy controls (control group) were enrolled. Relationship between HLA-DQB1 gene polymorphisms, perioperative blood transfusion, and clinical pathological parameters of patients with GC after operation was analyzed. Kaplan-Meier curve was applied for analyzing survival rate of patients with GC, and Cox multivariate regression analysis for prognostic factors of patients with GC., Results: The frequency of HLA-DQB1*03 gene was increased in patients with GC. Patients with GC with HLA-DQB1*03 genotype had higher number of tumor size >6 cm, deeper depth of infiltration, higher LNM rate, and later stage of disease. Patients with HLA-DQB1*03 genotype had lower survival rate compared with other genotypes. Anemia before operation, depth of infiltration in T3 stage and T4 stage, LNM in N1 stage and N2 stage, and HLA-DQB1*03 genotype were regarded as independent risk factors for patients with GC., Conclusion: These results demonstrate that HLA-DQB1*03 genotype and perioperative blood transfusion are not conducive to the prognosis of patients with GC, which could provide a reference for the treatment of GC., (© 2018 Wiley Periodicals, Inc.)

Background: Few studies have shown nomograms that may predict disease-specific survival (DSS) probability after curative D2 gastrectomy for advanced gastric cancer (AGC), particularly among Chinese patients. This study sought to develop an elaborative nomogram that predicts long-term DSS for AGC in Chinese patients., Methods: A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1, 2000 and December 31, 2012 from three large medical hospitals in China. We assigned patients from Sun Yat-sen University Cancer Center to the training set, and patients from the First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital to two separate external validation sets. A multivariate survival analysis was performed using Cox proportional hazards regression model in a training set, and a nomogram was constructed. Harrell's C-index was used to evaluate discrimination and calibration plots were used to validate similarities between survival probabilities predicted by the nomogram model and actual survival rates in two validation sets., Results: The multivariate Cox regression model identified age, tumor size, location, Lauren classification, lymphatic/venous invasion, depth of invasion, and metastatic lymph node ratio as covariates associated with survival. In the training set, the nomogram exhibited superior discrimination power compared with the 8th American Joint Committee on Cancer TNM classification (Harrell's C-index, 0.82 vs. 0.74; P < 0.001). In two validation sets, the nomogram's discrimination power was also excellent relative to TNM classification (C-index, 0.83 vs. 0.75 and 0.81 vs. 0.74, respectively; P < 0.001 for both). After calibration, the nomogram produced survival predictions that corresponded closely with actual survival rate., Conclusions: The established nomogram was able to predict 3-, 5-, and 10-year DSS probabilities for AGC patients. Validation revealed that this nomogram exhibited excellent discrimination and calibration capacity, suggesting its clinical utility.

Background: Conditional survival estimates, which take into consideration the changing risk with increasing survival time, provide a dynamic survival probability and more accurate survival information for clinician decision making. The objective of the current study was to evaluate the conditional disease-specific survival (DSS) for patients with gastric cancer who underwent curative surgery in China., Methods: In total, 7658 patients with gastric cancer from a multi-institutional cohort in China were included in the analyses. Actuarial DSS was estimated using the Kaplan-Meier method. Three-year conditional DSS (CDS 3 ) of patients who had already survived for x years was estimated as CDS 3 = DSS(x + 3)/DSS(x). Cox proportional hazards regression analyses were used to identify the factors related to DSS., Results: The 1-year, 3-year, and 5-year actuarial DSS rates were 88.2%, 64.5%, and 54.6%, respectively. By using CDS estimates, the probabilities that patients would remain alive for an additional 3 years given that they had already survived for 1, 3, and 5 years were 66.6%, 80.2%, and 88.3%, respectively. Patients who had unfavorable tumor characteristics diagnosed initially at surgery had the greatest improvement in CDS and the largest survival gap between actuarial DSS and CDS., Conclusions: The current results indicate that CDS estimates for Chinese patients with gastric cancer who underwent surgery were dynamic and increased with time elapsed. Patients who had unfavorable tumor characteristics had the greatest improvement in CDS. This valuable information could provide more a precise evaluation of long-term prognosis and may serve as an important prognostic index in clinical practice. Cancer 2018;124:916-24. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Although there is a general perception that, as the older population grows in number, more are undergoing surgery, there are few data on trends in major resections for cancer and short-term outcomes in this group., Methods: The Nationwide Inpatient Sample was (NIS) used to estimate the national trends of major upper abdominal resections (esophagus, stomach, liver, pancreas) for cancer in octogenarians (aged ≥80 years) from 2001 to 2011. Resection rates performed per year were incidence-adjusted within this age group for each cancer type as determined by the NIS database. Joinpoint regression was used to calculate average annual percentage changes (AAPC) when evaluating trends over time., Results: During the study period, octogenarians underwent an estimated 30,356 upper abdominal organ resections for cancer in the United States, representing 3.8% of all cancer admissions among octogenarians. Resection rates in octogenarians increased significantly over time (AAPC, 2.54; P < .001) secondary to increasing trends in pancreatic (AAPC, 11.52; P < .001) and hepatic (AAPC, 6.67; P < .001) resections. Elixhauser comorbidity index scores increased from a mean of 3.61 to 4.20 (AAPC, 1.31; P < .001), whereas inpatient mortality during this time decreased from 13.6% to 8.2% (AAPC, 5.58; P < .001)., Conclusions: Overall rates of major upper abdominal cancer resections in octogenarians are increasing over time, driven by increases in liver and pancreatic resections. These increases were observed despite a less favorable patient morbidity profile over time. These patterns may suggest shifting selection criteria for octogenarians undergoing major abdominal surgery over time in the context of diminishing postoperative mortality. Cancer 2018;124:125-35. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard options. In the current study, the authors used the National Cancer Data Base to compare overall survival (OS) between these regimens., Methods: Patients who underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through 2012 were divided into those treated with perioperative chemotherapy without RT versus those treated with adjuvant CRT. Survival was estimated and compared using univariate and multivariate models adjusted for patient and tumor characteristics, surgical margin status, and the number of lymph nodes examined. Subset analyses were performed for factors chosen a priori, and potential interactions between treatment and covariates were assessed., Results: A total of 3656 eligible patients were identified, 52% of whom underwent perioperative chemotherapy and 48% of whom received postoperative CRT. The median follow-up was 47 months, and the median age of the patients was 62 years. Analysis of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio, 0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity score-matched analysis also demonstrated improved OS with adjuvant RT (median of 49 months vs 39 months; P = .033). On subset analysis, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins, with a greater benefit of RT noted among patients with surgical margin-positive disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001)., Conclusions: In this National Cancer Data Base analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The survival advantage observed with adjuvant CRT was most pronounced among patients with positive surgical margins. Cancer 2017;123:3402-9. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Jejunostomy feeding tubes (JFTs) can be used to provide nutrition support to patients who have had surgery for esophagogastric cancer. Although previous research reports how patients cope with a gastrostomy tube, little is known about the impact of having a JFT. The aim of this qualitative study was to explore how patients and their informal caregivers experience living with a JFT in the first months following surgery., Methods: Participants were purposively sampled from a cohort of patients recruited to a trial investigating home enteral nutrition vs standard care after esophagogastric surgery for cancer. The sampling framework considered age, sex, and marital status. Informal caregivers were also invited to participate. Interviews were audio recorded, transcribed verbatim, and anonymized. Inductive thematic analysis was used to identify key themes related to living with a JFT., Results: Fifteen patient interviews were conducted; 8 also included a family caregiver. Analysis of the data resulted in 2 main themes: "challenges" and "facilitators" when living with a JFT. While "physical effects," "worries" and "impact on routine" were the main challenges, "support," "adaptation" and "perceived benefit" were what motivated continuation of the intervention., Conclusion: Findings suggest that participants coped well with a JFT, describing high levels of compliance with stoma care and the feeding regimen. Nonetheless, disturbed sleep patterns and stoma-related problems proved troublesome. A better understanding of these practical challenges, from the patient and family caregiver perspective, should guide healthcare teams in providing proactive support to avoid preventable problems.

Background: Surgical resection is the gold standard treatment for gastrointestinal stromal tumors (GISTs). This paper describes the authors' experience in the management of posterior gastric wall GISTs through the robotic surgical approach., Methods: A case-series analysis for surgically resected GISTs was conducted between 2009 and 2010. All patients were followed up until mid-2015., Results: Robotic resection was performed in four cases. There was no evidence of bleeding or leak in all cases. The median hospital length of stay was 8 (5-8) days. No post-operative morbidity or mortality was reported during the follow-up duration (mean ± SD; 40.25 ± 35 months)., Conclusion: Findings show that the robotic assisted surgical approach to the removal of posterior wall gastric stromal tumors is associated with 100% disease-free survival rate. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

This study evaluated the effect of an immune-modulatory diet on patients with gastric cancer and identified the parameters associated with postoperative outcomes. This was a single-arm prospective intervention study. At baseline, patients were assessed for nutrition (Patient-Generated Subjective Global Assessment), inflammatory markers (albumin, C-reactive protein, and interleukin 6 [IL-6]), and immune markers (percentage NK, CD4, CD8, and CD4:CD8 ratio); they also received nutrition counseling and high-calorie/protein supplement. A week before surgery, they were assessed for nutrition and inflammatory/immune markers and started on an immune-modulatory supplement until the day before surgery, when they were evaluated again. On the second postoperative day, patients were assessed for inflammatory/immune parameters, and a final nutrition evaluation was performed until the day of discharge. Complications were recorded daily and up to 30 days after discharge. Thirty-seven patients (60 ± 10 years old) were included, and 57% were classified as malnourished. Maintenance of nutrition and immune parameters occurred throughout the study period, but we found a preoperative increase in C-reactive protein (0.1-1.5 mg/dL) and IL-6 (2.0-14.2 pg/mL) and a postoperative increase in the CD4:CD8 ratio (2.3 ± 1.0). Complications and death were seen in 35%, especially patients with higher preoperative IL-6 (2.2-46 pg/mL), lower CD4:CD8 ratio (1.7 ± 0.5), and lower protein (1.2 ± 0.5 g/kg/d) and calorie intake (1552 ± 584 kcal/kg/d). The high-calorie/protein supplementation with the immune-modulating diet was able to maintain the nutrition and immune status of patients with gastric cancer.

Background: Robotic techniques are claimed to be an alternative to laparoscopic and open approaches for gastrointestinal stromal tumors (GIST) treatment. Our aim is to present our single center experience and a literature review., Materials and Methods: From June 2012 to August 2014, six patients with preoperative diagnosis of GIST were treated by robotic surgery at Sanchinarro University Hospital., Results: Two GIST tumors were localized in the second part of the duodenum, one in the first portion, two in the gastricantrum and another in the angular notch. Surgical procedures performed were two subtotal gastrectomies, one gastric wedge resection and three duodenal enucleations. None of the interventions needed conversion to open surgery. Mean operative time was 245 min (150-540). Mean hospital stay was 10.5 days (6-24). All lesions had microscopically negative resection margins. Mean follow-up was 24 months (8-33) with a disease-free survival rate of 100%., Conclusions: A robotic approach for GIST tumors is a safe and feasible procedure with a well-accepted oncological surgical result. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Intracorporeal digestive tract reconstruction after minimally invasive total gastrectomy may be challenging, even when using the da Vinci® Surgical System. This may be due to intrinsic difficulties during oesophago-jejunal anastomosis (EJA). The aim of this study was to describe a simple way to perform digestive tract reconstruction after robotic total gastrectomy (RTG) for gastric cancer and the results of its application in a small series of cases., Methods: In the last 2 years, six patients with gastric adenocarcinoma have been treated by RTG, four male and two female, with mean age of 59.8 (range 48-74) years. The tumour was located in the gastric body in three patients, the gastric antrum in two patients and the fundus in one patient with no need of splenectomy. In all cases, D2 lymphadenectomy was completed. A modified robotic reconstruction technique proposed by the authors was used in these operations, which consists in a latero-lateral EJA using a linear stapler. An entero-enterostomy is also performed in the upper abdomen., Results: The mean operative time was 408 (range 340-481) min. The mean time for digestive tract reconstruction was 57 (range 47-68) min. There were no conversions to open or laparoscopic surgery. The number of lymph nodes removed varied in the range 28-52 (average 40). There was no mortality. Postoperative staging showed three T1N0M0s, one T2N0M0, one T3N0M0 and one T3N2M0., Conclusion: This series, which despite being small, demonstrates that this robotic reconstruction technique is safe, with no major complications, demands a relatively short time for its accomplishment, even when dealing with initial experience. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: This study aims to evaluate the immediate outcomes of robotic and open gastrectomy for patients with locally advanced gastric adenocarcinomas., Methods: A retrospective analysis was performed on patients undergoing curative intent gastrectomies between 2004 and 2013 in our department. Operative and postoperative outcomes as well as long-term survival data were analysed., Results: Two groups of patients were analysed: the robotic group (n = 18) and the open surgery group (n = 29). Operating time in the robotic group (320.833 ± 85.186 min) was significantly longer (p = 0.0004) as compared with the open group (243.366 ± 57.973 min). The number of retrieved lymph nodes was not statistically different between the two groups (p = 0.108) and neither was the rate of postoperative complications (p = 0.294)., Conclusions: Robotic gastrectomy is a safe procedure, with satisfactory short- and long-term outcomes in locally advanced gastric cancer. Studies on a larger number of patients are necessary in order to confirm whether an immediate benefit in survival exists due to robotic surgery. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Gastric cancer is the third most common cause of cancer-related mortality in the world. Currently there are two surgical options for potentially curable patients (i.e. people with non-metastatic gastric cancer), laparoscopic and open gastrectomy. However, it is not clear whether one of these options is superior., Objectives: To assess the benefits and harms of laparoscopic gastrectomy or laparoscopy-assisted gastrectomy versus open gastrectomy for people with gastric cancer. In particular, we planned to investigate the effects by patient groups, such as cancer stage, anaesthetic risk, and body mass index (BMI), and by intervention methods, such as method of anastomosis, type of gastrectomy and laparoscopic or laparoscopically-assisted gastrectomy., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, ClinicalTrials.gov and the WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) until September 2015. We also screened reference lists from included trials., Selection Criteria: Two review authors independently selected references for further assessment by going through all titles and abstracts. Further selection was based on review of full text articles for selected references., Data Collection and Analysis: Two review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes, the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes and the hazard ratio (HR) for time-to-event outcomes. We performed meta-analyses where it was meaningful., Main Results: In total, 2794 participants were randomised in 13 trials included in this review. All the trials were at unclear or high risk of bias. One trial (which included 53 participants) did not contribute any data to this review. A total of 213 participants were excluded in the remaining trials after randomisation, leaving a total of 2528 randomised participants for analysis, with 1288 undergoing laparoscopic gastrectomy and 1240 undergoing open gastrectomy. All the participants were suitable for major surgery.There was no difference in the proportion of participants who died within thirty days of treatment between laparoscopic gastrectomy (7/1188: adjusted proportion = 0.6% (based on meta-analysis)) and open gastrectomy (4/1447: 0.3%) (RR 1.60, 95% CI 0.50 to 5.10; risk difference 0.00, 95% CI -0.01 to 0.01; participants = 2335; studies = 11; I(2) = 0%; low quality evidence). There were no events in either group for short-term recurrence (participants = 103; studies = 3), proportion requiring blood transfusion (participants = 66; studies = 2), and proportion with positive margins at histopathology (participants = 28; studies = 1). None of the trials reported health-related quality of life, time to return to normal activity or time to return to work. The differences in long-term mortality (HR 0.94, 95% CI 0.70 to 1.25; participants = 195; studies = 3; I(2) = 0%; very low quality evidence), serious adverse events within three months (laparoscopic gastrectomy (7/216: adjusted proportion = 3.6%) versus open gastrectomy (13/216: 6%) (RR 0.60, 95% CI 0.27 to 1.34; participants = 432; studies = 8; I(2) = 0%; very low quality evidence), long-term recurrence (HR 0.95, 95% CI 0.70 to 1.30; participants = 162; studies = 4; very low quality evidence), adverse events within three months (laparoscopic gastrectomy (204/268: adjusted proportion = 16.1%) versus open gastrectomy (253/1222: 20.7%) (RR 0.78, 95% CI 0.60 to 1.01; participants = 2490; studies = 11; I(2) = 38%; very low quality evidence), quantity of perioperative blood transfused (SMD 0.05, 95% CI -0.27 to 0.38; participants = 143; studies = 2; I(2) = 0%; very low quality evidence), length of hospital stay (MD -1.82 days, 95% CI -3.72 to 0.07; participants = 319; studies = 6; I(2) = 83%; very low quality evidence), and number of lymph nodes harvested (MD -0.63, 95% CI -1.51 to 0.25; participants = 472; studies = 9; I(2) = 40%; very low quality evidence) were imprecise. There was no alteration in the interpretation of the results in any of the subgroups., Authors' Conclusions: Based on low quality evidence, there is no difference in short-term mortality between laparoscopic and open gastrectomy. Based on very low quality evidence, there is no evidence for any differences in short-term or long-term outcomes between laparoscopic and open gastrectomy. However, the data are sparse, and the confidence intervals were wide, suggesting that significant benefits or harms of laparoscopic gastrectomy cannot be ruled out. Several trials are currently being conducted and interim results of these trials have been included in this review. These trials need to perform intention-to-treat analysis to ensure that the results are reliable and report the results according to the CONSORT Statement.

Background: The incidence of pathological lymph node metastases in patients with gastric cancer is 5% to 10%, which means that approximately 90% of patients with gastric cancer may undergo unnecessary lymphadenectomy. The precise intraoperative diagnosis of sentinel lymph node (SN) metastases is essential. The purpose of the current study was to verify the usefulness of a rapid reverse transcriptase-polymerase chain reaction (RT-PCR) system compared with hematoxylin and eosin staining for such diagnoses., Methods: A total of 113 patients with clinical T1-T2 (cT1-T2) gastric cancer, including 73 patients with cT1cN0 disease with a tumor diameter <4 cm, were enrolled in the current study. SNs were identified by a radioisotope method. Carcinoembryonic antigen and cytokeratin 19 were used as markers for RT-PCR and the cutoff values were set using 1701 lymph nodes harvested from 157 patients with gastric cancer., Results: SNs were detected in all 113 patients. Sensitivity and accuracy for detection by paraffin section were both 100% in patients with cT1 disease and were 60% and 90%, respectively, in patients with cT2 disease. The sensitivity of RT-PCR for the detection of pathological SN metastases was 92.3%. Furthermore, 11 patients had SN metastases detected only by RT-PCR, and these patients had frequent lymphatic invasion. Hematoxylin and eosin staining detected SN metastases in 6 of 73 patients with cT1cN0 gastric cancer; RT-PCR and frozen section detected SN metastases in 6 and 4 of these patients, respectively. Accordingly, the sensitivity of RT-PCR and frozen section for the detection of those pathological SN metastases were 100% and 66.6%, respectively., Conclusions: The rapid RT-PCR system appears to have clinical usefulness for the intraoperative detection of SN metastases in patients with gastric cancer., (© 2015 American Cancer Society.)

Background: The impact of lymphadenectomy extent on the survival of patients with primary resectable gastric carcinoma is debated., Objectives: We aimed to systematically review and meta-analyze the evidence on the impact of the three main types of progressively more extended lymph node dissection (that is, D1, D2 and D3 lymphadenectomy) on the clinical outcome of patients with primary resectable carcinoma of the stomach. The primary objective was to assess the impact of lymphadenectomy extent on survival (overall survival [OS], disease specific survival [DSS] and disease free survival [DFS]). The secondary aim was to assess the impact of lymphadenectomy on post-operative mortality., Search Methods: We searched CENTRAL, MEDLINE and EMBASE until 2001, including references from relevant articles and conference proceedings. We also contacted known researchers in the field. For the updated review, CENTRAL, MEDLINE and EMBASE were searched from 2001 to February 2015., Selection Criteria: We considered randomized controlled trials (RCTs) comparing the three main types of lymph node dissection (i.e., D1, D2 and D3 lymphadenectomy) in patients with primary non-metastatic resectable carcinoma of the stomach., Data Collection and Analysis: Two authors independently extracted data from the included studies. Hazard ratios (HR) and relative risks (RR) along with their 95% confidence intervals (CI) were used to measure differences in survival and mortality rates between trial arms, respectively. Potential sources of between-study heterogeneity were investigated by means of subgroup and sensitivity analyses. The same two authors independently assessed the risk of bias of eligible studies according to the standards of the Cochrane Collaboration and the quality of the overall evidence based on the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria., Main Results: Eight RCTs (enrolling 2515 patients) met the inclusion criteria. Three RCTs (all performed in Asian countries) compared D3 with D2 lymphadenectomy: data suggested no significant difference in OS between these two types of lymph node dissection (HR 0.99, 95% CI 0.81 to 1.21), with no significant difference in postoperative mortality (RR 1.67, 95% CI 0.41 to 6.73). Data for DFS were available only from one trial and for no trial were DSS data available. Five RCTs (n = 3 European; n = 2 Asian) compared D2 to D1 lymphadenectomy: OS (n = 5; HR 0.91, 95% CI 0.71 to 1.17) and DFS (n=3; HR 0.95, 95% CI 0.84 to 1.07) findings suggested no significant difference between these two types of lymph node dissection. In contrast, D2 lymphadenectomy was associated with a significantly better DSS compared to D1 lymphadenectomy (HR 0.81, 95% CI 0.71 to 0.92), the quality of the body of evidence being moderate; however, D2 lymphadenectomy was also associated with a higher postoperative mortality rate (RR 2.02, 95% CI 1.34 to 3.04)., Authors' Conclusions: D2 lymphadenectomy can improve DSS in patients with resectable carcinoma of the stomach, although the increased incidence of postoperative mortality reduces its therapeutic benefit.

S-1 is an oral 5-fluorouracil agent containing tegafur, 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate. This study explored the pharmacokinetics of S-1 and pharmacokinetic changes after gastric surgery in patients with resectable gastric cancer who received pre- and postoperative S-1 plus docetaxel. Serial blood was drawn before and after gastrectomy from 37 patients for pharmacokinetic analysis. The pharmacokinetics of tegafur, 5-fluorouracil, and CDHP were analyzed by noncompartmental analysis (NCA) methods and by modeling. In modeling analysis, CHDP concentrations were incorporated in the model as a time-varying covariate that inhibits the clearance of 5-fluorouracil following an inhibitory Emax model. In NCA, the pharmacokinetics of tegafur and 5-FU before and after gastric surgery were similar, although average maximum concentrations of 5-FU were decreased with statistical significance after gastrectomy. Median Tmax of tegafur was shorter after surgery without statistical significance. In modeling analysis, tegafur was best fitted by mixed zero and first-order absorption. The only difference in the final pharmacokinetic model around gastrectomy was the presence of an absorption lag of 0.23 hours before surgery. Incorporation of CDHP concentrations significantly improved the model. Although some pharmacokinetic results showed statistically significant changes after gastrectomy, these differences seem to be too small to have any clinical implication., (© 2015, The American College of Clinical Pharmacology.)