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Purpose: Perioperative surgical stress and systemic inflammation resulting from complex interactions between cancer and the host play an important role in cancer progression. This retrospective study compared the prognostic impact of various perioperative cumulative inflammation- and nutrition-based markers in patients with gastric cancer (GC)., Methods: This study included 301 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. Perioperative cumulative markers were calculated using the newly developed trapezoidal area method., Results: The cumulative prognostic nutritional index (cum-PNI) had the highest area under the receiver operating characteristic (ROC) curve for predicting the overall survival (OS) as well as the relapse-free survival (RFS). The cum-PNI was significantly correlated with tumor-related factors, including tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, vascular involvement, and TNM stage classification. The cum-PNI was also significantly correlated with surgical factors, including surgical approach, gastrectomy, lymphadenectomy, intraoperative blood loss, and postoperative complications. Furthermore, the OS and RFS were poorer in patients with a low cum-PNI (< 236.3) than in those with a high cum-PNI (> 236.3). A multivariate analysis indicated that a low cum-PNI was an independent prognostic indicator in patients with GC., Conclusions: The cum-PNI might be useful for predicting the prognosis and guiding the perioperative management of patients with GC., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Ferroptosis suppressor protein 1 and glutathione peroxidase 4 have been identified as key molecules in two independent pathways associated with ferroptosis inhibition. This study investigated the prognostic significance and clinical associations of FSP1 and GPX4 expression in esophageal squamous cell carcinoma (ESCC) and assessed the therapeutic potential of regulating these molecules in ESCC cells., Methods: Immunohistochemical analysis was performed on surgical specimens of 97 patients with ESCC for FSP1 and GPX4 expression. To identify the change in ESCC cell viability, FSP1 and GPX4 inhibitors were administered to three cell lines. In addition, ferroptosis as the cause of reduced cell viability by FSP1 and GPX4 inhibition was confirmed., Results: Prognosis was significantly worse for patients in the group positive for both FSP1 and GPX4 compared with the other groups (p < 0.001). In multivariate analysis, positivity for both FSP1 and GPX4 was an independent poor prognostic factor (p = 0.002). The combination of FSP1 and GPX4 inhibitors induced cell death more potently than each inhibitor did alone. Furthermore, the ferroptosis inhibitor markedly canceled this cell death., Conclusions: Overexpression of FSP1 and GPX4 is a poor prognostic factor for patients with ESCC. Simultaneous suppression of both FSP1 and GPX4 caused potent cell death, which was markedly abrogated by ferroptosis inhibitors. These findings indicate that simultaneous regulation of FSP1 and GPX4 may be a new therapeutic target in ESCC., (© 2022. The Author(s).)

Background: A drain is often placed in the abdominal cavity for postoperative monitoring and early detection of complications such as rebleeding and pancreatic or bile leaks. Since determining the color of the drainage fluid is subjective, an objective method of judging color is needed., Methods: The hemoglobin concentration of the drainage fluid after gastrointestinal surgery was measured using the Hemato Check Module, a newly developed instrument capable of absorbance analysis with an optical sensor. The correlation between the results and those measured by an existing blood count measuring device (XN3000) was investigated., Results: A total of 215 specimens were analyzed in 43 patients. For the correlation analysis, there was a strong positive correlation with a correlation coefficient of 0.884 ( P < 0.001). The Hemato Check Module showed a clear proportional error compared to the XN3000., Conclusion: The Hemato Check Module was a convenient and accurate instrument for measuring hemoglobin concentration in waste fluid to determine the presence of blood., Competing Interests: Conflict of interest: We received funding for this study from Ishida Medical Co., Ltd., (©2023 Tottori University Medical Press.)

Background: We compared short-term clinical outcomes between robotic-assisted minimally invasive esophagectomy (RAMIE) and video-assisted thoracic esophagectomy (VATS-E) using propensity score-matched analysis., Methods: We enrolled 114 patients with esophageal cancer who underwent esophagectomy at our institution from January 2013 to January 2022. Propensity score matching was performed to minimize selection bias between the RAMIE and VATS-E groups., Results: After propensity score matching, 72 patients (RAMIE group, n = 36; VATS-E group, n = 36) were selected for analysis. No significant differences in clinical variables were observed between the two groups. The RAMIE group had a significantly longer thoracic operation time (313 ± 40 vs. 295 ± 35 min, P = 0.048), a higher number of right recurrent laryngeal nerve lymph nodes (4.2 ± 2.7 vs. 2.9 ± 1.9, P = 0.039), and a shorter postoperative hospital stay (23.2 ± 12.8 vs. 30.4 ± 18.6 days, P = 0.018) than the VATS-E group. The RAMIE group tended to have a lower rate of anastomotic leakage (13.9% vs. 30.6%) than the VATS-E group, although the difference was not statistically significant ( P = 0.089). No significant differences were found in recurrent laryngeal nerve paralysis (11.1% vs. 13.9%, P = 0.722) or pneumonia (13.9% vs. 13.9%, P = 1.000) between the RAMIE group and the VATS-E group., Conclusion: Although RAMIE for esophageal cancer requires a longer thoracic surgery time, it might be a feasible and safe alternative to VATS-E for treating esophageal cancer. Further analysis is needed to clarify the advantages of RAMIE over VATS-E, especially in terms of long-term surgical outcomes., Competing Interests: The authors declare no conflict of interest., (©2023 Tottori University Medical Press.)

Background: Esophagectomy is an invasive and complication-prone surgical procedure. Therefore, a tool that can predict the occurrence of postoperative complications may be useful for perioperative management. In this study, we investigated whether the modified frailty index (mFI) could be a useful tool for predicting the postoperative complications of esophagectomy., Methods: In this study, 162 patients who underwent curative esophagectomy for esophageal squamous cell carcinoma from 2004 to 2019 at our institution were included. The patients were divided into the high mFI (≥ 0.27) and low mFI (< 0.27) groups, and the short-term postoperative outcomes of each group were examined retrospectively., Results: Regarding background factors, age and the American Society of Anesthesiologists physical status classification were significantly higher in the high mFI group ( P = 0.049 and P = 0.002, respectively); however, the other items were not significantly different between the two groups. Regarding surgical outcomes, no significant differences in operative time, blood loss, and hospital stay were observed between the two groups. Regarding postoperative complications, pneumonia was significantly more common in the high mFI group ( P = 0.035). In multivariate analysis, high mFI ( P = 0.034) was an independent predictor of pneumonia, along with operative time ≥ 613 min ( P = 0.03) and preoperative BMI < 20.48 ( P = 0.006)., Conclusion: The mFI is useful for predicting pneumonia after esophagectomy., Competing Interests: The authors declare no conflicts of interest., (©2023 Tottori University Medical Press.)

Background: The systemic inflammatory response resulting from the complex interactions between cancer and the host plays an important role in cancer development. Recently, the lymphocyte-C-reactive protein ratio (LCR), which is a hematological and biochemical marker that reflects the systemic inflammatory response and nutritional status, has been reported to be associated with poor survival. Similar results were observed in patients with certain cancer types. However, these studies focused on the preoperative LCR, and thus far, no studies have reported the relationship between postoperative LCR and prognosis in patients with gastric cancer (GC)., Methods: This study enrolled 455 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery at our institution between 2005 and 2018. The relationship between both the preoperative and postoperative LCR and the prognosis of patients with GC was retrospectively investigated., Results: Preoperative LCR showed significant correlations with tumor-related factors, such as tumor size, depth of invasion, and lymph node metastasis. By contrast, no correlation was observed between postoperative LCR and tumor-related factors. The 5 year survival rate was significantly worse in patients with low preoperative LCR than in those with high preoperative LCR (65.4% vs. 83.9%, p < 0.0001). Similarly, the 5 year survival rate was also significantly worse in patients with low postoperative LCR than in those with high postoperative LCR (67.0% vs. 84.1%, p < 0.0001). Furthermore, combination analysis of the pre- and postoperative LCR revealed that the prognosis of patients with both low pre- and postoperative LCR was worse in patients with GC (5 year survival rate was 52.0%). A multivariate analysis indicated that a low pre- and postoperative LCR and age and lymph node metastasis were independent prognostic indicators., Conclusions: The combination of preoperative and postoperative LCR appears to be useful in predicting the prognosis of patients with GC., (© 2022. The Author(s).)

Background: Thoracoscopic esophagectomy has been extensively used worldwide as a curative surgery for patients with esophageal cancer; however, complications such as anastomotic leakage and stenosis remain a major concern. Therefore, the objective of this study was to evaluate the efficacy of circular stapling anastomosis with indocyanine green (ICG) fluorescence imaging, which was standardized for cervical esophagogastric anastomosis after thoracoscopic esophagectomy., Methods: Altogether, 121 patients with esophageal cancer who underwent thoracoscopic esophagectomy with radical lymph node dissection and cervical esophagogastric anastomosis from November 2009 to December 2020 at Tottori University Hospital were enrolled in this study. Patients who underwent surgery before the anastomotic method was standardized were included in the classical group (n = 82) and patients who underwent surgery after the anastomotic method was standardized were included in the ICG circular group (n = 39). The short-term postoperative outcomes, including anastomotic complications, were compared between the two groups using propensity-matched analysis and the risk factors for anastomotic leakage were evaluated using logistic regression analyses., Results: Of the 121 patients, 33 were included in each group after propensity score matching. The clinicopathological characteristics of patients did not differ between the two groups after propensity score matching. In terms of perioperative outcomes, a significantly higher proportion of patients who underwent surgery using the laparoscopic approach (P < 0.001) and narrow gastric tube (P = 0.003), as well as those who had a lower volume of blood loss (P = 0.009) in the ICG circular group were observed after matching. Moreover, the ICG circular group had a significantly lower incidence of anastomotic leakage (39% vs. 9%, P = 0.004) and anastomotic stenosis (46% vs. 21%, P = 0.037) and a shorter postoperative hospital stay (30 vs. 20 days, P < 0.001) than the classical group. According to the multivariate analysis, the anastomotic method was an independent risk factor for anastomotic leakage after thoracoscopic esophagectomy (P = 0.013)., Conclusions: Circular stapling anastomosis with ICG fluorescence imaging is effective in reducing complications such as anastomotic leakage and stenosis., (© 2022. The Author(s).)

Background: Immune-check point inhibitors (ICPIs) for treatment of cancer patients sometimes induce potentially life-threatening immune-related adverse events (irAEs), which predict ICPIs treatment efficacy. Prediction of irAEs would be useful for management of irAEs and prediction of ICPIs efficacy. This study aimed to determine predictors of irAEs in patients with recurrent or unresectable advanced gastric cancer (RUGC) treated with nivolumab., Methods: Seventy-eight RUGC patients treated with nivolumab at nine institutions between January 2017 and April 2020 were included in this study. The usefulness of specific blood test results as predictors of irAEs was evaluated., Results: We observed irAEs in 15 (19.2%) patients. The disease control rate was significantly higher in the patients with irAEs than in those without (86.7% vs. 42.9%; P < 0.001). The median progression-free survival was significantly longer for patients with irAEs than for patients without (4.9 vs. 2.6 months; P = 0.018). The median survival time was longer for patients with irAEs than for those without (9.4 vs. 5.8 months; P = 0.041). The receiver operating characteristic (ROC) curves for irAEs indicated that the area under the curve (AUC) of carbohydrate antigen 19-9 (CA19-9) was highest (0.692; P = 0.022), followed by that for the platelet count × serum C-reactive protein (P-CRP) value (0.680; P = 0.032). The AUC for the CA19-9 + P-CRP combination was 0.782, which was more useful than that for either component and significantly associated with overall survival of nivolumab-treated RUGC patients., Conclusions: The CA19-9 + P-CRP combination was predictive of irAEs and prognosis in RUGC patients., (© 2022. The Author(s).)

Background: Patients who undergo gastrectomy for gastric cancer (GC) are likely to have nutritional difficulty after surgery. Readmission due to nutritional difficulty is common in such patients. Thus, in this study, we aim to identify the predictive indicators for readmission due to nutritional difficulty in patients who underwent gastrectomy for GC., Methods: We retrospectively reviewed surgical outcomes in 516 consecutive patients who underwent gastrectomy for GC., Results: The readmission rate within 1 year was 13.8%. Readmission due to nutritional difficulty was observed in 20 patients (3.9%); it was determined as the second leading cause of readmission. Multivariate analysis revealed that the type of gastrectomy and the modified frailty index (mFI) were independent predictive indicators of readmission due to nutritional difficulty. Patients were assigned 1 point for each predictive indicator, and the total points were calculated (point 0, point 1, or point 2). The readmission rates due to nutritional difficulty were 1.2%, 4.7%, and 11.5% in patients with 0, 1, and 2 points, respectively (P = 0.0008)., Conclusions: The readmission rate due to nutritional difficulty was noted to be high in patients who underwent total or proximal partial gastrectomy with high mFI. Intensive follow-up and nutritional support are needed to reduce readmissions due to nutritional difficulty. Reduced readmission rates can improve patient quality of life and reduce medical costs., (© 2021. The Author(s).)

Background: Colonic metastasis is uncommon in patients with hepatocellular carcinoma (HCC). In the past, extrahepatic metastasis of HCC was not treated aggressively because of its poor prognosis. Herein, we describe the case of a patient with HCC who survived for 30 months following resection of a metastatic tumor in the ascending colon., Case Presentation: An 80-year-old man presented at our hospital with symptoms of abdominal pain on the right side and fever. He had undergone transcatheter arterial chemoembolization and posterior segment resection of the liver because of HCC, followed by radiofrequency ablation for a recurrent intrahepatic lesion 5 and 3 years, respectively, prior to the visit. He was diagnosed with retroperitoneal hematoma, which was thought to be associated with diverticulitis and an extramural tumor in the ascending colon. A definitive diagnosis could not be reached; however, a right hemicolectomy of the colon was performed because of progression to anemia. A pathological examination revealed a metastatic tumor in the ascending colon extending from the subserosal layer to the muscularis propria layer. The patient was treated with lenvatinib after surgery, but presented with intrahepatic recurrence, lymph node metastasis, and peritoneal dissemination metastasis 15 months later. The progression of the disease could not be controlled and his postoperative survival time was 30 months., Conclusion: Resection of metastasis of HCC might contribute to prolonged survival in cases, where radical resection is possible., (© 2021. The Author(s).)

A 56-years old man was diagnosed with cervical esophageal cancer with lymph node metastasis. After definitive chemoradiotherapy as the first-line therapy, complete response(CR)was obtained. One year and 3 months after the therapy, lymph node dissection and postoperative chemotherapy was performed for the lymph node metastases of the left neck and axillary lymph node. After 3 years and 10 months from the first-line therapy, follow-up CT revealed left axillary lymph node swelling and diagnosed with lymph node recurrence. Chemoradiotherapy was performed for the recurrence of the lymph node and CR was achieved for the lymph node. However, left axillary lymph node swelling were detected again 6 years after the first-line therapy. After 6 months of chemotherapy with S-1, CR was achieved for the lymph node again. He is now alive without recurrence for 10 years after the first-line therapy.

Background: The mortality rate of patients with unresectable gastric cancer (UGC) has decreased with the development of chemotherapies and surgical techniques. However, the survival rate remains low. We retrospectively examined the prognostic significance of the pretreatment skeletal muscle mass index (SMI) and nutritional and inflammatory factors in patients with UGC., Methods: This study included 83 patients diagnosed with UGC at Tottori University Hospital who received palliative chemotherapy based on 5-fluorouracil. Pretreatment computed tomography (CT) measured overall skeletal muscle mass (SMM) and cross-sectional SMM at the third lumbar vertebra (L3). We focused on the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and platelet-to-lymphocyte ratio (PLR) as nutritional and inflammatory factors., Results: Receiver operating characteristic curve analysis was performed for median survival time (MST) after palliative chemotherapy. SMIs for males and females (43.9 cm 2 /m 2 and 34.7 cm 2 /m 2 , respectively) were the cutoff values, and patients were divided into high (SMI High ; n = 41) and low SMI groups (SMI Low ; n = 42). Body mass index (BMI) was significantly higher in patients in the SMI High group than in the SMI Low group (p < 0.001). The number of patients who received third-line chemotherapy was significantly higher in the SMI High group than in the SMI Low group (p = 0.037). The MST was significantly higher in the SMI High group than in the SMI Low group (17.3 vs. 13.8 months; p = 0.008). The incidence of grade 3 or 4 side effects was significantly higher in patients with SMI Low UGC (p = 0.028). NLR was significantly higher in patients with SMI Low than it was in those with SMI High . (p = 0.047). In the univariate analysis, performance status, SMI, histological type, lines of chemotherapy, and NLR were prognostic indicators. The multivariate analysis identified SMI (p = 0.037), NLR (p = 0.002), and lines of chemotherapy (p < 0.001) as independent prognostic factors., Conclusions: The SMI Low group had significantly more grade 3 or 4 side effects, were related to high NLR, and had a significantly worse prognosis than the SMI High group., Trial Registration: Retrospectively registerd., (© 2021. The Author(s).)

Background/aim: M1 macrophages have antitumour effects, while M2 macrophages promote tumour proliferation and invasion. The clinical significance of the M2-specific marker CD204 has not been elucidated in colorectal cancer (CRC). We investigated the prognostic significance of CD204- and CD68-positivity in specimens from patients with CRC and examined the effects of M2 polarized-macrophages on the proliferative and invasive potentials of CRC cell lines in vitro., Materials and Methods: Surgical tumour specimens from 206 patients with Stage II and III CRC were examined by immunohistochemistry. Proliferation and invasion assays and flow cytometry were used to investigate CD204 expression in macrophages co-cultured with three CRC cell lines., Results: Infiltration of CD204-positive cells was significantly associated with shorter overall survival and relapse-free survival; no association was observed for CD68. M2-polarized macrophages significantly promoted proliferation and invasion of CRC cells., Conclusion: Higher infiltration of CD204-positive macrophages into the tumour-microenvironment might be prognostically important in CRC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The standard treatment for resectable advanced esophageal squamous cell carcinoma in Japan is surgery followed by neoadjuvant chemotherapy, and it is important to predict the effect of neoadjuvant chemotherapy before treatment. Therefore, this study aims to extract conventional blood examination data, such as tumor markers and/or inflammatory/nutritional index levels, that can predict the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy., Methods: We retrospectively analyzed the medical records of 66 patients with thoracic esophageal squamous cell carcinoma who received neoadjuvant chemotherapy, followed by curative esophagectomy at Tottori University Hospital between June 2009 and December 2019., Results: We demonstrated that the product of the platelet-to-lymphocyte ratio (PLR) multiplied by the cytokeratin-19 fragment (CYFRA) level, which was termed "PLR-CYFRA," is the most accurate indicator that predicts the pathological response to neoadjuvant chemotherapy, with the highest area under the curve [0.795 (95% confidence interval: 0.665-0.925), P < 0.001] in receiver operating characteristic analyses. Therefore, we divided patients into the PLR-CYFRA Low (< 237.6, n = 21) and PLR-CYFRA High (≥ 237.6, n = 45) groups and found that the percentage of PLR-CYFRA Low was significantly higher in patients with a better pathological response ( P < 0.001). Furthermore, patients with good pathological response had significantly better prognoses in terms of disease-specific survival ( P = 0.014), recurrence-free survival ( P = 0.014), and overall survival ( P = 0.032). In the multivariate analysis, PLR-CYFRA was an independent predictor of the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy ( P = 0.002)., Conclusion: Pretreatment PLR-CYFRA might be a useful and simple tool that predicts the pathological effect of neoadjuvant chemotherapy in esophageal squamous cell carcinoma., Competing Interests: The authors declare no conflict of interest., (©2021 Tottori University Medical Press.)

Background: Due to its tumor-specific metabolic pathway characteristics, 5-aminolevulinic acid (5-ALA) is a natural amino acid widely used in cancer treatment. The current study, demonstrated that 5-ALA induced ferroptosis via glutathione peroxidase 4 (GPX4) and heme oxygenase 1 (HMOX1) and had an antitumor effect in esophageal squamous cell carcinoma (ESCC)., Methods: Expression of GPX4 and HMOX1 in pathologic specimens of 97 ESCC patients was examined, and prognostic analyses were performed. Real-time polymerase chain reaction (RT-PCR), RNA microarray, and Western blotting analyses were used to evaluate the role of 5-ALA in ferroptosis in vitro. In addition, this study used ferrostatin-1, a ferroptosis inhibitor, and a lipid peroxidation reagent against cell lines treated with 5-ALA. Finally, the role of 5-ALA was confirmed by its effect on an ESCC subcutaneous xenograft mouse model., Results: The study showed that upregulation of GPX4 and downregulation of HMOX1 were poor prognostic factors in ESCC. In an RNA microarray analysis of KYSE30, ferroptosis was one of the most frequently induced pathways, with GPX4 suppressed and HMOX1 overexpressed by 5-ALA treatment. These findings were verified by RT-PCR and Western blotting. Furthermore, 5-ALA led to an increase in lipid peroxidation and exerted an antitumor effect in various cancer cell lines, which was inhibited by ferrostatin-1. In vivo, 5-ALA suppressed GPX4 and overexpressed HMOX1 in tumor tissues and led to a reduction in tumor size., Conclusions: Modulation of GPX4 and HMOX1 by 5-ALA induced ferroptosis in ESCC. Thus, 5-ALA could be a promising new therapeutic agent for ESCC.

Background: We retrospectively examined the relationship among skeletal muscle mass index (SMI), prognosis, and chemotherapy side effects in patients with recurrent gastric cancer (RGC)., Methods: Sixty-seven patients who developed recurrence after undergoing curative gastrectomy for gastric cancer at Tottori University Hospital and received palliative chemotherapy were included in this study. Pretreatment computed tomography was performed to measure the skeletal muscle mass (SMM) and cross-sectional SMM at the third lumbar vertebra. We focused on haematologic toxicity (neutropenia, thrombocytopenia, and anaemia), febrile neutropenia, and gastrointestinal toxicity (diarrhoea, vomiting, and stomatitis) as the side effects of chemotherapy., Results: Median SMIs for males and females (43.9 and 34.7 cm 2 /m 2 , respectively) were used as cutoff values. The patients were classified into high (SMI High ; n = 34) and low SMI groups (SMI Low ; n = 33). The SMI Low group included more patients treated with monotherapy (P = 0.016) compared with the SMI High group, had a significantly lower number of chemotherapy lines (P = 0.049), and had a significantly higher incidence of grade 3 or 4 side effects (P = 0.010). The median survival rate was significantly higher in the SMI High group (17.8 vs 15.8 months; P = 0.034). In the univariate analysis, body mass index, SMI, histological type, and prognostic nutritional index were identified as prognostic indicators. The multivariate analysis identified SMI (P = 0.037) and histological type (P = 0.028) as independent prognostic factors., Conclusion: The incidence of grade 3 or 4 side effects was significantly higher in patients with SMI Low RGC. SMI was a useful prognostic marker of RGC.

Background: This study was conducted to assess the long-term outcomes of elderly patients among propensity-score-matched gastric cancer patients after curative gastrectomy and to propose the proper management of elderly gastric cancer patients., Methods: We enrolled 626 patients with gastric cancer who underwent curative gastrectomy at our institution between January 2004 and December 2015. To minimize selection bias among 2 groups, propensity score matching was performed., Results: Patients were divided into an elderly group over 75 years old (EP group; n = 186) and a non-elderly group (NEP group; n = 440). After propensity score matching, patients were divided into EP group (n = 178) and NEP group (n = 175). Five-year overall survival was significantly lower in the EP group than in the NEP group, consistent with a subgroup analysis of each stage. However, the 5-year disease-specific survival among all enrolled patients and those with stage I and II disease did not differ significantly. Moreover, in the subgroup of stage III patients, 5 year disease-specific survival was significantly lower in the EP group (23.0%) than in the NEP group (59.4%; P = 0.004). Because elderly patients with stage III disease had an extremely poor prognosis, we decided to compare the two groups with stage III. The EP group contained significantly fewer patients with D2 lymphadectomy (P = 0.002) and adjuvant chemotherapy (P < 0.001) than the NEP group. C-reactive protein to albumin ratio was significantly higher in patients in the EP group than in the NEP group (P = 0.046), and the prognostic nutritional index was significantly lower in patients in the EP group than in the NEP group (P = 0.045).　Multivariate analysis revealed that the prognostic nutritional index and lymphatic invasion were independent prognostic factors., Conclusions: Elderly gastric cancer patients with stage III disease showed poorer disease-specific survival compared with non-elderly patients, which may be due to a poorer nutritional and inflammatory background, fewer D2 lymphadenectomies, and a lack of adjuvant chemotherapy. The safe induction of standard lymphadenectomy and adjuvant chemotherapy with perioperative aggressive nutritional support may improve the prognosis of elderly gastric cancer patients with stage III disease.

Background: The purpose of this study was to compare postoperative complications and nutritional status between esophagogastrostomy and double-tract reconstruction in patients who underwent laparoscopic proximal gastrectomy, and assess the advantages of both surgical procedures., Methods: Between 2010 and 2018, 47 cases underwent proximal gastrectomy with esophagogastrostomy ( n = 23) or double-tract reconstruction ( n = 24) at our institution for the treatment of clinical T1N0 adenocarcinoma located in the upper third of the stomach. Patient clinical characteristics, short-term outcomes, nutrition status, and skeletal muscle index were compared among the two groups., Results: There was no significant difference between esophagogastrostomy and double-tract reconstruction in terms of operation time, blood loss, and length of postoperative hospital stay. Reflux symptoms and anastomotic stenosis were significantly higher in the esophagogastrostomy group compared with the double-tract reconstruction group ( P < 0.001 and P = 0.004, respectively). There was no significant difference in anastomotic leakage, surgical site infection, and pancreatic fistula. For the nutritional status, the decrease rate of cholinesterase was significantly higher in the esophagogastrostomy group compared with the double-tract reconstruction group at 6 months ( P = 0.008) There was no significant difference in the decrease rate of skeletal muscle mass index at 1 year after surgery., Conclusion: Compared with esophagogastrostomy, double-tract reconstruction tends to have better short-term nutritional status and postoperative outcomes in terms of preventing the occurrence of gastroesophageal reflux and anastomosis stenosis. These findings suggest that double-tract reconstruction may be a useful method in laparoscopic proximal gastrectomy., Competing Interests: The authors declare no conflict of interest., (©2020 Tottori University Medical Press.)

Background: Despite improved treatment for gastric cancer (GC), the prognosis of advanced disease remains poor. Further investigation of the oncogenic sequence for GC is needed., Materials and Methods: The expression of TYRO3 protein tyrosine kinase in five GC cell lines was confirmed using western blotting. TYRO3 knockdown in GC cells, and bromodeoxyuridine and Transwell assays were used to examine the functions of TYRO3 in tumor proliferation and invasion. Finally, TYRO3 expression in 138 patients who underwent curative gastric resection for advanced GC (Union for International Cancer Control stage II/III) was tested by immunohistochemistry, and the association between prognosis and TYRO3 expression was analyzed., Results: TYRO3 was detected at various levels in all the tested GC cell lines. Deleting TYRO3 significantly suppressed proliferation and invasion. Immunohistochemistry revealed TYRO3 expression was an independent prognostic factor for overall survival in patients with GC., Conclusion: TYRO3 appears to mediate tumor progression and predict prognosis of patients with GC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: We compared short- and long-term clinical outcomes including inflammatory marker levels between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) to define the advantages of RG over LG., Methods: We enrolled 209 patients with gastric cancer who underwent curative distal gastrectomy. We compared short- and long-term clinical outcomes including inflammatory marker levels between RG and LG to define the advantages of RG over LG. C-reactive protein (CRP) levels; the CRP-to-albumin, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios; and the prognostic nutritional index were compared as systemic inflammatory markers., Results: RG was associated with a longer operative time. The incidence of postoperative infectious complications of grade II or higher according to the Clavien-Dindo classification was not significantly different between the two groups. Amylase levels in drainage fluid on postoperative days 1 and 3 were significantly lower in the RG group than in the LG group. The incidence of pancreatic fistula in the RG group (4.3%) was lower than that in the LG group (7.5%), albeit without significance. There were no significant differences in inflammatory marker levels either before or after surgery between the two groups. The 3-year overall survival rate did not significantly differ between the RG and LG groups (91.1% vs. 91.1%). Similar results were observed regarding the 3-year disease-specific survival rate (100% vs. 97.1%)., Conclusion: RG might be feasible and safe for treating gastric cancer from both surgical and oncological perspectives. The use of robotic assistance is associated with decreased amylase levels in drainage fluid, which may reduce the risk of pancreatic fistula and prevent pancreatic injury., Competing Interests: The authors declare no conflict of interest., (©2020 Tottori University Medical Press.)

Background: Despite recent advances in systemic chemotherapy, the prognosis of patients with peritoneal metastases from gastric cancer still remains poor. Nonetheless, several efficacious intraperitoneal chemotherapy regimens have recently been developed for patients with peritoneal metastases. However, no study has investigated the effectiveness of intraperitoneal chemotherapy for metachronous peritoneal metastases from gastric cancer after curative surgery., Case Presentation: We herein report a case of a 65-year-old man who had metachronous peritoneal metastases from gastric cancer after curative total gastrectomy who had been successfully treated with intraperitoneal chemotherapy. One month after surgery, adjuvant chemotherapy with S-1 was initiated given a final pathological stage of IIIB (pT4aN2M0). However, during adjuvant chemotherapy 12 months after surgery, tumor marker levels, which had been within normal range before surgery, increased with abdominal contrast-enhanced computed tomography (CT) revealing pelvic ascites. Thereafter, staging laparoscopy was performed, and the patient was diagnosed with peritoneal recurrence of gastric cancer. Following staging laparoscopy, an intraperitoneal access port was subcutaneously implanted for subsequent intraperitoneal chemotherapy. Combined chemotherapy with intraperitoneal and intravenous administration of paclitaxel and oral S-1 was then provided. After one course of combined chemotherapy, peritoneal lavage cytology was negative for malignancy. CT showed gradually decreasing ascites, whereas tumor marker levels returned to normal. The patient continued chemotherapy without major side effects and remained progression-free for 33 months with 36 chemotherapy cycles., Conclusions: A combination regimen including intraperitoneal chemotherapy could be a promising option for patients with peritoneal recurrence after gastric cancer surgery.

Background: There have been two reports on preserving the proximal gastric tube by using intraoperative indocyanine green (ICG)-based photodynamic detection to evaluate blood flow through the anastomosis for gastric tube cancer after esophagectomy. However, in those cases, the period since the first operation was > 3 years 11 months, and there have been no reports of cases with < 1-year periods after the first operation., Case Presentation: A 59-year-old man underwent video-assisted thoracic subtotal esophagectomy and gastric tube reconstruction after two courses of preoperative chemotherapy for middle thoracic esophageal cancer. After half a year, follow-up upper gastrointestinal endoscopy showed a submucosal tumor in the posterior wall of the pre-pyloric region. We performed a biopsy, and the results led to a diagnosis of gastric cancer (moderately differentiated adenocarcinoma: tub2). Clinically, the patient was described as having stage IB (cT2N0M0) gastric cancer of the reconstructed gastric tube. To avoid total gastrectomy, we tried to evaluate the blood flow of the proximal part of the gastric tube by intraoperative ICG-based photodynamic detection. Intraoperative findings confirmed neo-vascularization from the remnant cervical esophagus to the upper region of the gastric tube approximately 7 cm through the esophagogastric anastomosis. Therefore, we dissected the distal part of the gastric tube approximately 4 cm from the esophagogastric anastomosis and then performed Roux-en-Y gastro-jejunostomy via the ante-sternum route. The postoperative course was stable, and the patient was discharged on the 14th postoperative day., Conclusions: ICG-based photodynamic diagnosis was found to be simple and less invasive. Therefore, even if the postoperative period is short, this method should be considered for evaluation of blood flow prior to performing less invasive surgery.

Background: Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. Although recent studies indicate that PD-1 is also expressed on other immune cells besides T cells, its role remains unclear. This study aims to evaluate PD-1 expression on macrophages and examine its effect on anti-tumor immunity in gastric cancer (GC) patients., Methods: The frequency of PD-1 + macrophages obtained from GC tissue was determined by multicolor flow cytometry (n = 15). Double immunohistochemistry staining of PD-1 and CD68 was also performed to evaluate the correlations among the frequency of PD-1 + macrophages, clinicopathological characteristics, and prognosis in GC patients (n = 102)., Results: The frequency of PD-1 + macrophages was significantly higher in GC tissue than in non-tumor gastric tissue. The phagocytotic activity of PD-1 + macrophages was severely impaired compared with that of PD-1 - macrophages. The 5-year disease-specific survival rates in patients with PD-1 + macrophage Low (the frequency of PD-1 + macrophages; < 0.85%) and those with PD-1 + macrophage High (the frequency of PD-1 + macrophages; ≥ 0.85%) were 85.9 and 65.8%, respectively (P = 0.008). Finally, multivariate analysis showed the frequency of PD-1 + macrophage to be an independent prognostic factor., Conclusions: The function of PD-1 + macrophage was severely impaired and increased frequency of PD-1 + macrophage worsened the prognosis of GC patients. PD-1-PD-L1 therapies may function through a direct effect on macrophages in GC.

Main Conclusion: The physiological importance of MpUVR8 in UV-B resistance and translocation in a UV-B-dependent manner from the cytosol into the nucleus is characterized in Marchantia polymorpha. UV RESISTANCE LOCUS 8 (UVR8) is an ultraviolet-B (UV-B) light receptor functioning for UV-B sensing and tolerance in Arabidopsis thaliana and other species. It is unclear whether UVR8 physiologically functions in UV-B-induced defense responses in Marchantia polymorpha, which belongs to the earliest diverging group of embryophyte lineages. Here, we demonstrate that UVR8 has a physiological function in UV-B tolerance and that there is a UVR8-dependent pathway involved. In addition, a UVR8-independent pathway is revealed. We examine the tissue-specific expression pattern of M. polymorpha UVR8 (MpUVR8), showing that it is highly expressed in the apical notch in thalli and gametangiophores, as well as in antheridial and archegonial heads. Furthermore, Mpuvr8 KO plant transformants, in which the MpUVR8 locus was disrupted, were produced and analyzed to understand the physiological and molecular function of MpUVR8. Analysis using these plants indicates the important roles of MpUVR8 and MpUVR8-regulated genes, and of MpUVR8-independent pathways in UV-B tolerance. Subcellular localization of Citrine-fused MpUVR8 in M. polymorpha cells was also investigated. It was found to translocate from the cytosol into the nucleus in response to UV-B irradiation. Our findings indicate strong conservation of the physiological function of UVR8 and the molecular mechanisms for UVR8-dependent signal transduction through regulation of gene expression in embryophytes.

The standard procedure for remnant gastric cancer after esophago-proximal gastrectomy is total resection of the remnant stomach considering blood supply. However, sometimes surgery may be too invasive due to severe adhesion in the thoracic and mediastinal cavity. The blood supply to the remnant stomach depends on the right gastroepiploic artery and the right gastric artery. Therefore, preservation of the proximal region of the remnant stomach is thought to be anatomically impossible. We report a case of remnant gastric cancer that developed more than 12 years after lower thoracic esophagectomy plus proximal gastrectomy for Siewert Type I squamous cell carcinoma. We used intra-operative indocyanine green (ICG) venous-injection to evaluate blood flow and distal gastrectomy of the remnant stomach was performed by preserving the proximal stomach in the thoracic cavity through an abdominal approach. There were no complications of the remnant stomach or the anastomosis to the jejunum after surgery. In this case, we focused on the blood supply by collateral circulation through the anastomotic line from the remnant esophagus. After confirming blood supply with intra-operative evaluation using ICG fluorescence, less-invasive distal gastrectomy was successfully performed. As the intra-operative ICG-based evaluation for blood supply is a simple and safe method, it might be useful for determining the resection margin of various organs and be effective for the introduction of less invasive surgery. Here, we report a case and a review of the literature.