記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.2169/internalmedicine.4160-24

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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：(一社)日本潰瘍学会  

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記述言語：日本語   出版者・発行元：(一社)日本潰瘍学会  

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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：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）  

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）  

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: 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：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）  

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

DOI： 10.1016/j.heliyon.2024.e28070

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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）  

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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）  

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）  

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：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 : 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：英語  

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

DOI： 10.3390/cancers15041328

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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

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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

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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

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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

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1186/s12885-022-10008-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.

DOI： 10.1007/s00535-022-01877-5

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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/a-1550-1913

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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

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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

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1186/s12866-022-02530-0

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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：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The importance of fall prevention rehabilitations has been well recognized. Recently telerehabilitation was developed, however, there have been no reports on telerehabilitation with direct support from specialists for fall prevention among the elderly. We herein reported telerehabilitation by caregivers educated by our novel educational program. METHODS: Caregivers were educated with our educational program using a telelecture system and supported telerehabilitation following instructions from rehabilitation specialists in our university using the telemedicine system every two to four weeks for three months. Caregivers were assessed with our original questionnaire before and after the telelecture. Participants were assessed by the Berg Balance Scale (BBS), Timed Up & Go test (TUG test), Hand-held dynamometer (HHD) and Mini-Mental State Examination (MMSE) before and after telerehabilitation. Wilcoxon's signed-rank test was used for the statistical analyses. A value of P<.05 was considered statistically significant. RESULTS: Nine elderly people were enrolled. The mean age was 84.7 (78-90) years old and the sex ratio was 1:8 (males:females). The average number of telerehabilitation sessions was 4.7. The average score of nineteen caregivers before the lecture was 15.3, while that after the lecture was 18.3. Caregivers' understanding was significantly increased after the telelecture (P<.001). No adverse events occurred during the study period. The median values of the BBSs, TUG test, right and left HHD and MMSE before and after 3 months' telerehabilitation were 43 (95% confidence interval [CI]: 40.10, 49.01) and 49 (95% CI: 41.75, 50.91), 17.89 (95% CI: 15.51, 23.66) and 18.53 (95% CI: 14.56, 25.67), 7.95 (95% CI: 4.38, 10.14) and 11.55 (95% CI: 7.06, 13.55), 9.85 (95% CI: 6.79, 12.59) and 13.20 (95% CI: 7.96, 14.42), and 19 (95% CI: 12.34, 21.66) and 16 (95% CI: 10.81, 21.00), respectively. Although approximately half of the participants showed improvement in the BBS, TUG test, right and left HHD and MMSE, no significant changes were observed (P=.7239, P=.3446, P=.1023, P=.3538 and P=.8253, respectively). CONCLUSIONS: Our telerehabilitation program exhibited significant effects in elderly people and improved the degree of understanding concerning rehabilitation among caregivers in facilities for elderly people.

DOI： 10.1097/MD.0000000000027451

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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  

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

DOI： 10.1177/20420986221100118

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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：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We previously showed that Lactobacillus brevis-derived polyphosphate (poly P) exerts a curative effect on intestinal inflammation. However, whether or not poly P improves the inflammation and injury of distant organs remains unclear. AIMS: We aimed to investigate the change in the intestinal microbiome and to evaluate the protective effect of poly P on injuries in a cerulein-induced acute pancreatitis (AP) mouse. METHODS: Poly P was orally administered to BALB/C mice every day for 24 days, and then mice were intraperitoneally injected with cerulein. Before cerulein injection, stool samples were collected and analyzed by 16S rRNA gene sequencing. Mice were sacrificed at 24 h after the last cerulein injection; subsequently, the serum, pancreas, and colon were collected. RESULTS: The microbial profile differed markedly between poly P and control group. Notably, the levels of beneficial bacteria, including Alistipes and Candidatus_Saccharimonas, were significantly increased, while those of the virulent bacteria Desulfovibrio were decreased in the poly P group. The elevations of the serum amylase and lipase levels by cerulein treatment were suppressed by the pre-administration of poly P for 24 days, but not for 7 days. The numbers of cells MPO-positive by immunohistology were decreased and the levels of MCP-1 significantly reduced in the AP + Poly P group. An immunofluorescence analysis showed that the ZO-1 and occludin in the colon was strongly augmented in the epithelial cell membrane layer in the AP + Poly P group. CONCLUSIONS: Poly P attenuates AP through both modification of the intestinal microbiome and enhancement of the intestinal barrier integrity.

DOI： 10.1007/s10620-020-06747-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The therapeutic goal in inflammatory bowel disease (IBD) patients has shifted from controlling the clinical activity alone to managing other associated problems. The concept of mucosal healing (MH) and deep remission (DR) are advocated and regarded as new therapeutic goals in IBD. However, the definition of MH still remains controversial. It is unclear whether or not the histological structures or functional factors should be included in the definition of DR in addition to clinical remission and MH. The classifications of white-light imaging (e.g. Mayo endoscopic subscore, UCEIS, CD Endoscopic Index of Severity, simple Endoscopic Score-CD) have been proposed and are now widely used to assess the severity as well as the MH of inflammation in IBD. In ulcerative colitis, magnifying chromoendoscopy has been shown to be useful to assess the MH of inflammation while other types of image-enhanced endoscopy, such as narrow-band imaging, have not. Endocytoscopy and confocal laser endomicroscopy (CLE) are also applied to assess the activity in IBD. These endoscopic procedures can estimate MH with more precision through observing the details of superficial structures, such as crypt openings. In addition, CLE can partially assess the mucosal function by detecting fluorescence leakage. Molecular imaging can possibly detect the molecules associated with inflammation, intestinal regeneration and differentiation, and various functions including the intestinal barrier and mucus secretion. These novel procedures may improve the diagnosis strategy of DR through the assessment of DR-associated factors such as the histological structures and functional factors in the near future.

DOI： 10.1111/den.13863

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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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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）  

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）  

Previous investigations have indicated that RNA-binding proteins (RBPs) are key molecules for the development of organs, differentiation, cell growth and apoptosis in cancer cells as well as normal cells. A bioinformatics analysis based on the mRNA expression and a somatic mutational database revealed the association between aberrant expression/mutations of RBPs and cancer progression. However, this method failed to detect functional alterations in RBPs without changes in the expression, thus leading to false negatives. To identify major tumor-associated RBPs, we constructed an siRNA library based on the database of RBPs and assessed the influence on the growth of colorectal, pancreatic and esophageal cancer cells. A comprehensive analysis of siRNA functional screening findings using 1198 siRNAs targeting 416 RBPs identified 41 RBPs in which 50% inhibition of cell growth was observed in cancer cells. Among these RBPs, 12 showed no change in the mRNA expression and no growth suppression in non-cancerous cells when downregulated by specific siRNAs. We herein report for the first time cancer-promotive RBPs identified by a novel functional assessment using an siRNA library of RBPs combined with expressional and mutational analyses.

DOI： 10.3390/cancers13133165

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記述言語：英語   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）  

Intake of probiotics or fermented food produced by some probiotic bacteria is believed to exert anti-tumor functions in various cancers, including pancreatic cancer, because several studies have demonstrated the anti-tumor effects of probiotic bacteria in vitro and in vivo in animal carcinogenesis models. However, the mechanisms underlying the anticancer effects of probiotics on pancreatic cancer have not been clarified. In this study, we assessed the anti-tumor effects of probiotic bacteria against pancreatic cancer cells. Among the known probiotic bacteria, Aspergillus oryzae exhibited a strong pancreatic tumor suppression effect. The culture supernatant of A. oryzae was separated by HPLC. Heptelidic acid was identified as an anti-tumor molecule derived from A. oryzae by LC-MS and NMR analysis. The anti-tumor effect of heptelidic acid was exhibited in vitro and in vivo in a xenograft model of pancreatic cancer cells. The anti-tumor effect of heptelidic acid was exerted by the p38 MAPK signaling pathway. Heptelidic acid traverses the intestinal mucosa and exerts anti-tumor effects on pancreatic cancer cells. This is a novel anti-tumor mechanism induced by beneficial bacteria against pancreatic cancer in which bacterial molecules pass through the intestinal tract, reach the extra-intestinal organs, and then induce apoptosis via an inducible signaling pathway.

DOI： 10.1038/s41598-021-90707-4

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記述言語：英語  

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：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Colorectal 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. METHODS: SRB 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. RESULTS: Ferrichrome 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. CONCLUSIONS: Ferrichrome 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）  

Inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD), is an intractable intestinal inflammation associated with the disruption of the intestinal mucosa. We previously demonstrated that Lactobacillus brevis-derived long-chain polyphosphate (poly P) improved the intestinal barrier function by the upregulation of cell adhesion and relieved intestinal inflammation, thereby exerting a curing effect on colitis in vitro, in vivo, and in an investigator-initiated clinical study of UC. However, how poly P improves mucosal defects induced by intestinal inflammation has not been elucidated. In this study, we detected the accumulation of platelets in inflamed tissues induced by poly P in a dextran sulfate sodium- (DSS-) induced colitis mouse model. A light transmission aggregometry analysis and scanning electron microscopy showed that poly P promoted the platelet aggregation. An SRB assay and ki-67 staining showed that the supernatant of poly P-treated platelet-rich plasma (PRP) increased intestinal epithelial cell growth. A wound healing assay showed that the supernatant of poly P-treated PRP, but not poly P itself, accelerated wound healing. A Western blotting analysis indicated that mitogen-activated protein kinase activation was induced by the supernatant of poly P-treated human PRP in the epithelial cells and its wound healing effect was significantly decreased by the inhibition of ERK signaling. These data suggested that platelet-derived mediators induced by poly P improved intestinal inflammation through the promotion of epithelial cell growth by the activation of the ERK signaling pathway. The mechanism is a novel host-microbe interaction through mammalian platelet-derived mediators induced by bacterial molecules.

DOI： 10.1155/2021/5582943

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

An attempt to use combination therapy with anti-tumor necrosis factor α (TNFα) 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-TNFα antibodies (TAC + anti-TNFα therapy) remains unclear. We examined the efficacy of various doses of TAC + anti-TNFα therapy in a mouse colitis model. Dextran sulfate sodium induced colitis model mice were divided into an anti-TNFα antibody monotherapy group and the groups that received various doses of TAC + anti-TNFα 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-TNFα 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-TNFα 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-TNFα antibodies in the high-dose TAC + anti-TNFα 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-TNFα antibody concentration. When administered in combination with anti-TNFα 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：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語  

Myeloid sarcoma (MS), which involves extramedullary lesions, is classified as a unique subtype of acute myeloid leukemia (AML). At present, no standard treatments for MS have been established. The patient was an 89-year-old man with myelodysplastic syndrome-excess blast-2 (MDS-EB-2) with a 2-year history of intermittent treatment with azacitidine (AZA) during a 4-year history of MDS. He developed painful cutaneous tumors 8 months after the second discontinuation of AZA. They were refractory for antibiotics and topical tacrolimus hydrate. A tumor biopsy was performed, and the histological findings of the tumor lesion showed a proliferation of tumor cells that were positive for myeloperoxidase and CD68 and negative for CD4 and CD123. The patient was diagnosed with MDS-associated MS. MDS-EB-2 quickly progressed to AML with the appearance of peripheral blood blasts and 25% bone marrow blasts. Monotherapy with reduced-dose AZA (37.5 mg/m2 for 7 days, every 4-6 weeks) was restarted, and the MS quickly disappeared. The patient's MS was successfully treated with 16 cycles of AZA treatment over a 22-month period. There have been 10 reported cases in which MS was successfully treated with AZA. Among the 10 cases, the patient in the present case was the oldest. Treatment with reduced-dose AZA should be considered as a therapeutic option for MS in elderly patients with MDS, especially patients who are ineligible for intensive chemotherapy.

DOI： 10.1155/2021/6640597

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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：英語   掲載種別：研究論文（学術雑誌）  

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, and en bloc resection of the tumor was successfully achieved. OUTCOMES: The histological findings showed two distinct components: neuroendocrine carcinoma (NEC) and well-differentiated adenocarcinoma, which comprised ∼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）  

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）  

We previously performed a randomized controlled trial (RCT) comparing targeted and random biopsy in neoplasia detection in patients with ulcerative colitis (UC), which showed the short-term effectiveness of targeted biopsy with one-time colonoscopy. In this retrospective cohort study, we investigated the long-term effectiveness of targeted biopsy in tertiary care hospitals, using the follow-up data from patients with UC for ≥ 8 years who had enrolled in the initial RCT. The primary outcome was death from colorectal cancer (CRC). Secondary outcomes were advanced neoplasia (CRC or high-grade dysplasia) and colectomy due to neoplasia after the RCT. We compared these outcomes between target and random groups. Data on 195 of the 221 patients (88.2%) enrolled in the previous RCT were collected from 28 institutions between 2008 and 2019. No patients died of CRC in either group, with a median 8.8-year follow-up demonstrating a robustness for targeted biopsy in terms of CRC death prevention. Advanced neoplasia was detected in four and three patients in the target and random groups, respectively. Colectomy was required due to neoplasia in three patients in each group. The chance of developing CRC in patients with a negative colonoscopy was low, and the targeted biopsy appeared effective in this population. Conversely, patients found with low-grade dysplasia at initial RCT have 10-fold higher risk of progression to high-grade dysplasia and/or CRC. Ten extracolonic malignancies were observed during the follow-up, resulting in four deaths. Panchromoendoscopy was used only in 4.6% and targeted biopsy was only performed in 59.1% of colonoscopies. We recommend targeted biopsy rather than > 33 random biopsies in real-world settings under adequate observation by specialists.

DOI： 10.3390/jcm9072286

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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）  

RNA regulation mediating RNA-binding proteins (RBPs) have been shown to be related to the maintenance of homeostasis as well as cancer progression. However, the tumor-associated functions as well as the detailed mechanisms underlying the anti-tumor effects of most RBPs have yet to be explored. We herein report that the phosphorylated heterogeneous ribonucleoprotein (hnRNP) A0 promotes mitosis through the RAS-associated protein 3 GTPase-activating protein catalytic subunit 1 (RAB3GAP1)-Zeste white 10 interactor (ZWINT1) cascade. The downregulation assay of 20 representative hnRNPs, a major family of RNA-binding proteins, in colorectal cancer cells revealed that hnRNPA0 is a strong regulator of cancer cell growth. The tumor promotive function of hnRNPA0 was confirmed in gastrointestinal cancer cells, including pancreatic, esophageal, and gastric cancer cells, but not in non-cancerous cells. Flow cytometry and Western blotting analyses revealed that hnRNPA0 inhibited the apoptosis through the maintenance of G2/M phase promotion in colorectal cancer cells. A comprehensive analysis of mRNAs regulated by hnRNP A0 and immunostaining revealed that mitotic events were regulated by the hnRNPA0-RAB3GAP1 mRNA-mediated ZWINT-1 stabilization in colorectal cancer cells, but not in non-tumorous cells. The interaction of hnRNP A0 with mRNAs was dramatically changed by the deactivation of its phosphorylation site in cancer cells, but not in non-tumorous cells. Therefore, the tumor-specific biological functions characterized by the abnormal phosphorylation of RBPs are considered to be an attractive target for tumor treatment.

DOI： 10.1038/s41419-020-2439-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The goal of ulcerative colitis (UC) treatment has recently been shown to be "mucosal healing," as no drug directly induces mucosal healing. Probiotics possess sufficient safety, but their efficacy in the treatment of UC remains controversial because of the influence of intestinal conditions. It is believed that the identification of bioactive molecules produced by probiotics and their application will help to solve this issue. We therefore identified a probiotic-derived long-chain polyphosphate as a molecule enhancing the intestinal barrier function. This study demonstrated that long-chain polyphosphate exhibited antiinflammatory effects in a human macrophage and interleukin-10 knockout transfusion mouse model. The first-in-human trial showed that 7 of the 10 enrolled patients acquired clinical remission, 4 of whom achieved endoscopic remission despite a history of treatment with anti-tumor necrosis factor (TNF)-α agents. No adverse reactions were observed. Long-chain polyphosphate might be useful for the treatment of refractory UC, even in patients with failure or intolerance to anti-TNF-α therapy.

DOI： 10.1002/cpt.1628

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記述言語：英語  

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：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12029-018-0078-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Steroid therapy is primarily used to prevent esophageal stricture after endoscopic submucosal dissection (ESD). However, esophageal stricture can still occur after preventive therapy, and the effect of preventive steroid therapy cannot be predicted before stricture formation. This study aimed to clarify the risk factors for esophageal stricture after preventive steroid therapy. METHODS: This was a retrospective study conducted at three institutions. From January 2011 to February 2018, 28 large-sized SENs in 26 patients who had a mucosal defect that involved more than three-quarters of the esophageal circumference were enrolled. We classified white coats on artificial ulcers after esophageal ESD into three groups (thin, moderately thick, thick) based on endoscopic images obtained on postoperative day 7. RESULTS: The white coat status on the artificial ulcer after ESD was a significant risk factor for post-ESD stricture (p < 0.05). The stricture rates in patients with thin, moderately thick and thick white coats were 10.0, 36.4 and 85.7%, respectively. When thin and moderately thick white coats were combined, the stricture rate was 23.8%. The rate of stricture in lesions with thick white coats was significantly higher than that in patients with thin white coats or thin to moderately thick white coats (p < 0.05). The multivariate analysis revealed that the white coat status was an independent factor related to esophageal stricture (odds ratio 13.70, 95% confidence interval 1.22-154.0; p = 0.034). CONCLUSIONS: The thickness of the white coat is a useful marker for predicting the risk of post-ESD stricture and the effectiveness of preventive steroid therapy.

DOI： 10.1007/s10388-019-00659-y

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記述言語：英語   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2019.03.1110

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記述言語：英語   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：研究論文（学術雑誌）  

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：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：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.14309/ajg.0000000000000069

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1159/000495289

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記述言語：英語  

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）  

BACKGROUND/AIMS: Venous thromboembolism (VTE) is a major extraintestinal manifestation in inflammatory bowel disease (IBD), regarded as an independent risk factor for VTE according to reports from Western countries. However, the incidence and risk factors of VTE in Asian IBD patients are not fully understood. We aimed to reveal the incidence and risk factors of VTE in Japanese IBD inpatients. METHODS: The incidence of VTE in inpatients with IBD (n=340), gastrointestinal cancers (n=557), and other gastrointestinal diseases (n=569) treated at our hospital from 2009 to 2013 was retrospectively investigated. The characteristics and laboratory data of IBD inpatients with and without VTE were compared in univariate and multivariate analyses. Clinical courses of VTE in IBD were surveyed. RESULTS: VTE was detected in 7.1% of IBD inpatients, significantly higher than in gastrointestinal cancer inpatients (2.5%) and inpatients with other gastrointestinal diseases (0.88%). The incidence of VTE in ulcerative colitis (UC) patients (16.7%) was much higher than that in those with Crohn's disease (3.6%). In the univariate analysis, the risk factors were an older age, central venous catheter, prednisolone, surgery, low serum albumin, high serum C-reactive protein and D-dimer. According to a multivariate analysis, >50 years of age and surgery were the only risk factors. The in-hospital mortality rate of IBD inpatients with VTE was 4.2%. CONCLUSIONS: The incidence of VTE with IBD, especially UC, was found to be high compared with other digestive disease, which was almost equivalent to that of Western countries. The efficacy of prophylaxis needs to be investigated in Asian IBD patients.

DOI： 10.5217/ir.2018.16.3.416

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記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.14309/00000434-201802001-00107

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers. METHODS: The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction. RESULTS: The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5-20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022). CONCLUSIONS: The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).

DOI： 10.1186/s12885-018-4006-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4103/eus.eus_90_17

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記述言語：英語  

BACKGROUND: Takayasu's arteritis (TA) is a large-vessel vasculitis pathologically characterized by granulomatous necrotizing vasculitis with giant cells. Although the cause of TA is still unclear, genetic factors as well as immunological abnormalities, particularly the overactivation of Th1 and Th-17, are considered to play important roles in the pathogenesis of this disease. Eosinophilic gastroenteritis (EGE) is a type of refractory inflammation in which numerous eosinophils infiltrate the inflammatory area. It is known that the overactivation of Th2 is associated with the pathogenesis of EGE, although the cause of EGE is still unclear. The immunological abnormalities in TA are therefore thought to be different from those in EGE. To date, no cases of complication of TA and EGE have been reported. CASE PRESENTATIONS: An 18 year-old female was diagnosed with EGE and treated with prednisolone. At 6 months after completion of the treatment, the patient experienced chest pain, and was diagnosed with TA. TH1 and TH17 immunity are thought to be involved with TA, while TH2 are considered to be involved with EGE. In this case, the expression of IL-17 mRNA in the colon mucosa greatly decreased after prednisolone treatment for EGE. CONCLUSIONS: This is the first report of TA complicated with EGE, and the overactivation of TH17 is considered to be associated with the pathogenesis of these two diseases.

DOI： 10.1186/s13099-018-0251-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Helicobacter pylori (H. pylori) eradication rarely develops into antibiotic-associated hemorrhagic colitis (AAHC), in which the etiology of colitis remains unclear. We herein report a rare case of AAHC caused by second-line therapy for H. pylori eradication. RESULTS: A 65-year-old female was administered second-line therapy for H. pylori composed of 1500 mg of amoxicillin, 500 mg of metronidazole and 40 mg of vonoprazan for 7 days because of first-line therapy failure. A day after completing second-line therapy, she complained of abdominal pain and hematochezia. Colonoscopy revealed a hemorrhage and edematous mucosa with no transparent vascular pattern in the transverse colon. A bacterial culture detected Klebsiella oxytoca (K. oxytoca), but no other pathogenic bacteria. A drug-induced lymphocyte stimulation test (DLST) showed positive reactions for both amoxicillin and metronidazole. According to these findings, the patient was diagnosed with AAHC. Bowel rest for 6 days relieved her abdominal pain and hematochezia. CONCLUSIONS: The present case developed AAHC caused by second-line therapy for H. pylori eradication. The pathogenesis is considered to be associated with microbial substitution as well as a delayed-type allergy to antibiotics, suggesting that AAHC is a potential adverse event of second-line therapy for H. pylori eradication.

DOI： 10.1186/s12941-017-0230-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Crohn's disease (CD) is a type of chronic inflammatory bowel disease (IBD) associated with ulceration, and the main foci of the inflammation in CD patients are typically the terminal ileum and colon. However, in the upper gastrointestinal tract (GIT), including the esophagus, stomach and duodenum, inflammatory lesions are also detected as well, with a relatively high frequency (30-75%). Recent advances in imaging modalities, including endoscopy, have aided in the diagnosis of CD. Various lesions, including aphtha, erosion, ulcers, bamboo-joint-like appearance and notch-like appearance, are detected in the upper GI of CD patients. Of these lesions, the bamboo-joint-like appearance in the gastric cardiac region and notch-like appearance in the second portion of the duodenum are highly specific for CD, regardless of the disease activity at other sites. These two findings, particularly a bamboo-joint-like appearance, have therefore been considered as potential biomarkers for CD. Although proton pump inhibitors (PPIs) are administered as an initial treatment for upper GIT lesions of CD, the efficacy of this treatment remains controversial. The administration of mesalazine, steroids, immunosuppressant and biologic agents is expected to be effective for treating such lesions.

DOI： 10.1007/s12328-017-0759-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

RATIONALE: Gastric adenocarcinoma of fundic gland mucosa type (GA-FGM) is a rare tumor composed of atypical cells with differentiation toward the fundic gland as well as the foveolar epithelium. Including our case, only 9 cases of GA-FGMs were reported from 2010 to 2016. CONCERNS OF THE PATIENT: An 87-year-old man was referred to our institution for endoscopic resection of a gastric lesion. The tumor was classified as type 0-I + IIa according to the Paris classification. Magnifying endoscopy with narrow band imaging (ME-NBI) revealed different structures of crypts and vessels among the components, illustrating the collision of 2 types of gastric cancer. INTERVENTIONS: We performed endoscopic submucosal dissection and successfully removed the tumor en bloc. OUTCOMES: The histological findings differed markedly between the 0-I lesion and the 0-IIa lesion. The superficial part of the 0-I lesion consisted of a papillary structure, and the deeper part consisted of a tubular structure that showed inverted downward growth to the submucosal layer with the lamina muscularis mucosae. Immunohistochemically, the superficial part of the 0-I lesion was positive for MUC5AC, which had differentiated to foveolar epithelium. The deeper part was positive for pepsinogen-I and MUC6, which had differentiated to fundic gland. The 0-I lesion was diagnosed as gastric phenotype of adenocarcinoma differentiated to fundic gland mucosa with upward growth in the superficial part and downward growth in the deeper part. The 0-IIa lesion was composed of a tubular structure positive for MUC2, and it was diagnosed as an intestinal phenotype of well differentiated adenocarcinoma. The boundary was clear, and no transitional tissue was observed between the 0-I and 0-IIa lesions, suggesting that the 0-I + IIa lesion was a gastric collision tumor of GA-FGM and well differentiated adenocarcinoma. LESSONS: We herein report the first case of inverted GA-FGM colliding with well differentiated adenocarcinoma. ME-NBI can be used to diagnose GA-FGM even if the lesion collides with other types of adenocarcinoma.

DOI： 10.1097/MD.0000000000007080

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ferrichrome is known to be a siderophore, but it was recently identified as a tumor-suppressive molecule derived from Lactobacillus casei ATCC334 ( L. casei). In the present study, we investigated the effects of ferrichrome in gastric cancer cells. Cell lines and xenograft models treated with ferrichrome demonstrated growth suppression. The expression levels of cleaved poly (adenosine diphosphate-ribose) polymerase, and cleaved caspase-9 were increased by ferrichrome treatment. Although the tumor-suppressive effects of ferrichrome were almost completely diminished by the iron chelation, the reduction in the intracellular iron by ferrichrome did not correlate with its tumor-suppressive effects. An exhaustive docking simulation indicated that iron-free ferrichrome can make stable conformations with various mammalian molecules, including transporters and receptors. In conclusion, probiotic-derived ferrichrome induced apoptosis in gastric cancer cells. The iron binding site of ferrichrome is the structure responsible for its tumor suppressive function.

DOI： 10.1177/1010428317711311

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記述言語：英語   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）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Image-enhanced endoscopy (IEE) has been developed and is applied in the clinical setting throughout the world. Most reports regarding IEE have evaluated the efficacy of narrow-band imaging (NBI) in the diagnosis of gastrointestinal disorders. Although autofluorescence imaging (AFI) is a form of IEE, its usefulness remains unclear. The present review focused on the efficacy of AFI in the diagnosis of colorectal disease, particularly neoplasia and ulcerative colitis (UC). AFI-based diagnoses are made via the subjective judgment of the color on the monitor. The efficacy of AFI in detection and differentiation in patients with colorectal neoplastic lesions remains controversial, which may be dependent on the study design and the diagnostic procedures. Although the number of the reports related to UC is very small, most suggest that AFI is effective in UC patients. AFI is distinct from other modalities in that it can quantitatively assess the lesion based on the fluorescence intensity without any morphological assessments. AFI could be useful for patients with colorectal disease.

DOI： 10.1007/s12328-016-0658-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The pathogenesis of autoimmune pancreatitis is unknown. In the present study we used high-throughput sequencing with next generation sequencing to identify the candidate genes associated with AIP. A total of 27 type 1 AIP patients and 30 healthy blood donors were recruited, and DNA samples were isolated from their mononuclear cells. A high-throughput sequencer with an original custom panel of 1031 genes was used to detect the genetic variants in each sample. Polymorphisms of CACNA1S (c.4642C>T), rs41554316, rs2231119, rs1042131, rs2838171, P2RX3 (c.195delG), rs75639061, SMAD7 (c.624delC) and TOP1 (c.2007delG), were identified as candidate genetic variants in patients with type 1 AIP. P2RX3 and TOP1 were significantly associated with AIP, even after adjusting bay means of Bonferroni's correction. In addition, we also identified eight candidate genetic variants that were associated with the relapse of type 1 AIP, namely: rs1143146, rs1050716, HLA-C (c.759_763delCCCCCinsTCCCG), rs1050451, rs4154112, rs1049069, CACNA1C (c.5996delC) and CXCR3 (c.630_631delGC). Finally polymorphisms of rs1050716 and rs111493987 were identified as candidate genetic variants associated with extra-pancreatic lesions in patients with type 1 AIP. These candidates might be used as markers of AIP susceptibility and could contribute to the pathogenesis of type 1 AIP.

DOI： 10.1016/j.bbrep.2016.03.005

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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  

全消化管に病変が出現するクローン病では、上部消化管病変が高頻度に見られる。竹の節状外観は、胃噴門部から胃体部の小彎にかけて襞を横切る亀裂状の陥凹とされている。クローン病診断における竹の節状外観の有用性を検討するために、上部消化管内視鏡画像を用いて3名の観察者に臨床情報をブラインドにして研究を行った。観察者それぞれのクローン病診断における竹の節状外観の感度は30.5%、56.9%、51.4%で、特異度は99.6%、98.5%、99.3%であった。したがって竹の節状外観はクローン病患者の拾い上げには十分に貢献しないが、本所見を認めたときはクローン病の可能性を考えて検査を進める必要がある。(著者抄録)

DOI： 10.11405/nisshoshi.113.1208

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J01118&link_issn=&doc_id=20160726150006&doc_link_id=1390001206403545472&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001206403545472&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To compare previously reported randomized controlled studies (RCTs) of cold and hot polypectomy, we systematically reviewed and clarify the utility of cold polypectomy over hot with respect to efficacy and adverse events. METHODS: A meta-analysis was conducted to evaluate the predominance of cold and hot polypectomy for removing colon polyps. Published articles and abstracts from worldwide conferences were searched using the keywords "cold polypectomy". RCTs that compared either or both the effects or adverse events of cold polypectomy with those of hot polypectomy were collected. The patients' demographics, endoscopic procedures, No. of examined lesions, lesion size, macroscopic and histologic findings, rates of incomplete resection, bleeding amount, perforation, and length of procedure were extracted from each study. A forest plot analysis was used to verify the relative strength of the effects and adverse events of each procedure. A funnel plot was generated to assess the possibility of publication bias. RESULTS: Ultimately, six RCTs were selected. No significant differences were noted in the average lesion size (less than 10 mm) between the cold and hot polypectomy groups in each study. Further, the rates of complete resection and adverse events, including delayed bleeding, did not differ markedly between cold and hot polypectomy. The average procedural time in the cold polypectomy group was significantly shorter than in the hot polypectomy group. CONCLUSION: Cold polypectomy is a time-saving procedure for removing small polyps with markedly similar curability and safety to hot polypectomy.

DOI： 10.3748/wjg.v22.i23.5436

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Squamous cell carcinoma of the extrahepatic bile duct is quite rare. A 77-year-old woman with jaundice and general fatigue was referred to our hospital. Multiphase contrast-enhanced computed tomography visualized a 17-mm solid mass in the junction of the cystic and common bile ducts. The patient underwent pylorus-preserving pancreaticoduodenectomy. The pathological findings demonstrated keratin-positive poorly differentiated squamous cell carcinoma of the extrahepatic bile duct (T3N0M0, stage IIIA). Although adjuvant chemotherapy with gemcitabine was administered, the patient exhibited local recurrence at the site of anastomosis of biliojejunostomy 20 months after resection and died 32 months after resection.

DOI： 10.2169/internalmedicine.55.6226

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記述言語：英語  

METHODS: Pneumocystis carinii pneumonia occasionally appears in immunodeficient patients. While several reports have shown that Pneumocystis carinii pneumonia occurred in the early phase of starting infliximab treatment in patients with Crohn's disease (CD), the present case suggests for the first time that an increased dosage of infliximab may also lead to pneumonia. RESULTS: A 51-year-old male had been taking 5 mg of infliximab for the treatment of CD for 10 years with no adverse events. Beginning in September 2013, the dose of infliximab had to be increased to 10 mg/kg because his status worsened. Thereafter, he complained of a fever and cough, and a CT scan revealed ground-glass opacities in the lower lobes of the bilateral lung with a crazy-paving pattern. Bronchoscopy detected swelling of the tracheal mucosa with obvious dilations of the vessels. A polymerase chain reaction using a bronchoalveolar lavage fluid sample detected specific sequences for Pneumocystis jirovecii; thus he was diagnosed with Pneumocystis carinii (jirovecii) pneumonia. After discontinuing infliximab and starting antibiotic treatment, his symptoms and CT findings were dramatically improved. CONCLUSIONS: The administration of an increased dosage of infliximab can cause Pneumocystis carinii pneumonia in CD patients.

DOI： 10.1186/s13099-016-0086-4

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記述言語：英語   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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

While the progress of chemotherapy and molecular targeted therapy has improved the outcome of colorectal cancer patients, the mortality of colon cancer remains high, indicating the need to develop novel therapeutic targets for improving the outcome of colon cancer. Heterogeneous ribonucleoprotein A1 (hnRNP A1) is highly expressed in colorectal cancer and its expression correlates with malignant transformation. In this study, we performed a microarray analysis with the RNA immunoprecipitation (RNA-IP) method and identified hnRNP A1-interacting miRs, including miR-26a and -584, in a colorectal cancer cell line, SW620. A SRB assay revealed the tumor suppressive effect of miR-26a and -584, and the tumor suppressive effect of these miRs was diminished by the downregulation of hnRNP A1. The combined method of a transcriptome analysis and RNA-IP revealed hnRNP A1-interacting mRNAs, including cyclin dependent kinase 6 (CDK6). A Western blot analysis revealed the downregulation of CDK6 in miR-26a and -584 overexpression cells, as well as hnRNP A1 knockdown cells. The binding assay indicated that the binding of hnRNP A1-CDK6 mRNA was reduced by transfection of miR-26a and -584. The expression of cleaved caspase-3 was induced in miR-26a and -584 overexpression cells. These data indicate that miR-26a and -584 inhibit the binding of hnRNP A1-CDK6 mRNA and induce colorectal cancer cell apoptosis.

DOI： 10.1016/j.bbrc.2015.10.055

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Probiotics exhibit beneficial functions for host homeostasis maintenance. We herein investigated the mechanism by which Lactobacillus brevis-derived poly P exhibited a beneficial function. Immunostaining indicated that poly P was captured in the plasma membrane via integrin β1 in Caco2/bbe cells. The uptake of poly P was reduced by the inhibition of integrin β1 as well as caveolin-1, a major component of lipid rafts. The function of poly P, including the induction of HSP27 and enhancement of the intestinal barrier function, was suppressed by the inhibition of caveolin-1, illustrating that the function of poly P was mediated by the endocytic pathway. High-throughput sequencing revealed that poly P induced tumor necrosis factor alpha-induced protein 3, which contributes to cytoprotection, including upregulation of the intestinal barrier function. The present study demonstrates a novel host-probiotic interaction through the uptake of bacterial substance into host cells, which is distinct from pattern recognition receptor pathways.

DOI： 10.1016/j.bbrc.2015.09.159

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記述言語：英語   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：英語   掲載種別：研究論文（学術雑誌）  

Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-β1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly decreased by poly P treatment. The expression levels of TGF-β1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1β and TGF-β1 in Caco-2/BBE cells and of TNF-α in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation.

DOI： 10.1016/j.trsl.2015.02.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The role of hnRNP A1 in the onset of intestinal inflammation remains unclear. This study investigated the function of hnRNP A1 in mice enteritis models. METHODS: C57Bl6/J mice were intraperitoneally injected with anti-CD3 antibodies to develop enteritis. In the DSS-induced colitis group, the mice were allowed free access to 3% DSS solution in their drinking water for 5 days. 3H-mannitol flux and complementary DNA array tests were used to assess the intestinal barrier function and messenger RNA (mRNA) expression, respectively. Real-time PCR was performed after immunoprecipitation with anti-hnRNP antibodies to determine the specific mRNA binding of hnRNP A1. RESULTS: The hnRNP A1 expression was increased in the intestine of the mouse at 24 hours after treatment with anti-CD3 antibodies and 5 days after starting DSS administration. Small interfering RNA (siRNA) against hnRNP A1 exacerbated the intestinal injuries in both models. According to the microarray analysis, trefoil factor 2 (TFF2) was identified as a candidate molecule targeted by hnRNP A1 in the anti-CD3 antibody-induced enteritis group. Moreover, the binding between hnRNP A1 and TFF2 mRNA significantly increased in the enteritis mice, and the administration of siRNA against either hnRNP A1 or TFF2 exacerbated the degree of intestinal injury. In the DSS-induced colitis group, treatment with the siRNA of hnRNP A1 worsened the intestinal injury, while the expression of TFF3 did not change. CONCLUSIONS: hnRNP A1 improves intestinal injury in anti-CD3 antibody-induced enteritis mice through the upregulation of TFF2, which regulates apoptosis and enhances epithelial restoration, whereas this molecule ameliorates DSS-induced colitis through a different pathway.

DOI： 10.1097/MIB.0000000000000401

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Multiple myeloma is characterized by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal protein. However, the involvement of pancreas is a rare event. We herein report a rare case of pancreatic plasmacytoma, which was detected before the diagnosis of multiple myeloma.An 83-year-old male was referred to our hospital for further evaluation of obstructive jaundice and a pancreatic mass. A contrast-enhanced computed tomography (CT) scan revealed solid masses with homogenous enhancement in the pancreatic head and retroperitoneum. The histological findings of the retroperitoneal mass obtained by CT-guided biopsy showed multiple sheets of atypical plasma cells, which were positively immunostained for CD79a, CD138, and the κ light chain. Serum immunoelectrophoresis detected M-component of immunoglobulin A-κ, and the histological findings of the bone marrow revealed an abnormally increased number of atypical plasma cells with irregular nuclei and cytoplasmic vacuolation. The patient was therefore diagnosed to have multiple myeloma involving the pancreas and retroperitoneum. Although chemotherapy was performed, the patient died 6 months after the diagnosis.The pancreatic plasmacytoma was detected before the multiple myeloma in the present case. It is difficult to diagnose a pancreatic plasmacytoma without a history of multiple myeloma and related disease.

DOI： 10.1097/MD.0000000000000914

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: EMR and endoscopic submucosal dissection (ESD) are used frequently to remove colon neoplasms. However, the predominance of these procedures has not yet been thoroughly explored. OBJECTIVE: To compare the efficacy and adverse events related to EMR with those related to ESD for colon neoplasms. DESIGN: A meta-analysis of 8 studies published between 2005 and 2013. SETTING: Multicenter review. PATIENTS: Patients from 8 studies yielding 2299 lesions. INTERVENTIONS: EMR or ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection, curative resection, recurrence, and adverse events. RESULTS: The pooled odds ratios (OR) (OR [95% confidence interval]) for the tumor size, length of the procedure, en bloc resection, curative resection, recurrence, additional surgery, delayed bleeding, and perforation by ESD versus EMR were 7.38 (6.42-8.34), 58.07 (36.27-79.88), 6.84 (3.30-14.18), 4.26 (3.77-6.57), 0.08 (0.04-0.17), 2.16 (1.16-4.03), 0.85 (0.45-1.60), and 4.96 (2.79-8.85), respectively. LIMITATIONS: This analysis included only nonrandomized studies. CONCLUSION: The size of the tumor and rate of en bloc resection and curative resection were higher, and the rate of recurrence was lower in the ESD group versus the EMR group. However, in the ESD group, the procedure was longer, and the rate of additional surgery and perforation was higher, suggesting that the indications for ESD should therefore be rigorously determined in order to avoid such problems.

DOI： 10.1016/j.gie.2014.07.034

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUNDS: The efficacy of clipping for preventing the delayed bleeding after the removal of colon polyps is still controversial. In order to clarify this efficacy, a randomized controlled study was performed. METHODS: One hundred and fifty-six patients with colon neoplasms (288 lesions) were enrolled in the study. The patients were randomly divided into two groups: clipping or nonclipping groups using a sealed envelope method before the endoscopic resections. Eight specialists and nine residents were invited to perform this procedure. The risk factors and the rates of delayed bleeding after the endoscopic resections in each group were investigated. RESULTS: There were no significant differences in the bleeding rate between the clipping and nonclipping groups, while the length of the procedure was significantly longer and the cost was higher in the clipping group than in the nonclipping group. The rate of bleeding was significantly higher in cases with polyps 2 cm or larger and with a longer procedure time, while none of the other factors affected the bleeding rate. CONCLUSIONS: This randomized controlled study revealed no significant effect of prophylactic clipping for preventing delayed bleeding after the endoscopic resection of colon polyps.

DOI： 10.1155/2015/490272

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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.2014.12.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: No method for sufficiently making the differential diagnosis of intestinal lymphoma resembling lymphoid hyperplasia (LH) on endoscopy has yet been established. OBJECTIVE: The aim of this study was to evaluate the usefulness of narrow-band imaging (NBI) in diagnosing intestinal lymphoma. DESIGN: Prospective study. SETTING: Single-center study. PATIENTS: Sixty-one patients with primary or systemic lymphoma were enrolled in this study. INTERVENTIONS: The terminal ileum and entire colon were observed by using conventional endoscopy. NBI was subsequently performed when small polypoid lesions were detected. A decrease in the number of vascular networks (DVNs) and the presence of irregular vessels on the surface of the epithelia were defined as characteristic findings of intestinal lymphoma. The diagnostic accuracy of these 2 findings in distinguishing intestinal lymphoma from LH was examined. MAIN OUTCOME MEASUREMENTS: The ability to use NBI to distinguish intestinal lymphoma from LH. RESULTS: Two hundred ninety-four small polypoid lesions, including 59 lymphomas and 235 LH lesions, were detected. The rates of detecting DVNs and the presence of irregular vessels were significantly higher in the lymphoma samples (81.4% and 62.7%) than in the LH samples (25.5% and 4.7%). Based on these findings, the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values for differentiating intestinal lymphoma from LH were 88.8%, 62.7%, 95.3%, 77.1%, and 91.1%, respectively, which are significantly higher than those of conventional endoscopy. LIMITATIONS: Single-center study. CONCLUSION: DVNs and the presence of irregular vessels on NBI are thus considered to be useful findings for differentiating intestinal lymphoma from benign LH.

DOI： 10.1016/j.gie.2014.03.030

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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  

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）  

BACKGROUND & AIMS: Little is known about the genetic factors that contribute to the development of sessile serrated adenomas (SSAs). SSAs contain somatic mutations in BRAF or KRAS early in development. However, evidence from humans and mouse models indicates that these mutations result in oncogene-induced senescence (OIS) of intestinal crypt cells. Progression to serrated neoplasia requires cells to escape OIS via inactivation of tumor suppressor pathways. We investigated whether subjects with multiple SSAs carry germline loss-of function mutations (nonsense and splice site) in genes that regulate OIS: the p16-Rb and ATM-ATR DNA damage response pathways. METHODS: Through a bioinformatic analysis of the literature, we identified a set of genes that function at the main nodes of the p16-Rb and ATM-ATR DNA damage response pathways. We performed whole-exome sequencing of 20 unrelated subjects with multiple SSAs; most had features of serrated polyposis. We compared sequences with those from 4300 subjects matched for ethnicity (controls). We also used an integrative genomics approach to identify additional genes involved in senescence mechanisms. RESULTS: We identified mutations in genes that regulate senescence (ATM, PIF1, TELO2,XAF1, and RBL1) in 5 of 20 subjects with multiple SSAs (odds ratio, 3.0; 95% confidence interval, 0.9–8.9; P =.04). In 2 subjects,we found nonsense mutations in RNF43, indicating that it is also associated with multiple serrated polyps (odds ratio, 460; 95% confidence interval, 23.1–16,384; P = 6.8 x 10(-5)). In knockdown experiments with pancreatic duct cells exposed to UV light, RNF43 appeared to function as a regulator of ATMATRDNA damage response. CONCLUSIONS: We associated germline loss-of-function variants in genes that regulate senescence pathways with the development of multiple SSAs.We identified RNF43 as a regulator of the DNA damage response and associated nonsense variants in this gene with a high risk of developing SSAs.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Acute lower gastrointestinal hemorrhage originating from the appendix is rare and often intractable, because it is almost impossible to approach the bleeding point by endoscopy. We herein describe the first case of bleeding from the appendix, which was successively controlled by a therapeutic barium enema administered into the appendix. CASE PRESENTATION: A 71-year-old male visited our hospital because of melena. He has been receiving an anti-coagulation drug, ticlopidine hydrochloride, for 10 years. By an emergency colonoscopy, a hemorrhage was detected in the appendix, and the lesion responsible for the bleeding was regarded to exist in the appendix. Two hundred milliliters of 50 W/V% barium was sprayed into the orifice of the appendix using a spraying tube. The bleeding could thus be immediately stopped, and a radiological examination revealed the accumulation of barium at the cecum and the orifice of the appendix. The barium accumulation disappeared by the next day, and no obvious anal bleeding was observed. Two weeks after stopping the bleeding from the appendix, an appendectomy was performed to prevent any further refractory hemorrhaging. The patient has had no complaints of any abdominal symptoms or anal bleeding for 10 months. CONCLUSIONS: A therapeutic barium enema is a useful procedure to control bleeding from the appendix and to avoid emergency surgery, such as partial cecectomy and hemicolectomy.

DOI： 10.1186/1471-230X-13-152

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Barrett's esophagus (BE) is metaplastic columnar epithelium converted from normal squamous epithelia in the distal esophagus that is thought to be a precancerous lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux disease (GERD), and therefore gastric acid or bile acids are thought to be factors that cause epithelial cell damage and inflammation in the gastro-esophageal junction. The decrease of adherent junction molecules, E-cadherin has been reported to be associated with the progression of the Barrett's carcinoma, but the initiation of BE is not sufficiently understood. BE is characterized by the presence of goblet cells and occasionally Paneth cells are observed at the base of the crypts. The Paneth cells possess dense granules, in which human antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the cells. This study determined the roles of HD-5 produced from metaplastic Paneth cells against adjacent to squamous cells in the gastro-esophageal junction. A human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as a model of squamous cell in the gastro-esophageal junctions, and alterations of E-cadherin were investigated. Immunocytochemistry, flowcytometry, and Western blotting showed that the expression of E-cadherin protein was decreased. And a partial recovery from the decrease was observed by treatment with a CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in squamous cells was reduced by HD-5 using in vitro experiments. In gastro-esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore accelerate the initiation of BE.

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：(一社)日本内科学会  

70歳代女。黒色便が出現し、その後排便時に暗赤色の下血があり、ふらつきも認めたため救急搬送された。下部消化管内視鏡では出血源を認めなかったが、回腸末端より血液流出があり、小腸出血が疑われた。入院時には活動性出血は認めず、経過観察としたが徐々に貧血が進行し、大量の下血と血圧低下、Hbも減少したため、中等症以上の消化管出血と診断し、RCC(濃厚赤血球)輸血を行った。Dynamic CTでは、近位空腸に造影剤の血管外漏出を認め、空腸出血が示唆された。緊急血管造影を行ったところ、上腸間膜動脈根部より3・4番目の空腸枝より造影剤の血管外漏出を認めたため、スポンゼルにて塞栓術を行った。下血は持続し開腹術を考慮したが、経口的DBE(ダブルバルーン内視鏡)を行った。空腸に多数の大小様々な憩室を認め、口側から3個目の憩室内に露出血管を認め、クリッピングを行った。経過良好で完全止血と判断し、第9病日に退院した。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J01159&link_issn=&doc_id=20130820020020&doc_link_id=1390001206446375040&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001206446375040&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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掲載種別：研究論文（学術雑誌）  

This review introduces the methodology and characteristic findings of autofluorescence imaging (AFI). AFI is a simple procedure for identifying abnormal lesions as areas with a magenta color, thus making it possible to achieve an objective and reproducible diagnosis. Sufficient preparations, clear and enfaced images with the appropriate extension of the colon are important for making an accurate diagnosis of colon disorders with AFI. AFI is useful for discriminating colon neoplasia from non-neoplasia, evaluating dysplastic grades of colon adenoma and assessing the severity of ulcerative colitis. AFI thus provides important information for deciding on the necessity of endoscopic resection and the staging of lymphoma, and designing a therapeutic strategy for ulcerative colitis. AFI with a high-tracking and high-resolution system will be developed and is considered to be a powerful clinical option for making an endoscopic diagnosis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The precise role of microRNAs in inflammatory disease is not clear. The present study investigated the effect of microRNA (miR-146b) with respect to improving intestinal inflammation. METHODS: The microRNA profile in interleukin-10 deficient mice was examined using microRNA arrays and miR-146b was selected for the subsequent experiments. The expression vectors containing either the whole sequence of miR-146b or small interfering RNA for miR-146b were intraperitoneally administered to the dextran sodium sulfate (DSS)-induced colitis mouse. The expression levels of inflammation-related mediators were examined by the reverse transcriptase-polymerase chain reaction and western blotting analysis. Intestinal barrier function was evaluated by an ex vivo mannitol flux study. RESULTS: The overexpression of miR-146b activated the NF-κB pathway, improved epithelial barrier function, relieved intestinal inflammation in the DSS-induced colitis mice, and improved the survival rate of mice with lethal colitis. Furthermore, this amelioration of intestinal inflammation by miR-146b was negated by the inhibitor for the NF-κB pathway. The overexpression of miR-146b decreased the expression of siah2, which has a target sequence for miR-146b, and promoted the ubiquitination of TRAF proteins. This suggests that the up-regulation of NF-κB by miR-146b was mediated by inhibition of the ubiquitination of TRAF proteins upstream of NF-κB. CONCLUSIONS: miR-146b improves intestinal inflammation by up-regulating NF-κB as a result of the decreased expression of siah2, which ubiquitinates TRAF proteins. Modulation of the miR-146b expression is a potentially useful therapy for the treatment of intestinal inflammation via activation of the NF-κB pathway.

DOI： 10.1002/jgm.2717

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIMS: While biological drugs are useful for relieving the disease activity and preventing abdominal surgery in patients with Crohn's disease (CD), it is unclear whether the use of biological drugs in CD patients with no history of abdominal surgery is appropriate. We evaluated the effects of infliximab and other factors on extending the duration until the first surgery in CD patients on a long-term basis. METHODS: The clinical records of 104 CD patients were retrospectively investigated. The cumulative nonoperation rate until the first surgery was examined with regard to demographic factors and treatments. RESULTS: The 50% nonoperative interval in the 104 CD patients was 107 months. The results of a univariate analysis revealed that a female gender, the colitis type of CD, and the administration of corticosteroids, immunomodulators, or infliximab were factors estimated to improve the cumulative nonoperative rate. A multivariate analysis showed that the colitis type and administration of infliximab were independent factors associated with a prolonged interval until the first surgery in the CD patients with no history of abdominal surgery. CONCLUSIONS: This study suggests that infliximab treatment extends the duration until the first surgery in CD patients with no history of abdominal surgery. The early use of infliximab before a patient undergoes abdominal surgery is therefore appropriate.

DOI： 10.1155/2013/879491

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. These probiotic effects are considered to be displayed through the mediation of effective molecules derived from these bacteria because live bacteria as well as their conditioned media exhibit beneficial effects in many cases. However, many of the probiotic-derived molecules which mediate such benefits have so far been poorly characterized. We previously found that competence and sporulation factor (CSF) activates the Akt and p38 MAPK pathways and protects epithelial cells from oxidant stress in the mammalian intestine. The purpose of this study is to determine the CSF effect on reducing intestinal inflammation. METHODS AND RESULTS: A protein array demonstrated that CSF induced the anti-inflammatory cytokine, IL-10, and decreased the release of pro-inflammatory mediators, IL-4, IL-6 and CXCL-1, induced by TNF-α in Caco2/bbe cells. CSF also induced the cytoprotective protein Hsp 27 in Caco2/bbe cells. The histological score of intestinal inflammation in 2% dextran sodium sulfate (DSS)-treated mice with the administration of 10 nM CSF was significantly lower than that of control mice. CSF also improved the survival rate of mice treated with a lethal concentration of DSS. CONCLUSION: Therefore, CSF is a potentially effective treatment for intestinal inflammation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   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.

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）  

Activating mutations in the KRAS oncogene are common in colorectal cancer. However, the complete spectrum of KRAS targets that mediate its tumorigenic effect has not yet been fully delineated. We identified bone morphogenetic protein 4 (Bmp4), a transforming growth factor-β family member that regulates development and tissue homeostasis, as a new target of KRAS. In SW480, Hela, and 293 cells, oncogenic KRAS(V12) downregulated BMP4 RNA levels, a BMP4 promoter luciferase construct, and Bmp4 protein levels. The MEK inhibitor PD98059 but not the phosphatidylinositol 3-kinase inhibitor LY294002 blocked this downregulation of BMP4. To identify the region of the BMP4 promoter that mediated this regulation by KRAS, serial 5'-deletions of the promoter were generated. An inhibitory region was identified between -3,285 and -3,258 bp in the Bmp4 promoter. In summary, oncogenic KRAS can downregulate Bmp4 through a transcriptional pathway that depends on ERK. These findings point to a unique link between two pathways that are frequently altered in colon cancer.

DOI： 10.1152/ajpgi.00047.2011

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: The F index of the high-grade adenomas was significantly lower than that of the low-grade adenomas, hyperplasia, and normal mucosa (p < 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. CONCLUSIONS: 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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0031-1291502

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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：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0030-1256776

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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-α), interleukin (IL)-1β 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.

DOI： 10.1002/ibd.21597

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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：GEORG THIEME VERLAG KG  

Background and study aims: Conventional colonoscopy can result in unnecessary biopsy or endoscopic resection due to its inability to distinguish adenomas from hyperplastic polyps. This study therefore evaluated the efficacy of high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) in discriminating colon adenoma from hyperplastic polyps.
Patients and methods: This was a prospective multicenter study in patients undergoing AFI and NBI examinations. HRE, AFI, and NBI images were classified into two groups based on morphological characteristics, the predominant color intensities, and the visibility of meshed capillary vessels, respectively. Each of the endoscopic photographs were independently evaluated by a single endoscopist. The images were then assessed by three specialists and three residents, the latter having performed &lt; 500 colonoscopies and &lt; 30 NBI and AFI examinations. Diagnostic test statistics were calculated to compare the accuracy in differentiating colon adenoma from hyperplastic polyps for each method.
Results: A total of 183 patients were enrolled in the study and 339 adenomas and 85 hyperplastic polyps were identified. AFI and NBI could distinguish adenoma from hyperplastic polyps with an accuracy of 84.9% and 88.4 %, respectively, whereas HRE exhibited an accuracy of 75.9 %. In the 358 lesions in which the AFI diagnosis was consistent with that of NBI, the accuracy, sensitivity, and specificity were high, at 91.9 %, 92.7 %, and 92.9 %, respectively. During the study comparing specialists and residents, AFI and NBI dramatically improved the diagnostic accuracy of residents from 69.1% to 86.1% and 84.7 %, respectively.
Conclusions: Both AFI and NBI are considered to be feasible tools that can discriminate colon adenoma from hyperplastic polyps, and their use may be particularly beneficial for less-experienced endoscopists.

DOI： 10.1055/s-0030-1256510

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

記述言語：英語   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.

DOI： 10.1111/j.1443-1661.2011.01150.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/gut.2009.205526

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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）  

Henoch-Schönlein purpura (HSP) is a type of systemic vasculitis of the small vessels, which frequently involves the skin, kidney and gastrointestinal tract. While the typical intestinal features of HSP include diffuse mucosal redness, small ring-like petechiae and haemorrhagic erosions, tumour-like lesions are rarely observed. The current study presents a rare case of HSP with an intestinal tumour-like lesion in the caecum. The intestinal lesion caused fresh melaena, and was completely resolved with the administration of factor XIII as described in previously reported cases. It is important to immediately undergo proper treatment for improving tumour-like lesions which may cause severe complications, such as excessive haemorrhage and stricture.

DOI： 10.1136/bcr.08.2010.3251

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Amyloidosis occurs as a result of the extracellular deposition of protein fibrils in organs and tissues, thus causing mild to severe pathophysiological changes. The gastrointestinal tract is a common site of amyloid deposition. While intestinal amyloidosis frequently results in polypoid lesions, ulcerations, nodules and petechial mucosal haemorrhage, tumour-like lesions are rarely developed and infrequently diagnosed before the resection because of the difficulty in differentiating them from colon cancer. The authors herein reported a case of intestinal amyloid A amyloidosis with a complication of a tumour-like lesion endoscopically resembling a malignant lesion, which was completely diminished after 1 month of observation with bowel rest. Such conservative treatment is a feasible option to cure intestinal tumour-like lesions in patients with intestinal amyloidosis when no neoplastic change is histologically detected, possibly decreasing the need for surgery of the fragile mucosa.

DOI： 10.1136/bcr.01.2011.3775

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Percutaneous endoscopic jejunostomy (PEJ) has been developed and is considered to be a better method than percutaneous endoscopic gastrostomy for preventing the occurrence of aspiration pneumonia. However, the incidence of other complications associated with this procedure is less clear. We herein report a rare case with a small intestinal intussusception due to a PEJ placement. In this case, a radiologic examination with gastrografin was useful to detect the typical findings of a small intestinal intussusception, a beak-like filling defect, and identify the location of the lesion. An endoscopic examination that was carefully performed with a thin scope was effective to observe the ischaemic change of the small intestine and immediately determine the indication for surgical treatment. This case highlights the necessity to carefully manage patients with a PEJ placement, considering the risk of small intestinal intussusceptions when the patient complains of symptoms that are suspicious for an intestinal obstruction.

DOI： 10.1136/bcr.07.2010.3169

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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.2010.05.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Diphyllobothrium is a member of Cestoda family, which is the largest parasite of humans. The diagnosis of diphyllobothriasis is based on the detection of eggs in the stool. Because the remainder of the scolex causes a relapse in diphyllobothriasis, the scolex must be completely discharged to cure the parasite infection. However, the scolex or forefront of the Diphyllobothrium is difficult to detect with gastroduodenoscopy and colonoscopy, because most Diphyllobothrium attach to the jejunal wall. In the present case, capsule endoscopy detected proglottids as well as forefront of the parasite at jejunum. Based on the results of capsule endoscopy, the patient underwent additional vermifuge (anthelminthic) treatment to cure the diphyllobothriasis and discharged a worm measuring 3 m in length with a scolex. Capsule endoscopy is a practical option to determine whether additional vermifuge treatment is required through the detection of the proglottids as well as a scolex or forefront of the parasite.

DOI： 10.1136/bcr.05.2010.3023

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We developed a novel method of methylation-specific PCR (MSP) using immunoprecipitation with anti-histone antibody (IP-MSP) to efficiently detect serum methylated DNA tightly bound to de-acetylated histones. MATERIALS AND METHODS: The detection limit of IP-MSP for p16 methylation was determined with a standard made by cell line (SKCO-1) lysate. p16 methylation of tumor and/or serum of 51 colorectal cancers and 10 adenoma patients, and 10 healthy volunteers was detected with conventional MSP or IP-MSP. RESULTS: IP-MSP detected p16 methylation from 0.5pg/mul of the cell lysate. The sensitivity of IP-MSP for detecting serum p16 methylation in 27 patients with tumors characterized by p16 methylation was significantly higher than that with conventional method (81% versus 59%), particularly in Stage II patients (91% versus 45%). IP-MSP detected no p16 hypermethylation in sera of adenoma patients and volunteers. CONCLUSIONS: IP-MSP is thus considered to be a promising procedure to detect serum methylated DNA in colorectal cancer patients.

DOI： 10.1016/j.canep.2010.01.004

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記述言語：日本語   掲載種別：研究論文（その他学術会議資料等）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Collagenous colitis (CC) is one of the causes of undefined watery diarrhea, which is histologically accompanied by thickening of the subepithelial collagen layer. CC associated with lansoprazole normally occurs within several weeks after initial administration, but no case presenting after long-term administration of lansoprazole has yet been reported. A 77-year-old male with 6-year history of administration of lansoprazole complained of watery diarrhea and weight loss. Colonoscopy revealed disappearance of vascular networks and red spots in the sigmoid colon. Biopsy specimen showed erosion and collagen bands thickened, so the patient was diagnosed as CC. After lansoprazole discontinuation, the watery diarrhea disappeared and histological abnormalities improved.

DOI： 10.1007/s12328-009-0126-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein present a quite atypical case of primary gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma in the transverse colon. Computed tomography and endoscopic ultrasonography revealed diffuse thickening of the wall, and colonoscopy showed a white-colored mucosa with reduced superficial vessels in the entire transverse colon. The lesion was diagnosed as MALT lymphoma by pathological examination of the biopsied specimen. Secondary macroglobulinemia of IgM-kappa type was also found in the present case. After chemotherapy and radiation, the lesions in the transverse colon improved and the patient has been in good condition without any evidence of recurrence for more than 1 year.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Intestinal metaplasia is considered to be a precursor lesion in both Barrett's and intestinal-type gastric cancer. The aim was to clarify the differences in molecular pathology between specialized intestinal metaplasia (SIM) in Barrett's oesophagus (BO), cardiac (CIM) and gastric intestinal metaplasia (GIM). METHODS AND RESULTS: Eighty-eight SIM cases with BO, 30 CIM cases and 52 GIM cases in patients with or without Helicobacter pylori infectionwere analysed for genetic instability and Das-1. Microsatellite instability and a loss of heterozygosity were evaluated at five microsatellite loci. The incidence of genetic instability was 55.7% in SIM, 40.0% in CIM and 23.1% in GIM, revealing a significant difference between SIM and GIM (P < 0.0005). For each microsatellite marker analysed, there were obvious differences in frequency among the three conditions. Das-1 reactivity was significantly higher in SIM than in CIM or GIM (P < 0.0001, both). Interestingly, both genetic instability and Das-1 reactivity in SIM showed a significantly higher incidence in patients with H. pylori infection than in those without (P < 0.005 and P < 0.01, respectively). CONCLUSIONS: SIM is distinct from CIM and GIM, and the pathogenesis of SIM, like that of GIM, is associated to some degree with H. pylori infection in a Japanese population.

DOI： 10.1111/j.1365-2559.2009.03370.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endoscopic mucosal resection (EMR) and endoscopic piecemeal resection (EPMR) are therapeutic options widely accepted for the treatment of colon adenoma, intramucosal cancer and minimally invasive submucosal cancer. Our retrospective investigation revealed that single EMR or EPMR with 2-channel procedure cured 913 (96.6%) of 945 flat and depressed tumors, verifying the significant role of certain procedures in the therapeutic strategy for colorectal neoplasm. Predicting the invasion depth and fibrotic change before resection are proposed to be necessary for improving complete resection rate of first EMR or EPMR. Hood, 2-channel method and the combination of EMR and circumferential mucosal incision are regarded to be practical procedures on EPMR.

DOI： 10.1111/j.1443-1661.2009.00861.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Genetic or epigenetic alterations in Barrett's esophagus (BE) with/without Helicobacter pylori (H. pylori) infection remain unclear. We examined the effects of H. pylori infection on genetic instability (GIN), the CpG island methylation status and a biomarker related to BE carcinogenesis. We analyzed 113 Japanese individuals with endoscopically suspected BE. The patients included, Group CLE (n = 25): no specialized intestinal metaplasia (SIM) in a columnar lined epithelium (control); Group BE (n = 88): all had SIM. Microsatellite instability and a loss of heterozygosity as GIN, the methylation status at hMLH1, E-cadherin, p16 and APC, and immunoreactivity using a monoclonal antibody (mAb) Das-1, which specifically reacts with BE, were evaluated. Nine additional patients with BE were prospectively followed up for 2 years after successful H. pylori eradication. The frequency of GIN, methylation at E-cadherin and APC, and mAb Das-1 reactivity in Group BE was significantly higher than that in Group CLE (p < 0.0001, p < 0.0001 and p < 0.005, and p < 0.0001, respectively). Furthermore, GIN, E-cadherin methylation and mAb Das-1 reactivity showed a significantly higher incidence in patients with H.pylori infection than in those without H. pylori infection (p < 0.01, p < 0.005, and p < 0.01, respectively). Interestingly, the patients from Group BE were observed to change to a stable state of molecular alterations in 60% for GIN, 42.9% for E-cadherin methylation and 55.6% for APC methylation, or a reduction of mAb Das-1 reactivity was noted in 25% following eradication. H. pylori infection may therefore affect these molecular alterations associated with the pathogenesis of BE, to some degree, in the Japanese population.

DOI： 10.1002/ijc.24092

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Small cell carcinoma of the oesophagus (SCCE) is an infrequent tumour associated with a poor prognosis. We herein propose the first case of SCCE treated by endoscopic mucosal resection (EMR) and its endoscopic images with narrow band imaging (NBI) and autofluorescence imaging (AFI). A 63-year-old man complained of a loss of appetite. An upper endoscopic examination revealed a 7 mm nodule located 33 cm from the incisors. A weakly stained area was shown by iodine staining. NBI detected brownish amorphous dots with irregular vessels on the surface of the nodule and AFI distinctly embossed the lesion magenta. A biopsy specimen obtained from the lesions revealed typical SCCE. The patient underwent EMR to remove the SCCE and thereafter remained in a state of clinical remission for 18 months. In summary, NBI and AFI may be useful for detecting and differentially diagnosing SCCE from the squamous cell carcinoma of the oesophagus. EMR is therefore considered to be a potentially useful therapeutic option for removing SCCE instead of performing an oesophagotomy.

DOI： 10.1136/bcr.06.2009.2048

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

An 83-year-old woman who was admitted to other hospital, was consulted us because of continuous tarry stool and abdominal fullness. On upper endoscopy, the submucosal tumor from greater curvature of gastric fornix invaginated into the duodenal bulbus, showing so-called "ball valve syndrome (BVS)". As the tumor incarcerted again on the following endoscoopy, she underwent laparoscopic partial gastrectomy. The submucosal tumor was diagnosed histologically as gastrointestinal stromal tumor (GIST) arising from the muscularis mucosae. This is the first report that GIST arising from the muscularis mucosae in gastric fornix showed a BVS.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The technical difficulties related to the insertion of a long intestinal tube into the jejunum under fluoroscopy present a considerable problem in patients with an intestinal obstruction. OBJECTIVE: To evaluate the usefulness of endoscopic long intestinal-tube placement with the ultrathin esophagogastroduodenoscope (UT-EGD). DESIGN: A prospective randomized clinical trial was conducted. PATIENTS: Twenty-eight consecutive patients who presented with an intestinal obstruction were included in the study. INTERVENTION: The UT-EGD was inserted nasally into at least the second portion of the duodenum or beyond. After a guidewire was introduced through the working channel, with fluoroscopic guidance, the UT-EGD itself was carefully removed with the guidewire left in place. Next, a hydrophilic intestinal tube was advanced over the guidewire into the jejunum, and then the guidewire was removed. MAIN OUTCOME MEASUREMENTS: Primary end points are the total procedure time, the radiation exposure time, and the rate of complications, all compared with the conventional method. RESULTS: The mean (+/-SD) total procedure time was 18.7 +/- 8.4 minutes for the UT-EGD method and 39.5 +/- 15.0 minutes for the conventional method, with a significant time difference between the 2 methods (P < .0005). The mean (+/-SD) radiation exposure time was also shorter with the UT-EGD method (11.1 +/- 6.0 minutes) than with the conventional method (30.3 +/- 13.7 minutes) (P < .0005). There were no complications, except for mild nasal bleeding with each method. CONCLUSIONS: The UT-EGD method has definite advantages in the placement of a long intestinal tube for patients with an intestinal obstruction in comparison with the conventional method.

DOI： 10.1016/j.gie.2008.01.043

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To clarify field cancerization in the stomach by genetic alterations, we studied 83 cases of intestinal-type gastric cancer (GC) and paired intestinal metaplasia (IM) distant from GC and 39 cases of chronic gastritis with IM (CG-IM) for genetic instability (GIN). Microsatellite instability (MSI) and loss of heterozygosity (LOH) were evaluated at 5 microsatellite loci. The incidence of GIN was 21% (8/39) in CG-IM, 48% (40/83) in GC-IM, and 65% (54/83) in GC and showed a significant difference among these 3 categories. By tumor location, MSI showed the highest incidence in GC and GC-IM with the tumor located in the upper third of the stomach. GIN in GC and GC-IM significantly increased with the progression of tumor invasion from mucosal to advanced cancer. GIN, especially LOH, was more frequently detected in cases with vs without lymphatic or vascular invasion and lymph node involvement in GC and GC-IM. The GIN of GC and GC-IM was significantly similar in relation to clinicopathologic features. Biologic detection of GIN in IM may be a surrogate marker for GC risk and for clinical evaluation of malignant potential. The condition is consistent with the hypothesis of field cancerization in the stomach.

DOI： 10.1309/DFLELPGPNV5LK6B1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

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記述言語：英語   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2007.03.989

Web of Science

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記述言語：日本語   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）  

We describe a case of acute myeloid leukemia (AML) showing myeloperoxidase (MPO)-positive and myeloid antigens negative. Although the leukemic cells showed few granules in May-Grünwald Giemsa staining, cytochemical MPO staining revealed that most of the blast cells strongly reacted with MPO. The leukemic cells did not express myeloid antigens (CD13, CD33), nor B-lymphoid or T-lymphoid antigens on the cell surface using flow cytometry, however. The cells did express CD34 and CD7. Discordant expression of MPO and myeloid antigens was also confirmed by electron microscopic MPO staining and by immunocytochemistry using a streptoavidin-biotin alkaline phosphatase labeling technique. Cytogenetic studies showed 46, XX, t(8
21) (q22
q22), del (9) (q22) in the bone marrow cells. In addition, AML1/ETO chimeric mRNA was detected from these cells. We summarize eight reported cases of MPO positive and myeloid antigens negative AML. Five of nine cases including our case had the same chromosomal abnormality of t(8
21) (q22
q22) and showed better prognosis than the other cases. © 1999 The Japanese Society of Hematology.

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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：(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：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：北海道医学会  

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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   出版者・発行元：(一社)日本癌学会  

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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：(一社)日本潰瘍学会  

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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  

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：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：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：(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：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)日本消化管学会  

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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：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)東京医学社  

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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   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   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：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：日本大腸検査学会  

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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：(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：(公社)日本薬学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

近年、炎症性腸疾患(IBD)の治療目標として粘膜治癒が求められるようになってきており、粘膜治癒を評価するうえで内視鏡は欠くことのできないmodalityである。内視鏡による評価は依然として通常内視鏡観察によるものが多く、IBDの粘膜炎症評価や再燃予測に有用である。また、現在では多くの内視鏡に拡大観察機能があることから色素拡大観察での評価もおこない、その所見を付加することによりIBD、とくに潰瘍性大腸炎に対する評価能の向上が期待される。(著者抄録)

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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   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：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：(公社)日本リハビリテーション医学会  

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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：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)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

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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：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)日本消化器がん検診学会  

びまん性発赤(以下、DR)は、Helicobacter pylori(以下、H.pylori)現感染を強く示唆する内視鏡所見であるが、機器の設定や内視鏡施行医の主観により判断が異なる問題点がある。そこで、画像解析ソフトによるDR数値化の有用性を検討した。上部消化管内視鏡検査及びH.pylori検査を行った115例を対象に、6名の内視鏡医(内視鏡専門医3名、非専門医3名)により後方視的に内視鏡画像でDR判定一致率(κ値)及びH.pylori判定正診率を検討したところ、前庭部と体部大彎の2画像評価では、一致率、正診率は0.31、55.8%、全画像評価の場合は、それぞれ0.43、67.7%と全画像評価で一致率が高く、H.pylori正診率も有意に高かった。非専門医と専門医で一致率、正診率を比較したところいずれも専門医が高かった。解析ソフトでDRを数値化した場合、一致率が0.93と最も高い結果であった。H.pylori正診率は64.1%と2画像評価より有意に高い結果であり、全画像評価と有意差は認めなかった。画像解析によるDRの数値化は内視鏡医間の一致率が向上することから検診での応用が期待される。(著者抄録)

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

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：(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：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：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：(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：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：(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：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：(公社)日本リハビリテーション医学会  

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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  

＜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：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)日本内科学会  

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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：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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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：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

潰瘍性大腸炎の内視鏡検査では白色光観察のほか,画像強調内視鏡(IEE)を組み合わせることで疾患の診断や,より詳細な重症度・治療効果の評価が行われてきている.IEEには消化管組織から出る微弱な自家蛍光を画像化し病理組織学的な炎症強度を数値として評価する客観性の高い自家蛍光内視鏡(AFI)や,粘膜表層の微細構造変化から炎症を評価する拡大内視鏡などがある.これらのIEEによる炎症の評価は病理組織学的活動性と相関するため,重症度や粘膜治癒の評価,再燃の予測が可能となり,最適な治療選択と長期の寛解維持へとつながることが期待される.(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：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.14309/00000434-201802001-00047

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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：日本語   出版者・発行元：北海道外科学会  

胃癌の内視鏡的治療は近年目覚ましく進歩している。以前は内視鏡的粘膜切除術(EMR)が内視鏡的治療において中心的な役割を果たしてきたが、内視鏡的粘膜下層剥離術(ESD)の登場によってEMRでは一括切除が困難であった病変も切除可能となり、現在胃癌に対する内視鏡的治療はESDが主流となっている。しかしESDは高い技術を要し、比較的長時間の治療手技であることから、病変によってはEMRを選択することで、治療時間短縮や不要なリスクを軽減できる場合もある。ESDの手技や用いるデバイスは年々進歩を遂げ、様々な工夫が行われているが、近年では、腹腔鏡と内視鏡を同時に用いて全層切除を行う新たな治療法も開発され注目されている。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01375&link_issn=&doc_id=20171031090006&doc_link_id=%2Fdc7hksrg%2F2017%2F006201%2F007%2F0029-0032%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdc7hksrg%2F2017%2F006201%2F007%2F0029-0032%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：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： 10.1016/S0016-5085(17)31144-7

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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：LIPPINCOTT WILLIAMS & WILKINS  

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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：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.2016.03.1026

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記述言語：日本語   出版者・発行元：(株)医学書院  

炎症性腸疾患における内視鏡検査は疾患の診断や鑑別のみならず,治療効果や経過の評価,治療方針の変更や継続,中止などの判断に重要な検査である.また,粘膜表層の微細構造を観察することのできる拡大内視鏡検査は,粘膜および粘膜下層を主体とした潰瘍性大腸炎の炎症の評価において,特に有用な手技であり,組織学的活動性,治癒過程の推移,再燃の予測が可能となる.潰瘍性大腸炎の拡大内視鏡所見を理解することで,粘膜治癒の評価を適切に行うことができ,症例ごとに最適な治療選択が可能となり,長期の寛解維持へとつながることが期待される.(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：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2016.03.466

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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   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：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)日本消化器がん検診学会  

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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.2015.03.1554

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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：(株)東京医学社  

大腸癌は腺腫からの悪性化が主な発生経路と考えられており、腺腫発見率が高いほど大腸癌のリスクを減らすことができる。自家蛍光内視鏡(autofluorescence imaging:AFI)は複雑な形態学的診断を単純化した検査方法で、異常の有無や程度を緑色とマゼンダ色の2色の色調変化として描出される。そのため、大腸上皮性腫瘍のスクリーニング検査において簡便に腫瘍を発見できることから、腺腫発見率上昇が期待される。当科の前向き試験では、特に平坦型や陥凹型腫瘍の発見や内視鏡初心者に有用性が高かった。また、AFIの色調変化を色度解析にて数値化することによって客観的で再現性の高い診断が可能となり、腫瘍と非腫瘍の鑑別、腫瘍異型度と内視鏡治療の必要性判断の情報となる。現在、AFIの問題点であった追従性や解像度が改善されてきており、今後の発展が期待される検査手技である。(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)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

完全摘除生検可能な大腸SM深部浸潤癌の術前診断における超音波内視鏡検査の有用性について解説した.超音波内視鏡検査は大腸癌の浸潤を垂直断面として直接観察できる唯一の検査法であり,組織上のSM浸潤距離をよく反映した.しかし,3,000μm以上のSM浸潤になると,浸潤距離の診断能が下がる傾向にあった.また,SM癌の深達度診断能は高いものの,MP癌については満足いくものではなく,その主な原因は超音波の深部減衰と考えられた.今後,低周波数の超音波内視鏡検査の併用も考慮し,より深部に浸潤したSM癌の浸潤距離診断能を向上させることが必要である.(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：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：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)先端医学社  

バレット食道は、逆流性食道炎に続発して発生、食道腺癌(バレット食道癌)の母地と考えられている。バレット食道やバレット食道癌の頻度はわが国でも増加する可能性がある。そのため、その病態を解明するモデル動物の開発は急務である。しかし、現状ではこの疾患病態を忠実に再現した動物モデルはない。現在用いられている動物モデルの大部分はラットとマウスであり、これらに外科的処置、発癌物質投与、さらに遺伝子改変などをおこなうことで、ヒトバレット食道やバレット食道癌を再現しようとしている。しかし、マウスやラットはヒトとの解剖学的な差異があることなどから、ヒトの病態を十分に再現できていないという問題が残っている。近年の遺伝子改変技術の進歩やマウスやラット以外の動物を用いるなどの工夫によって、ヒトでの本疾患病態を再現できる動物モデルが作製されつつある。(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：(株)メディカルレビュー社  

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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)日本内科学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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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)日本癌治療学会  

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記述言語：日本語   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：(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：(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：(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：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：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

自家蛍光内視鏡(Autofluorescence imaging;AFI)の検査手技や特徴的所見を中心に解説した。AFIは、異常所見を緑とマゼンタの2色の色調差として表現することで、複雑な形態学的診断を単純化した手技である。この特長を生かすことで、客観的で再現性の高い診断が可能となる。精度の高いAFI診断を行うには、十分な前処置のもと、病変を正面視し、適度な空気量で静止画を得ることが必須である。AFIの色調変化は、腫瘍と非腫瘍との鑑別、腫瘍の異型度、潰瘍性大腸炎の重症度を反映し、内視鏡治療の必要性の判断やリンパ腫の病期診断、炎症性腸疾患の治療方針の決定などに重要な情報を提供する。今後の機器の改良により、追従性や解像度が向上することで、より汎用性の高い内視鏡手技になるものと期待される。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00192&link_issn=&doc_id=20130128050009&doc_link_id=10.11280%2Fgee.55.58&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.55.58&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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：(有)科学評論社  

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記述言語：日本語   出版者・発行元：日本消化器免疫学会  

【背景・目的】DSS慢性腸炎モデルマウスに対する麦芽乳酸菌L.brevis SBC8803死菌体の治療効果を明らかにする。【結果】DSS慢性腸炎モデルマウスにL.brevis SBC8803死菌体を注腸投与したところ、1)腸管短縮を有意に抑制し、病理学的所見を有意に改善する。2)HSP25・70の発現を回復させる。3)TNF-α、IL-1βの発現を有意に抑制する。【まとめ】L.brevis SBC8803死菌体はHSPの発現誘導や炎症関連サイトカインの発現調節により慢性炎症に伴う腸管障害を軽減させる。炎症性腸疾患に対する新規治療薬としての臨床応用が期待される。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器がん検診学会  

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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：(株)先端医学社  

潰瘍性大腸炎における画像強調内視鏡の有用性と今後の展望について解説した。NBIは微細血管構造の観察にすぐれており、再生血管の多寡や構造異常を目安に疾患活動性の評価やdysplasiaの発見診断、質的診断に寄与する可能性がある。一方、AFIは、炎症細胞浸潤や浮腫、あるいは腫瘍細胞の有無などを包括的に反映し、単純な色調変化として描出することから、客観的な活動性の評価や腫瘍の発見診断に有用である可能性が示唆される。今後、十分なエビデンスをもつ臨床研究にもとづき、おのおのの画像強調内視鏡の診断的位置づけを確立するとともに、各診断手法の最適な組み合わせを模索する必要がある。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2011&ichushi_jid=J04938&link_issn=&doc_id=20111004400005&doc_link_id=%2Fae6ibdrd%2F2011%2F000503%2F007%2F0177-0184%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6ibdrd%2F2011%2F000503%2F007%2F0177-0184%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：(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：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)日本消化器がん検診学会  

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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：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：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：日本消化器免疫学会  

背景・目的;新規プロバイオティクスである麦芽乳酸菌(Lactobacillus brevis)SBC8803死菌の生理活性を解明するためにDSS腸炎モデルマウスを用いて検討をした。結果;麦芽乳酸菌SBC8803は急性炎症に伴う腸管の短縮を有意に抑制し、病理学的所見を改善させ、炎症性サイトカインである、TNF-α、IL-1β、IL-12を有意に抑制し、累積生存率を延長させた。総括;麦芽乳酸菌SBC8803死菌は抗炎症作用を有しており炎症性腸疾患などの消化器疾患への臨床応用の可能性がある。(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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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：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 CLINICAL ONCOLOGY  

DOI： 10.1200/jco.2011.29.4_suppl.212

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記述言語：日本語   出版者・発行元：(株)先端医学社  

Barrett食道癌は、食道扁平上皮から腸上皮化生を有しない円柱上皮化生粘膜、特殊腸上皮化生を経て生じると考えられており、特殊腸上皮化生は前癌病変と認識されている。これら一連の発癌過程においてエピジェネティクス異常の観点から解析が進み、発癌の各段階によってメチル化異常の頻度が変化しているだけでなく、遺伝子によっては発癌初期あるいは前癌病変であるBarrett食道の形成段階からメチル化異常を示すことが明らかとなった。さらに発癌促進因子であるH.pylori感染や胃・胆汁酸の逆流とメチル化異常との関連性や、ゲノム不安定性(GIN)とエピジェネティクス異常との関係も明らかにされ、Barrett食道癌の発生におけるエピジェネティクス異常の重要性が示唆される。また、近年盛んに研究されているマイクロRNA(miRNA)とBarrett食道/癌との関係についても明らかになってきており、このmiRNAの発現変化にもエピジェネティクス異常が密接に関係している可能性がある。Barrett食道癌の発生・進展においてエピジェネティクス異常はその主役をなすものであり、早期の診断マーカーとして、さらには治療のターゲットとして、今後の臨床応用が期待される。(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：(有)科学評論社  

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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：(株)先端医学社  

胃癌の発癌機構において、腸上皮化生は前癌病変と考えられ、その発現機序に関してゲノム不安定性(GIN)やメチル化異常に関するさまざまな解析がおこなわれ、これらの異常があった場合、染色体異常や遺伝子異常の蓄積が生じた結果、発癌初期に関与するとされている。一方、バレット食道および食道腺癌は、欧米では肥満をベースにした胃食道逆流症(GERD)の増加に伴い、著明に増加しているとされているが、わが国でもバレット食道の頻度は急激に増加し、内視鏡検査対象者のおよそ2割の頻度で認められているとの報告もあり、今後の食道腺癌の発生増加が懸念される。このバレット食道癌は、腸上皮化生を有しない円柱上皮化生粘膜から特殊腸上皮化生を経て生じるとされ、特殊腸上皮化生は前癌病変と認識されてきている。われわれは、今までおこなってきた胃癌の研究をもとに、発癌機構の類似したバレット食道癌の前癌病変である特殊腸上皮化生に注目してGIN、メチル化異常の解析をおこなってきた。GINの検討については、染色体構造の異常であるヘテロ接合性の消失(LOH)やミスマッチ修復遺伝子の異常によって引き起こされるマイクロサテライト不安定性(MSI)について、メチル化異常は遺伝子のプロモーター領域CpGアイランドにおけるメチル化異常の状態を検討することが一般的である。本稿では、われわれがおこなったバレット食道に関する検討を例にとり、これらの解析法について解説した。(著者抄録)

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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：日本語   出版者・発行元：(株)先端医学社  

潰瘍性大腸炎(ulcerative colitis:UC)はいまだに原因不明の疾患であり、根治的治療は確立されてはいない。拡大内視鏡を用いて粘膜表面の微細構造を観察することにより、UCの組織学的活動性の評価および再燃の予測が可能となる。とくに通常観察でMatts' grade 2相当の微細な変化のみの病変における活動性評価には、拡大観察がきわめて有用である。治療後の効果判定においても、拡大内視鏡所見を目安にすることにより、"粘膜治癒(mucosal healing)"が得られたかどうかを判断し、寛解維持期間の予測が可能である。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2010&ichushi_jid=J04938&link_issn=&doc_id=20100917430003&doc_link_id=%2Fae6ibdrd%2F2010%2F000403%2F004%2F0167-0174%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6ibdrd%2F2010%2F000403%2F004%2F0167-0174%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：(有)科学評論社  

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