Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Platelets form complexes with gastric cancer (GC) cells via direct contact, enhancing their malignant behavior. In the present study, the molecules responsible for GC cell-platelet interactions were examined and their therapeutic application in inhibiting the peritoneal dissemination of GC was investigated. First, the inhibitory effects of various candidate surface molecules were investigated on platelets and GC cells, such as C-type lectin-like receptor 2 (CLEC-2), glycoprotein VI (GPVI) and integrin αIIbβ3, in the platelet-induced enhancement of GC cell malignant potential. Second, the therapeutic effects of molecules responsible for the development and progression of GC were investigated in a mouse model of peritoneal dissemination. Platelet-induced enhancement of the migratory ability of GC cells was markedly inhibited by an anti-GPVI antibody and inhibitor of galectin-3, a GPVI ligand. However, neither the CLEC-2 inhibitor nor the integrin-blocking peptide significantly suppressed this enhanced migratory ability. In experiments using mouse GC cells and platelets, the migratory and invasive abilities enhanced by platelets were significantly suppressed by the anti-GPVI antibody and galectin-3 inhibitor. Furthermore, in vivo analyses demonstrated that the platelet-induced enhancement of peritoneal dissemination was significantly suppressed by the coadministration of anti-GPVI antibody and galectin-3 inhibitor, and was nearly eliminated by the combined treatment. The inhibition of adhesion resulting from GPVI-galectin-3 interaction may be a promising therapeutic strategy for preventing peritoneal dissemination in patients with GC.

DOI： 10.3892/ol.2023.14125

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Circular RNAs (circRNAs) comprise a large class of endogenous non-coding RNA with covalently closed loops and have independent functions as linear transcripts transcribed from identical genes. circRNAs are generated by a "back-splicing" process regulated by regulatory elements in cis and associating proteins in trans. Many studies have shown that circRNAs play important roles in multiple processes, including splicing, transcription, chromatin modification, miRNA sponges, and protein decoys. circRNAs are highly stable because of their closed ring structure, which prevents them from degradation by exonucleases, and are more abundant in terminally differentiated cells, such as brains. Recently, it was demonstrated that numerous circRNAs are differentially expressed in cancer cells, and their dysfunction is involved in tumorigenesis and metastasis. However, the crucial functions of these circRNAs and the dysregulation of circRNAs in cancer are still unknown. In this review, we summarize the recent reports on the biogenesis and biology of circRNAs and then catalog the advances in using circRNAs as biomarkers and therapeutic targets for cancer therapy, particularly esophageal cancer.

DOI： 10.3390/biomedicines10071643

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Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Recent studies have highlighted the importance of understanding trends in blood glucose levels. We examined the differences in blood glucose fluctuations according to the reconstruction method used after distal gastrectomy (DG) in patients with non-diabetic gastric cancer (GC). METHODS: Sixty-one patients who underwent DG followed by either Billroth 1 (B1) or Roux-en-Y (R-Y) reconstruction were enrolled in this study. We used flash continuous glucose monitoring (CGM), a new technique for assessing glycemic control, to document the post-gastrectomy glycemic profile. Immediately before discharge, a CGM sensor was placed subcutaneously to evaluate blood glucose trends for 2 weeks. RESULTS: The coefficient of variation of glucose levels was significantly higher in the Roux-en-Y (R-Y) group than in the Billroth I (B-I) group (p = 0.0260). The time below range (TBR, glucose levels of < 70 mg/dL) was also significantly higher in the R-Y group (p = 0.0115). Logistic regression analysis revealed that preoperative casual glucose levels of < 100 mg/dL and R-Y reconstruction were independently correlated with risk factors for a postoperative nocturnal TBR of > 30% (p = 0.006 and 0.042, respectively). CONCLUSION: Our findings provide new insights into the post-DG reconstruction method selected for patients with non-diabetic gastric cancer by assessing postoperative blood glucose fluctuations using flash CGM.

DOI： 10.1007/s00595-021-02404-4

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: High-mobility group box-1 (HMGB1) is involved in the tumorigenesis and metastasis of various cancers. The present study investigated the roles of extracellular HMGB1 in the progression of gastric cancer (GC) and the therapeutic effects of recombinant human soluble thrombomodulin (rTM) targeting HMGB1. METHODS: The effects of extracellular HMGB1 and rTM on GC cells were assessed using proliferation and Transwell assays. Their effects on local tumor growth and metastasis were evaluated using subcutaneous tumor and liver metastasis mouse models, respectively. Plasma HMGB1 concentrations in GC patients were measured using ELISA. The relationships between plasma HMGB1 concentrations and the prognosis and clinicopathological factors of patients were also investigated. RESULTS: GC proliferation, migration, and invasion abilities were promoted by increases in extracellular HMGB1 concentrations and alleviated by rTM. In the subcutaneous tumor model, local tumor growth was promoted by the addition of rhHMGB1 and alleviated by rTM. Similar changes occurred in the liver metastasis model. Recurrence-free survival (p &lt; 0.01) and overall survival (p = 0.01) were significantly worse in patients with high plasma HMGB1 concentrations. CONCLUSION: Plasma HMGB1 concentrations are a prognostic marker in GC patients. Extracellular HMGB1 promotes cancer progression and has potential as a novel treatment target in GC cells for rTM.

DOI： 10.3390/ijms23063264

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Circular RNA is a novel endogenous non-coding RNA with a stable loop structure, and theories for its biogenesis and usefulness as a biomarker in various cancers have been proposed. The present study investigated the significance of circular FAT1 (circFAT1) as a novel biomarker in esophageal squamous cell carcinoma (ESCC). METHOD: CircFAT1 expression levels were measured in ESCC cell lines and the effects of downregulating circFAT1 on cell migration and invasion were examined using a transwell assay. The functions of miR-548g, which will be sponged by circFAT1, were assessed. Furthermore, the expression of circFAT1 was evaluated in 51 radically resected ESCC tissue samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between circFAT1 expression, clinicopathological factors, and patient prognosis were analyzed. RESULTS: CircFAT1 expression levels were significantly lower in tumor tissue than in adjacent non-tumorous mucosal tissue (p = 0.01). The downregulation of circFAT1 expression promoted ESCC cell migration and invasive ability, but not proliferation. The expression of miR-548g was upregulated by the downregulation of circFAT1. The overexpression of miR-548g also promoted ESCC cell migration and invasion. Recurrence-free survival (p = 0.02) and cancer-specific survival (p = 0.04) rates were significantly higher in patients with elevated circFAT1 expression levels. CONCLUSION: The expression level of circFAT1 is a novel prognostic marker in ESCC patients. New treatment strategies may be developed using the tumor suppressive functions of circFAT1.

DOI： 10.1245/s10434-021-10089-9

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Anterior gradient 2 (AGR2) reportedly promotes tumor growth and has an unfavorable impact on survival in several cancers. However, no comprehensive functional analysis of AGR2 in esophageal squamous cell carcinoma (ESCC) has been performed. In the present study, the function and clinical significance of AGR2 were examined using ESCC cell lines and clinical samples. AGR2 was upregulated in EC tissue and ESCC cell lines. The downregulation of AGR2 suppressed cell proliferation and increased the proportion of G2/M‑phase cells and phosphorylation of p53 in TP53‑wild‑type ESCC and osteosarcoma cells. However, these changes were not observed in TP53‑mutant ESCC cells. In addition, immunohistochemistry results demonstrated that high AGR2 and low p53 expression levels in ESCC tissues were correlated with a worse prognosis. These results suggested that although AGR2 enhanced cell proliferation by inhibiting p53 phosphorylation in TP53‑wild‑type ESCC, the same mechanism did not regulate cell functions in TP53‑mutant ESCC. Thus, AGR2 served an important role in ESCC progression and might be a useful prognostic marker in patients with TP53‑wild‑type ESCC.

DOI： 10.3892/or.2021.8211

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The targeting of membrane proteins that are activated in cancer stem cells (CSCs) represents one of the key recent strategies in cancer therapy. The present study analyzed ion channel expression profiles and functions in pancreatic CSCs (PCSCs). Cells strongly expressing aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were isolated from the human pancreatic PK59 cell line using fluorescence‑activated cell sorting, and PCSCs were identified based on tumorsphere formation. Microarray analysis was performed to investigate the gene expression profiles in PCSCs. ALDH1A1 messenger RNA levels were higher in PCSCs compared with non‑PCSCs. PCSCs were resistant to 5‑fluorouracil and capable of redifferentiation. The results of the microarray analysis revealed that gene expression related to ion channels, including voltage‑gated potassium channels (Kv), was upregulated in PCSCs compared with non‑PCSCs. 4‑Aminopyridine (4‑AP), a potent Kv inhibitor, exhibited greater cytotoxicity in PCSCs compared with non‑PCSCs. In a xenograft model in nude mice, tumor volumes were significantly lower in mice inoculated with PK59 cells pre‑treated with 4‑AP compared with those in mice injected with non‑treated cells. The present results identified a role of Kv in the persistence of PCSCs and suggested that the Kv inhibitor 4‑AP may have potential as a therapeutic agent for pancreatic carcinoma.

DOI： 10.3892/ijo.2021.5256

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Language：English   Publishing type：Research paper (scientific journal)  

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DOI： 10.1245/s10434-021-10126-7

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Language：English   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Tissue biopsies are the gold-standard for investigating the molecular characterization of tumors. However, a "solid" biopsy is an invasive procedure that cannot capture real-time tumor dynamics and may yield inaccurate information because of intratumoral heterogeneity. In this review, we summarize the current state of knowledge about surgical treatment-associated "liquid" biopsy for patients with digestive organ tumors. A liquid biopsy is a technique involving the sampling and testing of non-solid biological materials, including blood, urine, saliva, and ascites. Previous studies have reported the potential value of blood-based biomarkers, circulating tumor cells, and cell-free nucleic acids as facilitators of cancer treatment. The applications of a liquid biopsy in a cancer treatment setting include screening and early diagnosis, prognostication, and outcome and recurrence monitoring of cancer. This technique has also been suggested as a useful tool in personalized medicine. The transition to precision medicine is still in its early stages. Soon, however, liquid biopsy is likely to form the basis of patient selection for molecular targeted therapies, predictions regarding chemotherapy sensitivity, and real-time evaluations of therapeutic effects.

DOI： 10.1007/s00595-020-02148-7

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: The regulation of gene expression by miRNAs plays an important role in cancer progression. Here, we investigated the role of miR-3663-3p in gastric cancer. PATIENTS AND METHODS: The relationship between miR-3663-3p expression, clinicopathological features and prognosis were retrospectively analyzed in 80 gastric cancer patients. RESULTS: miR-3663-3p expression was significantly lower in gastric cancer tissue than adjacent non-cancerous tissue (p=0.002). Recurrence free survival was significantly lower in patients with low miR-3663-3p expression (p=0.016). Low miR-3663-3p expression was also an independent predictive factor for recurrence (p=0.029). Overexpression of miR-3663-3p in gastric cancer cell lines significantly suppressed cell proliferation, migration/invasion, and induced G0/G1 arrest (p<0.01). Furthermore, overexpression of miR-3663-3p decreased Cyclin D1 mRNA and protein, and reduced the phosphorylation of Retinoblastoma (Rb) protein. CONCLUSION: miR-3663-3p is a clinically useful predictor of gastric cancer recurrence. It exhibits tumor suppressive features through limited entry into the cell cycle in a Cyclin D1-Rb dependent manner.

DOI： 10.21873/anticanres.15019

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Clinical significance of plasma urothelial carcinoma associated 1 (UCA1) in patients with colorectal cancer (CRC) remains unclear. This study investigated the usefulness of plasma UCA1 as a biomarker in patients with CRC. MATERIALS AND METHODS: UCA1 levels were measured in the plasma and tissue from patients with CRC by quantitative polymerase chain reaction. Relationships between plasma UCA1 and clinicopathological features were examined. RESULTS: Plasma UCA1 levels were significantly lower in patients with CRC than in healthy volunteers. UCA1 expression in B-Raf proto-oncogene serine/threonine kinase (BRAF)-mutant CRC tissue was also lower than that in non-cancerous tissue, although it was higher in CRC with wild-type BRAF. In right-sided CRC, a lower plasma UCA1 level was associated with pT4 and BRAF mutation. In contrast, in left-sided CRC, higher plasma UCA1 was associated with pT4 and pStage 3b-4. CONCLUSION: Plasma UCA1 is a useful biomarker for CRC detection and predicting clinicopathological features, particularly BRAF mutation.

DOI： 10.21873/anticanres.14941

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

DOI： 10.3892/ol.2021.12666

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)  

Background: TRIM37 (Tripartite Motif Containing 37) is an E3 ubiquitin ligase for histone H2A and inhibits transcription in several genes. However, it is not known whether it plays a role in gastric cancer (GC). In this study, we tested whether TRIM37 acts as a cancer-promoting factor by being overexpressed in GC. Methods: We analyzed GC cell lines and 124 primary tumors, which were curatively resected in our hospital between 2001 and 2003. Results: Overexpression of the TRIM37 protein was detected in almost all GC cell lines and GC samples (76 out of 124 cases) and was significantly correlated with lymphatic and venous invasion, advanced T-Stage, N-Stage, histology and high recurrence rate. Patients with TRIM37 overexpressing tumors had a worse survival rate than those with non-expressing tumors (P=0.0057). Moreover, TRIM37 positivity was identified as an independent factor predicting worse outcomes (P=0.018, Hazard ratio 3.41). The apoptotic cell analysis showed that the knockdown of TRIM37 increased apoptosis in comparison with the control. In TRIM37 overexpressing GC cells, knockdown of TRIM37 suppressed the migration and invasion. Conclusions: TRIM37 plays a crucial role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.

DOI： 10.7150/jca.47577

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Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1186/s12957-020-02052-x

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Language：English   Publishing type：Research paper (scientific journal)  

Cervical esophageal squamous cell carcinoma (CESCC) is less common compared with thoracic esophageal cancer, and few studies have investigated the clinicopathological features of CESCC. The present study analyzed 69 patients with CESCC who underwent various therapies at the University Hospital of Kyoto Prefectural University of Medicine between January 2000 and December 2016. The distance between the inferior border of the cricoid cartilage and upper edge of the tumor was evaluated using positron emission tomography and computed tomography. Positive and negative values indicated oral and anal directions, respectively. Using receiver operating characteristic curves, the cut-off value for laryngeal preservation was calculated as -5 mm. According to this value, the patients were divided into two groups: The short group (distance from the cricoid cartilage ≥-5 mm) and long group (distance from the cricoid cartilage <-5 mm). There were no significant differences in clinicopathological factors between the two groups except for body mass index. In univariate analysis, the 3-year overall survival rate was significantly lower in short group (45.4 vs. 79.6%; P=0.009). In multivariate analysis, short group was an independent prognostic risk factor (hazard ratio=2.65; P=0.039). This may be due to lymphatic flow around the cervical esophagus.

DOI： 10.3892/ol.2020.11901

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Circular RNA is a novel endogenous non-coding RNA that can serve as a biomarker because of its stable loop structure. We investigated and examined the utility of plasma circERBB2 as a prognostic biomarker in 70 patients with gastric cancer who underwent gastrectomy. We investigated by real-time quantitative PCR the circERBB2 concentrations in the preoperative and postoperative plasma and the circERBB2 expression in the resected tumors. The relationships between circERBB2 concentration in plasma and the clinicopathological features and prognosis were analyzed. circERBB2 was detected in the preoperative plasma samples of 37 patients. The presence of circERBB2 in preoperative plasma (high group) was significantly correlated with lymph node metastasis (P = .035) and tended to be correlated with men (P = .069). Both relapse-free and overall survival were significantly poor in the high group (P = .001 and P = .009, respectively). The Cox proportional-hazard model revealed that the high group was an independent prognostic factor of relapse-free survival (P = .038). Among 16 patients of the high group, 13 patients did not show circERBB2 in the postoperative plasma. The concentration of circERBB2 in plasma was significantly higher in patients with recurrent cancer than those recurrence-free patients (P < .001). In 2 patients with recurrent cancer, plasma circERBB2 concentrations were increased, whereas, in 2 recurrence-free patients, these concentrations hardly changed during the treatment progress. The circERBB2 concentrations in preoperative plasma samples can be considered as a noninvasive prognostic biomarker for gastric cancer. Furthermore, monitoring the postoperative plasma circERBB2 concentrations may be useful for detecting gastric cancer recurrences.

DOI： 10.1111/cas.14645

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Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Few studies have reported the function and activation mechanism of ANO9 in esophageal squamous cell carcinoma (ESCC). The current study aimed to investigate the role of ANO9 in the regulation of tumor progression. METHODS: Knockdown experiments with human ESCC cell lines were performed using ANO9 siRNA, and the effects on cell proliferation, the cell cycle, apoptosis, and cellular movement were analyzed. Immunohistochemistry (IHC) analysis was performed on 57 primary tumor samples obtained from ESCC patients. RESULTS: In an in vitro study, depletion of ANO9 reduced cell proliferation, invasion, and migration in KYSE150 and KYSE 790 cells. In the cell cycle analysis, depletion of ANO9 increased the number of cells in G0/G1 arrest. In addition, the knockdown of ANO9 increased apoptosis. The results of the microarray analysis indicated that various centrosome-related genes such as CEP120, CNTRL, and SPAST were up- or downregulated in ANO9-depleted KYSE150 cells. The IHC results showed that high expression of ANO9 was associated with poor prognosis. CONCLUSIONS: The results of the current study suggest that ANO9 regulates the cell cycle via centrosome-related genes in ESCC.

DOI： 10.1245/s10434-020-08368-y

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Cholestatic liver injury leads to liver dysfunction. The available evidence suggests that platelets can either promote or reduce liver injury and fibrosis. This study focused on the functions of the C-type lectin-like receptor 2 (CLEC-2), a new special platelet receptor that binds with podoplanin-activating platelets. The role of CLEC-2 and podoplanin in cholestatic liver injury was investigated. Mice were injected intraperitoneally with weekly doses of anti-CLEC-2 antibody (2A2B10) to achieve effective CLEC-2 inhibition in their platelets. Next, left and middle hepatic bile duct ligation (BDL) procedures were performed, and mice were euthanized 1 week later (2A2B10-BDL group). In addition, mice were prepared for control groups, and relevant histological and laboratory variables were compared among these groups. The inhibition of CLEC-2 resulted in increasing hepatocellular necrosis, hepatic inflammation, and liver fibrosis. In addition, podoplanin was strongly expressed in hepatic sinusoidal endothelial cells in BDL-treated mice. Moreover, in 2A2B10-BDL mice, total plasma bile acid levels were significantly increased. In summary, podoplanin is expressed on hepatic sinusoidal endothelial cells upon BDL. Platelets bind with podoplanin via CLEC-2 and become activated. As a result, the total bile acid pool is decreased. Therefore, the CLEC-2-podoplanin interaction promotes liver protection and inhibits liver fibrosis after cholestatic liver injury.

DOI： 10.1016/j.ajpath.2020.05.009

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BACKGROUND: High-mobility group box-1 (HMGB1) is involved in a broad range of inflammatory responses and the progression of various types of malignancy. However, the roles of HMGB1 in the progression of esophageal squamous cell carcinoma (ESCC) are unclear. The aim of this study was to investigate the significance of intracellular and extracellular HMGB1 in ESCC. METHODS: HMGB1 levels were measured in the tissue and plasma of patients with ESCC, or in ESCC cell lines and their conditioned medium. The effects of downregulation of intracellular HMGB1 or upregulation of extracellular HMGB1 on proliferation, cell migration, and invasion were evaluated using proliferation, transwell, and wound healing assays. RESULTS: Downregulation of HMGB1 expression inhibited cell proliferation, migration, and invasion. On the other hand, upregulation of extracellular HMGB1 level by addition of recombinant HMGB1 promoted the migratory and invasive abilities of ESCC cells through increases of phosphorylation of the signal-regulated kinase 1/2 and NF-κBp65 proteins. These effects of extracellular HMGB1 were attenuated by treatment with recombinant soluble thrombomodulin, which adsorbs HMGB1. The expression of HMGB1 was significantly higher in tumor tissue (p = 0.008), and the concentration of HMGB1 in the plasma was significantly higher in patients with ESCC than in healthy volunteers (p = 0.04). Cancer-specific survival was worse in patients with high concentration of plasma HMGB1 (p = 0.01). CONCLUSION: Increase of HMGB1 levels in tumor cells or plasma plays a crucial role in the malignant potential of ESCC. Intracellular and extracellular HMGB1 may be a therapeutic target in ESCC.

DOI： 10.1245/s10434-020-08363-3

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Diagnosing early gastric cancer (EGC) or advanced gastric cancer (AGC) according to T-category is important for optimal GC treatment; however, the clinical and pathological diagnosis of tumor depths can sometimes vary. This study investigated the accuracy of clinical diagnosis of the tumor depth from the viewpoint of tumor localization and prognosis of patients with GC with discordance between clinical and pathological findings. METHODS: This study enrolled 741 patients with primary GC who underwent curative gastrectomy. Based on the clinical and pathological diagnosis of T-category, the patients were classified into four groups: Early-look EGC, Early-look AGC, Advanced-look EGC, and Advanced-look AGC. Tumor localization was classified longitudinally (the upper [U], middle [M], and lower [L] parts and cross-sectionally (the anterior [Ant] and posterior [Post] walls, and the lesser [Less] and greater [Gre] curvatures). RESULTS: Of the 462 clinical EGC cases, 52 were Early-look AGC cases that exhibited a significant association of tumor localization with the Post and Less in the U and M locations (UM-PL; p = 0.037). An Advanced-look EGC (p = 0.031) and Advanced-look AGC (p = 0.025) were independent prognostic factors for relapse-free survival each in pathological EGC and AGC, respectively. CONCLUSIONS: Patients with clinically diagnosed EGC but with pathologically diagnosed AGC more frequently presented tumor in the UM-PL than in any other location. Selection of therapeutic strategy according to the clinical diagnosis might be critical; however, it should be also considered that the accuracy of preoperative assessments varies with tumor localization.

DOI： 10.1007/s00423-020-01971-3

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PURPOSE: The long-term prognostic impact of the hemoglobin A1c levels has not yet been evaluated in patients with gastric cancer. The present study investigated the clinical significance of the hemoglobin A1c levels in patients with gastric cancer. METHODS: We enrolled 294 patients with stage II, III, or IV gastric cancer who underwent gastrectomy. The patients were divided into high preoperative hemoglobin A1c (> 6.0%) and low preoperative hemoglobin A1c (≤ 6.0%) groups. RESULTS: In patients with stage III gastric cancer with severe postoperative complications, the high preoperative hemoglobin A1c group had a significantly worse prognosis than the low preoperative hemoglobin A1c group (p = 0.0409). In patients without severe postoperative complications, the high preoperative hemoglobin A1c group had a significantly favorable prognosis compared with the low preoperative hemoglobin A1c group (p = 0.0348). CONCLUSION: The prognosis of patients with stage III gastric cancer having high preoperative hemoglobin A1c levels greatly depended on the presence or absence of postoperative complications. To avoid postoperative complications, optimal perioperative management and personalized treatments are critical, particularly for these patients.

DOI： 10.1007/s00595-020-02103-6

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Postoperative complications have been recognized to have an adverse prognostic impact in various types of cancer. However, in a recent study, it has been reported that postoperative complications of total gastrectomy with splenectomy have little impact on the long-term outcomes of patients with gastric cancer. In addition, the mechanisms underlying the effect of postoperative complications on outcomes remain to be elucidated. We hypothesized that immunosuppression by postoperative complications may affect long-term outcomes in patients with esophageal cancer. METHODS: In this retrospective study, we assessed in 153 patients with esophageal cancer who underwent curative subtotal esophagectomy at our hospital and examined the correlation between postoperative complications, and multiple clinicopathological factors, and long-term outcomes with the patients stratified by total lymphocyte count (TLC). RESULTS: The median preoperative TLC was 1432. A total of 115 patients (75.2%) had a TLC of ≥ 1000/μL (high TLC group), and the remaining 38 patients (24.8%) had a TLC of < 1000/μL (low TLC group). Postoperative complications occurred in 39 of 153 cases (25.5%). There was no significant correlation between postoperative complications and any of the clinicopathological factors in either group. In the high TLC group, patients with postoperative complications had significantly lower overall and disease-free survival rates compared with those without complications (p < 0.001 and p < 0.01, respectively). In the low TLC group, no survival difference between patients with and without postoperative complications was observed. CONCLUSIONS: Postoperative complications may have a minimal impact on long-term outcomes in immunodeficient patients.

DOI： 10.1245/s10434-020-08245-8

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Language：English   Publishing type：Research paper (scientific journal)  

Patients with gastric cancer are often malnourished during tumor progression. Malnutrition is a risk factor for postoperative complications and a poor prognosis. Early evaluation and management of nutrition can improve these outcomes. Various combined indices in which albumin is the primary component are used to evaluate the nutritional status, including the Prognostic Nutritional Index, Glasgow Prognostic Score, and Controlling Nutritional Status score. Both the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism guidelines recommend immediate and early oral/enteral nutrition. However, few reports have described the additional effects of preoperative immunonutrition on clinical outcomes of gastric cancer surgery. Gastrectomy types and reconstruction methods that consider the postoperative nutritional status have been used when oncologically acceptable. Total gastrectomy has recently tended to be avoided because of its negative impact on nutritional status. New findings obtained from the emergence of continuous glucose measurement, such as glucose fluctuation and nocturnal hypoglycemia, may affect nutritional management after gastrectomy. Some prospective clinical studies on perioperative nutritional intervention have set postoperative body weight loss as a primary endpoint. It seems important to continue oral nutritional supplement, even in small doses, to reduce body weight loss after gastrectomy. Evidence generated by prospective, well-developed randomized controlled studies must be disseminated so that nutritional therapy is widely recognized as an important multimodal therapy in patients undergoing gastric cancer surgery.

DOI： 10.1002/ags3.12351

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BACKGROUND: Glucose fluctuation after gastrectomy represented by dumping syndrome is a well-known post-gastrectomy syndrome that negatively impacts patient quality of life. However, the current methods of post-gastrectomy glucose monitoring do not comprehensively capture the postoperative blood glucose fluctuations that characterize this. METHODS: We used a continuous glucose monitoring (CGM) system to document the glycemic profiles of patients undergoing gastrectomy and compared these between patients undergoing distal gastrectomy (DG) and total gastrectomy (TG). To evaluate post-gastrectomy syndromes, including dumping syndrome, we used the Post-gastrectomy Syndrome Assessment Scale 37-item questionnaire. The glycemic profiles were also compared using this tool. RESULTS: We studied 57 patients who had undergone DG and 13 who had undergone TG between September 2017 and September 2019. Our results revealed larger diurnal glycemic variability and longer periods of nocturnal hypoglycemia after gastrectomy. The dumping score was worse in the TG than in the DG group (TG 2.4 ± 1.4 vs. DG 1.3 ± 1.2, P = 0.0061). Importantly, 30 of 57 DG patients (52.6%) and 5 of 13 TG patients (38.5%) experienced postprandial hypoglycemia following hyperglycemia without hypoglycemic symptoms. There was no correlation between the dumping symptom score and glycemic variability (ρ = 0.0545, P = 0.6662). CONCLUSIONS: CGM demonstrated diurnal glycemic variability and nocturnal hypoglycemia in patients undergoing gastrectomy. Because some hypoglycemic patients did not develop symptoms and glycemic variability was not necessarily associated with dumping symptom, dumping syndrome must only partially explain the postoperative glucose fluctuations.

DOI： 10.1007/s10120-019-01036-5

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Ultrasonically activated surgical devices (USADs) have become indispensable instruments for gastrointestinal surgery. In this study, we investigated the oncological safety of the use of USADs. MATERIALS AND METHODS: We harvested and cultivated the splashes and mist scattered from an USAD when cutting MKN45-derived cancer nodules. Seven days later, we observed viable cancer cells and the total number of cells was counted. The histopathology of the nodules cut by the USAD was also examined. RESULTS: The existence of viable cancer cells was confirmed by ex vivo cell culture. The number of viable cancer cells was reduced by slow grasping of the USAD. The surface of cancerous tissue cut by the USAD was partially heat-denatured, however, there were some parts in which cancerous tissue was exposed on the surface. CONCLUSION: Surgeons should recognize the possibility that cancer cells may be scattered by USAD use.

DOI： 10.21873/anticanres.14298

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients. METHODS: Genes whose expression was increased and correlated with worse prognosis in GC were screened using datasets from the Cancer Genome Atlas and Gene Expression Omnibus. We examined Claudin-6 (CLDN6) immunoreactivity in GC tissues and the effect of CLDN6 on cellular functions in GC cell lines. The mechanisms underlying GC-promoting function of CLDN6 were also investigated. RESULTS: CLDN6 was identified as a gene overexpressed in GC tumors as compared with adjacent non-tumorous tissues and whose increased expression was positively correlated with worse overall survival of GC patients, particularly those with Lauren's intestinal type GC, in data from multiple publicly available datasets. Additionally, membranous CLDN6 immunoreactivity detected in intestinal type GC tumors was correlated with worse overall survival. In CLDN6-expressing GC cells, silencing of CLDN6 inhibited cell proliferation and migration/invasion abilities, possibly via suppressing transcription of YAP1 and its downstream transcriptional targets at least in part. CONCLUSIONS: This study identified CLDN6 as a GC-promoting gene, suggesting that CLDN6 to be a possible single prognostic marker and promising therapeutic target for a subset of GC patients.

DOI： 10.1007/s10120-019-01014-x

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Elevated neutrophil-lymphocyte ratio (NLR) has been reported to be a poor prognostic factor in patients with colorectal cancer (CRC). However, no studies have focused on the dynamic change of preoperative NLR (pre-NLR) in CRC patients. We investigated the prognostic value of the change in NLR (ΔNLR) in CRC patients before and after surgery. PATIENTS AND METHODS: We retrospectively analyzed the data from 307 patients with stage II or III CRC. We compared the clinicopathological factors, OS, and DFS among the various NLR factors. RESULTS: The 5-year OS rate of the high ΔNLR group was significantly lower than that of the low ΔNLR group (p<0.01). The 5-year DFS rates of the high ΔNLR groups were worse than those in the low ΔNLR groups. In the multivariate analysis, ΔNLR was an independent prognostic factor (p=0.011). CONCLUSION: Decreasing post-NLR was related to better OS and DFS even in high pre-NLR patients with CRC.

DOI： 10.21873/anticanres.14197

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: The prognostic nutritional index (PNI) is reported to affect postoperative complications and survival of patients with esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the clinical significance of PNI in treatment of ESCC. PATIENTS AND METHODS: Two hundred and sixty-three patients who underwent radical esophagectomy were retrospectively analyzed. PNI was calculated in the pretreatment (pre-Tx), post-neoadjuvant chemotherapy (post-NAC), and postoperative periods. RESULTS: Pre-Tx PNI positively correlated with prognosis irrespective of undergoing NAC (p<0.05). In the patients with NAC, pre-Tx PNI was one of the independent prognostic factors (p=0.04). In patients with low pre-Tx PNI, the prognosis was improved by increase of PNI after NAC (p=0.08), and two cycles of NAC significantly correlated with high post-NAC PNI (p=0.04). CONCLUSION: Pre-Tx PNI is an independent prognostic factor irrespective of NAC. Patients in whom the post-NAC PNI can be improved have a high probability of obtaining a good prognosis.

DOI： 10.21873/invivo.12184

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Precise staging is indispensable to select the appropriate treatment strategy for gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be improved. This study investigated the clinical significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) for the prediction of pathological lymph node metastasis (pN+) in GC. METHODS: This was a retrospective study of 429 patients with GC who underwent curative gastrectomy. The predictive ability of NLR for pN+ was examined in comparison with that of computed tomography. RESULTS: The preoperative NLR ranged from 0.6 to 10.8 (median, 2.0), and the optimal cut-off value for predicting pN+ was 1.6 according to the receiver operating characteristic curve with the maximal Youden index. Multivariate analysis identified a NLR ≥ 1.6 (odds ratio (OR) 3.171; 95% confidence interval (CI) 1.448-7.235, p = 0.004) and cN+ (OR 2.426; 95% CI 1.221-4.958, p = 0.011) to be independent factors associated with pN+ in advanced GC (cT2-T4). On the other hand, a NLR ≥ 1.6 was not useful for predicting pN+ in early GC (cT1). In advanced GC, a NLR ≥ 1.6 detected pN+ with a higher sensitivity (84.9%) and negative predictive value (NPV) (63.9%) than conventional modalities (50.0 and 51.7%, respectively). When the subjects were limited to those with advanced GC with cN0, the sensitivity and NPV of a NLR ≥ 1.6 for pN+ increased further (90.7 and 81.0%, respectively). CONCLUSION: The preoperative NLR may be a useful complementary diagnostic tool for predicting pN+ in advanced GC because of its higher sensitivity and NPV than conventional modalities.

DOI： 10.1186/s12885-019-6404-8

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: This study examined whether the prognostic nutritional index (PNI) is a useful predictor of pathological lymph node metastasis (pN+) in gastric cancer (GC). PATIENTS AND METHODS: This study retrospectively examined 167 patients with advanced GC (cT2-T4) undergoing curative gastrectomy. The predictive ability of PNI for pN+ was evaluated in comparison with that of clinical lymph node metastasis (cN+) determined by computed tomography (CT). RESULTS: The optimal cut-off value of PNI for predicting pN+ was 46 according to the receiver operating characteristic curve analysis. Multivariate analysis revealed a PNI<46 [odds ratio (OR)=2.905; 95% confidence interval (CI)=1.347-6.638, p=0.006], cN+ (OR=2.323; 95%CI=1.204-4.579, p=0.012), and undifferentiated-type adenocarcinoma (OR=2.032; 95%CI=1.060-3.947, p=0.033) to be independent predictors of pN+. PNI detected pN+ with a higher specificity (84.9%) and positive predictive value (PPV) (75.6%) than cN+ (68.5% and 68.1%, respectively). When the subjects were limited to patients with cN+, the specificity and PPV of a PNI<46 for pN+ became markedly high (91.3% and 90.5%, respectively). CONCLUSION: PNI predicts pN+ with a high specificity in patients with a clinical diagnosis of advanced GC; therefore, PNI may aid in the definitive diagnosis of pN+, especially in combination with CT findings.

DOI： 10.21873/anticanres.13901

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Transient receptor potential vanilloid 2 (TRPV2) was recently shown to be involved in migrant potentials. The present study aimed to investigate its role in esophageal squamous cell carcinoma (ESCC). METHODS: Knockdown experiments were conducted using TRPV2 siRNA in human ESCC cell lines, and anti-tumor effects were analyzed. The gene expression profiles of cells were analyzed using a microarray method. An immunohistochemical staining was performed on 62 primary tumor samples. RESULTS: TRPV2 overexpression was observed in TE15 and KYSE170 cells. TRPV2 depletion suppressed proliferation, cell cycle progression, and invasion/migration ability, and induced apoptosis. A pathway analysis of microarray data showed that TRPV2 depletion down-regulated WNT/β-catenin signaling-related genes and basal cell carcinoma signaling-related genes. The suppression of tumor functions, such as proliferation, invasion, and angiogenesis, was predicted in the ontology analysis. Immunohistochemical analysis revealed a correlation between strong TRPV2 expression and a poor prognosis in ESCC patients. CONCLUSION: The present results suggest that TRPV2 regulates cancer progression by affecting WNT/β-catenin or basal cell carcinoma signaling, and that TRPV2 strong expression is associated with a worse prognosis in ESCC patients. These results provide an insight into the role of TRPV2 as a novel therapeutic target or biomarker for ESCC.

DOI： 10.1038/s41598-019-52227-0

PubMed

Language：English  

DOI： 10.21873/invivo.11695

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Although peritoneal lavage with distilled water performed after surgery prevents peritoneal seeding, cancer cells may avoid rupture under mild hypotonicity through regulatory volume decrease (RVD), which is the homeostatic regulation of ion and water transport. The aim of the present study was to investigate the effect of low temperature on cell volume and cell death under hypoosmolal conditions and determine the underlying molecular mechanisms in gastric cancer (GC). Three human GC cell lines (NUGC4, KATO‑III and MKN45) were exposed to hypotonic solutions, and the effects of low temperature on cell volume and viability were examined. Low temperature‑induced changes in membrane transporters were evaluated, and knockdown and overexpression experiments were conducted to determine their effects on cell volume during hypotonic stimulation. Low temperature (24˚C) during hypotonic stimulation inhibited RVD and enhanced the cytocidal effects on GC cells. The expression of leucine‑rich repeat containing protein A (LRRC8A), a component of a Cl‑ channel, was decreased, and aquaporin 5 (AQP5) expression was increased at low temperatures. LRRC8A knockdown markedly slowed the decrease in cell volume following cell swelling by hypotonic shock. AQP5 overexpression enhanced initial cell swelling after hypotonic shock and increased the final cell volume. These results suggest that a hypotonic solution at low temperature increased initial water influx via activation of AQP5 and decreased Cl‑ efflux via inhibition of LRRC8A. Therefore, low temperature enhanced the hypotonicity‑induced cytocidal effects on GC cells, and these results may contribute to the development of a novel lavage method effective in reducing peritoneal recurrence in GC.

DOI： 10.3892/ijo.2019.4853

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The volume-regulated anion channel is composed of leucine-rich repeat-containing protein A (LRRC8A) and is activated by hypotonic conditions to implement the process of regulatory volume decrease. The role of LRRC8A in regulating genes related to progression of esophageal squamous cell carcinoma (ESCC) was investigated, as well as the prognostic significance of LRRC8A expression in this tumor. Knockdown experiments were conducted using ESCC cell lines and LRRC8A siRNA to assess the influence of this protein on tumor function. In addition, the gene expression profile of ESCC was determined by microarray analysis. Immunohistochemistry was performed on 64 primary tumor samples from ESCC patients receiving radical esophagectomy. It was found that depletion of LRRC8A decreased cell proliferation and migration and also promoted apoptosis. Microarray data demonstrated G1/S checkpoint regulation and up-regulation or down-regulation of phosphatidylinositol 3-kinase/AKT signaling, matrix metalloproteinase, and integrin signaling-related genes (including p21, p27, MMP1, and ITGAV) in LRRC8A-depleted cells. Immunohistochemistry showed that LRRC8A expression was related to the pathologic N and T stage categories, and strong LRRC8A expression was correlated with a worse prognosis of ESCC. These findings indicate that LRRC8A modulates tumor progression by influencing cell cycle, apoptosis, and migration, providing new insights into its function as an effector or biomarker of ESCC.

DOI： 10.1016/j.ajpath.2019.06.006

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Robotic surgical systems have advantages over laparoscopic surgery. The object of this study was to assess patients' postoperative outcomes after robotic distal gastrectomy (RDG) compared to laparoscopic distal gastrectomy (LDG). PATIENTS AND METHODS: We retrospectively evaluated 21 and 119 patients who underwent RDG and LDG, respectively, for stage I gastric cancer. Short-term outcomes were compared including drain amylase levels and quality of life using a post-gastrectomy syndrome questionnaire. RESULTS: No patients experienced pancreatic fistula or anastomosis-related complications following RDG. The rate of overall complications tended to be lower in patients undergoing RDG. In addition to drain amylase level, inflammatory findings were lower after RDG than LDG. Patients undergoing RDG experienced a better quality of life and less dissatisfaction in daily life. CONCLUSION: RDG is feasible and produced highly-satisfactory results for early gastric cancer. We believe that the effective use of robotic surgery will increase safety and precision in minimally invasive surgery.

DOI： 10.21873/anticanres.13694

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Immunonutritional status is a known prognostic correlate in the context of gastric cancer (GC). In the present study, we investigated the prognostic relevance of a lipid profile-based immunonutritional score in patients with GC. METHODS: Data pertaining to 224 patients with stage II and III GC who underwent curative gastrectomy were retrospectively analyzed. The total cholesterol-lymphocyte score (TL score) was defined as follows: patients with both low total cholesterol (TC) and total lymphocyte count were allocated a score of 2; patients with only one or none of these biochemical abnormalities were allocated a score of 1 or 0, respectively. RESULTS: Among the serum lipid indices, low TC was the strongest predictor of cancer-specific survival (CSS; p = 0.001). On multivariate analysis, both low prognostic nutritional index (PNI) (p < 0.001) and high TL score (p = 0.003) were independent prognostic factors. PNI was significantly associated with peritoneal recurrence (p = 0.047), while TL score was significantly associated with locoregional and distant metastasis (p = 0.004 and p = 0.003, respectively). CONCLUSIONS: TL score may facilitate risk stratification of patients based on CSS. TL score plus PNI may help predict the recurrence pattern in patients with stage II and III GC.

DOI： 10.1007/s00423-019-01824-8

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This study aimed to investigate the abilities of the modified Glasgow prognostic score (mGPS) and other inflammatory scores to predict recurrence-free survival (RFS) among patients with colon cancer (CC). In addition, we evaluated the abilities of the mGPS to predict recurrence of stage II disease and the efficacy of adjuvant chemotherapy (AC) for stage III disease. METHODS: This retrospective study evaluated 477 patients with stage I-III CC who underwent curative surgery. These patients were categorized as having a low mGPS (mGPS 0) or a high mGPS (mGPS 1-2). RESULTS: Patients in the high mGPS group had significantly poorer RFS than patients in the low mGPS group (p < 0.01). Multivariate analysis revealed that a high mGPS independently predicted poor RFS (p < 0.01). Among patients with stage II CC, multivariate analysis revealed that the independent predictors of poor RFS were pT4 status (p < 0.01) and a high mGPS (p = 0.04). Among patients with stage III CC, AC was not significantly associated with the 5-year RFS for patients with a low mGPS (p = 0.38), although AC significantly improved the 5-year RFS for patients with a high mGPS (p < 0.01). CONCLUSION: The preoperative mGPS significantly predicted recurrence among patients with CC, even among patients with stage II CC. In addition, mGPS may provide valuable information regarding subgroups of patients with stage III CC who might benefit from AC.

DOI： 10.1007/s00423-019-01811-z

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Surgical therapy for stage IV gastric cancer patients is still debatable. The clinical outcomes were compared between gastrojejunal bypass and gastrectomy for metastatic gastric cancer patients. PATIENTS AND METHODS: A total of 110 patients with metastatic gastric cancer who underwent surgery were retrospectively analyzed. Twenty-nine patients underwent gastrojejunal bypass (group B) and 81 underwent gastrectomy (group G). RESULTS: There was no significant difference in the 3-year overall survival between Group G patients with partial gastrectomy and total gastrectomy. However, patients in group G had a significantly better prognosis compared to patients in group B (p=0.01 and 0.03, respectively). The prognosis of patients with postoperative chemotherapy was significantly better in group G compared to group B (p=0.03), whereas it was not significantly different for the patients without postoperative chemotherapy (p=0.24). CONCLUSION: Gastrectomy in patients with metastatic gastric cancer may improve survival when combined with postoperative chemotherapy.

DOI： 10.21873/anticanres.13376

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Recent studies have described important roles for the sodium iodide symporter (NIS) in tumor behavior. The objectives of the present study were to investigate the role of NIS in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in gastric cancer (GC). METHODS: In human GC cell lines, knockdown experiments were conducted using NIS siRNA, and the effects on proliferation, survival, and cellular movement were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 145 primary tumor samples obtained from GC patients. RESULTS: NIS was strongly expressed in MKN45 and MKN74 cells. The depletion of NIS inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that various interferon (IFN) signaling-related genes, such as STAT1, STAT2, IRF1, and IFIT1, were up-regulated in NIS-depleted MKN45 cells. Furthermore, the down-regulation of NIS affected the phosphorylation of MAPKs and NF-kB. Immunohistochemical staining showed that NIS was primarily located in the cytoplasm or cell membranes of carcinoma cells, and its expression was related to the histological type or venous invasion. Prognostic analyses revealed that the strong expression of NIS was associated with shorter postoperative survival. CONCLUSIONS: These results suggest that NIS regulates tumor progression by affecting IFN signaling, and that its strong expression is related to a worse prognosis in patients with GC. These results provide an insight into the role of NIS as a mediator and/or a biomarker for GC.

DOI： 10.1007/s10120-018-0874-2

PubMed

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S-transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients.

DOI： 10.1111/cas.13896

PubMed

Language：English  

Recent studies identified that low levels of tumour suppressor microRNAs (miRNAs) in plasma/serum relate to tumour progression and poor outcomes in cancers. We selected six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in oesophageal squamous cell carcinoma (ESCC) by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Univariate and multivariate analysis revealed that the low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC.

DOI： 10.1186/s12943-018-0929-3

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: The present study aimed to clarify an accurate diagnostic method for lymph node metastasis (LN+) in rectal neuroendocrine tumors (rNETs). PATIENTS AND METHODS: This was a retrospective study of 14 rNETs and 45 rectal adenocarcinoma patients undergoing rectal resection. The short axis of LNs was measured using CT and pathological findings (43 paraffin-fixed LNs in rNETs and 786 LNs in adenocarcinoma). RESULTS: The size of LN+ in CT and pathological findings was smaller in rNETs than adenocarcinoma (p=0.082 and p<0.001, respectively). The AUC values of ROC curves for detecting LN+ using LN sizes on CT were 0.837 for rNETs and 0.885 for adenocarcinoma (Cut-off values: 5 mm for rNETs, 7 mm for adenocarcinoma). rNETs were diagnosed with high accuracy using the cut-off value of rNETs (5 mm) (sensitivity: 80.0%, and specificity: 87.5%). CONCLUSION: The size of LN+ was smaller in rNETs than in adenocarcinoma, suggesting the essentiality of diagnostic criteria specific for rNETs.

DOI： 10.21873/anticanres.13141

PubMed

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese   Publishing type：Research paper (scientific journal)  

The patient was a 67-year-old man. A Type 0-Ⅱa+Ⅱc tumor, 20mm in size was observed in the 1st portion of the duodenum under magnifying endoscopy. Mucosal cancer was suspected and endoscopic resection was performed, with pathological findings as follows: Type 0-Ⅱa+Ⅱc, 19×12 mm, tub1, pT1b(SM2: 700 mm), pUL0, Ly0, V0, pHM0, pVM0. He refused subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)because of the high morbidity and mortality rates. Instead, he underwent only laparoscopic sampling of No. 5, 6, 12b, and 13a lymph nodes, and metastasis in a No. 6 node was pathologically confirmed. He eventually underwent SSPPD with D2, but no metastases were found in other lymph nodes. Pancreaticoduodenectomy is currently considered the best treatment option for complete removal of regional lymph nodes in duodenal cancer despite high morbidity and mortality rates. Further studies are needed to determine the pattern and incidence of lymph node metastasis by location and depth of the primary tumor, to establish optimal treatment guidelines for duodenal cancer.

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Trans-hiatal and -cervical approach mediastinoscopic radical esophagectomy (TMrE) for esophageal cancers is a less-invasive procedure and does not require for trans-thoracic approach management. However, some patients suffer from pleural effusion after TMrE. In the present study, we investigated the clinicopathological factors of patients needing drainage of pleural effusion (DPE) after TMrE. PATIENTS AND METHODS: This study included 118 patients who underwent TMrE between 2010 and 2016. RESULTS: There were 43, 34 and 41 patients that underwent none, a single, and two or more DPEs respectively. Left-side DPE was significantly more frequent compared to right-side DPE. Change in the C-reactive protein (CRP) levels after surgery was significantly higher in patients with multiple DPEs than patients with none or a single DPE. The hospitalization days were significantly longer for patients with multiple DPEs. CONCLUSION: Pleural effusion accumulates due to continuous inflammation. Although a temporary DPE is sometimes performed, post-operative chest drainage tubes are not necessarily needed.

DOI： 10.21873/anticanres.13069

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Few studies have examined postoperative CRP in esophageal cancer. We investigated the relationship between postoperative CRP values according to the postoperative period and prognosis in esophageal cancer. PATIENTS AND METHODS: We performed a retrospective cohort study including 187 patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC) between January 2008 and October 2016. RESULTS: CRP within 1 month of surgery was not related to overall survival (OS) or recurrence-free survival (RFS). In a univariate analysis, postoperative 2 months (2M)-CRP ≥0.15 ml/dl was associated with poorer OS (41.4 vs. 71.4%, p=0.0002) and RFS (28.9 vs. 51.3%, p=0.007). In a multivariate analysis, 2M-CRP ≥0.15 ml/dl was an independent factor for poorer OS (HR=2.27, 95%CI=1.03-3.34, p=0.005) and RFS (HR=1.65, 95%CI=1.08-2.52, p=0.020). The incidence of postoperative pneumonia was significantly higher in the 2M-CRP ≥0.15 ml/dl group (p=0.026). CONCLUSION: 2M-CRP ≥0.15 ml/dl is an independent prognostic factor for ESCC. Furthermore, postoperative pneumonia may be associated with patient prognosis after esophagectomy.

DOI： 10.21873/anticanres.13016

PubMed

Language：Japanese  

DOI： 10.3919/jjsa.79.337

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Jejunostomy is an essential route for nutritional support after esophageal cancer surgery. However, catheter-related complications may occur. This study compared the complications of feeding jejunostomy between gastric tube and jejunum after esophageal cancer surgery. PATIENTS AND METHODS: The records of 215 patients with esophageal cancer who underwent radical esophagectomy with retrosternal gastric tube reconstruction between January 2010 and November 2016 were examined. One hundred and thirty-three patients underwent feeding jejunostomy via gastric tube and 82 patients underwent the procedure via the jejunum, and their records were reviewed for catheter-related complications. RESULTS: Catheter-related complications occurred in five patients in the gastric tube group and 12 in the jejunum group (3.8% vs. 14.6%, p=0.005). Mechanical bowel obstruction requiring surgical therapy occurred in three patients in the jejunum group, but in none in the gastric tube group (p=0.026). CONCLUSION: Feeding jejunostomy reconstruction via gastric tube appears to be a safe and useful procedure.

DOI： 10.21873/anticanres.12811

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Aquaporin 1 (AQP1) is a membrane protein whose main function is to transfer water across cellular membranes. Recent studies have described important roles for AQP1 in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AQP1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 50 primary tumor samples underwent esophagectomy. AQP1 was primarily located in the cytoplasm and/or the nuclear membrane of carcinoma cells. The 5-year survival rate of patients with the "cytoplasm dominant" expression of AQP1 (47.1%) was significantly lower than other patients (83.2%). The depletion of AQP1 using siRNA induced apoptosis in TE5 and TE15 cells. The results of microarray analysis revealed that Death receptor signaling pathway-related genes were changed in AQP1-depleted TE5 cells. In conclusion, the results of the present study suggested that the cytoplasm dominant expression of AQP1 is related to a poor prognosis in patients with ESCC, and that it activates tumor progression by affecting Death receptor signaling pathway. These results provide insights into the role of AQP1 as a mediator of and/or a biomarker for ESCC.

DOI： 10.18632/oncotarget.25722

PubMed

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(公大)京都府立医科大学  

症例は85歳、男性。胃癌、S状結腸癌に対して腹腔鏡下幽門側胃切除、S状結腸切除術を施行したところ、胃癌はT2N2M1(LYM:腹部大動脈周囲リンパ節)Stage IV、S状結腸癌はT2N0M0 Stage Iの最終診断であった。胃癌に対してS-1による術後補助化学療法を行ったが、10ヵ月目に腹部大動脈周囲リンパ節再発を認めたため、一次化学療法としてS-1 + Docetaxel(1年6ヵ月間)を、二次化学療法としてCPT-11 + Cisplatin(1年8ヵ月間)を施行したが不応となり、三次化学療法としてPaclitaxel(PTX)+ Ramucirumab(Rmab)を行った。有害事象として好中球減少(Grade 3)、血小板減少(Grade 2)、蛋白尿(Grade 2)、高血圧症(Grade 2)を認めたが、PTXならびにRmabの投与間隔を延長することでこれらは軽快し、1年5ヵ月間もの投与継続と病勢コントロールが可能であった。PTX+Rmab療法は、有害事象に注意すれば高齢者に対しても長期投与が可能であり、再発胃癌に対する有用なレジメンとなり得る。(著者抄録)

Language：Japanese   Publisher：(NPO)日本食道学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Preoperative precise staging is essential for the treatment of gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be increased. The present study investigated the clinical value of positron emission tomography-computed tomography (PET-CT) for the staging of GC. METHODS: This was a retrospective study of 117 patients with a clinical diagnosis of advanced GC who underwent PET-CT followed by gastrectomy. The incidence of FDG uptake in the primary tumor or lymph nodes and its relationship with clinicopathological factors, particularly pathological stage (pStage) III/IV, were examined. RESULTS: FDG uptake in the primary tumor was noted in 83 patients (70.9%). FDG uptake in the lymph nodes was detected in 21 patients (17.9%), and its sensitivity and specificity for lymph node metastasis were 22.7 and 90.5%, respectively. Multiple logistic regression analyses showed that FDG uptake in the primary tumor (odds ratio (OR) 2.764; 95% confidence interval (CI) 1.104-7.459, p = 0.029) and that in the lymph nodes (OR 4.660; 95% CI 1.675-13.84, p = 0.003) were factors independently associated with pStage III/IV. FDG uptake in the primary tumor detected pStage III/IV with higher sensitivity (80.4%) and that in lymph nodes found pStage III/IV with higher specificity (88.7%) than those of upper endoscopy plus CT (60.9 and 67.6%, respectively). CONCLUSIONS: PET-CT appears to be a useful complementary modality in the assessment of pStage III/IV because of the high sensitivity of FDG uptake in the primary tumor and the high specificity of FDG uptake in the lymph nodes.

DOI： 10.1245/s10434-018-6455-0

PubMed

Language：Japanese   Publisher：日本外科代謝栄養学会  

Language：Japanese   Publisher：日本外科代謝栄養学会  

Language：English   Publishing type：Research paper (scientific journal)  

Background: Recent studies have reported essential roles for various intracellular pH regulators in epithelial carcinogenesis and tumor progression. The aims of the present study were to investigate the role of anion exchanger 2 (AE2) in the regulation of tumor progression-related genes and the prognostic value of its expression in esophageal squamous cell carcinoma (ESCC). Results: AE2 was strongly expressed in KYSE170 and TE13 cells. The depletion of AE2 in these cells increased cell migration and inhibited the induction of apoptosis. The results of the microarray analysis revealed that various matrix metalloproteinase (MMP) signaling pathway-related genes, such as MMP1, MMP12, and TIMP4, were up- or down-regulated in AE2-depleted KYSE170 cells. Immunohistochemical staining showed that AE2 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its expression pattern at the invasive front of the tumor was related to the pT category. Prognostic analyses revealed that the low-grade expression of AE2 at the invasive front was associated with shorter postoperative survival. Conclusions: The results of the present study suggest that reductions in AE2 in ESCC enhance cellular movement by activating MMP signaling pathways and are related to a poor prognosis in patients with ESCC. Methods: In human ESCC cell lines, knockdown experiments were conducted using AE2 siRNA, and the effects on cellular movement and survival were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy.

DOI： 10.18632/oncotarget.25417

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Background: Recent studies have reported important roles for chloride intracellular channel 1 (CLIC1) in various cancers; however, its involvement in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of the present study was to investigate the role of CLIC1 in human ESCC. Methods: CLIC1 expression in human ESCC cell lines was analyzed by Western blotting. Knockdown experiments were conducted with CLIC1 siRNA, and their effects on cell proliferation, the cell cycle, apoptosis, migration, and invasion were analyzed. The gene expression profiles of cells were analyzed using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. Results: ESCC cells strongly expressed CLIC1. The depletion of CLIC1 using siRNA inhibited cell proliferation, induced apoptosis, and promoted cell migration and invasion. The results of the microarray analysis revealed that the depletion of CLIC1 regulated apoptosis via the TLR2/JNK pathway. Immunohistochemistry showed that CLIC1 was present in the cytoplasm of carcinoma cells, and that the very strong or very weak expression of CLIC1 was an independent poor prognostic factor. Conclusions: The present results suggest that the very strong expression of CLIC1 enhances tumor survival, while its very weak expression promotes cellular movement. The present study provides an insight into the role of CLIC1 as a switch among tumor behaviors in ESCC.

DOI： 10.18632/oncotarget.25296

PubMed

Language：Japanese  

J-GLOBAL

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：English   Publisher：(一社)日本胃癌学会  

Authorship：Lead author   Language：English   Publisher：(一社)日本胃癌学会  

Language：English   Publisher：(一社)日本胃癌学会  

Language：English   Publishing type：Research paper (scientific journal)  

Synovial sarcoma (SS) is genetically characterized by chromosomal translocation, which generates SYT-SSX fusion transcripts. Although SS can occur in any body part, primary gastric SS is substantially rare. Here we describe a detection of the fusion gene sequence of gastric SS in plasma cell-free DNA (cfDNA). A gastric submucosal tumor was detected in the stomach of a 27-year-old woman and diagnosed as SS. Candidate intronic primers were designed to detect the intronic fusion breakpoint and this fusion sequence was confirmed in intron 10 of SYT and intron 5 of SSX2 by genomic polymerase chain reaction (PCR) and direct sequencing. A locked nucleic acid (LNA) probe specific to the fusion sequence was designed for detecting the fusion sequence in plasma and the fusion sequence was detected in preoperative plasma cfDNA, while not detected in postoperative plasma cfDNA. This technique will be useful for monitoring translocation-derived diseases such as SS.

DOI： 10.3748/wjg.v24.i8.949

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Institute of Anticancer Research  

BACKGROUND: Neoadjuvant chemotherapy (NAC) with 5-fluorouracil and cisplatin (FP) has been administered to patients with clinical stage II or III esophageal squamous cell carcinoma (ESCC). We aimed to confirm the clinical efficacy and outcomes of NAC with FP. PATIENTS AND METHODS: The clinicopathological features and survival of 152 patients with clinical stage II/III ESCC who received NAC with FP followed by radical esophagectomy were analyzed. RESULTS: The R1/2 resection rate was higher (p=0.06) and the high histological response rate was significantly lower (p=0.05) in those with clinical stage III disease. Invasion depth significantly improved in those with less than cT3 (17/30. 57%), but did not in more invasive cases (35/122, 29%) (p=0.004). T Factor was frequently improved in those with clinical stage II (p=0.08). Five-year survival rates in clinical stage II and III were 73% and 41%, respectively. A multivariate analysis identified clinical stage (p=0.01) and residual tumor (p<0.01) as independent prognostic factors. CONCLUSION: NAC with FP is effective for patients with clinical stage II ESCC, while its potency may be lower for those with clinical stage III or cT3 disease.

DOI： 10.21873/anticanres.12317

Scopus

PubMed

Language：Japanese   Publisher：(一社)日本消化管学会  

Language：Japanese   Publisher：(一社)日本消化管学会  

Language：Japanese   Publisher：(一社)日本腹部救急医学会  

Language：Japanese   Publisher：(一社)日本消化管学会  

Language：Japanese   Publisher：(一社)日本消化管学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本消化管学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本消化管学会  

Language：Japanese   Publisher：(株)ジェフコーポレーション  

Language：English   Publishing type：Research paper (scientific journal)  

YEATS domain containing 4 (YEATS4) has functions of chromatin modification and transcriptional regulation and is in a gene-amplified region (12q13) in various human cancers. In this study, we tested whether YEATS4 acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). We analyzed 5 GC cell lines and 135 primary tumor samples of GC, which were curatively resected in our hospital. Overexpression of the YEATS4 protein was frequently detected in GC cell lines (5/5 cell lines, 100%) and primary GC tumor tissues (32/135 cases, 23.7%). Knockdown of YEATS4 inhibited proliferation, migration and invasion of GC cells through NOTCH2 down-regulation in a TP53 mutation-independent manner, and induced apoptosis in wild-type TP53 GC cells. Moreover, knockdown of YEATS4 improved chemosensitivity for CDDP and L-OHP. Overexpression of YEATS4 protein significantly correlated with more aggressive lymphatic invasion, larger tumor size, deeper tumor depth, positive lymph node metastasis and recurrence. Patients with YEATS4-overexpressing tumors had a lower overall survival rate than those with non-expressing tumors. Multivariate analysis demonstrated that YEATS4 was independently associated with poor outcomes. These findings suggest that YEATS4 plays a pivotal role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.

PubMed

Language：English  

J-GLOBAL

Authorship：Lead author   Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Authorship：Lead author   Language：Japanese  

J-GLOBAL

Authorship：Lead author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (commerce magazine)  

J-GLOBAL

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Language：Japanese   Publisher：生命科学系学会合同年次大会運営事務局  

Language：Japanese   Publisher：生命科学系学会合同年次大会運営事務局  

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Language：English  

A lymphocele is one of the complications of systematic pelvic or para-aortic lymphadenectomy. Although most patients are entirely asymptomatic, our patient exhibited an obstructive ileus at the jejunum compressed by a lymphocele. We report here a case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection. A 68-year-old woman with sigmoid colon cancer (T3N2bM1a) underwent laparoscopic sigmoidectomy. After 4 courses of chemotherapy (CapeOX + Bmab), para-aortic lymphadenectomy was additionally performed. One month later, an obstructive ileus occurred suddenly due to a lymphocele. A drainage catheter was placed into the lymphocele and a total of 35 mL of autologous peripheral blood was injected in 4 divided doses through the catheter. The volume of the lymphocele gradually reduced and the ileus improved after blood injection. This is the first report of a successful case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection without any complications.

DOI： 10.1016/j.radcr.2017.08.014

PubMed

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

Background: Peritoneal lavage with distilled water has been used for surgeries of various cancers to reduce peritoneal recurrence. This study examined whether blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects in gastric cancer (GC). Results: A potassium channel blocker inhibited the occurrence of regulatory volume decrease (RVD) induced by mild hypotonic stimulation, and significantly enhanced cytocidal effects on GC cells. Incubating MKN45 cells with hypotonic solutions containing a potassium channel blocker significantly reduced the formation of peritoneal metastases in nude mice. Methods: The three human GC cell lines (HGC-27, Kato III, and MKN45) were exposed to mild hypotonic solutions, and the effects of blockade of potassium ion transports during hypotonic stimulation on cell volume changes and cell viabilities were examined. In the in vivo study, MKN45 cells stimulated with mild hypotonic solutions were intraperitoneally injected into nude mice, and the effects of blockade of potassium ion transports during hypotonic stimulation on the formation of peritoneal metastases were evaluated. Conclusions: Blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects on GC cells, which may contribute to development of a novel lavage method for further reduction of peritoneal recurrence in GC.

DOI： 10.18632/oncotarget.20736

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein, which is involved in several post-transcriptional aspects of RNA metabolism, including microRNA (miRNA) biogenesis. It affects distinct cell functions in different tissues and can have an impact on various pathological conditions. In the present study, we investigated the oncogenic functions of KHSRP and their underlying mechanisms in the pathogenesis of esophageal squamous cell carcinoma (ESCC). KHSRP expression levels were elevated in ESCC tumors when compared with those in non-tumorous tissues by immunohistochemistry, and cytoplasmic KHSRP overexpression was found to be an independent prognosticator for worse overall survival in a cohort of 104 patients with ESCC. KHSRP knockdown inhibited growth, migration, and invasion of ESCC cells. KHSRP knockdown also inhibited the maturation of cancer-associated miRNAs, such as miR-21, miR-130b, and miR-301, and induced the expression of their target mRNAs, such as BMP6, PDCD4, and TIMP3, resulting in the inhibition of epithelial-to-mesenchymal transition. Our findings uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC.

DOI： 10.18632/oncotarget.20926

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

A 39-year-old woman visited our hospital because of epigastric pain. Gastrointestinal endoscopy revealed a gastric submucosal tumor, 30mm in size, with ulcer locating near to the esophagogastric junction, and it was diagnosed with GIST by the endoscopic ultrasonography-guided fine needle aspiration. Then, she underwent laparoscopic surgery for the removal of gastric GIST. After peeling around the upper stomach, the local resection of the stomach was performed with linear staplers in the minor axis direction under the vision of the endoscope and laparoscope. Histopathological examinations confirmed that the tumor was GIST with an intermediate risk, and all surgical margins were free of GIST cells. Local resection with the laparoscopy endoscopy cooperative surgery(LECS)technique is a very useful way of the removal of gastric GISTs locating near to the esophagogastric junction in terms of the remnant gastric functions. Meanwhile, because the standard LECS requires the opening of the gastric lumen, there remains concerns about the intraperitoneal tumor dissemination for the gastric GIST with ulcer. We herein reported a case of laparoscopic local resection for a gastric GIST with ulcer locating near to the esophagogastric junction without gastric opening.

PubMed

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：日本臨床外科学会  

DOI： 10.3919/jjsa.78.371

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：日本臨床外科学会  

DOI： 10.3919/jjsa.78.470

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：(一社)日本癌治療学会  

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：(一社)日本癌治療学会  

Authorship：Lead author   Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：日本臨床外科学会  

DOI： 10.3919/jjsa.78.643

Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

BACKGROUND/AIM: This study aimed to investigate the efficacy of additional surgical resection (ASR) after endoscopic submucosal dissection (ESD) for superficial esophageal cancer (SEC). PATIENTS AND METHODS: Clinicopathological features and prognoses were analyzed in esophageal cancer (EC) cases with the indication for additional treatments (AT) after ESD (37 cases) and in cases that underwent primary resection (13 cases). RESULTS: Sixteen out of 37 cases underwent ASR. The remaining 21 cases underwent other treatments or observation. Although all ASR cases are alive without recurrence, recurrence developed in 2 non-ASR cases. Residual tumors were detected in 2 ASR cases. All 4 cases were T1b and positive for lymph vessel invasion (ly+). No significant difference was observed in surgical outcomes between ASR and primary surgical resection (PSR) cases. CONCLUSION: AT need to be considered for T1b and ly+ cases, and ASR is one of the effective AT. The safety of ASR was similar to PSR for SEC.

DOI： 10.21873/anticanres.11956

Web of Science

PubMed

Language：Japanese   Publisher：日本Acute Care Surgery学会  

Language：English   Publisher：日本癌学会  

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

Language：Japanese   Publisher：(一社)日本肝臓学会  

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein-Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and clinical features. In this study, we aimed to determine the potential utility of circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC tumors and plasma samples were determined by quantitative real-time polymerase chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed by the conventional method. Circulating cell-free EBV DNA was detected in 14 patients with GC: the sensitivity and specificity of detection were 71.4% (10/14) and 97.1% (135/139), respectively. Plasma EBV ratios were significantly correlated with the size of EBVaGC tumors, and the plasma EBV DNA detected before surgery in EBVaGC cases disappeared after surgery. Patients with EBVaGC may have a better prognosis, but circulating cell-free EBV DNA had no or little impact on prognosis. In addition, repeated assessment of the plasma EBV ratio in EBVaGC showed a decrease and increase in plasma EBV DNA after treatment and during tumor progression/recurrence, respectively. These results suggest the potential utility of circulating cell-free DNA to reveal EBV DNA for the identification of the EBVaGC subtype and/or for real-time monitoring of tumor progression as well as treatment response in patients with EBVaGC.

DOI： 10.18632/oncotarget.15675

Web of Science

PubMed

Language：Japanese   Publisher：(一社)日本外科学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本外科学会  

Language：English   Publisher：(一社)日本胃癌学会  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BAISHIDENG PUBLISHING GROUP INC  

AIM: To investigate the efficacy of thrombomodulin (TM)-α for treatment of disseminated intravascular coagulopathy (DIC) in the field of gastrointestinal surgery. METHODS: Thirty-six peri-operative DIC patients in the field of gastrointestinal surgery who were treated with TM-α were retrospectively investigated. The relationships between patient demographics and the efficacy of TM-α were examined. Analysis of survival at 28 d was also performed on some parameters by means of the Kaplan-Meier method. Relationships between the initiation of TM-α and patient demographics were also evaluated. RESULTS: Abscess formation or bacteremia was the most frequent cause of DIC (33%), followed by digestive tract perforation (31%). Twenty-six patients developed DIC after surgery, frequently within 1 wk (81%). TM-α was most often administered within 1 d of the DIC diagnosis (72%) and was continued for more than 3 d (64%). Although bleeding tendency was observed in 7 patients (19%), a hemostatic procedure was not needed. DIC scores, systemic inflammatory response syndrome (SIRS) scores, quick-sequential organ failure assessment (qSOFA) scores, platelet counts, and prothrombin time ratios significantly improved after 1 wk (P < 0.05, for all). The overall survival rate at 28 d was 71%. The duration of TM-α administration (≥ 4 , ≤ 6) and improvements in DIC-associated scores (DIC, SIRS and qSOFA) at 1 wk were significantly better prognostic factors for 28-d survival (P < 0.05, for all). TM-α was administered significantly earlier to patients with severe clinical symptoms, such as high qSOFA scores, sepsis, shock or high lactate values (P < 0.05, for all). CONCLUSION: Early administration of TM-α and improvements in each parameter were essential for treatment of DIC. The diagnosis of patients with mild symptoms requires further study.

DOI： 10.3748/wjg.v23.i5.891

Web of Science

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

BACKGROUND: We previously demonstrated the potential of circulating tumor DNA (ctDNA) for the amplification of detecting HER2 in patients with gastric cancer (GC). In the present study, we focused on the clinical courses of patients who developed recurrence with GC, and investigated the potential clinical utility of the ddPCR-based HER2 copy number (CN) as a marker for the temporal and/or spatial heterogeneities of GC during treatment progress. METHOD: We enrolled 30 healthy volunteers and 60 patients with GC who underwent surgery, including 17 patients who developed recurrence. Using ribonuclease P RNA component H1 (RPPH1) as a reference gene, plasma HER2 to RPPH1 ratios (the HER2 ratio) were determined using ddPCR. RESULTS: The preoperative plasma HER2 ratio correlated with the tumor HER2 status (p < 0.001), and sensitivity and specificity were 0.733 and 0.933, respectively. Analyses of plasma samples during the postoperative follow-up periods revealed that high plasma HER2 ratios were detected at the time of recurrence in 7 of 13 cases, which were diagnosed as being HER2 negative at the time of surgery. These results were supported by continuously increasing HER2 ratios thereafter with the progression of recurrent cancer. CONCLUSION: The plasma HER2 ratio determined by ddPCR is a repeatable and noninvasive approach for real-time evaluations of the HER2 status to monitor the effects of treatments for patients with HER2-positive GC and enable treatment options for patients with HER2-negative GC but positive conversion of the HER2 status after recurrence.

DOI： 10.1007/s10120-016-0599-z

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

High-throughput next-generation sequencing is a powerful tool to identify the genotypic landscapes of somatic variants and therapeutic targets in various cancers including gastric cancer, forming the basis for personalized medicine in the clinical setting. Although the advent of many computational algorithms leads to higher accuracy in somatic variant calling, no standard method exists due to the limitations of each method. Here, we constructed a new pipeline. We combined two different somatic variant callers with different algorithms, Strelka and VarScan 2, and evaluated performance using whole exome sequencing data obtained from 19 Japanese cases with gastric cancer (GC); then, we characterized these tumors based on identified driver molecular alterations. More single nucleotide variants (SNVs) and small insertions/deletions were detected by Strelka and VarScan 2, respectively. SNVs detected by both tools showed higher accuracy for estimating somatic variants compared with those detected by only one of the two tools and accurately showed the mutation signature and mutations of driver genes reported for GC. Our combinatorial pipeline may have an advantage in detection of somatic mutations in GC and may be useful for further genomic characterization of Japanese patients with GC to improve the efficacy of GC treatments. J. Med. Invest. 64: 233-240, August, 2017.

DOI： 10.2152/jmi.64.233

PubMed

Language：Japanese  

J-GLOBAL

Language：Japanese  

J-GLOBAL

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

BACKGROUND: Extended indications for endoscopic resection for early gastric cancer (EGC) have been widely accepted. However, according to current guidelines, additional gastrectomy with lymph node dissection (LND) is recommended for patients proven to have potential risks of lymph node metastasis (LNM) on histopathological findings. The aim of this study was to elucidate the risk stratification of outcome and LNM according to the number of factors that meet the inclusion criteria for radical LND for possible LNM (LNM risk factors) in patients with negative endoscopic resection margin. METHODS: We enrolled 511 EGC patients whose tumors did not meet the absolute or extended indications for endoscopic resection, and investigated the risk stratification of prognosis and LNM according to the total number of LNM risk factors. RESULTS: Recurrence-free and overall survival rates were significantly higher in patients with fewer LNM risk factors for surgical indication (p = 0.0274 and 0.0002, respectively; log-rank test), and the total number of LNM risk factors and frequency of LNM were significantly correlated (p < 0.0001; Kruskal-Wallis test). When only one LNM risk factor was satisfied, the LNM ratio was 0.58 % (1/173, 95 % confidence interval 0.01-3.18). CONCLUSION: The present study suggested the possibility of using further minimally invasive treatment strategies based on the total number of LNM risk factors.

DOI： 10.1245/s10434-016-5553-0

Web of Science

PubMed

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Authorship：Lead author   Language：English   Publisher：日本癌学会  

Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：日本臨床外科学会  

DOI： 10.3919/jjsa.77.406

Language：English   Publisher：日本癌学会  

Language：Japanese   Publisher：日本臨床外科学会  

DOI： 10.3919/jjsa.77.768

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本癌治療学会  

Language：Japanese   Publisher：日本臨床外科学会  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

BACKGROUND: Peritoneal metastasis consists of a highly complex series of steps, and the details of the underlying molecular mechanism remain largely unclear. In this study, the effects of tumor-derived exosomes (TEX) on the progression of gastric cancers were investigated in peritoneal metastasis. RESULTS: TEX were internalized in both mesothelial and gastric cancer cells in a cellular origin non-specific manner. Internalization of TEX into mesothelial cells promoted significant adhesion between mesothelial and gastric cancer cells, and TEX internalization into gastric cancer cells significantly promoted migratory ability, while internalization of mesothelial cell-derived exosomes did not. Expression of adhesion-related molecules, such as fibronectin 1 (FN1) and laminin gamma 1 (LAMC1), were increased in mesothelial cells after internalization of TEX from gastric cancer cell line and malignant pleural effusion. METHODS: TEX were extracted from cell-conditioned medium by ultracentrifugation. The effects of TEX on the malignant potential of gastric cancer were investigated in adhesion, invasion, and proliferation assays. PCR array as well as western blotting were performed to determine the underlying molecular mechanisms. The molecular changes in mesothelial cell after internalization of TEX derived from malignant pleural effusion were also confirmed. CONCLUSIONS: TEX may play a critical role in the development of peritoneal metastasis of gastric cancer, which may be partially due to inducing increased expression of adhesion molecules in mesothelial cells.

DOI： 10.18632/oncotarget.10869

Web of Science

PubMed

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC.

DOI： 10.18632/oncotarget.7937

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Recent studies have shown that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was overexpressed in many human solid cancers, however, its roles in plasma of hepatocellular carcinoma (HCC) patients were unclear. The aim of this study was to investigate the significance of plasma MALAT1 levels in HCC patients. Plasma samples were collected from pre-operative HCC, hepatic disease patients, and healthy controls, and tissue samples from HCC patients and colorectal cancer patients with liver metastasis. Plasma and tissue MALAT1 levels were measured. Plasma MALAT1 levels were progressively and significantly higher in HCC patients than hepatic disease patients, and higher in hepatic disease patients than healthy controls. The expression of MALAT1 in HCC tissue was slightly higher than that in paired non-cancerous liver tissue, but not significant. The expression of MALAT1 in the non-cancerous liver tissue of 20 HCC patients was significantly higher than that in normal liver tissue of 13 colorectal cancer patients. In contrast, plasma MALAT1 levels were significantly low in HCC patients with hepatitis B infection, and significantly high in patients with liver damage B or liver cirrhosis. In a receiver-operator curve analysis of HCC and hepatic disease patients, the cut-off value of plasma MALAT1 was 1.60 and the area under the curve was 0.66. Plasma MALAT1 levels were not correlated with α-fetoprotein or protein induced by vitamin K absence II, whereas sensitivity and specificity for the detection of HCC with the combination of MALAT1, α-fetoprotein, and protein induced by vitamin K absence II were 88.6% and 75%, respectively. In conclusion, the plasma MALAT1 level is associated with liver damage, and has clinical utility for predicting development of HCC.

DOI： 10.1111/cas.12854

Web of Science

PubMed

Authorship：Lead author   Language：Japanese  

J-GLOBAL

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Merkel cell carcinoma (MCC) is a rare endocrine tumor that presents as a rapidly growing skin nodule of the body, and it is aggressive with regional nodal and distant metastases without clearly defined treatment. There are no reports of long survivors among patients with liver metastasis of MCC. The current case was a patient who underwent surgical resection for liver metastasis of Merkel cell carcinoma. CASE PRESENTATION: This case describes a 73-year-old female with a papule on the dorsal side of the right third finger and liver tumor. The papule of the right third finger was histologically diagnosed as MCC by the skin biopsy. She underwent extensive resection and lymph node dissection of the right third finger and partial resection of the liver. The liver tumor was histologically diagnosed as liver metastasis of MCC. The patient remains well without any evidence of tumor recurrence more than 5 years after surgery. CONCLUSIONS: This is the first report of a long-term survival of more than 5 years following liver metastasis of MCC, which was surgically resected. Patients with small and solitary metastatic liver tumor of MCC may have a chance for a long-term survival following the hepatic resection.

DOI： 10.1186/s40792-015-0015-7

PubMed

Language：English   Publisher：(公社)日本生化学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND: Thrombocytosis in patients with cancer is reportedly associated with an increased expression of angiogenic factors and a poor prognosis in some cancer types. The aim of this study was to analyze the clinicopathological significance and prognostic value of platelet counts in patients with gastric cancer. METHODS: Preoperative platelet counts were measured in 306 patients with gastric cancer who underwent surgery between 2001 and 2010.We used the cut-off level of 250.9×10(3) mL (mean) to define thrombocytosis and then analyzed the correlation between platelet count and clinicopathological factors. The multivariate prognostic value was determined using the Cox proportional hazards model. RESULTS: Platelet counts were significantly elevated in patients with lymph node metastasis (p=0.0349) and pStage Ⅲdisease (p=0.0326). Adjusting for venous invasion and pStage, multivariate analysis indicated that thrombocytosis as defined in this study was an independent prognostic factor (hazard ratio=1.50, 95%CI: 1.07-2.36, p=0.0402). CONCLUSION: A high platelet count is associated with tumor progression and poor survival in patients with gastric cancer.

PubMed

Authorship：Lead author   Language：English   Publisher：日本癌学会  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: We used real-time quantitative polymerase chain reaction (rqPCR) to detect human epidermal growth factor receptor 2 (HER2) amplification in the circulating cell-free DNA (cfDNA) of patients with gastric cancer (GC), which shows the spatial and temporal intrinsic heterogeneity of HER2 expression/copy number during progression, for liquid biopsy and treatment monitoring. METHODS: We first enrolled 52 patients with advanced GC who underwent surgery and 40 healthy volunteers. For patients with GC, plasma cfDNA was obtained before surgery (43 patients) and during postoperative treatment (nine of 43 patients). After ribonuclease P RNA component H1 (RPPH1) had been selected as a reference gene for HER2 CN assessment by rqPCR in GC tumours and plasma, plasma HER2-to-RPPH1 ratios were determined retrospectively in a development cohort and an additional independent validation cohort. RESULTS: The HER2-to-RPPH1 ratio of GC tissues determined by rqPCR was concordant with routinely determined HER2 status. The plasma HER2-to-RPPH1 ratio was significantly higher for patients with HER2-positive tumours than for those with HER2-negative tumours. The sensitivity and specificity of the plasma HER2-to-RPPH1 ratio test were 0.539 and 0.967, respectively, in the development cohort, and 0.667 and 1.000, respectively, in the validation cohort. HER2 amplifications acquired and lost during tumour progression and treatment, respectively, were apparently detected by repeated assessments of plasma HER2-to-RPPH1 ratios during postoperative treatment. CONCLUSION: Our preliminary data demonstrated the potential clinical use of circulating cfDNA to detect HER2 amplification as a therapeutic marker to detect and monitor HER2 CN status for effective molecular targeted therapy in patients with GC.

DOI： 10.1007/s10120-014-0432-5

PubMed

Language：English   Publishing type：(MISC) Summary of the papers read (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-2119

Web of Science

Authorship：Lead author   Language：Japanese   Publisher：(NPO)日本食道学会  

Language：Japanese   Publisher：日本外科系連合学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The association between intraoperative hemorrhage and the type of recurrence was examined, with a focus on peritoneal metastasis. METHODS: A total of 540 patients who underwent macroscopically curative gastrectomy for advanced gastric cancers were reviewed for various clinicopathological characteristics, such as the amount of intraoperative hemorrhage and the pattern of recurrence. Additionally, adhesion assays using gastric cancer cells and mesothelial cells were performed in the presence of blood plasma to assess its effects on cell adhesion. RESULTS: Large intraoperative hemorrhages were correlated with a higher risk of peritoneal metastasis, while small hemorrhages were not. However, there were no significant differences in the incidence of all recurrences or other types of recurrence between both groups. Multivariate analysis of all cases (T2-4) revealed that large intraoperative hemorrhages were not an independent risk factor for peritoneal recurrence (p = 0.144); however, the large hemorrhage group developed peritoneal recurrence more frequently than the small hemorrhage group in each T stage. In the adhesion assay, the ability of cancer cells and mesothelial cells to adhere to each other was enhanced by the addition of plasma to the culture medium. The addition of heparin significantly decreased the plasma-induced enhancement of cell adhesion of Kato III, but not MKN45 or MKN74. CONCLUSIONS: Advanced gastric cancer patients accompanied by a large amount of intraoperative hemorrhage are more likely to develop peritoneal recurrence, and this risk might be due, at least in part, to the increased ability of cancer cells and mesothelial cells to adhere to each other.

DOI： 10.1245/s10434-014-4060-4

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BAISHIDENG PUBLISHING GROUP INC  

AIM: To analyze hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) using the tumor-node-metastasis (TNM) staging system. METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009. We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system (7(th) edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center. Portal vein invasion (vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein, vp2 as an invasion or tumor thrombus in the second branch of the portal vein, vp3 as an invasion or tumor thrombus in the first branch of the portal vein, and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side. RESULTS: The cumulative 5-year overall survival (5yrOS) and 5-year disease-free survival (5yrDFS) rates of the 372 patients were 58.3% and 31.3%, respectively. The 5yrDFS and 5yrOS of vp3-4 patients (n = 10) were 20.0%, and 30.0%, respectively, which was comparable with the corresponding survival rates of vp1-2 patients (P = 0.466 and 0.586, respectively). In the subgroup analysis of patients with macroscopic PVTT (vp2-4), the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not (P = 0.747). There was a significant difference in the DFS between patients with stage I HCC and those with stage II HCC (5yrDFS 39.2% vs 23.1%, P < 0.001); however, the DFS for stage II was similar to that for stage III (5yrDFS 23.1% vs 13.8%, P = 0.330). In the subgroup analysis of stage II-III HCC (n = 148), only alpha-fetoprotein (AFP) > 100 mg/dL was independently associated with DFS. CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2. AFP stratified the stage II-III HCC patients according to prognosis.

DOI： 10.3748/wjg.v21.i1.246

Web of Science

PubMed

Authorship：Lead author   Language：Japanese  

J-GLOBAL

Language：English   Publisher：日本癌学会  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

Hu antigen R (HuR) regulates stress responses through stabilizing and/or facilitating the translation of target mRNAs. The human TRA2β gene encodes splicing factor transformer 2β (Tra2β) and generates 5 mRNA isoforms (TRA2β1 to -5) through alternative splicing. Exposure of HCT116 colon cancer cells to sodium arsenite stimulated checkpoint kinase 2 (Chk2)- and mitogen-activated protein kinase p38 (p38(MAPK))-mediated phosphorylation of HuR at positions S88 and T118. This induced an association between HuR and the 39-nucleotide (nt) proximal region of TRA2β exon 2, generating a TRA2β4 mRNA that includes exon 2, which has multiple premature stop codons. HuR knockdown or Chk2/p38(MAPK) double knockdown inhibited the arsenite-stimulated production of TRA2β4 and increased Tra2β protein, facilitating Tra2β-dependent inclusion of exons in target pre-mRNAs. The effects of HuR knockdown or Chk2/p38(MAPK) double knockdown were also confirmed using a TRA2β minigene spanning exons 1 to 4, and the effects disappeared when the 39-nt region was deleted from the minigene. In endogenous HuR knockdown cells, the overexpression of a HuR mutant that could not be phosphorylated (with changes of serine to alanine at position 88 [S88A], S100A, and T118A) blocked the associated TRA2β4 interaction and TRA2β4 generation, while the overexpression of a phosphomimetic HuR (with mutations S88D, S100D, and T118D) restored the TRA2β4-related activities. Our findings revealed the potential role of nuclear HuR in the regulation of alternative splicing programs under oxidative stress.

DOI： 10.1128/MCB.00333-14

Web of Science

PubMed

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Books

Language：Japanese   Publisher：(一財)日本消化器病学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本胃癌学会  

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND: Coagulation factor XIII( Fibrogammin P, F XIII) has been used to treat postoperative pancreatic fistulas following gastrectomy for gastric cancer in Japan. However, little is known about the best timing to start this treatment for early recovery. This study was designed to examine the appropriate time to start Fibrogammin P treatment for pancreatic fistulas, based on nutritional and inflammatory parameters. METHOD: We retrospectively examined 27 consecutive patients with Grade B or C pancreatic fistulas as defined by the International Study Group of Pancreatic Fistula( ISGPF) classification who underwent gastrectomy at our institute between 1997 and 2011. We analyzed data on total protein( TP), albumin (Alb), C-reactive protein( CRP), and hemoglobin( Hb) concentrations and white blood cell( WBC) and lymphocyte counts. We used this information to determine laboratory cut-off values that indicate the most advantageous time to start the administration of Fibrogammin P in order to achieve early recovery within 2 weeks. RESULT: When Fibrogammin P administration was based on more than 2 cut-off values such as Alb>2.6 g/dL and Hb>9.0 g/dL and WBC<9,000/μL (p= 0.1563), early cure of pancreatic fistulas was achieved. CONCLUSION: The use of nutritional and inflammatory parameter values to determine the best time to administer Fibrogammin P may shorten the treatment period.

PubMed

Authorship：Lead author   Language：Japanese   Publisher：(株)癌と化学療法社  

背景:胃癌膵液瘻治療に血液凝固第XIII因子製剤(フィブロガミン)を使うことがあるが、使用する症例や時期に関して明確な指標は存在しない。今回われわれは、栄養・炎症学的数値を指標にしたフィブロガミンの至適投与時期を検討した。対象と方法:胃癌術後膵液瘻でISGPFスコアGrade B、Grade Cと診断した27例を対象とした。検討項目はTP、Alb、CRP、Hb、WBC、リンパ球数とした。フィブロガミン使用群が非使用群に比べ、2週間未満の膵液瘻治癒症例の割合が最も高くなるカットオフ値を決定した。結果:Alb 2.6g/dL以上、Hb 9.0g/dL以上、WBC 9,000/μL以下のうち少なくとも2項目以上を満たす場合、使用群の2週間未満の膵液瘻治癒症例割合が高い傾向を認めた(p=0.1563)。総括:栄養・炎症学的数値を指標にしたフィブロガミン投与は、膵液瘻治療期間短縮に有用である。(著者抄録)

Authorship：Lead author   Language：English   Publisher：日本癌学会  

Language：English   Publishing type：Research paper (scientific journal)  

Glutathione S-transferases (GSTs) have been reported to be activated in several types of cancers, including esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate whether GSTP1 protein expression is a useful predictor of the clinical outcome or drug resistance in ESCC. Immunohistochemistry was conducted with 75 ESCC resected specimens using a monoclonal antibody against GSTP1. The patients were divided into two groups according to the degree of GSTP1 staining, and the relationship between the GSTP1 level and the clinicopathological features was examined. Seventy-five patients were divided into low (grade 1, n=36) and high (grade 2, n=39) GSTP1 expression groups. The overall survival was significantly worse in the grade 2 patients than in the grade 1 patients (5‑year survival rate, 78.5 vs. 51.2%; p=0.027). Cox proportional hazard analysis revealed that macroscopic type 3 or 4 disease (p=0.001), lymph node metastasis (p=0.010), and high GSTP1 expression (p=0.029) were independent predictors of a poor prognosis. With regard to the subgroup analysis among the 31 patients undergoing adjuvant chemotherapy, the grade 2 patients had a worse prognosis than did the grade 1 patients (5‑year survival rate, 45.0 vs. 81.8%; p=0.081). This tendency was not observed in the subgroup without adjuvant chemotherapy (5‑year survival rate, 51.7 vs. 59.9%; p=0.979). In conclusion, the GSTP1 expression is a good predictor of prognosis, and it may be closely related to the chemotherapeutic efficacy of 5-FU plus cisplatin in ESCC patients.

DOI： 10.3892/or.2013.2606

PubMed

Language：Japanese   Publisher：日本ストレス学会  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

BACKGROUND: The aim of the present study was to determine the suitable postoperative management of patients with gastric cancer. PATIENTS AND METHODS: A total of 161 patients with gastric cancer who developed recurrence after curative resection were reviewed retrospectively to investigate the clinicopathological characteristics of recurrence in subgroups classified according to the Japanese Classification of Gastric Cancer (JCGC) staging system. RESULTS: Survival analysis of recurrent cases alone demonstrated significant differences in disease-free survival (DFS) among groups according to the pN stage (p=0.0009); however, there was no significant difference among groups according to the pT stage (p=0.39). Eighty percent of recurrences developed within 32, 25, and 15 months in the N0, N1/2 and N3 groups, respectively. CONCLUSION: The present study demonstrated that DFS and post-recurrent survival significantly differed among groups according to pN stage. These findings may provide useful information for maximizing the efficiency of postoperative follow-up.

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: We examined the levels of long non-coding RNAs (lncRNAs) in the plasma of patients with gastric cancer to assess their clinical significance for diseases diagnosing and monitoring. MATERIALS AND METHODS: We investigated the stability of plasma lncRNAs, and then confirmed the appropriateness of the lncRNA assay with a pre-amplification method. The levels of plasma lncRNAs, H19, HOX antisense intergenic RNA (HOTAIR), and metastasis associated lung adenocarcinoma transcript-1 (MALAT1), were then analyzed in patients with gastric cancer (GC) and healthy controls. RESULTS: Plasma lncRNAs exhibited minimal gradual instability only under several severe conditions. Analysis showed that samples with pre-amplification had a higher level of linearity in the reverse transcription polymerase chain reaction (RT-PCR) assay than those without pre-amplification. Plasma H19 levels were significantly higher in patients than in healthy controls. Plasma H19 levels were significantly reduced in postoperative samples. CONCLUSION: Circulating lncRNAs can be detectable in plasma, and the detection of circulating lncRNAs may provide new complementary tumor markers for gastric cancer.

PubMed

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本消化器外科学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本胃癌学会  

Language：Japanese   Publisher：(一社)日本消化器がん検診学会  

Authorship：Lead author   Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：(株)医学書院  

症例は52歳,女性.胃上部に大きさ5mm程度の多発粘膜下腫瘍を認め,生検によりカルチノイド腫瘍と診断された.血液検査では,抗胃壁細胞抗体陽性および二次性高ガストリン血症を認めた.A型胃炎に伴う多発性胃カルチノイドと診断し,血中ガストリン値を低下させる目的で,腹腔鏡補助下幽門側胃切除術を施行した.術翌日には,血中ガストリン値はほぼ正常化し,術後1年の内視鏡検査では,新病変の出現なく腫瘍の縮小を認めた.本疾患の治療は,これまでリンパ節郭清を伴う胃全摘術の報告が多かったが,腹腔鏡下幽門側胃切除術など,より低侵襲な術式も考慮すべきである.(著者抄録)

DOI： 10.11477/mf.1407103519

CiNii Books

Other Link： http://search.jamas.or.jp/link/ui/2011148742

Language：Japanese   Publisher：(一社)日本消化器外科学会  

症例は51歳の男性で,2006年11月より前立腺印環細胞癌の診断の下,放射線治療およびホルモン療法を施行されていた.2007年6月頃よりイレウス症状を認め,下部消化管内視鏡にて回盲部末端にbridging fold様に見える部位を伴う腫瘍を認め,印環細胞癌が検出された.手術所見では腹腔内は広範に腹膜播種を来しており,根治性はなくイレウス解除を目的に回盲部切除を施行した.病理所見では免疫染色で盲腸,前立腺の腫瘍共にサイトケラチン20(CK20)(+),サイトケラチン7(CK7)(-),前立腺特異抗原(PSA)(-)であることから,盲腸原発の印環細胞癌の前立腺転移であると考えられた.術後化学療法にFOLFOX+bevacizumab|FOLFIRIを行い,24ヵ月の無症状生存期間を得,27ヵ月目に原病死された.大腸癌の前立腺転移の報告例は自験例が本邦2例目であり文献的考察を加え報告する.(著者抄録)

Language：Japanese   Publisher：(NPO)日本小児外科学会  

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Authorship：Lead author   Language：Japanese   Publisher：日本臨床外科学会  

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本乳癌学会  

Language：Japanese   Publisher：(一社)日本胃癌学会  

Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

Authorship：Lead author   Language：Japanese   Publisher：日本臨床外科学会  

Authorship：Lead author   Language：Japanese   Publisher：京都府立与謝の海病院  

55歳女。検診後の精査での胸部CTで膵体部に最大径約2cmの嚢胞性病変を指摘された。画像所見、超音波所見等により、嚢胞内に隔壁構造を、嚢胞壁に一部結節性病変を認め、粘液性嚢胞性膵腫瘍(MCT)の術前診断で膵体尾部切除術を施行した。術中迅速病理検査ではsimple cyst or retention cystと診断された。所属リンパ節の腫脹は認めなかったため、リンパ節郭清は行わなかった。摘出標本の肉眼的所見では隔壁構造を有する嚢胞性病変を認めたが、小結節部分は明らかでなかった。病理組織学的所見で卵巣様間質の存在が示唆されたが、最終的には嚢胞壁が異型のない単層円柱上皮に覆われていたためsimple cystと診断した。重篤な術後合併症もなく退院し、術後6ヵ月の現在、再発の徴候はない。

Language：Japanese   Publisher：京都府立与謝の海病院  

86歳女。胸部圧迫感、呼吸苦を主訴とした。心電図、胸部X線所見により急性冠症候群による心不全と診断し緊急入院した。緊急冠動脈造影を施行したところ、#6 75%狭窄、#7 90%狭窄を認めた。同部位に経皮的冠動脈形成術を施行し、それぞれ0%への改善を認めた。術終了後血行動態は安定していたが、心臓超音波で前壁中隔の無収縮所見と、心尖部側にL→Rシャントを認めた。心筋梗塞後の心室中隔穿孔による心不全と診断したが、肺体血流比の増加を認めなかったため床上安静下の内科的治療を優先した。しかしその後も心不全症状は改善せず、心臓超音波上、短絡血流の増加所見を認め、待機的心室中隔穿孔閉鎖術適応と判断した。手術は右室切開アプローチによるパッチ閉鎖術が施行された。術後、重篤な合併症もなく、速やかに自立歩行が行えるほどに改善した。術後から腎機能障害が進行したため、維持透析を導入し独歩退院した。

Authorship：Lead author   Language：Japanese   Publisher：京都府立与謝の海病院  

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Language：Japanese   Presentation type：Poster presentation  

Venue：横浜  

Event date： 2023.10

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：横浜  

Event date： 2023.10

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：横浜  

Event date： 2023.10

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：横浜  

Event date： 2023.10

Language：Japanese   Presentation type：Poster presentation  

Venue：横浜  

Event date： 2023.10

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：横浜  

Event date： 2023.10

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：横浜  

Event date： 2023.10

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：横浜  

Event date： 2023.9

Language：Japanese   Presentation type：Poster presentation  

Venue：横浜  

Event date： 2023.9

Language：Japanese   Presentation type：Poster presentation  

Venue：横浜  

Event date： 2023.9

Language：Japanese   Presentation type：Poster presentation  

Venue：横浜  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：福井  

Event date： 2023.9

Language：English   Presentation type：Poster presentation  

Venue：France  

Event date： 2023.9

Language：English   Presentation type：Poster presentation  

Venue：France  

Event date： 2023.8

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：埼玉  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：大阪  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：函館  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京  

Event date： 2023.6 - 2023.7

Language：English   Presentation type：Oral presentation(general)  

Event date： 2023.6

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：大阪  

Event date： 2023.6

Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

Event date： 2023.6

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：千葉  

Event date： 2023.6

Language：English   Presentation type：Poster presentation  

Venue：Roma  

Event date： 2023.6

Language：English   Presentation type：Poster presentation  

Venue：Roma  

Event date： 2023.6

Language：English   Presentation type：Oral presentation(general)  

Venue：Roma  

Event date： 2023.6

Language：English   Presentation type：Poster presentation  

Venue：Roma  

Event date： 2023.6

Language：English   Presentation type：Poster presentation  

Event date： 2023.6

Language：English   Presentation type：Poster presentation  

Event date： 2023.6

Language：English   Presentation type：Poster presentation  

Event date： 2023.6

Language：English   Presentation type：Poster presentation  

Event date： 2023.6

Language：English   Presentation type：Oral presentation(general)  

Event date： 2023.6

Language：English   Presentation type：Oral presentation(general)  

Event date： 2023.6

Language：English   Presentation type：Oral presentation(general)  

Event date： 2023.6

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：横浜  

Event date： 2023.6

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：横浜  

Event date： 2023.6

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：新潟  

Event date： 2023.6

Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：名古屋  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：神戸  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：神戸  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：神戸  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：神戸  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：神戸  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：神戸  

Event date： 2023.4

Language：Japanese   Presentation type：Poster presentation  

Venue：東京   Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Poster presentation  

Venue：東京   Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Poster presentation  

Venue：東京   Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京   Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京  

Event date： 2023.4

Language：Japanese   Presentation type：Poster presentation  

Venue：東京   Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Venue：東京   Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Poster presentation  

Venue：東京   Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Poster presentation  

Event date： 2023.4

Language：Japanese   Presentation type：Poster presentation  

Venue：東京   Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：東京   Country：Japan  

Event date： 2023.3

Language：Japanese   Presentation type：Poster presentation  

Venue：WEB開催  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：WEB開催  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：WEB開催  

Event date： 2023.3

Language：Japanese   Presentation type：Poster presentation  

Venue：WEB開催  

Event date： 2023.3

Language：Japanese   Presentation type：Poster presentation  

Venue：WEB開催  

Event date： 2023.2

Language：Japanese   Presentation type：Poster presentation  

Venue：札幌  

Event date： 2023.2

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：札幌  

Event date： 2023.2

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：札幌  

Event date： 2023.2

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：札幌  

Event date： 2023.2

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：札幌  

Event date： 2023.2

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：神奈川  

Event date： 2023.2

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：神奈川  

Event date： 2023.2

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：名古屋  

Event date： 2022.12

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：名古屋  

Event date： 2022.12

Language：English   Presentation type：Poster presentation  

Venue：WEB開催  

Event date： 2022.12

Language：English   Presentation type：Poster presentation  

Venue：WEB開催  

Event date： 2022.12

Language：English   Presentation type：Poster presentation  

Venue：WEB開催  

Event date： 2022.12

Language：English   Presentation type：Poster presentation  

Venue：WEB開催  

Event date： 2022.12

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：名古屋  

Event date： 2022.12

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：名古屋  

Event date： 2022.12

Language：Japanese   Presentation type：Symposium workshop panel(public)  

Venue：名古屋