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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 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 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: 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: 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: 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.)

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: 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: 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 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 albumin-bilirubin (ALBI) score is a promising tool for the evaluation of the perioperative hepatic function. The present study aimed to evaluate the clinical impact of the preoperative ALBI status in patients with gastric cancer (GC) who received curative treatment., Patients and Methods: The present study included 244 patients who underwent curative treatment for GC between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified., Results: Based on the 3- and 5-year OS rates, we set the cut-off value for the ALBI score at -2.7849. The 3- and 5-year OS rates were 87.3% and 80.9%, respectively, in the ALBI-low group, and 66.9% and 60.6% in the ALBI-high group; these differences were statistically significant (p<0.001). The ALBI score was included in the final multivariate analysis model [Hazard ratio (HR)=2.120, 95% confidence interval (CI)=1.177-3.818, p=0.012]. Similar results were observed for RFS. In addition, the ALBI score correlated with the introduction of postoperative adjuvant chemotherapy., Conclusion: The preoperative ALBI score correlated with both the OS and RFS of GC patients as well as the clinical course of adjuvant chemotherapy. Taken together, the ALBI score is a promising prognostic factor for GC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This prospective multi-central randomized phase II trial evaluated the efficacy and safety of oral Vitamin B12 500 μg/day replacement compared with oral Vitamin B12 1,500 μg/day in patients with Vitamin B12 deficiency after total gastrectomy for gastric cancer., Patients and Methods: Patients were randomly assigned to receive oral Vitamin B12 500 μg/day or Vitamin B12 1,500 μg/day in a 1:1 ratio with a minimization method. The primary endpoint was the incidence of a normal serum Vitamin B12 level at three months after treatment., Results: From January 2018 to December 2021, 3 institutions collaborated with the present study, and 74 patients were registered from these 3 institutions. The study was prematurely closed due to poor accrual after reaching almost 50% of its goal. Among the 74 recruited patients, 36 were allocated to the Vitamin B12 500 μg/day arm and 38 to Vitamin B12 1,500 μg/day arm. The incidences of patients with a normal Vitamin B12 level at 3 months (serum Vitamin B12 level >200 pg/ml) were 91.7% (33/36) in the Vitamin B12 500 μg/day arm and 100% (38/38) in the Vitamin B12 1,500 μg/day arm (p=0.3587). The types of clinical symptoms with Vitamin B12 deficiency that improved with Vitamin B12 treatment and the degree of improvement were also similar., Conclusion: Although the primary endpoint of the present study was not met, it was found that oral Vitamin B12 500 μg/day replacement is as effective and safe as oral Vitamin B12 1,500 μg/day replacement for Vitamin B12 deficiency., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Epiregulin (EREG) is a ligand of the epidermal growth factor receptor (EGFR) and promotes tumour progression mainly by stimulating the EGF pathway. We investigated the clinical significance of EREG mRNA expression in cancer tissues from patients with gastric cancer (GC) in pathological (p) Stage II/III who have undergone curative surgery., Patients and Methods: Expression of EREG mRNA was measured in cancer tissues obtained from 253 patients with pStage II/III GC who underwent curative surgery. Patients were divided into groups based on high or low expression of EREG mRNA. We examined the relationship between EREG mRNA expression levels and clinicopathological features and survival., Results: Clinicopathological features did not vary between the high and low EREG mRNA expression groups. Overall survival was significantly lower in the high-expression group compared to that in the low-expression group (5-year survival probability: 55.0% vs. 73.0%; p=0.005). Multivariate analysis showed EREG mRNA expression to be an independent predictor of poor survival (hazard ratio=1.794; 95% confidence interval=1.186-2.712; p=0.006)., Conclusion: Expression of EREG mRNA in cancer tissue from patients with pStage II/III GC may be a useful prognostic marker after curative surgery., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Perioperative systemic inflammation affects the long-term oncological outcomes in cases of malignancies. We evaluated the clinical impact of the preoperative systemic inflammation score (SIS) in resectable esophageal cancer patients who received curative treatment., Patients and Methods: This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified., Results: Based on the 3- and 5-year OS rate, we set the cut-off value for SIS at 2 in the preset study. Among the 168 total patients, 119 were categorized as the Low-SIS group, and 49 were categorized as the High-SIS group. The respective 3- and 5-year OS rates were 61.9% and 52.4% in the Low-SIS group and 33.3% and 26.6% in the High-SIS group. There were significant differences in OS (p<0.001). The SIS was therefore selected for the final multivariate analysis model (hazard ratio=2.094, 95% confidence interval=1.355-3.234, p<0.001). On comparing the perioperative clinical course between the High- and Low-SIS groups, there were significant differences in the rate of postoperative anastomosis leakage of grade ≥2 between the groups (61.5% in the High-SIS group vs. 30.3% in the Low-SIS group; p=0.021)., Conclusion: The systemic inflammation score had a clinical effect on the long-term oncological outcomes in esophageal cancer patients, suggesting that it might be a promising prognostic factor for esophageal cancer patients., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The current expectancy of long-term survival of patients with pathological stage (pStage) III gastric cancer (GC) is not satisfactory. However, neoadjuvant chemotherapy (NAC) is expected to improve survival rates in these patients. An appropriate pretherapeutic diagnostic strategy is necessary for selecting patients who are eligible for NAC. Surgical findings can often identify serosal invasion or metastatic lymphadenopathy, thereby facilitating the selection of candidates for NAC. Therefore, we aimed to evaluate the accuracy and potential of surgical staging in improving the management and survival of patients with GC., Patients and Methods: We assessed the accuracy of surgical staging in comparison to preoperative staging using data from patients who underwent gastrectomy for GC. In addition, differences in survival after using the surgical staging criterion were assessed., Results: A total of 915 patients were evaluated in this study. The sensitivity of surgical staging in detecting pStage III in the surgical T4N0-3 plus surgical T3N1-3 group was satisfactory (79.3%). The proportion of patients with pStage I using the surgical staging criterion was 7.8%., Conclusion: Surgical staging using laparoscopy or laparotomy may assist in selecting candidates for enrollment in clinical trials for NAC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Secondary mutation of mutated RAS, induced by chemotherapy, is thought to be rare. However, introduction of liquid biopsy (LB) has made it possible to monitor RAS status in patients' plasma throughout the course of chemotherapy for metastatic colorectal cancer (mCRC), and disappearance of the RAS mutation (RAS-mt), i.e., the NeoRAS-wt phenomenon, has been reported and is receiving attention, especially with respect to treatment implications., Patients and Methods: A prospective study of 129 patients undergoing chemotherapy for mCRC (RAS-wt, n=65; RAS-mt, n=64) was carried out. Plasma RAS status was monitored in these patients by LB. Relations between secondary genetic change, chemotherapy, and 6-month disease outcomes were analyzed. The effect of anti-EGFR mAb therapy on NeoRAS-wt mCRC was also examined., Results: NeoRAS-wt was detected in 27 (43.5%) RAS-mt patients overall and in all patients with a G12S or Q61H mutation. First-line treatment was more effective among NeoRAS-wt patients than non-NeoRAS-wt patients (70.9% vs. 48.6% overall response rate, p=0.087), and the time from treatment to LB was shorter in this group. Six-month outcomes were significantly better in the NeoRAS-wt group (p<0.001), and conversion to NeoRAS-wt was found to be predictive of a good outcome (OR=7.886, 95% CI=2.458-25.30; p<0.001). Anti-EGFR mAb therapy was found to restrict disease progression in NeoRAS-wt patients., Conclusion: Conversion to NeoRAS-wt is relatively frequent, and it may predict good responses to treatment. Anti-EGFR mAb therapy was effective for our NeoRAS-wt patients. Detection of NeoRAS-wt by LB may significantly change the indication for anti-EGFR mAb therapy and the mCRC treatment strategy., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Postoperative complications are associated with increased recurrence in colorectal cancer (CRC). We investigated the impact of infectious complications on the recurrence of CRC and overall survival after curative surgery in a single study group., Patients and Methods: In total, 1,668 patients who underwent radical resection for CRC in Yokohama City University, Yokohama Minami Kyosai Hospital, and Kanagawa Cancer Center between 2011 and 2019 were reviewed. Patients were classified into those with infectious complications (IC group) and those without infectious complications (Non-IC group). The risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed., Results: Postoperative complications were found in 560 of the 1,668 patients (33.5%), and IC, which occurred in 312 patients (18.7%), included pneumonia, anastomotic leakage, and intraperitoneal abscess. The 5-year OS rates in the Non-IC and IC groups were 95.5% and 90.4%, respectively, while the 5-year RFS rates were 74.4% and 68.1%, respectively. The multivariate analysis demonstrated that postoperative IC were significant independent risk factors for OS and RFS., Conclusion: The presence of postoperative IC after CRC resection is associated with decreased long-term survival. The surgical procedure, surgical strategy, and perioperative care should be carefully planned in order to avoid causing IC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To evaluate the impact of development of nivolumab monotherapy-induced immune-related adverse events (irAEs) and continuing nivolumab with irAEs on the survival of patients with gastric cancer (GC)., Patients and Methods: Patients with unresectable advanced GC and recurrence after curative resection who received nivolumab monotherapy were included in the study. Survival was compared between patients who did and did not develop irAEs, and between those who continued and discontinued treatment due to irAEs., Results: Of 110 GC patients, 22 developed irAEs. Grade ≥3 IrAEs included rash and diarrhoea associated with enteritis. Progression-free and overall survival (OS) were significantly better in patients with irAEs than in those without. The overall survival of patients who continued treatment despite irAEs was better than that of those who discontinued treatment., Conclusion: irAE development was associated with better survival in patients with GC who received nivolumab monotherapy. Continuing nivolumab with appropriate treatment in GC patients with irAEs may improve survival., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The number of patients who have cardiovascular-morbidities and use antiplatelet and/or anticoagulation therapy is rapidly growing worldwide. The present study evaluated the safety and feasibility of gastrectomy for gastric cancer in patients who received antiplatelet and/or anticoagulation therapy in the perioperative period., Patients and Methods: Cases were selected from the medical records of consecutive patients who were diagnosed with gastric cancer and underwent complete resection at the Kanagawa Cancer Center from 2013 to 2017. The patients were divided into the antiplatelet and/or anticoagulation treatment group and the non-antiplatelet and/or anticoagulation treatment group., Results: Five hundred and six patients underwent gastrectomy for gastric cancer and were analyzed in the present study. Among them, 62 patients (12.3%) received anticoagulation therapy (anticoagulation group). When the anticoagulation and non-anticoagulation groups were compared, although there were some differences in patient background factors, the surgical findings, perioperative clinical course, and details of postoperative complications were similar. The incidence of postoperative bleeding was 0.8% (4/506) in all patients. The incidence of postoperative bleeding was 1.6% (1/62) in the anticoagulation group and 0.7% (3/446) in the non-anticoagulation group. Preoperative anticoagulation therapy was not identified as a significant independent risk factor for postoperative bleeding., Conclusion: These results suggest that curative gastrectomy for gastric cancer is safe and feasible, regardless of the perioperative use of antiplatelet and/or anticoagulation treatment. In addition, the perioperative use of antiplatelet and/or anticoagulation treatment was not a significant risk factor for postoperative bleeding after gastrectomy for gastric cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Population aging results in increasing numbers of elderly persons undergoing surgery for colorectal cancer. We sought to identify objective preoperative indicators of outcomes, with a view toward development of safe, effective treatments for such patients., Patients and Methods: The study included 99 patients aged 80 years or more, who were treated surgically for stage I- III colorectal cancer. Preoperative nutritional status was compared retrospectively between those who suffered postoperative complications (n=40) and those who did not (n=59)., Results: Univariate analysis revealed low prealbumin (PreAlb) concentration (p=0.032) and low platelet-to-lymphocyte ratio (p=0.116) as risk factors for postoperative complications. Multivariate analysis showed preoperative PreAlb concentration to be an independent risk factor (OR=0.884; 95% confidence interval=0.791-0.989; p=0.024) associated with postoperative length of hospital stay (coef.=-0.336, p=0.002)., Conclusion: PreAlb, a rapid turnover protein, shows promise as a simple predictor of postoperative complications in elderly patients treated for colorectal surgery., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: D3 lymph node dissection (LND) for stage II and III colon cancer has been shown to improve prognosis, however, it generally increases surgical stress. Studies have reported that the C-reactive protein/albumin ratio (CAR) may be a useful inflammatory-nutritional biomarker to predict postoperative complications and poor prognosis for with various types of cancer. Our purposes were to assess the short- and long-term outcomes of D3 LND in patients with a high preoperative CAR (≥ 0.04)., Patients and Methods: This was a retrospective cohort analysis reviewing a prospectively collected database of Yokohama City University and three affiliated hospitals. A total of 449 patients with stage II or III colon cancer with high CAR who underwent primary resection with D2 or D3 LND were identified between 2008 and 2020. The primary and secondary outcomes of interests were the 3-year recurrence-free survival and postoperative complication rates., Results: After propensity matching, 230 patients were evaluated. There was no significant difference between the D3 and D2 groups in the rate of postoperative complications overall (14.8% versus 11.3%, p=0.558), however, the incidence of anastomotic leakage tended to be greater in the D3 group (9.6% versus 2.6%, p=0.050). The long-term findings showed that there was no significant difference between the two groups (3-year recurrence-free survival rate: 77.2% versus 77.2%, p=0.880)., Conclusion: D3 LND did not improve survival outcomes for patients with colon cancer with a poor CAR in this study. D2 LND may be a treatment option for patients with stage II-III colon cancer with a high preoperative CAR., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC)., Patients and Methods: We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction., Results: High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC., Conclusion: Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC)., Patients and Methods: PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated., Results: No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049)., Conclusion: PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To compare the mid-term oncological results between patients with low rectal cancer who underwent minimally invasive laparoscopic surgery (MILS) and those who underwent open surgery (OS)., Patients and Methods: Overall, 262 matched patients who underwent primary resection for low rectal cancer between 2000 and 2019 were divided into MILS (n=131; n=107, conventional laparoscopic surgery; n=24, robotic surgery) and OS (n=131) groups. The short- and mid-term outcomes were compared., Results: Similar baseline characteristics were noted. The operative time was longer and blood loss was lesser in the MILS group; the conversion rate was 3.8%. The incidence of postoperative complications was similar. The 2-year cumulative incidence of local recurrence was noted to be much lower in the MILS group (1.9%) than in the OS group (8.4%). MILS had a significantly low hazard ratio (0.208, p=0.036)., Conclusion: MILS has potential benefits in reducing local recurrence of low rectal cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC)., Patients and Methods: Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction., Results: Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival., Conclusion: High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Cancer stem cells (CSCs) are involved in cancer metastasis and relapse. Therefore, identification of CSC biomarkers might help determine the success of a treatment. In this study, we examined the expression of four CSC markers: Cluster of differentiation 44 variant (CD44v), leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), frizzled 7 (FZD7), and muscle, intestine and stomach expression 1 (MIST1), in cancer tissues of patients with non-small-cell lung cancer at >5 years after resection, and its clinical significance., Patients and Methods: We examined the expression of each CSC marker in 360 patients with NSCLC (n=360) who underwent curative resection by immunohistochemical analysis of tissue microarrays, and determined its relationship with survival., Results: High expression of MIST1 was related to better overall survival (p<0.05); high CD44v expression was associated with poor overall and recurrence-free survival (p<0.001 for both) and thus, CD44v was defined as an independent prognostic factor (p<0.05), according to a multivariate analysis., Conclusion: Tumoral CD44v expression might be a useful prognostic marker for patients after curative resection of NSCLC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC)., Patients and Methods: GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated., Results: Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]., Conclusion: GLI1 expression may be a useful prognostic marker in patients with locally advanced GC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer., Patients and Methods: Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses., Results: A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p<0.001) were higher in comparison to the NC group. The operation time was longer (p<0.001) and the incidence of intestinal-type histology was higher (p=0.017) in the IC group. The 5-year overall survival rates of the IC and NC groups were 59.8% and 83.2%, respectively (p<0.001). Univariate and multivariate analyses demonstrated that postoperative infectious complications were a significant risk factor for poorer overall survival (hazard ratio=2.38; 95% confidence interval=1.47-3.85, p<0.001)., Conclusion: Perioperative management is necessary to reduce the incidence of postoperative infectious complications and improve the survival of patients after curative resection of gastric cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)