記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A young patient diagnosed with advanced colon cancer and liver metastasis was found to have familial adenomatous polyposis (FAP) through comprehensive genomic analysis. Whole-genome array comparative genomic hybridization (aCGH) revealed germline deletions at chromosome 5q22.1-22.2 encompassing the entire APC gene. The patient and her son exhibited mild intellectual disability without developmental delay. This case highlights the need for further exploration of the characteristics associated with whole APC deletions. aCGH is a valuable tool for studying FAP and provides a detailed analysis of large deletions.

DOI： 10.1038/s41439-024-00270-3

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

DOI： 10.3164/jcbn.23-82

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Lateral femoral cutaneous nerve (LFCN) injury is a potential complication after the direct anterior approach for total hip arthroplasty (DAA-THA). The aim of this study was to determine how the location of the fasciotomy in DAA-THA affects LFCN injury. METHODS: In this trial, 134 patients were randomized into a lateral fasciotomy (n = 67) or a conventional fasciotomy (n = 67) group. This study was a dual-centre, double-blind, prospective randomized controlled two-arm trial with parallel group design and a 1:1 allocation ratio. The primary endpoint was the presence of LFCN injury, which was determined by the presence of numbness, decreased sensation, tingling, jolt-like sensation, or pain over the lateral aspect of the thigh, excluding the surgical scar, using a patient-based questionnaire. The secondary endpoints were patient-reported outcome measures (PROMs) using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ), and the Forgotten Joint Score-12 (FJS-12). Assessments were obtained three months after surgery. RESULTS: The incidence of LFCN injury tended to be lower in the lateral fasciotomy group (p = 0.089). In the lateral fasciotomy group, there were no significant differences in the mean PROM scores between patients with and without LFCN injury (FJS-12: 54.42 (SD 15.77) vs 65.06 (SD 26.14); p = 0.074; JHEQ: 55.21 (SD 12.10) vs 59.72 (SD 16.50); p = 0.288; WOMAC: 82.45 (SD 6.84) vs 84.40 (SD 17.91); p = 0.728). In the conventional fasciotomy group, there were significant differences in FJS-12 and JHEQ between patients with and without LFCN injury (FJS-12: 43.21 (SD 23.08) vs 67.28 (SD 20.47); p < 0.001; JHEQ: 49.52 (SD 13.97) vs 59.59 (SD 15.18); p = 0.012); however, there was no significant difference in WOMAC (76.63 (SD 16.81) vs 84.16 (SD 15.94); p = 0.107). CONCLUSION: The incidence of LFCN injury at three months after THA was comparable between the lateral and conventional fasciotomy groups. Further studies are needed to assess the long-term effects of these approaches.

DOI： 10.1302/0301-620X.105B12.BJJ-2023-0375.R1

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on CGP tests discussed by the expert panel at Hokkaido University Hospital between August 2019 and May 2021. The median number of previous treatment lines was two; three or more lines accounted for 49%. Information on genotype-matched therapies was provided to 277 (63%). Genotype-matched clinical trials were ineligible because of an excess number of previous treatment lines or use of specific agents were found in 66 (15%) patients, with the highest proportion in breast and prostate cancers. Many patients met the exclusion criteria of one to two or more treatment lines across cancer types. In addition, previous use of specific agents was a frequent exclusion criterion for breast, prostate, colorectal, and ovarian cancers. The patients with tumor types with a low median number (two or fewer) of previous treatment lines, including most rare cancers, primary unknown cancers, and pancreatic cancers, had significantly fewer ineligible clinical trials. The earlier timing of CGP tests may improve access to genotype-matched clinical trials, with their proportion varying by cancer type. Each relevant society needs to advocate the desirable timing of CGP testing nationwide.

DOI： 10.1111/cas.15837

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Accumulating evidence suggest that ghrelin plays a role as an antiseptic peptide. The present study aimed to clarify whether the brain may be implicated ghrelin's antiseptic action. We examined the effect of brain ghrelin on survival in a novel endotoxemic model achieved by treating rats with lipopolysaccharide (LPS) and colchicine. The observation of survival stopped three days after chemicals' injection or at death. Intracisternal ghrelin dose-dependently reduced lethality in the endotoxemic model; meanwhile, neither intraperitoneal injection of ghrelin nor intracisternal des-acyl-ghrelin injection affected the mortality rate. The brain ghrelin-induced lethality reduction was significantly blocked by surgical vagotomy. Moreover, intracisternal injection of a ghrelin receptor antagonist blocked the improved survival achieved by intracisternal ghrelin injection or intravenous 2-deoxy-d-glucose administration. Intracisternal injection of an adenosine A2B receptor agonist reduced the lethality and the ghrelin-induced improvement of survival was blocked by adenosine A2B receptor antagonist. I addition, intracisternal ghrelin significantly blocked the colonic hyperpermeability produced by LPS and colchicine. These results suggest that ghrelin acts centrally to reduce endotoxemic lethality. Accordingly, activation of the vagal pathway and adenosine A2B receptors in the brain may be implicated in the ghrelin-induced increased survival. Since the efferent vagus nerve mediates anti-inflammatory mechanisms, we speculate that the vagal cholinergic anti-inflammatory pathway is implicated in the decreased septic lethality caused by brain ghrelin.

DOI： 10.1007/s13105-023-00962-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

炎症性腸疾患(IBD)患者の基幹病院と地域中核病院における医療連携の確立は,本邦において重要な課題となっている.本研究は,北海道内の多施設による後ろ向きコホート研究とアンケート調査から,その診療実態と医療連携構築の課題を明らかにすることを目的とした.その結果,IBD患者の基幹病院へ集中と診療格差が明らかとなり,地域中核病院での病院機能,メディカルスタッフのIBD診療理解度の低さが逆紹介の課題と考えられた.課題の解決には,重症度に応じた診療の棲み分け,教育活動やチーム医療の充実化が重要と考える.基幹病院と地域中核病院でIBD医療連携が進むことで,IBD診療の均てん化を実現できると考える.(著者抄録)

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その他リンク： 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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Leaky gut, an altered intestinal barrier function, has been described in many diseases such as irritable bowel syndrome (IBS). We have recently demonstrated that orexin in the brain blocked leaky gut in rats, suggesting that the brain plays a role in regulation of intestinal barrier function. In the present study, we tried to clarify whether GLP-1 acts centrally in the brain to regulate intestinal barrier function and its mechanism. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Intracisternal injection of GLP-1 analogue, liraglutide dose-dependently abolished increased colonic permeability in response to lipopolysaccharide. Either atropine or surgical vagotomy blocked the central GLP-1-induced improvement of colonic hyperpermeability. Intracisternal GLP-1 receptor antagonist, exendin (9-39) prevented the central GLP-1-induced blockade of colonic hyperpermeability. In addition, intracisternal injection of orexin receptor antagonist, SB-334867 blocked the GLP-1-induced improvement of intestinal barrier function. On the other hand, subcutaneous liraglutide also improved leaky gut but larger doses of liraglutide were needed to block it. In addition, neither atropine nor vagotomy blocked subcutaneous liraglutide-induced improvement of leaky gut, suggesting that central or peripheral GLP-1 system works separately to improve leaky gut in a vagal-dependent or independent manner, respectively. These results suggest that GLP-1 acts centrally in the brain to reduce colonic hyperpermeability. Brain orexin signaling and the vagal cholinergic pathway play a vital role in the process. We would therefore suggest that activation of central GLP-1 signaling may be useful for leaky gut-related diseases such as IBS.

DOI： 10.1016/j.brainres.2023.148371

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記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：英語  

BACKGROUND: Mucinous adenocarcinoma of the colorectum is a rare histological subtype characterized by an abundant mucinous component. Mucinous tumors are frequently diagnosed at an advanced stage, which indicates an aggressive subtype. However, few case reports have been published, and little information is available concerning genetic alterations in mucinous adenocarcinoma. CASE SUMMARY: A 76-year-old man underwent en bloc endoscopic submucosal dissection (ESD) for the management of a type 0-Is+IIa lesion. Histological examination revealed an intramucosal mucinous adenocarcinoma with signet-ring cell carcinoma and well-to-moderately differentiated tubular adenocarcinoma. Three years after the ESD, local recurrence was detected by an endoscopic examination, revealing a new 0-Is+IIa lesion with a phenotype similar to the previously resected lesion. Re-ESD was chosen for the management of the recurrent tumor, and the histological examination showed positive tumor infiltration at the vertical margin. Additional surgical resection was performed for the curative treatment. Genetic analysis showed pathogenic alterations in RNF43 and TP53 in the adenoma and an additional SMAD4 alteration in the carcinoma. CONCLUSION: This mucinous mucosal adenocarcinoma case was suggested to have an aggressive phenotype and a careful and close follow-up are required.

DOI： 10.4251/wjgo.v15.i1.186

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.gie.2022.02.009

PubMed

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記述言語：日本語   出版者・発行元：日本大腸検査学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.

DOI： 10.3389/fonc.2022.988527

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞潰瘍性大腸炎やCrohn病は炎症性腸疾患と総称され,潰瘍形成と組織再生を慢性的に繰り返すことによって,多彩な内視鏡所見を呈し,診断に苦慮する症例も少なくない.本稿では,敷石像・炎症性ポリポーシス・多発隆起などの特徴的な所見に焦点を当て,炎症性腸疾患の鑑別診断について解説する.敷石像,炎症性ポリポーシス,多発隆起はいずれも背景粘膜の炎症や潰瘍,浮腫により形成される非腫瘍性の変化であり,隆起部分のみにとらわれることなく,背景粘膜の炎症や併存する縦走潰瘍の存在などの腸管全体像を正確に把握することが鑑別診断のポイントとなる.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endoscopic finding of immune checkpoint inhibitor-related gastritis is characterized as shallow network-like erosion, which is termed spiderwebs-like appearance.

DOI： 10.1002/jgh3.12657

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Gastric cancer is a heterogenous disease with different phenotypes, genotypes, and clinical outcomes, including sensitivity to treatments and prognoses. Recent medical advances have enabled the classification of this heterogenous disease into several groups and the consequent analysis of their clinicopathological characteristics. Gastric cancer associated with Epstein-Barr virus (EBV) and microsatellite-unstable tumors are considered to be the two major subtypes as they are clearly defined by well-established methodologies, such as in situ hybridization and polymerase chain reaction-based analyses, respectively. However, discrepancies in the histological diagnosis of gastric neoplasms remain problematic, and international harmonization should be performed to improve our understanding of gastric carcinogenesis. We re-evaluated Japanese cases of early gastric cancer according to the current World Health Organization (WHO) criteria and classified them into genomic subtypes based on microsatellite instability (MSI) and EBV positivity to determine the initial genetic events in gastric carcinogenesis. A total of 113 Japanese early gastric cancers (including low- and high-grade dysplasias) treated with endoscopic resection over 5 years were archived in our hospital. A histological re-evaluation according to the WHO criteria revealed 54 adenocarcinomas, which were divided into 6 EBV-positive (11.1%), 7 MSI-high (MSI-H, 13.0%), and 41 microsatellite stable cases (75.9%). MSI-H adenocarcinoma was confirmed by an immunohistochemistry assay of mismatch repair proteins. Programmed death-ligand 1 immunostaining with two antibodies (E1L3N and SP263) was positive in tumor cells of one MSI-H adenocarcinoma case (1/7, 14.3%). The proportion of stained cells was higher with clone SP263 than with E1L3N. Histologically, EBV-positive carcinomas were poorly differentiated (83.8%), and MSI-H cancers were frequent in well to moderately differentiated adenocarcinoma (85.7%), indicating that the EBV-positive subtype presented with high-grade morphology even when an early lesion. Our study indicates that the WHO criteria are useful for subdividing Japanese early gastric cancers, and this subdivision may be useful for comparative analysis of precursor lesions and early carcinoma.

DOI： 10.1002/cjp2.209

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Leaky gut that is a condition reflecting intestinal barrier dysfunction has been attracting attention for its relations with many diseases such as irritable bowel syndrome or Alzheimer dementia. We have recently demonstrated that ghrelin acts in the brain to improve leaky gut via the vagus nerve. In the present study, we tried to clarify the precise central mechanisms by which ghrelin improves intestinal barrier function through the vagus nerve. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), blocked the intracisternal ghrelin-induced improvement of intestinal hyperpermeability while dopamine, cannabinoid or opioid receptor antagonist failed to prevent it. Since DPCPX can block adenosine A1 and adenosine A2B receptors, we examined which subtype is involved in the mechanism. Intracisternal injection of adenosine A2B agonist but not adenosine A1 agonist improved colonic hyperpermeability, while peripheral injection of adenosine A2B agonist failed to improve it. Intracisternal adenosine A2B agonist-induced improvement of colonic hyperpermeability was blocked by vagotomy. Adenosine A2B specific antagonist, alloxazine blocked the ghrelin- or central vagal stimulation by 2-deoxy-d-glucose-induced improvement of intestinal hyperpermeability. These results suggest that activation of adenosine A2B receptors in the central nervous system is capable of improving intestinal barrier function through the vagal pathway, and the adenosine A2B receptors may mediate the ghrelin-induced improvement of leaky gut in a vagal dependent fashion. These findings may help us understand the pathophysiology in not only gastrointestinal diseases but also non-gastrointestinal diseases associated with the altered intestinal permeability.

DOI： 10.1016/j.expneurol.2021.113708

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掲載種別：研究論文（学術雑誌）  

TRIAL DESIGN: Elimination of small colorectal polyps with cold snare polypectomy (CSP) is reported to be as safe as hot snare polypectomy (HSP). The effectiveness of CSP has not been clearly defined, and the incidence of long-term recurrence has not been determined. We conducted a randomized control study and one-year follow-up study to assess their safety and efficacy. METHODS: Patients with small colorectal polyps were randomized to receive CSP or HSP. Polypectomy was performed to determine the pathological curability, and patients completed a questionnaire about the tolerability of the procedure. Follow-up colonoscopy was performed to determine the local recurrence of adenoma. The major outcome was the non-inferiority of CSP to HSP in the rate of delayed bleeding and minor outcomes, including the incidence of immediate bleeding and perforation, procedural time, and the resection rate. RESULTS: A total of 119 participants were recruited in this randomized study and underwent polypectomy. Among the 458 polyps, 332 eligible polyps were analyzed. The rate of adverse events was 0.6% (1/175) for CSP and 0% (0/157) for HSP, which showed the non-inferiority of CSP. While the complete resection rate of CSP was very high (100%), the R0 rate was not satisfactory (horizontal margin, 65.5%; vertical margin, 89.1%). Two local recurrences (2.5%) were observed in the follow-up of 80 adenomas treated with CSP. No recurrence was found in 79 lesions in the HSP group, which was not significant (P = .06). CONCLUSIONS: Colorectal polyps were safely resected using CSP, similar to HSP. Most would agree to say that CSP is considered safer than HSP. The main question is then related to efficacy. Our results of the present study demonstrate that recurrence after CSP should be carefully managed for curative treatment.

DOI： 10.1097/MD.0000000000026296

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tildrakizumab is a high-affinity, humanized immunoglobulin G1κ, anti-interleukin-23p19 monoclonal antibody recently approved in Japan for treatment of plaque psoriasis. We report results from Japanese patients treated with tildrakizumab in the multinational, randomized, double-blind, placebo-controlled reSURFACE 1 study (clinicaltrials.gov NCT01722331). Adults with moderate to severe plaque psoriasis were randomized (2:2:1) to receive subcutaneous tildrakizumab 100 or 200 mg or placebo every 12 weeks. Placebo recipients were rerandomized to tildrakizumab 100 or 200 mg at week 12. The global study coprimary endpoints were the proportions of patients achieving 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) and Physician Global Assessment (PGA) response (0/1 with ≥2 grade reduction from baseline) at week 12. Analyses included 158 Japanese patients randomized to tildrakizumab 100 (n = 64) or 200 mg (n = 62) or placebo (n = 32). Japanese patients had higher mean baseline body surface area involvement and PASI versus all reSURFACE 1 patients. At week 12, significantly more Japanese patients receiving tildrakizumab 100 and 200 mg versus placebo achieved PASI 75 (54.7% and 54.8% vs 6.3%, respectively, both nominal p < 0.001) and PGA 0/1 response (54.7% and 56.5% vs 9.4%, respectively, both nominal P < 0.001). Response rates increased over time with maximal efficacy after 22-28 weeks; >80% of patients achieving PASI 75 or PASI 90 at week 28 and continuing tildrakizumab treatment at the same dose maintained response at week 64. From baseline to week 28, absolute PASI decreased from >12 in all patients to ≤2 in >40% and ≤3 in >50% of patients receiving tildrakizumab. Tildrakizumab was generally well tolerated with an adverse event profile similar to that of placebo. Tildrakizumab treatment was associated with durable efficacy in Japanese patients with moderate to severe plaque psoriasis despite greater baseline disease severity versus the global reSURFACE 1 population.

DOI： 10.1111/1346-8138.15789

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019. METHODS: We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020. RESULTS: All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling. CONCLUSIONS: The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved.

DOI： 10.1093/jjco/hyaa277

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

An attempt to use combination therapy with anti-tumor necrosis factor alpha (TNF alpha) antibodies and tacrolimus (TAC) has been tried to induce remission in ulcerative colitis (UC). However, the optimal dose of TAC in combination therapy with anti-TNF alpha antibodies (TAC + anti-TNF alpha therapy) remains unclear. We examined the efficacy of various doses of TAC + anti-TNF alpha therapy in a mouse colitis model. Dextran sulfate sodium induced colitis model mice were divided into an anti-TNF alpha antibody monotherapy group and the groups that received various doses of TAC + anti-TNF alpha therapy. The nuclear factor expression of activated T-cells, cytoplasmic 1 (NFATc1) in the nuclei and the mRNA expression of inflammatory cytokines were assessed by immunohistochemistry and RT-PCR, respectively. The serum anti-TNF alpha antibody concentration was measured with an enzyme-linked immunosorbent assay. The colon length and histological severity were significantly improved in the groups that received any dose of TAC + anti-TNF alpha therapy. The nuclear expression of NFATc1 was inversely proportional to the administered doses of TAC. The expression levels of inflammatory cytokines tended to decrease in proportion to the dose of TAC. The serum concentration of anti-TNF alpha antibodies in the high-dose TAC + anti-TNF alpha therapy was significantly higher than those in the other groups. Low-dose TAC exerted its immunosuppressive effect on T-cells, and additionally, high-dose TAC maintained the serum anti-TNF alpha antibody concentration. When administered in combination with anti-TNF alpha antibodies, the dose of TAC should be adjusted according to the disease severity.

DOI： 10.1248/bpb.b20-00916

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KOREAN GASTRIC CANCER ASSOC  

Gastric adenocarcinoma of the fundic gland mucosa type (GA-FGM) was proposed as a new variant of gastric adenocarcinoma of the fundic gland type (GA-FG). However, at present, the influence of Helicobacter pylori and the speed of progression and degree of malignancy in GA-FGM remain unclear. Herein, we report the first case of intramucosal GA-FGM that was endoscopically observed before and after H. pylori eradication over 15 years. The lesion showed the same tumor size with no submucosal invasion and a low MIB-1 labeling index 15 years after its detection using endoscopy. The endoscopic morphology changed from 0-IIa before H. pylori eradication to 0-IIa+IIc and then 0-I after H. pylori eradication. These findings suggest that the unaltered tumor size reflects low-grade malignancy and slow growth, and that the endoscopic morphology is influenced by H. pylori eradication.

DOI： 10.5230/jgc.2021.21.e11

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMC  

BackgroundColorectal cancers develop through several pathways, including the adenoma-carcinoma sequence and colitis-associated carcinogenesis. An altered intestinal microflora has been reported to be associated with the development and progression of colorectal cancer via these pathways. We identified Lactobacillus casei-derived ferrichrome as a mediator of the bacterial anti-tumor effect of colorectal cancer cells through the upregulation of DDIT3. In this study, we investigated the anti-tumor effects of ferrichrome on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer.MethodsSRB and MTT assays were performed to assess growth inhibition in vitro. Eighteen organoids were prepared from biopsy specimens obtained by colonoscopy. An AOM-DSS carcinogenesis model and xenograft model of colorectal cancer cells were generated for the assessment of the tumor suppressive effect of ferrichrome in vivo.ResultsFerrichrome inhibited the cell growth of colorectal cancer cells in vitro and in in vivo xenograft models. Ferrichrome exerted a strong tumor-suppressive effect that was superior to that of currently available anti-tumor agents, including 5-FU and cisplatin, both in vitro and in vivo. The tumor-suppressive effect of the combination of ferrichrome and 5-FU was superior to that of single treatment with either drug. The tumor suppressive effects of ferrichrome were confirmed through the upregulation of DDIT3 in patient-derived organoids of adenoma and carcinoma. Ferrichrome inhibited the tumor progression in the AOM-DSS model while exhibiting no anti-inflammatory effect in the DSS-colitis model, suggesting that ferrichrome inhibited cancer cells, but not a precancerous condition, via the colitis-associated pathway.ConclusionsFerrichrome exerts a tumor suppressive effect on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. The anti-tumor effect of ferrichrome was mediated by the upregulation of DDIT3, and was superior to that of 5-FU or cisplatin. These results suggest that Lactobacillus brevis-derived ferrichrome may be a candidate anti-tumor drug for the treatment of colorectal neoplasms.

DOI： 10.1186/s12935-020-01723-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBLISHING GROUP INC  

BACKGROUND Fecal impaction is defined as a large mass of compacted feces in the colon and has the potential to induce a serious medical condition in elderly individuals. Fecal impaction is generally preventable, and early recognition of the typical radiological findings is important for making an early diagnosis. The factors that lead to fecal impaction are usually similar to those causing constipation. Few cases with fecal impaction associated with a diverticulum have been reported.CASE SUMMARY We present the case of a 62-year-old woman who suffered from abdominal pain and vomiting, had a medical history of repeated acute abdomen and was diagnosed with fecal impaction in the descending colon based on X-ray and computed tomography (CT) imaging. After examination by gastrografin-enhanced colonography following colonoscopy and CT colonography, the fecalith was suspected to have been produced at the site of a large diverticulum in the transverse colon. The fecalith was surgically resected, and a histological diagnosis of pseudodiverticulum was made. There was no recurrence during 33 mo of follow-up.CONCLUSION This case highlights the importance of accurate identification and treatment of a fecal impaction. This case indicated that the endoscopic evacuation and subsequent colonography were effective for identifying a diverticulum that might have caused fecal impaction. A fecal impaction was associated with the diverticulum. Consequently, the planned diverticulectomy was performed. Appropriate emergency medical treatment and maintenance treatments should be selected in such cases to prevent recurrence.

DOI： 10.12998/wjcc.v9.i2.416

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

A 60-year-old man had received octreotide for a metastatic neuroendocrine tumor (NET) in the rectum. Computed tomography and ultrasonography revealed a cardiac tumor, diffuse thickness of the ventricular wall and pericardial effusion, which was diagnosed as cardiac metastasis. The metastatic lesions continued to grow despite the alteration of chemotherapy, and the patient complained of repeated syncope and was admitted to our hospital at 11 months after the diagnosis of cardiac metastasis. An electrocardiogram during syncope showed sustained ventricular tachycardia, which was considered to be caused by the cardiac metastasis. We herein report a case of NET with cardiac metastasis which caused lethal arrhythmia along with a review of the pertinent literature.

DOI： 10.2169/internalmedicine.5208-20

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掲載種別：研究論文（学術雑誌）  

BACKGROUND Fecal impaction is defined as a large mass of compacted feces in the colon and has the potential to induce a serious medical condition in elderly individuals. Fecal impaction is generally preventable, and early recognition of the typical radiological findings is important for making an early diagnosis. The factors that lead to fecal impaction are usually similar to those causing constipation. Few cases with fecal impaction associated with a diverticulum have been reported. CASE SUMMARY We present the case of a 62-year-old woman who suffered from abdominal pain and vomiting, had a medical history of repeated acute abdomen and was diagnosed with fecal impaction in the descending colon based on X-ray and computed tomography (CT) imaging. After examination by gastrografin-enhanced colonography following colonoscopy and CT colonography, the fecalith was suspected to have been produced at the site of a large diverticulum in the transverse colon. The fecalith was surgically resected, and a histological diagnosis of pseudodiverticulum was made. There was no recurrence during 33 mo of follow-up. CONCLUSION This case highlights the importance of accurate identification and treatment of a fecal impaction. This case indicated that the endoscopic evacuation and subsequent colonography were effective for identifying a diverticulum that might have caused fecal impaction. A fecal impaction was associated with the diverticulum. Consequently, the planned diverticulectomy was performed. Appropriate emergency medical treatment and maintenance treatments should be selected in such cases to prevent recurrence.

DOI： 10.12998/wjcc.v9.i2.416

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Introduction: Familial adenomatous polyposis (FAP) is typically characterized by more than hundred adenomatous polyps in the colorectum, caused by germline APC mutation. A small proportion of the polyps progress to colorectal adenocarcinoma via adenoma-carcinoma sequence. Serrated lesions and polyps, characterized by a serrated architecture of the epithelium, are noted for two types of genetic pathways in colorectal carcinogenesis. BRAF and KRAS mutations are observed in the serrated pathway. Case Report: We report a young FAP patient with rectal serrated adenomas that were removed by colonoscopic procedures. The histological features with villiform projections and slit-like serration indicated traditional serrated adenoma. A genetic examination with next-generation sequencing showed a somatic BRAF mutation in the serrated adenoma and APC mutations in the tubular adenomas. His germline mutation was found at APC p.Q1928fs*. Conclusion: Serrated adenomas with dual genetic alterations in a FAP patient may be associated with colorectal carcinogenesis and should be considered a target lesion for treatment. The present study demonstrated the malignant potential of serrated adenoma in a FAP patient.

DOI： 10.1007/s00384-020-03657-0

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本小腸学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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掲載種別：研究論文（学術雑誌）  

© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. Background: Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and adenocarcinoma that is frequently accompanied by extracolonic neoplasm. The risk of gastric carcinoma is increasing in Western FAP patients as well as Asian patients. Methods: We report the case of an FAP patient with fundic gland polyposis who developed gastric adenocarcinoma and metachronous pyloric gland adenomas. These tumors were endoscopically resected, and immunohistochemistry with gastric mucin (i.e., MUC6, MUC5AC) showed that the tumors belonged to the gastric subtype. Somatic mutation profiles were determined by target amplicon sequencing using a next-generation sequencer. Results: Germline APC variant c.5782delC was found by direct sequencing and somatic KRAS mutations in these tumors were identified by next-generation sequencing. Different KRAS mutation alleles (KRAS p.Gly12Ala, p.Gly12Arg, and p.Gly12Asp) indicated these dysplastic lesions developed from a distinct origin in fundic gland polyposis. Sequential mutations of the APC and KRAS were judged—based on a database search—to be characteristic of the adenoma-carcinoma sequence in colorectal carcinogenesis. Conclusion: The colonic adenoma-carcinoma sequence among gastric adenocarcinoma and dysplastic lesions was indicated in FAP-associated gastric carcinogenesis.

DOI： 10.1002/mgg3.1348

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background Endoscopic submucosal dissection (ESD) is currently a common procedure although it requires a long procedural time. We conducted a prospective study to determine the efficacy and safety of lidocaine injection for shortening the procedural time and relieving bowel peristalsis during ESD.Methods A multicenter randomized controlled study was conducted in three hospitals. Ninety-one patients who underwent colorectal ESD were enrolled. Patients were randomly divided into two groups using the envelope method: the lidocaine group and saline group. The primary endpoint was the procedural time, and the secondary endpoints were the procedural time in each part of the colon and the grade of bowel peristalsis and the incidence and amounts of antispasmodic drugs use and adverse events.Results The patients' demographics were not markedly different between the two groups. The mean procedural time in the lidocaine group was not markedly different from that in the saline group. In contrast, at the proximal site, the procedural time in the lidocaine group (57 min) was significantly shorter in the saline group (80 min). The grade of bowel peristalsis in the lidocaine group (0.67) was significantly lower than in the saline group (1.17). Antispasmodic drug use was significantly rarer in the lidocaine group than in the saline group. The incidence of adverse events was not markedly different between the two groups.Conclusions Local lidocaine injection is a feasible option for preventing bowel peristalsis, particularly in the proximal colon, leading to a reduced procedural time for ESD and decreased antispasmodic drug use.University Hospital Medical Information Network Center (UMIN number: 000022843).

DOI： 10.1007/s00464-020-08017-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Rationale: Gastric mixed adenoneuroendocrine carcinoma (gMANEC) is a rare malignant tumor. Most gMANECs are diagnosed at an advanced stage and have a worse prognosis than gastric adenocarcinoma. In order to improve the prognosis, it is necessary to diagnose gMANEC at an early stage. However, the endoscopic features of early gMANECs are unclear. We, herein, report a case of early gMANEC that showed characteristic magnifying endoscopic findings. Patient concerns: A 78-year-old man was referred to our institution for endoscopic resection of a gastric lesion. He had a medical history of distal gastrectomy due to early gastric cancer with negative surgical margins 9 years previously. Diagnosis: Esophagogastroduodenoscopy showed a reddish depressed lesion on the suture line of the gastric remnant, which was classified as type 0-IIc according to the Paris classification. ME-NBI at the oral side of the lesion revealed the absence of the microsurface pattern (MSP) and scattered microvessels with dilation and caliber variation, while ME-NBI at the anal side showed an irregularly tubular MSP. An endoscopic forceps biopsy showed a well- to moderately differentiated adenocarcinoma. Interventions: We performed endoscopic submucosal dissection, anden blocresection of the tumor was successfully achieved. Outcomes: The histological findings showed two distinct components: neuroendocrine carcinoma (NEC) and well-differentiated adenocarcinoma, which comprised similar to 60% and 40% of the tumor, respectively. The NEC component corresponded to the site with the absence of an MSP and scattered microvessels on ME-NBI, while the well-differentiated adenocarcinoma component corresponded to the site with an irregularly tubular MSP. The pathological diagnosis was mixed adenoneuroendocrine carcinoma, infiltrating into the deep submucosal layer. Lessons: We propose that the absence of an MSP plus an irregular MSP is characteristics of gMANEC, which was useful for the diagnosis of gMANEC before treatment.

DOI： 10.1097/MD.0000000000022306

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI  

The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP H1 downregulation. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed the anti-apoptotic effect of hnRNP H1 in colorectal cancer cells. An RNA immunoprecipitation assay revealed that hnRNP H1 bound to sphingosine-1-phosphate lyase 1 (SGPL1). Reverse transcription-polymerase chain reaction revealed the high expression of hnRNP H1 mRNA in colorectal cancer cells and Spearman's rank correlation coefficient showed a strong positive correlation between hnRNP H1 mRNA and SGPL1 mRNA. An siRNA of hnRNP H1 decreased SGPL1 mRNA expression in colorectal cancer cells, but not in non-tumorous cells. These findings suggested that hnRNP H1 increased SGPL1 mRNA expression specifically in cancer cells through direct binding. Targeted knockdown of hnRNP H1 or SGPL1 with siRNAs upregulated p53 phosphorylation and p53-associated molecules, resulting in cell growth inhibition, while hnRNP H1 upregulated the mRNA of SGPL1 and inhibited p53 activation, thereby promoting tumor cell growth. This is a novel mechanism underlying colorectal cancer cell progression mediated by hnRNP H1-SGPL1 mRNA stabilization.

DOI： 10.3390/ijms21124514

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Introduction: Surgical management is not a standard treatment option for metastatic recurrence of pancreatic adenocarcinoma. However, the surgical management of a solitary metastasis is useful in selected cases. Patient concerns: A 42-year-old woman was referred to our hospital on account of epigastric pain associated with a mass in the pancreatic body. The patient had a family history of branch duct-type intraductal papillary mucinous neoplasm of the pancreas. Diagnosis: The patient was diagnosed with pancreatic ductal adenocarcinoma (PDA) complicated with pancreatitis due to pancreatic duct involvement. Interventions: The patient underwent distal pancreatectomy, and pathological examination revealed a tubular adenocarcinoma. Solitary liver and lung metastatic tumors were found 6 and 43 months after the initial presentation, respectively, and sequential metastasectomies were performed. Outcomes: The patient survived until 8 years after her initial presentation. The genetic profiles of the resected specimens, primary PDA, and recurrent tumors in the liver and lung possessed identical KRAS mutations at codon 12, whereas there were no mutations in the main tumor suppressor genes, such as TP53, CDKN2A, and SMAD4. Multiplex polymerase chain reaction-based microsatellite instability assay demonstrated microsatellite stability. Conclusion: In our case, the patient with pancreatic adenocarcinoma survived for over 8 years following the resection of the primary tumor and resections of metachronous metastatic tumors. The outcome of PDA may be associated with the genetic profile that regulates its biological behavior. Operative management of solitary metastatic tumors may be a therapeutic options for selected patients with pancreatic cancer.

DOI： 10.1097/MD.0000000000020564

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

炎症性腸疾患(IBD)にはCrohn病(CD)と潰瘍性大腸炎(UC)が存在し、いずれの疾患も下部消化管が病変の主座の慢性炎症性疾患である。しかし上部消化管にも特徴的所見を伴うことがあり、診断確定に寄与する症例が少なくない。そのためIBD上部消化管病変の特徴を把握し診療にあたる必要がある。CDでは、胃体部～穹窿部の竹の節状外観や縦走配列の幽門部びらん、十二指腸病変としてはnotch様外観や数珠状隆起などの所見が高い特異性を示し、確定診断の一助となる。またUCの上部消化管病変は、大腸病変に類似したびまん性の脆弱な細顆粒状の粘膜であり、出血を伴う場合はUCに準じた治療が必要となる。以上から、IBD診断においては下部に加え、上部消化管内視鏡検査を行うべきである。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J02312&link_issn=&doc_id=20200225170019&doc_link_id=%2Faq9syokd%2F2020%2F003202%2F020%2F0290-0296%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9syokd%2F2020%2F003202%2F020%2F0290-0296%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：FRONTIERS MEDIA SA  

Background: Immuno-oncology is a novel target of cancer therapy. Nivolumab is a monoclonal anti-programed death-1 antibody recently used to treat patients with chemotherapy-resistant gastric and gastroesophageal cancer. Although the disease control rate is reported to be very high, few cases demonstrate a complete response. Case Presentation: A 25-year-old man diagnosed with gastroesophageal cancer was treated with chemotherapy followed by surgical resection. Pathological diagnosis was poorly differentiated adenocarcinoma with distant lymph node metastasis. Residual lymph node metastasis was treated with nivolumab monotherapy, resulting in complete disappearance. No recurrence has been observed for 2 years since discontinuation of nivolumab. This rare case was additionally subjected to pathological and genetic analysis, suggesting that a high tumor mutation burden (10.7 mutations/Mb) might be associated with sensitivity to nivolumab. Summary: We reported a case of advanced gastroesophageal junction cancer with distal lymph node metastasis that was successfully treated with chemotherapy, surgical resection, and nivolumab therapy. An aggressive search for biomarkers implying benefit effects of nivolumab should be performed.

DOI： 10.3389/fonc.2019.01375

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background: Venous thromboembolism (VTE) has been shown to be more frequent in inflammatory bowel disease (IBD) than in the general population in Western studies. However, the actual state of VTE in Asian IBD remains poorly understood. Aims: To reveal the incidence of VTE in IBD patients in Japan. Methods: Eighty-five patients admitted to 3 gastroenterology centers were registered from 2013 to 2018. The incidence of VTE in patients with IBD (n = 42) was prospectively compared to that among patients with other digestive diseases (n = 43). The presence of VTE was surveyed using contrast-enhanced computed tomography and/or ultrasonography at admission and at 1-2 weeks after admission. The patient characteristics and laboratory data of IBD patients with or without VTE were compared to determine the risk factors for VTE. Results: The incidence of VTE with IBD was 16.7%, which was significantly more frequent than with other digestive diseases (2.3%; p = 0.0296). In IBD patients, VTE was detected in 6 of 22 patients with ulcerative colitis (27.2%) but in only 1 of 20 patients with Crohn's disease (5.0%). VTE was diagnosed at admission in 4 IBD patients and 2 weeks after admission in 3 IBD patients. The risk factors of VTE in IBD were the presence of an indwelling central venous catheter, a low level of total protein, a low activated partial thromboplastin time, and a high level of fibrinogen degradation products. Conclusion: VTE was frequently detected in Japanese IBD patients both at and after admission. Adequate screening and prophylaxis for VTE is deemed necessary in IBD. (C) 2018 S. Karger AG, Basel

DOI： 10.1159/000495289

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本小腸学会  

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掲載種別：研究論文（学術雑誌）  

BACKGROUND Epstein-Barr virus (EBV)-associated carcinoma is a gastric cancer subtype with a morphology characterized by gastric carcinoma with lymphoid stroma (GCLS). Clinicopathological studies have indicated a better prognosis for GCLS than for common gastric carcinomas. Some previous cases of early gastric cancer associated with EBV had been diagnosed by endoscopic resection. CASE SUMMARY We present two GCLS cases subjected to endoscopic submucosal dissection (ESD) for a definitive diagnosis. A protruded gastric lesion was identified by routine endoscopic examination, but forceps biopsy showed no atypical cells before ESD. The resected specimen showed a poorly differentiated adenocarcinoma with lymphoid cells involving the mucosa and submucosa. The final diagnosis was submucosa-invasive poorly differentiated gastric adenocarcinoma. Accordingly, additional gastrectomy was recommended to obtain a complete cure. One patient underwent additional distal gastrectomy with lymph node dissection, but the other was refused because of cardiovascular complications. Both patients remained in remission for more than half a year. EBV positivity was determined by EBV-encoded RNA in situ hybridization. We also conducted a literature review of cases of early gastric cancer associated with EBV that had been diagnosed by ESD. CONCLUSION Submucosa-invasive GCLS could be dissected using ESD, and EBV positivity should be subsequently assessed to determine whether or not any additional curative surgery is required. Further prospective investigations on the prevalence of lymph node metastasis in EBV-associated carcinoma should be performed to expand the indications for endoscopic resection.

DOI： 10.4251/wjgo.v11.i10.925

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

DOI： 10.1007/s12029-018-0078-3

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記述言語：英語  

Endoscopic ultrasound-guided sampling is indicated to achieve an accurate diagnosis of subepithelial lesions of the stomach when a standard biopsy fails. Gastric carcinoma with lymphoid stroma (GCLS) is located under the epithelial layer with dense lymphocytic infiltration, making a pathological diagnosis by a biopsy difficult. We herein report a case of the pathological diagnosis of GCLS using an endoscopic ultrasound-guided fine-needle biopsy. The patient underwent distal gastrectomy and was diagnosed with Epstein-Barr virus-negative cancer.

DOI： 10.1002/jcu.22696

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞消化管は悪性リンパ腫の好発部位であり,肉眼型は多彩である.悪性リンパ腫の確定診断には,生検または外科的切除標本における病理組織学的診断が必要である.消化管の中でも,小腸は診断が最も困難な部位であり,CTやPET-CTなどのモダリティーでは小腸悪性リンパ腫の検出は困難な場合が多く,カプセル内視鏡やダブルバルーン内視鏡を用いた小腸精査を積極的に行うべきである.また腸管悪性リンパ腫と良性リンパ濾胞過形成の鑑別には積極的にNBI拡大観察を併用し,血管網減少や不整血管出現などの特徴的所見を拾い上げることが,リンパ腫の小病変の診断に有用である.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI  

Background: Autofluorescence imaging (AFI) is useful for diagnosing colon neoplasms, but what affects the AFI intensity remains unclear. This study investigated the association between AFI and the histological characteristics, aberrant methylation status, and aberrant expression in colon neoplasms. Methods: Fifty-three patients with colorectal neoplasms who underwent AFI were enrolled. The AFI intensity (F index) was compared with the pathological findings and gene alterations. The F index was calculated using an image analysis software program. The pathological findings were assessed by the tumor crypt density, cell densities, and N/C ratio. The aberrant methylation of p16, E-cadherin, Apc, Runx3, and hMLH1 genes was determined by a methylation-specific polymerase chain reaction. The aberrant expression of p53 and Ki-67 was evaluated by immunohistochemical staining. Results: An increased N/C ratio, the aberrant expression of p53, Ki-67, and the altered methylation of p16 went together with a lower F index. The other pathological findings and the methylation status showed no association with the F index. Conclusions: AFI reflects the nuclear enlargement of tumor cells, the cell proliferation ability, and the altered status of cell proliferation-related genes, indicating that AFI is a useful and practical method for predicting the dysplastic grade of tumor cells and cell proliferation.

DOI： 10.3390/molecules24061106

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   出版者・発行元：OXFORD UNIV PRESS  

DOI： 10.1093/ecco-jcc/jjy222.738

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語  

Background and study aims  Symptomatic capsule retention is a very rare adverse event following patency capsule, and the vast majority of cases are resolved without either surgical or endoscopic intervention. We herein describe a rare case of small bowel perforation after swallowing a patency capsule in a 37-year-old man suspected of having Crohn's disease.

DOI： 10.1055/a-0752-9903

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本小腸学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMC  

Background: All Helicobacter pylori-infected patients are recommended for eradication with an appropriate regimen in each geographic area. The choice of the therapy is somewhat dependent on the antimicrobial susceptibility. The rate of clarithromycin resistance has been increasing and is associated with failure; thus, susceptibility testing is recommended before triple therapy with clarithromycin. However, antimicrobial susceptibility testing is not yet clinically available and an alternative newly developed acid inhibitor vonoprazan is used for triple therapy in Japan. The aim of this study was to determine whether vonoprazan-based triple therapy is plausible treatment in H. pylori eradication.Methods: A retrospective observational study of H. pylori eradication was conducted in a single institute. The patients who requested antimicrobial susceptibility testing were treated with susceptibility-guided proton pump inhibitor-based triple therapy in International University of Health and Welfare Hospital from 2013 to 2016. Other patients were treated with empirical treatment with a proton pump inhibitor. From 2015 to 2016, vonoprazan-based triple treatment (vonoprazan, 20 mg; amoxicillin, 750 mg; and clarithromycin, 200 or 400 mg, b.i.d.) was conducted, and its effectiveness was compared with susceptibility-guided proton pump inhibitor-based triple therapy. We also investigated the improvement in eradication rate when antimicrobial susceptibility testing was performed, and compared the outcomes of vonoprazan-based and proton pump inhibitor-based empirical therapy.Results: A total of 1355 patients who received first-line eradication treatment were enrolled in the present study. The eradication rates of the empirical proton pump inhibitor-based therapy and the vonoprazan-based therapy group in a per-protocol analysis were 86.3% (95% CI 83.8-88.8) and 97.4% (95% CI 95.7-99.1), respectively. In 212 patients who received antimicrobial susceptibility testing, the rate of clarithromycin resistant was 23.5% and the eradication rate in susceptibility-guided treatment was 95.7% (95% CI 92.9-98.4). The difference between susceptibility-guided and vonoprazan-based therapy was - 1.7% (95% CI - 4.9 to 1.5%), and the non-inferiority of vonoprazan-based triple therapy was confirmed.Conclusions: Vonoprazan-based triple therapy was effective as susceptibility-guided triple therapy for H. pylori eradication. An empirical triple therapy with vonoprazan is preferable even in area with high rates of clarithromycin-resistance.

DOI： 10.1186/s12941-018-0281-x

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記述言語：英語   出版者・発行元：SPRINGER  

Background Eradication therapies for Helicobacter pylori infection are advancing as new acid inhibitory reagents approved. The aim of this study was to assess the efficacy and safety of vonoprazan-based triple treatment.
Materials and Methods Triple therapy with vonoprazan and two antibiotics (amoxicillin and clarithromycin or metronidazole) received focus in this analysis. We performed a multicenter retrospective study of patients who received vonoprazan-based eradication therapy between February 2015 and February 2016 and conducted a review of the literature.
Results The eradication rate among the 799 patients in our multicenter study was 94.4% (95% confidence interval [CI] 92.6-96.2%) in the per-protocol analysis for first-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg, twice a day for 7 days) and 97.1% (95% CI 93.0-101.1%) for second-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and metronidazole 250 mg, twice a day for 7 days). The overall incidence of adverse events was 4.4% in an intention-to-treat analysis with no patients hospitalized. In a literature review, six reports, in which 1380 patients received vonoprazan-based first-line eradication therapy, were included and were all reported by Japanese researchers. The eradication success rates in per-protocol analysis were between 85 and 93%, which was roughly the same among the studies.
Conclusions Vonoprazan-based triple therapy was effective and safe for Helicobacter pylori eradication in real-world experience, confirmed by a multicenter study and a review of the pertinent literature.

DOI： 10.1007/s10620-017-4664-1

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掲載種別：研究論文（学術雑誌）  

Purpose Endoscopic retrograde ileography (ERIG) is developed in our institute and applied clinically for the diagnosis and assessment of the Crohn's disease activity. We have further improved the technique using 3-dimensional – computed tomography enteroclysis (3D-CTE) and conducted a retrospective study to determine the feasibility and the diagnostic value of endoscopic retrograde 3D-CTE (ER 3D-CTE) in Crohn's disease patients in a state of remission. Methods Thirteen Crohn's patients were included in this pilot study. CTE was performed after the infusion of air or CO2 through the balloon tube following conventional colonoscopy. The primary endpoint of this study was to assess the safety of this method. Secondarily, the specific findings of Crohn's disease and length of the visualized small intestine were assessed. Results The procedures were completed without any adverse events. Gas passed through the small intestine and enterographic images were obtained in 10 out of 13 cases, but, in the remaining patients, insertion of the balloon tubes into the terminal ileum failed. Various features specific to Crohn's disease were visualized using ER 3D-CTE. A cobble stone appearance or hammock-like malformation was specific and effective for diagnosing Crohn's disease and the features of anastomosis after the surgical operations were also well described. Therefore, this technique may be useful after surgery. Conclusion In this study, ER 3D-CTE was performed safely in Crohn's disease patients and may be used for the diagnosis and follow-up of this disease.

DOI： 10.1016/j.ejro.2017.04.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Purpose: Endoscopic retrograde ileography (ERIG) is developed in our institute and applied clinically for the diagnosis and assessment of the Crohn's disease activity. We have further improved the technique using 3-dimensional - computed tomography enteroclysis (3D-CTE) and conducted a retrospective study to determine the feasibility and the diagnostic value of endoscopic retrograde 3D-CTE (ER 3D-CTE) in Crohn's disease patients in a state of remission.Methods: Thirteen Crohn's patients were included in this pilot study. CTE was performed after the infusion of air or CO2 through the balloon tube following conventional colonoscopy. The primary endpoint of this study was to assess the safety of this method. Secondarily, the specific findings of Crohn's disease and length of the visualized small intestine were assessed.Results: The procedures were completed without any adverse events. Gas passed through the small intestine and enterographic images were obtained in 10 out of 13 cases, but, in the remaining patients, insertion of the balloon tubes into the terminal ileum failed. Various features specific to Crohn's disease were visualized using ER 3D-CTE. A cobble stone appearance or hammock-like malformation was specific and effective for diagnosing Crohn's disease and the features of anastomosis after the surgical operations were also well described. Therefore, this technique may be useful after surgery.Conclusion: In this study, ER 3D-CTE was performed safely in Crohn's disease patients and may be used for the diagnosis and follow-up of this disease.

DOI： 10.1016/j.ejro.2017.04.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Previous reports have suggested that some probiotics inhibit tumorigenesis and cancer progression. However, the molecules involved have not yet been identified. Here, we show that the culture supernatant of Lactobacillus casei ATCC334 has a strong tumour-suppressive effect on colon cancer cells. Using mass spectrometry, we identify ferrichrome as a tumour-suppressive molecule produced by L. casei ATCC334. The tumour-suppressive effect of ferrichrome is greater than that of cisplatin and 5-fluorouracil, and ferrichrome has less of an effect on non-cancerous intestinal cells than either of those agents. A transcriptome analysis reveals that ferrichrome treatment induces apoptosis, which is mediated by the activation of c-jun N-terminal kinase (JNK). Western blotting indicates that the induction of apoptosis by ferrichrome is reduced by the inhibition of the JNK signalling pathway. This we demonstrate that probiotic-derived ferrichrome exerts a tumour-suppressive effect via the JNK signalling pathway.

DOI： 10.1038/ncomms12365

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掲載種別：研究論文（学術雑誌）  

Upper gastrointestinal (GI) lesions are frequently reported in Crohn's disease, in which the entire GI tract is affected. In these cases, erosive fissures regularly transversing folds that are longitudinally aligned along the lesser curvature of the gastric body and cardia are described as having a "bamboo joint-like appearance". We designed a blinded experiment in which upper GI imaging without a final diagnosis was checked by three observers to determine the usefulness of the bamboo joint-like appearance in the diagnosis of Crohn's disease. For the three observers, sensitivities of appearance were 30.5%, 56.9%, and 51.4%, while specificities were 99.6%, 98.5%. and 99.3%. Thus, the bamboo joint-like appearance was not useful for the identification of Crohn's disease patients. Nevertheless, patients exhibiting the bamboo joint-like appearance in upper GI imaging should undergo further examination due to the high probability of Crohn's disease.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Although probiotics are known to have antitumor activity, few bacteria-derived antitumor molecules have been identified. The present study explored an antitumor molecule derived from Lactobacillus brevis SBL8803 (L. brevis 8803) and the mechanisms that underlie its effects. Cell viability and apoptosis were assessed by a sulforhodamine B assay and terminal deoxynucleotidyl transferase dUTP staining, respectively. Phosphorylated extracellular signal-regulated kinase (ERK) and cleaved poly ADP-ribose polymerase (PARP) expression were detected by western blotting. The conditioned medium of L. brevis 8803 inhibited SW620 cells viability and the effect was reduced by the degradation of polyphosphate (poly P) in the conditioned medium. A xenograft model showed that poly P inhibited the growth of SW620 cells. Poly P induced the apoptosis of SW620 cells through activation of the ERK pathway. In contrast, in primary cultured cells derived from normal mouse, poly P did not affect cell viability. Probiotic-derived poly P is expected to be an antitumor drug with fewer adverse effects than conventional drugs.

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DOI： 10.5114/pjp.2016.61449

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掲載種別：研究論文（学術雑誌）  

Background and aims: No endoscopic examination has been able to evaluate severity of ulcerative colitis (UC) by quantification. This prospective study investigated the efficacy of quantifying autofluorescence imaging (AFI) to assess the severity of UC, which captures the fluorescence emitted from intestinal tissue and then quantifies the intensity using an image-analytical software program. Materials and methods: Eleven endoscopists separately evaluated 135 images of conventional endoscopy (CE) and AFI from a same lesion. A CE image corresponding to Mayo endoscopic subscore 0 or 1 was defined as being inactive. The fluorescence intensities of AFI were quantified using an image-analytical software program (F index; FI). Active inflammation was defined when Matts’ histological grade was 2 or more. A cut-off value of the FI for active inflammation was determined using a receiver operating characteristic (ROC) analysis. The inter-observer consistency was calculated by unweighted kappa statistics. Results: The correlation coefficient for the FI was inversely related to the histological severity (r = −0.558, p < 0.0001). The ROC analysis showed that the optimal cut-off value for the FI for active inflammation was 0.906. The average diagnostic accuracy of the FI was significantly higher than those of the CE (84.7 vs 78.5 %, p < 0.01). The kappa values for the inter-observer consistency of CE and the FI were 0.60 and 0.95 in all participants, 0.53 and 0.97 in the less-experienced endoscopists group and 0.67 and 0.93 in the expert group, respectively. Conclusions: The quantified AFI is considered to be an accurate and objective indicator that can be used to assess the activity of ulcerative colitis, particularly for less-experienced endoscopists.

DOI： 10.1007/s00384-015-2332-5

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DOI： 10.1016/j.bbrc.2015.09.159

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DOI： 10.1016/j.bbrc.2015.10.055

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掲載種別：研究論文（学術雑誌）  

The clinical importance of Crohn's disease (CD)-specific lesions in the upper gastrointestinal tract (upper GIT) has not been sufficiently established. The aim of this case-control study is to investigate the characteristic findings of CD in the upper GIT. In 2740 patients who underwent gastroduodenoscopy at Asahikawa Medical University between April 2011 and December 2012, 81 CD patients, 81 gender- and age-matched non-IBD patients, and 66 ulcerative colitis (UC) patients were investigated in the present study. (1) The diagnostic ability and odds ratio of each endoscopic finding (a bamboo joint-like appearance in the cardia, erosions, and/or ulcers in the antrum, notched signs, and erosions and/or ulcers in the duodenum) were compared between the CD and non-IBD patients or UC patients. (2) The interobserver agreement of the diagnosis based on the endoscopic findings was evaluated by 3 experienced and 3 less-experienced endoscopists. The incidence of detecting a bamboo joint-like appearance, notched signs, and erosions and/or ulcers in the duodenum was significantly higher in the CD patients than in the non-IBD and UC patients. In addition, the diagnostic ability and odds ratio of a bamboo joint-like appearance for CD were higher than those for the other findings. Kendall's coefficients of concordance in the group of experienced and less-experienced endoscopists were relatively high for a bamboo joint-like appearance (0.748 and 0.692, respectively). A cardiac bamboo joint-like appearance is a useful finding for identifying high-risk groups of CD patients using only gastroduodenoscopy.

DOI： 10.1097/MD.0000000000001500

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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DOI： 10.1016/j.trsl.2015.02.002

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DOI： 10.1097/MIB.0000000000000401

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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DOI： 10.1155/2015/490272

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DOI： 10.1016/j.gie.2014.03.030

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掲載種別：研究論文（学術雑誌）  

It is well known that microRNAs (miRs) are abnormally expressed in various cancers and target the messenger RNAs (mRNAs) of cancer-associated genes. While (miRs) are abnormally expressed in various cancers, whether miRs directly target oncogenic proteins is unknown. The present study investigated the inhibitory effects of miR-18a on colon cancer progression, which was considered to be mediated through its direct binding and degradation of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). An MTT assay and xenograft model demonstrated that the transfection of miR-18a induced apoptosis in SW620 cells. A binding assay revealed direct binding between miR-18a and hnRNP A1 in the cytoplasm of SW620 cells, which inhibited the oncogenic functions of hnRNP A1. A competitor RNA, which included the complementary sequence of the region of the miR-18a-hnRNP A1 binding site, repressed the effects of miR-18a on the induction of cancer cell apoptosis. In vitro single and in vivo double isotope assays demonstrated that miR-18a induced the degradation of hnRNP A1. An immunocytochemical study of hnRNP A1 and LC3-II and the inhibition of autophagy by 3-methyladenine and ATG7, p62 and BAG3 siRNA showed that miR-18a and hnRNP A1 formed a complex that was degraded through the autophagolysosomal pathway. This is the first report showing a novel function of a miR in the autophagolysosomal degradation of an oncogenic protein resulting from the creation of a complex consisting of the miR and a RNA-binding protein, which suppressed cancer progression.

DOI： 10.1038/onc.2013.429

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Human peripheral blood mononuclear cells (PB-MNCs) have angiogenic properties, which make them promising cells for use in angiogenic therapy approaches in regenerative medicine. To explore an efficient method for expanding pro-angiogenic cells from PB-MNCs, we developed a novel serum-free culture system composed of X-VIVO15 medium supplemented with vascular endothelial growth factor, basic fibroblast growth factor, and thrombopoietin (TPO). Using this ex vivo culture, we obtained floating spheres composed mainly of CD11b(+) monocytes expressing c-Mpl (TPO receptor) and which exhibited acetylated low-density lipoprotein uptake and phagocytosis. Expression of IL-8, CXCR4, and vasohibin-2 mRNA was upregulated in these cells. In the presence of TPO, the number and size of the spheres were increased. In a nude mouse hind-limb ischemia model, the intramuscular injection of spheroid cells treated with TPO rescued blood perfusion more effectively than that without TPO. These results indicate that the ex vivo addition of TPO augments the pro-angiogenic activity of peripheral CD11b(+) monocytes, suggesting that this method shows promise for uses in human cell therapy aimed at the induction of vascular regeneration by activating the angiogenic properties of human peripheral blood-derived monocytes.

DOI： 10.1007/s12185-013-1423-8

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その他リンク： http://orcid.org/0000-0002-1068-7024

DOI： 10.1016/j.bbrc.2013.08.026

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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DOI： 10.1002/jgm.2717

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記述言語：日本語   出版者・発行元：(株)医学書院  

Crohn病(CD)と潰瘍性大腸炎(UC)は原因不明の慢性炎症性腸疾患(IBD)であり,CDでは口腔から肛門までの消化管のあらゆる部位に炎症性変化を認め,上部消化管病変の出現頻度も高い.一方,UCは大腸に限局して炎症が起こるとされており,上部消化管病変の出現頻度は低い.CDの上部消化管病変として,特徴的なものは,胃の竹の節状外観であり,その他に前庭部びらん,胃潰瘍,十二指腸のnotch様陥凹などがみられる.UCにおいては胃・十二指腸の多発びらんやアフタ,潰瘍,顆粒状変化など大腸にみられるUC病変に類似した所見を認める.各所見の観察には色素撒布が有用である.治療としてはプロトンポンプ阻害薬(PPI)などの通常の潰瘍治療薬は無効な場合が多く,原疾患の治療が効果的である.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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DOI： 10.1155/2013/879491

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記述言語：日本語   出版者・発行元：北海道外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Some patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma.
Methods: This study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital. A randomly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy (HRE). Then the colonoscopist changed the mode to AFI and handed to the scope to another colonoscopist who knew no information about the HRE. Then the second colonoscopist observed the sigmoid colon and rectum. Each colonoscopist separately recorded the findings. The detection rate, miss rate and procedural time were assessed in prospective manner.
Results: The detection rate of flat and depressed adenoma, but not elevated adenoma, by AFI is significantly higher than that by HRE. In less-experienced endoscopists, AFI dramatically increased the detection rate (30.3%) and reduced miss rate (0%) of colorectal adenoma in comparison to those of HRE (7.7%, 50.0%), but not for experienced endoscopists. The procedural time of HRE was significantly shorter than that of AFI.
Conclusions: AFI increased the detection rate and reduced the miss rate of flat and depressed adenomas. These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE.

DOI： 10.1186/1471-230X-12-75

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その他リンク： http://orcid.org/0000-0002-1068-7024

記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

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掲載種別：研究論文（学術雑誌）  

Metachronous gastric cancer (MGC) after endoscopic resection (ER) of gastric cancer still occurs to some degree even after Helicobacter pylori (H. pylori) treatment. We evaluated whether two biomarkers related to carcinogenesis expressed in intestinal metaplasia (IM) become predictors for MGC development after eradication. We performed a hospital-based, case-control study of 75 patients, including 50 mucosal cancer patients who had undergone ER (Group DYS), and 25 age- and sex-matched chronic gastritis patients for whom H. pylori had been successfully eradicated (control). Additionally, Group DYS patients were divided into two groups: 25 successfully H. pylori-eradicated (eradicated group) and 25 un-eradicated patients (persistent group). All patients were followed for 1 year. We analyzed microsatellite instability (MSI) and immunoperoxidase assays using a monoclonal antibody for the colonic phenotype (Das-1). Both MSI and Das-1 reactivity in IM were significantly higher in Group DYS than in the control (p < 0.05 and p < 0.01, respectively). MSI and Das-1 reactivity were strong and independent predictors for gastric cancer (OR = 7.09, 95% CI 1.27-39.6, p = 0.03 for MSI and OR = 4.96, 95% CI 1.64-15.0, p = 0.005 for Das-1 reactivity). The incidence of MSI tended to decrease in the eradicated group (p = 0.07), but not in the persistent group. The Das-1 immunoreactivity in IM also declined in both the eradicated group and the control. Interestingly, all MGCs after ER were positive for MSI or Das-1 reactivity. MSI or Das-1 reactivity in IM strongly predicts the development of MGC. Patients in whom these biomarkers persist after eradication may therefore have a high risk of developing MGC. © 2011 UICC.

DOI： 10.1002/ijc.26275

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Metachronous gastric cancer (MGC) after endoscopic resection (ER) of gastric cancer still occurs to some degree even after Helicobacter pylori (H. pylori) treatment. We evaluated whether two biomarkers related to carcinogenesis expressed in intestinal metaplasia (IM) become predictors for MGC development after eradication. We performed a hospital-based, casecontrol study of 75 patients, including 50 mucosal cancer patients who had undergone ER (Group DYS), and 25 age- and sex-matched chronic gastritis patients for whom H. pylori had been successfully eradicated (control). Additionally, Group DYS patients were divided into two groups: 25 successfully H. pylori-eradicated (eradicated group) and 25 un-eradicated patients (persistent group). All patients were followed for 1 year. We analyzed microsatellite instability (MSI) and immunoperoxidase assays using a monoclonal antibody for the colonic phenotype (Das-1). Both MSI and Das-1 reactivity in IM were significantly higher in Group DYS than in the control (p < 0.05 and p < 0.01, respectively). MSI and Das-1 reactivity were strong and independent predictors for gastric cancer (OR = 7.09, 95% CI 1.2739.6, p = 0.03 for MSI and OR = 4.96, 95% CI 1.6415.0, p = 0.005 for Das-1 reactivity). The incidence of MSI tended to decrease in the eradicated group (p = 0.07), but not in the persistent group. The Das-1 immunoreactivity in IM also declined in both the eradicated group and the control. Interestingly, all MGCs after ER were positive for MSI or Das-1 reactivity. MSI or Das-1 reactivity in IM strongly predicts the development of MGC. Patients in whom these biomarkers persist after eradication may therefore have a high risk of developing MGC.

DOI： 10.1002/ijc.26275

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DOI： 10.1620/tjem.227.39

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/s-0031-1291502

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Autofluorescence imaging (AFI) is a novel technology which can capture fluorescence emitted from intestinal tissues. While AFI is useful for detecting colorectal neoplasms, it is unclear whether AFI can facilitate the diagnosis by differentiating the extent of dysplasia of colorectal neoplasms. This study investigated the efficacy of AFI in discriminating high-grade from low-grade adenoma.
Sixty-seven patients who underwent colonoscopy with AFI were enrolled in this study. The AFI images obtained from 158 lesions in these patients were visually classified into four categories, namely, green (G), green with magenta spots (GM), magenta with green spots (MG), and magenta (M), according to their color intensities, immediately after the examination. The AFI images of the lesions were quantified using an image-analytical software program (F index). Either the F index or the visual assessment was prospectively compared with the dysplastic grade.
The F index of the high-grade adenomas was significantly lower than that of the low-grade adenomas, hyperplasia, and normal mucosa (p &lt; 0.05). The incidence of the lesions classified into the M classification for high-grade adenomas (55.6%) was significantly higher than that of either low-grade adenomas (20.8%) or hyperplasia (0%). No correlation was observed between the F index or the visual classification and the tumor shape. The F index was not influenced by the size of the lesion, while the size was significantly associated with the visual classification of AFI.
AFI, particularly the F index, is considered to be a useful procedure for estimating the dysplastic grade of colonic adenomas.

DOI： 10.1007/s00384-011-1311-8

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その他リンク： http://orcid.org/0000-0002-1068-7024

記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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DOI： 10.1007/s00384-012-1416-8

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その他リンク： http://orcid.org/0000-0002-1068-7024

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掲載種別：論文集(書籍)内論文  

Digestive enzymes in the human gut play major roles in digesting food so that nutrients can be absorbed through epithelial sheets in the intestinal lumen. Trypsin, one of the digestive enzymes, is mainly produced in the pancreas and secreted in the duodenum. Recent finding have shown that small intestinal epithelial cells produce trypsin peptide, which plays an important role in the human innate immune system. The digestive organs, contributing to the absorption of nutrients on one side and protecting the host from the numerous bacteria residing in the gut microbiota, also protects against external infectious microbes on the other side. Paneth cells, one of the secretory epithelial cells in the small intestine, express and secrete antimicrobial peptide, human alpha-defensin (HD). HD is an innate immune molecule that directly eliminates bacteria to maintain homeostasis in the gut's ecosystem. A specific pattern of trypsin isozymes is also expressed in Paneth cells, and trypsin co-localizes with HD to cleave propeptides to mature forms identical to those isolated in vivo. HD is stored in secretory vesicles as a propeptide, but the mature peptides isolated from the intestinal lumen are proteolytically processed forms. HD is produced and stored as a propeptide in Paneth cell granules, secreted in response to stimulation by cholinergic reagents or bacterial antigens, and finally activated by trypsin in the intestinal lumen in order to produce mature functional HD. Therefore, trypsin is involved in the regulation of innate immunity in the small intestine by acting as a prodefensin convertase in human Paneth cells. The activating process is critical for its antibacterial role and it is also a bridge to acquired immunity. This chapter reviews the novel functional role of trypsin which is produced in the small intestine. © 2012 by Nova Science Publishers, Inc. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background: Probiotics have been clinically administered to improve intestinal damage in some intestinal inflammations. However, probiotic treatments are not always effective for these intestinal disorders because live bacteria must colonize and maintain their activity under unfavorable conditions in the intestinal lumen when displaying their functions. This study investigated the physiological functions of a heat-killed body of a novel probiotic, Lactobacillus brevis SBC8803, on the protection of intestinal tissues, the regulation of cytokine production, the improvement of intestinal injury, and the survival rate of mice with dextran sodium sulfate (DSS)-induced colitis.
Methods: Heat shock protein (Hsp) induction and mitogen-activated protein kinase (MAPK) phosphorylation in intestinal epithelia by heat-killed L. brevis SBC8803 were examined by Western blotting. The barrier function of intestinal epithelia was measured with [(3)H]-mannitol flux in the small intestine under oxidant stress. The effects of the bacteria on improving epithelial injury and cumulative survival rate were investigated with a DSS colitis model.
Results: Heat-killed L. brevis SBC8803 induced Hsps, phosphorylated p38 MAPK, regulated the expression of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1 beta and IL-12, and improved the barrier function of intestinal epithelia under oxidant stress. The induction of Hsp and the protective effect were negated by p38 MAPK inhibitor. These functions relieve intestinal impairments and improve the survival rate in mice with lethal colitis.
Conclusions: The administration of heat-killed L. brevis SBC8803 helps to successfully maintain intestinal homeostasis, while also curing intestinal inflammation. A therapeutic strategy using heat-killed bacteria is expected to be beneficial for human health even in conditions unsuitable for live probiotics because the heat-killed body is able to exhibit its effects without the requirement of colonization. (Inflamm Bowel Dis 2011;17:2235-2250)

DOI： 10.1002/ibd.21597

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その他リンク： http://orcid.org/0000-0002-1068-7024

掲載種別：研究論文（学術雑誌）  

There have been no reports of Cronkhite-Canada syndrome (CCS) associated gastric cancer resected with endoscopy because it is very difficult to identify small cancers that are candidates for endoscopic resection. We report a case of CCS with gastric cancer treated with endoscopic submucosal dissection, and we evaluate the molecular pathological analysis of malignant transformation in patients with CCS. A 74-year-old man had an advanced rectal cancer and gastrointestinal polyposis after presenting with hypoproteinemia, partial hair loss and atrophic nails as well as hyperpigmentation on the hands. He was diagnosed as having CCS. On upper endoscopy, a 7 mm discolored polyp with an irregular microvascular pattern revealed by magnified narrow-band imaging (NBI) was identified in gastric diffuse CCS polyposis. This lesion was treated with endoscopic submucosal dissection and diagnosed as a flat, elevated-type, mucosal well-differentiated tubular adenocarcinoma without lymphatic or venous infiltration, and with tumor-free margins. Microsatellite instability was detected in both the cancer and the surrounding CCS polyps. Mucin-histochemical analysis of the cancer area showed the complete intestinal type, and thus may have differentiated the CCS polyps from that of the common gastric hyperplastic polyps. This case illustrates that a clue to detecting small cancers may be to look for the discolored lesion among reddish CCS polyposis and thereafter to observe the irregular vascular pattern with NBI endoscopy. From the viewpoint of genetic alterations, patients with CCS polyps are considered to be at high risk for developing gastric cancer, and therefore careful follow-up examinations are necessary for the early detection of malignancies. © 2011 Japan Gastroenterological Endoscopy Society.

DOI： 10.1111/j.1443-1661.2011.01150.x

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

Paneth細胞は細菌感染などに反応して,抗菌物質を分泌し自然免疫による感染防御を担っている.最近,クローン病患者で抗菌ペプチドα-defensinの発現低下が見出され,抗菌ペプチドの機能異常とIBDの病態との関連性が示唆された.α-defensinは,殺細菌作用のみならず,未熟樹状細胞を遊走させ獲得免疫の発動に関与すること,上皮細胞を刺激しIL-8などのケモカインを発現させ腸管局所免疫に関与することが明らかになってきた.本稿では,自然・獲得免疫システムにおける抗菌物質の作用について解説し,その発現異常や機能低下とIBD発症・進展との関連性について最新の知見を紹介する.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background: A method for the differential diagnosis of intestinal lymphomas resembling lymphoid hyperplasia (LH) by endoscopy remains to be clearly established.
Objective: To evaluate the usefulness of autofluorescence imaging (AFI) in diagnosing intestinal lymphoma.
Setting: Single-center study.
Design: Prospective study.
Patients: One hundred forty-three samples obtained from the intestinal tissues of 21 patients with malignant lymphoma were included in the study.
Interventions: The terminal ileum and entire colon were observed using conventional endoscopy equipped with AFI. The AFI images were taken by 3 endoscopists and then were evaluated by 3 predominant color intensities; green, magenta, and blended. To quantify the strength of fluorescence captured by AFI, the area of the obtained biopsy specimens on images was manually traced, the signal density of either magenta or green was measured, and then the ratio of the reverse gamma value of green divided by that of magenta was defined as the Fluorescence index (F index).
Main Outcome Measurements: The ability to use AFI to distinguish intestinal lymphoma from normal or LH.
Results: The cell density is inversely proportional to the F index. The F index of lymphoma was significantly lower than that of normal mucosa or LH. The visual classification of AFI showed the overall accuracy in diagnosing lymphoma was 91.5%, and was well correlated with the F index.
Limitations: Single-center study.
Conclusions: AFI-embossed lymphoma lesions seemed as magenta and could be discriminated from LH or normal mucosa with a high overall accuracy through perception of the cell density of the lesion. Therefore, AFI is considered to be an effective procedure for determining the accurate stage and appropriate therapy in intestinal lymphoma.

DOI： 10.1097/MCG.0b013e3181fbe22a

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Paneth cells at the base of small intestinal crypts secrete microbicidal α-defensins, termed cryptdins (Crps) in mice, as mediators of innate immunity. Proteomic studies show that five abundant Paneth cell α-defensins in C57BL/6 mice are strain specific in that they have not been identified in other inbred strains of mice. Two C57BL/6-specific peptides are coded for by the Defcr20 and -21 genes evident in the NIH C57BL/6 genome but absent from the Celera mixed-strain assembly, which excludes C57BL/6 data and differs from the NIH build with respect to the organization of the α-defensin gene locus. Conversely, C57BL/6 mice lack the Crp1, -2, -4, and -6 peptides and their corresponding Defcr1, -2, -4, and -6 genes, which are common to several mouse strains, including those of the Celera assembly. In C57BL/6 mice, α-defensin gene diversification appears to have occurred by tandem duplication of a multigene cassette that was not found in the mixed-strain assembly. Both mouse genome assemblies contain conserved α-defensin pseudogenes that are closely related to functional myeloid α-defensin genes in the rat, suggesting that the neutrophil α-defensin defect in mice resulted from progressive gene loss. Given the role of α-defensins in shaping the composition of the enteric microflora, such polymorphisms may influence outcomes in mouse models of disease or infection.

DOI： 10.1128/IAI.00996-10

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.gie.2010.05.018

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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出版者・発行元：1  

DOI： 10.1159/000242114

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J-GLOBAL

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DOI： 10.1002/ibd.21253

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その他リンク： http://orcid.org/0000-0002-1068-7024

DOI： 10.1016/j.canep.2010.01.004

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その他リンク： http://orcid.org/0000-0002-1068-7024

DOI： 10.1007/s12328-009-0126-4

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その他リンク： http://orcid.org/0000-0002-1068-7024

記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

潰瘍性大腸炎(UC)患者のうち発症時に直腸炎型であった症例は22.6%であり,さらにその中で41.9%は口側進展した.直腸炎型のおよそ半数は左側結腸炎型あるいは全大腸炎型の初期病変であり,経過中に口側進展を来す可能性がある.口側進展に関与する因子を明らかにする目的で,(1)男女別,(2)発症年齢別,(3)初発時重症度別,(4)skip病変の有無,について検討したが,いずれも有意な危険因子ではなかった.口側進展を認めず直腸炎のみで手術に至る例はなく口側進展が手術の危険因子であると考えられた.初発時直腸炎型の累積手術率は5年で12.2%,10年で23.3%であり,さらに口側進展し手術に至った症例の80%が口側進展を認めてから2年以内に手術に至っていた.直腸炎型でcolitic cancerを発症した症例はなかった.活動性粘膜の範囲を正確に診断し,口側進展をくいとめることが手術率・腸管外合併症やcolitic cancerの合併を軽減する可能性が示唆された.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

バレット食道およびバレット食道癌の発生機序とその分子機構に関わるH. pylori感染の影響について検討した。組織学的にSIMを認めず、円柱上皮化生粘膜のみのバレット粘膜症例43例(CLE群)、SIMを認めた症例88例(SIM群)、早期バレット食道癌症例8例(BE-ca群)の3群で比較した。その結果、1)CLE群、SIM群、BE-ca群へと食道病変が進展するに従い、ゲノム不安定性、E-cadherin、p16、APC遺伝子のプロモーター領域CpGアイランドのメチル化異常の頻度が増加した。2)ゲノム不安定性やhMLH1、E-cadherin、p16のメチル化異常はCLE群ではほとんど認めず、SIM群、BE-ca群に多く認めたことから、これらのDNA異常は前癌病変とされるバレット食道のSIMおよびバレット食道癌の発生に関与している可能性が示唆された。3)H. pylori感染例ではゲノム不安定性とE-cadherinのメチル化異常の頻度が高く、H. pylori感染とこれら分子異常との関連性が示唆された。

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記述言語：日本語   出版者・発行元：(株)先端医学社  

炎症性腸疾患(IBD)において破綻した自然免疫機構が明らかになりつつある。とくに、クローン病(CD)では、腸管における自然免疫担当細胞であるPaneth細胞が注目される。オートファジー遺伝子ATG16L1がCDの疾患感受性遺伝子として発見され、その欠損によりPaneth細胞の分泌顆粒の形成異常が認められる。また、NOD2蛋白がPaneth細胞で特異的に発現し、CD患者でその遺伝子異常が報告され、その背景に抗菌ペプチドの一つディフェンシンの発現低下がみられる。つまり、Paneth細胞とその分泌顆粒のおもな構成成分であるディフェンシンの異常がCDの発症に関与することが示唆される。さらに最近の研究で、抗菌ペプチドと称されるディフェンシンが抗菌活性以外に免疫調節作用をもち、腸管上皮細胞を刺激して獲得免疫を誘導することが見出された。それらの活性を応用して、ディフェンシン投与による腸炎の新規治療の可能性が検討されている。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J04151&link_issn=&doc_id=20090612440004&doc_link_id=%2Fae6mogab%2F2009%2F000602%2F005%2F0133-0139%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6mogab%2F2009%2F000602%2F005%2F0133-0139%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

腸管リンパ腫の光デジタル内視鏡所見について概説した.腸管リンパ腫の病変は,NBIでやや薄い茶色の領域として描出される場合が多く,拡大観察の併用により,不規則に走行する口径不同の微細血管が観察される.また小腸においては,通常,絨毛内をループ状に描出される血管が不整に蛇行,あるいは無秩序に走行する所見や絨毛内のうっ血が認められる.AFIでは,リンパ腫病巣は,マゼンタの色調を呈する.また,画像解析ソフトにより色調の変化を数値化した結果,リンパ腫病変では良性のリンパ濾胞過形成に比べ色調変化が著しいことから,リンパ腫細胞の浸潤は自家蛍光の減弱を引き起こすことが示された.今後さらに症例を蓄積し,リンパ腫病変の拾い上げにおける光デジタル内視鏡の有用性を検討するとともに,原発性と全身性リンパ腫との所見の差異,組織型や進行度による違いなどを明らかにする必要がある.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2009&ichushi_jid=J00081&link_issn=&doc_id=20090507190012&doc_link_id=10.11477%2Fmf.1403101668&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1403101668&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

記述言語：日本語   出版者・発行元：日本消化器免疫学会  

【背景】腸管では自然免疫機構が即時的な生体防御反応を担っている。ヒトPaneth細胞はα-defensin(HD5、HD6)を分泌し、腸管での最初の抗菌バリアー因子として働くが、その後の獲得免疫発動への関与を明らかにすることを目的とした。【結果】ヒトPaneth細胞分泌物およびHD5は未熟樹状細胞に対して化学遊走因子として働いた。Paneth細胞分泌物、HD5、HD6はT84細胞を刺激しIL-8を分泌させ、Paneth細胞分泌物が同様にTNF-αを分泌させた。【結論】Paneth細胞は腸管自然免疫において重要であるだけでなく、獲得免疫の発動に関与することで腸管粘膜の炎症反応の制御に関わっている可能性がある。(著者抄録)

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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DOI： 10.1136/bcr.06.2009.2048

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その他リンク： http://orcid.org/0000-0002-1068-7024

記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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DOI： 10.11405/nisshoshi.105.1337

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

症例は83歳女性。持続する黒色便にて当科紹介。胃穹窿部大彎の粘膜下腫瘍が十二指腸に脱出し、ball valve syndrome(BVS)を呈していた。胃部分切除術を施行し、粘膜筋板由来のgastrointestinal stromal tumor(GIST)と診断した。胃穹窿部での粘膜筋板由来の粘膜下腫瘍がBVSを呈することはまれであり、文献的考察をふくめ報告する。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2008&ichushi_jid=J01118&link_issn=&doc_id=20080909170005&doc_link_id=1390001206399581696&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001206399581696&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

DOI： 10.1016/j.gie.2008.01.043

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記述言語：日本語   出版者・発行元：(株)医学書院  

近年,新しいautofluorescence imaging(AFI)システムが開発され,消化器領域に応用されるようになってきた.AFIを用いると正常の大腸は強い自家蛍光が検出されるため鮮明な緑色として捉えられるが,腫瘍や炎症などは自家蛍光が減弱するため暗紫色として捉えられる.われわれは便宜上,AFIで捉えられる病変の色調を自家蛍光の強い順にG(green)からGP(green/purple),PG(purple/green),P(purple)の4段階に分類し,評価を行った.大腸腫瘍では過形成性ポリープはGからGPを呈するのに対し,腺腫や癌はPGからPを呈し,病変の質的鑑別が可能であった.しかし腺腫,早期癌,進行癌の鑑別は困難であった.潰瘍性大腸炎では病理学的活動性が高いとPまたはPGを呈し,活動性が低いとGまたはGPを呈する傾向にあり,また数値化を行うことによって,より客観的に評価できると考えられた.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cgh.2007.12.044

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

潰瘍性大腸炎(UC)の初期病変をとらえるのはしばしば困難である。呈示する症例は40歳代女性で全大腸炎型の潰瘍性大腸炎である。当初、虚血性腸炎と診断したが、緩解期拡大内視鏡所見から潰瘍性大腸炎を疑い治療したにもかかわらず、その後再燃・緩解をくり返し、最終的に典型的な潰瘍性大腸炎へ進展した。潰瘍性大腸炎の自然史および縦走潰瘍の成因について示唆に富む症例と考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

腸管免疫におけるinnate immunity(自然免疫)の重要性が明らかとなるとともに炎症性腸疾患とのかかわりがクローズアップされてきた。クローン病で疾患感受性遺伝子NOD2が発見され、NOD2蛋白が細菌抗原を認識する細胞内レセプターで自然免疫においてきわめて重要な役割を担っていることから、クローン病と自然免疫との詳細な研究が進められた。NOD2蛋白が小腸Paneth細胞に特異的に発現すること、NOD2遺伝子改変マウスではPaneth細胞ディフェンシンの発現が低下するなど、腸管粘膜上皮が自然免疫に貢献することがわかりつつある。しかし、NOD2遺伝子の変異は日本人ではみられず、わが国ではクローン病とPaneth細胞、ディフェンシンとの関係は明らかではない。小腸陰窩の単離法の確立により、われわれはクローン病のPaneth細胞の殺菌作用が低下していることを見出した。その活性低下にディフェンシンの構造異常が関与している可能性が示唆された。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J04151&link_issn=&doc_id=20070531340004&doc_link_id=%2Fae6mogab%2F2007%2F000402%2F005%2F0110-0115%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6mogab%2F2007%2F000402%2F005%2F0110-0115%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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DOI： 10.1016/j.gie.2007.03.989

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Small intestinal Paneth cells secrete alpha-defensin microbicidal peptides as mediators of innate enteric immunity. In mice, production of mature Paneth cell alpha-defensins, termed cryptdins (Crps), requires proteolytic activation of inactive precursors (pro-Crps) by the convertase matrix metalloproteinase-7. Proteolysis of mouse (pro-Crp4)(20-92) produces the specific cleavage intermediates pro-Crp4(44-92), pro-Crp4(54-92), and pro-Crp4(59-92). To identify which cleavage event enables bactericidal activity, recombinant pro-Crp4-processing intermediates were purified to homogeneity and assayed for bactericidal peptide activity. The in vitro bactericidal activities of pro-Crp4-processing intermediates were very similar to fully processed Crp4, contrasting the lack of bactericidal and membrane-disruptive activity shown by pro-Crp4(20-92). Thus, cleavage of pro-Crp4(20-92) at Ser(43) downward arrowIle(44) is sufficient to activate bactericidal activity, and amino acids in the pro-Crp4(20-43) of the proregion maintain the precursor in an inactive state. Because cationic Arg residues are determinants of Crp4 bactericidal peptide activity, we hypothesized that Asp and Glu residues in pro-Crp4(20-43) neutralize Crp4 Arg side chains in pro-Crp4(20-92). Therefore, a pro-Crp4(20-92) variant with Gly substitutions at all pro-Crp4(20-43) Asp and Glu positions ((DE/G)-pro-Crp4) was prepared, and it was bactericidal and lysed phospholipid vesicles under conditions where native pro-Crp4(20-92) lacks activity. These findings show that MMP-7 proteolysis of pro-Crp4(20-92) at Ser(43) downward arrowIle(44) converts inactive precursors to bactericidal forms by removal of covalently associated, inhibitory acidic amino acids from proximity with the Crp4 component of the molecule.

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The enteric pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) encounters a variety of anti-microbial peptides during the course of infection. We report here that the extracytoplasmic sigma factor sigma(E) (RpoE) is required for Salmonella resistance to killing by the bactericidal/permeability-increasing protein (BPI)-derived peptide P2 and the murine alpha-defensin cryptdin-4 (Crp4). Moreover, sigma(E)-deficient S. Typhimurium is attenuated for virulence after oral infection of immunocompromised gp91phox(-/-) mice that lack a functional NADPH phagocyte oxidase, suggesting that sigma(E) plays an important role in resistance to non-oxidative mucosal host defences such as anti-microbial peptides. Although both P2 and Crp4 target the cell envelope, bacterial killing by these peptides appears to occur by distinct mechanisms. Formate enhances bacterial resistance to P2, as previously demonstrated, but not to Crp4. Both sigma(E) and cytoplasmic membrane-associated formate dehydrogenase are required for the protective effect of formate against P2. In contrast to P2, Crp4 does not inhibit bacterial respiration at lethal concentrations. However, both peptides induce expression of rpoE, suggesting that they trigger a common mechanism for sensing extracytoplasmic stress.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mammalian defensins are abundant antimicrobial peptides that contribute to host defense. They are characterized by several conserved amino acids, including six invariant cysteine residues which form three intramolecular disulfide bonds and stabilize the tertiary structure. Cryptdin-4 (Crp4), a mouse alpha-defensin with potent in vitro bactericidal activity, has a primary structure distinct from all known alpha-defensins in that its polypeptide backbone uniquely lacks three residues between Cys(IV) and Cys(V). NMR diffusion experiments showed that Crp4 is monomeric in solution, and its three-dimensional solution structure, determined by two-dimensional proton NMR, consists of a triple-stranded antiparallel beta-sheet with the beta-strands joined to each other by a series of tight turns and a beta-hairpin. However, the overall beta-sheet content in Crp4 is lower than that of other alpha-defensin structures, while the shape and orientation of the Crp4 beta-hairpin also differ from those of other alpha-defensin structures. These structural characteristics combined with the high overall cationicity of Crp4 may contribute to its broad bactericidal spectrum and membrane disruptive activity.

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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出版者・発行元：42  

DOI： 10.1074/jbc.M406154200

PubMed

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記述言語：日本語   出版者・発行元：(株)医学書院  

76歳女性.患者は56歳時に癌で横行結腸切除術の既往があり,今回,空腹時の胸やけにて受診となった.下部消化管内視鏡ではS状結腸に径1.5cm,Is型の易出血性陥凹を伴う隆起性病変を認め,拡大観察ではIIIL型pitが主体で,陥凹内に一部pit構造が不明瞭な部分を認めた.注腸X線ではS状結腸に径1.5cmの透亮像を認め,境界明瞭な隆起で半月ひだをまたぐように存在しており,深達度m～sm1の癌と考えた.更にHFUP(高周波超音波細径プローブ検査)では第1層から第3層深部に達する低エコー領域を認め,内部エコーは不均一で最深部および辺縁部にcystic echoを示す部分を認めた.以上より,深達度sm3,sm垂直浸潤距離2600μm,一部にmucinous componentを有する浸潤癌と診断し,S状結腸切除術を行った.病理組織所見ではT1(sm1,sm浸潤距離100μm),N0,M0,atage Iの高分化型腺癌と診断された

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Paneth cells of intestinal crypts contribute to host defense by producing antimicrobial peptides that are packaged as granules for secretion into the crypt lumen. Here, we provide evidence using light and electron microscopy that postsecretory Paneth cell granules undergo limited dissolution and accumulate within the intestinal crypts of cystic fibrosis (CF) mice. On the basis of this finding, we evaluated bacterial colonization and expression of two major constituents of Paneth cells, i.e., alpha-defensins (cryptdins) and lysozyme, in CF murine intestine. Paneth cell granules accumulated in intestinal crypt lumens in both untreated CF mice with impending intestinal obstruction and in CF mice treated with an osmotic laxative that prevented overt clinical symptoms and mucus accretion. Ultrastructure studies indicated little change in granule morphology within mucus casts, whereas granules in laxative-treated mice appear to undergo limited dissolution. Protein extracts from CF intestine had increased levels of processed cryptdins compared with those from wild-type (WT) littermates. Nonetheless, colonization with aerobic bacteria species was not diminished in the CF intestine and oral challenge with a cryptdin-sensitive enteric pathogen, Salmonella typhimurium, resulted in greater colonization of CF compared with WT intestine. Modest downregulation of cryptdin and lysozyme mRNA in CF intestine was shown by microarray analysis, real-time quantitative PCR, and Northern blot analysis. Based on these findings, we conclude that antimicrobial peptide activity in CF mouse intestine is compromised by inadequate dissolution of Paneth cell granules within the crypt lumens.

PubMed

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記述言語：日本語   出版者・発行元：(株)医学書院  

粘膜下腫瘍(SMT)様の形態を示した消化管癌の鑑別診断について解説した.SMT様の形態をとる食道癌の多くは特殊組織型である.胃癌ではリンパ球浸潤の強い(lymphoid stroma)癌や粘液癌,大腸癌ではnon-polypoid growthを示すもの,粘液癌が多い.SMT様癌と鑑別が必要な非上皮性腫瘍は悪性リンパ腫,カルチノイド腫瘍,GISTを含む間葉系腫瘍,転移性癌である.また,部位別にみると食道では顆粒細胞腫,胃では迷入膵,異所性胃粘膜,inflammatory fibroid polyp,大腸では直腸粘膜脱症候群や脂肪腫である.いずれもヨード染色や色素撤布法を併用しわずかな上皮性変化を捉えることが重要である

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2004&ichushi_jid=J00081&link_issn=&doc_id=20040713330015&doc_link_id=10.11477%2Fmf.1403100494&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1403100494&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

出版者・発行元：2  

DOI： 10.1007/s00535-003-1260-2

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J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The bactericidal activity of mouse Paneth cell alphadefensins, or cryptdins, is dependent on processing of cryptdin precursors (pro-Crps) by matrix metalloproteinase-7 (MMP-7) (Wilson, C. L., Ouellette, A. J., Satchell, D. P., Ayabe, T., Lopez-Boado, Y. S., Stratman, J. L., Hultgren, S. J., Matrisian, L. M., and Parks, W. C. (1999) Science 286, 113-117). To investigate the mechanisms of pro-Crp processing by this enzyme, recombinant pro-Crp4, a His-tagged chimeric pro-Crp (pro-CC), and site-directed mutant precursors of each were digested with MMP-7, and the cleavage products were analyzed by NH(2)-terminal peptide sequencing. Proteolysis of pro-Crp4 with MMP-7 activated in vitro bactericidal activity to the level of the mature Crp4 peptide by cleaving pro-Crp4 at Ser(43) downward arrow Ile(44) and Ala(53) downward arrow Leu(54) in the proregion and near the Crp4 peptide NH(2) terminus between Ser(58) downward arrow Leu(59). Because the Crp4 NH(2) terminus occurs at Gly(61), not Leu(59), MMP-7 is necessary but insufficient to complete the processing of Crp4. Crp activating proteolysis at S58 downward arrow L59 was unaffected by I44S/I44D or L54S/L54D loss-of-function mutations in pro-Crp4, and a (L59S)-pro-CC mutant was cleaved normally at Ser(43) downward arrow Val(44) and Ser(53) downward arrow Leu(54) sites but not at the peptide NH(2) terminus. C57BL/6 mice contain an abundant (L59S)-Crp4 mutant peptide with Leu(54) at its NH(2) terminus resulting from Ala(53) downward arrow Leu(54) cleavage and loss-of-function at the Ser(58) downward arrow Ser(59) cleavage site. Thus, alpha-defensins resulting from mutations at MMP-7 cleavage sites exist in mouse populations. A pro-CC substrate containing both L54S and L59S mutations resisted cleavage at Ser(43) downward arrow Val(44) completely, showing that cleavage at one or both downstream sites must precede proteolysis at Ser(43) downward arrow Val(44). These findings show that MMP-7 activation of pro-Crps can occur without proteolysis of the proregion, and prosegment fragmentation depends, at least in part, on the release of the Crp peptide from the precursor.

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出版者・発行元：7  

DOI： 10.1074/jbc.M109410200

PubMed

J-GLOBAL

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DOI： 10.1016/S0016-5107(97)70100-7

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2019.03.1110

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-北海道支部  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/hel.12111

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：日本語  

雑誌掲載版食道癌は悪性度が高く治療困難な癌のひとつであるが、積極的な治療効果向上の努力の結果、外科手術、内視鏡治療、化学放射線治療がめざましく進歩してきた。食道癌の特徴のひとつとして高齢者に多く発生することがあげられる。治療の問題点として、リンパ節郭清や再建臓器の点で外科手術の侵襲がきわめて高いことがあげられる。しかし、食道癌は他の消化器癌に比較して抗癌剤や放射線の感受性が高く、積極的に化学放射線療法が選択されることが多い。1998年1月から2011年12月までに筆者らが化学放射線治療を実施した高齢者食道癌症例を集計し、その効果と長期予後について検討した。化学放射線治療を行った45症例(55〜81歳)のうち、65歳以上の高齢者は26症例(57.8%)みられた。高齢者食道癌の進行度別内訳は、stage I 6例、stage II 3例、stage III 8例、stage IV 9例で、外科切除可能と考えられるstage III以下の症例が17例含まれていた。放射線療法は54〜66Gyの線量で、化学療法は5-FU/CDDPが多く、23例で治療が完遂できた。全生存期間の中央値は30.1ヵ月であり、治療効果がCRに至った14例(56.0%)の生存期間は100.5ヵ月であった。高齢者の食道癌患者は化学放射線治療を実施されることが多く、治療効果は良好であった。PR、SD症例は食道癌の再発により死亡していたが、CR症例は長期予後が得られた。高齢者食道癌においても化学放射線療法を実施する際にはCRを目指して積極的に治療することが重要と考えられた。

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その他リンク： http://search.jamas.or.jp/link/ui/2013171306

記述言語：日本語  

雑誌掲載版

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その他リンク： http://search.jamas.or.jp/link/ui/2012283975

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：日本語  

雑誌掲載版小胞体ストレスとは、さまざまな生理的な条件下で小胞体の蛋白フォールディングが障害される状態であり、小胞体ストレス応答(UPR)とよばれる複雑なシグナル伝達系が誘導される。ストレスに対する細胞の適応現象と考えられるが、UPRで十分に適応できないときには小胞体ごと除去するオートファジーの機構がはたらく。それらでも十分な効果を示さないときにはアポトーシスやオートファジー細胞死により、最終的に異常な細胞は駆除されている。最近では、腫瘍細胞が発生や増殖の段階で、UPRやそれにつづくオートファジーを利用していることが明らかにされてきた。さらに、治療のターゲットとしての研究が進められている。

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その他リンク： http://search.jamas.or.jp/link/ui/2012166926

記述言語：英語   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2010.05.018

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記述言語：日本語   出版者・発行元：(株)医学書院  

バルーン小腸内視鏡やカプセル内視鏡など全小腸を検索できるモダリティが普及し,これまでX線検査ではとらえきれなかった微細な病変も検出できるようになってきた.Crohn病の診断においても同様であるが,X線検査は病変の大きさ,範囲,分布,配列などを客観的に把握でき,内視鏡の到達しえない狭窄病変の先の情報も得られる点で有用であり,状況に応じて使い分けることが重要である.(著者抄録)

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2010.03.509

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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DOI： 10.1111/j.1365-2559.2009.03370.x

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DOI： 10.1002/ijc.24092

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

Background and Aims: Chronic gastritis is caused by Helicobacter pylori infection, and gastritis is classified as inflammation, atrophy, and intestinal metaplasia. Detailed pathologic studies have shown that H. pylori settles on the surface of gastric mucosa, and that it is eliminated from metaplastic mucosa. However, its mechanism of natural protection is not well known.
Methods: Antimicrobial human enteric defensin expression was determined in the RNA and protein levels. Recombinant enteric defensins were produced with a bacterial expression system and their anti-H. pylori activities were assessed by bactericidal assay.
Results: Human enteric defensin (HD)-5 and HD-6 were detected in Paneth cells, which are observed in the gastric metaplastic mucosa as well as small intestinal epithelia. HD-5 protein was coexpressed with trypsin, which is considered to be an activating enzyme of HD-5. Less H. pylori was observed in the intestinal metaplasia with HD-5 expressing Paneth cells. The recombinant defensins showed killing activity against H. pylori at a low concentration in vitro.
Conclusions: The human defensins that are expressed in the metaplastic Paneth cells eliminate H. pylori. Metaplastic change may be a purposive development of the human stomach.

DOI： 10.1111/j.1523-5378.2008.00621.x

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：MOSBY-ELSEVIER  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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DOI： 10.11477/mf.1403101404

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DOI： 10.1309/DFLELPGPNV5LK6B1

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記述言語：英語   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

alpha-Defensin is an antimicrobial peptide which plays an important role in innate immunity. Human defensin (HD)-5 is stored in the Paneth cells of the small intestine as a pro-form and is cleaved by trypsin, which is co-secreted from the Paneth cell granules. The mature HD-5 is protected from further digestion by the proteolysis enzyme, We generated both recombinant HD-5 and proHD-5, and the reduced form of each peptide in order to determine their physiological roles of the disulfide bonds. The reduced proHD-5 attenuated the bactericidal activity and the stability against the trypsin digestion. Human defensin was protected from the enzymatic degradation by disulfide bridges. We further purified the HD-5 with a disulfide variation in the small intestine of Crohn's disease patients. The HD-5 was sensitive to the trypsin treatment. These observations evidently predict that a defensin deficiency may be caused by a disulfide disorder in the disease. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2007.04.132

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PubMed

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記述言語：日本語  

DOI： 10.11477/mf.1403101017

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記述言語：日本語  

DOI： 10.11477/mf.1403101093

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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DOI： 10.11477/mf.1403101244

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DOI： 10.1136/jcp.2006.041939

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE BV  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：MOSBY-ELSEVIER  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：FEDERATION AMER SOC EXP BIOL  

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記述言語：日本語  

DOI： 10.11477/mf.1403100180

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記述言語：英語   出版者・発行元：AMER SOC MICROBIOLOGY  

Mouse Paneth cells respond to bacteria and bacterial cell surface antigens by discharging secretory granules into the lumen of small intestinal crypts (T. Ayabe et al., Nat. Immunol. 1:113-118, 2000). To investigate mechanisms regulating these responses, purified surface glycolipid molecules with known acyl chain modifications and attenuated properties were tested for the ability to stimulate Paneth cell secretion. The antigens included lipopolysaccharide (LPS) from wild-type and msbB-null Escherichia coli and phoP-null and phoP-constitutive Salmonella enterica serovar Typhimurium strains, as well as LPS, lipid A, and lipoteichoic acid from Pseudomonas aeruginosa and Listeria monocytogenes grown in Mg2+-limited media. Measurements of total secreted protein, secreted lysozyme, and the bactericidal peptide activities of collected secretions showed that the purified antigens elicited similar secretory responses from Paneth cells in mouse crypts ex vivo, regardless of glycolipid acyl chain modification. Despite their impaired Tlr4 pathway, Paneth cells in ex vivo C3H/HeJ mouse crypts released equivalent amounts of bactericidal peptide activity in response to purified bacterial antigens, including lipid A. Thus, mouse Paneth cells respond equivalently to purified bacterial cell envelope glycolipids, regardless of functional Tlr4, the structural properties of glycolipid acyl chains, or their association with virulence in humans.

DOI： 10.1128/IAI.73.4.2312-2320.2005

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：MOSBY, INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：FEDERATION AMER SOC EXP BIOL  

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DOI： 10.1007/s00535-004-1561-0

PubMed

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記述言語：英語   出版者・発行元：AMER SOC MICROBIOLOGY  

In addition to their antibacterial activities, certain antimicrobial peptides inactivate enveloped viruses, including the human immunodeficiency virus (HIV). To determine whether peptide bactericidal activities are predictive of antiviral activity, the anti-HIV properties of recombinant human et-defensin 5, mouse alpha-defensins, cryptdins (Crp) 3 and 4, and rhesus macaque myeloid alpha-defensins (RMADs) 3 and 4 were determined in vitro. The peptides, purified to homogeneity, had equivalent bactericidal activities that were similar to those of the native molecules. Nuclear magnetic resonance spectroscopy showed RMAD-4 and Crp3 had characteristic alpha-defensin tridisulfide arrays. Of the peptides analyzed, only RMAD-4 inhibited HIV infectivity at 150 mug/ml, and Crp3 unexpectedly increased HIV replication. Quantitative real-time PCRs for minus-strand strong stop DNA and complete viral cDNA synthesis were used to distinguish between preentry and postentry anti-HIV effects by RMAD-4. Viral exposure to RMAD-4 for 1 h prior to infection reduced HIV minus-strand strong stop DNA and HIV cDNA by 4- to 20-fold during the first round of replication, showing that RMAD-4-exposed virions were not entering cells during the first 24 h. On the other hand, when RMAD-4 was added coincident with HIV inoculation, no anti-HIV activity was detected. Viral exposure to Crp3 resulted in a threefold increase in both HIV minus-strand strong stop DNA and HIV cDNA over the first round of replication. Therefore, two alpha-defensins, RMAD-4 and Crp3, inhibit or augment HIV replication, respectively, by mechanisms that precede reverse transcription.

DOI： 10.1128/JVI.78.21.11622-11631.2004

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Paneth cells secrete microbicidal enteric alpha-defensins into the small intestinal lumen, and cryptdin-4 (Crp4) is the most bactericidal of the mouse alpha-defensin peptides in vitro. Here, site-directed Arg to Asp mutations in Crp4 have been shown to attenuate or eliminate microbicidal activity against all of the bacterial species tested regardless of the Arg residue position. R31D/R32D charge-reversal mutagenesis at the C terminus and mutations at R16D/R18D, R16D/R24D, and R18D/R24D in the Crp4 polypeptide chain eliminated in vitro bactericidal activity, blocked peptide-membrane interactions, as well as Crp4-mediated membrane vesicle disruption. Lys for Arg charge-neutral substitutions in (R16K/R18K)-Crp4 did not alter the bactericidal activity relative to Crp4, showing that bactericidal activity appears not to require the guanidinium side chain of Arg at those two positions. Partial restoration of (R31D/R32D)-Crp4 bactericidal activity occurred when an electropositive Arg for Gly substitution was introduced at the peptide N terminus and the (G1R/R31D/R32D)-Crp4 peptide exhibited intermediate membrane binding capability. Also, the loss of peptide bactericidal activity in (G1D/R31D/ R32D)-Crp4 and (R16D/R24D)-Crp4 mutants corresponded with diminished phospholipid vesicle disruptive activity. Fluorophore leakage from anionic phospholipid vesicles induced by the charge-reversal variants was negligible relative to Crp4 and lower than that induced by pro-Crp4, the inactive Crp4 precursor. Thus, Arg residues function as determinants of Crp4 bactericidal activity by facilitating or enabling target cell membrane disruption. The role of the Arg residues, however, was surprisingly independent of their position in the polypeptide chain.

DOI： 10.1074/jbc.M310251200

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記述言語：英語   出版者・発行元：AMER SOC MICROBIOLOGY  

Antimicrobial peptides are secreted by small intestinal Paneth cells as components of innate immunity. To investigate the role of alpha-defensins in enteric host defenses in nonhuman primates, alpha-defensin cDNAs were isolated, alpha-defensin peptides were purified from rhesus macaque small bowel, and the bactericidal activities of the peptides were measured. Six rhesus enteric alpha-defensin (RED) cDNAs, RED-1 to RED-6, were identified in a jejunum cDNA library; the deduced RED peptides exhibited extensive diversity relative to the primary structures of rhesus myeloid alpha-defensins. RED-4 was purified from monkey jejunum, and N-terminal peptide sequencing of putative RED-4 peptides identified two N termini, RTCYCRTGR... and TCYCRTGRC...; these corresponded to alternative N termini for the RED-4 molecules, as deduced from their molecular masses and RED cDNAs. In situ hybridization experiments localized RED mRNAs exclusively to small intestinal Paneth cells. Recombinant RED-1 to RED-4 were purified to homogeneity and shown to be microbicidal in the low micromolar range (less than or equal to10 mug/ml) against gram-positive and gram-negative bacteria, with individual peptides exhibiting variable target cell specificities. Thus, compared to myeloid alpha-defensins from rhesus macaques, enteric alpha-defensin peptides are highly variable in both primary structure and activity. These studies should facilitate further analyses of the role of alpha-defensins in primate enteric immunity.

DOI： 10.1128/IAI.72.3.1470-1478.2004

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

DOI： 10.1016/S0016-5085(03)82978-5

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：日本語  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

DOI： 10.11280/gee1973b.38.2865

CiNii Books

J-GLOBAL

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開催年月日： 2021年10月

記述言語：英語   会議種別：口頭発表（一般）  

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開催地：兵庫  

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開催年月日： 2020年11月

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開催地：兵庫  

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開催地：広島  

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開催年月日： 2020年10月

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開催地：広島  

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開催年月日： 2020年8月

記述言語：日本語   会議種別：ポスター発表  

開催地：東京  

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開催年月日： 2020年8月

記述言語：日本語   会議種別：ポスター発表  

開催地：東京  

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開催地：小田原  

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開催年月日： 2019年6月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：名古屋  

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開催年月日： 2019年4月

記述言語：日本語   会議種別：ポスター発表  

開催地：名古屋  

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