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

DOI： 10.1016/j.trsl.2015.02.002

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

DOI： 10.1016/j.gie.2014.07.034

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

DOI： 10.1016/j.gie.2014.03.030

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

DOI： 10.1038/onc.2013.429

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Authorship：Lead author,　Corresponding author   Language：English  

DOI： 10.1016/j.gie.2012.07.031

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

DOI： 10.1371/journal.pone.0023278

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DOI： 10.1002/ibd.21444

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DOI： 10.1053/j.gastro.2007.09.026

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

DOI： 10.1016/j.chom.2007.05.004

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Familial Mediterranean fever (FMF) rarely presents without a periodic fever. We report the case of a 16-year-old girl who developed recurrent abdominal pain after COVID-19 without fever. The initial evaluation, including endoscopy, was unremarkable, except for mildly elevated fecal calprotectin (182.1 μg/g). On readmission, peritoneal signs, mild pleural effusion, and elevated serum amyloid A (113.9 mg/L) were noted, while the C-reactive protein level remained normal. Colchicine promptly suppressed these attacks. MEFV sequencing revealed a homozygous E148Q mutation, supporting an atypical FMF. Fecal calprotectin and serum amyloid A levels normalized within one month. This case underscores the importance of FMF in post-infectious recurrent abdominal pain and highlights targeted biomarkers and genetics for making a timely diagnosis.

DOI： 10.2169/internalmedicine.6541-25

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Despite extensive technological advances and an ever-growing body of literature, liquid biopsy has yet to achieve reliable early detection of pancreatic ductal adenocarcinoma (PDA). Numerous studies have investigated circulating tumor-derived components, including cell-free DNA (cfDNA), cell-free RNA (cfRNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs), primarily using peripheral blood samples; however, their clinical utility for early-stage disease remains limited. The fundamental obstacles are biological rather than purely technical: early PDA and its precursor lesions, such as pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN), are characterized by minimal tumor burden, low levels of nucleic acid shedding, and substantial background signals from non-neoplastic tissues. Increasing analytical complexity through multilayered liquid biopsy approaches, including analyses from pancreas-associated fluid, has not consistently translated into improved diagnostic performance and, in some cases, has amplified issues related to specificity, reproducibility, and interpretability. Moreover, molecular alterations detected in body fluids may reflect clonal expansion without inevitable malignant progression, raising concerns regarding overdiagnosis and clinical decision-making. Pre-analytical variability, lack of standardization, and limited access to tumor-adjacent fluids further hinder clinical implementation. Liquid biopsy should therefore be regarded as a complementary modality rather than a substitute for histopathological diagnosis, with its precise clinical role in early detection still ill-defined. In this review, we critically examine why liquid biopsy has not yet succeeded in early PDA detection, highlighting the key biological, technical, and clinical barriers that must be addressed to move the field beyond exploratory research toward meaningful clinical application.

DOI： 10.3390/cancers18030525

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

RNA dysregulation mediated by aberrant RNA-binding proteins (RBPs) is closely associated with tumorigenesis. However, the tumorigenic mechanisms of each RBP remained unclear. In this study, we demonstrate that downregulation of Splicing factor 3A1 (SF3A1) markedly suppressed the proliferation of colorectal cancer (CRC) cells, with minimal cytotoxicity observed in non-cancerous epithelial cells. The tumor-promoting function of SF3A1 was further validated in an HCT116 xenograft mouse model. Multiple apoptosis assays—including TdT-mediated dUTP nick end labeling (TUNEL) staining, poly-ADP-ribose polymerase (PARP) immunoblotting, and caspase-3/7 activity measurements—showed that SF3A1 inhibited apoptotic signaling in CRC cells. Transcriptome analysis, combined with RNA-immunoprecipitation (RIP), identified Syntaxin 12 (STX12) as a downstream effector of SF3A1. Knockdown of STX12 induced apoptosis in CRC cells but had no effect on the viability of non-cancerous HCEC-1CT epithelial cells. Furthermore, STX12 mRNA levels were significantly reduced following SF3A1 knockdown, indicating that SF3A1-mediated stabilization of STX12 contributes to apoptosis resistance in CRC cells. Collectively, our findings establish that SF3A1 promotes CRC progression by stabilizing STX12 mRNA and selectively inhibiting apoptosis in malignant cells, thereby identifying the SF3A1–STX12 regulatory axis as a novel and selective therapeutic target for CRC.

DOI： 10.3390/ijms27031195

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

DOI： 10.1186/s12876-025-04599-z

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Publishing type：Research paper (scientific journal)   Publisher：BMFH Press  

DOI： 10.12938/bmfh.2025-040

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INTRODUCTION: Vedolizumab (VDZ) has been available for Japanese patients with ulcerative colitis (UC). However, real-world data regarding the long-term efficacy and safety of VDZ in Japanese patients with active UC remain limited. This study aimed to evaluate the long-term outcomes of VDZ and identify prognostic factors in Japanese patients with UC. METHODS: This retrospective multicenter cohort study was conducted at six hospitals and one clinic in Hokkaido, Japan. A total of 172 patients with UC who received VDZ treatment between November 2018 and October 2022 were included. Treatment persistence rates at 52, 104, and 156 weeks were evaluated. The median follow-up duration was 51 weeks (range: 1-156). Clinical response, clinical remission, and mucosal healing rates were assessed at weeks 6 and 52. Prognostic factors for treatment response were analyzed using univariate and multivariate logistic regression analyses. RESULTS: The cumulative treatment persistence rates at weeks 52, 104, and 156 were 68.1%, 58.1%, and 50.7%, with 64, 32, and 17 patients remaining on VDZ at those respective weeks. Clinical response and remission rates at week 6 were 63.3% and 52.3%, while clinical remission, corticosteroid-free remission, and mucosal healing rates at week 52 were 59.3%, 53.9%, and 52.3%, respectively. Multivariable analysis identified male sex and absence of prior anti-tumor necrosis factor (TNF) exposure as factors associated with clinical response at week 6 (odds ratio [OR] 2.17, p = 0.045; OR 2.26, p = 0.046). Clinical response at week 6 was strongly associated with clinical remission at week 52 (OR 14.5, p < 0.01). Among patients previously treated with anti-TNF agents, those with secondary loss of response had significantly higher remission rates at week 52 than did those with primary non-response (p < 0.01). Adverse events were observed in 6 patients, with one case leading to treatment discontinuation; no severe adverse events were reported. CONCLUSIONS: VDZ demonstrated favorable long-term treatment persistence, efficacy, and safety in Japanese patients with UC. The efficacy of VDZ may vary depending on prior anti-TNF therapy outcomes, particularly the reasons for discontinuation. These findings provide valuable insights for optimizing treatment strategies in UC patients, although further prospective studies are warranted.

DOI： 10.1159/000549358

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INTRODUCTION: Vedolizumab binds to α4β7 integrin, thereby inhibiting lymphocyte migration into the gastrointestinal tract. It is used to treat moderate to severe ulcerative colitis (UC) and Crohn's disease. This study evaluated vedolizumab concentrations, α4β7 integrin saturation, and T lymphocyte immunophenotype proportions in blood, serum and inflamed colorectal tissue according to treatment efficacy in patients with moderate to severe UC. METHODS: This was a phase 4, multicenter, open-label, single-arm study. Patients were observed for a total of 54 weeks. Clinical remission was defined as complete Mayo score ≤ 2 or partial Mayo score ≤ 1. RESULTS: The study included 11 patients with UC, 10 of whom were tumor necrosis factor alpha antagonist therapy-naïve. Seven and six patients were in remission at weeks 14 and 54, respectively. Vedolizumab concentrations and lymphocyte α4β7 integrin saturation in serum and inflamed colorectal tissue at weeks 14 and 54 did not differ significantly between remitters and non-remitters. The proportion of T cell subsets differed in remitters and non-remitters for CD4+ T cells in blood at week 14 (62.7% vs 47.4%, p = 0.0061) and CD161+ memory CD4+ T cells (65.7% vs 53.1%, p = 0.0357) in inflamed colorectal tissue at week 54. Week 54 remitters had higher proportions of CD161+ memory CD4+ T cells in inflamed colorectal tissue at baseline (before vedolizumab treatment) than did week 54 non-remitters (48.5% vs 31.3%, p = 0.0303). CONCLUSION: T cell immunophenotype may be a promising predictive biomarker of vedolizumab treatment efficacy.

DOI： 10.1371/journal.pone.0340271

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Purpose

Genetic mutations in the tumor suppressor gene APC and the oncogene KRAS are an initial event in the colorectal adenoma-carcinoma sequence. Multistep carcinogenesis has been discovered through the study of familial adenomatous polyposis (FAP), an inherited disease with a germline APC variant. We aimed to determine the premalignant mutational genotypes that progress to colorectal neoplasia using target sequencing to compare the characteristics of FAP patients with sporadic cases.

Experimental design

A total of 197 samples from 20 FAP and 13 sporadic cases were analyzed using next-generation sequencing (NGS) with a cancer panel. The analysis of APC germline variants identified FAP patients with a germline variant, those with whole APC deletion, and those with no alterations. The association between pathogenic germline variants and somatic mutations was assessed.

Results

Colorectal tumors of FAP and non-polyposis patients showed a similar frequency of mutations ( APC, 76% and 75%; KRAS , 32% and 25%). Somatic APC mutations in FAP patients was observed in the mutation cluster region (63.3%). In FAP, many colorectal tumors (57.5%) harbored two APC hits, whereas in sporadic cases, one or two hits were more common (44.4% and 22.2%, respectively). Of the 99 tumors in FAP patients with APC germline variants as the first hit, 74 tumors (74.7%) acquired somatic mutations as the second hit, and 9 tumors (9.9%) further gained a third hit, indicating a ‘three-hit’ alteration.

Conclusion

An identical cancer pathway may be associated with multistep carcinogenesis, accompanied by APC mutations in mutation hotspots. A combined analysis of germline and somatic alterations revealed ‘three-hit’ alterations in the APC gene among the FAP patients, suggesting that the heterogeneity of colorectal carcinogenesis contribute to these genetic changes.

DOI： 10.3389/fgene.2025.1668133

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

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

DOI： 10.1007/s00432-025-06295-7

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.biopha.2025.118436

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BACKGROUND: Cancer of unknown primary (CUP) is a challenging malignancy characterized by metastatic tumors with an unidentified primary site, even after extensive pathological and radiographic evaluation. Recent advancements in gene expression profiling and comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) have enabled the identification of potential tissue origins, thereby facilitating personalized treatment strategies. Although most cases of CUP present as adenocarcinomas or poorly differentiated tumors, the treatment remains largely empirical, with limited success from molecularly tailored therapies. However, advances in tumor DNA sequencing and targeted therapies hold great promise for enhancing patient outcomes. CASE: A 72-year-old woman presented with epigastric pain and was diagnosed with a duodenal tumor and gastric ulceration via esophagogastroduodenoscopy. A histological evaluation revealed poorly differentiated adenocarcinoma in the duodenum, and the immunohistochemistry findings supported a pancreatobiliary origin. An endoscopic ultrasound-guided biopsy confirmed poorly differentiated adenocarcinoma in the duodenum, while a subsequent gastric examination revealed well-differentiated adenocarcinoma, suggesting dual malignancies. The patient underwent neoadjuvant chemotherapy, followed by pancreatoduodenectomy with distal gastrectomy. The CUP was staged as poorly differentiated adenocarcinoma (pStage IVB), while the gastric cancer was staged as well-differentiated adenocarcinoma (pStage IA). Despite adjuvant TS-1 therapy, lymph node metastasis near the superior mesenteric artery continued to progress. CGP revealed high microsatellite instability and a high tumor mutational burden, along with multiple actionable genetic mutations. Pembrolizumab monotherapy was initiated, leading to complete remission, with no recurrence observed at 1 year after treatment cessation. Genetic and immunohistochemical investigations have identified microsatellite instability in both CUP and gastric cancer tissues, suggesting a shared origin. Targeted gene sequencing confirmed common genetic variations, ultimately revealing that the CUP originated from gastric cancer cells. CONCLUSION: This case highlights the critical role of CGP in the diagnosis and treatment of CUP. The use of advanced molecular techniques, including NGS, revealed the gastric origin of CUP and identified actionable biomarkers, leading to successful treatment with immune checkpoint inhibitors.

DOI： 10.1002/cnr2.70338

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BACKGROUND: Inflammatory bowel disease (IBD) significantly impacts employment and work productivity, necessitating support for balancing work and treatment (SBWT). While SBWT systems have been formalized in Japan, awareness among healthcare professionals remains low. This study aimed to evaluate the effectiveness of an educational program on SBWT for healthcare professionals in Hokkaido, Japan. METHODS: A 2-year questionnaire-based study was conducted across eight medical facilities in Hokkaido, Japan, from November 2022 to November 2024. The educational program, comprising lecture-based and self-directed learning formats, addressed six key components of SBWT. Pre- and post-program surveys assessed changes in awareness, interest, and behaviors related to SBWT. RESULTS: Pre-program awareness of SBWT was low (36.7% among doctors, 28.2% among medical staff). Post-program, awareness increased significantly to 81.3% and 58.3%, respectively (p < 0.01). Interest in SBWT improved across several categories for both groups, with greater gains among medical staff. Behavioral changes, such as detailed employment-related consultations with IBD patients and improved reporting practices from medical staff to doctors, were observed but not statistically significant. Lecture-based learning was more effective than self-directed methods, in increasing awareness, interest, and engagement with SBWT, particularly for medical staff. CONCLUSIONS: The educational program successfully enhanced awareness and interest in SBWT, with lecture-based methods proving more effective for medical staff. These findings emphasize the need for tailored educational strategies based on baseline knowledge. Future initiatives should focus on sustaining knowledge acquisition, expanding programs nationwide, and assessing long-term impacts on healthcare practices and patient outcomes.

DOI： 10.1007/s00535-025-02248-6

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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

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BACKGROUND: Endoscopic phenotypes of pouchitis according to the Chicago Classification have been reported to be associated with poor pouch outcomes in ulcerative colitis (UC). Here, we aimed to assess the prevalence of endoscopic phenotypes and their predictability for pouch outcomes. METHODS: This retrospective multicenter study included UC patients aged 18 years or older who underwent total colectomy between January 2000 and March 2020. The primary endpoints were frequencies of endoscopic phenotypes of the Chicago Classification and their predictability for chronic pouchitis and pouch failure. Endoscopic findings were evaluated at the initial pouchoscopy and at 3 and 10 years after ileostomy takedown. RESULTS: A total of 392 eligible patients were identified. The frequencies of chronic pouchitis and pouch failure were 32% and 4.9%, respectively. Focal inflammation and inlet involvement at the initial postoperative pouchoscopy were significantly associated with subsequent risk of chronic pouchitis and pouch failure, respectively. Thirty percent of the patients with focal inflammation progressed to diffuse inflammation when chronic pouchitis developed. Multivariate analysis showed chronic pouchitis was significantly associated with diffuse inflammation and cuffitis observed throughout the clinical course. The proportion of pouch-related fistula was significantly lower in our cohort than in the US cohort (4.8% vs 19%, P < 0.001), and pouch-related fistula was an independent risk factor for pouch failure. CONCLUSIONS: We demonstrated the predictability of the Chicago Classification for pouch outcomes, and a lower prevalence of pouch-related fistula, resulting in a lower pouch failure risk in our multicenter cohort.

DOI： 10.1007/s00535-025-02231-1

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Ulcerative colitis (UC) is a chronic inflammatory condition requiring lifelong management, with anti-tumor necrosis factor α (anti-TNF-α) agents often used for refractory cases. However, secondary loss of response (LOR) to these agents, due to anti-drug antibodies, poses a significant therapeutic challenge. This report describes a case where granulocyte and monocyte adsorptive apheresis (GMA) maintenance therapy successfully restored the efficacy of an anti-TNF-α agent in a 26-year-old male with active UC experiencing LOR to infliximab. Following GMA induction therapy and continued infliximab administration, clinical symptoms improved, fecal calprotectin levels decreased, and clinical remission was achieved. Long-term maintenance with GMA enabled sustained clinical remission, with mucosal healing observed one year post-therapy. This case suggests that GMA maintenance therapy may serve as a novel therapeutic approach for patients with active UC experiencing LOR to anti-TNF-α agents. However, further studies are warranted to elucidate the underlying mechanisms and validate its efficacy.

DOI： 10.1002/jca.70030

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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is often managed with surgery, which is the first-line treatment option for stage I-III lesions. However, definitive chemoradiotherapy (dCRT) is associated with a recurrence rate of 30% in stage I ESCC and higher rates in advanced-staged lesions. However, several patients prefer dCRT because their general condition is poor. Salvage therapies, including esophagectomy and endoscopic resection [endoscopic submucosal dissection (ESD)/endoscopic mucosal resection], are important for residual or recurrent tumors that develop after dCRT. Esophagectomy can have curative potential. However, it has high complication and mortality rates. Therefore, ESD is a safer alternative. CASE SUMMARY: A Japanese man in his 70s was concurrently diagnosed with right hypopharyngeal cancer (T2N1M0, cStage III), left oropharyngeal cancer (T1N0M0, cStage I), and left hard palate cancer (T1N0M0, cStage I). Esophagogastroduodenoscopy (EGD) revealed a 20 mm reddish 0-Is+IIb lesion in the upper thoracic esophagus, with an invasion depth of SM2. The lesion was diagnosed as an esophageal moderately differentiated squamous cell carcinoma (T1bN0M0, cStage I). As the pharyngeal cancers were in advanced stages, chemoradiotherapy (docetaxel and cisplatin with a radiation dose of 66 Gy) was prioritized. Post-chemoradiotherapy EGD showed that the lesion had flattened into a 0-IIb lesion, thereby indicating a reduced invasion depth (epithelium or lamina propria mucosa). ESD achieved en bloc and histologically confirmed curative resection. At 22 months after ESD, the patient did not present with signs of recurrence. CONCLUSION: This case emphasizes that ESD can be successfully utilized as a salvage treatment for ESCC after chemoradiotherapy for otolaryngological cancers.

DOI： 10.4251/wjgo.v17.i4.101123

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Multiple myeloma (MM) is a hematological malignancy characterized by a poor prognosis. While certain probiotics have been shown to produce antitumor molecules that inhibit solid tumor progression, it remains unclear whether probiotic-derived compounds can exert similar effects on hematological tumors, such as MM. In this study, we screened the cell-free culture supernatants (CFCS) of 24 probiotic strains for antitumor effects against multiple myeloma (MM) cells and identified that the CFCS from Clostridium butyricum (C. butyricum) demonstrated the most significant reduction in MM cell viability. Further fractionation of this CFCS through reverse-phase and gel filtration chromatography revealed a high enrichment of butyrate in the antitumor fraction, as confirmed by gas chromatography-mass spectrometry. Butyrate reduced MM cell viability in a concentration-dependent manner. Butyrate was significantly more cytotoxic to RPMI-8226 cells than peripheral blood mononuclear cells (PBMCs) isolated from two non-cancerous individuals. In the xenograft model of RPMI-8226 cells, butyrate showed significant inhibition of tumor formation. Cell cycle analysis showed that butyrate induced G1 phase arrest and increased sub-G1 phase, suggesting DNA fragmentation. Western blot analysis demonstrated that butyrate treatment led to cleaved poly ADP-ribose polymerase (PARP) accumulation. Additionally, flow cytometry showed an increase in annexin V positive MM cells, indicating apoptosis. Butyrate also exhibited synergistic antitumor activity when combined with bortezomib, a proteasome inhibitor. These findings suggest that probiotic-derived molecules, including butyrate, may enhance the therapeutic effect of hematological malignancy, such as MM.

DOI： 10.1038/s41598-025-97038-8

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A man in his 70s with antiphospholipid syndrome (APS) presented with a hepatic mass. Initial imaging suggested hepatic infarction, as the liver tumor markers were normal, and coagulation tests indicated a hypercoagulable state. Three years later, follow-up imaging revealed tumor enlargement, leading to a biopsy-confirmed hepatocellular carcinoma diagnosis. Transarterial embolization was performed followed by lenvatinib therapy. The patient achieved complete response with no recurrence for over eight months. This case highlights the potential of APS to contribute to liver carcinogenesis in non-cirrhotic patients and illustrates the need for individualized treatment strategies.

DOI： 10.2169/internalmedicine.5081-24

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

In recent years, we have seen a considerable increase in the number of patients with inflammatory bowel diseases of unknown etiology, including both Crohn's disease and ulcerative colitis. Inflammatory bowel diseases can cause intestinal lesions throughout the gastrointestinal tract, necessitating gastrointestinal endoscopy for examining all relevant aspects, especially lesion characteristics, for differential diagnosis and histological diagnosis, to select the appropriate treatment options, determine treatment effectiveness, etc. Specific guidelines are necessary to ensure that endoscopy can be performed in a safe and more tailored and efficient manner, especially since gastrointestinal endoscopy, including enteroscopy, is a common procedure worldwide, including in Japan. Within this context, the Japan Gastroenterological Endoscopy Society has formulated the “Guidelines for the Endoscopic Diagnosis and Treatment of Inflammatory Bowel Diseases” to provide detailed guidelines regarding esophagogastroduodenoscopy, enteroscopy, and colonoscopy procedures for definitive diagnosis, as well as determination of treatment effectiveness in clinical cases of inflammatory bowel diseases.

DOI： 10.1111/den.15002

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

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The challenge of effectively eliminating air during gastrointestinal endoscopy using ultrasound techniques is apparent. This difficulty arises from the intricacies of removing concealed air within the folds of the gastrointestinal tract, resulting in artifacts and compromised visualization. In addition, the overlap of folds with lesions can obscure their depth and size, presenting challenges for an accurate assessment. Conversely, in intricately folded regions of the gastrointestinal tract, such as the stomach, intestine, and colon, insufficient delivery of air or CO2 into the cavity impedes luminal expansion, hindering the accurate visualization of lesions concealed within the folds. Although this underscores the requirement for substantial airflow, excessive airflow can hinder visualization of bleeding lesions and other abnormalities. Considering these challenges, an ideal endoscopic device would facilitate the observation of lesions without the requirement for air or CO2 delivery whereas, ensuring optimal expansion of the gastrointestinal tract. Recently, transparent gels with specific viscosities have been employed more frequently to address this issue. This review aims to elucidate how these gels address these challenges and provide a solution for enhanced endoscopic visualization.

DOI： 10.3748/wjg.v31.i4.101288

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BACKGROUND: Crohn's disease (CD) is a refractory inflammatory bowel disease with an unclear etiology. CircularRNA (circRNA) has been highlighted as a novel class of functional noncoding RNAs associated with the pathogenesis of various diseases. However, the functions of circRNA in CD remain unclear. METHODS: Biopsies were obtained from noninflammatory sites in the terminal ileum of the CD group (n = 4) and non-CD group (n = 4) and analyzed for circRNA expression using RNA sequencing. The significantly altered circRNAs were validated in the CD group (n = 45) and non-CD group (n = 15) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Transcriptome analysis was conducted using circRNA-downregulated macrophage-like THP-1 cells. Reactive oxygen species (ROS) levels, cytokine mRNA expression, phagocytosis, and migration were evaluated in circRNA-downregulated THP-1 cells. RESULTS: CircularRNA sequencing analysis revealed significant differences in 31 circRNAs between the CD group and non-CD group. Quantitative reverse transcriptase-polymerase chain reaction analysis for each circRNA demonstrated significant upregulation of hsa_circ_0015388 in the CD group. Hsa_circ_0015388 was expressed in THP-1 cells, but not in HCEC-1CT and Caco-2/bbe. Transcriptome analysis in THP-1 cells transfected with scramble or hsa_circ_0015388 siRNA (small interfering RNA) showed a significant alteration in innate immune response related pathway. Reactive oxygen species production was significantly increased in the hsa_circ_0015388 downregulated THP-1 cells. Reactive oxygen species induction in the hsa_circ_0015388 knocked down THP-1 was diminished by the inhibition of TNFSF10. CONCLUSION: A comprehensive analysis of circRNA expression revealed that 31 circRNAs were dysregulated in the CD group. Hsa_circ_0015388 is expressed in macrophages and negatively regulates ROS function inhibiting the TNFSF10 pathway. This study first revealed that hsa_circ_0015388 plays a role in the pathogenesis of CD by suppressing ROS production in macrophages.

DOI： 10.1093/ibd/izae317

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BACKGROUND AND STUDY AIMS: To address the challenges of difficult colorectal endoscopic submucosal dissection (ESD), conversion to snare resection (rescue-snare ESD: rSnare), a variant of hybrid ESD, is commonly proposed. However, rSnare is associated with a lower en bloc resection rate compared with conventional ESD. Traction-assisted ESD has emerged as a technique to facilitate dissection, but its effectiveness as a rescue method remains unclear. This study was the first to compare the effectiveness of rSnare and rescue-traction-assisted ESD (rTraction). PATIENTS AND METHODS: This retrospective study involved 1464 consecutive lesions from 1372 patients with superficial colorectal neoplasms across eight institutions. Among these, 162 lesions required rescue methods of rSnare or rTraction. After propensity score matching, 88 lesions treated with either rSnare or rTraction were analyzed. RESULTS: The rTraction group exhibited significantly higher en bloc resection and R0 resection rates (93.2% and 77.3%, respectively) compared with the rSnare group (45.5% and 38.6%, respectively). However, average procedure time was significantly longer in the rTraction group (122.3 ± 72.5 min) compared with the rSnare group (92.2 ± 54.2 min). In the rTraction group, univariable and multivariable analyses identified traction initiation time > 75 minutes as the only independent predictor of procedure durations exceeding 120 minutes. CONCLUSIONS: Utilizing a traction device as a rescue technique in difficult colorectal ESD resulted in higher en bloc and R0 resection rates compared with conversion to snare resection. Initiating traction within 75 minutes may contribute to reducing overall procedure time for challenging colorectal ESD cases.

DOI： 10.1055/a-2544-3279

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We report the rare case of severe cognitive disorder and ataxia caused by entrectinib in a patient with NTRK1 fusion gene-positive intrahepatic cholangiocarcinoma. The case was a 56-year-old woman after nine courses of GCS therapy. The patient experienced grade 1 muscle weakness on day 4 and grade 3, cognitive disorder on day 7 after receiving entrectinib, which led to hospitalization. The symptoms were reversible and tended to improve after withdrawal of entrectinib. It is crucial to increase awareness of TRKi-specific adverse events and their proper management.

DOI： 10.1007/s12328-024-02076-w

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by germline variants in the APC gene, leading to the development of numerous colorectal polyps and significantly increases the risk of colorectal cancer. A diagnosis is typically made using colonoscopy, and genetic testing can assist in patient surveillance and carrier identification. Recent advances include the use of whole-genome array comparative genomic hybridization (a-CGH), which provides better resolution of genetic imbalances. We aimed to explore the specific features of FAP patients with whole APC gene deletions using high-resolution a-CGH and to compare patient characteristics. Two polyposis patients with whole APC deletions were identified, and the lost genetic sizes ranged from 0.3–1.1 Mb. Nervous abnormalities were a characteristic symptom in a patient with a 1.1 Mb loss. A patient with an approximately 0.3 Mb loss, which included the entire APC gene, presented a polyposis phenotype without intellectual disability. The comparison of genetic losses, with or without intellectual disability, revealed 7 genetic changes. Consequently, EPB41L4A is a candidate gene associated with the neurogenic phenotype.

DOI： 10.1038/s41439-024-00301-z

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Other Link： https://www.nature.com/articles/s41439-024-00301-z

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We herein present the case of a 30-year-old Japanese male patient with ulcerative colitis (UC) who was admitted to our hospital because of significant ascites. Upon evaluation, the patient was diagnosed with unresectable UC-associated cancer (UCAC), localized in the transverse colon. Using gene profiling of the tumor tissue, anti-epidermal growth factor receptor (EGFR) antibody combination chemotherapy was selected. Subsequently, the patient exhibited a temporary response to this regimen, with an enhancement in his quality of life and he was able to survive for 12 months. This case underscores the potential benefits of aggressive chemotherapy tailored to the gene profile in UCAC treatment, offering insights into potential avenues for improving the patient prognosis.

DOI： 10.2169/internalmedicine.4160-24

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

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

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

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

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Language：Japanese   Publisher：(一社)日本潰瘍学会  

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Language：Japanese   Publisher：(一社)日本潰瘍学会  

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INTRODUCTION: Unsedated peroral endoscopy, including ultrathin endoscopy (UE) and conventional endoscopy (CE), is feasible in clinical practice but requires improved endoscopic operability and patient tolerance. Currently, the impact of breathing method on these factors remains unclear. We conducted the first randomized controlled trial comparing oral breathing (OB) and nasal breathing (NB) during both UE and CE to assess their influence. METHODS: 252 eligible patients undergoing CE or UE were randomly assigned to OB or NB groups. Endoscopists and patients rated endoscopic operability and patient tolerance using a 100-mm visual analog scale (VAS). Visibility from the oral cavity to the middle pharynx was recorded. RESULTS: OB led to a higher rate of improved visibility from the oral cavity to the middle pharynx compared to NB, ranging from 79.3% to 81.0%. Multivariate correlation analyses showed significantly lower VAS scores for endoscopic operability with OB compared to NB in both UE and CE groups (p < 0.05). No significant differences were found in the overall evaluation of patient tolerance between OB and NB groups in UE and CE, while the smaller diameter of UE exhibited better patient tolerance compared to CE. Discriminant analysis comparing endoscope types and breathing methods revealed that UE with OB outperformed other combinations in the overall evaluation of endoscopic operability and patient tolerance (p < 0.05). CONCLUSIONS: OB facilitates endoscopic operability compared to NB in peroral endoscopy. UE with OB is recommended as the preferred choice for unsedated peroral endoscopy in daily practice.

DOI： 10.14309/ajg.0000000000003040

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(株)メディカルアイ  

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INTRODUCTION: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) was given to patients with Crohn's disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with CD remains unclear. METHODS: This study evaluated the clinical efficacy and subsequent clinical progression after GMA in patients with CD who underwent GMA in seven independent institutions in Japan from 2010 to 2023. RESULTS: Sixteen patients were enrolled. The overall remission and response rates were 25.0% and 68.8%, respectively. All patients responding to GMA received biologics that were continuously used and 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to biologics. CONCLUSION: GMA may exhibit effectiveness even in cases with refractory CD. Moreover, it represents a potential novel therapeutic option for refractory CD with loss of response to biologics.

DOI： 10.1111/1744-9987.14103

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Background and study aims Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by an elevated lesion with vessel dilation exhibiting branching architecture (DVBA). However, this feature is also found in fundic gland polyps (FGPs), posing a challenge in their differentiation. In this study, we aimed to investigate the clinicopathological features of gastric elevated lesions with DVBA and assess the efficacy of the white ring sign (WRS) as a novel marker for distinguishing between FGPs and GA-FGs. Methods We analyzed 159 gastric elevated lesions without DVBA and 51 gastric elevated lesions with DVBA, further dividing the latter into 39 in the WRS-positive group and 12 in the WRS-negative group. The clinicopathological features, diagnostic accuracy, and inter-rater reliability were analyzed. Results Univariate and multivariate analyses for gastric elevated lesions with DVBA identified the histological type consistent with FGPs and GA-FGs, along with the presence of round pits in the background gastric mucosa, as independent predictors. FGPs were present in 92.3% (36/39) of the WRS-positive group and GA-FGs were observed in 50.0% (6/12) of the WRS-negative group. WRS positivity and negativity exhibited high diagnostic accuracy, with 100% sensitivity, 80.0% specificity, and 94.1% accuracy for FGPs, and 100% sensitivity, 86.7% specificity, and 88.2% accuracy for GA-FGs. Kappa values for WRS between experts and nonexperts were 0.891 and 0.841, respectively, indicating excellent agreement. Conclusions WRS positivity and negativity demonstrate high diagnostic accuracy and inter-rater reliability for FGPs and GA-FGs, respectively, suggesting that WRS is a useful novel marker for distinguishing between FGPs and GA-FGs.

DOI： 10.1055/a-2301-6248

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Language：Japanese   Publisher：日本大腸検査学会  

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INTRODUCTION: Carbazochrome sodium sulfonate (CSS) is a hemostatic agent that reduces capillary permeability and enhances capillary resistance. However, its specific effects on colorectal endoscopic submucosal dissection (ESD) outcomes remain uncertain. This study aimed to assess the risk factors for post-ESD bleeding and the effect of CSS on colorectal ESD outcomes. METHODS: First, we retrospectively analyzed the risk factors for post-ESD bleeding using data from 1,315 lesions in 1,223 patients who underwent ESD for superficial colorectal neoplasms at eight institutions. Second, patients were divided into CSS and non-CSS groups using propensity score matching, and their outcomes from colorectal ESD were analyzed. RESULTS: The risk factors for post-colorectal ESD bleeding were identified as age of ≥70 years, tumor located in the rectum, tumor size of ≥40 mm, and post-ESD defect unclosure in both univariate and multivariate analyses. The CSS and non-CSS groups each consisted of 423 lesions after propensity score matching. The post-colorectal ESD bleeding rate was 3.5% (15/423) and 3.3% (14/423) in the CSS and non-CSS groups, respectively, indicating no significant differences. Among patients with the high-risk factors for post-ESD bleeding, the administration of CSS also did not demonstrate a significant reduction in the post-ESD bleeding rate compared to the non-CSS group. CONCLUSION: CSS administration is ineffective in preventing post-colorectal ESD bleeding in both the general population and individuals at a high risk for such bleeding. Our results indicate the necessity to reconsider the application of CSS for preventing post-colorectal ESD bleeding.

DOI： 10.1159/000539367

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

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

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

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

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BACKGROUND AND AIM: Image enhancement endoscopy techniques, such as linked color imaging (LCI) and autofluorescence imaging (AFI), have shown promise in diagnosing mucosal inflammation in ulcerative colitis (UC). However, no studies have directly compared the diagnostic efficacy of LCI and AFI. This prospective observational study aimed to compare their diagnostic accuracy for histological healing in UC. METHODS: This study included 81 UC patients, resulting in a total of 204 endoscopic images captured using LCI and AFI, respectively. Spearman's rank correlation coefficients assessed the correlation between LCI and AFI coloration and Geboes histopathology score (GHS). Six endoscopists, who were blinded to clinicopathological features, evaluated these images, and subsequently, the diagnostic accuracy was evaluated. RESULTS: Spearman's rank correlation coefficients between LCI index, AFI index (reverse gamma value), and GHS were 0.324 and -0.428, respectively (P < 0.001), indicating a significant correlation between LCI and AFI coloration and histological healing. In LCI and AFI classifications, mean values for diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 76.3 ± 2.2 versus 77.8 ± 2.7, 91.8 ± 4.0 versus 83.2 ± 7.6, 53.4 ± 10.0 versus 70.0 ± 5.3, 74.0 ± 3.5 versus 80.0 ± 1.6, and 82.9 ± 5.2 versus 75.5 ± 7.5, respectively. No significant difference in diagnostic accuracy existed between LCI and AFI classifications. However, LCI displayed higher sensitivity than AFI while AFI showed higher specificity compared with LCI (P < 0.05). CONCLUSIONS: LCI and AFI offer comparable diagnostic accuracy for histological healing. Clinically, it is necessary to recognize diagnostic features characterized by higher sensitivity in LCI and greater specificity in AFI.

DOI： 10.1111/jgh.16586

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death, thus a novel chemotherapeutic agent for colon cancer therapy is needed. In this study, analogues of echinomycin, a cyclic peptide natural product with potent toxicity to several human cancer cell lines, were synthesized, and their biological activities against human colon cancer cells were investigated. Analogue 3 as well as 1 inhibit HIF-1α-mediated transcription. Notably, transcriptome analysis indicated that the cell cycle and its regulation were involved in the effects on cells treated with 3. Analogue 3 exhibited superior in vivo efficacy to echinomycin without significant toxicity in mouse xenograft model. The low dose of 3 needed to be efficacious in vivo is also noteworthy and our data suggest that 3 is an attractive and potentially novel agent for the treatment of colon cancer.

DOI： 10.1038/s41598-024-58196-3

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Other Link： https://www.nature.com/articles/s41598-024-58196-3

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

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BACKGROUND: Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC. METHODS: Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses. RESULTS: Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%. CONCLUSIONS: This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.

DOI： 10.1093/crocol/otae024

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

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J02312&link_issn=&doc_id=20240507090026&doc_link_id=10.24479%2Fendo.0000001326&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fendo.0000001326&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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

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

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Esophageal cancer, which is common among the elderly, has the poorest prognosis among gastrointestinal cancers. Previously, we demonstrated that ferrichrome, produced by the probiotic Lactobacillus casei, exhibited anti-tumor effects in various gastrointestinal cancers, including colorectal and gastric cancers, with minimal effects on non-cancerous intestinal cells. However, it remains unclear whether ferrichrome exerts anti-tumor effects in esophageal cancer. A sulforhodamine B assay revealed that ferrichrome suppressed esophageal adenocarcinoma (OE33, OE19) and squamous cell carcinoma (KYSE70) cells. Ki-67 staining indicated that ferrichrome inhibited the proliferation of esophageal cancer cells. Cell cycle analysis showed that ferrichrome inhibited the DNA synthesis. TUNEL staining revealed that ferrichrome-induced DNA fragmentation. We also confirmed the cleavage of caspase-9 and PARP in ferrichrome-treated cells. Reverse transcription polymerase chain reaction demonstrated an increase in the mRNA of DNA damage-inducible transcript 3 (DDIT-3), a key regulator of programmed cell death, in ferrichrome-treated OE33 cells. In an in vivo OE33 xenograft model, intraperitoneal administration of 5-mg/kg ferrichrome for 14 days resulted in an almost complete inhibition of tumor growth. However, 14 days of intraperitoneal administration of 20-mg/kg 5-fluorouracil (5-FU), but not 20-mg/kg ferrichrome, induced weight loss and myelosuppression in both young and aged mice. Our findings indicate that ferrichrome induces DNA damage-inducible transcript-3, thereby producing anti-tumor effects, including cell cycle arrest and apoptosis, with minimal adverse effects in esophageal cancer cells. This illustrates the high potential of ferrichrome as an anti-tumor drug against esophageal carcinoma.

DOI： 10.1016/j.heliyon.2024.e28070

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The combination or sequential use of systemic therapies, such as lenvatinib and locoregional therapies, can improve the curability rate of hepatocellular carcinoma. This is based on the notion that lenvatinib remodels abnormal tumor vessels into normal vessels, potentially enhancing the efficacy of locoregional therapies. In this case report, we achieved noninvasive visualization of tumor blood vessels by applying superb microvascular imaging (SMI) to contrast-enhanced ultrasonography (CEUS). A man in his 80s with a borderline resectable hepatocellular carcinoma received preoperative therapy using lenvatinib. The patient achieved a complete response after lenvatinib therapy, underwent hepatectomy, and maintained a cancer-free status. CEUS and SMI revealed a decrease in tumor blood vessels at 1 week after lenvatinib administration and a decrease in tumor perfusion at 2 weeks. Although CEUS alone is adequate for noninvasive real-time evaluation of tumor perfusion, it is not sufficient to achieve accurate assessments of tumor blood vessels. We performed a noninvasive time-course evaluation of vascular normalization after lenvatinib administration by applying SMI. The evaluation of vascular normalization with lenvatinib therapy using CEUS and SMI can support the decision to proceed to conversion therapies.

DOI： 10.3390/diagnostics14070678

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BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.

DOI： 10.1007/s00464-024-10762-6

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A woman in her 60s presented with a small pancreatic head tumor. Imaging studies revealed a 13-mm well-defined pancreatic head tumor. A neuroendocrine neoplasm was suspected, and the patient opted for observation at that time. After 8 months, the patient began experiencing sweating while fasting, and blood tests during regular follow-up visits showed hypoglycemia. Hypoglycemia was induced during fasting test. The tumor exhibited clear features of an insulinoma during follow-up observation. While small neuroendocrine neoplasms are often managed through observation, caution should be exercised regarding their transformation into functional neuroendocrine tumors.

DOI： 10.2169/internalmedicine.3194-23

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

Objectives

The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)–encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs.

Materials and Methods

Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR.

Results

Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA, in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA, which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC, which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA, HULC, or CA19-9 alone.

Conclusions

Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

DOI： 10.1097/mpa.0000000000002315

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BACKGROUND AND AIMS: EUS-guided biliary drainage (EUS-BD) has been performed increasingly worldwide, especially in patients with malignant tumors in which ERCP is difficult, patients with surgically altered GI tracts, and older patients who are at high risk for surgery. EUS-BD requires high-level skills and has limited options for managing adverse events, particularly when stent migration and cholangitis occur. Adverse events, such as persistent bile leakage from the fistula and continuous reflux from the GI tract, are believed to always have a risk of severe exacerbation that could threaten the patient's life. METHODS: We encountered 2 cases of stent migrations and 1 case with repeated cholangitis in patients with malignant tumors among the patients who underwent EUS-BD. The migrated stent was visualized under EUS in 2 patients with stent migration, and an EUS-guided FNA needle was used to puncture the mesh of the stent. The cannulation catheter was directly inserted into the mesh of the stent in 1 case with repeated retrograde cholangitis, while the stent was visualized with an endoscope. Subsequently, a guidewire was inserted through the puncture site, and a second metal stent was deployed between the meshes of the first stent, bridging the GI wall again (Lambda stenting technique). All procedures were performed with the patient under general anesthesia, and the patients safely completed the intervention. RESULTS: Patients' conditions significantly improved after the second stent insertion, allowing for chemotherapy resumption while maintaining their activities of daily living. The second stent remained in place without any migration, and the stent successfully prevented further cholangitis. CONCLUSIONS: The Lambda stenting technique is considered highly effective for managing stent migration and repeated cholangitis, which is a major EUS-BD adverse event. This procedure helps avoid more invasive surgeries when stent migration and cholangitis occur and contributes to expanding EUS-BD applicability.

DOI： 10.1016/j.vgie.2023.10.010

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RATIONALE: Both ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases with unknown etiologies and are rare. However, the odds ratio in UC patients has been reported to range from 1.7 to 2.1, suggesting a potential etiology between sarcoidosis and UC. Furthermore, the underlying etiologies of UC and sarcoidosis remain unidentified. Sharing the experience of a UC patient with cardiac sarcoidosis could provide valuable insights to prevent sudden death in UC patients. PATIENT CONCERNS: A 71-year-old Japanese woman was diagnosed with UC at 58-year-old and maintained remission on mesalazine treatment. She complained of just palpitation; therefore, she consulted a cardiologist. DIAGNOSES: The patient received a diagnosis of cardiac sarcoidosis with complicating ulcerative colitis based on the results of N-terminal prohormone of the brain natriuretic peptide (NT-proBNP), imaging examinations, and histology. INTERVENTION: The patient was treated with prednisolone and methotrexate. The prednisolone was then tapered, and the methotrexate dose was adjusted based on her symptoms, imaging results, and laboratory findings. OUTCOME: She no longer had any symptoms, and the abnormal FDG uptake had disappeared after 2 years. LESSON: In UC patients, periodic or additional (in case of symptomatic) electrocardiography and NT-proBNP are recommended for the early detection of cardiac sarcoidosis, a life-threatening complication.

DOI： 10.1097/MD.0000000000036207

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

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Language：Japanese   Publisher：(株)メディカルアイ  

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Language：Japanese   Publisher：北海道医学会  

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BACKGROUND: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). METHODS: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT. RESULTS: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization. CONCLUSION: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.

DOI： 10.1007/s00535-023-02048-w

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Neurosurgery Publishing Group (JNSPG)  

OBJECTIVE

Antithrombotic medications pose a challenge for conducting surgical or invasive procedures, because their discontinuation is required to avoid postprocedural hemorrhagic complications but potentially increases the ischemic risk for the patient. This study aimed to estimate the increased risk of developing cerebral ischemic events during hospitalization requiring discontinuation of antithrombotic therapy.

METHODS

This investigation was a single-center retrospective observational study. Clinical data in patients scheduled for admission between January 1, 2021, and December 31, 2022, were collected. Patients requiring discontinuation of antithrombotic therapy were identified by referring to the admission database. Patients who developed cerebral ischemia were identified by referring to the institution’s stroke center database.

RESULTS

Seven hundred ninety-six patients scheduled for nonneurosurgical procedures and 39 scheduled for neurosurgical procedures underwent discontinuation of antithrombotic therapy. Anticoagulation therapy was prescribed in 40.0%, and antiplatelet therapy was prescribed in 69.1% of the patients. A total of 9.2% of the entire cohort of patients were receiving both anticoagulation and antiplatelet therapy. Bridging therapy was administered in 20.9% of nonneurosurgical patients. No ischemic event was observed in the patients undergoing neurosurgical procedures. Among the entire cohort, 3 patients encountered some kind of thrombotic event—2 of which were cerebral ischemia—accounting for an incidence of 0.24%, which was significantly higher than incidental in-hospital stroke unrelated to discontinuation of antithrombotic therapy (p = 0.04). Patients undergoing both anticoagulation and antiplatelet therapy harbored a significantly higher risk for cerebral ischemia related to discontinuation of antithrombotic therapy (p &lt; 0.0001).

CONCLUSIONS

Discontinuing antithrombotic therapy during hospitalization for elective invasive procedures—including neurosurgical procedures—entailed a relatively small risk of developing cerebral ischemic events, but the risk was significantly higher compared to hospitalized patients without discontinuation of antithrombotic therapy.

DOI： 10.3171/2023.7.focus23341

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Other Link： https://thejns.org/downloadpdf/journals/neurosurg-focus/55/4/article-pE7.xml

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BACKGROUND AND AIM: There have been several reports that some probiotics improve non-alcoholic fatty liver disease (NAFLD); however, many studies have involved cocktail therapies. We evaluated whether heat-killed Lactobacillus brevis SBL88 (L. brevis SBL88) monotherapy improves the clinical features of NAFLD. METHODS: The NAFLD model was induced in mice fed a high-fat diet (HFD) (HFD mice) or HFD + 1% heat-killed L. brevis SBL88 (SBL mice) for 16 weeks. Histopathological liver findings were analyzed. To evaluate the gut microbiota, a modified terminal restriction fragment length polymorphism analysis of the feces was performed. RNA sequencing in the liver was performed with Ion Proton™. To investigate the direct effects of heat-killed L. brevis SBL88, an in vitro study was performed. RESULTS: Histopathological findings revealed that fat droplets in the liver were significantly reduced in SBL mice; however, terminal restriction fragment length polymorphism did not show alterations in the gut microbiota between HFD mice and SBL mice. RNA sequencing and pathway analysis revealed that the regulation of lipid and insulin metabolism was affected. The mRNA expression of insulin receptor substrate 2 (IRS-2) was significantly higher in SBL mice, whereas the expression of IRS-1 was not significantly different. Phospho-IRS-2 expression was also significantly increased in SBL mice. In addition, an in vitro study revealed significant alterations in IRS-2 and forkhead box protein O1 expression levels. CONCLUSION: SBL mice exhibited partially improved selective hepatic insulin resistance. Our data suggest that heat-killed L. brevis SBL88 could attenuate the clinical features of NAFLD that are not mediated by alterations in the gut microbiota.

DOI： 10.1111/jgh.16337

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

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

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

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

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

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Language：Japanese   Publisher：(一社)日本潰瘍学会  

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

RATIONALE: Latent tuberculosis (TB) infection screening before inducing anti-tumor necrosis factor (anti-TNF) alpha agents is important to prevent TB reactivation. However, latent TB infection reactivation may still occur, and the ideal therapeutic strategy for patients with inflammatory bowel disease (IBD) who develop active TB infection has not been established. Vedolizumab (VDZ) has a good safety profile, with low incidence rates of serious infections. However, its safety in patients with latent TB infection reactivation associated with anti-TNF-alpha agents remains unknown. PATIENT CONCERNS: A 21-year-old Vietnamese male patient presented to our hospital with hemorrhagic stool. He had no personal or family history of IBD or TB. DIAGNOSES: Colonoscopy revealed multiple longitudinal ulcers and a cobblestone appearance in the terminal ileum, as well as multiple small erosions and aphtha throughout the colon. Computed tomography revealed a right lung nodular lesion. Serological interferon-gamma release assay and several culture tests were all negative. Thus, he was diagnosed with ileocolonic Crohn's disease (CD) without TB. INTERVENTIONS: The intravenous anti-TNF-alpha agent administration with an immunomodulator was initiated. OUTCOMES: Computed tomography revealed nodular lesion expansion at the right lung, and serological interferon-gamma release assay was positive. He was diagnosed with latent TB infection reactivation. Anti-TNF-alpha agent with an immunomodulator was immediately discontinued, and anti-TB therapy was initiated. His endoscopic findings were still active, and VDZ was selected for maintenance therapy because VDZ has a favorable safety profile with low incidence rates of serious infections. Consequently, mucosal healing was achieved without active TB relapse. LESSONS: This case report presented a patient in whom VDZ was continued as maintenance therapy without inducing TB relapse in a patient with CD who developed latent TB infection reactivation associated with anti-TNF-alpha agents and summarized the safety profile of VDZ for patients with IBD with active or latent TB infection. VDZ may be a safe option for induction and maintenance therapy in patients with CD, even in cases with latent TB infection reactivation.

DOI： 10.1097/MD.0000000000034331

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

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01118&link_issn=&doc_id=20230721350007&doc_link_id=1390015333244307072&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390015333244307072&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(株)メディカルアイ  

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

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

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

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

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

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

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

BACKGROUND : Transnasal endoscopy presents a technical difficulty when inserting the flexible endoscope. It is unclear whether a particular breathing method is useful for transnasal endoscopy. Therefore, we conducted a prospective randomized controlled trial to compare endoscopic operability and patient tolerance between patients assigned to nasal breathing or oral breathing groups. METHODS : 198 eligible patients were randomly assigned to undergo transnasal endoscopy with nasal breathing or with oral breathing. Endoscopists and patients answered questionnaires on the endoscopic operability and patient tolerance using a 100-mm visual analog scale ranging from 0 (non-existent) to 100 (most difficult/unbearable). The visibility of the upper-middle pharynx was recorded. RESULTS : Patient characteristics did not differ significantly between the groups. Nasal breathing showed a higher rate of good visibility of the upper-middle pharynx than oral breathing (91.9 % vs. 27.6 %; P < 0.001). Nasal breathing showed lower mean [SD] scores than oral breathing in terms of overall technical difficulty (21.0 [11.4] vs. 35.4 [15.0]; P < 0.001). Regarding patient tolerance, nasal breathing showed lower scores than oral breathing for overall discomfort (22.1 [18.8] vs. 30.5 [20.9]; P = 0.004) and other symptoms, including nasal and throat pain, choking, suffocating, gagging, belching, and bloating (all P < 0.05). The pharyngeal bleeding rate was lower in the nasal breathing group than in the oral breathing group (0 % vs. 9.2 %; P = 0.002). CONCLUSIONS : Nasal breathing is superior to oral breathing for those performing and undergoing transnasal endoscopy. Nasal breathing led to good visibility of the upper-middle pharynx, improved endoscopic operability, and better patient tolerance, and was safer owing to decreased pharyngeal bleeding.

DOI： 10.1055/a-1900-6004

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(株)先端医学社  

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

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

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Language：English  

Recent technological advancements have enabled us to analyze a variety of aspects of colorectal cancer (CRC), including both clinical and basic science [...].

DOI： 10.3390/cancers15041328

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Publishing type：Research paper (scientific journal)   Publisher：Baishideng Publishing Group Inc.  

DOI： 10.4251/wjgo.v15.i1.186

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BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn has been used as a remission induction therapy for patients with active ulcerative colitis (UC). Herein, we investigated the influence of concomitant medications in the remission induction of GMA in patients with active UC. METHODS: This multicenter retrospective cohort study included patients with UC underwent GMA in five independent institutions in Japan from January 2011 to July 2021. Factors including concomitant medications associated with clinical remission (CR) were analyzed statistically. RESULT: A total of 133 patients were included. Seventy-four patients achieved a CR after GMA. The multivariable analysis revealed that concomitant medication with 5-aminosalicylic acid, Mayo endoscopic subscore (MES), and concomitant medication with immunosuppressors (IMs) remained as predictors of CR after GMA. In the subgroup analysis in patients with MES of 2, concomitant medication with IMs was demonstrated as a significant negative factor of CR after GMA (P = .042, OR 0.354). Seventy-four patients who achieved CR after GMA were followed up for 52 weeks. In the multivariable analysis, the maintenance therapy with IMs was demonstrated as a significant positive factor of sustained CR up to 52 weeks (P = .038, OR 2.214). Furthermore, the rate of sustained CR in patients with biologics and IMs was significantly higher than that in patients with biologics only (P = .002). CONCLUSION: GMA was more effective for patients with active UC that relapsed under treatment without IMs. Furthermore, the addition of IMs should be considered in patients on maintenance therapy with biologics after GMA.

DOI： 10.1002/jca.22040

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

A 24-year-old woman was admitted to our hospital due to abdominal pain and a high fever. She was diagnosed with ileocolonic Crohn's disease (CD), complicated with a gastro-colic fistula and splenomegaly. After initial treatment with an infliximab-biosimilar, all blood cell line counts markedly decreased. Three-dimensional reconstructed computed tomography revealed splenic vein narrowing. Thus, her pancytopenia was deemed to have likely been caused by hypersplenism. Surgery was performed, and clinical remission was maintained without pancytopenia. This is the first report of a CD patient with pancytopenia caused by hypersplenism that was triggered by gastro-colic fistula-associated splenic vein obstruction.

DOI： 10.2169/internalmedicine.9590-22

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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

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

BACKGROUND: Infliximab (IFX) effectively treats patients with inflammatory bowel disease (IBD). IFX-biosimilar (IFX-BS) has the same amino acid sequence as that of the IFX originator, and its increasing use is expected to reduce national healthcare costs. Long-term efficacy and safety of IFX-BS in patients with Crohn's disease (CD) and ulcerative colitis (UC) have not been completely investigated. METHODS: We conducted a retrospective, multicenter observational study of patients with IBD who received IFX-BS treatment at three hospitals between October 2016 and April 2022. Clinical data were collected from electronic medical records and evaluated for achieving clinical remission (CR) using Crohn's disease activity index (CDAI) and partial Mayo (pMayo) score, persistency of long-term IFX-BS administration, and clinical response rate in the bio-naïve and bio-failure groups. RESULTS: A total of 117 patients with IBD (90 CD and 27 UC) were included. The study findings indicated that both bio-naïve and bio-failure groups of patients with UC showed similar effectiveness of IFX-BS. The treatment persistence rate in patients with CD was significantly higher in the bio-naïve (P = 0.042) and switch (P = 0.010) groups than in the bio-failure group. In the former two groups, the treatment persistence rate was high at two years after administration (more than 80%). In patients with UC, the findings indicated higher treatment persistence rate in the switch group than in the bio-naïve group. Univariable and multivariable analyses for treatment persistence rate showed that the albumin level at the initial IFX-BS administration and groups (bio-naïve, bio-failure and switch) were effective factors for patients with CD. Adverse events were reported in 18 patients (15.4%). CONCLUSION: The present study demonstrates the long-term effectiveness and safety of IFX-BS. In addition to the favorable remission induction in the bio-naïve and bio-failure groups, we demonstrated remission maintenance and treatment persistence rates beyond two years. Albumin level and groups were associated with better treatment persistence in patients with CD.

DOI： 10.1371/journal.pone.0288393

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

In Japan, establishing a medical cooperation system for patients with inflammatory bowel disease (IBD) between IBD flagship and local care hospitals is a crucial task. Thus, this retrospective multicenter cohort study aims to examine the actual state of medical treatment in patients with IBD via a questionnaire survey administered to eight dependent institutes in Hokkaido, Japan. The present results clarified the clinical disparities of IBD treatment and hospital function between IBD flagship hospitals and local care hospitals. Moreover, the understanding level of IBD treatment in medical staff was significantly lower in local care than in IBD flagship hospitals. Furthermore, an abounding experience of IBD treatment affected the understanding level of IBD treatment of both medical doctors and staff. These findings indicate that selecting patients with IBD corresponding to disease activity, educational system for the current IBD treatment, and promotion of team medicine with multimedical staff can resolve clinical discrepancies between IBD flagship and local care hospitals. The IBD treatment inequities in Japan will be eliminated with the development of an appropriate medical cooperation system between IBD flagship and local care hospitals.

DOI： 10.11405/nisshoshi.120.590

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A 63-year-old man with hepatitis C was treated with atezolizumab plus bevacizumab for unresectable diffuse hepatocellular carcinoma (HCC). After four cycles of atezolizumab plus bevacizumab, the diffuse HCC markedly shrank; however, he complained of general fatigue, loss of appetite, and slight loss of muscle strength in the lower legs. He was diagnosed with isolated adrenocorticotropic hormone deficiency (IAD), hypothyroidism, and myopathy, suggesting multisystem immune-related adverse events (irAEs). After administration of hydrocortisone, the clinical symptoms rapidly disappeared. Patients with multisystem irAEs can have favorable outcomes; thus, to continue immune-checkpoint inhibitors therapy, a correct diagnosis and management of multisystem irAEs are important.

DOI： 10.2169/internalmedicine.9393-22

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

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Language：Japanese   Publisher：日本小腸学会  

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Language：Japanese   Publisher：(一社)日本アフェレシス学会  

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

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Language：Japanese   Publisher：(株)東京医学社  

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

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

Various heterogeneous nuclear ribonucleoproteins (hnRNPs) have been reported to be associated with cancer cell growth. However, it remains unclear whether hnRNP G-T, which is specifically expressed in the testis, is expressed in tumor cells, and whether hnRNP G-T expressed in colorectal cancer (CRC) cells is associated with tumor progression. We herein report that hnRNP G-T promoted cancer cell growth and stabilized mRNA of ZDHHC11 in CRC. The cell growth was inhibited by transfection of siRNA of hnRNP G-T in cancer cells, but not in non-cancerous epithelial cells. The tumor promotive effect of hnRNP G-T was confirmed in an HCT116 transplanted mouse model. RT-PCR and western blotting indicated the augmentation of hnRNP G-T in CRC in comparison to non-cancerous cells. The downregulation of hnRNP G-T inhibited cancer cell growth and promoted apoptosis in CRC. A transcriptome analysis combined with immunoprecipitation revealed that hnRNP G-T stabilized 174 mRNAs, including ZDHHC11 mRNA. The cell growth was also suppressed by the transfection of siRNA of ZDHHC11 and the mRNA and the protein expression were decreased by the transfection of siRNA of hnRNP G-T. These results suggested that hnRNP G-T promotes the cell growth of CRC by regulating the mRNA of ZDHHC11. Therefore, hnRNP G-T will be highlighted as an effective therapeutic target with less adverse effects in CRC therapy.

DOI： 10.1002/cam4.4738

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

BACKGROUND: Carbazochrome sodium sulfonate (CSS) is conventionally administered to prevent post-endoscopic submucosal dissection (ESD) bleeding in many institutions, but research on its preventive efficacy is lacking. Therefore, we investigated the risk of post-ESD bleeding and the preventive efficacy of CSS administration. METHODS: We retrospectively reviewed 304 lesions in 259 patients with gastric neoplasms who underwent ESD at Asahikawa Medical University Hospital from 2014 to 2021. In the CSS group, CSS 100 mg/day was intravenously infused with maintenance fluid replacement on postoperative days 0-2. The risk factors of post-ESD bleeding, including CSS administration, were investigated. RESULTS: The overall rate of post-ESD bleeding was 4.6% (14/304). The univariate analysis showed that atrial fibrillation (Af), warfarin intake, heparin replacement, and tumor location in the lower third were significant risk factors for increasing the likelihood of postoperative bleeding. In the multivariate analysis, Af (odds ratio [OR] 3.83, 95% CI 1.02-14.30; p &lt; 0.05), heparin replacement (OR 4.60, 95% CI 1.02-20.70; p &lt; 0.05), and tumor location in the lower third of the stomach (OR 6.67, 95% CI 1.43-31.00; p &lt; 0.05) were independent factors for post-ESD bleeding. Post-ESD bleeding was observed in 5.2% (9/174) of the CSS group and 3.8% (5/130) of the non-CSS group, with no significant difference between the two groups (p = 0.783). Additionally, CSS was not shown to have preventive effects in groups with higher-risk factors, such as Af diagnosis, warfarin use, heparin replacement, and tumor location in the lower third of the stomach. CONCLUSION: CSS administration was not effective for the prevention of the post-ESD bleeding in the overall patient population as well as in higher-risk patients. This suggests that the administration of CSS for post-ESD bleeding prevention may need to be reconsidered.

DOI： 10.1007/s00464-022-09171-4

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

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

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

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

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

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

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

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

BACKGROUND: Life-threatening cytomegalovirus infection (CMVI) has been reported even in patients with malignant lymphoma (ML) who have not received hematopoietic stem cell transplantation (w/o HSCT) but had been treated with chemotherapy or radiotherapy. However, the CMVI incidence and risk factors (RFs) in patients with ML w/o HSCT have not been fully elucidated. This study aimed to evaluate the clinical aspects, including incidence and RFs, of CMVI in patients with ML w/o HSCT. METHODS: We retrospectively reviewed all patients with ML who received chemotherapy or radiotherapy in our department from 2005 to 2013. The overall survival (OS), incidence and RFs of CMVI, and other characteristics of patients with CMVI were analyzed. RESULTS: Overall, 236 patients with ML w/o HSCT were evaluated. Of these, 5.5% (13/236) developed CMVI; 54% (7/13) received steroid pretreatment before primary therapy (PT) for ML; and 62% (8/13) received > 2 therapeutic regimens for ML. The OS curve of patients with CMVI was significantly worse than that of patients without CMVI (p < 0.0001, log-rank test). A univariate analysis identified B symptoms (p = 0.00321), serum albumin < 3.5 g/dL (p = 0.0007837), C-reactive protein level > the upper limit of normal (p = 0.0006962), steroid pretreatment before PT for ML (p = 0.0004262), > 2 therapeutic regimens for ML (p = 0.0000818), T cell lymphoma (p = 0.006406), and non-complete remission (p = 0.02311) as RFs for CMVI. A multivariate analysis identified steroid pretreatment before PT for ML [odds ratio (OR): 4.71 (95% confidence interval [CI]: 1.06-21.0); p = 0.0419] and > 2 therapeutic regimens for ML [OR: 9.25 (95% CI: 2.33-36.8); p = 0.00159] as independent RFs for CMVI in patients with ML w/o HSCT. CONCLUSIONS: Attention should be paid to CMVI development in patients with ML w/o HSCT pretreated with steroids or who had multiple therapeutic regimens.

DOI： 10.1186/s12885-022-10008-5

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

DOI： 10.1055/a-1550-1913

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Background and study aims  Recent advances in cancer treatment have involved the clinical application of immune checkpoint inhibitors (ICIs) for various type of cancers. The adverse events associated with ICIs are generally referred to as immune-related adverse events (irAEs). Gastrointestinal irAEs are a major disorder, but gastritis is not frequently observed. The aims of this study were to elucidate the clinical, endoscopic, and histological characteristics of irAE gastritis. Patients and methods  Information on patients treated with ICIs were collected from a single institute over 3 years. IrAE gastritis was identified based on the clinical course and endoscopic and histopathological findings. Of the 359 patients treated with ICIs, four cases of irAE gastritis were identified in clinical records from the endoscopy unit. The endoscopic and histopathological findings were analyzed, and further immunohistochemical studies with immune subtype markers and programmed cell death ligand-1 (PD-L1) antibody were conducted. Results  Among four patients with irAE gastritis, the remarkable endoscopic characteristics were network-pattern erosion, erythematous and edematous mucosa with thick purulent discharge, and fragile mucosa. Corresponding histological features were fibrinopurulent exudate, severe inflammatory cell infiltration, and epithalaxia, respectively. The PD-L1 expression rate was ≥ 1 % in the gastric tissue of all patients with gastritis. These patients were treated with prednisolone (PSL) and their symptoms improved within a few days to 2 weeks. Conclusions  IrAE gastritis were characterized by specific endoscopic findings. The appropriate endoscopic diagnosis may lead to effective treatment with PSL.

DOI： 10.1055/a-1839-4303

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DOI： 10.1016/j.gie.2022.02.009

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

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DOI： 10.1111/den.14281

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BACKGROUND: Several microorganisms inhabit the mammalian gastrointestinal tract and are associated with the pathogenesis of various diseases, including cancer. Recent studies have indicated that several probiotics produce antitumor molecules and inhibit host tumor progression. We demonstrated that heptelidic acid (HA), a sesquiterpene lactone derived from the probiotic Aspergillus oryzae, exerts antitumor effects against pancreatic cancer in vitro and in vivo. In this study, the antitumor effects of HA against extraintestinal melanoma were assessed in vitro and in vivo. RESULTS: Sulforhodamine B (SRB) assay revealed that the growth of B16F10 cells was significantly inhibited by HA in a concentration-dependent manner. The enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) decreased in proportion with the growth inhibition effect of HA. Moreover, oral HA administration significantly suppressed the growth of transplanted B16F10 tumors without any significant changes in biochemical test values. Moreover, GAPDH activity in the transplanted tumor tissues in the HA group significantly decreased compared with that in the PBS group. CONCLUSION: This study suggests that orally administered HA was absorbed in the gastrointestinal tract, reached the cancer cells transplanted in the skin, and inhibited GAPDH activity, thereby inhibiting the growth of extraintestinal melanoma cells. Thus, this study proposes a novel system for extraintestinal tumor regulation via gut bacteria-derived bioactive mediators.

DOI： 10.1186/s12866-022-02530-0

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Language：Japanese   Publisher：日本大腸検査学会  

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

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

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

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

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

BACKGROUND: Reconstruction surgery-associated stricture frequently occurs in patients with long-gap esophageal atresia (LGEA). While several endoscopic dilatation methods have been applied and would be desirable, endoscopic recanalization is very difficult in cases with complete esophageal closure. Surgical treatment has been performed for a severe stricture, which causes extensive damage to the infant. No reports have described successful endoscopic recanalization for complete closure due to scarring after surgery for LGEA. We herein report the case of successful endoscopic recanalization by single endoscopist in an LGEA patient with complete closure after reconstruction surgery. CASE PRESENTATION: A seven-month-old boy with LGEA who received reconstruction surgery and gastrostomy immediately after birth presented to our unit due to vomiting and malnutrition. Contrast radiography and peroral endoscopy detected complete closure of the esophagus at the anastomotic site. After confirming the length of stricture as several millimeters, we punctured the center of the lumen with a 25-G puncture needle under fluoroscopy. An endoscope was then inserted via the gastrostomy and the puncture hole was detected at the center of the lumen. After passing the guidewire, endoscopic balloon dilation was performed three times, and the hole was sufficiently dilatated. Oral ingestion was feasible, and his nutritional condition was improved. CONCLUSIONS: To our knowledge, this is the first report to propose a less invasive endoscopic approach to recanalize a site of complete esophageal closure in a LGEA patient after reconstruction surgery by single endoscopist. Our endoscopic procedure using an ultrathin endoscope and puncture needle may be a therapeutic option for the treatment of patients with complete esophageal closure in a LGEA patient after reconstruction surgery.

DOI： 10.1186/s12876-022-02207-y

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Frostbite occurs when the skin is exposed to localized low temperatures. The main causes of frostbite are thought to be direct cell injury due to freezing of cells and tissue ischemia due to abnormal blood circulation. However, the molecular mechanism of frostbite has not been elucidated. This study aims to explain the molecular dynamics of frostbite using a mouse frostbite model and keratinocyte cell culture. Comprehensive gene expression analysis performed on mouse skin samples revealed that β-catenin signaling is activated by frostbite. Immunohistochemistry showed nuclear translocation of β-catenin in the skin of frostbite model mice that was not observed in mice subjected to a mechanical skin damage model induced by tape stripping. Tissue hypoxia, as detected by pimonidazole staining, coexisted with nuclear expression of β-catenin. In keratinocyte cell cultures, nuclear translocation of β-catenin was induced by hypoxia, but not by low temperature. Hypoxia induced epithelial-mesenchymal transition - an important biological event in the healing process of skin - and in vitro wound-healing activity, both of which were suppressed by β-catenin inhibition. Our results suggest that during frostbite, impaired blood flow causes hypoxia, which in turn activates β-catenin that promotes keratinocyte motility and tissue repair.

DOI： 10.1016/j.bbadis.2022.166385

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

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Language：Japanese   Publisher：(株)日本臨床社  

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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BACKGROUND: Mutations in GNAS drive pancreatic tumorigenesis and frequently occur in intraductal papillary mucinous neoplasm (IPMN); however, their value as a therapeutic target is yet to be determined. This study aimed at evaluating the involvement of mutant GNAS in tumor aggressiveness in established pancreatic cancer. METHODS: CRISPR/Cas9-mediated GNAS R201H silencing was performed using human primary IPMN-associated pancreatic cancer cells. The role of oncogenic GNAS in tumor maintenance was evaluated by conducting cell culture and xenograft experiments, and western blotting and transcriptome analyses were performed to uncover GNAS-driven signatures. RESULTS: Xenografts of GNAS wild-type cells were characterized by a higher Ki-67 labeling index relative to GNAS-mutant cells. Phenotypic alterations in the GNAS wild-type tumors resulted in a significant reduction in mucin production accompanied by solid with massive stromal components. Transcriptional profiling suggested an apparent conflict of mutant GNAS with KRAS signaling. A significantly higher Notch intercellular domain (NICD) was observed in the nuclear fraction of GNAS wild-type cells. Meanwhile, inhibition of protein kinase A (PKA) induced NICD in GNAS-mutant IPMN cells, suggesting that NOTCH signaling is negatively regulated by the GNAS-PKA pathway. GNAS wild-type cells were characterized by a significant invasive property relative to GNAS-mutant cells, which was mediated through the NOTCH regulatory pathway. CONCLUSIONS: Oncogenic GNAS induces mucin production, not only via MUC2 but also via MUC5AC/B, which may enlarge cystic lesions in the pancreas. The mutation may also limit tumor aggressiveness by attenuating NOTCH signaling; therefore, such tumor-suppressing effects must be considered when therapeutically inhibiting the GNAS pathway.

DOI： 10.1007/s00535-021-01846-4

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DOI： 10.1111/den.14180

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

BACKGROUND: Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later-line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens. PATIENTS AND METHODS: A regional cohort study was undertaken to determine the real-world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated. RESULTS: In total, 70 patients who received nivolumab as ≥third-line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8-10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68-0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2-positive status (27.3%) or microsatellite instability-high (27.3%) status. CONCLUSIONS: The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.

DOI： 10.1002/cam4.4461

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UNLABELLED: Inflammatory bowel diseases (IBDs) are chronic immune disorders of unclear etiology. Tumor necrosis factor (TNF) inhibitors are effective for IBD treatment and are cost-effective because they reduce hospital admissions and are associated with fewer surgery requirements and a better quality of life in IBD patients. A large number of clinical trials of infliximab biosimilar (CT-P13) have suggested that the administration of biosimilars provides high efficacy and safety similar to that of the originators, with a lower cost, so switching from the original to a biosimilar is considered an acceptable treatment. While several abnormalities of blood examination have been observed in patients with CT-P13 administration, no cases of drug-induced liver injury (DILI) caused by CT-P13 has been reported. A 23-year-old woman had been diagnosed with Crohn's disease and was treated with original infliximab (O-IFX) for 9 years. She developed severe jaundice 1 month after switching from O-IFX to CT-P13. Serologic tests of autoimmune and hepatitis viruses were negative, and ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography revealed no abnormalities. A liver biopsy showed prominent pericentral canalicular cholestasis, without features of steatosis or sclerosing cholangitis, which was consistent with drug-induced cholestasis. The cholestasis improved 10 weeks after the discontinuation of CT-P13, and no DILI redeveloped even after re-switching from CT-P13 to O-IFX. This is the first report of DILI due to switching from O-IFX to CT-P13. While the efficacy and safety of CT-P13 are considered equal to those of O-IFX, clinicians need to be alert for certain severe DILIs when switching from O-IFX to CT-P13 with careful monitoring and appropriate treatment. PLAIN LANGUAGE SUMMARY: A case report of drug-induced liver injury due to switch from original infliximab to infliximab biosimilar Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the entire gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor (TNF) inhibitors are effective for IBD treatment and are cost-effective because they reduce hospital admissions and are associated with fewer surgery requirements and a better quality of life in IBD patients. A biological medicinal product that contains a version of the active substance of an already authorized biological medicinal product. Biosimilars of TNF inhibitors, such as CT-P13, are thought to possess equal efficacy and safety to the original with a lower cost, so switching from the original to a biosimilar considered an acceptable treatment. While several serious adverse reactions of TNF inhibitors have been reported, drug-induced liver injury (DILI) is uncommon, and liver dysfunction due to the administration of CT-P13 has not been reported in IBD patients. We herein report the first case of DILI due to CT-P13 after switching from original infliximab (O-IFX) in a patient with Crohn's disease. While the efficacy and safety of CT-P13 are considered equal to those of O-IFX, clinicians need to be alert for certain severe DILIs when switching from O-IFX to CT-P13 with careful monitoring and appropriate treatment.

DOI： 10.1177/20420986221100118

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Background: The impact of the body composition on the pathophysiology and clinical course of Crohn's disease (CD) has not been fully elucidated. Aims: To reveal the correlations among body composition and long-term outcomes in CD after anti-TNF therapy. Methods: Ninety-one patients who received anti-TNF therapy as their first biologic treatment were enrolled. The skeletal muscle index (SMI), visceral and subcutaneous fat area (VFA, SFA), and the ratio of the VFA to SFA (mesenteric fat index; MFI) at the 3rd lumbar level were measured using computed tomography (CT) imaging before the induction. The correlation among the body composition and outcomes were retrospectively analyzed. Results: The 5-year cumulative secondary failure- and resection-free rates in patients with a low SMI (39.1% and 64.8%) were significantly lower than those with a high SMI (67.5% and 92.7%; p = 0.0071 and 0.0022, respectively). The 5-year cumulative secondary failure-free rate in the patients with low VF (45.0%) was significantly lower than that in those with high VF (77.6%; p = 0.016), and the 5-year cumulative resection-free rate in patients with a high MFI (68.9%) was significantly lower than that in those with a low MFI (83.0%; p = 0.031). Additionally, patients with low age and BMI had significantly lower cumulative secondary failure- and resection-free rates than those with high age and BMI (low age: 37.4% and 71.2%; high age: 70.7% and 88.9%; p = 0.0083 and 0.027, respectively) (low BMI: 27.2% and 64.8%; high BMI: 68.3% and 87.9%; p = 0.014 and 0.030, respectively), respectively. In the multivariate analyses, a low SMI was the only independent risk factor for secondary failure (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.04-4.44), while low age (HR 4.06, 95% CI 1.07-15.4), a low SMI (HR 4.19, 95% CI 1.01-17.3) and high MFI were risk factors for bowel resection (HR 4.31, 95% CI 1.36-13.7). Conclusion: The skeletal muscle mass and ratio of visceral to subcutaneous fat were suggested to reflect the long-term clinical outcome and may be helpful as prognostic markers after anti-TNF therapy in CD.

DOI： 10.3389/fnut.2022.765209

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Language：Japanese   Publisher：(株)先端医学社  

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BACKGROUND: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. AIMS: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. METHODS: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. RESULTS: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. CONCLUSION: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed.

DOI： 10.1007/s00535-021-01829-5

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MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA-protein systems in cancer progression and its future applications in cancer treatment.

DOI： 10.3390/ijms222212303

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DOI： 10.1093/jjco/hyab125

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Language：Japanese   Publisher：(株)医学書院  

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

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

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BACKGROUND: Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor inhibitors (TNF-I) are effective for the treatment. Recently, biosimilars of TNF-I, such as CT-P13, have been developed and are thought to possess equal efficacy and safety to the original TNF-I. Sarcoidosis is also a systemic granulomatous disease of unknown etiology. In steroid-resistant cases of sarcoidosis, TNF-I have been reported effective for achieving resolution. However, the progression of sarcoidosis due to the TNF-I also has been reported. We herein report a case of pulmonary sarcoidosis with a Crohn's disease (CD) patient developed after a long period administration (15 years) of TNF-I. CASE PRESENTATIONS: A 37-year-old woman with CD who had been diagnosed at 22 years old had been treated with the TNF-I (original infliximab; O-IFX and infliximab biosimilar; IFX-BS). Fifteen years after starting the TNF-I, she developed a fever and right chest pain. Chest computed tomography (CT) revealed clustered small nodules in both lungs and multiple enlarged hilar lymph nodes. Infectious diseases including tuberculosis were negative. Bronchoscopic examination was performed and the biopsy specimens were obtained. A pathological examination demonstrated noncaseating granulomatous lesions and no malignant findings. TNF-I were discontinued because of the possibility of TNF-I-related sarcoidosis. After having discontinued for four months, her symptoms and the lesions had disappeared completely. Fortunately, despite the discontinuation of TNF-I, she has maintained remission. CONCLUSIONS: To our knowledge, this is the first case in which sarcoidosis developed after switching from O-IFX to IFX-BS. To clarify the characteristics of the cases with development of sarcoidosis during administration of TNF-I, we searched PubMed and identified 106 cases. When developing an unexplained fever, asthenia, uveitis and skin lesions in patients with TNF-I treatment, sarcoidosis should be suspected. Once the diagnosis of sarcoidosis due to TNF-I was made, the discontinuation of TNF-I and administration of steroid therapy should be executed promptly. When re-starting TNF-I, another TNF-I should be used for disease control. Clinicians should be aware of the possibility of sarcoidosis in patients under anti-TNF therapy.

DOI： 10.1186/s12876-021-01948-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc  

DOI： 10.1002/jgh3.12657

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

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

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for &amp;gt;3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed <italic>TP53</italic> Q192X mutation, whereas <italic>SMAD4</italic> S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in <italic>TP53</italic>. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the <italic>TP53</italic> gene might have occurred during the differentiation of the founder clone into NEC, while a <italic>SMAD4</italic> mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.

DOI： 10.3389/fgene.2021.608324

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本潰瘍学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients. METHODS: In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration. RESULT: Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively. CONCLUSION: We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA.

DOI： 10.1186/s12876-021-01889-0

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DOI： 10.3390/cancers13133165

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DOI： 10.1002/cjp2.209

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Language：Japanese   Publisher：(株)メディカルアイ  

肝癌の悪性度診断における造影3D超音波のMPR画像の有用性について検討した。造影3Dを施行した5cm以下の切除肝細胞癌19症例23結節を対象とした。MPR画像にて不整欠損像を認めたものを非単純結節型(20/23)、それ以外を単純結節型(3/23)と判定し、切除標本との対比を行った。その結果、造影3Dの後血管像における肝癌肉眼型の正診率は100%(23/23)であった。輪郭不明瞭型の83%(10/12)は中分化型肝癌、残りの17%(3/12)は高分化型であり、低分化型肝癌は1例も認めなかった。それに対し、輪郭明瞭型では中分化型肝癌9%(1/11)、低分化型肝癌73%(8/11)、硬化型肝癌9%(1/11)、混合型肝癌9%(1/11)であり、高悪性度癌の占める割合が有意に高率であった。また、輪郭明瞭型は輪郭不明瞭型に比べ有意にKupffer phase ratioが低値を示した。さらに、対照群を中分化型肝癌と低分化型肝癌に分けて検討した。その結果、低分化型肝癌は中分化型肝癌に比べ有意にKupffer phase ratioが低値を示し、そのカットオフ値は0.34であった。

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DOI： 10.1097/MD.0000000000026296

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

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

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

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DOI： 10.1248/bpb.b20-00916

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DOI： 10.1155/2021/6640597

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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DOI： 10.1155/2021/5582943

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

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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

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Language：Japanese   Publisher：(公社)日本薬学会  

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DOI： 10.5230/jgc.2021.21.e11

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DOI： 10.1016/j.gie.2020.10.008

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

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J04447&link_issn=&doc_id=20210125350004&doc_link_id=10.11404%2Fjsgcs.59.42&url=https%3A%2F%2Fdoi.org%2F10.11404%2Fjsgcs.59.42&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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

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DOI： 10.12998/wjcc.v9.i2.416

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DOI： 10.1007/s10620-020-06747-9

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Non-coding RNAs (ncRNAs), or RNA molecules that do not code for proteins, are generally categorized as either small or long ncRNA (lncRNA) and are involved in the pathogenesis of several diseases including many cancers. Identification of a large number of ncRNAs could help to elucidate previously unknown mechanisms in phenotype regulation. Some ncRNAs are encapsulated by extracellular vesicles (EVs) and transferred to recipient cells to regulate cellular processes, including epigenetic and post-transcriptional regulations. Recent studies have uncovered novel molecular mechanisms and functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC), one of the most intractable cancers that is highly invasive and metastatic. As the epithelial-mesenchymal transition (EMT) triggers tumor cell invasion and migration, clarification of the roles of lncRNA in EMT and tumor cell stemness would be critical for improving diagnostic and therapeutic approaches in metastatic cancers. This review provides an overview of relevant studies on lncRNA and its involvement with EMT in PDAC. Emerging knowledge offers evidence for the dysregulated expression of lncRNAs and essential insights into the potential contribution of both lncRNAs and EVs in the pathogenesis of PDAC. Future directions and new clinical applications for PDAC are also discussed.

DOI： 10.3389/fmolb.2021.717890

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：W.B. Saunders  

DOI： 10.1016/j.cgh.2020.08.039

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc  

DOI： 10.1111/den.14150

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.pan.2021.03.002

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DOI： 10.2169/internalmedicine.5208-20

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