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Background/aim: The Inflammatory Burden Index (IBI) has been reported as a novel prognostic indicator in several cancers and diseases. However, research on the IBI in patients with gastric cancer (GC) after gastrectomy is insufficient. This study investigated the utility of the preoperative IBI as a prognostic indicator in patients with GC., Patients and Methods: This retrospective study enrolled 459 patients undergoing gastrectomy for GC between 2013 and 2017 at the Kanagawa Cancer Center, Kanagawa, Japan. The IBI was calculated from preoperative blood test data. We evaluated the relationship between the preoperative IBI and clinicopathologic factors, overall survival (OS), and recurrence-free survival (RFS) after gastrectomy for GC, using propensity score matched analysis., Results: Regarding the association between IBI and clinicopathologic features, the high-IBI group was significantly older and had more lymphatic invasion and more progressive pT status than the low-IBI group before propensity score-matched analysis. OS and RFS after curative surgery were significantly lower in patients with a high IBI than in those with a low IBI (77.5% vs. 86.1%; p=0.02 and 74.3% vs. 85.1%; p=0.03, respectively). Multivariate analysis identified high IBI as an independent predictor of both OS and RFS., Conclusion: Preoperative IBI may serve as a valuable prognostic indicator for patients undergoing curative gastrectomy for GC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex., Patients and Methods: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis., Results: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females., Conclusion: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In East Asia, the standard treatment for resectable advanced gastric cancer involves gastrectomy and postoperative adjuvant chemotherapy; nevertheless, neoadjuvant chemotherapy is also expected to improve survival rates. However, it remains unclear whether the same criteria can be used to select adjuvant chemotherapy for patients treated with neoadjuvant chemotherapy, or how survival varies between post-chemotherapy pathological Stage (ypStage) and pathological Stage without chemotherapy (pStage). This study evaluated the long-term outcomes of ypStage and pStage in gastric cancers and investigated the optimal intensity of adjuvant chemotherapy for patients who have received preoperative chemotherapy., Patients and Methods: From January 2007 to November 2019, 1,585 patients underwent radical gastrectomy for gastric cancer at the Kanagawa Cancer Center. The patient background was adjusted by propensity score matching, and recurrence-free survival was compared between the two groups. In addition, a prognostic factor analysis was conducted for each yp/pStage., Results: The 5-year recurrence-free survival rates for yp/pStage I were 77.1% and 90.9%, respectively, with no significant difference (p=0.342). The 5-year recurrence-free survival rates for yp/pStage II were 50.4% and 69.1%, respectively, with no significant difference (p=0.062). The 5-year recurrence-free survival rates for yp/pStage III were 42.9% and 68.7%, respectively, with a significant difference observed (p=0.016). In the prognostic factor analysis for each stage, the presence or absence of preoperative chemotherapy was selected as an independent prognostic factor for yp/pStage I [hazard ratio (HR)=17.72; p=0.001] and yp/pStage II (HR=2.655, p=0.003)., Conclusion: ypStage tends to have a worse prognosis than pStage, and further development of multidisciplinary treatment is necessary., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The prognostic nutritional index (PNI) is used as a marker to evaluate the nutritional and immunological status of patients with various cancers. This study aimed to investigate whether preoperative PNI is a prognostic factor in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection., Patients and Methods: We retrospectively enrolled 232 pancreatic cancer patients who underwent surgical resection with perioperative adjuvant chemotherapy between January 2013 and December 2022. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression models., Results: The optimal cutoff value for the preoperative PNI was 44.3 in the present study. PNI <44.3 was associated with older age (p<0.001) and affected the clinical course of postoperative adjuvant chemotherapy. The PNI <44.3 had an important influence on the decreased OS (25.1 vs. 39.0 months) and RFS (13.1 vs. 22.8 months). In univariate and multivariate analyses, the preoperative PNI was an independent prognostic factor for OS [hazard ratio (HR)=1.682, 95% confidence interval (CI)=1.059-2.673, p=0.028] and RFS (HR=1.559, 95% CI=1.037-2.344, p=0.033)., Conclusion: Preoperative PNI is a prognostic factor for both OS and RFS in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. This study suggests that a low PNI may cause a lack of full-dose adjuvant chemotherapy, leading to recurrence and resulting in a poor prognosis for surgical pancreatic cancer patients treated with perioperative adjuvant chemotherapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The CRP-albumin-lymphocyte (CALLY) index is a promising biomarker. We clarified the clinical impact of the CALLY index in gastric cancer patients who received curative treatment., Patients and Methods: Consecutive patients who underwent curative resection for gastric cancer at Yokohama City University from 2005 to 2020 were selected based on medical records. The CALYY index was calculated as follows: serum ALB level (g/dl) × lymphocyte count (cells/μl)/C-reactive protein (mg/dl) ×10 4 Results: Two hundred fifty-nine patients were included in the present study. The three- and five-year overall survival (OS) rates were 64.8% and 57.0%, respectively, in the CALLY index-low group, and 86.2% and 78.2%, respectively, in the CALLY index-high group. There were significant differences between the two groups. A multivariate analysis demonstrated that the CALLY index was an independent prognostic factor for overall survival (hazard ratio=1.791; 95% confidence interval=1.067-3.009; p=0.028). When comparing the perioperative clinical course between the CALLY index-low and CALLY index-high groups, there were significant differences in postoperative surgical complications and adjuvant chemotherapy., Conclusion: The CALLY score was an independent prognostic factor for patients with gastric cancer. Our results suggest that the CALLY index is a promising tool for assessing inflammation and nutritional status in patients undergoing gastric cancer treatment and management., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The aim of the present study was to evaluate the clinical impact of the pretreatment lymphocyte-to-monocyte ratio (LMR) on both short- and long-term oncological outcomes in patients with resectable gastric cancer (GC)., Patients and Methods: The patients were chosen based on our medical records from consecutive cases of curative resection for GC performed at Yokohama City University from 2005 to 2020. The LMR was calculated as the lymphocyte count divided by the monocyte count measured before surgery., Results: The three- and five-year overall survival (OS) rates were 63.1% and 57.4%, respectively, in the low-LMR subgroup and 86.4% and 77.5%, respectively, in the high-LMR subgroup. According to multivariate analysis, the LMR was an independent prognostic factor for OS [hazard ratio (HR)=1.926, 95% confidence interval (CI)=1.143-3.245, p=0.014]. In addition, the three- and five-year RFS rates were 54.4% and 50.7%, respectively, in the low-LMR subgroup and 84.0% and 76.0% in the high-LMR subgroup. According to multivariate analysis, the LMR was an independent prognostic factor for OS (HR=2.031, 95%CI=1.266-3.258, p=0.003). When comparing the sites of recurrence between the low-LMR and high-LMR groups, there were significant differences in hematologic recurrence, lymph node recurrence, and peritoneal recurrence., Conclusion: Preoperative LMR might be a promising tool for the treatment and management of GC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Gastric cancer is a common cause of cancer death worldwide, especially in East Asia. This study evaluated the impact of preoperative modified Neutrophil-Platelet Score (mNPS) on the survival and recurrence of patients with resectable gastric cancer., Patients and Methods: The study analyzed 168 patients who underwent curative gastrectomy and subsequently received adjuvant treatment for gastric cancer between 2015 and 2021. Univariate and multivariate analyses were performed to identify the risk factors for overall survival (OS) and recurrence-free survival (RFS)., Results: Patients were divided into two groups: 76 patients with an mNPS of 0 were classified into the low-mNPS group, whereas 92 patients with an mNPS of ≥1 were classified into the high-mNPS group. The 3- and 5-year OS rates in the low-mNPS group were 65.6% and 56.2%, respectively, and those in the high-mNPS group were 45.3% and 36.9%, respectively. The difference in OS between the two groups was statistically significant (p=0.007). The 3- and 5-year RFS rates in the low-mNPS group were 45.6% and 38.7%, respectively, whereas those in the high-mNPS group were 33.4% and 28.1%, respectively. The difference in RFS between the two groups was statistically significant (p=0.043). A multivariate analysis showed that the mNPS was a significant independent prognostic factor for OS and RFS., Conclusion: mNPS is a potential prognostic marker for patients with gastric cancer who underwent curative gastrectomy. Higher mNPS values were associated with lower 3- and 5-year OS and RFS rates, indicating a potential correlation between elevated mNPS and worse outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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 C-reactive 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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to compare dietary intake (DI) after gastrectomy for gastric cancer between patients with (C group) and without (NC group) postoperative surgical complications., Patients and Methods: This prospective observational study enrolled patients who underwent gastrectomy for gastric cancer. DI was assessed using a food frequency questionnaire with 82 food items (FFQW82) during nutritional counseling before surgery and at one and three months after surgery., Results: A total of 225 patients participated in this study. Of the 225 patients, 193 had no postoperative complications, and 32 had postoperative complications (Clavien-Dindo grade ≥2). The median DI at 1 month postoperatively was 1508 kcal/day in the NC group and 1,470.5 kcal/day in the C group (p=0.175). The median DI at 3 months postoperatively was 1,623 kcal/day in the NC group and 1575 kcal/day in the C group (p=0.473). There was a significant difference between the NC and C groups in the rate of decrease in DI at one month (median: -8.44% vs. -15.37%, p=0.032) and at three months postoperatively (median: -3.58% vs. -6.12%, p=0.038)., Conclusion: There was a statistically significant difference in the rate of decrease in DI after gastrectomy between the C and NC groups at 1 and 3 months postoperatively. Our results suggest that patients with postoperative surgical complications require additional nutritional treatment for decreased DI., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The tryptophanyl-tRNA synthetase 1 gene (WARS1), encodes a tryptophan-tRNA synthetase involved in the amino acidification of tryptophan-tRNA and has been reported to be involved in cancer cell growth, metastasis promotion, and drug resistance in a variety of cancers. This study investigated the clinical significance of WARS1 expression as a biomarker in gastric cancer tissues obtained from patients with locally advanced gastric cancer (GC) who underwent radical resection., Patients and Methods: WARS1 expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection was determined using quantitative polymerase chain reaction (PCR). Association of WARS1 expression levels, categorized into high and low expression based on the median expression levels, with clinicopathological factors and overall survival (OS) of these patients was assessed., Results: The low-WARS1 expression group had significantly higher serosal invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage than did the high-WARS1 expression group. OS was significantly worse in the low- than in the high-WARS1 expression group (5-year survival 52.2% vs. 75.9%; p=0.0001). Furthermore, in multivariate analysis, low WARS1 expression was an independent predictor for poor OS (hazard ratio=2.101; 95% confidence interval=1.328-3.322; p=0.002)., Conclusion: In patients with locally advanced GC, after curative resection, WARS1 expression in GC tissue may be a useful prognostic marker., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Perioperative inflammation and the nutritional status affect both short- and long-term oncological outcomes in various malignancies. We clarified the clinical impacts of the CRP-albumin-lymphocyte (CALLY) index in patients with esophageal cancer who received curative treatment., Patients and Methods: The present study included 180 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters were compared between a high-fibrinogen group and a low-fibrinogen group., Results: The 3- and 5-year overall survival rates were 50.0% and 42.6%, respectively, in the CALLY index-low group, and 75.9% and 66.6% in the CALLY index-high group. The differences between the two groups were statistically significant (p<0.001). Univariate and multivariate analyses demonstrated that the CALLY index was an independent prognostic factor [hazard ratio=2.310, 95% confidence interval=1.416-3.767, p<0.001]. Similar results were observed in recurrence-free survival. When comparing the details of postoperative surgical complications, there was a significant difference in the incidence of anastomotic leakage. The incidence of anastomotic leakage was 40.2% in the CALLY index-low group, while it was 27.5% in the CALLY index-high group (p=0.030)., Conclusion: The pretreatment CALLY index is one of the independent prognostic factors for esophageal cancer. The CALLY index might become a promising biomarker for the treatment and management of esophageal cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The prognosis of patients with pancreatic cancer remains poor, despite recent advances in surgical techniques, perioperative care, neoadjuvant and adjuvant chemotherapy. This study aimed to investigate the preoperative neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor and determine the optimal cutoff value in surgical patients with pancreatic cancer., Patients and Methods: We retrospectively enrolled 461 patients with pancreatic cancer who underwent resection between January 2013 and December 2022 in the Department of Gastrointestinal Surgery at Kanagawa Cancer Center. The association between continuous or categorical variables and NLR was analyzed using the Mann-Whitney U-test and Fisher's exact test. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional-hazard regression models., Results: The optimal cutoff value for the preoperative NLR was 3.2. The NLR≥3.2 was associated with a large tumor size (p=0.005), poor histological differentiation (p=0.002), and less adjuvant chemotherapy (p=0.048). The NLR≥3.2 had an important influence on the decreased OS (21.6 vs. 25.8 months), and RFS (10.3 vs. 14.3 months). In univariate and multivariate analyses, the preoperative NLR was an independent prognostic factor for OS (p=0.022) and RFS (p=0.002)., Conclusion: Preoperative NLR (cutoff value: 3.2) within two weeks before surgery is a prognostic factor for OS and RFS in surgical patients with pancreatic cancer. This study could help establish evidence on the immune system's impact and a unified treatment strategy pre-surgery, potentially improving the prognosis for patients with pancreatic cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The perioperative nutritional status has recently been reported to influence the prognosis of various types of cancer. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and overall survival (OS) and recurrence-free survival (RFS) in patients with esophageal cancer who received radical and adjuvant therapy., Patients and Methods: Patients who underwent radical resection for esophageal cancer at our hospital (n=187) were included. Background characteristics, surgical factors, and OS were examined retrospectively. The GNRI was calculated using preoperative values, with GNRI <98 classified as low-GNRI., Results: Seventy-five and 112 patients were classified into the GNRI-low and -high groups, respectively. The 3- and 5-year OS rates were 75.7% and 66.7%, respectively, in the GNRI-high group and 43.2% and 36.7% in the GNRI-low group; the difference was statistically significant (p<0.001). In the univariate and multivariate analyses, low-GNRI was selected as a risk factor for OS. The hazard ratio for low-GNRI was 2.184 (95% confidence interval=1.361-3.508, p=0.001). The 5-year RFS rate in the high- and low-GNRI groups was 54.6% and 25.0%, respectively (p=0.001). In the univariate and multivariate analyses, low-GNRI was a risk factor for RFS. The hazard ratio for low-GNRI was 1.704 (95%CI=1.121-2.590, p=0.013). Regarding the type of recurrence, lymph node recurrence was significantly more common in the low-GNRI group (p=0.008)., Conclusion: Low-GNRI was an independent risk factor for OS and RFS after radical resection of esophageal cancer. The preoperative GNRI may be a useful prognostic factor after esophageal cancer surgery., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Chitinase-3-like protein 1 (CHI3L1), encoded by CHI3L1, is thought to be involved in growth, invasion, migration, and resistance to chemotherapy in cancer. This study aimed to investigate the clinical significance of CHI3L1 expression as a biomarker in gastric cancer (GC) tissues of patients with locally advanced GC after curative resection., Patients and Methods: Quantitative polymerase chain reaction (PCR) was used to determined CHI3L1 expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection. We compared the expression levels in GC tissues and adjacent normal gastric mucosa, and examined the relationship between expression in GC tissues and clinicopathological factors and overall survival (OS) in these patients., Results: CHI3L1 expression was significantly associated with lymph-node metastasis and venous invasion. OS rate was significantly lower in the high- than in the low-CHI3L1 expression group (5-year survival 55.5% vs. 72.6%; p=0.009). Furthermore, in multivariate analysis, high CHI3L1 gene expression was an independent factor for poor OS (hazard ratio=2.030; 95% confidence interval=1.318-3.127; p=0.001)., Conclusion: In patients with locally advanced GC after curative resection, expression of the CHI3L1 in GC tissue may be a useful prognostic marker., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The asialoglycoprotein receptor 2 gene (ASGR2) encodes a subunit of the asialoglycoprotein receptor, a transmembrane protein, which has recently been reported to be involved in gastric cancer (GC) progression. This study aimed to investigate the clinical significance of ASGR2 expression in GC tissues of patients with locally advanced gastric cancer (LAGC) after curative resection., Patients and Methods: ASGR2 expression was measured in GC tissues and adjacent normal gastric mucosa in 253 patients with pStage II/III GC who underwent curative resection, by using quantitative polymerase chain reaction. We compared the expression levels in GC tissues and adjacent normal stomach mucosa, and evaluated the relationship of its expression in GC tissues with clinicopathological factors and overall survival (OS)., Results: ASGR2 expression was significantly associated with lymph node metastasis and venous invasion. The high ASGR2-expression group demonstrated significantly lower survival than the low expression group (5-year survival 55.5% vs. 72.6%; p=0.009). Furthermore, in multivariate analysis, high ASGR2 expression was an independent factor for poor OS (hazard ratio=2.030; 95% confidence interval=1.318-3.127; p=0.001)., Conclusion: ASGR2 expression in GC tissues may be a useful prognostic marker in patients with LAGC after curative resection., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study evaluated the clinical impact of the lymphocyte-to-monocyte ratio (LMR) in patients with esophageal cancer who received curative treatment and perioperative adjuvant treatment. The association between LMR and the clinicopathological characteristics of patients with esophageal cancer was also investigated., Patients and Methods: This study included 181 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters of patients with high and low LMR statuses were analyzed., Results: The OS rates at 3 and 5 years after surgery were significantly lower (40.6% and 33.8%, respectively) in the low-LMR group than in the high-LMR group (67.1% and 58.4%, respectively). The pretreatment LMR was selected as an independent prognostic factor in the multivariate analysis model [hazard ratio (HR)=2.606; 95%CI=1.504-4.516, p<0.001]. Similar results were observed for RFS. Furthermore, LMR was associated with the occurrence of postoperative surgical complications and hematological recurrence. The incidence of anastomotic leakage was 63.3% in the low-LMR group and 27.2% in the high-LMR group (p<0.001). Moreover, the hematologic recurrence rate in the low-LMR group was significantly higher than that in the high-LMR group (46.7% vs. 23.8%, p=0.011)., Conclusion: The LMR may be a promising prognostic and predictive factor for esophageal cancer, and may be used to select optimal treatment strategies in the future., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Pretreatment fibrinogen levels are a promising prognostic marker for some malignancies. The aim of the present study was to evaluate the clinical impact of fibrinogen levels before treatment in patients with esophageal cancer who underwent curative resection., Patients and Methods: This study included 123 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters in the high fibrinogen and low fibrinogen groups were analyzed., Results: Overall survival (OS) stratified by individual clinical factors was compared using the log-rank test, and a significant difference was observed when a pretreatment fibrinogen level of 400 g/dl was used as a cutoff value. The comparison of the patient background factors between the high fibrinogen (400 g/dl) and low fibrinogen (<400 g/dl) groups revealed significant differences in pathological T status and lymph node metastasis. In the low fibrinogen group, the OS rates at 3 and 5 years after surgery (71.4% and 58.1%, respectively) were significantly higher than those in the high fibrinogen group (38.3% and 32.4%, respectively). Univariate and multivariate analyses for OS showed that the fibrinogen level prior to treatment was a significant prognostic factor. Similar results were observed for recurrence-free survival. In addition, when the first recurrence site was compared, there were marginally significant differences in hematologic recurrence., Conclusion: Pretreatment fibrinogen levels are a significant risk factor in patients with esophageal cancer. Therefore, pretreatment fibrinogen levels are a promising prognostic factor for patients with esophageal cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: A new modified nutritional risk index (mNRI), calculated using serum albumin (g/l)+body mass index (BMI) [weight (kg&#95;/height 2 (m 2 )], 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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Dietary intake (DI) loss after gastrectomy is a serious problem for patients with gastric cancer. This study compared the dietary intake after surgery in patients with early gastric cancer who received laparoscopic distal gastrectomy (LDG) versus those who underwent conventional open distal gastrectomy (ODG)., Patients and Methods: This was a prospective, observational study enrolling patients who underwent gastrectomy for gastric cancer. Dietary intake was assessed using the food frequency questionnaire with eighty-two food items (FFQW82) at nutritional counseling before surgery and one and three months after surgery., Results: A total of 118 patients were included. Among them, 69 (58.5%) were male, and 49 (41.5%) were female. Seventy-five (63.6%) received LDG, and 43 (36.4%) received ODG. At 1 month postoperatively, the median DI in the LDG group was 1,540 (1,014-2,195) kcal/day, whereas that in the ODG group was 1547 (986-2,143) kcal/day (p=0.891). At 3 months postoperatively, the median DI in the LDG group was 1,624 (1,050-2,443) kcal/day, and that in the ODG group was 1,652 (917-2,144) kcal/day (p=0.749). There was no significant difference in the DI loss rate at 1 month (median: -8.2% vs. -9.3%, p=0.398) and 3 months (median: -3.2% vs. -3.7%, p=0.635) between the LDG and ODG groups., Conclusion: Minimally invasive laparoscopic surgery may not prevent postoperative DI loss after distal gastrectomy. Therefore, methods other than laparoscopic surgery are needed to prevent post-gastrectomy DI loss., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Based on gastric shape, patients with gastric cancer can be divided into storage (hook-shaped and ptotic stomach) and reverse outflow (steer-horn 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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Pregnancy zone protein (PZP), encoded by PZP, belongs to the α-2-macroglobulin superfamily, and plays an important role in inflammatory responses and immune cell activation in cancer. However, the relationship between gastric cancer (GC) and PZP is poorly studied. This study investigated the clinical significance of PZP expression in GC tissues of patients with locally advanced GC after curative resection., Patients and Methods: Using quantitative polymerase chain reaction, we measured PZP expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection. We compared the expression levels of PZP in GC tissues and adjacent normal gastric mucosa and examined the relationship of PZP expression in GC tissues with clinicopathological factors and overall survival (OS)., Results: PZP expression was significantly associated with histology, venous invasion, and pathological stage. The high PZP expression group had significantly worse OS than did the low expression group (5-year survival 48.6% vs. 68.5%, p=0.0003). Furthermore, in multivariate analysis, high PZP expression was an independent factor for poor OS (hazard ratio=1.984, 95% confidence interval=1.307-3.012, p=0.0013)., Conclusion: In post-curative resection patients with locally advanced GC, PZP expression in GC tissue may be a useful prognostic marker., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: We evaluated the clinical impact of the Geriatric Nutritional Risk Index (GNRI) in patients who received curative treatment and perioperative adjuvant treatment. We also investigated the association between the GNRI and the clinicopathological features of patients with GC., Patients and Methods: This study included 280 patients who underwent curative treatment for GC between 2005 and 2020. The prognosis and clinicopathological parameters of the high-GNRI and low-GNRI groups were compared., Results: In the GNRI-high group, the overall survival (OS) rates at 3 and 5 years after surgery were significantly lower (82.7% and 77.9%, respectively) than those in the GNRI-low group (56.4% and 40.8%). The GNRI was selected for the final multivariate analysis model for OS. The GNRI was also a significant prognostic factor for recurrence-free survival (RFS). The RFS rates at 3 and 5 years after surgery were 79.1% and 74.8%, respectively, in the GNRI-high group, and 48.0% and 38.6% in the GNRI-low group. The GNRI was selected for the final multivariate analysis model for RFS. The GNRI was also found to affect the postoperative clinical course, including postoperative surgical complications and postoperative adjuvant chemotherapy., Conclusion: The GNRI may be a promising prognostic and predictive factor for gastric cancer. In the future, the GNRI may be used to select optimal treatment strategies., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The platelet-to-lymphocyte ratio (PLR) is a promising prognostic marker in some malignancies. The present study evaluated the clinical impact of the PLR in patients with gastric cancer who underwent curative resection., Patients and Methods: This study included 258 patients who underwent curative treatment for gastric cancer between 2005 and 2020. The prognosis and clinicopathological parameters between the high- and low-PLR statuses were analyzed., Results: The overall survival (OS) stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed using a pretreatment PLR of 150. When comparing the patient backgrounds between the high-PLR (PLR≥150) and low-PLR (PLR<150) groups, there were no significant differences between the two groups. The OS rates at 3 and 5 years after surgery were significantly higher at 70.8% and 60.4%, respectively, for the high-PLR group than at 83.6% and 79.7%, respectively, for the low-PLR group. Univariate and multivariate analyses of the OS showed that the PLR was a significant prognostic factor. In addition, when comparing the first recurrence sites, there were significant differences in peritoneal recurrence., Conclusion: The PLR is a significant risk factor for gastric cancer, making it a promising prognostic factor for patients with gastric cancer., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Intraoperative blood loss (IBL) has been reported to decrease survival after surgical resection of some malignancies; however, there are few reports on the effects of IBL on recurrence and survival in locally advanced esophageal cancer. Therefore, we investigated the relationship between IBL and postoperative recurrence and overall survival in patients who underwent surgery for esophageal cancer., Patients and Methods: One hundred and ninety-eight patients with locally advanced esophageal cancer who underwent preoperative adjuvant chemotherapy and curative resection as standard treatment were included in this study. Based on a defined cut-off value for IBL, 27 and 171 patients were classified into the high and low IBL groups, respectively. The relationship between each group and clinicopathological factors, postoperative recurrence, and overall survival were investigated., Results: In terms of the relationship between IBL and clinicopathological factors, the high IBL group had significantly more patients with pathological T4, longer operative time, and higher incidence of postoperative complications than the low IBL group. Both recurrence-free and overall survival were significantly worse in the high IBL group than in the low IBL group. Furthermore, multivariate analysis identified high IBL as an independent factor for predicting poor reference free survival and overall survival., Conclusion: Heavy IBL in patients with locally advanced esophageal cancer may be a useful predictor of postoperative recurrence and overall survival., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The C-reactive protein to prealbumin ratio (CPAR) has been proposed and introduced in gastrointestinal cancer management. This study aimed to evaluate the clinical impact of the CPAR in patients with gastric cancer (GC) who received curative treatment., Patients and Methods: This study included 447 patients who underwent curative treatment for GC between 2013 and 2017. The prognosis and clinicopathological parameters were compared between patients with high and low CPARs., Results: Overall survival (OS) stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed using a pretreatment CPAR of 5.0. Significant differences were observed in the 3- and 5-year OS rates of the CPAR-low (CPAR <5.0) and CPAR-high (CPAR ≥5.0) groups. The 3- and 5-year OS rates were 92.6% and 87.8%, respectively, in the CPAR-low group and 88.0% and 75.4% in the CPAR-high group. The CPAR was determined to be a significant prognostic factor for OS in a multivariate analysis (p=0.032). Similar results were observed for recurrence-free survival., Conclusion: The CAPR is a prognostic factor for GC patients. Therefore, the CAPR may be a promising nutritional biomarker of inflammation that can be applied in the management of GC patients., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: We investigated the influence of the preoperative Oral Health Assessment Tool (OHAT) score on the outcomes of patients with esophageal cancer after curative surgery., Patients and Methods: This study included 90 patients with esophageal cancer who underwent curative surgery and who were screened with the OHAT between 2008 and 2021. The OHAT consists of eight categories with three possible scores. The risk factors for 5-year overall survival (OS) and recurrence-free survival (RFS) were identified., Results: Patients were divided into healthy (n=42) and unhealthy (n=48) groups. The OHAT score was identified as a significant risk factor for postoperative pneumonia (11.9% vs. 43.8%, p=0.001) and postoperative hospital stay (20.5 days vs. 50.1 days, p=0.042). The 5-year OS rate after surgery was 71.2% in the healthy group and 43.2% in the unhealthy group, which was a significant difference (p=0.015). A multivariate analysis showed that a high OHAT score was a significant independent factor for 5-year OS (p=0.034)., Conclusion: The OHAT score was a useful prognostic marker in patients who underwent curative surgery for esophageal cancer. To improve the oncological outcomes of patients with esophageal cancer, it is necessary to carefully plan perioperative oral/dental care using the OHAT score., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Perioperative adjuvant treatment and complete resection is the standard treatment for resectable pancreatic cancer and systemic chemotherapy is standard treatment for unresectable pancreatic cancer. To improve the survival of patients with pancreatic cancer, it is necessary to identify promising biomarkers to optimize the treatment. The availability of biomarkers may allow patients to receive a more aggressive or less toxic treatment. Recent studies showed that the inflammatory and nutritional status perioperatively and/or during chemotherapy affect short and long-term oncological outcomes in pancreatic cancer. Introduction of inflammatory and nutritional status evaluation in pancreatic cancer treatment might improve the postoperative surgical complications or chemotherapy-induced adverse events. However, to introduce these various nutritional and inflammation assessment tools in daily clinical practice, it is necessary to understand the characteristics of each nutrition and inflammation assessment tool. This review summarizes the background, current status, and future perspectives of nutrition and inflammation assessment tools in pancreatic cancer treatment., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Gastrectomy with lymphadenectomy is a standard treatment for gastric cancer. Anastomotic leakage remains a potentially fatal complication of gastrectomy. Forceful stapler extraction may cause anastomotic complications. We focused on the duodenal peristalsis, as we hypothesized that it might cause forceful stapler extraction. We then retrospectively investigated duodenal peristalsis and reviewed videos of Da Vinci system cases to clarify the relationship between peristalsis and anastomotic complications., Patients and Methods: Forty-nine cases with stored videos of laparoscopic surgery using the Da Vinci system from 2015 to March 2021 were included. Peristalsis was defined by repeated contraction and expansion that was clearly visible three or more times in a row. The duodenum was investigated because it is frequently observed during gastrectomy. Suture failure was evaluated in cases with and without peristalsis., Results: The study population included 49 patients [male, n=32; female, n=17; median age, 71 (42-82) years]. Duodenal peristalsis was observed in 14 (28.6%) cases. Three patients experienced complications. A comparative study of cases with and without complications showed significant peristalsis in cases with complications (p=0.0198)., Conclusion: A new definition to evaluate duodenal peristalsis was established. Anastomotic complications were significantly more frequent in cases with peristalsis (p=0.0198). Our results suggest the utility of manual over-sewing or the use of reinforcement material., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: When nivolumab is administered as second-line therapy for esophageal cancer, radiotherapy may also be provided in cases either concurrently or sequentially. The aim of this study was to retrospectively examine whether the incidence of adverse events increases in such cases., Patients and Methods: Twenty-two esophageal cancer patients [17 males and 5 females; mean age 71 years (range=58-87 years)] treated with nivolumab were included. Patients were divided into two treatment groups: nivolumab alone (N group) (12 patients) and nivolumab combined with radiotherapy (R group) (10 patients). All patients had squamous cell carcinoma. The primary outcomes measured were the severity and frequency of adverse events., Results: Adverse events were seen in 6 of the 12 patients in the N group and 8 of the 10 in the R group. There were significantly more adverse events in the R group (p=0.035), but no difference in Grade 3 or higher adverse events (p=0.781), indicating that the adverse events were controllable. There was no significant difference in treatment effect between the N and R groups., Conclusion: In this report, 50% of adverse events in the N group were grade 3-4, 25% of which were grade 4, as seen in previous reports. In the present study, the side effects were not enhanced by treatment with immune checkpoint inhibitors plus radiotherapy. Immune checkpoint inhibitors plus radiation therapy would be a relatively safe treatment and may become an option for esophageal cancer treatment in the future., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To determine the clinical significance of pre-treatment circumferential tumor location within the esophageal wall in patients with locally advanced esophageal squamous cell carcinoma who underwent curative resection after neoadjuvant chemotherapy., Patients and Methods: Patients (n=96) with cStage IB-III esophageal squamous cell carcinoma who underwent curative resection after neoadjuvant chemotherapy were categorized into two groups based on the circumferential tumor location within the esophageal wall on diagnostic endoscopy: left or anterior wall group (L/A patients, n=49); right or posterior wall group (R/P patients, n=47). Analyses were conducted to examine the relationship between circumferential tumor location, clinicopathological characteristics, 3-year overall survival (3Y-OS), and 3-year recurrence-free survival (3Y-RFS)., Results: The lymph node status and recurrence rates of mediastinal lymph node metastases were significantly higher in patients with L/A than in patients with R/P. Furthermore, patients with L/A had significantly poorer 3Y-OS and 3Y-RFS than those with R/P. Tumor location within the esophageal wall was identified in multivariate analysis as an independent risk factor for 3Y-RFS (hazard ratio=2.92, 95% confidence interval=1.35-6.32, p=0.0064)., Conclusion: Pre-treatment of circumferential tumor located within the esophageal wall may be a useful prognostic factor in patients with cStageIB-III esophageal squamous cell carcinoma who underwent curative resection after neoadjuvant chemotherapy., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Mucinous gastric carcinoma (MGC) has a poor prognosis. Due to the differences in clinicopathology factors between MGC and non-MGC (NMGC), it is difficult to compare them. In this study, we compared the clinicopathological characteristics and prognosis of MGC and NMGC patients., Patients and Methods: For gastric carcinoma (GC), 3,042 gastrectomy patients were included in the study and divided into the MGC (n=86) and NMGC (n=2,956) groups. The characteristics and prognoses of patients in both groups were compared before and after (both groups, n=86) propensity score matching., Results: Significant differences were observed in the tumor location (upper) (MGC group: 28.0% vs. NMGC group: 24.7%, p=0.003), tumor diameter (median) [65 mm (8-200 mm) vs. 40 mm (2-75 mm), p<0.001], lymph node metastasis (70.9% vs. 37.3%, p<0.001), venous invasion (57.0% vs. 40.4%, p<0.001), and lymphatic invasion (62.8% vs. 34.9%, p<0.001) before propensity score matching. The 5-year overall survival (OS) (70.9% vs. 76.2%, p=0.006) and cancer-specific survival (CSS) (75.5% vs. 82.4%, p=0.014) rates were significantly lower in the MGC group. After propensity score matching, there were no significant differences in either the 5-year OS (70.9% vs. 73.7%, p=0.230) or CSS (75.5% vs. 75.7%, p=0.587) rates. In addition, no substantial difference was observed in either of the recurrence forms., Conclusion: MGC is rare and usually diagnosed at a more advanced stage. However, MGC and NMGC have similar prognoses., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The prognostic nutritional index (PNI) has been reported as an immunonutritional index that can easily evaluate nutritional status and immunocompetence from blood tests. The purpose of this study was to investigate the usefulness of PNI as a prognostic factor in postoperative gastric cancer patients., Patients and Methods: In this retrospective cohort study, we evaluated 258 patients with pStage I-III gastric cancer who underwent radical resection at Yokohama City University Hospital, from 2015 to 2021. To examine the association with prognosis, we analyzed clinicopathological factors including PNI (<47/≥47), age (<75/≥75), sex (male/female), depth (pT1/≥pT2), lymph node metastasis (pN+/pN-), lymphatic invasion (ly+/ly-), vascular invasion (v+/v-), histological type (enteric/spread) and postoperative complications., Results: In univariate analysis, PNI (p<0.001), depth of tumor invasion (p<0.001), lymph node involvement (p<0.001), age (p=0.002), lymphatic invasion (p<0.001), vascular invasion (p<0.001), and postoperative complications (p=0.003) were associated with overall survival. In multivariate analysis, PNI (HR=2.100, 95% confidence interval 1.225-3.601, p=0.007), tumor invasion, lymph node metastasis, and postoperative complications were shown as poor prognostic factors for overall survival., Conclusion: PNI is an independent prognostic factor for overall and recurrence-free survival in postoperative gastric cancer patients. PNI could be implemented in clinical practice to identify patients at higher risk for poor outcomes., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Peritoneal lavage cytology positivity (CY1) has been identified as a prognostic factor for distant metastases that is equivalent to peritoneal dissemination in Japan. Peritoneal lavage cytology is usually diagnosed by microscopic findings; a diagnostic procedure using a liquid biopsy (LB) technique has not yet been established., Patients and Methods: We evaluated the feasibility of a LB approach using peritoneal lavage samples from 15 patients with gastric cancer. Samples were collected from both the Douglas pouch and the left subdiaphragmatic area, and cell-free DNA was extracted for analysis of TP53 mutations using droplet digital polymerase chain reaction., Results: All 10 patients with CY1 had positive cytology for the left subdiaphragmatic specimen. However, only six out of the 10 patients had positive cytology for their Douglas pouch specimens, and these six patients had peritoneal tumor DNA (ptDNA) in these specimens. In all five patients with CY0, ptDNA was not detected. The overall survival was significantly shorter in the ptDNA-positive group than in the ptDNA-negative group. The survival of the group with a high amount of DNA from free intraperitoneal cells (ficDNA) was significantly worse than that of those with a low amount. In contrast, the group with a high amount of DNA from peritoneal cell-free DNA (pcfDNA) had significantly better survival than the group with a low amount., Conclusion: LB cytology showed equivalent utility to that of conventional microscopic examinations regarding its diagnostic ability. Therefore ptDNA, pcfDNA and ifcDNA are expected to be useful as prognostic factors., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to examine the clinical significance of the protein expression of the cancer stem cell (CSC) markers ALDH1A1, CD133, CD44, and MSI-1 in primary and metastatic tissues of patients with breast cancer (BC)., Patients and Methods: ALDH1A1, CD133, CD44, and MSI-1 protein expression in pairs of primary and metastatic tissues of 55 patients with BC with metastases treated at Kanagawa Cancer Center between January 1970 and December 2016 were evaluated using immunohistochemical assay and their association with clinicopathological factors and survival was examined., Results: There were no significant differences in CSC marker expression rates between primary and metastatic tissues for any CSC markers. Regarding the relationship between CSC marker expression in primary tissues and survival, patients with high CD133 expression had significantly lower recurrence-free survival (DFS) and overall survival. On multivariate analysis, they were also a poor independent predictor of DFS (hazard ratio=4.993, 95%CI=2.189-11.394, p=0.0001). In contrast, there was no significant association between the expression of any CSC marker in metastatic tissues and survival., Conclusion: CD133 expression in the primary BC tissue may be a useful risk factor for recurrence in patients with BC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Trifluridine/tipiracil (FTD/TPI) is an anticancer-agent that is administered as third-line or later chemotherapy for metastatic gastric/gastroesophageal junction cancer (mGC/GEJC). Although inflammatory and nutritional statuses have attracted attention as prognostic factors for patients with mGC/GEJC in this therapy, their usefulness has not been fully clarified. Thus, this study investigated the clinical significance of prognostic nutritional index (PNI), neutrophil/lymphocyte ratio (NLR), and NLR/serum albumin (Alb) ratio in patients administered FTD/TPI., Patients and Methods: This retrospective study included 64 patients who underwent FTD/TPI treatment for mGC/GEJC at Kanagawa Cancer Center, Kanagawa, Japan, between October 2019 and June 2022. Patients were divided into high and low PNI, NLR, and NLR/Alb groups according to their pretreatment blood data. This study evaluated the associations between the inflammatory and nutritional indexes and survivals., Results: Overall survival (OS) and progression-free survival (PFS) of patients with low PNI were significantly poorer than those with high PNI. However, low PNI was not an independent prognostic factor for OS and PFS. There was no significant association between NLR and OS or PFS. In contrast, the OS of patients with high NLR/Alb was significantly poorer than those with high PNI and low NLR/Alb. Furthermore, multivariate analysis showed that high NLR/Alb was an independent prognostic factor for OS., Conclusion: The NLR/Alb may be a useful prognostic factor in patients with mGC/GEJC being administered FTD/TPI as third-line or later chemotherapy., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Pancreatic cancer has the highest risk of venous thromboembolism (VTE). Additionally, chemotherapy for cancer patients increases the risk of developing VTE. Due to recent advances in neoadjuvant chemotherapy (NAC) regimens, more patients with resectable pancreatic cancer will receive NAC. However, the incidence, risk, and predictors of developing VTE in these patients have not been fully evaluated., Patients and Methods: We retrospectively evaluated the incidence, risk, and predictors of VTE among 67 consecutive patients with resectable pancreatic cancer who received neoadjuvant combination therapy with gemcitabine+S-1 (NAC-GS) followed by surgery and 45 patients with resectable pancreatic cancer who underwent upfront surgery (Up-S)., Results: The incidence of VTE in the NAC-GS and Up-S groups was 10.4% and 6.6%, respectively. Preoperative D-dimer levels were significantly higher in the NAC-GS group, and D-dimer levels were significantly increased during NAC-GS. Preoperative D-dimer level was the only predictor for VTE in patients with resectable pancreatic cancer who received NAC-GS., Conclusion: There is an increased risk of developing VTE during NAC. Screening with D-dimer and taking appropriate measures to suppress critical VTE is essential to provide NAC to patients with resectable pancreatic cancer., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The prognosis of anaplastic thyroid carcinoma (ATC) is poor, and there is currently no established treatment to improve its outcome. We previously reported that enhancer of zeste homolog 2 (EZH2) was highly expressed in ATC, and may be a therapeutic target; however, the effects of EZH2 on ATC growth currently remain unknown., Materials and Methods: We investigated the effects of an EZH2 inhibitor (DZNep) on four ATC cell lines (8305C, KTA1, TTA1 and TTA2). We performed a gene panel analysis of all ATC cell lines to identify differences in DZNep sensitivity between the cell lines. To investigate the effects of DZNep on the recovery of differentiation, we assessed changes in thyroid differentiation markers (TDMs) before and after the DZNep treatment using PCR., Results: EZH2 was expressed in all ATC cell lines. The cell-reducing effects of DZNep were detected in all ATC cell lines, and were the strongest in KTA1 cells followed by TTA2 cells. The TTA1 and 8305C cell lines, which showed weak cell-reducing effects, had TP53 mutations. No changes in TDMs were observed in any ATC cell line., Conclusion: DZNep, an EZH2 inhibitor, exerted suppressive effects on the growth of ATC cell lines and has potential as a therapeutic strategy; however, its effects may be attenuated in ATC with TP53 mutations., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Patients are at-risk for vitamin B12 deficiency after total gastrectomy due to a lack of intrinsic factors. The aim of the study was to clarify the clinical course and risk factors for vitamin B12 deficiency after total gastrectomy for gastric cancer patients., Patients and Methods: Patients who underwent curative resection for gastric cancer were selected from the medical records of the Yokohama City University from 2000 to 2020. A logistic regression analysis was performed to identify risk factors for vitamin B12 deficiency., Results: We evaluated 47 patients. The median serum vitamin B12 levels before surgery were 359 pg/ml, while those at 3, 6, 9, and 12 months after surgery these were 255 pg/ml, 197.5 pg/ml, 195 pg/ml, and 206 pg/ml, respectively. Univariate analyses to identify factors associated with vitamin B12 deficiency at 6 months after surgery showed that the occurrence of postoperative complications was a significant risk factor (OR=6.347, 95%CI=1.607-25.774, p=0.009), while adjuvant chemotherapy was a marginally significantly risk factor (OR=3.562, 95%CI=0.877-14.477, p=0.076)., Conclusion: Almost half of the patients were diagnosed with vitamin B12 deficiency at 6 months after total gastrectomy for gastric cancer. In addition, the occurrence of postoperative complications and adjuvant chemotherapy were risk factors for vitamin B12 deficiency at 6 months after surgery., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: SEC11A gene encodes the SPC18 protein, which has been implicated in tumour progression by inducing the secretion of various growth factors. We investigated the clinical significance of SEC11A expression in gastric cancer (GC) tissues in patients with locally advanced gastric cancer (LAGC) after curative resection., Patients and Methods: We estimated SEC11A expression in cancer tissues from 253 pStage II/III GC patients who underwent curative resection using quantitative polymerase chain reaction (PCR) and investigated the relationship of SEC11A expression with clinicopathological factors and survival., Results: SEC11A expression was significantly related to serosal invasion, lymph node metastasis, lymphatic invasion, and pathological stage. The high-SEC11A expression group had a significantly lower survival rate than the low group (5-year survival 52.3% vs. 75.9%; p<0.005). Furthermore, in multivariate analysis, high-SEC11A expression was an independent factor of poor survival (hazard ratio, 2.010; 95% confidence interval=1.303-3.100; p=0.002)., Conclusion: SEC11A expression in cancer tissue may be a useful prognostic marker in patients with LAGC after curative resection., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The systemic inflammation score (SIS) is a promising tool for the evaluation of prognosis. The present study aimed to evaluate the clinical impact of the preoperative SIS status in gastric cancer (GC) patients who underwent curative resection., Patients and Methods: This study retrospectively analyzed 258 patients with primary gastric cancer who received curative treatment at Yokohama City University. The SIS was evaluated before surgery as determined by the lymphocyte-to-monocyte ratio (cut-off value=4.44) and serum albumin level (cut-off value=4.0 g/dl)., Results: A high SIS was identified as an independent predictor of overall survival [hazard ratio (HR)=1.784, p<0.05] and multivariate analysis showed marginal significance for recurrence-free survival (HR=1.710, p<0.05)., Conclusion: The preoperative SIS score was correlated with both the OS and RFS of GC patients, as well as the clinical course of adjuvant chemotherapy. Thus, the SIS score is a promising prognostic factor for GC., Competing Interests: The Authors declare no conflicts of interest in association with the present study., (Copyright 2022, International Institute of Anticancer Research.)

Background/aim: The present study evaluated the clinical impact of other metachronous or synchronous primary cancer (OPC) in patients who received curative treatment for esophageal cancer., Patients and Methods: The present study included 168 patients who underwent curative treatment for esophageal cancer between 2005 and 2018. Prognosis and differences between the OPC status (metachronous/synchronous) and clinic pathological parameters was analyzed., Results: A total of 168 patients were included in this study. Forty patients were diagnosed with metachronous/synchronous OPC. When comparing the clinicopathological factors between the patients with and without OPC, the patients' background and postoperative clinical courses were very similar between the two groups. The 3- and 5-year overall survival rates in patients with esophageal cancer with OPC were 66.0% and 54.5%, respectively, while those in patients without OPC were 50.1% and 41.4%, respectively. There was no statistically significant difference in these rates (p=0.156). The OPC status was not included in the final multivariate analysis model., Conclusion: The OPC status was not found to be a prognostic factor for patients who received curative treatment for esophageal cancer. Therefore, it is not necessary to avoid performing curative treatment for esophageal cancer because of a patient's OPC status., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Preoperative sarcopenia is associated with various cancers and affects the long-term prognosis of patients. After gastrectomy for gastric cancer, dynamic changes in body composition occur, and sarcopenia becomes more apparent after surgery than before surgery. However, the relationship between sarcopenia in the early postoperative period and long-term survival is not fully understood. The aim of this study was to determine the effects of surgical sarcopenia on long-term outcomes of patents with gastric cancer., Patients and Methods: We included 408 patients who underwent curative gastrectomy (distal or total gastrectomy) for gastric cancer at the Kanagawa Cancer Center from December 2013 to November 2017. Sarcopenia was defined using the skeletal muscle index (SMI), using computed tomography (CT) one month after gastrectomy. We compared the long-term outcomes between patients with and without sarcopenia., Results: The 5-year overall survival (OS) rates were 83.2% and 91.4% in the surgical and non-surgical sarcopenia groups, respectively. The hazard ratio (HR) of surgical sarcopenia for OS was 2.410 (95% confidence interval (CI)=1.321-4.396). In addition, surgical sarcopenia was associated with non-cancer-related deaths and deaths from other cancers., Conclusion: Patients with surgical sarcopenia after gastrectomy should be carefully monitored not only for gastric cancer recurrence but also for the occurrence of other diseases, including other cancers., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The present study evaluated the clinical characteristics and prognostic factors of gastric cancer (GC) patients with synchronous and metachronous other primary cancer who received curative treatment for GC., Patients and Methods: The study included 244 patients who underwent curative treatment for GC between 2005 and 2018. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified., Results: A total of 244 patients were included in this study. Among them, 58 patients were diagnosed with synchronous and metachronous other primary cancer. When comparing the patient background characteristics and clinical course between GC patients without and with synchronous and metachronous other primary cancer, the background, postoperative surgical complications, and details of adjuvant treatment were similar between the two groups. The 3- and 5-year OS rates in GC patients with synchronous and metachronous other primary cancer were 69.7% and 48.0%, respectively, while those in patients without synchronous and metachronous other primary cancer were 80.6% and 74.3%, respectively, showing a statistically significant difference (p<0.001) The synchronous and metachronous other primary cancer status was included in the final multivariate analysis model (hazard ratio=2.201; 95% confidence interval=1.229-3.942; p=0.008)., Conclusion: Synchronous and metachronous other primary cancer status is a prognostic factor in GC patients. Therefore, synchronous and metachronous other primary cancer patients need both other primary cancer and GC follow-up to improve their survival., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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 χ 2 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., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)