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Background/aim: The development of new biomarkers to predict cancer patient prognosis is expected to aid in treatment selection, contributing to improved outcomes. In this study, we extracted a candidate gene associated with patient prognosis from a public database and investigated the molecular and biological functions and clinical significance of the gene in gastric cancer., Materials and Methods: We analyzed The Cancer Genome Atlas database and identified the family with sequence similarity 32 member a (FAM32A) as a candidate gene. We investigated the clinicopathological significance of FAM32A mRNA and protein expression in 300 and 176 gastric cancer patients respectively. We evaluated the molecular and biological functions by suppressing FAM32A expression in gastric cancer cell lines using small interfering RNA., Results: In the polymerase chain reaction (PCR) cohort, low FAM32A expression group showed significantly shorter disease-specific survival (DSS) [hazard ratio (HR)=1.586; 95% confidence interval (95% CI)=1.056-2.382, p=0.026]. In the immunohistochemistry cohort, the FAM32A(-) group had significantly shorter overall survival (HR=1.703; 95% CI=1.050-2.764, p=0.031) and DSS (HR=2.123; 95% CI=1.185-3.804, p=0.011). Multivariate Cox hazard analysis revealed that FAM32A(-) was an independent adverse prognostic factor for DSS (p<0.001). AGS cell lines with FAM32A knockdown exhibited significant resistance to 5-fluorouracil (5-FU) and reduced apoptosis upon 5-FU administration. Gene set enrichment analysis indicated decreased gene expression related to the p53 signaling pathway in AGS cells with FAM32A knockdown that were treated with 5-FU., Conclusion: FAM32A suppression decreases 5-FU-induced apoptosis. Low FAM32A expression is associated with a poor prognosis in gastric cancer, suggesting its potential as a biomarker., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The severe malignancy of pancreatic ductal adenocarcinoma (PDAC) is mainly due to frequent local invasiveness and distant metastasis. As for local invasiveness, we previously reported that cancer-specific molecular alterations detected on resected PDAC specimen surfaces, so-called molecular surgical margin (MSM) positiveness, were significantly associated with postoperative locoregional recurrence and distant metastasis. However, due to anatomical limitations, achieving adequate surgical margins during pancreatic cancer resection is often challenging. Therefore, predicting local invasiveness based on the primary tumor's gene profile is crucial to avoid positive MSM., Materials and Methods: Genome-wide miRNA expression profiles were examined and compared between MSM-positive and negative cases. Candidate miRNAs were evaluated in another validation cohort, and their clinicopathological characteristics were examined. Mimic or inhibitor constructs of the candidate miRNA were transfected to PDAC cell lines to evaluate the miRNA function in the pancreatic cancer cell lines and detect the downstream targets., Results: Among some candidates with highly expressed miRNAs in MSM-positive cases by miRNA expression array, recurrence-free survival (RFS) was significantly shorter in the miR-210-3p high expression group (p=0.015). High miR-210-3p was significantly associated with large tumor diameter (p=0.001), anterior invasion positive (p=0.010), and positive lymph node metastasis (p<0.001). miR-210-3p inhibition in PDAC cell lines resulted in decreased proliferation and invasiveness. The iron-sulfur cluster assembly enzyme (ISCU) gene was identified as a target of miR-210-3p. ISCU reduction was significantly observed in PDAC primary tumors with high levels of miR-210-3p, leading to mitochondrial dysfunction in miR-210-3p-overexpressing PDAC cell lines, as demonstrated by glycolysis stress tests., Conclusion: Highly expressed hypoxia-inducible miR-210-3p in primary PDAC tissues induces locally invasive characteristics through mitochondrial dysfunction by suppressing ISCU expression, which may result in poor postoperative RFS outcomes., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Catheter-related bloodstream infections (CRBSIs) caused by Lactobacillus spp. and Lacticaseibacillus spp. are rare, and their clinical course and optimal treatment remain uncertain. In this report, we present a 46-year-old male patient who experienced clinically diagnosed Lacticaseibacillus paracasei CRBSI on four separate occasions, despite receiving systemic administration of antibiotics and antimicrobial lock therapy. The patient did not develop L. paracasei bacteremia after catheter removal. This case report furthers our knowledge of CRBSI caused by Lactobacillus and related genera and highlights the need for further research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background/aim: Organs of the digestive system are frequent sites of cancer development, and digestive tract cancers are the leading causes of death worldwide, including in Japan. Most of these cancers are associated with smoking or drinking habits. This study focused on the clinical and genomic characteristics of patients with these cancers using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which comprises a large volume of data on Japanese patients who have undergone tumor profiling gene panel tests., Patients and Methods: The genomic and clinical data from patients with digestive tract cancers registered in C-CAT between 2019 and 2023 were retrospectively reviewed. The data were derived from 412 patients with esophageal squamous cell carcinoma, 558 with gastric adenocarcinoma, 3,368 with colorectal adenocarcinoma, 139 with hepatocellular carcinoma, 2,050 with cholangiocarcinoma, and 2,552 with pancreatic ductal adenocarcinoma., Results: CDKN2A, CDKN2B, and MTAP mutations were associated with both smoking and drinking history, and patients with these mutations had a worse prognosis. Almost all gene alterations in CDKN2B and MTAP were deletions, often accompanied by CDKN2A deletion. CDKN2A mutation emerged as the most decisive prognostic factor among these mutations. Although CDKN2A mutations were frequently seen in esophageal squamous cell carcinoma, cholangiocarcinoma, and pancreatic ductal adenocarcinoma, statistically significant differences in survival outcomes were only identified in the latter two., Conclusion: CDKN2A mutations were associated with smoking and drinking in digestive cancers. This mutation was prevalent among patients with cholangiocarcinoma and pancreatic ductal adenocarcinoma, for whom they could serve as prognostic factors., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Enterovesical fistula (EVF) in Crohn's disease (CD) often does not improve with medical treatment and requires surgical treatment. The surgical treatment strategy for EVF in CD is definitive resection of the intestinal tract side, and performing a leak test using dye injection into the bladder after EVF dissection to determine the appropriate surgical procedure for the bladder side. This study aimed to evaluate the outcomes of surgical treatment for EVF in CD. Twenty-one patients who underwent surgery for EVF between 2006 and 2021 were included and retrospectively evaluated for clinical background, surgical procedures, and postoperative complications. The most common origin of EVF was the ileum (17 cases; 81%), and the most common site of EVF formation was the apex (12; 57%). Surgical approaches were laparotomy in 11 (52%) cases and laparoscopy in 10 (48%). Surgical procedures on the bladder side were fistula dissection in 13 (62%) cases and sutured closure of fistula in 8 (38%). A comparison of approaches revealed no significant difference in operative time, but the amount of blood loss was significantly less in the laparoscopy (p < 0.01). There was no significant difference in the occurrence of postoperative complications between approaches. Postoperative anti-TNF-α antibody agents were used in 17 (81%) cases, and there were no cases of recurrent EVF. In conclusion, definitive resection of the intestinal tract and minimal treatment on the bladder side were sufficient to achieve satisfactory outcomes for EVF in CD., Competing Interests: The authors report no conflicts of interest.

Background: Abnormal activation of the coagulation system is associated with malignant tumor progression. Although neoadjuvant treatment (NAT) for resectable esophageal squamous cell carcinoma (ESCC) is the standard of care, the correlation between coagulation status and prognosis of patients undergoing preoperative treatment is insufficiently understood., Methods: Patients (n = 200) who underwent radical subtotal esophagectomy after preoperative treatment for ESCC between January 2012 and December 2021were included in the analysis. Plasma D-dimer and fibrinogen levels and their combined indices (non-hypercoagulation; D-dimer and fibrinogen levels within the upper normal limit, or hypercoagulation; D-dimer or fibrinogen levels above the upper normal limit) were determined before and after NAT and correlated to clinicopathological factors and prognosis., Results: The nonhypercoagulation group achieved superior overall survival (OS) than the hypercoagulation group (5-year OS rates = 89% vs. 55%; hazard ratio 3.62, P = 0.0008) when determined according to coagulation status after NAT. Multivariate analysis showed that hypercoagulation after NAT served as an independent factor for poor postoperative OS (hazard ratio 3.20; P = 0.0028). The nonhypercoagulation group achieved significantly better disease-free survival (76% vs. 54%; P = 0.0065) than the hypercoagulation group that experienced a significantly higher rate of hematogenous metastasis as an initial recurrence (P = 0.0337)., Conclusions: Hypercoagulation state after NAT served as a valid indicator correlating with postoperative outcomes of patients with ESCC who underwent NAT followed by radical subtotal esophagectomy., (© 2024. Society of Surgical Oncology.)

Background: Advanced gastric cancer (GC) has a poor prognosis. This study aimed to identify novel GC-related genes as potential therapeutic targets., Methods: Killer cell lectin-like receptor G2 (KLRG2) was identified as a candidate gene by transcriptome analysis of metastatic GC tissues. Small interfering RNA-mediated KLRG2 knockdown in human GC cell lines was used to investigate KLRG2 involvement in signaling pathways and functional behaviors in vitro and in vivo. Clinicopathological data were analyzed in patients stratified according to tumor KLRG2 mRNA expression., Results: KLRG2 knockdown in GC cells decreased cell proliferation, migration, and invasion; caused cell cycle arrest in G 2 /M phase; induced apoptosis via caspase activation; suppressed JAK/STAT and MAPK-ERK1/2 pathway activities; and upregulated p53 and p38 MAPK activities. In mouse xenograft models of peritoneal metastasis, the number and weight of disseminated GC nodules were decreased by KLRG2 knockdown. High tumor levels of KLRG2 mRNA were significantly associated with lower 5-year overall survival (OS) and relapse-free survival (RFS) rates in patients with Stage I-III GC (5-year OS rate: 64.4% vs. 80.0%, P = 0.009; 5-year RFS rate: 62.8% vs. 78.1%, P = 0.030)., Conclusions: KLRG2 knockdown attenuated the malignant phenotypes of GC cells via downregulation of JAK/STAT and MAPK-ERK1/2 pathway activity and upregulation of p38 MAPK and p53. Targeted suppression of KLRG2 may serve as a new treatment approach for GC., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background/aim: Proximal gastrectomy (PG) is a therapy for early-stage proximal gastric cancer and offers advantages such as the preservation of food storage capacity and less body weight loss (BWL). Nevertheless, significant BWL following PG may occur, affecting the patient's well-being and survival. In this study, we aimed to identify the relevant factors for BWL following PG by analyzing an institutional database of patients., Patients and Methods: We enrolled 58 consecutive patients who underwent PG for gastric or esophagogastric junction cancer at our institution between April 2004 and March 2021. Based on BWL at 12 months postoperatively, we retrospectively compared and examined patient characteristics, surgical details, and nutritional markers., Results: The mean BWL of the 58 patients included in this analysis was 14.0±7.2%. When the patients were divided into BWL-moderate (n=29) and BWL-severe (n=29) groups using a cutoff value of 15.7%, the latter experienced early BWL within 1 month postoperatively, primarily due to body fat mass reduction, with no recovery during the 60 months of follow up. In contrast, gradual recovery was observed among patients in the BWL-moderate group after experiencing the lowest body weight 24 months postoperatively. A greater decrease in body fat mass than in muscle mass was observed in both groups. Blood hemoglobin levels did not recover in the BWL-severe group., Conclusion: The BWL-severe group after proximal gastrectomy demonstrated significantly greater early postoperative BWL, primarily attributed to a reduction in body fat mass, with hardly any recovery. Early postoperative nutritional intervention might be proposed to prevent long-term BWL., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Despite recent advances in the development of therapeutic antibodies, the prognosis of unresectable or metastatic gastric cancer (GC) remains poor. Here, we searched for genes involved in the malignant phenotype of GC and investigated the potential of one candidate gene to serve as a novel therapeutic target. Analysis of transcriptome datasets of GC identified natriuretic peptide receptor 1 (NPR1), a plasma membrane protein, as a potential target. We employed a panel of human GC cell lines and gene-specific small interfering RNA-mediated NPR1 silencing to investigate the roles of NPR1 in malignancy-associated functions and intracellular signaling pathways. We generated an anti-NPR1 polyclonal antibody and examined its efficacy in a mouse xenograft model of GC peritoneal dissemination. Associations between NPR1 expression in GC tissue and clinicopathological factors were also evaluated. NPR1 mRNA was significantly upregulated in several GC cell lines compared with normal epithelial cells. NPR1 silencing attenuated GC cell proliferation, invasion, and migration, and additionally induced the intrinsic apoptosis pathway associated with mitochondrial dysfunction and caspase activation via downregulation of BCL-2. Administration of anti-NPR1 antibody significantly reduced the number and volume of GC peritoneal tumors in xenografted mice. High expression of NPR1 mRNA in clinical GC specimens was associated with a significantly higher rate of postoperative recurrence and poorer prognosis. NPR1 regulates the intrinsic apoptosis pathway and plays an important role in promoting the GC malignant phenotype. Inhibition of NPR1 with antibodies may have potential as a novel therapeutic modality for unresectable or metastatic GC., (© 2023 UICC.)

To maintain fertility, male mice re-repress transposable elements (TEs) that were de-silenced in the early gonocytes before their differentiation into spermatogonia. However, the mechanism of TE silencing re-establishment remains unknown. Here, we found that the DNA-binding protein Morc1, in cooperation with the methyltransferase SetDB1, deposits the repressive histone mark H3K9me3 on a large fraction of activated TEs, leading to heterochromatin. Morc1 also triggers DNA methylation, but TEs targeted by Morc1-driven DNA methylation only slightly overlapped with those repressed by Morc1/SetDB1-dependent heterochromatin formation, suggesting that Morc1 silences TEs in two different manners. In contrast, TEs regulated by Morc1 and Miwi2, the nuclear PIWI-family protein, almost overlapped. Miwi2 binds to PIWI-interacting RNAs (piRNAs) that base-pair with TE mRNAs via sequence complementarity, while Morc1 DNA binding is not sequence specific, suggesting that Miwi2 selects its targets, and then, Morc1 acts to repress them with cofactors. A high-ordered mechanism of TE repression in gonocytes has been identified., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Some conventional prognostic biomarkers for esophageal squamous cell carcinoma (ESCC) have the disadvantage that they have only been investigated at the level of either mRNA or protein levels or only in individual cohorts. Associations between Syntaxin 3 (STX3) expression and malignancy have been reported in several tumor types but not in ESCC. Here, we investigated the levels of both STX3 mRNA and protein, and its prognostic potential in two independent cohorts of patients with ESCC., Methods: STX3 mRNA levels were examined in surgical specimens by quantitative PCR in a cohort that included 176 ESCC patients. STX3 protein levels were investigated in surgically resected ESCC tissues by immunohistochemistry using tissue microarrays in a different cohort of 177 ESCC patients. Correlations were analyzed between the expression of STX3 mRNA and protein with clinicopathological factors and long-term prognosis., Results: Quantitative PCR indicated a significant association between high level of STX3 mRNA expression and lymph node involvement, pathological stage, and poor overall survival. The multivariate analysis demonstrated that high STX3 mRNA expression was independently associated with poor overall survival outcomes. Immunohistochemistry revealed that STX3 protein expression in ESCC tissues and high STX3 protein expression were also significantly correlated with unfavorable overall survival., Conclusions: Overexpression of STX3 mRNA and protein may serve as potential prognostic biomarkers for ESCC patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Staging laparoscopy (SL) has been advocated for pancreatic cancer, mainly to evaluate the peritoneal washing cytology (CY) status, which seems to impact the prognosis of pancreatic cancer. To establish an optimal treatment strategy for CY positive (CY+) pancreatic cancer cases, real-world clinical data about CY status-depending surgical outcomes should be accumulated., Methods: Peritoneal washing samples were collected from 183 consecutive patients who could be classified as either resectable or borderline resectable (BR) pancreatic cancer between January 2012 and December 2020. Correlations between the CY status and other clinicopathological parameters with the recurrence patterns and survival outcomes were examined. In addition, we analyzed several risk factors for the CY+ status and attempted to identify the patient population that may benefit most from SL., Results: A total of 24 of the 183 patients were CY+. Peritoneal recurrence occurred more frequently in CY+ cases than in CY- cases (29% vs. 6%, p < .001) and median survival time after surgery was significantly shorter in CY+ cases than in CY- cases (28.5 months vs. 67.5 months; p < .001). In detail, almost all CY+ patients among curative resection-intended cases had either elevated preoperative serum CA19-9 levels (≥250 U/mL) or DUPAN-2 levels (≥150 U/mL). Significant predictive factors of CY positivity were BR status (p = .028) and serum CA19-9 level exceeding 250 U/mL (p = .008)., Conclusion: CY status was identified as an independent prognostic factor, and SL examination should be recommended, especially for patients with risk factors for CY positivity, such as BR cancer and elevated serum CA19-9 levels., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/aim: To improve patient management, new biomarkers are required that stratify prognosis. Here we focused on glutamic acid decarboxylase 1 (GAD1), which is associated with proliferation of lung cancer cells, and investigated its expression and function in esophageal squamous cell carcinoma (ESCC)., Materials and Methods: We evaluated changes in the proliferative potential of ESCC cell lines using small interfering RNA-mediated GAD1 knockdown techniques. We analyzed GAD1 protein expression using a tissue microarray (TMA) and measured GAD1 mRNA expression to evaluate correlations between the expression level of each tissue and postoperative outcomes of two independent cohorts (the TMA and mRNA cohorts) of patients who underwent radical esophagectomy., Results: GAD1 knockdown reduced cell proliferation. In the TMA cohort, high GAD1 expression significantly correlated with lymph node metastasis and advanced stage. Disease-free survival was significantly shorter in the group with high GAD1 expression, as was overall survival. Multivariate analysis of overall survival showed that positivity for GAD1 was an independent prognostic factor for poor survival. In the mRNA cohort, GAD1 mRNA expression in ESCC tissues was significantly up-regulated compared with that in adjacent noncancerous mucosal tissues. When patients were divided into high- and low-expression groups according to the median GAD1 mRNA expression level in ESCC tissues, overall survival was significantly shortened in the high GAD1 expression group. The incidence of initial hematogenous recurrence was significantly higher in the group with high GAD1 expression., Conclusion: GAD1 expression mediates the proliferative potential of ESCC cells, and a high level may serve as a useful prognostic biomarker for patients with ESCC., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients., Aim: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC., Discussion: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

There is a need for serum diagnostic biomarkers to improve the prognosis of solid malignant tumors. Here, we conducted a single-institutional study to evaluate the diagnostic performance of serum stromal cell-derived factor 4 (SDF4) levels in cancer patients. Serum samples were collected from a total of 582 patients with solid cancers including gastric cancer (GC) and 80 healthy volunteers. SDF4 protein levels in sera, and conditioned media or lysates of human GC cell lines were measured by enzyme-linked immunosorbent assay, and those in GC tissue by immunohistochemistry. Serum SDF4 levels were higher in patients with cancer than the healthy control in all cancer type. Regarding GC, serum SDF4 levels distinguished healthy controls from GC patients with the area under the curve value of 0.973, sensitivity of 89%, and specificity of 99%. Serum SDF4 levels were significantly elevated in patient with early stage GC. In immunohistochemistry, the frequency of SDF4-positive GC tumors did not vary significantly between GC stages. The ability of human GC cell lines to both produce and secrete SDF4 was confirmed in vitro. In conclusion, serum SDF4 levels could be a promising candidate for a novel diagnostic biomarker for GC and other malignancies., (© 2023. Springer Nature Limited.)

Purposes: Systemic inflammation and immune status play a critical role in the development and progression of cancers. We evaluated the clinical significance of the preoperative systemic immune-inflammation index (SII) for predicting the long-term outcomes of patients who received neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC)., Methods: The subjects of this study were 277 patients who underwent curative resection of ESCC after neoadjuvant therapy. The SII was calculated as follows: SII = neutrophil × platelet/lymphocyte counts. Patients were stratified into high and low preoperative SII groups according to the cut-off value calculated by a receiver operating characteristic curve analysis. The Kaplan-Meier method and Cox proportional regression analysis were used to evaluate the correlation of SII to prognosis., Results: The optimal cutoff of the preoperative SII was set at 700. Patients were categorized into preoperative SII-low (n = 203) and SII-high (n = 74) groups. The preoperative SII was significantly associated with tumor size. The relapse-free survival of patients in the SII-high group was significantly shorter (P = 0.0087) and preoperative SII-high was identified as an independent prognostic factor (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.06-2.28, P = 0.0229). The prevalence of hematogenous recurrence was significantly higher in the SII-high group. When we stratified patients into three groups with an additional cutoff value of 1200, we observed an incremental decrease in relapse-free survival rates., Conclusions: High preoperative SII was associated with shorter relapse-free survival times for ESCC patients who underwent curative resection after neoadjuvant therapy., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background/aim: Pancreatic cancer cells release certain tissue factors into the bloodstream. It is well known that pancreatic cancer progresses with thrombus formation. Because we routinely measure serum D-dimer levels in preoperative patients as a screening marker of deep venous thrombosis, we examined its association with high serum D-dimer in our cohort of pancreatic cancer resected cases., Patients and Methods: We examined 315 patients with pancreatic ductal adenocarcinoma who underwent surgical resection in our department from January 2012 to July 2021. All cases were divided into high D-dimer cases (n=118) and low D-dimer cases (n=197) using the cut-off value of 1.0 μg/ml, an institutional upper limit. Clinicohistological characteristics and postoperative survival outcomes were evaluated., Results: Preoperative high D-dimer cases showed significantly worse progression-free survival (PFS) (p=0.021) and overall survival (OS) (p=0.027) than low D-dimer cases; median PFS was 13.9 months versus 21.4 months, and that of OS was 33.4 months versus 68.0 months. Clinicohistological characteristics of high D-dimer cases were age over 70 years (p<0.001), pathological portal vein invasion (p=0.003), and initially borderline resectable or unresectable cases (p=0.027). Multivariate analysis indicated that preoperative high D-dimer was a significant prognostic factor of PFS (hazard ratio=1.42, p=0.025) and OS (hazard ratio=1.51, p=0.036)., Conclusion: Preoperative high serum D-dimer over 1.0 μg/ml was associated with pathological portal vein invasion and could be an unfavorable prognostic marker of PFS and OS after surgery, typically due to distant metastasis., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Few studies have examined whether family caregivers' own primary care providers can affect caregiving-specific well-being, such as caregiver stress. In this pilot study, we explored whether primary care experiences when family caregivers report as patients were associated with the stress of caregiving., Methods: We used cross-sectional data from a survey conducted in Japan between November and December 2020. We recruited family caregivers aged 40-74 years who were caring for community-dwelling adults with chronic conditions. We assessed primary care experience using the Japanese version of the Primary Care Assessment Tool Short Form (JPCAT-SF) and caregiver stress using the Japanese short version of the Zarit Caregiver Burden Interview., Results: In total, 406 family caregivers were included in the analysis. The mean JPCAT-SF total score was 42.1 out of 100 points. The proportion of caregivers who had higher caregiver stress was 48.8%. After adjusting for possible confounders, the JPCAT-SF score was found to be significantly associated with caregiver stress (lower stress = 0 vs. higher stress = 1; adjusted prevalence ratio per 1 SD increase in JPCAT-SF score = 0.89; 95% CI 0.80-0.98). Among the subscales of the JPCAT-SF, longitudinality, and comprehensiveness (services available) were associated with caregiver stress., Conclusions: Better primary care experiences when family caregivers reported as patients were associated with lower caregiver stress. Longitudinality, which includes focusing attention on the individual as a whole person, and comprehensiveness in the context of building provider-patient relationships that make consultation easier when needed, were associated with lower stress., Competing Interests: The authors declare no conflict of interest in connection with this article., (© 2023 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Background: Small intestine carcinoma (SIC) cases in Japan have recently been treated with chemotherapy according to colorectal carcinoma classification, while papilla of Vater carcinoma (PVC) cases according to cholangiocarcinoma (CHC) classification. However, few research reports support the molecular genetic validity of these therapeutic choices., Patients and Methods: Here, we investigated the clinicopathological and molecular genetic factors of SIC and PVC. We used the data from the Japanese version of The Cancer Genome Atlas. Additionally, molecular genetic data on gastric adenocarcinoma (GAD), colorectal adenocarcinoma (CRAD), pancreatic ductal adenocarcinoma (PDAC), and CHC were also referred to., Results: This study consisted of tumor samples from 12 patients of SIC and three patients of PVC treated from January 2014 to March 2019. Among them, six patients had pancreatic invasion. t-Distributed stochastic neighbor embedding analysis showed that the gene expression pattern of SIC was similar not only to those of GAD and CRAD, but also to that of PDAC in the pancreatic invasion patients. In addition, PVC resembled the GAD, CRAD, and PDAC, rather than the CHC. The molecular genetic characteristics of the six patients with pancreatic invasion were: one had high microsatellite instability, two had a TP53 driver mutation, and three had tumor mutation burden values <1 mutation/Mb with no driver mutation., Conclusions: In this study, the extensive gene expression profiling of organ carcinomas newly suggests that SIC or PVC may resemble GAD, CRAD, and PDAC. In addition, the data demonstrate that pancreatic invasive patients may be classified into several subtypes using molecular genetic factors., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Although healthcare professionals pay attention to the drugs prescribed by physicians, few studies have assessed self-medication by family caregivers. Family caregivers' experience of interprofessional care in the care of patients can influence caregivers' health behaviors., Objectives: This study aimed to describe self-medication among family caregivers of community-dwelling adult patients, and to assess association between family caregivers' experience of interprofessional care and their self-medication, adjusting for possible confounding factors., Methods: We conducted a cross-sectional survey from November to December 2020 in Ibaraki Prefecture, Japan. Family caregivers between 40 and 74 years old and caring for community-dwelling adult patients with chronic conditions were recruited. The use of any self-medication in the last 2 weeks by family caregivers was the outcome variable. The explanatory variable was family caregivers' experience of interprofessional care in the care of patients, using the Japanese version of the Caregivers' Experience Instrument (J-IEXPAC CAREGIVERS). Adjusted covariates were age, gender, educational attainment, annual household income, self-rated health, and caregiving time of family caregivers., Results: Of 1091 recruited family caregivers, 750 were included in the analysis. A total of 258 (34.4%) family caregivers reported having used self-medication in the past 2 weeks. Logistic regression analysis showed that having a higher score on the J-IEXPAC CAREGIVERS (odds ratio 0.80 per 1 standard deviation increase) was associated with less use of self-medication by caregivers., Conclusions: This study revealed that about one-third of family caregivers self-medicate, and this practice is associated with a less positive experience of interprofessional care. These results suggest that it is important for healthcare professionals to be aware of the health condition of family caregivers and to provide appropriate advice regarding self-medication., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer., Methods: This multi-institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI)., Results: Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm., Conclusion: This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer., Competing Interests: Hideki Ueno, Hideo Baba, Jun Watanabe, and Kenichi Hakamada are editorial board members of Annals of Gastroenterological Surgery., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Purpose: An animal model of laparoscopic hepatectomy showed that bleeding from the hepatic vein is influenced by airway pressure. However, there are little research reports on how airway pressure leads to risks in clinical practice. The main objective of this study was to investigate the impact of preoperative forced expiratory volume % in 1 s (FEV1.0%) on intraoperative blood loss in laparoscopic hepatectomy., Methods: All patients who underwent pure laparoscopic or open hepatectomy from April 2011 to July 2020 were classified into two groups by preoperative spirometry: those with obstructive ventilatory impairment (obstructive group; FEV1.0% < 70%) and those with normal respiratory function (ormal group; FEV1.0% ≥ 70%). Massive blood loss was defined as 400 mL for laparoscopic hepatectomy., Results: In total, 247 and 445 patients underwent pure laparoscopic and open hepatectomy, respectively. Regarding laparoscopic hepatectomy group, blood loss was significantly greater in the obstructive group (122 vs. 100 mL, P = 0.042). Multivariate analysis revealed that high IWATE criteria which classify the surgical difficulty of laparoscopic hepatectomy (≥ 7, odds ratio (OR): 4.50, P = 0.004) and low preoperative FEV1.0% (< 70%, OR: 2.28, P = 0.043) were independent risk factors for blood loss during laparoscopic hepatectomy. In contrast, FEV1.0% did not affect the blood loss (522 vs. 605 mL, P = 0.113) during open hepatectomy., Conclusion: Obstructive ventilatory impairment (low FEV1.0%) may affect the amount of bleeding during laparoscopic hepatectomy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Neoadjuvant treatment is currently the gold standard for advanced esophageal squamous cell carcinoma (ESCC). Several studies have examined the value of blood count-based indexes for predicting short- and long-term outcomes after esophagectomy for ESCC, but the relative predictive value of pretreatment, preoperative, and postoperative indexes has not yet been examined., Methods: This study included 320 patients with thoracic ESCC who underwent subtotal esophagectomy after neoadjuvant chemotherapy or chemoradiotherapy at our institution. A total of 19 candidate blood parameters were measured before neoadjuvant treatment as well as preoperatively and postoperatively. The ability of the parameters to predict postoperative complications, overall survival (OS), and relapse-free survival (RFS) was assessed using receiver operating characteristic (ROC) curve analysis and Cox regression analysis., Results: ROC curve analysis indicated that preoperative platelet to lymphocyte ratio (PLR) had the best predictive value with an optimal cutoff value of 166. Patients with high preoperative PLR (≥166) had significantly shorter OS and RFS and significantly higher incidences of hematogenous recurrence and postoperative pneumonia compared with patients with low preoperative PLR (&lt;166). In multivariate analysis, high preoperative PLR and high preoperative serum carcinoembryonic antigen level were independent predictors of poor prognosis., Conclusion: Preoperative PLR is a good predictor of short- and long-term prognosis in patients with advanced ESCC who receive neoadjuvant treatment followed by radical resection., (© 2023 S. Karger AG, Basel.)

Background: The pretreatment albumin-globulin ratio (AGR) is a frequently used inflammation-associated factor that has been reported to have associations with the survival outcomes of various malignancies., Methods: We retrospectively analyzed 162 patients with pancreatic cancer who underwent preoperative treatment followed by curative surgery at Nagoya University Hospital between April 2010 and December 2020. Representative nutritional status indicators of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin-globulin ratio (AGR) were calculated for each case., Results: Among pretreatment blood examination parameters, only AGR (cutoff: 1.33) showed a significant difference in overall survival time (OS) and progression-free survival time (PFS) from the beginning of the preoperative treatment. Median PFS was 22.3 mo, in high AGR cases and 17.1 mo, in low AGR cases ( P  = 0.019). Median OS was 48.7 mo, in high AGR cases and 32.9 mo, in low AGR cases ( P  = 0.043)., Conclusion: High pretreatment AGR may be a favorable prognostic factor for pancreatic cancer patients who received preoperative multimodal therapy followed by curative cancer resection. It may imply that nutritional status and inflammation control before the multimodal treatment affect the survival outcomes of pancreatic cancer cases and needs to be optimized.

Background: Usefulness of various nutritional indices for management of patients with esophageal squamous cell carcinoma (ESCC) has been reported. Although Controlling Nutritional Status (CONUT) score is among promising indices to predict outcome, the optimal timing for its measurement during the perioperative period remains unknown. Here the prognostic value of the CONUT score was assessed among patients with ESCC., Methods: We analyzed 464 patients who underwent subtotal esophagectomy of ESCC, of which 276 patients were treated with neoadjuvant treatment (NAT). The significance of the associations between candidate parameters including the CONUT score and postoperative prognosis were evaluated., Result: Among the 25 candidate predictors, the preoperative CONUT score had the highest correlation with overall survival (OS) after surgery. Patients were categorized as follows: normal, mild, and moderate or severe, on the basis of the preoperative CONUT score. OS was significantly shortened as the CONUT score worsened. Multivariable analysis revealed that the CONUT scores of the subgroups mild (Hazard ratio [HR] 1.69) and moderate or severe (HR 2.18) were independent predictors of poor prognosis for OS. Furthermore, in an analysis limited to patients who underwent NAT, OS was significantly shortened as the preoperative CONUT score worsened. On the contrary, there was no significant difference in RFS among patient groups stratified by the CONUT score determined before NAT., Conclusions: Our study indicates that the preoperative CONUT score serves as a prognosticator in resectable ESCC. The preoperative CONUT value was more useful than that before NAT in patients administered NAT., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: For family caregivers, who are generally regarded as a vulnerable population, having regular checkups is a desirable health behavior. This study examined family caregivers' habit of having regular checkups prior to becoming involved with professionals who care for patients, and whether they had had recent checkups. We then examined the association between family caregivers' experience with professionals and their participation in checkups after adjusting for the past habit., Methods: We conducted a cross sectional survey in Japan between November and December 2020. We recruited family caregivers who were aged 40-74 years and caring for community-dwelling adult patients. The outcome variable was whether family caregivers had undergone any health checkups since April 2019. We assessed family caregivers' experience using the Japanese version of the Caregivers' Experience Instrument (J-IEXPAC CAREGIVERS)., Results: Of the 1091 recruited family caregivers, 629 were included in the analysis. Of these, 358 had previously undergone regular checkups, and 158 had no checkups or selected the option "unknown." Outcome rates in each group were 74.6% and 43.0%, respectively, and 62.0% for all 629 caregivers. Multivariate modified Poisson regression analysis revealed that among the J-IEXPAC CAREGIVERS scores, only the domain score for attention for the caregiver was significantly associated with family caregivers' participation in checkups (adjusted prevalence ratio per 1 SD increase = 1.07; 95% CI 1.01-1.14)., Conclusions: Among family caregivers' experience with professionals, the factor that focused on caregivers themselves was significantly associated with their participation in checkups. This finding underscores the significance of caregiver-focused care., Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article., (© 2022 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Crohn's disease patients suffer from symptoms originating from small bowel lesions, including strictures. As many of these patients also have a potential risk of surgery, it is important to consider various therapeutic strategies for small bowel lesions. We retrospectively analyzed the therapeutic effects of ustekinumab, interleukin-12 and -23 blocker, for small intestinal lesions and intestinal stenosis in order to contribute to the optimal management of Crohn's disease. Patients who underwent total colonoscopy or small bowel endoscopy before and after the introduction of ustekinumab were enrolled in this study. The colonoscopy findings were evaluated by the simple endoscopic score for Crohn's disease, and small bowel endoscopy findings were evaluated using the modified simple endoscopic score for Crohn's disease. Endoscopic scores were compared before and after the introduction of ustekinumab and between the responders and non-responders to ustekinumab. Responders were defined as those whose Crohn's disease activity index score at 24 weeks fell below 150 points, or those whose score decreased by more than 100 points from the pre-induction level. A total of 50 patients were enrolled in the study, and the number of responders was 35. Pre-induction simple endoscopic scores were lower for responders, but no significant difference was observed in the modified simple endoscopic scores. The total decrease in the endoscopic score was significantly higher in the responders for both the small and large intestine. Use of ustekinumab as a first-line treatment for patients with small bowel lesions or stricture-prone lesions may be a new treatment consideration in the future., Competing Interests: Masanao Nakamura, Takeshi Yamamura and Tsunaki Sawada were supported by Janssen Pharmaceutical KK, which manufactured ustekinumab, in the form of lecture fee. Other authors have no COI to disclose.

Background: The axon guidance gene family, SLIT/ROBO pathway, controls neural network formation, which correlates with the development of several cancers., Methods: We found through analysis of the public database that ROBO4, one of the axon guidance molecules among the SLIT/ROBO family, is significantly downregulated in primary pancreatic cancer tissues compared with adjacent normal tissues. We carried out transfection experiments using three pancreatic cancer cell lines (MiaPaCa-2, BxPC-3, and SW1990) and one pancreatic duct epithelial cell line (HPDE6c7). A total of 51 clinical samples were then examined by immunohistochemical staining to find an association between ROBO4 expression at the protein level, clinical characteristics, and surgical outcomes., Results: ROBO4 overexpression suppressed the invasion and migration abilities in MiaPaCa-2 and BxPC-3, while ROBO4 siRNA transfection to SW1990 and HPDE6c7 enhanced those activities. PCR-based profiling detected MMP-9 as a candidate downstream target of ROBO4, which was validated by decreased MMP-9 activity after the ROBO4 overexpression assay. High ROBO4 expression clinical samples had significantly better overall survival rather than low ROBO4 cases (P = 0.048)., Conclusion: These findings suggest that decreased ROBO4 expression activates malignant phenotypes in cancer cells and is correlated with poor survival outcomes in pancreatic cancer., (© 2022. Society of Surgical Oncology.)

Background: Localized gastric cancer (GC) becomes fatal once recurring. We still have room for improving their prognoses., Methods: Transcriptomic analysis was done on surgically resected specimens of 16 patients with UICC stage III GC who underwent curative gastrectomy and adjuvant oral fluoropyrimidine monotherapy. Four of them were free from disease for longer than 5 years, and the others experienced metachronous metastasis within 2 years after surgery. Quantitative RT-PCR determined mRNA expression levels of primary gastric cancer tissues, which were collected from 180 patients who underwent gastric resection for stage II-III GC without preoperative treatment between 2001 and 2014. We tested alteration of malignant phenotypes including drug resistance of GC cell lines by siRNA and shRNA-mediated knockdown and forced expression experiments., Results: CPLX1 was identified as a candidate biomarker for GC recurrence among 57,749 genes. Inhibiting and forced expression experiments indicated that CPLX1 promotes proliferation, motility, and invasiveness of GC cells, and decreases apoptosis and sensitivity to fluorouracil. Subcutaneous xenograft mouse models revealed that shRNA-mediated knockdown of CPLX1 also attenuated tumor growth of MKN1 cells in vivo. Overexpression of CPLX1 in gastric cancer tissue correlated with worse prognosis and was an independent risk factor for peritoneal recurrence in subgroups receiving adjuvant chemotherapy., Conclusions: CPLX1 may represent a biomarker for recurrence of gastric cancer and a target for therapy., (© 2022. Japanese Society of Gastroenterology.)

Background/aim: The regimen of nanoliposomal irinotecan plus 5-fluorouracil and leucovorin (Nal-IRI/FL) was approved in Japan as second-line chemotherapy after gemcitabine-based treatment for pancreatic ductal adenocarcinoma (PDAC) in 2020. We examined the difference in outcome between patients treated with second-line folinic acid, fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX) and those treated with nal-IRI/FL after first-line gemcitabine and nab-paclitaxel (GnP)., Patients and Methods: The outcomes of 34 patients with PDAC who received second-line FOLFIRINOX (n=21) or nal-IRI/FL (n=13) after GnP at our Department from January 2016 to June 2021 were reviewed retrospectively., Results: Patient backgrounds did not differ between the groups. Dose reduction was more frequently required for treatment with FOLFIRINOX than with nal-IRI/FL (86% vs. 46%, p=0.022). Pegfilgrastim and aprepitant were used more frequently in the FOLFIRINOX group (both p<0.01). Progression-free survival (5.9 vs. 8.3 months) and overall survival (9.1 vs. 11.2 months) did not differ significantly between the groups. The frequency of grade 3 (Common Terminology Criteria for Adverse Events) or higher adverse events was similar between the groups. All-grade peripheral neuropathy was more common in the FOLFIRINOX group (100% vs. 77%, p=0.048)., Conclusion: FOLFIRINOX and nal-IRI/FL as second-line therapy after GnP provided similar prognoses, although supportive treatment and dose reduction were more frequently required for FOLFIRINOX., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Surgical resection is the standard treatment for bile duct cancer. However, even when surgical resection is possible, the 5-year survival rate is reportedly 25.0-55.0%. Therefore, bile duct cancer is associated with poor prognoses. We conducted a clinicopathological investigation, focusing on the histological phenomenon of tumour budding, which has previously been reported to be correlated with the survival of patients with a variety of cancers., Patients and Methods: To investigate the significance of tumour budding in distal bile duct cancer, we recruited 65 patients who underwent pancreatoduodenectomy at our institution between 1995 and 2011. Tumour budding was observed and evaluated using the 'hot spot method'. The 'low' budding group comprised 0-4 cell clusters and the 'high' budding group ≥5 cell clusters. Additionally, immunostaining was performed in high-budding areas., Results: Tumour budding and stage were confirmed using a Cox proportional hazards model as independent prognostic factors for overall survival (p<0.05) in all patients. There was a significant association between budding and zinc finger E-box binding homeobox 1 expression, an endothelial-mesenchymal transition-induced transcription factor. In stage II cases, the prognosis was significantly worse in the 'high' budding group compared to that in the 'low' budding group., Conclusion: The budding phenomenon is an independent prognostic factor for patients with distal bile duct cancer. Understanding the mechanisms underlying tumour budding in distal bile duct cancer and its relationship with poor prognoses may be useful for the development of novel treatments for this disease., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

To improve the outcome of gastric cancer, novel markers that predict postoperative prognosis are required. For this purpose, the function of cellular retinoic acid binding protein 1 ( CRABP1 ) in gastric cancer cells was investigated and it was determined whether it serves as a novel biomarker for gastric cancer. Reverse transcription‑quantitative (RT‑q)PCR and a PCR‑array method were used to determine whether the expression of CRABP1 mRNA in gastric cancer cell lines correlated with the expression of cancer‑related genes. The correlations of CRABP1 mRNA expression in tissues with clinicopathological factors of 230 patients who underwent radical gastrectomy were further evaluated. CRABP1 mRNA levels varied among gastric cancer cell lines and showed significant positive correlations with numerous epithelial‑mesenchymal transition factors. Additionally, CRABP1 knockdown significantly suppressed the proliferation, migration and invasion of gastric cancer cell lines. In a mouse xenograft model of peritoneal metastasis of gastric cancer, it was found that the total weight of disseminated nodules was lower in the group, in which CRABP1 mRNA levels were knocked down compared with those of the untransfected group. Disease‑free survival (DFS) was significantly shorter in patients with high expression of CRABP1 , and multivariate analysis of DFS revealed that high expression of CRABP1 in the tumor area and lymph node metastasis served as an independent factor associated with poor prognosis. High expression of CRABP1 in cancer tissues was associated with a greater incidence of peritoneal recurrences after curative gastrectomy. These findings indicated that CRABP1 contributes to the malignant phenotype of gastric cancer cells and may serve as a biomarker for prognosing recurrence after curative resection, particularly peritoneal dissemination.

Background/aim: Antiangiogenic chemotherapy is the backbone of the various anticancer therapies. To date no practical biomarker predicting their antitumor effects and toxicity has been reported. We aimed to determine the feasibility of direct retinal observation as a practical biomarker in antiangiogenic chemotherapy., Patients and Methods: By direct retinal observation using a nonmydriatic retinal camera, we measured retinal microvessel diameters in 10 patients with colorectal cancer before and after intravenous infusion of bevacizumab and oxaliplatin. All patients also received oral capecitabine during their therapy., Results: Retinal microvessel diameters were decreased from baseline temporarily by 14.5±6.5% after infusion of bevacizumab and oxaliplatin in five patients who responded to treatment and 8.8±6.2% in the other five patients (p=0.008)., Conclusion: Measurement of retinal microvessel diameters by direct observation appears to be feasible in patients receiving systemic chemotherapy. The decrease of retinal microvessel diameters might indicate improved tumor response to treatment with bevacizumab-containing systemic chemotherapy., Competing Interests: Dr. Ando reports grants and personal fees from Chugai Pharmaceutical Co., Ltd., grants and personal fees from Kyowa Kirin Co., Ltd., grants and personal fees from Nippon Kayaku Co., Ltd., grants and personal fees from Yakult Honsha Co., Ltd., grants and personal fees from Ono Pharmaceutical Co., Ltd., grants and personal fees from Taiho Pharmaceutical Co., Ltd., grants and personal fees from Daiichi-Sankyo Co., Ltd., grants and personal fees from Eisai Co., Ltd., personal fees from Eli Lilly Japan K.K., personal fees from Novartis Pharma K.K., personal fees from Bayer Holding Ltd., personal fees from Bristol-Myers Squibb, personal fees from Sawai Pharmaceutical Co., Ltd, personal fees from Roche Diagnostics K.K., personal fees from MSD K.K, personal fees from Astellas Pharma Inc., personal fees from Otsuka Holdings Co., Ltd., personal fees from Sanwa Kagaku Kenkyusho Co., Ltd., personal fees from Hisamitsu Pharmaceutical Co., Inc., and grants from Mochida Pharmaceutical Co., Ltd. Dr. Nakayama reports personal fees from Chugai Pharmaceutical Co., Ltd., personal fees from Yakult Honsha Co., Ltd., personal fees from Taiho Pharmaceutical Co., Ltd., personal fees from Eli Lilly Japan K.K., personal fees from Miyarinsan Pharmaceutical Co., Ltd., personal fees from Takeda Pharmaceutical Co., Ltd., and research funding to his institution from Eli Lilly Japan K.K. as outside the submitted work. All remaining Authors have declared no conflicts of interest., (Copyright 2022, International Institute of Anticancer Research.)

Background: Metastatic gastric cancer (GC) has a poor prognosis, and elucidating the molecular mechanisms involved in metastasis may lead to the development of novel therapeutic modalities., Methods: Transcriptome analysis of surgically resected metastatic tissue from GC patients and noncancerous tissue was performed to identify novel metastasis-related genes. Analyses of in vitro cell function, apoptosis, the cell cycle and cancer stemness were performed using GC cell lines with a stable knockout of a candidate gene. In vivo percutaneous, peritoneal dissemination and liver metastasis xenograft models were also generated. PCR array and proteome analyses were performed. Expression of the candidate gene was analyzed in GC tissues from 300 patients., Results: Lysosomal Associated Membrane Protein Family Member 5 (LAMP5) was upregulated in the metastatic tissues. LAMP5 knockout significantly suppressed proliferation, invasion, and migration of GC cells and increased apoptosis, cell cycle arrest and cancer stemness. LAMP5 knockout virtually suppressed tumor growth in in vivo percutaneous, peritoneal dissemination and liver metastasis models. EMT- and autophagy-related genes were associated with LAMP5. High LAMP5 mRNA levels were significantly associated with a worse prognosis., Conclusion: LAMP5 plays a vital role in metastasis formation and may be a promising novel target of drug development for metastatic GC in the future., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Despite numerous studies of peripancreatic inflammatory fluid collection (PIFC) that report on the relevance of the drain amylase concentration (D-AMY), early prediction using this assay is problematic. This study aimed to investigate the clinical significance of measuring the D-AMY at 3 h after gastrectomy (POD0) for gastric cancer., Methods: This retrospective analysis included consecutive patients who underwent gastrectomy combined with peripancreatic lymph node dissection. The predictive value of D-AMY on POD0 and postoperative day 1 (POD1) for clinically relevant PIFC was evaluated together or individually., Results: Analyses were performed in 204 patients. Twenty (9.8%) patients experienced PIFC. D-AMY cutoffs of 721 IU/L on POD0 and 1695 IU/L on POD1 were determined using the receiver operating characteristic curve analysis for predicting PIFC. The D-AMY on POD0 had higher sensitivity (80%) but lower specificity (66.3%) for prediction of PIFC, compared with those of D-AMY on POD1 (65%, 89.1%, respectively). When combination marker analysis was performed, the highest risk group (D-AMY ≥ the cutoff values of POD0 and POD1) were associated with an elevated rate of occurrence (44%) and a high positive likelihood ratio (7.36) compared with those of the single cutoff group. The lowest risk group (D-AMY < the cutoff values on POD0 and POD1) was associated with a low rate of occurrence (2.5%) and low negative likelihood ratio (0.24) compared with those of the single cutoff group., Conclusions: Combined measurements of D-AMYs on POD0 and POD1 enhanced early prediction of PIFC after gastrectomy., (© 2021. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Aim: To examine the relationship between the use of home-visit nursing services (VNS) for patients and their family caregivers' experience of interprofessional care, which is an indicator of the care process., Methods: We used data from a cross-sectional survey in Japan, 2020. Family caregivers 40-74 years old and caring for community-dwelling patients with chronic conditions were recruited. The outcome variable was family caregivers' experience, reflecting the quality of interprofessional care for patients and their caregivers. We used the Japanese version of the Caregivers' Experience Instrument (J-IEXPAC CAREGIVERS), which includes two domains: attention for the patient and attention for the caregiver. The main factor was the use of VNS, and covariates were socioeconomic factors of the caregivers and the use of other health and social care services. J-IEXPAC CAREGIVERS scores were divided into two groups by median values and analyzed by multivariate logistic regression analyses., Results: A total of 566 caregivers were included in the analysis. The median age was 62 years old. VNS was used in 86 cases (15.2%). Logistic regression analyses revealed that the use of VNS was significantly associated with a higher total score group for J-IEXPAC CAREGIVERS (odds ratio = 3.02; 95% confidence interval 1.54-5.91). Of the J-IEXPAC CAREGIVERS domains, attention for the patient was significant., Conclusions: We found that the use of VNS was likely to provide a better experience among family caregivers. Our findings suggest that visiting nurses fulfill their expected role as core members of a multidisciplinary team.