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Abstract Background Esophageal cancer is one of the most common types of cancer in Japan. Herein, we report the efficacy and safety of E7389-LF plus the immune checkpoint inhibitor, nivolumab, from the esophageal cancer cohort of the phase 2 part of Study 120. Methods Eligible patients received E7389-LF 2.1 mg/m2 plus nivolumab 360 mg intravenously Q3W. The primary objective was to evaluate the objective response rate (ORR); other objectives included safety, progression-free survival (PFS), and overall survival (OS). Results Of the 35 Japanese patients enrolled, 7 (20.0%) had a partial response as their best overall response, and 14 (40.0%) had stable disease. The ORR was 20.0% (95% CI 8.4–36.9). The duration of response was 5.6 months (95% CI 1.7–not estimable [NE]). The median PFS was 2.81 months (95% CI 1.31–4.17). The median OS was not reached (95% CI 6.54 months–NE). The most common treatment-emergent adverse events were neutropenia (65.7%), pyrexia (60.0%), and leukopenia (57.1%). Select plasma endothelial cell markers levels increased from day 1 of cycle 1 and changes were pronounced between days 8–15 of each cycle. Conclusions E7389-LF plus nivolumab showed antitumor activity in patients with unresectable and pretreated esophageal cancer and should be evaluated further in a broader population. Clinical Trial Registration NCT04078295.

Abstract Background Intraductal oncocytic papillary neoplasm (IOPN), previously classified as a subtype of intraductal papillary mucinous neoplasm (IPMN), has been described as an independent disease by the WHO since 2019. IOPN is a rare tumor, with few reported cases. Herein, we report a case of resected non-invasive IOPN that formed a lesion protruding toward the duodenum from the accessory papilla. Case presentation An 80-year-old woman was referred to our hospital because of a giant mass in the pancreatic head detected on abdominal contrast-enhanced computed tomography (CT) performed for a close examination of a mass in the right breast. CT revealed a 90-mm-sized tumor with a mixture of solid and cystic components, with contrast enhancement in the pancreatic head, and a dilated main pancreatic duct. Esophagogastroduodenoscopy revealed a semi-circumferential papillary tumor protruding toward the duodenal lumen, which did not protrude from the papilla of Vater. Transpapillary biopsy led to a preoperative diagnosis of IPMN with an associated invasive carcinoma. As there were no distant metastasis, open subtotal stomach-preserving pancreaticoduodenectomy was performed. Analysis of the surgical specimen and histopathological examination revealed that the tumor was an IOPN that protruded toward the duodenal mucosa from the accessory papilla while replacing the duodenal mucosa with no obvious stromal invasion. Conclusion IOPN is a rare and poorly recognized tumor with few reported cases. There have been no reports describing IOPN forming a protruding lesion toward the duodenum from the accessory papilla. Therefore, further accumulation of cases such as this one is important to advance the study of IOPN.

Abstract Aim While surgery is essential for curative treatment of gastric cancer with oligometastasis, its target, timing, and possibility of combination with other treatments are unclear. We herein investigated the clinical course and long‐term outcomes of gastric cancer with oligometastasis in the real world setting to determine the optimal therapeutic strategy. Methods The present study retrospectively analyzed 992 patients who received any treatment for metastatic or recurrent gastric adenocarcinoma at Tokyo Metropolitan Komagome Hospital between 2007 and 2019. Oligometastasis was defined as any one of the following: liver metastases (HEP)

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.

Abstract Aim Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions. Subjects and method In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C > A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data. Results The most frequent base substitutions were G:C > A:T transition in all the areas investigated. The G:C > A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C > A:T transition in CpG sites and A:T > G:C mutation was more prevalent in Asian countries. Conclusion The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Abstract Biomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy (sequential paclitaxel) were investigated using tissue samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC resection samples. The expression of 105 genes was quantified using real-time PCR. Genes predicting the benefit of sequential paclitaxel on overall survival, disease-free survival, and cumulative incidence of relapse were identified based on the ranking of p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy groups. Low VSNL1 and CD44 expression predicted the benefit of sequential paclitaxel treatment for all three endpoints. Patients with combined low expression of both genes benefitted most from sequential paclitaxel therapy (hazard ratio = 0.48 [95% confidence interval, 0.30–0.78]; p

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 The biological complexity reflected in histology images requires advanced approaches for unbiased prognostication. Machine learning and particularly deep learning methods are increasingly applied in the field of digital pathology. In this study, we propose new ways to predict risk for cancer‐specific death from digital images of immunohistochemically (IHC) stained tissue microarrays (TMAs). Specifically, we evaluated a cohort of 248 gastric cancer patients using convolutional neural networks (CNNs) in an end‐to‐end weakly supervised scheme independent of subjective pathologist input. To account for the time‐to‐event characteristic of the outcome data, we developed new survival models to guide the network training. In addition to the standard H&E staining, we investigated the prognostic value of a panel of immune cell markers (CD8, CD20, CD68) and a proliferation marker (Ki67). Our CNN‐derived risk scores provided additional prognostic value when compared to the gold standard prognostic tool TNM stage. The CNN‐derived risk scores were also shown to be superior when systematically compared to cell density measurements or a CNN score derived from binary 5‐year survival classification, which ignores time‐to‐event. To better understand the underlying biological mechanisms, we qualitatively investigated risk heat maps for each marker which visualised the network output. We identified patterns of biological interest that were related to low risk of cancer‐specific death such as the presence of B‐cell predominated clusters and Ki67 positive sub‐regions and showed that the corresponding risk scores had prognostic value in multivariate Cox regression analyses (Ki67&CD20 risks: hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.15–1.89, p = 0.002; CD20&CD68 risks: HR = 1.33, 95% CI = 1.07–1.67, p = 0.009). Our study demonstrates the potential additional value that deep learning in combination with a panel of IHC markers can bring to the field of precision oncology.

Abstract Background Neuroendocrine carcinoma (NEC) originating from the extrahepatic bile duct (EHBD) is very rare but is known for its aggressiveness and poor prognosis. We herein report a case of rapidly progressed NEC in the extrahepatic bile duct. Case presentation An 84-year-old man was referred to our facility with obstructive jaundice and abdominal pain. Imaging studies revealed an irregular filling defect in the middle bile duct by endoscopic retrograde cholangiopancreatography and an enhanced wall thickening from the middle to distal portion by enhanced computed tomography. The patient was initially diagnosed with extrahepatic cholangiocarcinoma by a bile duct biopsy and underwent pancreatoduodenectomy with lymph node dissection. The pathological findings showed an NEC with an adenosquamous carcinoma component in the extrahepatic bile duct with lymph node metastases. The patient experienced multiple liver metastases 1 month after surgery and died 3 months after surgery. Due to the rapid progression of his disease, his general condition deteriorated, and he was unable to receive any additional treatments, such as chemotherapy. Conclusion As shown in our case, NEC of the EHBD has an extremely poor prognosis and can sometimes progress rapidly. Multimodality treatment should be considered, even in cases of locoregional disease.

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.

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.

Background: Routine therapy of metabolic bone disorder (MBD) after gastrectomy for gastric cancer has not been established yet. We have reported that administering an active vitamin D3 agent to patients who had undergone gastrectomy for gastric cancer improved MBD. Recently, the usefulness of alendronate, an osteoclast inhibitor, has been reported for MBD. Here we report the effects of alendronate for MBD after gastrectomy for gastric cancer. Methods: Dual energy X-ray absorptiometry was performed consequently in 14 patients, who had been gastrectomized for gastric cancer and survived more than 5 years without recurrence, to evaluate the MBD and compared before and after treatment. The 14 patients were divided into two groups: in group VD3, 1 μg/d of alfacalcidol, an active vitamin D3 agent, was administered; and in group ALN, 5 mg/d or 35 mg/wk of alendronate or both alfacalcidol and alendronate were administered. These drugs had been administered to the patients for > 2 years, and the patients were followed up. Results: After 12 months, dual energy X-ray absorptiometry revealed that bone mineral density and T score were significantly increased in group ALN. Changes in serum bone-specific alkaline phosphatase after 24 months were −9.1 μg/L in the ALN group and 3.75 μg/L in the VD3 group, showing a significant difference (p = 0.02). No serious adverse events were observed in either group. Conclusion: These results showed the usefulness of alendronate and alendronate+activated vitamin D3 combination therapy, suggesting that these treatments might prevent postgastrectomic MBD.

Summary: Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor-infiltrating B and T cells in gastric cancers was carried out to help reveal the architecture of B cell immunity in cancer. Humoral immunity in cancer was shown to involve oligoclonal expansions of tumor-specific and private B cell repertoires. We find that B cell repertoires in cancer are shaped by somatic hypermutation (SHM) either with or without positive selection biases, the latter of which tended to be auto-reactive. Importantly, we identified sulfated glycosaminoglycans (GAGs) as major functional B cell antigens among gastric tumors. Furthermore, natural anti-sulfated GAG antibodies discovered in gastric cancer tissues showed robust growth-suppressive functions against a wide variety of human malignancies of various organs. : Katoh et al. profile immunoglobulin repertoires of tumor-infiltrating B cells, identifying sulfated glycosaminoglycan as a major functional B cell antigen in tumors. Repertoire profiling for tumor-infiltrating B cells may pave the way to the development of therapeutic antibodies. Keywords: repertoire sequence, immunogenetics, tumor immunity, tumor-infiltrating B cell, sulfated glycosaminoglycan, therapeutic antibody, gastric cancer

Background/Aim: Systemic immune-inflammation index (SII) was developed and evaluated for various malignancies. This study evaluated the clinical impact of the SII in patients with gastric cancer (GC) who received curative treatment. Patients and Methods: Patients who underwent curative resection for GC at Yokohama City University between 2005 and 2020 were chosen consecutively based on their medical records. SII was calculated as follows: platelet (cell/mm³ ×10³)× neutrophil (cell/mm³)/lymphocyte (cell/mm³). Three measurements were obtained preoperatively. Results: In total, 258 patients were enrolled in this study. Based on the 3- and 5-year survival rates and previous studies, we set the cutoff value of the SII to 550. The 258 patients were classified into the SII-low (n=152) and SII-high (n=106) groups, respectively. The 3- and 5-year overall survival (OS) rates were 82.6% and 78.7%, respectively, in the SII-low group and 74.5% and 61.9%, respectively, in the SII-high group. There were significant differences between the two groups (p<0.001). In the multivariate analysis of factors associated with OS, the SII was identified as an independent prognostic factor (hazard ratio=1.816; 95% confidence interval=1.075-3.069, p=0.026). Similar results were observed for recurrence-free survival. In addition, the incidence of postoperative surgical complications was 30.9% in the SII-low group and 45.2% in the SII-high group (p=0.019). Conclusion: The SII was an independent prognostic factor for GC. Thus, the SII may be a promising biomarker for the treatment and management of GC. [ABSTRACT FROM AUTHOR]

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: The aim of the present study was to evaluate the clinical impact of the Global Immune-NutritionInformation Index (GINI) in patients with gastric cancer (GC) who received curative treatment and to clarify the potential of the GINI as a biomarker. Patients and Methods: Patients who underwent curative resection for GC at Yokohama City University between 2005 and 2020 were selected based on their medical records. The GINI was calculated as follows: GINI=[C-reactive protein × platelet × monocyte × neutrophil]/[albumin × lymphocyte]. Results: A total of 258 patients were included in this study. Of these, 169 patients were categorized into the GINI-low group and 89 into the GINI-high group using a cut-off value of 1,730. The three- and five-year overall survival (OS) rates were 86.4% and 78.4%, respectively, in the GINI-low group, and 66.4% and 58.3% in the GINI-high group (p<0.001). In a multivariate analysis for OS, the GINI was identified as an independent prognostic factor [hazard ratio (HR)=1.772; 95% confidence interval (CI)=1.053-2.979, p=0.031]. Similar results were observed for RFS. In addition, the GINI affected the perioperative clinical course, including postoperative surgical complications and postoperative adjuvant treatment. Conclusion: The GINI is a promising biomarker for the treatment and management of GC. [ABSTRACT FROM AUTHOR]

Background/Aim: The albumin to fibrinogen ratio (AFR) has been identified as a promising prognostic marker for some malignancies. The aim of the present study was to evaluate the clinical impact of AFR in esophageal cancer patients who received curative resection. Patients and Methods: The present study included 123 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters were compared between patients with high and low AFRs. Results: The overall survival (OS) stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed when using a pretreatment AFR of 1.23. When comparing the patient backgrounds between the high-AFR (AFR ≥12.3) and low- AFR (AFR<12.3) groups, significant differences were noted in the pathological T status. The high-AFR group had significantly higher OS rates at 3 years (70.8%) and 5 years (59.3%) after surgery in comparison to the low-AFR group (46.6% and 37.4%, respectively). Univariate and multivariate analyses for OS showed that the AFR was a significant prognostic factor. In addition, when comparing the site of first recurrence, a marginally significant difference was noted in hematological recurrence. Conclusion: The AFR is a significant risk factor in patients with esophageal cancer, holding promise as a valuable prognostic factor. [ABSTRACT FROM AUTHOR]

Background: We investigated the impact of the prognostic nutritional index (PNI) on esophageal cancer survival and recurrence after curative treatment. Methods: This study included 120 patients who underwent curative surgery followed by the adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: The PNI of 49 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rate. The OS rates at three and five years after surgery were 47.4% and 36.0% in the PNI low group, respectively, and 62.5% and 56.5% in the PNI high group, which amounted to a statistically significant difference (P = 0.020). The RFS rates at three and five years after surgery were 31.0% and 24.8% in the PNI low group, respectively, and 50.9% and 42.8% in the PNI high group, which amounted to a statistically significant difference (P = 0.020). A multivariate analysis demonstrated that the PNI was a significant independent risk factor for the OS and a marginally significant independent risk factor forRFS. Conclusion: The PNI was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the PNI. [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: The albumin-globulin ratio (AGR) is a useful biomarker for predicting postoperative complications and a poor prognosis in patients with various types of cancer and can be evaluated without invasive testing or surgery. In this study, we aimed to evaluate the usefulness of the AGR in predicting the short- and long-term prognoses of patients with gastric cancer who underwent radical resection at our institution. Patients and Methods: This study is a retrospective cohort analysis in which eligible patients were selected from the medical records of patients who underwent radical resection for gastric cancer at Yokohama City University from 2000 to 2020 and their medical records were reviewed. A total of 240 patients with gastric cancer were classified into high-AGR (>1.57) and low-AGR (=1.57) groups and their overall survival (OS), recurrence-free survival (RFS), and postoperative complication rates were compared. Results: Of the total 240 patients, 87 were classified into the high AGR group and 153 were classified into the low AGR group; the incidence of postoperative complications in the two groups did not differ to a statistically significant extent (34.4% vs. 39.2%, p=0.491). The long-term findings showed that the 5-year OS and RFS rates were significantly better in the high AGR group [84.0% vs. 64.8% (p=0.005), 80.0% vs. 61.9% (p=0.015), respectively]. Conclusion: Preoperative low AGR is a risk factor for OS and DFS in patients with gastric cancer who undergo surgery. The AGR may be a useful biomarker that can be applied as a prognostic indicator for patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background/Aim: This study aimed to evaluate the clinical impact of the Naples Prognostic Score (NPS) in patients with gastric cancer and to clarify the potential of the NPS as a nutritional and inflammation evaluation system. Patients and Methods: This study included 158 patients who underwent curative treatment for gastric cancer between 2005 and 2020. The prognosis and clinical pathological parameters of the high-NPS (NPS >2) and low-NPS (NPS=0, 1) groups were analyzed. Results: The overall survival (OS) rates at 3 and 5 years were 86.7% and 77.7%, respectively, in the low-NPS group and 55.4% and 47.4%, respectively, in the high-NPS group. There were significant differences in OS between the two groups. Uni- and multivariate analyses demonstrated that the NPS was an independent prognostic factor for OS (HR=2.495, 95%CI=1.240-5.451). In addition, the 3- and 5-year recurrence-free survival (RFS) rates were 82.1% and 76.0%, respectively, in the NPS-low group, and 43.8% and 36.6% in the NPS-high group. Univariate and multivariate analyses demonstrated that the NPS was an independent prognostic factor for RFS (HR=2.739, 95%CI=1.509-4.972). When the first site of recurrence was compared between the low-NPS group and high-NPS group, there were significant differences in peritoneal recurrence (8.7% vs. 34.3%, p=0.001) and hematologic recurrence (5.6% vs. 21.9%, p=0.004). Conclusion: The NPS was a significant prognostic factor in patients with gastric cancer who received curative treatment. The NPS may be a promising biomarker for the treatment and management of gastric cancer. [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]

In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m2 ) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer. [ABSTRACT FROM AUTHOR]