Prognostic utility of adequate nutritional support in critically ill surgical patients as revealed by the modified nutrition risk in critically ill score.

BACKGROUND: The modified Nutrition Risk in the Critically Ill (mNUTRIC) score was developed to identify patients most likely to benefit from nutritional therapies and to stratify or select subjects for clinical trials. However, the validity of the score and the association between that score and the prognosis of patients in surgical intensive care units (SICUs) remain unclear. This study explored whether the score was a useful prognostic indicator for SICU patients, and whether survival could be improved via nutritional interventions based on mNUTRIC status. METHODS: This retrospective observational study enrolled 123 patients admitted to our SICU for critical care from January 2018 to December 2019. Among these, mNUTRIC medical data were available for 116. In-hospital mortality rates were compared based on both mNUTRIC status and the adequacy of nutritional supplementation. RESULTS: mNUTRIC-high status (5 points or more) was apparent in 16 â€‹% of all critically ill surgical patients. In-hospital mortality was significantly higher in those with mNUTRIC-high scores (42.1 â€‹% vs. 15.5 â€‹%, P â€‹= â€‹0.023). Both groups exhibited less mortality when nutrition was adequate vs. inadequate (5.0 â€‹% vs. 40.9 â€‹% and 26.7 â€‹% vs. 100 â€‹%, respectively). In multivariate analysis, mNUTRIC-high scores and inadequate nutritional support were significant risk factors for in-hospital mortality (hazard ratios 7.336 and 13.636, P â€‹= â€‹0.027 and 0.002, respectively). CONCLUSION: In critically ill surgical patients, those identified as nutritionally high-risk using the mNUTRIC classification had poor in-hospital survival. Moreover, patients who received adequate nutritional support had a better prognosis than those who did not.

Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer.

Early detection and surgical treatment are essential to achieve a good outcome in gastric cancer (GC). Stage IV and recurrent GC have a poor prognosis. Therefore, new treatments for GC are needed. We investigated the intestinal microbiome of GC patients and attempted to reverse the immunosuppression of the immune and cancer cells of GC patients through the modulation of microbiome metabolites. We evaluated the levels of programmed death-ligand 1 (PD-L1) and interleukin (IL)-10 in the peripheral blood immunocytes of GC patients. Cancer tissues were obtained from patients who underwent surgical resection of GC, and stained sections of cancer tissues were visualized via confocal microscopy. The intestinal microbiome was analyzed using stool samples of healthy individuals and GC patients. Patient-derived avatar model was developed by injecting peripheral blood mononuclear cells (PBMCs) from advanced GC (AGC) patients into NSG mice, followed by injection of AGS cells. PD-L1 and IL-10 had higher expression levels in immune cells of GC patients than in those of healthy controls. The levels of immunosuppressive factors were increased in the immune and tumor cells of tumor tissues of GC patients. The abundances of Faecalibacterium and Bifidobacterium in the intestinal flora were lower in GC patients than in healthy individuals. Butyrate, a representative microbiome metabolite, suppressed the expression levels of PD-L1 and IL-10 in immune cells. In addition, the PBMCs of AGC patients showed increased levels of immunosuppressive factors in the avatar mouse model. Butyrate inhibited tumor growth in mice. Restoration of the intestinal microbiome and its metabolic functions inhibit tumor growth and reverse the immunosuppression due to increased PD-L1 and IL-10 levels in PBMCs and tumor cells of GC patients.

Effect of IL-10-producing B cells in peripheral blood and tumor tissue on gastric cancer.

BACKGROUND: Interleukin (IL)-10-producing B (B10) cells are generated in response to signals from the tumor microenvironment and promote tumor growth by interacting with B10 cells. We investigated the distributions of immune cells in peripheral blood and tumor tissue samples from patients with gastric cancer (GC). METHODS: Patients with GC who underwent radical gastrectomy in Seoul St. Mary's Hospital between August 2020 and May 2021 were enrolled in this study. Forty-two samples of peripheral blood were collected, and a pair of gastric mucosal samples (normal and cancerous mucosa; did not influence tumor diagnosis or staging) was collected from each patient after surgery. B10 cells in peripheral blood and cancer mucosa samples were investigated by flow cytometry and immunofluorescence. AGS cells, gastric cancer cell line, were cultured with IL-10 and measured cell death and cytokine secretion. Also, AGS cells were co-cultured with CD19 + B cells and measured cytokine secretion. RESULTS: The population of B10 cells was significantly larger in the blood of patients with GC compared with controls. In confocal images of gastric mucosal tissues, cancerous mucosa contained more B10 cells than normal mucosa. The population of B10 cells in cancerous mucosa increased with cancer stage. When AGS cells were cultured under cell-death conditions, cellular necrosis was significantly decreased, and proliferation was increased, for 1 day after IL-10 stimulation. Tumor necrosis factor (TNF)-α, IL-8, IL-1ß, and vascular endothelial growth factor secretion by cancer cells was significantly increased by coculture of AGS cells with GC-derived CD19+ B cells. CONCLUSIONS: B cells may be one of the populations that promote carcinogenesis by inducing the production of inflammatory mediators, such as IL-10, in GC. Targeting B10 cells activity could improve the outcomes of antitumor immunotherapy. Video Abstract.

Prognostic significances of PD-L1- and CTLA-4-positive T cells and positive correlations of immunosuppressive marker expression between cancer tissue and peripheral blood in patients with gastric cancer.

Introduction: Although tumor, node, metastasis (TNM) staging has been used for prognostic assessment of gastric cancer (GC), the prognosis may vary among patients with the same TNM stage. Recently, the TNM-Immune (TNM-I) classification staging system has been used for prognostic assessment of colorectal cancer based on intra-tumor T-cell status, which is a superior prognostic factor compared with the American Joint Committee on Cancer staging manual. However, an immunoscoring system with prognostic significance for GC has not been established. Method: Here, we evaluated immune phenotypes in cancer and normal tissues, then examined correlations between tissues and peripheral blood. GC patients who underwent gastrectomy at Seoul St. Mary's Hospital between February 2000 and May 2021 were included. We collected 43 peripheral blood samples preoperatively and a pair of gastric mucosal samples postoperatively, including normal and cancer mucosa, which did not influence tumor diagnosis and staging. Tissue microarray samples of GC were collected from 136 patients during surgery. We investigated correlations of immune phenotypes between tissues and peripheral blood using immunofluorescence imaging and flow cytometry, respectively. GC mucosa exhibited an increased number of CD4+ T cells, as well as increased expression levels of immunosuppressive markers (e.g., programmed death-ligand-1 [PD-L1], cytotoxic T lymphocyte antigen-4 [CTLA-4], and interleukin-10), in CD4+ T cells and non-T cells. Result: The expression levels of immunosuppressive markers were significantly increased in cancer tissues and peripheral blood mononuclear cells. In gastric mucosal tissues and peripheral blood of GC patients, similar immunosuppression phenotypes were observed, including increased numbers of PD-L1- and CTLA-4-positive T cells. Discussion: Therefore, peripheral blood analysis may be an important tool for prognostic assessment of GC patients.

Radical gastrectomy is safe for treatment of gastric cancer patients on immunosuppressive drugs after organ transplantation.

Background: De novo malignancies are major causes of death after organ transplantation because the recipients subsequently receive immunosuppressant drugs. When gastric cancer develops, the clinical course of the tumor may be particularly aggressive. However, there are few reliable studies of gastric cancer treatment after organ transplantation. This study examined the clinicopathological characteristics of gastric cancer patients after organ transplantation and evaluated treatment outcomes after gastrectomy. Methods: Clinical data were collected from 54 patients who were diagnosed with gastric cancer after organ transplantation. Of these, 30 who underwent surgery for gastric cancer while on immunosuppressant medications were compared with a control group of 625 gastric cancer patients. To compensate for clinical differences between the two groups, 1:1 propensity-score matching was performed. Results: Among the 30 gastric cancer patients on immunosuppressants, kidney transplantation was the most common procedure (19/30, 63.3%) followed by bone marrow (6) and liver transplantation (4); among all 54 patients, 45 were on one or two immunosuppressants. Up-migration to an advanced pathological stage was more frequent in the transplant group. In multivariate analysis, transplantation was a significant risk factor for up-migration from the T, M, and final stages after surgery. When the 30 patients on immunosuppressants who underwent gastric cancer surgery were compared with the matched controls, the total incidence (30.0 vs 40.0%, P = 0.417) and the number of severe postoperative complications (16.7 vs 13.4%, P = 0.417) did not differ significantly between groups after propensity score matching. In terms of overall survival, the transplant group showed significantly worse prognosis in stages I, II, and IV (P < 0.001, P = 0.039 and 0.007, respectively). Conclusion: Radical gastrectomy can be a safe oncological procedure for gastric cancer patients on immunosuppressants after transplantation. Considering their immunosuppressed condition and the possibility of underestimation of the stage of gastric cancer, early detection with endoscopic screening is needed to allow curative treatment.

Rebamipide treatment ameliorates obesity phenotype by regulation of immune cells and adipocytes.

Obesity is a medical term used to describe an over-accumulation of adipose tissue. It causes abnormal physiological and pathological processes in the body. Obesity is associated with systemic inflammation and abnormalities in immune cell function. Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, has been used as a therapeutic for the protection from mucosal damage. Our previous studies have demonstrated that rebamipide treatment regulates lipid metabolism and inflammation, leading to prevention of weight gain in high-fat diet mice. In this study, mice were put on a high calorie diet for 11 weeks while receiving injections of rebamipide. Rebamipide treatment reduced the body weight, liver weight and blood glucose levels compared to control mice and reduced both glucose and insulin resistance. Fat accumulation has been shown to cause pro-inflammatory activity in mice. Treatment with rebamipide decreased the prevalence of inflammatory cells such as Th2, Th17 and M1 macrophages and increased anti-inflammatory Treg and M2 macrophages in epididymal fat tissue. Additionally, rebamipide addition inhibited adipocyte differentiation in 3T3-L1 cell lines. Taken together, our study demonstrates that rebamipide treatment is a novel and effective method to prevent diet-induced obesity.

Effects of Reproductive Factors on Lauren Intestinal-Type Gastric Cancers in Females: A Multicenter Retrospective Study in South Korea.

Background/Aims: Gastric cancers (GCs), particularly the Lauren intestinal type, show a male predominance. The aim of this study was to investigate the effects of reproductive factors on GCs in females, according to Lauren classification. Methods: Medical records of 1,849 males and 424 females who underwent radical gastrectomy or endoscopic resection for GCs between 2010 and 2018 were reviewed. The incidences of intestinal-type GCs were compared between males and groups of females stratified according to postmenopausal period. Associations between reproductive factors in females and intestinaltype GCs were analyzed using multivariate models. Results: The proportions of intestinal-type GCs were significantly lower in premenopausal (19%), less than 10 years postmenopausal (30.4%), and 10 to 19 years postmenopausal females (44.1%) than in males (61.0%) (p<0.05 for all). Females ≥20 years postmenopause had a proportion of intestinal-type GCs similar to that in males (60.6% vs 61.0%; p=0.948). Multivariate analysis revealed that age (odds ratio [OR], 1.075; 95% confidence interval [CI], 1.039 to 1.113; p<0.001) and parity ≥3 (OR, 1.775; 95% CI, 1.012 to 3.114; p=0.045) were positively associated with an increased risk of intestinal-type GCs in postmenopausal females, while long fertility duration (OR, 1.147; 95% CI, 1.043 to 1.261; p=0.005) was positively associated with an increased risk of intestinal-type GCs in premenopausal females. Conclusions: There were no significant differences in the proportions of intestinal-type GCs between males and females ≥20 years postmenopause, suggesting that female reproductive factors play a role in the prevention of intestinal-type GC.

Hybrid Robotic and Laparoscopic Gastrectomy for Gastric Cancer: Comparison with Conventional Laparoscopic Gastrectomy.

PURPOSE: The benefits of robotic gastrectomy remain controversial. We designed this study to elucidate the advantages of a hybrid robot and laparoscopic gastrectomy over conventional laparoscopic surgery. MATERIALS AND METHODS: A total of 176 patients who underwent gastrectomy for gastric cancer were included in this study. We compared 88 patients treated with hybrid robotic and laparoscopic gastrectomy (HRLG) and 88 patients who underwent conventional laparoscopic gastrectomy (CLG). In HRLG, suprapancreatic lymph node (LN) dissection was performed in a robotic setting. Clinicopathological characteristics, operative details, and short-term outcomes were analyzed for the patients. RESULTS: The number of LNs retrieved from the suprapancreatic area was significantly greater in the HRLG group (11.27±5.46 vs. 9.17±5.19, P=0.010). C-reactive protein levels were greater in the CLG group on both postoperative day (POD) 1 (5.11±2.64 vs. 4.29±2.38, P=0.030) and POD 5 (9.86±6.51 vs. 7.75±5.17, P=0.019). In addition, the neutrophil-to-lymphocyte ratio was significantly greater in the CLG group on both POD 1 (7.44±4.72 vs. 6.16±2.91, P=0.031) and POD 5 (4.87±3.75 vs. 3.81±1.87, P=0.020). Pulmonary complications occurred only in the CLG group (4/88 [4.5%] vs. 0/88 [0%], P=0.043). CONCLUSIONS: HRLG is superior to CLG in terms of suprapancreatic LN dissection and postoperative inflammatory response.

Advanced Diagnostic Technology of Volatile Organic Compounds Real Time analysis Analysis From Exhaled Breath of Gastric Cancer Patients Using Proton-Transfer-Reaction Time-of-Flight Mass Spectrometry.

BACKGROUND: Screening endoscopy is considered to be the most accurate tool for early detection of gastric cancer, but it is both invasive and costly. It is therefore essential to develop cost-effective and non-invasive diagnostic tools for gastric cancer. The aim of this study is to investigate the presence of certain volatile organic compounds (VOCs) associated with gastric cancer and to survey the usefulness of VOCs as screening tools of gastric cancer. METHODS: The present study was conducted prospectively to identify the relationship between gastric cancer and specific VOCs quantified by mass spectrometry. Exhaled breath samples from a total of 43 participants were analysed. This study was approved by the Institutional Review Board of the College of Medicine, Catholic University of Korea (KC16TISI0598), and registered to clinical research information service (KCT0004356). RESULTS: Nine VOCs differed significantly between the control and cancer patient groups. When participants were divided into control, early gastric cancer (EGC), and advanced gastric cancer (AGC) groups, seven VOCs remained significantly different. Of these, four (propanal, aceticamide, isoprene and 1,3 propanediol) showed gradual increases as cancer advanced, from normal control to EGC to AGC. In receiver operating characteristic curves for these four VOCs, the area under the curve for gastric cancer prediction was highest (0.842) when more than two VOCs were present. CONCLUSIONS: The present study offers potential directions for non-invasive gastric cancer screening, and may inspire advanced diagnostic technologies in the era of smart home healthcare. However, despite the high accuracy, cancer-specific VOCs from several studies on different populations, and analytic methods show inconsistency, it is necessary to establish standards for each analytical method, and to validate on each population.

GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance.

Obesity, a condition characterized by excessive accumulation of body fat, is a metabolic disorder related to an increased risk of chronic inflammation. Obesity is mediated by signal transducer and activator of transcription (STAT) 3, which is regulated by genes associated with retinoid-interferon-induced mortality (GRIM) 19, a protein ubiquitously expressed in various human tissues. In this study, we investigated the role of GRIM19 in diet-induced obese C57BL/6 mice via intravenous or intramuscular administration of a plasmid encoding GRIM19. Splenocytes from wild-type and GRIM19-overexpressing mice were compared using enzyme-linked immunoassay, real-time polymerase chain reaction, Western blotting, flow cytometry, and histological analyses. GRIM19 attenuated the progression of obesity by regulating STAT3 activity and enhancing brown adipose tissue (BAT) differentiation. GRIM19 regulated the differentiation of mouse-derived 3T3-L1 preadipocytes into adipocytes, while modulating gene expression in white adipose tissue (WAT) and BAT. GRIM19 overexpression reduced diet-induced obesity and enhanced glucose and lipid metabolism in the liver. Moreover, GRIM19 overexpression reduced WAT differentiation and induced BAT differentiation in obese mice. GRIM19-transgenic mice exhibited reduced mitochondrial superoxide levels and a reciprocal balance between Th17 and Treg cells. These results suggest that GRIM19 attenuates the progression of obesity by controlling adipocyte differentiation.

Modified controlling nutritional status score: A refined prognostic indicator depending on the stage of gastric cancer.

BACKGROUND: The role of controlling nutritional status (CONUT) score in predicting cancer survival remains uncertain. This study aimed to investigate the predictive value of the CONUT score and to develop a more appropriate scoring system beyond CONUT for gastric cancer. METHODS: We retrospectively reviewed 1307 patients who underwent curative gastrectomy between 2009 and 2015. The CONUT and three modified scores with modified lipid components (L-CONUT: albumin/total lymphocyte count [TLC]/low density lipoprotein, H-CONUT: albumin/TLC/high density lipoprotein, and T-CONUT: albumin/TLC/triglyceride) were calculated. The predictive value of each scoring system on long-term survival was assessed. RESULTS: The values of the four nutritional scores were categorized into four groups (normal, light, moderate, and severe). The CONUT (P < 0.001), L-CONUT (P < 0.001), H-CONUT (P < 0.001), and T-CONUT (P < 0.001) scores showed significant differences in overall survival in between groups. Survival analysis according to the pathological stage showed that advanced age, Eastern Cooperative Oncology Group performance status, male sex, and moderate H-CONUT score (HR, 3.970; 95% CI, 1.826-8.633; P = 0.001) were independent worse prognostic factors for overall survival in the stage I group. In the stage II group, light CONUT score (HR, 2.230; 95% CI, 1.067-4.664; P = 0.033) and moderate CONUT score (HR, 5.077; 95% CI, 1.647-15.650; P = 0.005) were significantly associated with poor prognosis. In the stage III group, no scoring system showed significant results. CONCLUSION: In advanced gastric cancer (beyond stage II), the prognostic impact of the nutritional scoring system was uncertain. However, the H-CONUT score is a promising indicator of prognosis in stage I, and the CONUT score is useful for predicting long-term survival in stage II gastric cancer.

Operative safety of curative gastrectomy after endoscopic submucosal dissection (ESD) for early gastric cancer - 1:2 propensity score matching analysis: A retrospective single-center study (cohort study).

BACKGROUND: This study aimed to evaluate the operative safety and long-term outcomes of additional curative gastrectomy (ACG) after non-curative endoscopic submucosal dissection (ESD), as compared with standard gastrectomy (SG) without ESD in patients with early gastric cancer. MATERIALS AND METHODS: Data from 101 patients receiving ACG after non-curative ESD (Post-ESD group) and 1080 patients after SG without ESD (Surgery-only group), between 2009 and 2016, were reviewed retrospectively. Clinicopathologic characteristics, overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were compared between groups, using propensity score matching analysis. RESULTS: After propensity score matching, a total of 101 patients in the post-ESD group and 202 patients in the surgery-only group were analyzed. The post-ESD group had shorter operation times than did the surgery-only group (p = 0.005). Estimated blood loss and the incidence of postoperative morbidity did not differ between the two groups, and no differences were observed in pathologic outcomes, including N stage (p = 0.268). In addition, 5-year OS, DSS, and RFS rates were not significantly different between groups (OS; 95.1% vs. 98.2%, p = 0.535, DSS; 98.2% vs. 98.7%, p = 0.956, and RFS; 98.6% vs. 98.9%, p = 0.757, respectively). CONCLUSION: ACG can be performed safely after non-curative endoscopic submucosal dissection, with good operative outcomes.

Regional Lymph Node Dissection as an Additional Treatment Option to Endoscopic Resection for Expanded Indications in Gastric Cancer: a Prospective Cohort Study.

PURPOSE: Expanded indications for endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) remain controversial due to the potential risk of undertreatment after adequate lymph node dissection (LND). Regional LND (RLND) is a novel technique used for limited lymphadenectomy to avoid gastrectomy. This study established the safety and effectiveness of RNLD as an additional treatment option after ESD for expanded indications. MATERIALS AND METHODS: A total of 69 patients who met the expanded indications for ESD were prospectively enrolled from 2014 to 2017. The tumors were localized using intraoperative esophagogastroduodenoscopy (EGD) before RLND. All patients underwent RLND first, followed by conventional radical gastrectomy with LND. The locations of the preoperative and intraoperative EGD were compared. Pathologic findings of the primary lesion and the RLND status were analyzed. RESULTS: The concordance rates of tumor location between the preoperative and intraoperative EGD were 79.7%, 76.8%, and 63.8% according to the longitudinal, circumferential, and regional locations, respectively. Of the 4 patients (5.7%) with metastatic LNs, 3 were pathologically classified as beyond the expanded indication for ESD and 1 had a single LN metastasis in the regional lymph node. CONCLUSIONS: RLND is a safe additional option for the treatment of EGC in patients meeting expanded indications after ESD.

Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection according to lymph node ratio and N stage.

BACKGROUND: We sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging. METHODS: Patients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0-0.1, 0.1-0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups. RESULTS: After PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16~124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group. CONCLUSIONS: LNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1. TRIAL REGISTRATION: Not applicable (retrospective study).

The Effect of Metformin on Prognosis in Patients With Locally Advanced Gastric Cancer Associated With Type 2 Diabetes Mellitus.

OBJECTIVES: This study examined the effect of metformin use on the prognosis of gastric cancer patients. MATERIALS AND METHODS: The study population comprised 2187 patients who underwent curative gastrectomy for the treatment of gastric cancer. They were divided into 3 groups: metformin (n=103), non-metformin (n=139), and non-diabetes mellitus (DM) (n=1945) according to their history of type 2 DM and metformin use. Survival, disease recurrence, and the pathologic stage were analyzed. RESULTS: Overall survival was better in the metformin group than in the non-DM group (P=0.005). Metformin use was an independent prognostic factor of overall survival, cancer recurrence, and peritoneal recurrence. An effect of metformin use was especially notable in patients with T4 or N0 disease. CONCLUSIONS: Metformin improves the survival of patients with gastric cancer and type 2 DM.

Stage-specific difference in timing and pattern of initial recurrence after curative surgery for gastric cancer.

BACKGROUND: Gastric cancer (GC) follow-up schedule after curative surgery is universally recommended based on the pathologic stage, but their details, including intervals and modalities of surveillance have not yet been standardised. The aim of this study was to investigate the characteristics of GC recurrence by stage to establish optimal postoperative surveillance strategies. METHODS: Medical information on 5095 patients with GC who underwent curative intent gastrectomy in our institution between January 1989 and December 2013 was reviewed retrospectively. Moreover, 656 patients who had recurrences after radical surgery were identified. Clinicopathologic characteristics, timing and pattern of recurrence, and survival data of these patients were analysed. RESULTS: Among the 656 patients, 50 (7.6%), 123 (18.8%), and 483 (73.6%) had stages I, II, and III GC, respectively. The median times to initial recurrence in patients with stages I, II, and III GC were 23.5 months (interquartile range [IQR], 13.0-33.0 months), 13.0 months (IQR, 9.0-25.0 months), and 12.0 months (IQR, 7.0-21.0 months), respectively. In patients with stage I GC, more than half (58%) of them had distant organ metastasis; otherwise, peritoneal dissemination (39%) was the most common pattern in patients with stage III GC. CONCLUSIONS: Despite the low incidence, the time of initial recurrence in stage I GC was longer than those in stage II and III GC. Moreover, the pattern of initial recurrence was also different according to the pathologic stage. Therefore, clinicians should consider stage-specific differences of recurrence in setting up surveillance strategies after curative surgery for GC patients.

The Relevance of Serosal Exposure Without Nodal Metastasis in Resectional Gastric Cancer.

BACKGROUND: According to 8th AJCC/UICC TNM criteria, stage IIB includes pT1N3M0, pT2N2M0, pT3N1M0, and pT4aN0M0, which includes not only early gastric cancer but also locally advanced cancer. There are currently no data about whether there is any additional impact of serosal exposed cancer without nodal metastasis (pT4aN0) on patients' survival outcomes compared with other subgroups in IIB. METHODS: Patients who underwent radical gastrectomy for gastric cancer patients were enrolled, including 427 patients in stage IIB; 20 (4.68%), 104 (24.35%), 172 (40.28%), and 131 (30.67%) patients were classified as pT1N3a, pT2N2, pT3N1, and pT4aN0, respectively. Clinicopathological characteristics, recurrence pattern, and survival and recurrence rates were analyzed according to the TNM subgroups. RESULTS: Cancer-specific and relapse-free survival were significantly worse in serosal exposed cancer than in nonserosal exposed cancer in stage IIB (P = 0.019 and P = 0.015). Recurrence rate was highest in the pT4aN0 subgroup (29.0%) in stage IIB, and peritoneal metastasis was the most common pattern. Survival outcomes of the pT4aN0 subgroup were not significantly different from those of the stage IIIA or pT4aN1 subgroups. CONCLUSIONS: Patients with serosal exposed cancer without nodal metastasis shows worse cancer specific and disease-free survival with higher incidence of peritoneal metastasis than other subgroups in stage IIB. Further surveillance studies, including staging laparoscopy and active adjuvant therapy, are required in this subgroup of patients.

Three-Port Right-Side Approach-Duet Totally Laparoscopic Distal Gastrectomy for Uncut Roux-en-Y Reconstruction.

BACKGROUND: This study presents the initial feasibility of three-port right-side approach-duet totally laparoscopic distal gastrectomy (R-duet TLDG) with uncut Roux-en-Y (R-Y) reconstruction for the treatment of lower- or middle-third gastric cancer. METHODS: A total of 30 patients who underwent R-duet TLDG with uncut R-Y reconstruction for gastric cancer were enrolled. All patients were treated at the Catholic Medical Center. Reconstructions were performed intracorporeally without special instruments. The clinicopathological characteristics, operative details, postoperative short-term outcomes, and postoperative follow-up endoscopy results were analyzed retrospectively. RESULTS: All operations were performed by three-port R-duet TLDG. There were no conversions to an open approach, and no additional ports were placed. The mean operating time was 170 minutes, and the mean number of retrieved lymph nodes was 44. Three patients experienced mild postoperative complications, including small bowel ileus and pneumonia. Follow-up endoscopy was carried out at 3 months. No patients had experienced moderate-or-severe food stasis, alkaline gastritis, or bile reflux during the follow-up period. Recanalization of the biliopancreatic limb was not observed. CONCLUSIONS: R-duet TLDG with uncut R-Y reconstruction could be safely performed as a reduced port surgery without special instruments.

Venous Thromboembolism Incidence and Prophylaxis Use After Gastrectomy Among Korean Patients With Gastric Adenocarcinoma: The PROTECTOR Randomized Clinical Trial.

Importance: The guidelines by the National Comprehensive Cancer Network and the American Society for Clinical Oncology recommend the routine use of thromboprophylaxis for patients with gastric adenocarcinoma. However, many physicians in Asian countries use venous thromboembolism (VTE) prophylaxis much less often because of the perceived lower VTE incidence in this population. Objectives: To evaluate the incidence of postgastrectomy VTE in Korean patients with gastric adenocarcinoma, and to identify the complications and evaluate the efficacy and safety of VTE prevention methods. Design, Setting, and Participants: The Optimal Prophylactic Method for Venous Thromboembolism After Gastrectomy in Korean Patients (PROTECTOR) randomized clinical trial was conducted between August 1, 2011, and March 31, 2015. Patients with histologically confirmed gastric adenocarcinoma presenting to a single center (Seoul St Mary's Hospital in Seoul, South Korea) were enrolled. Patients were randomized to either an intermittent pneumatic compression (IPC)-only group or an IPC+low-molecular-weight (LMW) heparin sodium group. The data were analyzed on intention-to-treat and per protocol bases. Data analysis was performed from April 1, 2016, to October 30, 2017. Main Outcomes and Measures: Venous thromboembolism incidence was the primary outcome. Postoperative complications, particularly those associated with VTE prophylaxis methods, were the secondary end point. Results: Of the 682 patients enrolled and randomized, 447 (65.5%) were male and 245 (34.5%) were female, with a mean (SD) age of 57.67 (12.94) years. Among the 666 patients included in the analysis, the overall incidence of VTE was 2.1%. The incidence of VTE was statistically significantly higher in the IPC-only group compared with the IPC+LMW heparin group (3.6%; 95% CI, 2.05%-6.14% vs 0.6%; 95% CI, 0.17%-2.18%; P = .008). Among the 14 patients (2.1%) with VTE, 13 were asymptomatic and received a deep vein thrombosis diagnosis, whereas 1 patient received a symptomatic pulmonary thromboembolism diagnosis. The overall incidence of bleeding complications was 5.1%. The incidence of bleeding complications was significantly higher in the IPC+LMW heparin group compared with the IPC-only group (9.1% vs 1.2%; P < .001). No cases of VTE-associated mortality were noted. Conclusions and Relevance: Use of IPC alone is inferior to the use of IPC+LMW heparin in preventing postoperative VTE. Because LMW heparin is associated with a high bleeding risk, further study is needed to stratify the patients at high risk for perioperative development of VTE. Trial Registration: ClinicalTrials.gov Identifier: NCT01448746.