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Abstract Background First‐line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab‐containing regimens in many countries. We report longer‐term follow‐up data. Methods This open‐label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression‐free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD‐L1) expression of ≥1% and then in the overall population. Results A total of 970 patients were randomly assigned. After 29 months of minimum follow‐up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46–0.76]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65–0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48–0.80]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65–0.92]). In patients with tumor cell PD‐L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51–0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79–1.36]). Among all treated patients (n = 936), Grade 3–4 treatment‐related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. Conclusions Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow‐up, further supporting use as first‐line standard treatment options for patients with advanced ESCC.

Abstract The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol‐voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol‐voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC.

Abstract Background Although immune checkpoint inhibitors (ICI) targeting for PD-1 axis is a promising approach for advanced gastric cancer (GC) patients, the response rate is still limited. Induction of synergistic effect of irradiation with ICI targeting for the PD-1 axis can be an attractive strategy. The aim of this study was to assess the effect of the combination of irradiation with anti-PD-1 therapy for advanced GC. Methods We conducted a single-arm, phase I/II trial in GC patients treated with a combination of nivolumab and oligo-fractionated irradiation (22.5 Gy/5 fractions/5 days) (NCT03453164). Eligible patients (n = 40) had unresectable advanced or recurrent GC which progressed after primary and secondary chemotherapy with more than one lesion. The primary endpoint is the disease control rate (DCR) of non-irradiated target lesions and the secondary endpoints are the median survival time (MST), safety, and DCR of irradiated lesions. Results We observe that the DCR for the non-irradiated target as the abscopal effect is 22.5% (90% confidence interval (CI), 12.3–36.0), and the DCR for the irradiated lesion is 40.0% (90% CI, 26.9–54.2). The median survival time is 230 days (95% CI, 157–330), and grade 3 and higher adverse events (AEs) are observed in 16 patients (39 %) with no obvious additional AEs when adding irradiation. Conclusions The present study suggests that the combination of nivolumab with oligo-fractionated irradiation has the potential to induce a promising anti-tumor effect for advanced GC.

Background Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown.Methods Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor β-chain (TCRβ), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB).Results Although most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRβ clonality (inverted Pielou’s evenness) increased and TCRβ diversity (Pielou’s evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023).Conclusion Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.

Background and Aims: Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. Methods: This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. Results: LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). Conclusion: Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

There are few reports of conversion surgery (CS) after nivolumab monotherapy because it is considered as a third-line standard chemotherapy for unresectable or recurrent gastric cancer. Here, we report a rare case of stage IV gastric cancer effectively treated with CS after nivolumab monotherapy as a third-line chemotherapy. A 73-year-old man was referred to our hospital with loss of appetite and abdominal discomfort. Stage IV gastric cancer with liver metastasis was diagnosed via upper gastrointestinal endoscopy and CT. Twelve courses of capecitabine, cisplatin, and trastuzumab were administered as the first-line treatment, 25 courses of paclitaxel plus ramucirumab as the second-line treatment, and 31 courses of nivolumab monotherapy as the third-line treatment. After 31 courses of nivolumab monotherapy, CT showed that the primary tumor shrank with no liver metastasis or ascites. Diagnostic laparoscopy was performed with no peritoneal dissemination (P0), and the peritoneal lavage cytology was negative (CY0). CS was performed with total gastrectomy and D2 lymph node dissection (R0 resection). The pathological diagnosis was U, Ant-Less, Type 2, 70 × 63 mm, poorly differentiated adenocarcinoma (ypT3N0M0 ypStage IIA). R0 resection was performed, and the histological response was grade 1a. The patient did not show recurrence for 9 months after CS.

Abstract Background Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD). Methods Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients. Results A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors. Conclusions The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.

Peritoneal metastasis (PM) is one of the most frequent forms of gastric cancer recurrence. In this study, we aimed to use computed tomography (CT) colonography (CTC) to detect signs of PM earlier in patients in whom PM was suspected but not yet diagnosed. CTC was used to evaluate patients with clinical symptoms or general CT findings that were suspicious but not sufficient to confirm PM. In total, 18 patients with suspected PM were enrolled. Ten patients (55.6%) had PM on CTC. Abnormal colonic deformities were identified at locations other than those of the lesions detected by general CT in seven patients. The sensitivity and specificity of CTC for the detection of PM were 83.3% and 100%, respectively. The median overall survival after CTC was 201 days in the CTC-positive group, which was significantly shorter than that in the CTC-negative group (945 days, p = 0.01). In the multivariate analysis, a positive CTC finding was the only factor independently associated with survival (p = 0.005). According to our experience with 18 patients, CTC can be an alternative to conventional imaging for early detection of PM. Further prospective studies with larger sample sizes are warranted to confirm and validate these findings. University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000044167.

Background The effects of sleep quality on the risk of developing non-alcoholic fatty liver disease (NAFLD) remain uncertain. The purpose of this study was to clarify the association between sleep quality and NAFLD.Methods The data of 4828 participants who underwent health check-ups at four hospitals were analysed. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI), which comprised seven elements scored from 0 to 3. The global PSQI score and the score for each element were compared between NAFLD and non-NAFLD groups separately by sex. Logistic regression analysis was performed to determine the association between NAFLD and each PSQI score.Results In both men and women, the mean PSQI score for sleep medication use was significantly higher in non-NAFLD than in NAFLD. With regard to sleep medication use in men, the OR (95% CI) for NAFLD was lower with a score of 3 (OR 0.60, 95% CI 0.38–0.95) than with a score of 0 on multivariate logistic regression analysis adjusted for age, smoking habits and physical activity. The OR for NAFLD based on daytime dysfunction was also higher with a score of 3 than with a score of 0 in both men (OR 2.82, 95% CI 1.39–5.75) and women (OR 2.08, 95% CI 1.10–3.92). After adjustment for body mass index, the sleep latency scores in men and daytime dysfunction in women were associated with NAFLD.Conclusion Sleep quality was associated with NAFLD, and there were sex differences.

Summary: Background: Body weight loss (BWL) is frequently observed in gastric cancer patients who undergo gastrectomy for gastric cancer. The risk factors for severe BWL after gastrectomy remain unclear. Methods: The present study retrospectively examined patients who underwent curative gastrectomy for gastric cancer between January 2012 and June 2014 at Kanagawa Cancer Center. All patients received perioperative care based on the enhanced recovery after surgery protocol. The %BWL value was calculated based on the percentage of body weight at 1 month after surgery in comparison to the preoperative body weight. Severe BWL was defined as %BWL > 10%. The risk factors for severe BWL were determined by both univariate and multivariate logistic regression analyses. Results: There were 278 patients examined. The median age of the patients was 68 years. The operative procedures included total gastrectomy [n=97; open (n=61) and laparoscopic {n=36)] and distal gastrectomy (n=181). Surgical complications of grade ≥ 2 (as defined by the Clavien–Dindo classification) were observed in 37 patients, these included: pancreatic fistula (n=9), anastomotic leakage (n=5), and abdominal abscess (n=3). There were no cases of surgery-associated mortality. Both univariate and multivariate logistic analyses demonstrated that surgical complications, and total gastrectomy were significant risk factors for severe BWL. Conclusions: Surgical complications and total gastrectomy were identified as being significant risk factors for severe BWL in the 1st month after gastrectomy. To maintain body weight after gastrectomy, physicians should pay careful attention to patients who undergo total gastrectomy and those who develop surgical complications. : Synopsis: This report demonstrates for the first time that the type of gastrectomy and surgical complications were significant independent risk factors for severe body weight loss in patients who received perioperative care using an enhanced recovery after surgery program after gastrectomy. Keywords: body weight loss, gastrectomy, gastric cancer

Abstract Background Serum C-reactive protein (CRP) level can be an indicator of the early stage of infectious complications. However, its utility in advanced esophageal cancer patients who receive radical esophagectomy with two- or three-field lymph node dissection with perioperative steroid therapy and enhanced recovery after surgery (ERAS) care is unclear. Methods The present study retrospectively examined 117 consecutive esophageal cancer patients who received neoadjuvant chemotherapy followed by radical esophagectomy. All patients received perioperative steroid therapy and ERAS care. The utility of the CRP value in the early detection of serious infectious complications (SICs) was evaluated based on the area under the receiver operating characteristic curve (AUC). Univariate and multivariate logistic regression analyses were performed to identify the risk factors for SICs. Results SICs were observed in 20 patients (17.1%). The CRP level on postoperative day (POD) 4 had superior diagnostic accuracy for SICs (AUC 0.778). The cut-off value for CRP was determined to be 4.0 mg/dl. A multivariate analysis identified CRP ≥ 4.0 mg/dl on POD 4 (odds ratio, 18.600; 95% confidence interval [CI], 4.610–75.200) and three-field lymph node dissection (odds ratio, 7.950; 95% CI, 1.900–33.400) as independent predictive factors. Conclusions CRP value on POD 4 may be useful for predicting SICs in esophageal cancer patients who receive radical esophagectomy with perioperative steroid therapy and ERAS care. This result may encourage the performance of imaging studies to detect the focus and thereby lead to the early medical and/or surgical intervention to improve short-term outcomes.

Creep damage preferentially extends at a stress concentration portion in components such as steam turbines and boilers. Therefore, in order to maintain reliable operation of these components, it is necessary to clarify the relationship between the creep damage extension process and the stress states in the stress concentration portion. In this study, creep tests using four kinds of round notch bar specimens with different notch radius (notch tip radius 0.1mm(R0.1), 0.5mm(R0.5), 2.0mm(R2.0) and 4.0mm(R4.0)) on a Mod. 9Cr-1Mo steel have been conducted to clarify influence of stress conditions on creep damage extension process and rupture time. Creep rupture time increases with increasing elastic stress concentration factor under the same nominal stress. Distribution pattern of measured void number density from notch root surface to specimen center was different depending on the notch radius. The void number density around the notch root surface is higher than that around the specimen center in R0.1 and R0.5, while the void number density increases toward the specimen center in R2.0 and R4.0. Finite element creep analyses of the round notch bar specimens indicate that triaxial tensile stress yields on the notch root section with different distribution of the triaxiality factor depending on the notch radius. The distribution of the triaxiality factor of each round notch bar specimen corresponded to the distribution of the void number density. Rupture time of the round notch bar specimens can not be predicted by applying the representative stress such as the maximum stress and Mises equivalent stress. A new rupture time prediction procedure using an area average creep damage evaluation method, in which total creep damage accumulated on the notch root section of the specimen was divided by area of the section, was proposed. Rupture times of the notch specimens were accurately predicted by the proposed procedure without showing any dependency of the elastic stress concentration factor.

Creep-fatigue damage preferentially exceeds at stress concentration portions in high temperature components such as steam turbine rotors during cyclic start up- shut down operation. Therefore development of an accurate crack initiation life assessment method under creep-fatigue conditions at the stress concentration portions under multiaxial stress states is necessary to maintain reliable operation. In this study, creep-fatigue tests using circular notch bar specimens on a CrMoV forging steel have been conducted to clarify effect of stress conditions on failure life. Three dimensional finite element elastic-plastic creep analyses have been performed. Fatigue lives of the notch specimens are about 10 times shorter than those of plain specimens, and the lives of the notch specimen under the creep-fatigue condition are about 1/5 times of the plain specimen. From observation of notch root of the creep-damage specimens, it suggested that most of the creep-fatigue life was occupied by crack propagation up to 1mm from the notch surface. It was also indicated that triaxial tension stress state occurs around the notch root surface and stresses decrease with distance from the notch root surface by the inelastic analysis. A new creep-fatigue life evaluation procedure of notch specimens, in which concept of a damage evaluation area was introduced, was proposed by considering damage extension and the stress component distribution around the notch root. As a result, creep-fatigue lives of the notch specimens were accurately predicted by coupling of the new procedure and the nonlinear damage accumulation rule.

Creep damage preferentially extends at a stress concentration portion in high temperature components such as steam turbine rotors. Therefore development of an accurate damage assessment method for creep damage process at the stress concentration portion under multiaxial stress states is necessary to maintain reliable operation. In this study, creep tests using a plain specimen and two kinds of round bar notch specimens with different notch radius on a CrMoV forging steel have been conducted to clarify effect of stress conditions on creep damage extension process. Three dimensional finite element creep analyses have been performed to discuss relation between the creep damage and stress conditions. Creep rupture time of the plain specimen is shorter than those of the notch specimens. Creep rupture time of the notch specimen with lower stress concentrate factor is longer than that with higher stress concentration factor. In the notch specimens, the maximum stresses occur at notch root at initial loading and portions of the maximum stresses gradually change to inside of the specimens with time due to stress redistribution. Triaxial tensile stress yields at the notch root sections with different distributions of the triaxiality factor depending on the notch radius. Void number densities at the maximum stress portion in the notch specimens are ten times larger than that in the plain specimen. The void growth simulation method developed previously was applied to predict the void number density under multiaxial stress states in the notch specimens. Distributions of the void number density from notch root to center of the specimen both in the notch specimens were quantitatively predicted by the void growth simulation method. An equation, which predicts change of void number density with time under a certain maximum stress and a triaxiality factor, was derived based on the void growth simulation under different multiaxial stress states.

Mod.9Cr-1Mo steel(P91) is widely used for high temperature pipes in ultra-super-critical thermal power plants. However it was recently reported that the creep damage was detected at heat affected zone(HAZ) in welded joints of the pipes so-called the “Type IV” damage. So far, study on damage and life assessment methods for the welded joints of the P91 steel were concentrated on longitudinal welded pipes. On the other hand, circumferential welded joints are also susceptible to yield creep damage because of increase of axial stress by thermal stress superimposed with pipe weight itself. In this study, the effect of additional axial stress to the axial stress by the internal pressure on damage and rupture property is discussed based on internal pressure creep tests adding different levels of the axial stress using the P91 circumferential welded pipe. Rupture time of the circumferential welded pipe decreases with increasing additional axial stress level. The longitudinal cracking in the weld metal was observed in the specimen tested under lower additional stress level, and the “Type IV” cracking was observed in those under higher additional stress levels. The stress analysis results indicate that axial stress in the HAZ increases as increasing the additional stress level causing the “Type IV” cracking at a certain value of ratio of the total axial stress to the circumferential stress. Under the test condition where the “Type IV” cracking occurs is significantly shorter than predicted rupture time based on internal creep rupture data of the longitudinal welded pipes. The limited creep strain is introduced to predict rupture time of the circumferential welded pipe by considering the effect of stress multiaxiality. Eventually, times to rupture caused by the “Type IV” cracking of both the longitudinal and the circumferential welded pipes were accurately predicted by the limited creep strain concept.

Background/Aim: This study aimed to investigate the differences in the postoperative dietary intake (DI) loss between men and women after radical resection for early gastric cancer (GC), and to identify effective nutritional support for both sexes. Patients and Methods: This prospective, observational study enrolled patients who underwent gastrectomy for GC. DI was assessed using the food frequency questionnaire containing 82 food items (FFQW82) during nutritional counseling before surgery and one and three months postoperatively. Results: The median preoperative DI of all participants was 1,856.3 kcal/day, and DI at 1 and 3 months were 1,532.5 kcal/day and 1,637 kcal/day, respectively. The median preoperative DI was 1805 kcal/day (1,300-2,330 kcal/day) and 1481 kcal/day (1,126-1,957 kcal/day) in men and women, respectively (p<0.0001). The median DI at 1 month was 1627 (1,101-2,195) kcal/day and 1,308 (986-1,915) kcal/day in men and women, respectively (p<0.0001). At 3 months postoperatively, the median DI was 1737 (1,130-2,443) kcal/day in men and 1428 (816-2,005) kcal/day in women (p<0.0001). However, there was no significant difference in the DI loss rate at 1 month (median: -9.7% vs. -9.3%, p=0.765) and 3 months (median: -3.5% vs. -4.8%, p=0.137) between men and women. Conclusion: Although the DI loss rate in men and women after gastrectomy for GC was almost similar, the postoperative DI and DI loss differed significantly. Therefore, differences in DI loss after gastrectomy between men and women should be considered while assessing the efficacy of additional nutritional support such as oral nutritional supplements after gastrectomy. [ABSTRACT FROM AUTHOR]

Background/Aim: Recently, preoperative inflammatory, immune, and nutritional statuses have attracted attention as prognostic factors in post-curative gastrectomy patients with gastric cancer (GC). The usefulness of the Creactive protein-albumin-lymphocyte (CALLY) index as a prognostic factor in patients with various cancers, has been reported. However, reports on the clinical significance of the CALLY index in patients with GC after gastrectomy remain inadequate. In this prospective study, we focused on the preoperative CALLY index and investigated its usefulness as a prognostic factor in patients with GC. Patients and Methods: This study included 459 patients who underwent gastrectomy for GC between December 2013 and November 2017 at Kanagawa Cancer Center, Kanagawa, Japan. The preoperative CALLY index was calculated based on the preoperative blood test data. Patients were divided into high- and low-CALLY groups. The associations of the preoperative CALLY scores with clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS) after gastrectomy for GC were evaluated. Results: The low-CALLY group was significantly older, had higher venous invasion, and a more progressive pStage than did the high-CALLY group. OS and RFS after gastrectomy in the low-CALLY group were significantly worse than those in the high-CALLY group (77.9% vs. 88.9%; p<0.001 and 73.8% vs. 87.1%; p<0.001, respectively). In the multivariate analysis, a low CALLY score was an independent prognostic factor of worse OS and RFS. Conclusion: Preoperative CALLY levels may be a useful prognostic predictor in patients with GC after curative gastrectomy. [ABSTRACT FROM AUTHOR]

Background/Aim: Radical resection after preoperative adjuvant chemotherapy (NAC) is a standard treatment for patients with locally advanced esophageal squamous cell carcinoma (LAESCC), but its outcome remains unsatisfactory. In order to develop a personalized treatment program for LAES, we herein compared the survival prediction utility of five pre-NAC nutritional, inflammatory, and immune indexes in patients with LAESCC. Patients and Methods: We evaluated the survival of 203 patients with LAESCC who underwent radical resection after NAC from January 2011 to September 2019 for the following representative pre-NAC nutritional, inflammatory, and immune indices: modified Glasgow Prognostic Score, Prognostic Nutritional Index, C-reactive protein/albumin ratio, serum neutrophil/lymphocyte ratio, and Geriatric Nutrition Risk Index (GNRI) were evaluated for their impact on survival. Results: Of the five indices, GNRI was the best predictor of survival as determined by the area under the curve (p<0.05). When patients were divided into three groups according to the nutritional risk assessment of Bouillanne et al. using the pre-NAC GNRI, the 5-year overall survival (OS) and recurrence-free survival (RFS) were significantly stratified (p<0.001). On multivariate analysis, the GNRI independently identified a poor OS group [group 1: hazard ratio (HR)=2.598, p=0.002; group 2: HR=6.257, p<0.001] and a high recurrence risk group (group 1: HR=1.967, p=0.016; group 2: HR=4.467, p<0.001). Conclusion: In patients with LAESCC, GNRI may be the most accurate, reliable, and useful prognostic factor among the five major systemic inflammatory and nutritional indices. [ABSTRACT FROM AUTHOR]

Background/Aim: Based on gastric shape, patients with gastric cancer can be divided into storage (hook-shaped and ptotic stomach) and reverse outflow (steerhorn and cascade stomach) groups. In patients with gastric cancer, postoperative loss of lean body mass (LBM) is associated with a poor prognosis. This study investigated the influence of preoperative gastric shape on LBM loss 1 month after curative distal gastrectomy. Patients and Methods: Between May 2011 and May 2019, we enrolled 487 patients with pathological stage IA/IB/IIA gastric cancer who underwent curative distal gastrectomy and did not receive adjuvant chemotherapy. Patients were divided into storage (n=370) and outflow (n=117) groups according to whether barium was stored in the stomach during the preoperative fluoroscopic examination. Clinicopathological features, LBM 1 month after gastrectomy, and predictors of postoperative LBM loss were compared between the groups using multivariable logistic regression. Results: The incidence of >5% LBM loss and >7.5% body weight loss 1 month postoperatively were significantly higher in the storage group than in the outflow group (p=0.003 and p=0.009, respectively). Multivariable analysis revealed that gastric shape [odds ratio (OR)=3.30, 95% confidence interval (CI)=1.95-5.59, p<0.001], male sex (OR=3.20, 95% CI=2.07-4.96, p<0.001), and Roux-en-Y reconstruction (OR=1.69, 95% CI=1.08-2.64, p=0.02) were independent predictors of LBM loss. Postoperative dietary problems, especially dumping syndrome, diarrhea, and reflux were more common in the storage group (p<0.001). Conclusion: Gastric shape may be a useful independent predictor of postoperative LBM loss in patients with gastric cancer undergoing distal gastrectomy. [ABSTRACT FROM AUTHOR]

Background/Aim: Radical esophagectomy after preoperative neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, careful treatment selection is required when considering organ function in elderly patients. Prealbumin, a rapid turnover protein, is a short-term dynamic nutritional index, and its relationship with long-term postoperative survival in various cancers has been previously reported. However, the association between serum prealbumin level before NAC and survival in elderly patients remains unclear. This study investigated the clinical significance of prealbumin level measurement before NAC in elderly patients with locally advanced ESCC who underwent surgery after NAC. Patients and Methods: Eighty patients aged =65 years diagnosed with cStage II/III ESCC and undergoing radical esophagectomy after cisplatin and 5-fluorouracil therapy as NAC, were included. The cutoff value of the serum prealbumin level before NAC was set at 18.2 mg/dl using receiver operating characteristic curve analysis, and postoperative complications, recurrence, and overall survival were compared between the low and high prealbumin groups. Results: There were no differences in patient background, clinicopathological characteristics, postoperative complications, or recurrence-free survival between the two groups. Overall survival (OS) was significantly worse in the low prealbumin group than in the high prealbumin group (5-year survival, 33.3% vs. 67.0%; p=0.0341). Furthermore, on univariate and multivariate analysis, low prealbumin level was an independent poor OS factor (p=0.036). Conclusion: In elderly patients with locally advanced ESCC, serum prealbumin level before NAC may be a useful prognostic factor and may be important in selecting a treatment strategy that considers individual organ function. [ABSTRACT FROM AUTHOR]

Background/Aim: A new modified nutritional risk index (mNRI), calculated using serum albumin (g/l)+body mass index (BMI) [weight (kg_/height² (m²)], is a good predictor of postoperative complications and cancer survival. However, no study has used this index in patients with gastric cancer (GC). Therefore, we aimed to investigate the clinical significance of the preoperative mNRI values in patients with GC who underwent curative resection. Patients and Methods: We examined 449 patients who underwent curative resection for GC at Kanagawa Cancer Center between 2013 and 2017. The mNRI cutoff value obtained using a receiver operating characteristic analysis was 23.31. Patients were divided into high and low mNRI groups according to the cutoff value, and the clinicopathological characteristics and outcomes were compared between the two groups. Results: In terms of clinicopathological characteristics, the high mNRI group had a higher proportion of men, higher BMI, and a higher proportion of patients with American Society of Anesthesiologists physical status class 2/3 compared with the low mNRI group; the low mNRI group had significantly worse 5-year recurrence-free survival (RFS) and overall survival (OS) than the high mNRI group (OS, p=0.005) (OS, p=0.006; RFS, p=0.018) did. In the multivariate analysis, a low mNRI was an independent predictor of OS (p=0.006) and RFS (p=0.013). Conclusion: Preoperative mNRI may be a useful recurrence and prognostic biomarker in patients with GC who have undergone curative resection. [ABSTRACT FROM AUTHOR]

Background/Aim: Clinical staging in the eighth edition of the Union for International Cancer Control TNM classification (TNM8) is reported to predict the prognosis of patients with gastric cancer. However, there have been no reports on using the TNM8 for prognostic stratification of patients with adenocarcinoma of the esophagogastric junction (AEG). This study aimed to investigate whether it was possible to stratify the prognosis of patients who underwent curative surgery for Siewert type II/III AEG according to the TNM8 clinical stage (cStage). Patients and Methods: This study included patients with Siewert type II/III AEG who underwent curative surgery between 2000 and 2019 at Kanagawa Cancer Center. Those who received neoadjuvant chemotherapy were excluded. We investigated the survival of patients with AEG of each TNM8 cStage. Results: This study included 138 patients, among whom 102 (74%) had Siewert type II and 36 (26%) had Siewert type III AEG. A total of 50, 38, 43, and seven patients were classified with cStage I, II, III, and IV, respectively. The median duration of follow-up of the survivors was 54.7 months. The 5-year overall survival rate of the entire cohort was 65.8%, whereas for patients with cStage I, II, III and IV was 81.6%, 69.0%, 54.3% and 14.3%, respectively. The hazard ratio with reference to cStage I was 1.83, 3.07, and 8.13 for cStage I, III, and IV, respectively, increasing in a stepwise manner. Conclusion: TNM8 Clinical staging is able to stratify the prognosis of patients with Siewert type II/III AEG. [ABSTRACT FROM AUTHOR]

Background/Aim: To clarify the clinical significance of measuring the mean corpuscular volume (MCV) of red blood cells before applying neoadjuvant chemotherapy (NAC) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who will receive NAC followed by curative resection. Patients and Methods: We retrospectively investigated 169 eligible patients at the Kanagawa Cancer Center between 2011-2018. The patients were divided into high and low-MCV groups. The cutoff value of the MCV was determined by the maximum χ2 statistic value on the log-rank test and was set at 92.8 fl. Clinicopathological features and outcomes were compared between the two groups. Results: There was no significant association between the MCV and clinicopathological features. Both five-year recurrence-free survival (RFS) and overall survival (OS) in the high-MCV group were significantly poorer than those in the low-MCV group (RFS, p=0.026; OS, p=0.006). On multivariate analysis, a high-MCV was an independent predictive survival factor for RFS [hazard ratio (HR)=1.728; 95% confidence interval (CI)=1.033-2.891; p=0.037] and OS (HR=1.836; 95%CI=1.002-3.365; p=0.049). Conclusion: Measurement of the MCV before NAC may be a useful prognostic biomarker in patients with locally advanced ESCC who will receive NAC followed by curative resection. [ABSTRACT FROM AUTHOR]

Background: We investigated the influence of the preoperative Controlling Nutritional Status (CONUT) score on survival and recurrence of gastric cancer in patients after curative treatment. Patients and Methods: This study included 331 patients who underwent curative surgery followed by adjuvant treatment for gastric cancer between 2013 and 2017. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: Based on the 1-, 3- and 5-year survival rates, a CONUT score of 2 was regarded as the optimal cut-off value for classification. The 3- and 5-year OS rates were 93.6% and 88.6%, respectively in the low-CONUT group, and 82.7% and 73.6% in high-CONUT group (p=0.022). The 3- and 5- year RFS rates were 78.8% and 68.7%, respectively, in the low-CONUT group, and 89.3% and 86.6%, respectively, in the high-CONUT group (p=0.05). A multivariate analysis showed that the CONUT score was a significant independent predictive factor for OS and RFS. Conclusion: The CONUT score was a predictive factor for survival in patients who underwent curative treatment for gastric cancer. It is necessary to develop an effective plan for perioperative care and surgical strategy according to the CONUT score. [ABSTRACT FROM AUTHOR]

Background/Aim: We investigated the association of the preoperative lymphocyte-to-C-reactive-protein ratio (LCR) with gastric cancer survival and recurrence after curative treatment. Patients and Methods: This study included 480 patients who underwent curative surgery followed by adjuvant treatment for gastric cancer between 2013 and 2017. The prognostic factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: A LCR of 7,000 was regarded as the optimal critical point of classification, considering the 1-, 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 84.4% and 73.9% in the low-LCR group, respectively, and 92.4% and 87.0% in the high- LCR group, respectively, and were statistically significantly different. The RFS rates at 3 and 5 years after surgery were 78.8% and 68.7% in the low-LCR group, respectively, and 89.3% and 86.6% in the high-LCR group, respectively, with a statistically significant difference. A multivariate analysis showed that the LCR was a significant independent prognostic factor for both OS and RFS. Conclusion: The LCR was a significant prognostic factor for survival in patients who underwent curative treatment for gastric cancer. [ABSTRACT FROM AUTHOR]

Background: We investigated the impact of the pre-surgical C-reactive protein-to-albumin ratio (CAR) on survival and recurrence after curative treatment for gastric cancer. Patients and Methods: This study included 481 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The risk factors for overall (OS) and recurrence-free (RFS) survival were identified. Results: A CAR of 0.05 was regarded as the optimal critical point of classification considering the 3- and 5-year survival rates and patients were divided according to their CAR. The OS rates at 3 and 5 years after surgery were significantly higher at 92.5% and 87.9%, respectively, in the low-CAR group compared with 84.9% and 71.9%, respectively, in the high- CAR group. The corresponding RFS rates were 89.1% and 85.5%, and 81.0% and 72.2%, respectively, also a significant difference. A multivariate analysis demonstrated that the CAR was a significant independent risk factor for the OS and marginally significant independent risk factor for the RFS. In addition, the incidences of pancreatic fistula and abdominal abscess were significantly higher and the rate of introduction of adjuvant chemotherapy significantly lower in the high-CAR group. Conclusion: The CAR was a risk factor influencing survival in patients who underwent curative treatment for gastric cancer. An effective perioperative care plan and surgical strategy need to be developed according to the CAR. [ABSTRACT FROM AUTHOR]

Background/Aim: Cancer stem cells (CSCs) are reported to associated with cancer metastasis, relapse, and chemoresistance. This study examined the clinical significance of the expression of two CSC markers, the transporter associated with antigen processing 1 (TAP1) and the Deltalike 4 (DLL4) protein, in patients with locally advanced GC. Patients and Methods: This study was performed using samples obtained from 413 pathological stage II/III GC patients after curative gastrectomy. We examined TAP1 and DLL4 expression using immunohistochemical analysis with tissue microarray and examined the association between TAP1 or DLL4 expression, clinicopathological factors and survival. Results: High TAP1 expression was associated with better overall survival compared to low TAP1 expression (p=0.004). Furthermore, in multivariate analysis, high TAP1 expression was defined as a predictive factor for good survival. There was no significant difference between DLL4 expression and clinicopathological features and overall survival. Conclusion: TAP1 expression may be a useful prognostic marker in patients with locally advanced GC. [ABSTRACT FROM AUTHOR]

Background/Aim: The changes of dietary intake (DI) after gastrectomy have not been objectively reported. It has not been clear how much DI loss is experienced after total gastrectomy (TG) in comparison to after distal gastrectomy (DG). This study quantified the changes of DI after gastrectomy, and clarified how much DI loss is experienced after TG. Patients and Methods: This was a prospective observational study. Patients who underwent gastrectomy for gastric cancer were enrolled. The DI loss was evaluated at 1 and 3 months postoperatively. Results: Thirty-three patients underwent TG, and 117 patients underwent DG. The median %DI loss of the overall study population at 1 and 3 months after surgery was -9.3% and -3.6%. The median %DI loss at 1 and 3 months postoperatively was -15.6% and -5.3% in TG group, -8.9% and -3.3% in DG group (p=0.10 and 0.49, respectively). Conclusion: The patients experienced DI loss of approximately 10% at 1 month after gastrectomy. Patients who received TG tended to show a greater %DI loss at 1 month postoperatively. [ABSTRACT FROM AUTHOR]

Background/Aim: We hypothesised that the prognostic nutrition index (PNI) is useful for evaluating host immunity and response to immune checkpoint inhibitors. We investigated the effect of PNI on nivolumab monotherapy efficacy in advanced or recurrent gastric cancer (GC) or gastro-oesophageal junction cancer (GOC) patients. Patients and Methods: We retrospectively examined 110 patients, divided them into a high-PNI group and a low-PNI group, and compared treatment efficacy, adverse events (AEs), and survival between the groups. Results: Median overall survival (OS) was significantly longer in the high-PNI group than in the low-PNI group (205 vs. 109 days; p<0.001). Multivariate analysis revealed that low PNI was an independent risk factor for OS (hazard ratio=2.398; 95% confidence interval=1.384-4.154; p=0.002). The overall response rate and frequency of AEs were not significantly different between the groups. Conclusion: PNI could be a useful prognostic factor in GC or GOC patients undergoing nivolumab monotherapy. [ABSTRACT FROM AUTHOR]