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Few studies have examined the association between mortality and malnutrition diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria for routine nutritional assessment; thus, this association is not well known. We aimed to clarify the association between GLIM-defined malnutrition and mortality in a large population of hospitalized patients.In this retrospective cohort study, we enrolled adult patients admitted to Aichi Medical University Hospital between April 2019 and March 2021, who underwent nutritional assessment using the GLIM criteria. In November 2021, we collected the following data from electronic medical records: demographic, clinical, and laboratory data upon admission; nutritional data assessed using GLIM criteria; and data on final patient outcomes.In this study, we included 9372 hospitalized patients who were identified to be at risk by the validated nutritional screening tools (50.6% men, median age 75.0 [67.0-82.0] years, 69.2% patients aged ≥70 years). The number of patients with no, moderate, and severe GLIM-defined malnutrition was 4145 (44.2%), 2799 (29.9%), and 2428 (25.9%), respectively. Kaplan-Meier survival curve analysis showed a significant increase in mortality with worsening nutritional status (log-rank test, P 0.001). After adjusting for age and sex, multivariable Cox regression analysis revealed that both moderate (Hazard ratio [HR] 2.0, 95% confidence interval [CI] 1.79-2.23, P 0.001) and severe malnutrition (HR 3.06, 95% CI 2.74-3.40, P 0.001) were independent risk factors for mortality. Moreover, multivariable analysis showed that four of the five GLIM sub-criteria (except low body mass index) were independently associated with prognosis.Malnutrition and its severity, routinely assessed using the GLIM criteria, are associated with high mortality in hospitalized patients at nutritional risk. Further research is needed to evaluate the usefulness of the GLIM sub-criteria, including low body mass index, in these patients.

To investigate the postoperative quality of life (QOL) in patients with proximal gastric cancer (PGC) or esophago-gastric junction cancer, a nationwide multi-institutional study (PGSAS NEXT trial) was conducted.Patients who had undergone radical resection more than 6 months previously were enrolled from 70 Japanese institutions between July 2018 and June 2020. The Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 questionnaire was distributed to eligible patients, and responses were collected by mail. The main outcome measures of the PGSAS-45 were then calculated and compared.Questionnaires were retrieved from 1950 participants, and data from 300 patients who had undergone a proximal gastrectomy (PG) with esophagogastrostomy for PGC were analyzed. The mean esophageal reflux subscale value was 1.9 among the 276 patients who underwent an anti-reflux procedure, which was significantly better than the mean value (2.6) for the 21 patients who did not undergo an anti-reflux procedure (p = 0.002). The esophageal reflux subscale values were also compared among 3 major anti-reflux procedures: the double-flap technique (N = 153), the pseudo-fornix and/or His angle formation (N = 67), and fundoplication (N = 44); no statistically significant differences were observed.An anti-reflux procedure during esophagogastrostomy after PG for PGC is necessary to improve postoperative esophageal reflux symptoms, regardless of the type of procedure.The PGSAS NEXT study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; registration number: 000032221).

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition.

Patients with peritoneal dissemination of gastric cancer have poor oral intake caused by malignant bowel obstruction (MBO). Palliative surgery has often been undertaken to improve quality of life (QOL), but few prospective studies on palliative surgery in this patient population have been published. We prospectively investigated the significance of palliative surgery using patient-reported QOL measures. Patients underwent palliative surgery by small intestine/colon resection or small intestine/colon bypass or ileostomy/colostomy for MBO. The primary endpoint was change in QOL assessed at baseline, 14 days, 1 month, and 3 months following palliative surgery using the Euro QoL Five Dimensions (EQ-5D™) questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications. Between April 2013 and March 2018, 63 patients were enrolled from 14 institutions. The mean EQ-5D™ utility index baseline score of 0.6 remained consistent. Gastric-specific symptoms mostly showed statistically significant improvement from baseline. Forty-two patients (67%) were able to eat solid food 2 weeks after palliative surgery and 36 patients (57%) tolerated it for 3 months. The rate of overall morbidity of ≥ grade III according to the Clavien–Dindo classification was 16% (10 patients) and the 30-day postoperative mortality rate was 3.2% (2 patients). In patients with MBO caused by peritoneal dissemination of gastric cancer, palliative surgery did not improve QOL while improving solid food intake, with an acceptable postoperative morbidity and mortality rate.

Summary: Background: In 2012, the Japanese Society for Surgical Metabolism and Nutrition introduced the Essential Strategy for Early Normalization after Surgery with Patient's Excellent Satisfaction (ESSENSE) program to improve the perioperative management of gastrointestinal surgery. The ESSENSE program aimed to minimize ineffective perioperative management practices, and achieve adequate analgesia to expedite the return to work and activities of daily living. Methods: After educating relevant facilities about the ESSENSE program in 2012, we conducted questionnaire-based surveys in selected institutions in 2013 and 2016. Results: ESSENSE was implemented in 65% of the specified gastrointestinal surgical procedures in 2016. Oral fluids were discontinued >10 h before anesthesia induction by 33% and 9% of respondents in 2013 and 2016, respectively, and 2 h before anesthesia induction by 23% and 38% in 2013 and 2016, respectively. Fasting was initiated >10 h before anesthesia induction by 75% and 29% of respondents in 2013 and 2016, respectively, and 6–8 h before anesthesia induction by 20% and 60% in 2013 and 2016, respectively. Oral rehydration with a carbohydrate-containing beverage was performed 2 h preoperatively by 23% and 47% of respondents in 2013 and 2016, respectively. The median postoperative periods after which water and solids intakes were resumed were significantly shorter in 2016 than in 2013 after five surgical procedures; the exceptions were esophagectomy, laparoscopic cholecystectomy, and hepatectomy. Conclusions: There was a high level of implementation of the ESSENSE program in participating institutions in 2016, suggesting that it is possible to achieve widespread implementation of a preoperative management protocol. Keywords: Gastrointestinal surgery, Perioperative management, Questionnaire, Survey

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition.

Background In this study, the accuracy of preoperative staging for gastric stump cancer, which has not been thoroughly investigated since the condition is rare, was investigated using computed tomography and gastroscopic imaging. Methods Between February 1994 and April 2018, 49 patients with gastric stump cancer, following subtotal or total gastrectomy, were reviewed retrospectively. Preoperative diagnoses of clinical T and clinical N categories were compared with post-operative pathological diagnoses (pT and pN categories). Positive predictive values, accuracy, sensitivity and specificity were also evaluated. Results The overall accuracy of T staging was 40.8%. The positive predictive value for cT3/T4 was 96.3%, whereas the positive predictive value for cT1/T2 was 72.7%. The overall accuracy for N staging was 61.2%. The positive predictive value of lymph node positive patients was 73.3%. The positive predictive value and sensitivity of over stage II were 96.6% and 84.8%, respectively. Conclusions The accuracy of preoperative diagnosis using both computed tomography and gastroscopy imaging may be feasible for T3/T4 advanced gastric stump cancer, whereas diagnosing T1/2 gastric stump cancer must be carefully considered due to high misdiagnosis rates, relating to depth.

BACKGROUND The effects of various gastrectomy procedures on the patient’s quality of life (QOL) are not well understood. Thus, this nationwide multi-institutional cross-sectional study using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45), a well-established questionnaire designed to clarify the severity and characteristics of the postgastrectomy syndrome, was conducted. AIM To compare the effects of six main gastrectomy procedures on the postoperative QOL. METHODS Eligible questionnaires retrieved from 2368 patients who underwent either of six gastrectomy procedures [total gastrectomy with Roux-en-Y reconstruction (TGRY; n = 393), proximal gastrectomy (PG; n = 193), distal gastrectomy with Roux-en-Y reconstruction (DGRY; n = 475), distal gastrectomy with Billroth-I reconstruction (DGBI; n = 909), pylorus-preserving gastrectomy (PPG; n = 313), and local resection of the stomach (LR; n = 85)] were analyzed. Among the 19 main outcome measures of PGSAS-45, the severity and characteristics of postgastrectomy syndrome were compared for the aforementioned six gastrectomy procedures using analysis of means. RESULTS TGRY and PG significantly impaired the QOL of postoperative patients. Postoperative QOL was excellent in LR (cardia and pylorus were preserved with minimal resection). In procedures removing the distal stomach, diarrhea subscale (SS) and dumping SS were less frequent in PPG than in DGBI and DGRY. However, there was no difference in the postoperative QOL between DGBI and DGRY. The most noticeable adverse effects caused by gastrectomy were meal-related distress SS, dissatisfaction at the meal, and weight loss, with significant differences among the surgical procedures. CONCLUSION Postoperative QOL greatly differed among six gastrectomy procedures. The severity and characteristics of postgastrectomy syndrome should be considered to select gastrectomy procedures, overcome surgical shortcomings, and enhance postoperative care.

Summary Background & aims Nutrition education is not well represented in the medical curriculum. The aim of this original paper was to describe the Nutrition Education in Medical Schools (NEMS) Project of the European Society for Clinical Nutrition and Metabolism (ESPEN). Methods On 19 January 2020, a meeting was held on this topic that was attended by 51 delegates (27 council members) from 34 countries, and 13 European University representatives. Results This article includes the contents of the meeting that concluded with the signing of the Manifesto for the Implementation of Nutrition Education in the Undergraduate Medical Curriculum. Conclusion The meeting represented a significant step forward, moved towards implementation of nutrition education in medical education in general and in clinical practice in particular, in compliance with the aims of the ESPEN Nutrition Education Study Group (NESG).

This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay. The subjects of this study were patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for gastric cancer between January 2014 and December 2015. Patients were randomly assigned to the early oral feeding group (intervention group) or the conventional postoperative management group (control group) for each procedure. We evaluated the length of postoperative hospital stay and the incidence of postoperative complications in each group. No significant differences in length of postoperative stay were found between the intervention and control groups of the patients who underwent DG. The incidence of postoperative complications was significantly greater in the DG intervention group. In contrast, the length of postoperative stay was significantly shorter in the TG intervention group, although the TG group did not attain the established target sample size. Early oral feeding did not shorten the postoperative hospital stay after DG. The higher incidence of postoperative complications precluded the unselected adoption of early oral feeding for DG patients. Further confirmative studies are required to definitively establish the potential benefits of early oral feeding for TG patients.

Background: The current pooled analysis evaluated the efficacy of Hangeshashinto (TJ-14) in the prevention and/or treatment of chemotherapy-induced oral mucositis (COM) in gastric cancer and colorectal cancer using two prospective, multi-institutional, randomized, double-blind, placebo-controlled phase II trials. Patients and Methods: HANGESHA-G and HANGESHA-C randomly assigned patients with gastric cancer or colorectal cancer who developed moderate to severe COM (grade ≥1) during any cycle of chemotherapy to receive either TJ-14 or a placebo as a double-blind trial. The patients received a placebo or TJ-14 for four to six weeks, according to the chemotherapy regimen, from the start of their next course of chemotherapy. The primary endpoint was the incidence of grade ≥2 COM in the protocol treatment course, and the secondary endpoints were the time to disappearance of COM and the incidence of adverse events. Results: The pooled population included 181 patients. The incidence of grade ≥2 COM in the TJ-14 group was 55.7% (49 patients), while that in the placebo group was 53.8% (50 patients); there was no significant difference between the two groups (p=0.796). The median time to remission of grade ≥2 COM to grade

We performed transabdominal preperitoneal inguinal hernia repair in 46 patients (58 diseases), two of whom experienced early recurrence after mesh repair. Case 1 was a 76-year-old man with a bilateral inguinal hernia (recurrence site, left indirect hernia) after appendectomy. The recurrence occurred 1 month after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using the direct Kugel® patch with an anterior technique. Case 2 was a 79-year-old man with a bilateral inguinal hernia (recurrence site, right direct hernia with an orifice >3 cm) after appendectomy. The recurrence occurred 3 months after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using an ULTRAPRO® Plug with an anterior technique under laparoscopic observation. We believe the recurrences resulted from insufficient internal exfoliation and fixation affected by complicated exfoliation of the preperitoneal space with omental adhesion after intraperitoneal surgery.

Purposes. During esophageal surgery, clamping injury and injury associated with the use of energy devices are common mechanisms underlying intraoperative recurrent laryngeal nerve (RLN) damage. Recently, intraoperative neuromonitoring (IONM) has been applied to prevent RLN injury. This study was aimed at investigating the changes in the EMG signals associated with clamping injury of the RLN caused by picking up of the nerve with tweezers in domestic pigs. Methods. Six domestic pigs (12 RLNs) underwent continuous IONM (CIONM) by our original automated periodic vagal nerve stimulation method. Results. Our system can be used safely and accurately. The signals showed a decrease of the amplitude when the RLN was picked up and closed slowly by the double-action Maryland with jaw covers. If the clamp was released before the signal amplitude decreased to 50% of the baseline, the signal showed gradual recovery to the baseline in 12 ± 3 minutes. Conclusion. Although there were limitations in our study using domestic pig, including the small sample size, our results are expected to contribute to a decrease in the incidence of RLN damage during esophageal surgery.

Background: The measurement of a single abdominal image on computed tomography (CT) can provide an estimate of the total body skeletal muscle. We evaluate the change of the area of the psoas major muscle (PMMA) in a CT which was performed routinely after gastrectomy in gastric cancer. Methods: A total of 119 gastric cancer patients who underwent gastrectomy were enrolled for the study. A CT image at the top of the iliac crest level was obtained at the following times: 3 postoperative months (POM), 6 POM, 1 postoperative year (POY), 2 POY, 3 POY, and 5 POY. We analyzed the change rate of PMMA after gastrectomy and before or after recurrence. Results: PMMA change after gastrectomy was approximately between -8 and -10% over the 5-year observation period. PMMA in the R2 (macroscopic residual tumor)/recurrence group was lower than that in the no recurrence group, and a significant difference was observed at 2 POY (-21.7 ± 3.6% vs. -7.9 ± 2.3%, p < 0.01). PMMA after freshly diagnosed recurrence had decreased significantly by 14.1 ± 1.8% (p < 0.01). Conclusions: Evaluation of PMMA change by CT after gastrectomy could assist in the diagnosis of the progression of cancer state in gastric cancer patients.

[Introduction] Immune checkpoint inhibitors (ICIs) are widely used for the treatment of several malignancies. Despite their effectiveness, they may cause immune-related adverse effects on endocrine organs. Here we describe three cases of isolated ACTH deficiency (IAD) that has occurred after ICI therapy. [Case presentation] Case 1: An 80-year-old female patient with advanced melanoma received nivolumab (NIVO) (3 mg/kg intravenously (IV) every two weeks) for 16 weeks, followed by ipilimumab (3 mg/kg IV every three weeks). After the third injection of ipilimumab, she was alert but complained of general fatigue and anorexia. Her laboratory tests revealed hyponatremia (Na 126 mEq/l), hypoglycemia (Glu 65 mg/dl), low ACTH (ACTH

Rationale: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. Methods: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. Results: A two-step approach for the malnutrition diagnosis was selected, i.e. first screening to identify “at risk” status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. Conclusion: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3–5 years., SCOPUS: ar.j, info:eu-repo/semantics/published

In patients with gastric cancer (GC), peritoneal recurrence is a common risk and associated with poor prognosis. A novel biomarker for the prediction of high-risk peritoneal recurrence in patients with GC is desirable. The present study investigated the effectiveness of exosome-encapsulated microRNAs (ex-miRNAs) as minimally invasive biomarkers in patients with GC that received curative surgery. Recurrence-specific ex-miRNAs were selected following comparison of miRNA microarray data from patients with TNM stage II GC with peritoneal recurrence (n=3) and without peritoneal recurrence following curative surgery (n=3), and three healthy volunteers. In this analysis, exosome-encapsulated miRNA-21 (ex-miR-21) and exosomal miR-92a (ex-miR-92a) exhibited the greatest alterations in expression patterns. Using plasma exosome samples collected from another 129 patients with stage II and III GC, the present study investigated the potential value of ex-miR-21 and ex-miR-92a as biomarkers. Ex-miRNA levels were measured using TaqMan miRNA assays. Ex-miR-21 levels were significantly higher and ex-miR-92a levels were significantly lower in samples from patients with GC compared with healthy controls. The overall survival (OS) and peritoneal recurrence-free survival (PRFS) were poorer in stage II and III patients with high ex-miR-21 levels than in patients with low miR-21 levels. OS and PRFS of stage II and III patients with low ex-miR92a levels were significantly worse than those with high ex-miR92a levels. Cox multivariate analyses indicated that ex-miR-21 and ex-miR-92a were independent prognostic factors for OS and PRFS in stage II and III GC. A negative correlation was detected between expression levels of miR-21 and programmed cell death protein 4 mRNA, and miR-92a and prostaglandin E receptor 4 mRNA. Therefore, ex-miR-21 and ex-miR-92a may function as effective and minimally invasive biomarkers for the prediction of peritoneal recurrence and the prognosis of patients with stage II/III GC.

In pure hydrophobic 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, [C n C m im][TFSI] (2 ≤ n ≤ 10, m = 1), the crossover alkyl side-chain length of the C n C 1 im + cation ( n c ) is found to be equal to 6 by a simultaneous X-ray diffraction and differential scanning calorimetry. By adding butanol, a geometrical factor of butanol isomers became dominant in the liquid–liquid phase equilibrium (LLE) above n c . In the LLE of [C n C 1 im][TFSI]–butanol, upper critical solution temperatures ( T UCST ) and critical concentration ( x c ) at the top of the phase separation depended extensively on n and the butanol isomer effect. In primary alcohol (C l H 2l + 1 OH), the alkyl chain length of alcohols, l , enables it to increase the T UCST at a fixed n . Density at T UCST and x c have the opposite tendency in the two-length scale ( n and l ). In Raman spectroscopy, the conformation ratio of the TFSI − anion as an instability factor of liquid mixing exhibits an anomaly in the vicinity of n c .

4529 Background: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of IP paclitaxel (PTX) combined with S-1 and intravenous PTX over S-1/cisplatin (SP), the standard of care as a first-line treatment in Japan, the sensitivity analysis suggested clinical efficacy of the IP PTX. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy have been warranted. After a dose-finding study, we sought to explore efficacy of a new regimen that combined IP PTX with SP. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled in the phase II multi-institutional prospective trial. In addition to the established SP regimen (S-1 administered orally at a dose of 80 mg/m2 bid for 21 days followed by a 14-day rest and cisplatin administered intravenously at a dose of 60 mg/m2 on day 8), IP PTX was administered on days 1, 8 and 22 at a dose of 20 mg/m2. The primary endpoint is overall survival (OS) rate at one year after treatment initiation. Secondary endpoints are progression free survival (PFS), response rate and toxicity. Results: Fifty-three patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 7 (range 1-20). The 1-year OS rate was 74% (95% CI, 60-83%). The median survival time was 19.4 months (95% CI, 16.7 months-). The 1-year PFS rate was 57% (95% CI, 42-69%). The overall response rate was 20% (95% CI, 1-72%) in 5 patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 23 (64%) of 36 patients. Fourteen (26%) patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), anemia (29%), diarrhea (13%) and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in 4 patients. There was 1 treatment-related death. Conclusions: IP PTX combined with SP is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000023000 .

Purpose Intraperitoneal paclitaxel plus systemic chemotherapy demonstrated promising clinical effects in patients with gastric cancer with peritoneal metastasis. We aimed to verify its superiority over standard systemic chemotherapy in overall survival. Patients and Methods This randomized phase III trial enrolled patients with gastric cancer with peritoneal metastasis who had received no or short-term (< 2 months) chemotherapy. Patients were randomly assigned at a two-to-one ratio to receive intraperitoneal and intravenous paclitaxel plus S-1 (IP; intraperitoneal paclitaxel 20 mg/m2 and intravenous paclitaxel 50 mg/m2 on days 1 and 8 plus S-1 80 mg/m2 per day on days 1 to 14 for a 3-week cycle) or S-1 plus cisplatin (SP; S-1 80 mg/m2 per day on days 1 to 21 plus cisplatin 60 mg/m2 on day 8 for a 5-week cycle), stratified by center, previous chemotherapy, and extent of peritoneal metastasis. The primary end point was overall survival. Secondary end points were response rate, 3-year overall survival rate, and safety. Results We enrolled 183 patients and performed efficacy analyses in 164 eligible patients. Baseline characteristics were balanced between the arms, except that patients in the IP arm had significantly more ascites. The median survival times for the IP and SP arms were 17.7 and 15.2 months, respectively (hazard ratio, 0.72; 95% CI, 0.49 to 1.04; stratified log-rank P = .080). In the sensitivity analysis adjusted for baseline ascites, the hazard ratio was 0.59 (95% CI, 0.39 to 0.87; P = .008). The 3-year overall survival rate was 21.9% (95% CI, 14.9% to 29.9%) in the IP arm and 6.0% (95% CI, 1.6% to 14.9%) in the SP arm. Both regimens were well tolerated. Conclusion This trial failed to show statistical superiority of intraperitoneal paclitaxel plus systemic chemotherapy. However, the exploratory analyses suggested possible clinical benefits of intraperitoneal paclitaxel for gastric cancer.

Recently, exosome‑encapsulated microRNAs (miRNAs) have been attracting attention as stable and minimally invasive biomarkers in cancer patients. The aim of the present study was to clarify the value of plasma exosomal microRNA‑23b (miR‑23b) as a diagnostic and prognostic biomarker in gastric cancer (GC) patients at each tumor stage. We first selected recurrence specific exosomal miRNA by miRNA microarray from 6 GC patients (stage I) with or without recurrence, and 3 healthy volunteers. In this analysis, miR‑23b demonstrated the most significant change. Subsequently, we validated the usefulness of miR‑23b as a biomarker using the plasma exosome samples collected from 232 GC patients and 20 healthy volunteers. miR‑23b levels were evaluated by Taqman microRNA assays. Exosomal miR‑23b levels of GC patients were significantly lower than those of the healthy controls. A significant association was revealed between the plasma exosomal miR‑23b levels and the expression of miR‑23b in primary tumor tissues. Concerning the pathological condition, miR‑23b demonstrated a significant association with tumor size, depth of invasion, liver metastasis and TNM stage. The overall survival (OS) rates of low‑miR‑23b patients were significantly worse than those of high‑miR‑23b patients at stage I, II, III and IV. The disease‑free survival (DFS) rates of low exosomal miR‑23b patients were significantly worse than those of high‑miR‑23b patients at stage I, II and III. Cox multivariate analysis indicated that exosomal miR‑23b was an independent prognostic factor for OS and DFS at each tumor stage. Our results revealed that exosomal miR‑23b has potential as minimally invasive predictive biomarker for the recurrence and prognosis of GC in patients at all stages.

Background Capecitabine plus cisplatin (XP) is a standard global regimen, while S-1 plus cisplatin (SP) is a Japanese standard for first-line treatment of advanced gastric cancer (AGC). We conducted a phase II trial comparing XP with SP for patients with AGC to confirm whether these regimens can be used as controls in a phase III study and to explore whether histological subtypes favour XP or SP. Patients and methods Eligible patients were randomised to receive either S-1 40 mg/m2 for 21 days plus cisplatin 60 mg/m2 (q5w) or capecitabine 1000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w). The primary end-point was progression-free survival (PFS). The secondary end-points were overall survival (OS), overall response rate (ORR) and safety. Results In 110 eligible patients, 24-week PFS was higher in both groups (SP 50.9%, XP 43.5%) than the protocol-specified threshold of 40%. The median PFS for SP versus XP was 5.6 and 5.1 months (hazard ratio [HR], 1.126; p = 0.5626); OS was 13.5 and 12.6 months (HR, 0.942; p = 0.7769) and the ORR was 42.4% and 69.4% (p = 0.0237), respectively. The most common grade ≥3 adverse events with SP/XP were anaemia (16%/20%), neutropenia (9%/18%) and anorexia (18%/13%). Subgroup analysis by histological classification showed no statistical difference between treatments. Conclusions XP and SP are comparable and can be recommended as control arms in a phase III study for AGC. Histological subtypes were not sensitive markers for the selection of XP or SP. Clinical trial registration NCT00140624 .

It is important for cancer patients to receive end-of-life care at the desired place.To identify issues in selection of place for end-of-life care of cancer patients to realize their optimal survivorship.Between September 2015 and January 2016, a questionnaire consisting of 33 items, including end-of-life care place preferences, was administered to cancer patients who attended three university hospitals in Japan.A total of 971 questionnaires were collected (response rate, 88.4%). Fifty-eight percent of patients preferred to stay at home to receive end-of-life care. In contrast, more than 80% of patients did not know the details of healthcare services. The factors significantly associated with patients' choice for place of end-of-life care at home were "male gender" (odds ratio [OR] = 1.43, p = 0.030), "living in a one-person household" (OR = 0.21, p 0.001), "feeling close to friends" (OR = 0.94, p = 0.049), "thinking that the family is burdened" (OR = 0.55, p 0.001), "thinking that pain is controllable at home" (OR = 1.39, p 0.001), and "thinking that society should establish a system of home palliative care" (OR = 1.93, p 0.001).This study identified six factors influencing the selection of a place for end-of-life care. Most patients have a desire for a social system that allows end-of-life care at home where they can live with their family, but have anxiety about treatment to deal with symptom change, with concern about burden on their family. These issues should be addressed in the future.

Response to the letter: Comment on "GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community" : Some considerations about the GLIM criteria - A consensus report for the diagnosis of malnutrition by Drs. LB da Silva Passos and DA De -Souza

The enhanced recovery after surgery (ERAS) protocol first established in the colorectal surgery has now been extended to application to various types of surgical procedures such as gastrectomy. Many gastric surgeons consider that it is feasible and useful to apply most of the ERAS elements to gastric surgery, but one of the greatest concerns for gastric surgeons is early postoperative feeding, especially early oral feeding.

Background Esophageal perforation after aortic replacement/stenting for aortic dissection or aneurysm is a rare but severe complication. However, its cause, standard treatment, and prognosis are unclear. We analyzed the treatment and outcome retrospectively from seven cases experienced at our hospital. Case presentation The median age of the patients was 70 years (range, 41–86), and six of the seven cases were male. As the first treatment, aortic replacement techniques were performed in five, and thoracic endovascular aortic repair (TEVAR) procedure was performed in two. We evaluated the treatment of the perforation, the cause of death, and the median survival time after reparative surgery (esophagectomy). Initial treatment of the perforation was esophagectomy without reconstruction in six and esophagogastric bypass (later, esophagectomy was performed) in one. Three of seven cases could be discharged from hospital or moved to another hospital, but two of these three cases died of major bleeding on postoperative days 320 and 645. The other four esophagectomy cases died in hospital because of sepsis on postoperative days 14, 30, and 41 and major bleeding on postoperative day 54. The one surviving case was a 65-year-old man who underwent reconstruction, and was still alive without signs of infection at 424 days postoperatively. Conclusion The prognosis of esophageal perforation cases after aortic replacement/stenting for thoracic aortic dissection or aneurysm is poor, though there were some cases with relatively long survival. Therefore, the indication for invasive esophagectomy should be decided carefully. Control of infection including regional infection is essential for successful treatment.

We performed transabdominal preperitoneal inguinal hernia repair in 46 patients (58 diseases), two of whom experienced early recurrence after mesh repair. Case 1 was a 76-year-old man with a bilateral inguinal hernia (recurrence site, left indirect hernia) after appendectomy. The recurrence occurred 1 month after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using the direct Kugel® patch with an anterior technique. Case 2 was a 79-year-old man with a bilateral inguinal hernia (recurrence site, right direct hernia with an orifice3 cm) after appendectomy. The recurrence occurred 3 months after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using an ULTRAPRO® Plug with an anterior technique under laparoscopic observation. We believe the recurrences resulted from insufficient internal exfoliation and fixation affected by complicated exfoliation of the preperitoneal space with omental adhesion after intraperitoneal surgery.

Proximal gastrectomy with esophagogastrostomy (PGEG) has been widely applied as a comparatively simple method. In this study, we used a questionnaire survey to evaluate the influence of various surgical factors on post-operative quality of life (QOL) after PGEG. In this post-gastrectomy syndrome assessment study, we analyzed QOL in 2,368 cases. Among these, 193 had undergone proximal gastrectomy and 115 had undergone PGEG. The Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45 is a questionnaire consisting of 45 items, including the SF-8, the Gastrointestinal Symptom Rating Scale (GSRS), and other symptom items seemed to be specific to post-gastrectomy. The 23 symptom items were composed of seven symptom subscales (SS), including esophageal reflux, abdominal pain, and meal-related distress. These seven SS, total symptom score, ingested amount of food per meal, necessity for additional meals, quality of ingestion SS, ability to work, dissatisfaction with symptoms, dissatisfaction with the meal, dissatisfaction with working, dissatisfaction with daily life SS and change in body weight were evaluated as main outcome measures. In PGEG cases, we evaluated the influence on QOL of various surgical factors, such as procedures to prevent gastroesophageal regurgitation and size of the remnant stomach. The scores for esophageal reflux and dissatisfaction with the meal were higher in patients who had not undergone an anti-reflux procedure. In most cases, the preserved remnant stomach was more than two-thirds the size of the pre-operative stomach. When comparing patients with a remnant stomach two-thirds the pre-operative size and those with more than three-quarters, the diarrhea SS and necessity for additional meals scores were lower in the group with more than three-quarters. The indigestion, constipation, and abdominal pain subscales, and the total symptom score, were higher in patients who had not undergone pyloric bougie than in those who had. These results indicated that QOL was better in patients with a large remnant stomach. Procedures to prevent gastroesophageal reflux, and the use of pyloric bougie as a complementary drainage procedure, were considered effective ways to reduce the deterioration of QOL.

Summary Background The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1. Methods We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20–80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0–1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m 2 per day), S-1 only (80 mg/m 2 per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m 2 ) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082. Findings We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2–57·6) and that of sequential treatment was 57·2% (53·4–60·8; hazard ratio [HR] 0·92, 95% CI 0·80–1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2–56·6) and that of the S-1 group was 58·2% (54·4–61·8; HR 0·81, 95% CI 0·70–0·93, p=0·0048; p non-inferiority =0·151). The most common grade 3–4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3–4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively). Interpretation Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan. Funding Epidemiological and Clinical Research Information Network.

90 Background: Patients with peritoneal dissemination of gastric cancer have poor oral intake caused by bowel obstruction. Palliative surgery has often been undertaken to improve quality of life (QoL), but there is no prospective study on palliative surgery. Methods: We prospectively examined the significance of palliative surgery for patients with poor oral intake caused by peritoneal dissemination of gastric cancer using a patient-reported QoL measures. Eligibility criteria included histologically proven primary gastric adenocarcinoma presenting with bowel obstruction caused by peritoneal dissemination; presence of non-curable factors; extremely poor or no oral intake requiring parenteral nutrition. Patients underwent palliative surgery by small intestine/colon resection, small intestine/colon bypass or ileostomy/colostomy for bowel obstruction. The primary endpoint was change in QoL assessed at baseline, 14 days, 1 month and 3 months following surgical palliation by means of the Euro QoL Five Dimensions (EQ-5D) questionnaire and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications. Results: Between May 2013 and March 2018, 63 patients (33 bypass and 28 stoma, 3 exploratory laparotomy) were enrolled from 14 institutions. The mean EQ-5D utility index baseline score of 0.6 remained consistent. Gastric-specific symptoms mostly showed statistically significant improvement from baseline. 42 patients (67%) were able to eat solid food 2 weeks after palliative surgery and 36 patients (57%) tolerated it for 3 months. The rate of overall morbidity of grade III or more according to the Clavien–Dindo classification was 15.8 per cent (10 patients) and the 30-day postoperative mortality rate was 3.2 per cent (2 patients). Conclusions: In patients with bowel obstruction caused by peritoneal dissemination of gastric cancer, palliative surgery maintained QoL while improving solid food intake, with acceptable operative morbidity and mortality rate. Clinical trial information: 000023495.

Paclitaxel–cisplatin (TC) combination is effective and well tolerated in patients with unresectable gastric cancer. We investigated the efficacy and safety of TC for locally advanced gastric cancers in a neoadjuvant setting. Patients received 2–4 courses of paclitaxel (80 mg/m2) and cisplatin (25 mg/m2) on days 1, 8, and 15 in a 4-weekly schedule, followed by radical gastrectomy. Primary endpoint was the pathological response rate: percentage of tumors in which one-third or more parts were affected. All 52 patients enrolled were eligible. Thirty-six (69.7 %) patients completed two or more courses of chemotherapy. Forty-three patients (82.7 %) underwent surgery, 33 (63.5 %) had R0 resection, and there was no treatment-related death. The pathological response was 34.6 % (95 % CI 22.0–49.1) for all registered patients; the null hypothesis of tumor response ≤10 % was rejected (p

Background Open total gastrectomy carries a high risk of surgical-site infection (SSI). This study evaluated the non-inferiority of antimicrobial prophylaxis for 24 compared with 72 h after open total gastrectomy. Methods An open-label, randomized, non-inferiority study was conducted at 57 institutions in Japan. Eligible patients were those who underwent open total gastrectomy for gastric cancer. Patients were assigned randomly to continued use of β-lactamase inhibitor for either 24 or 72 h after surgery. The primary endpoint was the incidence of SSI, with non-inferiority based on a margin of 9 percentage points and a 90 per cent c.i. The secondary endpoint was the incidence of remote infection. Results A total of 464 patients (24 h prophylaxis, 228; 72 h prophylaxis, 236) were analysed. SSI occurred in 20 patients (8·8 per cent) in the 24-h prophylaxis group and 26 (11·0 per cent) in the 72-h group (absolute difference −2·2 (90 per cent c.i. −6·8 to 2·4) per cent; P < 0·001 for non-inferiority). However, the incidence of remote infection was significantly higher in the 24-h prophylaxis group. Conclusion Antimicrobial prophylaxis for 24 h after total gastrectomy is not inferior to 72 h prophylaxis for prevention of SSI. Shortened antimicrobial prophylaxis might increase the incidence of remote infection. Registration number: UMIN000001062 (http://www.umin.ac.jp).

Background: The transcription-reverse transcription concerted reaction (TRC) test is a novel molecular-based procedure, which can assess nodal metastasis accurately and quickly. We examined the usefulness of the TRC test with a double marker, cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA, to detect sentinel lymph nodes (SLN) metastasis in breast cancer patients. Methods: A total of 264 SLNs from 131 breast cancer patients were assigned to a training set (109 SLNs from 50 patients) and validation set (155 SLNs from 81 patients). Cytokeratin 19 and CEA mRNA were detected by TRC tests, and the sensitivity and specificity of the SLN metastasis between the TRC and histology cohorts were compared. Results: Mean copy numbers of CK19 and CEA by TRC tests were increased according to the metastatic size. In the training set, TRC test showed 100% sensitivity, specificity and concordance rates against the permanent histopathology test. In the validation set, sensitivity was 97.1%, specificity was 99.2% and the concordance rate was 99.4%. Conclusion: Our results showed that the detection of CK19 and CEA mRNA using the TRC test is, an accurate and rapid method for detection of SLN metastasis and can be applied as an intraoperative molecular diagnosis in breast cancer patients.

To investigate the trends of antimicrobial resistance in pathogens isolated from surgical site infections (SSI), a Japanese surveillance committee conducted the first nationwide survey. Seven main organisms were collected from SSI at 27 medical centers in 2010 and were shipped to a central laboratory for antimicrobial susceptibility testing. A total of 702 isolates from 586 patients with SSI were included. Staphylococcus aureus (20.4 %) and Enterococcus faecalis (19.5 %) were the most common isolates, followed by Pseudomonas aeruginosa (15.4 %) and Bacteroides fragilis group (15.4 %). Methicillin-resistant S. aureus among S. aureus was 72.0 %. Vancomycin MIC 2μg/ml strains accounted for 9.7 %. In Escherichia coli, 11 of 95 strains produced extended-spectrum β-lactamase (Klebsiella pneumoniae, 0/53 strains). Of E. coli strains, 8.4 % were resistant to ceftazidime (CAZ) and 26.3 % to ciprofloxacin (CPFX). No P. aeruginosa strains produced metallo-β-lactamase. In P. aeruginosa, the resistance rates were 7.4 % to tazobactam/piperacillin (TAZ/PIPC), 10.2 % to imipenem (IPM), 2.8 % to meropenem, cefepime, and CPFX, and 0 % to gentamicin. In the B. fragilis group, the rates were 28.6 % to clindamycin, 5.7 % to cefmetazole, 2.9 % to TAZ/PIPC and IPM, and 0 % to metronidazole (Bacteroides thetaiotaomicron; 59.1, 36.4, 0, 0, 0 %). MIC90 of P. aeruginosa isolated 15 days or later after surgery rose in TAZ/PIPC, CAZ, IPM, and CPFX. In patients with American Society of Anesthesiologists (ASA) score ≥3, the resistance rates of P. aeruginosa to TAZ/PIPC and CAZ were higher than in patients with ASA ≤2. The data obtained in this study revealed the trend of the spread of resistance among common species that cause SSI. Timing of isolation from surgery and the patient’s physical status affected the selection of resistant organisms.