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Laparoscopic gastrectomy (LG) has gradually increased for treating advanced gastric cancer (AGC). However, there is a lack of evidence on oncologic safety for AGC, especially with serosal invasion. This study evaluates the surgical and oncologic outcomes between laparoscopic and open gastrectomy (OG) for gastric cancer with serosal invasion.We retrospectively reviewed 256 patients who underwent OG and 147 patients who underwent LG for gastric cancer with serosal invasion between August 2005 and December 2017. Finally, 124 patients in the LG group and 124 in the OG group were enrolled according to one-to-one propensity score matching (PSM) analysis. We evaluated surgical and oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS).There were no statistical differences in hospital stay and major complications between the two groups. The retrieved lymph nodes of the LG group were similar to those of OG (40 ± 16.23 vs. 38 ± 14.42, p = 0.306), and it showed a similar operation time compared with the other (164 ± 43.86 vs. 156 ± 37.66, p = 0.063). There was no statistical difference in OS (p = 0.761) and RFS (p = 0.121) for survival analysis between the two groups.LG for gastric cancer with serosal invasion is feasible and could be considered as a standard treatment.

Although the criteria for the indication of endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD-EGC) have been recently proposed, accumulating reports on the non-negligible rate of lymph node metastasis (LNM) after indicated ESD raise questions on the reliability of the current criteria.To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD.We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center, a tertiary university hospital in Korea. To identify the risk factors of LNM of UD-EGC meeting the expanded criteria for ESD, we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4. We reviewed the clinical, endoscopic, and histologic features of the cases to identify features with a significant difference according to the presence of LNM. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios (ORs).Of the 4780 UD-EGC cases, 1240 (25.9%) were identified to meet the expanded indication for ESD. Of the 1240 cases, 14 (1.1%) cases had LNM. Among the various clinical, endoscopic, and histopathological features that were evaluated, mixed histology (tumors consisting of 10%-90% of signet ring cells) had a marginally significant association (The risk of LNM is higher than expected when using the current expanded indication for UD-EGC. Histological evaluation could provide useful clues for reducing the risk of LNM.

Knowledge on the optimal extent of lymphadenectomy among elderly patients with advanced gastric cancer is limited. This study was designed to compare standard D2 and limited lymphadenectomy for evaluating the appropriate extent of lymphadenectomy.We retrospectively reviewed patient's data based on a prospectively collected gastric cancer registry. The inclusion criteria were age above 75 years and histologically confirmed stage II or more advanced gastric cancer. In this study, 103 patients who underwent limited lymph node dissection and 134 patients who underwent standard D2 lymph node dissection were included to evaluate surgical and oncological outcomes using propensity score matching (PSM) analysis.The mean age after PSM was approximately 78 years in both groups. The Charlson Comorbidity Index was 5.81 ± 0.87 and 5.75 ± 0.76, respectively, and 12.5% of the patients in both groups had American Society of Anesthesiologists scores of more than 3. The limited lymphadenectomy group showed a shorter operation time and fewer retrieved lymph. However, other surgical outcomes and pathological data were not significantly different between the groups. No postoperative mortality within 30 days was observed. There were no significant differences in overall complications between the groups. The 3-year overall survival rates of the limited and standard lymphadenectomy groups were 58.3% and 73.6%, respectively. The 3-year recurrence-free survival rate of the limited lymphadenectomy group was lower than that of the standard lymphadenectomy group; however, the difference was not statistically significant.Standard D2 lymphadenectomy has better oncological outcomes in elderly patients with advanced gastric cancer.

Purpose The aim of this study was to show that bariatric surgery (BS) is more effective than medical therapy (MT) in Asian obese patients. Methods In this prospective, multicenter, nonrandomized, controlled trial, obese patients with body mass index of ≥35 kg/m2 or 30.0–34.9 kg/m2 with obesity-related comorbidities were assigned to undergo BS, such as laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass, or MT. Patients who underwent BS were evaluated 4, 12, 24, and 48 weeks after surgery, whereas patients who received MT were monitored at a hospital every 6 weeks for 1 year. At each visit, weight, waist and hip circumference, and blood pressure were measured, and patients underwent physical examination and laboratory testing. Health-related quality of life (HQOL) was investigated using Euro QOL-5 Dimension, Impact of Weight on Quality of Life questionnaire-Lite and Obesity-related Problems scale. Results The study included 264 patients from 13 institutions; of these, 64 underwent BS and 200 received MT. Of the patients who underwent BS, 6.3% experienced early complications. Relative weight changes from baseline to 48 weeks were significantly greater in the BS than in the MT group (26.9% vs. 2.1%, P < 0.001), as were the rates of remission of diabetes (47.8% vs. 16.7%, P = 0.014), hypertension (60.0% vs. 26.1%, P < 0.001), and dyslipidemia (63.2% vs. 22.0%, P < 0.001). HQOL was better in the BS than in the MT group at 48 weeks. Conclusion BS was safe and effective in Korean obese patients, with greater weight reduction, remission of comorbidities, and quality of life improvement than MT.

PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

Background: Immune checkpoint inhibitors have shown survival benefits in unresectable/metastatic gastric cancer (GC), esophageal cancer (EC), and hepatocellular carcinoma (HCC). Based on scientific rationale for neoadjuvant immunotherapy, we conducted a phase II study of neoadjuvant IMC-001, a novel PD-L1 targeting fully human monoclonal antibody, for resectable GC, EC, and HCC. Methods: This is a prospective, phase II study of neoadjuvant IMC-001 (20 mg/kg iv every 2 weeks for 2 cycles) across three cohorts of resectable GC, EC, and HCC. The primary endpoint is major pathologic response rate ( Results: From Sep. 2019 to Nov. 2022, 50 patients (pts) were enrolled and treated (safety analysis population), and among them, 48 pts were evaluable for the efficacy analysis (16 HCC; 16 GC; 16 EC); male (81%), median age=62 yrs (range, 39-77), and clinical stage (AJCC 8th ed.) I (56%)/II (33%)/III (10%). All tumors were microsatellite stable and 33% of tumors were PD-L1+. 45 pts (94%) completed 2 cycles of neoadjuvant IMC-001, all pts underwent surgery, and only one pt’s surgery was delayed due to immune-related hepatitis. No pts had disease progression during neoadjuvant therapy, and among the 17 pts with measurable lesion(s) by RECIST 1.1, 3 pts (18%) showed partial response (PR) and 14 pts (82%) had stable disease (SD). Among 30 metabolic response-evaluable pts by EORTC criteria, 7 pts (15%) showed metabolic PR, 20 pts (43%) had metabolic SD, and 3 pts (6%) had metabolic PD. Among 2 of 3 pts with metabolic PD, surgical pathology showed increased tumor infiltrating lymphocytes and tumor regression. The median change of the sum of SUVmax was -13% (range, -76% to 59%). All pts underwent R0 resection with pathologic stage of I (75%)/II (13%)/III (13%). Although there was no major pathologic response, 51% of pts showed various degree of tumor necrosis or fibrosis and 7 pts (15%) had residual viable tumor cells less than 50%. Except for grade 3 AST/ALT elevation (6%), all treatment-related adverse events (TRAEs) were grade 1 or 2. TRAEs occurring in ≥5% of pts were hyperthyroidism (18%), hypothyroidism (14%), fatigue (14%), pruritus (12%), skin rash (8%), infusion-related reaction (6%), and diarrhea (6%). Conclusions: Neoadjuvant IMC-001 was well tolerated and demonstrated antitumor activity in microsatellite stable, resectable GC, EC, and HCC pts. The updated clinical and biomarker results will be presented. Citation Format: Sook Ryun Park, Joon Seon Song, In Hye Song, Moon-Won Yoo, Yong-Hee Kim, Hyeong Ryul Kim, Ju Hyun Shim, Danbi Lee, Jonggi Choi, Ki Won Song. A phase II study of neoadjuvant immune checkpoint inhibitor IMC-001 (anti-PD-L1 antibody) in patients with resectable upper gastrointestinal cancers (Neo-Chance Study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT147.

Purpose Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.Results The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.

Purpose The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk calculator is useful in predicting postoperative adverse events. However, its accuracy in specific disorders is unclear. We validated the ACS NSQIP risk calculator in patients with gastric cancer undergoing curative laparoscopic surgery. Materials and Methods We included 207 consecutive early gastric cancer patients who underwent laparoscopic gastrectomy between January 2018 and January 2019. The preoperative characteristics and risks of the patients were reviewed and entered into the ACS NSQIP calculator. The estimated risks of postoperative outcomes were compared with the observed outcomes using C-statistics and Brier scores. Results Most of the patients underwent distal gastrectomy with Roux-en-Y reconstruction (74.4%). We did not observe any cases of mortality, venous thromboembolism, urinary tract infection, renal failure, or cardiac complications. The other outcomes assessed were complications such as pneumonia, surgical site infections, any complications requiring re-operation or hospital readmission, the rates of discharge to nursing homes/rehabilitation centers, and the length of stay. All C-statistics were

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

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.

Bariatric surgery is known to be the most effective treatment for weight loss in obese patients and for the rapid remission of obesity-related comorbidities. These short-term improvements result from not only limited digestion or absorption but also dynamic changes in metabolism throughout the whole body. However, short-term metabolism studies associated with bariatric surgery in Asian individuals have not been reported. The aim of this study was to investigate the short-term metabolome changes in the serum promoted by laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and to determine the underlying mechanisms that affect obesity-related comorbidities. Serum samples were collected from Korean patients who underwent RYGB or SG before and 4 weeks after the surgery. Metabolomic and lipidomic profiling was performed using UPLC-Orbitrap-MS, and data were analyzed using statistical analysis. Metabolites mainly related to amino acids, lipids (fatty acids, glycerophospholipids, sphingolipids, glycerolipids) and bile acids changed after surgery, and these changes were associated with the lowering of risk factors for obesity-related diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and atherosclerosis. Interestingly, the number of significantly altered metabolites related to the lipid metabolism were greater in SG than in RYGB. Furthermore, the metabolites related to amino acid metabolism were significantly changed only after SG, whereas bile acid changed significantly only following RYGB. These differences could result from anatomical differences between the two surgeries and could be related to the gut microbiota. This study provides crucial information to expand the knowledge of the common but different molecular mechanisms involved in obesity and obesity-related comorbidities affected by each bariatric procedure.

The advantages of laparoscopic resection over open surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) are not conclusive. This study aimed to evaluate the postoperative and oncologic outcome of laparoscopic resection for gastric GIST, compared to open surgery. We retrospectively reviewed the prospectively collected database of 1019 patients with gastric GIST after surgical resection at 13 Korean and 2 Japanese institutions. The surgical and oncologic outcomes were compared between laparoscopic and open group, through 1:1 propensity score matching (PSM). The laparoscopic group (N = 318) had a lower rate of overall complications (3.5% vs. 7.9%, P = 0.024) and wound complications (0.6% vs. 3.1%, P = 0.037), shorter hospitalization days (6.68 ± 4.99 vs. 8.79 ± 6.50, P

BackgroundThe incidence and costs of medical disputes in Korea are increasing annually. The purpose of this study was to identify the characteristics of medical dispute cases and analyze compensation costs in gastric cancer patients who were admitted for surgery at a single large-volume center. MethodsGastric cancer patients who were admitted for surgery and received compensation after filing medical disputes with the legal affairs team at our center between January 2012 and December 2017 were retrospectively registered for the study. The characteristics of and information on the disputes were reviewed and the amount of awarded compensation was analyzed according to different factors.ResultsThere were 20 cases of medical disputes associated with gastric cancer surgery during the study period. In five cases, evidence of medical negligence was detected. There were 17 morbidity cases and four mortality cases. The mean compensation cost paid for settlement was USD 7,502. Length of hospital stay (p=0.009) and morbidity (p=0.004) were significantly associated with compensation.Conclusion Our results demonstrate foundational information on disputes regarding surgery in gastric cancer patients and the accompanying compensation costs for settlement.

This article compares clinical outcomes of two groups of patients with advanced gastrointestinal stromal tumors: patients who underwent resection plus imatinib dose escalation or maintenance and patients who were treated with imatinib dose escalation alone., Background. There are limited data on the clinical benefits of adding surgical resection in patients with focally progressive gastrointestinal stromal tumor (GIST). This study aims to compare the clinical outcomes of resection plus imatinib dose escalation or maintenance (S group) with imatinib dose escalation alone (NS group) in patients with advanced GIST following focal progression (FP) with standard doses of imatinib. Materials and Methods. A total of 90 patients with advanced GISTs who experienced FP with standard doses of imatinib were included in this retrospective analysis. The primary endpoints were time to imatinib treatment failure (TTF) and overall survival (OS). Results. Compared with the NS group (n = 52), patients in the S group (n = 38) had a higher proportion of primary tumor site involvement and lower tumor burden at FP. With a median follow‐up duration of 31.0 months, patients in the S group had significantly better TTF and OS than patients in the NS group (median TTF: 24.2 vs. 6.5 months, p < .01; median OS: 53.2 vs. 35.1 months, p = .009). Multivariate analysis showed that S group independently demonstrated better TTF (hazard ratio [HR], 0.29; p < .01) and OS (HR, 0.47; p = .01). Even after applying inverse probability of treatment‐weighting adjustments, S group demonstrated significantly better TTF (HR, 0.36; p < .01) and OS (HR, 0.58; p = .049). Conclusion. Our results suggested that resection following FP with standard doses of imatinib in patients with advanced GIST provides additional benefits over imatinib dose escalation alone. Implications for Practice. This is the first study to compare the clinical outcomes of resection plus imatinib dose escalation or maintenance (S group) with imatinib dose escalation alone (NS group) in patients with advanced gastrointestinal stromal tumor (GIST) following focal progression (FP) with standard doses of imatinib. These findings suggest that resection can be safely performed following FP, and the addition of surgical resection provides further clinical benefit over imatinib dose escalation alone. Based on these results, the authors recommend resection following FP in patients with advanced GIST provided that an experienced multidisciplinary team is involved in the patient's treatment.

The long‐term effects of tyrosine kinase inhibitors (TKIs), including imatinib, and surgical intervention on advanced gastrointestinal stromal tumor (GIST) were evaluated. All 379 patients had metastatic or recurrent GIST and started 400 mg/d imatinib at the Asan Medical Center in periods 1 and 2 [2001‐2007 (33.2%) and 2008‐2014 (66.8%), respectively]. Men constituted 60.4%; median patient age and tumor size at the initiation of imatinib were 58.6 (14.6‐85.5) years and 51 (0‐324) mm, respectively, without differences between periods except for older age and less preimatinib surgery in period 2. Response and disease control rates with imatinib in measurable GIST were 63.1% and 94.3%, respectively, without differences between periods. More patients in period 2 underwent surgical resection for TKI‐responsive diseases within the first 2 years (24.9%, P = 0.006). With a median follow‐up of 6.1 years (2.5‐16.0) in survivors, median progression‐free survival (PFS) was 5.4 years [95% confidence interval (CI), 4.0‐6.9]. Subsequent sunitinib (P = 0.066) and regorafenib (P = 0.003) were more commonly administered in period 2. Median overall survival (OS) was 8.8 years (95% CI, 7.8‐9.7). PFS with imatinib (P = 0.002) and OS (P = 0.019) were significantly longer in period 2. Young age, smaller tumor size at the initiation of imatinib, KIT exon 11 mutation, surgical intervention, and period 2 were favorable factors for PFS and OS. Patients with advanced GIST showed better prognosis with the optimal use of imatinib, along with active surgical intervention and more common use of subsequent TKIs in period 2.

Summary: Background: With the increase in the prevalence of overweight, percentage of overweight patients with gastric cancer has also increased. This 5-year retrospective cohort study was performed to investigate long-term changes in the metabolic and nutritional parameters of early gastric cancer (EGC) patients with overweight after gastrectomy. Methods: EGC patients who underwent gastrectomy were followed up over a 5-year period. We included 393 patients (261 men, 132 women) who had an initial body mass index (BMI) of ≥23 kg/m2, and analyzed the longitudinal changes in the metabolic and nutritional parameters. Results: Body weight and random glucose, alanine aminotransferase (ALT), hemoglobin, and serum calcium levels significantly decreased, while serum protein and albumin levels increased in both men and women after gastrectomy. The odds ratios (ORs) for BMI ≥ 25 kg/m2 (P 40 IU/dL (men; P

A temperature-responsive hydrogel (PF-72; TGel Bio, Inc., Ltd, Seoul, Korea), developed as a sustained drug delivery device, can be mixed with ropivacaine to reduce pain in the incision area. The hydrogel is soluble at low temperatures (2-8 °C) and is converted into a gel at high temperatures ( 30 °C). We aimed to evaluate whether the administration of ropivacaine using PF-72 at incision sites reduces pain until 72 h postoperatively in patients undergoing laparoscopic stomach or colorectal surgery.Patients were randomly assigned to the control group (0.75% ropivacaine) or PF-72 group (PF-72 mixed with 0.75% ropivacaine). Before surgical incision closure, 0.75% ropivacaine or PF-72 mixed with 0.75% ropivacaine was injected into the subcutaneous fat and muscle of all incisions. Postoperative pain was evaluated by the Numerical Rating Scale (NRS, 0 = no pain, 10 = most severe pain) for wound pain at 3, 6, 24, 48, and 72 h after the end of surgery.Ninety-nine patients (control, n = 51; PF-72, n = 48) were included in the analysis. The areas under the curve of NRS for wound pain until 72 h in the control group and the PF-72 group were 188.7 ± 46.1 and 135.3 ± 49.9 h, respectively (P 0.001). The frequency of the administration of rescue analgesics in the general ward was similar between the two groups.PF-72 mixed with 0.75% ropivacaine reduced postoperative pain until 72 h in patients undergoing laparoscopic surgery. Although the study population was not large enough for safety evaluation, no adverse events associated with PF-72 were observed.

Bariatric surgery is known to be the most effective treatment for weight loss in obese patients and for the rapid remission of obesity-related comorbidities. These short-term improvements result from not only limited digestion or absorption but also dynamic changes in metabolism throughout the whole body. However, short-term metabolism studies associated with bariatric surgery in Asian individuals have not been reported.The aim of this study was to investigate the short-term metabolome changes in the serum promoted by laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and to determine the underlying mechanisms that affect obesity-related comorbidities.Serum samples were collected from Korean patients who underwent RYGB or SG before and 4 weeks after the surgery. Metabolomic and lipidomic profiling was performed using UPLC-Orbitrap-MS, and data were analyzed using statistical analysis.Metabolites mainly related to amino acids, lipids (fatty acids, glycerophospholipids, sphingolipids, glycerolipids) and bile acids changed after surgery, and these changes were associated with the lowering of risk factors for obesity-related diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and atherosclerosis. Interestingly, the number of significantly altered metabolites related to the lipid metabolism were greater in SG than in RYGB. Furthermore, the metabolites related to amino acid metabolism were significantly changed only after SG, whereas bile acid changed significantly only following RYGB.These differences could result from anatomical differences between the two surgeries and could be related to the gut microbiota. This study provides crucial information to expand the knowledge of the common but different molecular mechanisms involved in obesity and obesity-related comorbidities affected by each bariatric procedure.

Purpose This study aimed to compare the surgical outcomes of total laparoscopic total gastrectomy without mesentery division (LTG without MD) and conventional total laparoscopic total gastrectomy (CLTG), as well as evaluate the appropriate method for esophagojejunostomy (EJ) reconstruction after total laparoscopic total gastrectomy (TLTG). Materials and methods We retrospectively analyzed data from 301 consecutive patients who underwent TLTG for upper or middle third gastric cancer between January 2016 and May 2019. After propensity score matching, 95 patients who underwent LTG without MD and 95 who underwent CLTG were assessed. Data on clinical characteristics and surgical outcomes, including operation time, length of postoperative hospital stay, pathological findings, and postoperative complications were analyzed. Results The LTG without MD group showed a shorter time to first flatus (3.26±0.80 vs. 3.62±0.81 days, P=0.003) and a shorter time to soft diet (2.80±2.09 vs. 3.52±2.20 days, P=0.002). The total EJ-related complications in the LTG without MD group were comparable to those in the CLTG group (9.47% vs. 3.16%, P=0.083). EJ-related leakage (6.32% vs. 3.16%, P=0.317) and EJ-related stricture (3.16% vs. 1.05%, P=0.317) rates were not significantly different between the LTG without MD and CLTG groups. No significant differences were found between the two groups in terms of other early surgical outcomes such as early complications, late complications, hospital stay, and readmission rate. Conclusions LTG without MD is a safe surgical treatment for upper or middle third gastric cancer. LTG without MD may be an alternative procedure for EJ anastomosis during TLTG.

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

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.

This study was conducted to determine the recommended dose (RD) of intraperitoneal docetaxel (ID) in combination with systemic capecitabine and cisplatin (XP) and to evaluate its efficacy and safety at the RD in advanced gastric cancer (AGC) patients with peritoneal metastasis. AGC patients with peritoneal metastasis received XP ID, which consists of 937.5 mg/m2 of capecitabine twice daily on days 1–14, 60 mg/m2 of intravenous cisplatin on day 1, and intraperitoneal docetaxel at 3 different dose levels (60, 80, or 100 mg/m2) on day 1, every 3 weeks. In the phase I study, the standard 3 + 3 method was used to determine the RD of XP ID. In the phase II study, patients received RD of XP ID. In the phase I study, ID 100 mg/m2 was chosen as the RD, with one dose-limiting toxicity (ileus) out of six patients. The 39 AGC patients enrolled in the phase II study received the RD of XP ID. The median progression-free survival was 11.0 months (95% CI 6.9–15.1), and median overall survival was 15.1 months (95% CI 9.1–21.1). The most frequent grade 3/4 adverse events were neutropenia (38.6%) and abdominal pain (30.8%). The incidence of abdominal pain cumulatively increased in the later treatment cycles. Our study indicated that XP ID was effective, with manageable toxicities, in AGC patients with peritoneal metastasis. As the cumulative incidence of abdominal pain was probably related to bowel irritation by ID, it might be necessary to modify the dose.

Endoscopic submucosal dissection (ESD) has become accepted as the standard treatment for early gastric cancer. However, comparative outcomes of ESD and surgery have not been evaluated for adenocarcinoma in the esophagogastric junction (EGJ). We investigated the long-term outcomes of ESD compared with those of surgery for adenocarcinoma in the EGJ. Patients who underwent ESD or surgery for Siewert type II adenocarcinoma between 2005 and 2010 and who met the absolute and expanded criteria for endoscopic resection were eligible. Clinical features and treatment outcomes were retrospectively reviewed using medical records. Of the 79 patients included, 40 underwent ESD and 39 underwent surgery. During the median follow-up period of 60.9 months (range, 13.1–125.4 months), the 5-year overall survival rates were 93.9% and 97.3% for the ESD and surgery groups, respectively (p = 0.376). There were no gastric cancer-related deaths in either group. Adverse events occurred in 11 patients (13.9%) overall, and the incidence of treatment-related adverse events was similar between the two groups (10.0% vs. 17.9%, p = 0.308). ESD may be an effective alternative to surgery for the treatment of early gastric cancer in the EGJ based on the comparable long-term outcomes.

BACKGROUND In South Korea, which has a high incidence of gastric cancer, the most common de novo malignancy associated with liver transplantation is gastric cancer. This study sought to identify clinicopathologic characteristics in gastric cancer patients after liver transplantation, and to help manage these cases. MATERIAL AND METHODS We investigated gastric cancer patients after liver transplantation at Asan Medical Center. We analyzed sex, age, cause of liver transplantation, initiating immunosuppressant, pre-transplantation gastric fibroscopy findings, time interval between transplantation and gastric cancer occurrence, follow-up period, existence of gastric cancer screening, Helicobacter pylori infection, family cancer history, gastric cancer treatment, cancer location, size of tumor, macroscopic gross type, WHO histologic type, Lauren's classification, TNM stage, and survival. RESULTS Of 2968 adult liver transplantation patients at our hospital, 19 were diagnosed with gastric cancer. The mean age at the time of gastric cancer diagnosis was 60.2±6.8 (46-71) years and mean time interval between liver transplantation and diagnosis of gastric cancer was 56.0±30.7 (3.20-113) months. Endoscopic submucosal dissection was done for 10 patients, 4 of whom underwent surgical resection. Surgical resection as an initial treatment was done in 8 patients. One patient received chemotherapy first. The standard incidence ratio of gastric cancer in these patients was 1036 per 100 000 persons (95% CI, 623.7-1,619) in men and 318.9 per 100 000 (95% CI, 4.170-1,774) in women. CONCLUSIONS For long-term survival of liver transplant patients, early detection of de novo cancer is necessary. Therefore, annual screening for gastric cancer after liver transplantation is needed, especially in areas where the incidence of gastric cancer is high, such as South Korea.

Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005–2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma., Graphical Abstract

Oral fluoropyrimidine S-1 contains tegafur, which is metabolized to 5-fluorouracil by cytochrome P450 2A6 (CYP2A6). We here examined associations between CYP2A6 polymorphisms and treatment outcomes of adjuvant S-1 in gastric cancer patients. Patients received adjuvant S-1 (40 mg/m2 twice daily, days 1–28, every 6 weeks for eight cycles) after curative surgery for pathological stage II–III gastric cancer. We analyzed the wild-type allele (W) (CYP2A6*1) and four variant alleles (V) (CYP2A6*4, *7, *9, *10) that abolish or reduce this enzyme activity. Patients (n = 200) were enrolled between November 2007 and July 2013 with the following clinical characteristics: median age, 57 years (range, 32–83 years); 128 men, 72 women. With a median follow-up of 46.4 months, the 3-year relapse-free survival (RFS) and overall survival (OS) rates were 83.1 % (95 % CI, 77.7–88.5 %) and 94.8 % (95 % CI, 91.6–98.0 %), respectively. Genotype distributions were as follows: W/W (n = 49, 24.5 %), W/V (n = 94, 47.0 %), and V/V (n = 57, 28.5 %). Overall toxicity did not differ according to genotype for any grade (p = 0.612) or grade ≥3 (p = 0.143). However, RFS differed significantly according to CYP2A6 genotype. The 3-year RFS rates were 95.9 % for W/W, 83.1 % for W/V, and 72.5 % for V/V (p = 0.032). Carriers of W/V and V/V genotypes had a poorer RFS with a hazard ratio of 3.41 (95 % CI, 1.01–11.52; p = 0.049) and 4.03 (95 % CI, 1.16–13.93; p = 0.028), respectively, compared with the W/W genotype. CYP2A6 polymorphisms are not associated with toxicity of S-1 chemotherapy, but correlate with the efficacy of S-1 in the adjuvant setting for gastric cancer.

Postoperative chemotherapy with S-1 or capecitabine plus oxaliplatin is a standard treatment for resectable gastric cancer (GC). However, survival outcomes of stage IIIB–IV (M0) GC cases are still poor. We investigated the efficacy and safety of docetaxel, capecitabine, and cisplatin (DXP) in patients with stage IIIB–IV GC. This was a single-arm phase 2 study that included patients with stage IIIB–IV GC who underwent D2 gastrectomy. Patients received six cycles of docetaxel [60 mg/m2 on day 1 (D1)], capecitabine (1,875 mg/m2/day on D1–14), and cisplatin (60 mg/m2 on D1) every 3 weeks. The primary end-point was recurrence-free survival (RFS). A total of 46 GC patients between January 2007 and August 2008 were included. After a median follow-up of 56.1 months (range 52.2–64.1), the median RFS and overall survival (OS) were 26.9 months (95 % CI 7.5–46.4) and 43.9 months (95 % CI 29.2–58.7), respectively. The 5-year RFS and OS rates were 39.1 and 41.3 %, respectively. The most common grade 3/4 toxicities were neutropenia (40 %), anorexia (22 %), and febrile neutropenia (15 %). Adjuvant DXP is feasible and effective for patients with stage IIIB–IV GC. A phase 3 study comparing triplet and doublet regimens for these patients is ongoing.

e16542 Background: Immune checkpoint inhibitors have shown survival benefits in unresectable/metastatic gastric cancer (GC), esophageal cancer (EC), and hepatocellular carcinoma (HCC). Based on scientific rationale for neoadjuvant immunotherapy, including enhanced immune recognition, we initiated a phase II study of IMC-001, a novel PD-L1 targeting fully human monoclonal Ab in the neoadjuvant setting for resectable GC, EC, and HCC. Methods: This is a prospective, open-label, phase II study of neoadjuvant IMC-001 (20 mg/kg iv every 2 weeks for 2 cycles) across three cohorts of resectable gastrointestinal cancers (GC, EC, HCC). The primary endpoint is major pathologic response rate ( < 10% of viable tumor cells) and secondary endpoints include safety, feasibility, R0 resection rate, clinical tumor response rate/disease control rate (DCR), progression-free survival, relapse-free survival, and overall survival. Exploratory endpoints include immune monitoring and biomarker analysis in tumor tissues, blood, and stool. Results: From Sep. 2019 to Feb. 2020, 14 eligible patients (pts) (6 HCC; 5 GC; 3 EC) were enrolled; male (79%), median age = 63 yrs (range, 40-72), clinical stage (AJCC 8th) I (57%)/II (21%)/III (21%). 12 pts completed 2 cycles of neoadjuvant IMC-001 and one pt stopped after one cycle due to G3 autoimmune hepatitis, which was only G3 adverse event (AE) and resolved with steroid. Other AE included G2 hyperthyroidism (n = 1), G1 pruritus (n = 2), G1 rash (n = 1), G1 myalgia (n = 1), G1 arthralgia (n = 1), G1 diarrhea (n = 1), G1 cough (n = 1), G1 palate discomfort (n = 1), and G1 chest discomfort (n = 1). So far, 10 clinical response-evaluable pts showed a 100% DCR and underwent surgery, which was all R0 resection. Post-treatment surgery specimens showed various degrees of lymphocyte infiltration in intratumoral or peritumoral areas ranging from 10% to 90%, which was increased compared to pre-treatment biopsies. In HCC pts, adjacent hepatic parenchyma showed mild to moderate, diffuse portal inflammation regardless of Hepatitis B virus status and minimal and moderate fatty change. IHC for PD-L1 using 22C3, SP263 and SP142 clones showed similar results among three Abs with relatively low expression regardless of tumor types (range, 0-20%). Conclusions: Neoadjuvant IMC-001 seems to be well tolerated and have preliminary immune modulating activity in resectable GC, EC, and HCC pts. The study is ongoing and the updated clinical and immunologic results will be presented. Clinical trial information: NCT04196465 .