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S6. Relative abundance of CM and CMM gene pairs across tumor types.

Table S1. Top 10 significant molecular terms (MSigDB c2cp; Curated Pathways) enriched in correlated and inversely-anticorrelated genes with tumor purity. Table S2. The GSEA results from individual tumor types. Table S3. Immune cell type-specific genes. Table S4. GSEA of genes with high/low differential correlation coefficients.

Surgical archives of tumor specimens are often impure. The presence of RNA transcripts from nontumor cells, such as immune and stromal cells, can impede analyses of cancer expression profiles. To systematically analyze the impact of tumor purity, the gene expression profiles and tumor purities were obtained for 7,794 tumor specimens across 21 tumor types (available in The Cancer Genome Atlas consortium). First, we observed that genes with roles in immunity and oxidative phosphorylation were significantly inversely correlated and correlated with the tumor purity, respectively. The expression of genes implicated in immunotherapy and specific immune cell genes, along with the abundance of immune cell infiltrates, was substantially inversely correlated with tumor purity. This relationship may explain the correlation between immune gene expression and mutation burden, highlighting the need to account for tumor purity in the evaluation of expression markers obtained from bulk tumor transcriptome data. Second, examination of cluster membership of gene pairs, with or without controlling for tumor purity, revealed that tumor purity may have a substantial impact on gene clustering across tumor types. Third, feature genes for molecular taxonomy were analyzed for correlation with tumor purity, and for some tumor types, feature genes representing the mesenchymal and classical subtypes were inversely correlated and correlated with tumor purity, respectively. Our findings indicate that tumor purity is an important confounder in evaluating the correlation between gene expression and clinicopathologic features such as mutation burden, as well as gene clustering and molecular taxonomy. Cancer Immunol Res; 6(1); 87–97. ©2017 AACR.

Esophagojejunal anastomosis (EJA) complications after total gastrectomy are related to significant morbidity and mortality. The aim of this study was to evaluate the association between arterial calcifications and EJA complications such as leak and stricture for gastric cancer. Between January 2014 and October 2019, 30 patients with EJA complications after total gastrectomy were enrolled and matched to 30 patients without complications through retrospective data review. Arterial calcification grade on preoperative computed tomography (CT) was reported in the abdominal aorta and superior mesenteric artery (SMA) as “absent”, “minor”, or “major”, and in the jejunal vascular arcade (JVA) and left inferior phrenic artery (LIPA) as “absent” or “present”. A Chi-square test was used to compare the variables between the two groups. p-Value < 0.050 was considered statistically significant. Among 30 patients, the numbers of patients with leak and stricture were 23 and seven, respectively. Aortic calcifications were not associated with EJA complications regardless of their grade (p = 0.440). Only major SMA calcifications were associated with EJA complications, as they were present in five patients (16.7%) in the complication group and absent in the non-complication group (p = 0.020). Major SMA calcifications were more related to anastomotic stricture than leak. Three (13.0%) out of 23 patients with leak and two (28.6%) out of seven with stricture had major SMA calcifications (p = 0.028). No calcifications were detected in the JVA or LIPA in any of the 60 patients. Major SMA calcifications were found to be associated with EJA complications, especially in stricture.

Background Weight changes after gastrectomy affect not only quality of life but also prognosis and survival. However, it remains challenging to predict the weight changes of individual patients. Using clinicopathological variables, we built a user-friendly tool to predict weight change after curative gastrectomy for gastric cancer. Methods The clinical data of 984 patients who underwent curative gastrectomy between 2009 and 2013 were retrospectively reviewed and analyzed. Multivariate logistic regression was performed to identify variables predictive of postoperative weight change. A nomogram was developed and verified via bootstrap resampling. Results Age, sex, performance status, body mass index, extent of resection, pathological stage, and postoperative weight change significantly influenced postoperative weight recovery. Postoperative levels of hemoglobin, albumin, ferritin and total iron-binding capacity were significant covariates. The nomogram performed well (concordance index = 0.637); calibration curves indicated appropriate levels of agreement. We developed an online weight prediction calculator based on the nomogram (http://gc-weightchange.com/en/front/). Conclusions The novel, Web-calculator based on the predictive model allows surgeons to explore patient weight patterns quickly. The model identifies patients at high risk for weight loss after gastrectomy; such patients require multidisciplinary medical support.

Background The relative prognostic value of each lymph node (LN) station remains undefined in the treatment of gastric cancer. This study aimed to develop a new method to evaluate LN station ranking and define the optimal extent of lymphadenectomy for early gastric cancer. Methods Clinical and histopathological information from patients who underwent curative gastrectomy with lymphadenectomy between 1989 and 2018 was reviewed. The LN station power index (LNPI) of each station was estimated using a LN retrieval frequency and the 5-year overall survival of patients with absence of LN at each station. External validation was conducted to evaluate the relevance of the LNPI. Results A training set was developed from examination of 7009 patient records. For most nodal stations, the absence of LN was significantly associated with a poor prognosis. For the perigastric stations, the prognostic value assessed using the LNPI was in the following order: LN 4 (LNPI = 19.68), LN 3 (LNPI = 17.58), LN 6 (LNPI = 15.16), LN 1 (LNPI = 6.71), LN 2 (LNPI = 4.64) and LN 5 (LNPI = 2.86). The value rank of the extra-gastric stations was in the following order: LN 8a (LNPI = 12.93), LN 7 (LNPI = 10.51) and LN 9 (LNPI = 9.70), but the index of LN 12a (LNPI = 4.79) was higher than that of LN 11 (LNPI = 4.78). These trends in the LNPI were similar in the validation patient cohort. Conclusions The LNPI is a simple tool to rank the priority of each LN station dissection. The optimal extent of D1 + lymphadenectomy using LNPI was determined to be D1 with LNs 7, 8a and 9.

Background The aim of this study was to elucidate the correlation of high-mobility group protein A2 overexpression with gastric cancer prognosis and compare its prognostic power with that of pre-existing markers. Methods Malignant tissues from 396 patients with gastric cancer who underwent gastrectomy from 2008 to 2012 were examined. High-mobility group protein A2 expression was assessed by immunohistochemistry and the sensitivity and specificity for predicting disease progression and overall survival of high-mobility group protein A2 and the prognostic biomarkers p53, Ki-67, human epidermal growth factor receptor 2, cyclooxygenase-2, and epidermal growth factor receptor were compared. Results A total of 95 samples (24.1%) showed high-mobility group protein A2 overexpression, which was related to advanced stage, undifferentiated histology, and lymphatic and perineural invasion. Additionally, high-mobility group protein A2 overexpression was an independent prognostic factor in multivariate analysis for disease progression and overall survival. Based on Kaplan-Meier survival analysis disease progression and overall survival, the high-mobility group protein A2-overexpressing patients showed worse survival. The recurrence pattern of peritoneal dissemination was more frequently observed in high-mobility group protein A2-positive group. Moreover, chemoresistance was more frequently observed in the high-mobility group protein A2-positive group. High-mobility group protein A2 exhibited a better ability for predicting disease progression and overall survival than other markers, and the prognostic power was enhanced when high-mobility group protein A2 was used with these markers. Conclusion High-mobility group protein A2 overexpression is associated with chemoresistance and a propensity for carcinomatosis peritonei after surgery in patients with gastric cancer. The power to predict the prognosis of patients with gastric cancer can be enhanced with the use of preexisting biomarkers and high-mobility group protein A2.

ImportancePatients undergoing proximal gastrectomy (PG) with double-tract reconstruction (DTR) have been reported to have an incidence of reflux esophagitis that is as low as that observed after total gastrectomy (TG). It is unclear whether PG has an advantage over TG for the treatment of patients with upper early gastric cancer (GC).ObjectiveTo evaluate the effect of laparoscopic PG with DTR (LPG-DTR) vs laparoscopic TG (LTG) on levels of hemoglobin and vitamin B12 supplementation required among patients with clinically early GC in the upper third of the stomach (upper-third early GC).Design, Setting, and ParticipantsThis multicenter open-label superiority randomized clinical trial was conducted at 10 institutions in Korea. A total of 138 patients with upper-third cT1N0M0 GC were enrolled between October 27, 2016, and September 9, 2018. Follow-up ended on December 3, 2020.InterventionsPatients were randomized to undergo either LPG-DTR or LTG.Main Outcomes and MeasuresThe primary co–end points were change in hemoglobin level and cumulative amount of vitamin B12 supplementation at 2 years after LPG-DTR or LTG. The secondary end points included morbidity, postoperative reflux esophagitis, quality of life, overall survival, and disease-free survival. Quality of life outcomes were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) 30-item core questionnaire (C30) and the EORTC QLQ stomach cancer–specific questionnaire at 3 months, 12 months, and 24 months.ResultsAmong 138 patients (mean [SD] age, 60.0 [10.9] years; 87 men [63.0%]; all of Asian race and Korean ethnicity), 68 (mean [SD] age, 56.7 [10.4] years; 39 men [57.4%]) were randomized to receive LPG-DTR and 69 (mean [SD] age, 61.3 [11.3] years; 48 men [69.6%]) were randomized to receive LTG. The mean (SD) changes in hemoglobin levels from baseline to month 24 were −5.6% (7.4%) in the LPG-DTR group and −6.9% (8.3%) in the LTG group, for an estimated difference of −1.3% (95% CI, −4.0% to 1.4%; P = .35). The mean (SD) cumulative amount of vitamin B12 supplementation was 0.4 (1.3) mg in the LPG-DTR group and 2.5 (3.0) mg in the LTG group, for an estimated difference of 2.1 mg (95% CI, 1.3-2.9 mg; P P = .31). The incidence of reflux esophagitis was not different between the LPG-DTR and LTG groups (2.9% vs 2.9%; P = .99). Compared with the LTG group, the LPG-DTR group had better physical functioning scores (85.2 [15.6] vs 79.9 [19.3]; P = .03) and social functioning scores (89.5 [17.9] vs 82.4 [19.4]; P = .03) on the EORTC QLQ-C30. Two-year overall survival (98.5% vs 100%; P = .33) and disease-free survival (98.5% vs 97.1%; P = .54) did not significantly differ between the LPG-DTR vs LTG groups.Conclusions and RelevanceIn this study, patients with upper-third early GC who received LPG-DTR required less vitamin B12 supplementation than those who received LTG, with no increase in complication rates and no difference in overall and disease-free survival rates. There was no difference in change in hemoglobin level between groups. In addition, the LPG-DTR group had better physical and social functioning than the LTG group. These findings suggest that LPG-DTR may be as safe as LTG and may be a function-preserving procedure for the treatment of patients with upper-third early GC.Trial RegistrationClinicalTrials.gov Identifier: NCT02892643

Purpose Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively). Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P

Laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) is a function-preserving procedure performed for treating upper early gastric cancer (EGC). However, few studies have compared the outcomes of LPG-DTR with those of laparoscopic total gastrectomy (LTG). This study aimed at comparing the short-term outcomes of LPG-DTR between LTG and upper EGC.For upper-third EGC, a multicenter, prospective, randomized trial was performed to compare those who underwent LPG-DTR with those who underwent LTG. Short-term outcomes, including clinicopathologic results, morbidity, mortality, and postoperative courses, were evaluated using a full analysis set based on the intention-to-treat principle and the per-protocol set.Of the patients, 138 who fulfilled the criteria were randomized to each group. One patient in the LPG-DTR group withdrew consent. Sixty-eight patients underwent LPG-DTR and 69 underwent LTG. The operative time (LPG-DTR=219.4 minutes; LTG=201.8 minutes; PThe short-term outcomes of LPG-DTR for upper EGC were comparable to those of LTG.ClinicalTrials.gov Identifier: NCT02892643.

Endoscopic evaluation of the stomach is essential for preoperative planning and post-surgical surveillance for various diseases of the stomach, including malignancy. The gastroscopy education program for surgeons is currently in its infancy and is not systematically organized in Korea. This study aimed to introduce the first systematic gastroscopy education program for surgeons in Korea.The gastroscopy education program entitled "Gastroscopy School for Surgeons (GSS)" comprised of theoretical education, dry lab hands-on training, and clinical practice. All participants were beginners without any gastroscopy experience. Clinical practice started after the completion of the theoretical and dry lab training. The gastroscopy practices utilized simple luminal observation, biopsy, localization using clips or dye injection, and limited therapeutic gastroscopy. The educational performances and surveys from 33 participants were analyzed.The participants consisted of surgical residents, general surgeons, gastrointestinal-specialized surgeons, and physicians. Participants performed a total of 2,272 gastroscopies, 2,008 of which were post-gastrectomy cases. Currently, of the 33 participants, 7 (21.2%) of the participants performed gastroscopy regularly, and 7 (21.2%) occasionally. According to the self-reported survey, one participant assessed their current gastroscopic technique to be at the expert level, and 25 (75.8%) at a proficient level. All participants considered gastroscopy education for surgeons to be necessary, and 28 (84.8%) stated that systematic education is not currently provided in Korea.We introduced the first systematic gastroscopy education program for surgeons in Korea, namely the GSS, which is practical and meets clinical needs. More training centers are needed to expand gastroscopy training among Korean surgeons.

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.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.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.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.

Remnant gastric cancer (RGC) has a major impact on the long-term survival of postgastrectomy patients. In this study, we established surveillance endoscopy guidelines for postgastrectomy patients based on the risk of RGC. A total of 6365 patients who underwent gastrectomy at Seoul St. Mary’s Hospital from September 2005 to June 2018 were retrospectively reviewed; 85 patients were identified as having RGC. We divided the RGC patients into subgroups according to the interval between primary and secondary gastrectomy. The curative resection rate was significantly lower in patients with an interval of ≤ 5 years versus > 5 years (p = 0.017). RGC developed more frequently after Billroth II reconstruction, and at the anastomotic site, in patients with a > 10- versus ≤ 10-year interval (p = 0.006 and p = 0.014, respectively). Similar results were observed based on the 15-year interval cutoff (p = 0.001 and 0.018, respectively). The 5-year overall survival rate of patients with a ≤ 5-year interval was significantly lower than that of patients with a > 5-year interval (60.0% versus 85.7%, p = 0.015), while overall survival did not differ between the ≤ 10- and > 10-year, or ≤ 15- and 15-year interval groups. RGC incidence showed a decrease after around 20 years postoperatively. Thorough endoscopic examination should be conducted for up to 5 years postgastrectomy. Routine annual endoscopic follow-up should be performed for up to 20 years after the primary operation for gastric cancer, to allow for early detection of RGC.

Purpose To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC). Materials and Methods This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively. Results The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693-4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664-1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595-85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502-5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618-3.028; P

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.

Endoscopic submucosal dissection (ESD) for gastric cancer produces an artificial ulcer, and negative effects on the surgical outcomes of additional gastrectomy after ESD are anticipated. The aim of this study is to analyze the effect of ESD on subsequent laparoscopic radical gastrectomy procedures and to compare the surgical results of post-ESD patients with the control group using propensity score (PS) methods. From 2013 to 2018, 1446 patients underwent totally laparoscopic distal gastrectomy in our center. Among these patients, the clinicopathological factors and short-term surgical outcomes of 107 patients who underwent ESD before surgery (the ESD group) were evaluated. A 1:4 PS matching and inverse probability weighting method was utilized to compare the short-term surgical outcomes of the ESD group with those of a matched control group. A longer operation time was required for the patients who underwent gastrectomy earlier than 24 days after ESD than for the patients who did not. Patients whose ulcer size, due to previous ESD, exceeded 4.6 cm required longer operation times and exhibited more intraoperative blood loss than patients whose ulcer size was small. In the PS matching analysis, patients who underwent distal gastrectomy within 24 days after ESD showed more frequent postoperative morbidity than non-ESD patients. ESD after laparoscopic distal gastrectomy is largely safe in terms of short-term surgical outcomes, but a short interval between the two procedures and a large ESD scar can make subsequent operation difficult.

IntroductionPatients who underwent curative gastrectomy for gastric cancer are regularly followed-up for the early detection of recurrence and postoperative symptom management. However, there is a lack of evidence with regard to proper surveillance intervals and diagnostic tools. This study aims to evaluate whether frequent surveillance tests have a survival benefit or improve the quality of life in patients who underwent curative resection for advanced gastric cancer.Methods and analysisThe STOFOLUP trial is an investigator-initiated, parallel-assigned, multicentre randomised controlled trial involving 16 hospitals in the Republic of Korea. Patients (n=886) diagnosed with pathological stage II or III gastric adenocarcinoma will be randomised to either the 3-month or the 6-month group at a 1:1 ratio, stratified by trial site and tumour stage. Patients allocated to the 3-month group will undergo an abdominal CT scan every 3 months postoperatively and those allocated to the 6-month group will undergo CT every 6 months. The primary endpoint is 3-year overall survival and the secondary endpoints are quality of life, as assessed using KOrean QUality of life in Stomach cancer patients Study group-40, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the stomach cancer-specific module (STO22), and nutritional outcomes. Other survival data including data concerning 3-year disease-free survival, recurrence-free survival, gastric cancer-specific survival and postrecurrence survival will also be estimated. The first patient was enrolled on July 2021 and active patient enrolment is currently underway.Ethics and disseminationThis study has been approved by the Institutional Review Board of eight of the participating hospitals (NCC 2021-0085, KBSMC2021-01-059, SMC 2021-01-140, KC21OEDE0082, 4-2021-0281, AJIRB-MED-INT-20-608, 2021-0515 and H-2102-093-1198). This study will be disseminated through peer-reviewed publications, national or international conferences.Trial registration numberNCT04740346.

Adjuvant chemotherapy (AC) after curative gastrectomy is the standard treatment for patients with locally advanced gastric adenocarcinoma in East Asia; however, for various reasons, some patients do not receive this treatment. The aim of this study was to develop a system that reflects the survival rate of patients who do not receive AC.A modified tumor-node-metastasis (TNM) staging system was developed based on the overall survival (OS) of gastric cancer patients after curative gastrectomy without AC at Seoul St. Mary's hospital. A survival prediction model was developed based on the modified staging system and risk factors for OS, which were examined using the Cox proportional hazards regression model. The model was internally validated for the power of prediction and discrimination, compared with the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition; it was externally validated using data from two other tertiary teaching hospitals.Of the 185 patients in the development set, the 5-year OS rates for modified stages IIA, IIB, IIC, IIIA, and IIIB were 80.2%, 74.0%, 56.7%, 50.0%, and 25.0%, respectively; the median OS intervals for modified stages IIIC and IIID were 21.0 and 11.0 months, respectively. Age, American Society of Anesthesiologists physical status, and postoperative complications were significantly associated with OS. The concordance index (0.768 vs. 0.686), Akaike Information Criterion (745.88 vs. 794.84), and estimated area under the curve (0.7567 vs. 0.6655) were all superior for the prediction model, compared with the AJCC TNM stage. For the validation set of 157 patients, the model performed better for the prediction and discrimination of OS.The newly developed survival prediction model improves the accuracy of OS prediction for stage II and III gastric cancer patients without AC after curative gastrectomy.

Introduction There are few guidelines for screening of osteoporosis in patients who have undergone gastrectomy. This study aimed to develop and validate a nomogram to predict the risk of osteoporosis after gastrectomy in patients with gastric cancer. Methods Bone densitometry results for 522 patients with gastric cancer and 2088 individuals from a health-promotion centre were compared using propensity score matching to develop a nomogram to predict osteoporosis after gastrectomy. External validation was performed using an independent data set. Results In the 10 years after gastrectomy 53.5 per cent of patients developed osteoporosis. In multivariable analysis, the odds ratios of subtotal gastrectomy and total gastrectomy were 5.46 and 8.69 (P < 0.001 for both). Seven risk factors (type of gastrectomy, age, sex, BMI, and serum levels of albumin, creatinine and phosphorus) were incorporated into the nomogram. The prediction accuracy of the nomogram in the development set was 0.830 (area under the curve (AUC)); (95 per cent c.i. 0.812 to 0.848). In the validation set, the AUC was 0.807 (95 per cent c.i. 0.741 to 0.873). Conclusion Gastrectomy was a risk factor for osteoporosis, and its incidence in the first 10 years after surgery was high. This nomogram can help clinicians to identify patients with gastric cancer most at risk of developing osteoporosis after surgery., There are only a few guidelines for screening of patients with gastric cancer for osteoporosis after gastrectomy. The authors developed a nomogram to predict the risk of osteoporosis after gastrectomy for gastric cancer. This prediction model can help clinicians to identify patients with gastric cancer who should undergo bone densitometry.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the "proven GERD" with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

BackgroundScreening 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.MethodsThe 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).ResultsNine 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.ConclusionsThe 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.

KLASS (the Korean Laparoendoscopic Gastrointestinal Surgery Study) is a time-honored study group that has established laparoscopic surgery for gastrointestinal disease in Korea and has performed some important studies for the rationale of laparoscopic gastrointestinal surgery. A multi-center RCT (randomized controlled trial) to compare the quality of life (QOL) of patients undergoing totally laparoscopic distal gastrectomy (TLDG) and laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer, named as KLASS 07, has been currently prepared in Korea. Patients diagnosed as gastric cancer, with clinical stage IA (T1N0M0) or IB (T1N1M0 / T2N0M0) according to the 7th edition of the Americal Joint Committee on Cancer System, were randomized to receive either TLDG or LADG. For surgical quality control, the surgeons participating in this trial had to have performed at least 50 gastrectomies and at least 30 gastrectomies annually (regardless of open or laparoscopic surgery for gastric cancer). The patients who are allocated to TLDG group undergo intracorporeal anastomosis and those who are assigned to LADG undergo extracorporeal anastomosis for gastrointestinal reconstruction. Thirty-one surgeons from 26 institutions were engaged in this trial. The primary endpoint is 30-day morbidity, and secondary endpoint is QOL assessed by the questionnaire score. The KLASS 07 trial is the first multi-center RCT to investigate whether there are significant and quantifiable differences between the QOL of TLDG and LADG. The findings from this trial are expected to be the critical clues for designing the detailed procedures during laparoscopic surgery for gastric cancer. The protocol of KLASS 07 (CKLASS 01) was registered in http://register.clinicaltrials.gov as NCT03393182 (Date of registration: January 2nd, 2018.).

Purpose With advances in surgical techniques, reduced-port laparoscopic surgery is increasingly being performed for the treatment of gastric carcinoma. Many studies have reported satisfactory short-term outcomes after reduced 3-port laparoscopic gastrectomy (LG). The aim of this study was to investigate the long-term oncological outcomes of 3-port LG in patients with gastric carcinoma. Materials and methods We reviewed the medical records of 1,117 patients who underwent LG for gastric carcinoma in three major institutions between 2012 and 2015. The data showed that 460 patients underwent 3-port LG without assistance, and 657 underwent conventional 5-port LG. We compared the overall and disease-free survival rates between the 2 groups. Results There were 642 male and 475 female patients with a mean age of 56.1 years. Among them, 1,028 (92.0%) underwent distal gastrectomy and 89 (8.0%) underwent total gastrectomy. In the final pathologic examination, 1,027 patients (91.9%) were stage I, 73 (6.5%) were stage II, and 17 (1.5%) were stage III, and there were no significant difference in the pathologic stage between groups. The 3- and 5-port LG groups showed no significant differences in the 5-year overall survival (94.3% vs. 96.7%, P=0.138) or disease-free survival (94.3% vs. 95.9%, P=0.231). Stratified analyses according to pT and pN stages also showed no significant differences in overall or disease-free survival between the two groups. Conclusions Long-term survival after 3- and 5-port LG was comparable in patients with early-stage gastric carcinoma. The 3-port technique requiring limited surgical assistance may be an appropriate surgical option for this patient population.

We investigated the clinicopathological features and management for superficial nonampullary duodenal tumors (SNADTs). The safety and feasibility of laparoscopic management, especially laparoscopic endoscopic cooperative surgery (LECS), were evaluated.A total of 59 patients with SNADTs who underwent operations from January 2009 to December 2018 at all 8 institutions of the Catholic Medical Center were identified in our comprehensive multi-institutional database. Clinicopathological and surgical data on the 4 anatomical regions of the duodenum were collected and compared. Characteristics of conventional laparoscopic procedure (laparoscopy-only) and LECS procedures were also compared.There were significantly more asymptomatic patients with tumors in the first and secondMost of the SNADTs located in proximal duodenum were detected incidentally. GISTs were the most common diagnoses of SNADTs in all locations. In treating these tumors, laparoscopic resection is safe and feasible. Especially, LECS may be ideal for treating small endophytic tumors, minimizing over-resection and postoperative complications.

Tegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) are standard adjuvant chemotherapies (ACs) administered after gastrectomy to patients with stage II or III gastric cancer. However, the efficacy of AC in elderly patients remains unclear. The objective of this retrospective multicenter cohort study was to compare the efficacies of S-1 and CAPOX AC in patients aged ≥70 years.Nine hundred eighty-three patients who were treated with AC using S-1 (768 patients) or CAPOX (215 patients) were enrolled in this study. Each patient underwent AC after curative gastrectomy for stage II or III gastric cancer at one of 27 hospitals in the Republic of Korea between January 2012 and December 2013. Relapse-free survival (RFS) and overall survival (OS) were analyzed according to AC regimen and age group.Of the 983 patients, 254 (25.8%) were elderly. This group had a similar RFS (P=0.099) but significantly poorer OS (p=0.003) compared with the non-elderly group. Subgroup analysis of the non-elderly group revealed no AC-associated differences in survival. Subgroup analysis of the elderly group revealed significantly better survival in the S-1 group than in the CAPOX group (RFS, P0.001; OS, P0.001). Multivariate analysis revealed that the CAPOX regimen was an independent poor prognostic factor for RFS (hazard ratio [HR], 1.891; 95% confidence interval [CI], 1.072-3.333; P=0.028) and OS (HR, 2.970; 95% CI, 1.550-5.692; P=0.001).This multicenter observational cohort study found significant differences in RFS and OS between S-1 and CAPOX AC among patients with gastric cancer aged ≥70 years.

Few studies have presented evidence pertaining to the adequate minimum number of adjuvant chemotherapy (AC) cycles required to achieve an oncologic benefit for gastric cancer. From January 2012 to December 2013, data from patients who underwent curative radical gastrectomy and consequently received AC for pathologic stage 2 or 3 gastric cancer at 27 institutions in South Korea were analyzed. The study enrolled 925 patients, 661 patients (71.5%) who completed 8 cycles of AC and 264 patients (28.5%) who did not. Compared with the mean disease-free survival (DFS) of the patients who completed 8 AC cycles (69.3 months), the mean DFS of patients who completed 6 AC cycles (72.4 months; p = 0.531) and those who completed 7 AC cycles (63.7 months; p = 0.184) did not differ significantly. However, the mean DFS of the patients who completed 5 AC cycles (48.2 months; p = 0.016) and those who completed 1–4 AC cycles (62.9 months; p = 0.036) was significantly lower than the DFS of those who completed 8 AC cycles. In the multivariate Cox proportional hazards analysis, the mean DFS was significantly affected by advanced stage, large tumor size, positive vascular invasion, and number of completed AC cycles (1–5 cycles: hazard ratio 1.45; 95% confidence interval 1.01–2.08; p = 0.041). The current multicenter observational cohort study showed that the mean DFS for 6 or 7 AC cycles was similar to that for 8 AC cycles as an adjuvant treatment for gastric cancer.

IMPORTANCE: The incidence of gallstones has been reported to increase after gastrectomy. However, few studies have been conducted on the prevention of gallstone formation in patients who have undergone gastrectomy. OBJECTIVE: To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing gallstone formation after gastrectomy in patients with gastric cancer. DESIGN, SETTING, AND PARTICIPANTS: The PEGASUS-D study (Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study) was a randomized, double-blind, placebo-controlled clinical trial conducted at 12 institutions in the Republic of Korea. Adults (aged ≥19 years) with a diagnosis of gastric cancer who underwent total, distal, or proximal gastrectomy were enrolled between May 26, 2015, and January 9, 2017; follow-up ended January 8, 2018. Efficacy was evaluated by both the full analysis set, based on the intention-to-treat principle, and the per-protocol set; full analysis set findings were interpreted as the main results. INTERVENTIONS: Eligible participants were randomly assigned to receive 300 mg of UDCA, 600 mg of UDCA, or placebo at a ratio of 1:1:1. Ursodeoxycholic acid and placebo were administered daily for 52 weeks. MAIN OUTCOMES AND MEASURES: Gallstone formation was assessed with abdominal ultrasonography every 3 months for 12 months. Randomization and allocation to trial groups were carried out by an interactive web-response system. The primary end point was the proportion of patients developing gallstones within 12 months after gastrectomy. RESULTS: A total of 521 patients (175 received 300 mg of UDCA, 178 received 600 mg of UDCA, and 168 received placebo) were randomized. The full analysis set included 465 patients (311 men; median age, 56.0 years [interquartile range, 48.0-64.0 years]), with 151 patients in the 300-mg group, 164 patients in the 600-mg group, and 150 patients in the placebo group. The proportion of patients developing gallstones within 12 months after gastrectomy was 8 of 151 (5.3%) in the 300-mg group, 7 of 164 (4.3%) in the 600-mg group, and 25 of 150 (16.7%) in the placebo group. Compared with the placebo group, odds ratios for gallstone formation were 0.27 (95% CI, 0.12-0.62; P = .002) in the 300-mg group and 0.20 (95% CI, 0.08-0.50; P

Background Isoform 2 of the tight junction protein claudin-18 (CLDN18.2) is a potential target of gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC).Methods We evaluated CLDN18.2, RhoGAP, and E-cadherin expression by performing two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line, platinum-based chemotherapy between March 2015 and February 2017.Results CLDN18.2 and E-cadherin expression was significantly reduced in patients with peritoneal metastasis (PM) compared with those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), while it was significantly higher in patients who never exhibited PM from diagnosis to death than in those who did (p=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin were expressed at significantly higher levels in patients with bone metastasis than in those without it (p=0.010 and 0.001, respectively). We identified a positive correlation between the expression of CLDN18.2 and E-cadherin (p < 0.001), RhoGAP and CLDN18.2 (p=0.004), and RhoGAP and E-cadherin (p=0.001). CDLN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival.Conclusions CLDN18.2 expression was reduced in PM but significantly intact in bone metastasis. Furthermore, a positive correlation was identified between the expression of CLDN18.2 and other adherens junction molecules, which has clinical implications for mDGC and PM pathogenesis.