Phase II Study of Intraperitoneal Administration of Paclitaxel Combined with S-1 and Cisplatin for Gastric Cancer with Peritoneal Metastasis.

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Pembrolizumab plus cisplatin and fluorouracil as induction chemotherapy followed by definitive chemoradiotherapy for patients with cT4 and/or supraclavicular lymph node metastasis (M1Lym) of esophageal squamous cell carcinoma.

Definitive chemoradiotherapy (DCRT) is administered as standard treatment for patients with cT4 and/or M1Lym esophageal squamous cell carcinoma (ESCC); however, its long-term result is inadequate. Although several studies have reported that conversion surgery can improve the survival of these patients, none have identified significantly better long-term survival than that achieved by DCRT. Thus, enhancing DCRT seems important to improve the survival of these patients. A strategy of shrinking tumor volume before DCRT and providing consolidation chemotherapy for systemic control is expected to improve the survival of these patients. Pembrolizumab plus cisplatin and fluorouracil has demonstrated good local control and significant improvement in the survival of patients with advanced esophageal cancer. Based on these results, the following strategy is proposed: This protocol should be applied as induction for these patients; then, DCRT should be provided depending on the initial response; and finally, adjuvant chemotherapy with an immune checkpoint inhibitor should be given to all responders.

A comparison of the effects of anti-reflux procedures during esophagogastrostomy after proximal gastrectomy on the postoperative quality of life.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: An anti-reflux procedure during esophagogastrostomy after PG for PGC is necessary to improve postoperative esophageal reflux symptoms, regardless of the type of procedure. TRIAL REGISTRATION: The PGSAS NEXT study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; registration number: 000032221).

Accuracy of preoperative staging of gastric stump cancer.

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.

QOL assessment after palliative surgery for malignant bowel obstruction caused by peritoneal dissemination of gastric cancer: a prospective multicenter observational study.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Change in antimicrobial susceptibility of pathogens isolated from surgical site infections over the past decade in Japanese nation-wide surveillance study.

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014-2015 surveillance studies. Although the rate of detection of extended-spectrum ß-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014-2015, the incidence decreased to 8.7% in 2018-2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 µg/mL). By contrast, relatively low geometric mean MICs (0.397 µg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018-2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014-2015, and 38.9% in 2018-2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group.

Effect of early oral feeding on length of hospital stay following gastrectomy for gastric cancer: a Japanese multicenter, randomized controlled trial.

PURPOSE: This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical Significance of Area of Psoas Major Muscle on Computed Tomography after Gastrectomy in Gastric Cancer Patients.

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.

Continuous Intraoperative Neuromonitoring Study Using Pigs for the Prevention of Mechanical Recurrent Laryngeal Nerve Injury in Esophageal 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.

Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial.

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; pnon-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.

Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients.

BACKGROUND: Chemoradiation therapy (CRT) has been widely used for unresectable esophageal squamous cell carcinoma (ESCC) patients. However, many patients develop local recurrence after CRT. In this study, we hypothesized that the immunotherapy by peptide vaccine may be effective for the eradication of minimal residual cancer cells after CRT. This study was conducted as a phase I clinical trial of multiple-peptide vaccine therapy combined with CRT on patients with unresectable ESCC. PATIENTS AND METHODS: HLA-A*2402 positive 11 unresectable chemo-naïve ESCC patients were treated by HLA-A*2402-restricted multi-peptide vaccine combined with CRT. The peptide vaccine included the 5 peptides as follows; TTK protein kinase (TTK), up-regulated lung cancer 10 (URLC10), insulin-like growth factor-II mRNA binding protein 3 (KOC1), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). CRT consisted of radiotherapy (60 Gy) with concurrent cisplatin (40 mg/m²) and 5-fluorouracil (400 mg/m²). Peptide vaccines mixed with incomplete Freund's adjuvant were injected subcutaneously once a week on at least 8 occasions combined with CRT. RESULTS: Vaccination with CRT therapy was well-tolerated, and no severe adverse effects were observed. In the case of grade 3 toxicities, leucopenia, neutropenia, anemia and thrombocutopenia occurred in 54.5%, 27.3%, 27.3% and 9.1% of patients, respectively. Grade 1 local skin reactions in the injection sites of vaccination were observed in 81.8% of patients. The expressions of HLA class I, URLC10, TTK, KOC1, VEGFR1 and VEGFR2 antigens were observed in the tumor tissues of all patients. All patients showed peptide-specific cytotoxic T lymphocytes responses in at least one of the 5 kinds of peptide antigens during the vaccination. Six cases of complete response (CR) and 5 cases of progressive disease (PD) were observed after the 8th vaccination. The 4 CR patients who continued the peptide vaccination experienced long consistent CR for 2.0, 2.9 4.5 and 4.6 years. CONCLUSIONS: A combination therapy of multi-peptide vaccine with CRT can successfully be performed with satisfactory levels of safety, and application of this combination therapy may be an effective treatment for patients with unresectable ESCC. TRIAL REGISTRATION: ClinicalTrial.gov, number NCT00632333.

Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: early results of the randomized phase II COMPASS trial.

BACKGROUND: The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients received S-1 (80 mg/m(2) for 21 days with 1 week's rest)/cisplatin (60 mg/m(2) at day 8) or paclitaxel/cisplatin (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week's rest) as neoadjuvant chemotherapy. RESULTS: Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms. CONCLUSIONS: Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.

Recurrent laryngeal nerve monitoring during thoracoscopic esophagectomy.

INTRODUCTION: There have been several reports on the feasibility and curability of thoracoscopic esophagectomy, which may reduce injury to the thoracic cage and decrease the invasiveness of surgery. Although the recurrent laryngeal nerve (RLN) is identified and kept intact during operations, RLN palsy sometimes occurs. Currently, surgical aides, including intraoperative neurological monitoring, are being utilized to avoid RLN injury during thyroid surgery. This system is utilized during thoracoscopic esophagectomy in the prone position. PATIENTS AND METHODS: Seven consecutive patients (six men, one woman; age range 62-74 years; mean 68 years) were included. Patients underwent general anesthesia and were intubated using the NIM TriVantage™ electromyography (EMG) tube. One-lung ventilation was performed with an endobronchial blocker. Thoracoscopic esophagectomy was performed in the prone position. The nerve stimulator was calibrated to 0.5 mA, and after the RLN was visually identified it was subsequently stimulated, which also confirmed normal machine functioning. In some situations, in the absence of a response, stimuli were increased to 1.0 mA and then 2.0 mA. RESULTS: Intraoperatively, all seven patients had their nerve signals monitored. In one case, a nerve signal disappeared after complete lymph node dissection along the left RLN. This system could identify the site of injury, and the thoracoscopic magnified view allowed the disrupted point to be located precisely. When we checked VTR after surgery, the source of injury was one point tension of the nerve pulled by fiber during lymph node dissection. CONCLUSIONS: Intraoperative RLN monitoring during thoracoscopic esophagectomy in the prone position, with one-lung ventilation performed using the TriVantage™ EMG tube and a bronchial blocker, is technically feasible, easy, and reliable.

Evaluation of QOL after proximal gastrectomy using a newly developed assessment scale (PGSAS-45).

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Feasibility of enhanced recovery after surgery in gastric surgery: a retrospective study.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs have been reported to be feasible and useful for maintaining physiological function and facilitating recovery after colorectal surgery. The feasibility of such programs in gastric surgery remains unclear. This study assessed whether an ERAS program is feasible in patients who undergo gastric surgery. METHODS: The subjects were patients who underwent gastric surgery between June 2009 and February 2011 at the Department of Gastrointestinal Surgery, Kanagawa Cancer Center. They received perioperative care according to an ERAS program. All data were retrieved retrospectively. The primary end point was the incidence of postoperative complications. The secondary end point was postoperative outcomes. RESULTS: A total of 203 patients were studied. According to the Clavien-Dindo classification, the incidence of ≥ grade 2 postoperative complications was 10.8% and that of ≥ grade 3 complications was 3.9%. Nearly all patients did not require delay of meal step-up (95.1%). Only 6 patients (3.0%) underwent reoperation. The median postoperative hospital stay was 9 days. Only 4 patients (2.0%) required readmission. There was no mortality. CONCLUSIONS: Our results suggest that our ERAS program is feasible in patients who undergo gastric surgery.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the etiologic criterion for inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified-Delphi review. A multi-round review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable with 99 % overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (mg/dL or mg/L) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgement based upon underlying diagnosis or condition, clinical signs, or CRP.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.

Prognostic implications of the global leadership initiative on malnutrition criteria as a routine assessment modality for malnutrition in hospitalized patients at a university hospital.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens.

BACKGROUND: Since a phase I clinical trial using three HLA-A24-binding peptides from TTK protein kinase (TTK), lymphocyte antigen-6 complex locus K (LY6K), and insulin-like growth factor-II mRNA binding protein-3 (IMP3) had been shown to be promising for esophageal squamous cell carcinoma (ESCC), we further performed a multicenter, non-randomized phase II clinical trial. PATIENTS AND METHODS: Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+)) and -negative (24(-)) groups. RESULTS: The OS in the 24 (+) group (n = 35) tended to be better than that in the 24(-) group (n = 25) (MST 4.6 vs. 2.6 month, respectively, p = 0.121), although the difference was not statistically significant. However, the PFS in the 24(+) group was significantly better than that in the 24(-) group (p = 0.032). In the 24(+) group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+) group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. CONCLUSIONS: The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00995358.