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

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Language：English   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：(有)科学評論社  

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DOI： 10.14309/ajg.0000000000001367

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BACKGROUND: Involuntary weight loss related to cachexia is common in patients with advanced cancer, but the association between body composition changes and survival is still unclear in pancreatic cancer. METHODS: We retrospectively reviewed the clinical outcomes of 55 patients with advanced pancreatic cancer undergoing palliative therapy or best supportive care (BSC). The skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR) were calculated based on the cross-sectional area on two sets of computed tomography images obtained at cancer diagnosis and 1 month later before treatment. The prognostic value of body composition indexes at diagnosis and the changes in those indexes over 1 month was then evaluated. RESULTS: In total, 45 patients (81.8%) received chemotherapy, chemoradiation, or radiation therapy, whereas the remaining patients underwent BSC. There were 27 patients (49.1%) who had low SMI at cancer diagnosis. Univariate analysis showed no significant associations between the baseline body composition indexes including SMI, VATI, SATI, and VSR and survival. Meanwhile, male sex (HR, 2.79; 95% CI, 1.16-6.71, p = 0.022) and higher decrease in VATI over 1 month (HR, 2.41; 95% CI, 1.13-5.13, p = 0.023) were identified as independent risk factors for mortality in multivariate analysis. CONCLUSION: Rapid decline in VAT over 1 month is closely associated with poorer survival in unresectable advanced pancreatic cancer. A short-term assessment of body composition changes may be a rational approach to predict prognosis in these patients.

DOI： 10.1002/cam4.3964

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

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Language：English   Publisher：日本消化器病学会-甲信越支部  

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It is reported that an increase in aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon are major causes of diversion colitis. However, the precise pathogenesis of this condition remains unclear. The aim of the present study was to examine the microbiota, intestinal SCFAs, and immunoglobulin A (IgA) in the diverted colon. Eight patients underwent operative procedures for colostomies. We assessed the diverted colon using endoscopy and obtained intestinal samples from the diverted colon and oral colon in these patients. We analyzed the microbiota and SCFAs of the intestinal samples. The bacterial communities were investigated using a 16S rRNA gene sequencing method. The microbiota demonstrated a change in the proportion of some species, especially Lactobacillus, which significantly decreased in the diverted colon at the genus level. We also showed that intestinal SCFA values were significantly decreased in the diverted colon. Furthermore, intestinal IgA levels were significantly increased in the diverted colon. This study was the first to show that intestinal SCFAs were significantly decreased and intestinal IgA was significantly increased in the diverted colon. Our data suggest that SCFAs affect the microbiota and may play an immunological role in diversion colitis.

DOI： 10.1016/j.bbrep.2020.100892

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BACKGROUND/AIMS: Patients with achalasia have a high incidence of esophageal squamous cell carcinoma (ESCC), which may be associated with alterations in oral and esophageal microbiota caused by food stasis. This study compared the oral and esophageal microbiota of patients with achalasia before and after peroral endoscopic myotomy (POEM). It also compared patients with achalasia to those with ESCC. MATERIALS AND METHODS: The study prospectively examined 6 patients with achalasia and 14 with superficial ESCC. Oral samples obtained from the buccal mucosa using a swab and esophageal samples obtained from the mid-esophagus using a brush via endoscopy were analyzed by 16S rRNA metagenome sequencing. Additionally, endoscopic and histological findings of patients with achalasia before and after POEM were prospectively compared. RESULTS: In patients with achalasia, Streptococcus was most abundant in both the oral and the esophageal microbiota, and these microbiota were significantly different. Although the overall structure of the oral and esophageal microbiota did not change after POEM, the relative abundance rate of Haemophilus and Neisseria increased in the esophagus, and endoscopic findings of inflammation improved after POEM (P = .04). The relative abundance of microbiota was not different among patients with achalasia from those with ESCC. CONCLUSIONS: The oral and esophageal microbiota were significantly different in patients with achalasia, and some of the composition of the esophageal microbiota changed after POEM. However, these findings and disease-specific microbiota should be further evaluated in large-scale studies.

DOI： 10.5152/tjg.2020.19995

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DOI： 10.1002/jhbp.884

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BACKGROUND: A type 2b immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) without autoimmune pancreatitis is a rare condition with IgG4-SC. While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC, however, the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition. Therefore, the information of our recent case and reported cases have been summarized. CASE SUMMARY: We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4, narrowing of the bile duct, its wall thickness, no complication of autoimmune pancreatitis, and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes. The cholangiogram revealed type 2b according to the classification. Corticosteroid treatment showed a favorable effect, with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness. CONCLUSION: As isolated type 2b, IgG4-SC is rare, the images, histological findings, and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.

DOI： 10.12998/wjcc.v8.i22.5821

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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

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

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

Pancreatic pseudocyst-portal vein (PP-PV) fistula, mostly occurring after pseudocyst formation following acute/chronic pancreatitis, is a rare but life-threatening condition. The majority of treatments are based on conservative or surgical interventions. We report the case of a 70-year-old man with a PP-PV fistula and PV thrombosis. We adopted conservative treatment at first due to his mild symptoms. However, after resuming food intake, the patient had severe abdominal pain. Following endoscopic retrograde cholangiopancreatography, we found that the pseudocyst was connected with the PV through the fistula. Subsequently, an endoscopic nasopancreatic drainage (ENPD) catheter was inserted into the main pancreatic duct to establish pancreatic drainage, which resulted in a decrease in the abdominal pain. After the ENPD tube had been exchanged for endoscopic pancreatic stenting, his abdominal pain did not recur. Therefore, this case demonstrated endoscopic treatment as an effective treatment option for PP-PV fistula.

DOI： 10.1159/000510331

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

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

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

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

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

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BACKGROUND: This study aimed to identify the risk factors for walled-off necrosis (WON) associated with severe acute pancreatitis (SAP). METHODS: This retrospective study was conducted in eight institutions in Japan between 2014 and 2017. We analyzed WON incidence, patient characteristics, and risk factors for WON in patients with SAP who were observed for >28 days. RESULTS: Of 134 patients with SAP, WON occurred in 40 (29.9%). Male sex (P = .045), body mass index (BMI) ≥25 (P < .001), post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (P = .020), and disseminated intravascular coagulation (DIC) (P = .001) were more frequent in the WON group than in the non-WON group. On admission, the frequency of white blood cell counts ≥ 12 000/µL (P = .037) and hypoenhanced pancreatic lesion on computed tomography (P = .047) were significantly higher in the WON group. In multivariate analysis, BMI ≥ 25 (odds ratio [OR] 5.73, 95% confidence interval [CI] 1.95-16.8; P = .002), post-ERCP (OR 8.08, 95% CI 1.57-41.7; P = .013), and DIC (OR 3.52, 95% CI 1.20-10.4; P = .022) were independent risk factors for WON. CONCLUSIONS: High BMI, post-ERCP pancreatitis, and DIC are risk factors for the development of WON associated with SAP.

DOI： 10.1002/jhbp.787

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

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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

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

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

BACKGROUND AND AIM: Patients with achalasia experience weight loss because of dysphagia caused by impaired relaxation of the lower esophageal sphincter. This study aimed to use dual bioelectrical impedance analysis (BIA) to determine the change in bodyweight and body composition in patients with achalasia before and after peroral endoscopic myotomy (POEM). METHODS: Patients with achalasia who underwent POEM from 2013 to 2018 (n = 72) were retrospectively analyzed for change in bodyweight before and after 3 months. Additionally, change in body composition was prospectively investigated in the final 10 of 72 patients using non-radiation dual BIA. RESULTS: Twenty patients (27.8%) were underweight (body mass index < 18.5) before undergoing POEM. No clinical parameters were identified to be associated with the underweight condition before POEM and be predictive of an increase in bodyweight after POEM. Low visceral fat volume observed on dual BIA correlated closely with the result obtained using computed tomography (Pearson correlation coefficient: r = 0.850, P < 0.01). Patients with achalasia had a statistically significant increase in visceral (P < 0.01) and subcutaneous fat volumes (P < 0.01) after POEM. Skeletal muscle mass index slightly increased (P = 0.02), although the value after POEM was still low. No blood biomarkers were indicators for low bodyweight or low visceral fat volume. CONCLUSIONS: Dual BIA is an effective non-invasive tool to evaluate the change in body composition of underweight patients with achalasia. Skeletal muscle volume was not enough after POEM, although a rapid increase in the intra-abdominal fat volume was observed. Additional studies are warranted to understand the pathological implications.

DOI： 10.1111/jgh.14847

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Language：English   Publisher：WOLTERS KLUWER MEDKNOW PUBLICATIONS  

DOI： 10.4103/eus.eus_55_18

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Language：Japanese   Publisher：医歯薬出版(株)  

腹部超音波はその非侵襲性と簡便性のため、検診的なスクリーニングから緊急時のスクリーニング、造影超音波や穿刺治療など、幅広い場面で日常診療において使用されている。したがって、腹部超音波の技術の習得は実臨床において非常に重要である。腹部超音波診断ファントムは、生体と同じようにプローベを当てることができ、腹部臓器の基本描出の習得に有用である。また、バーチャル技術を用いたシミュレータでは超音波画像と周囲臓器の超音波の断面を同時に見ることができ、超音波検査における臓器の解剖学的位置関係の理解や技術習得の助けとなる。また、近年では腹部消化器領域、とくに胆膵領域の診断と治療において超音波内視鏡が必須となってきている。超音波内視鏡の画像読影と技術の習得には修練を要するが、専用のファントムやバーチャル技術を用いたシミュレータが使用可能となってきており、技術の習得が、より容易になることが期待される。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00060&link_issn=&doc_id=20190624030012&doc_link_id=%2Faa7ayuma%2F2019%2F026912%2F013%2F0945-0948%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2019%2F026912%2F013%2F0945-0948%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

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

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

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

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

Inflammatory bowel diseases (IBDs) are sometimes refractory to current therapy or associated with severe adverse events during immunosuppressive therapy; thus, new therapies are urgently needed. Recently, mesenchymal stem cells (MSCs) have attracted attention based on their multitude of functions including anti-inflammatory effects. However, proper timing of MSC therapy and the mechanisms underlying the therapeutic effects of MSCs on colitis are not fully elucidated. Human adipose tissue-derived mesenchymal stem cells (hAdMSCs; 1 x 10(6)) were administrated via the tail vein on day 3 (early) or 11 (delayed) using a 7-day dextran sulfate sodium (DSS)-induced mouse model of colitis. The effects were evaluated based on colon length, disease activity index (DAI) and histological score. Cytokine-encoding mRNA levels T cells and macrophages were evaluated by real-time PCR and flow cytometry. Regarding the timing of administration, early (day 3) injection significantly ameliorated DSS-induced colitis in terms of both DAI and histological score, compared to those parameters with delayed (day 11) injection. With early cell injection, the tissue mRNA levels of anti-inflammatory cytokine genes (Il10, Tgfb) increased, whereas those of inflammatory cytokine genes (Il6, Tnfa and Il17a) decreased significantly. Regarding the associated mechanism, hAdMSCs suppressed T cell proliferation and activation in vitro, increased the number of regulatory T cells in vivo and changed the polarity of macrophages (into the anti-inflammatory M2 phenotype) in vitro. Timing of injection is critical for the effective therapeutic effects of hAdMSCs. Furthermore, part of the associated mechanism includes T cell activation and expansion and altered macrophage polarization.

DOI： 10.1007/s00441-018-02981-w

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

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DOI： 10.1111/jgh.14312

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Language：Japanese   Publisher：日本消化器病学会-甲信越支部  

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We describe a novel therapeutic approach for cirrhosis using mesenchymal stem cells (MSCs) and colony-stimulating factor-1-induced bone marrow-derived macrophages (id-BMMs) and analyze the mechanisms underlying fibrosis improvement and regeneration. Mouse MSCs and id-BMMs were cultured from mouse bone marrow and their interactions analyzed in vitro. MSCs, id-BMMs, and a combination therapy using MSCs and id-BMMs were administered to mice with CCl4 -induced cirrhosis. Fibrosis regression, liver regeneration, and liver-migrating host cells were evaluated. Administered cell behavior was also tracked by intravital imaging. In coculture, MSCs induced switching of id-BMMs toward the M2 phenotype with high phagocytic activity. In vivo, the combination therapy reduced liver fibrosis (associated with increased matrix metalloproteinases expression), increased hepatocyte proliferation (associated with increased hepatocyte growth factor, vascular endothelial growth factor, and oncostatin M in the liver), and reduced blood levels of liver enzymes, more effectively than MSCs or id-BMMs monotherapy. Intravital imaging showed that after combination cell administration, a large number of id-BMMs, which phagocytosed hepatocyte debris and were retained in the liver for more than 7 days, along with a few MSCs, the majority of which were trapped in the lung, migrated to the fibrotic area in the liver. Host macrophages and neutrophils infiltrated after combination therapy and contributed to liver fibrosis regression and promoted regeneration along with administered cells. Indirect effector MSCs and direct effector id-BMMs synergistically improved cirrhosis along with host cells in mice. These studies pave the way for new treatments for cirrhosis. Stem Cells Translational Medicine 2019;8:271&284.

DOI： 10.1002/sctm.18-0105

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

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

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Language：Japanese   Publisher：新潟医学会  

近年、様々な疾患で体組成が病態や予後と関連していることが報告されている。我々の検討で、経動脈的治療を行った進行肝細胞癌症例のうち、骨格筋の6ヵ月間変化率が-4.6%未満の症例は予後不良であることが明らかとなった。また低皮下脂肪量も予後不良因子の一つであることを見出した。膵癌非切除例においては、内臓脂肪量が1ヵ月間で大きく減少した群で予後不良だった。進行消化器癌においては体組成、特にその変化率と予後が密接に関連していることが示唆された。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00990&link_issn=&doc_id=20200305060005&doc_link_id=%2Fdg3nigta%2F2018%2F013210%2F005%2F0350-0352%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2018%2F013210%2F005%2F0350-0352%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Georg Thieme Verlag  

Background Esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (MM) and submucosa up to 200μm (SM1) has a risk of metastasis. The aims of this study were to investigate the long-term outcome of endoscopic submucosal dissection (ESD) for MM/SM1 ESCC and to assess the management after ESD in our hospital. Methods This was a retrospective cohort study conducted at a single institution. Patients with MM or SM1 ESCC who were treated with ESD were included. Additional prophylactic therapy was added if lymphovascular involvement (LVI) was noted in the ESD specimens. Results A total of 102 patients were analyzed. The median length of follow-up was 71.5 months (range 9-144 months) and the median number of CTs was 6 (range 0-24). LVI was found in 21 patients (20.6%), and 12 patients underwent additional prophylactic therapy. The 5-year overall survival, disease-specific survival, and tumor-free survival rates were 84.1%, 97.5%, and 82.1%, respectively. A total of 26 patients died, but only 2 of them died from ESCC. The cumulative metastasis rate was 11.8%, and LVI was a significant predictor of metastasis (hazard ratio 5.42, 95% confidence interval 1.39-21.18
P =0.02). There were no differences between patients with MM ESCC and those with SM1 ESCC. Conclusions The long-term outcome after ESD for MM/SM1 ESCC was favorable with additional prophylactic therapy and strict adherence to follow-up.These results indicate that our management decision based on LVI is a valid approach and that ESD can be offered as a therapeutic option to MM/SM1 ESCCs.

DOI： 10.1055/s-0043-124433

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Language：English   Publisher：MOSBY-ELSEVIER  

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Language：English   Publisher：MOSBY-ELSEVIER  

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Language：English   Publisher：MOSBY-ELSEVIER  

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Language：English   Publisher：MOSBY-ELSEVIER  

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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

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

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Ltd  

Background: Previously, the mucosal histology in achalasia has only been investigated using superficial biopsy or surgically resected esophageal specimens in end-stage cases. We investigated the histology of the full-layer mucosa in early and advanced achalasia. Methods: Endoscopy was performed for the pinstripe pattern (PSP) (an early achalasia indicator) and dilation and thickening of the mucosa (advanced achalasia indicators). A mucosal entry site for peroral endoscopic myotomy was created using cap-fitted endoscopic mucosal resection to access the full-layer mucosa and the submucosa. Key Results: Mucosal histology was compared between 32 patients with achalasia and 15 controls. Histological esophagitis with findings of inflammatory cell infiltration and dilated intercellular spaces was observed more in patients with achalasia than in controls (87.5% vs 13.3%, P&lt
.001
84.4% vs 46.7%, P=.049). Muscularis mucosae (MM) atrophy and epithelial wave were only observed in achalasia (40.6% vs 0%, P=.005
28.1% vs 0%, P=.043). Fibrosis was more common in achalasia, but without statistical significance (31.3% vs 20.0%, P=.503). In achalasia with endoscopic dilation and thickening of the mucosa, MM atrophy was observed histologically, and in cases involving endoscopic PSP, the histological epithelial wave was observed. Conclusions &amp
Inferences: Histological findings of esophagitis were observed endoscopically even in early achalasia. Pinstripe pattern corresponds to the epithelial wave observed histologically in achalasia, whereas endoscopic findings in advanced achalasia correspond to MM atrophy. Appropriate management is necessary during early achalasia to prevent progression to advanced achalasia with more severe histological changes.

DOI： 10.1111/nmo.13168

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Language：English   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.9734-17

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Background: Pancreatic tumors are often difficult to diagnose in atypical cases, and a pancreatic schwannoma is very rare. We present a case of pancreatic schwannoma with calcification diagnosed preoperatively by endoscopic ultrasonography (EUS)-guided fine needle aspiration (FNA) and treated with laparoscopic distal pancreatectomy. Presentation: A 72-year-old-woman was admitted to our hospital due to a 6 × 4.5 cm large tumor in the pancreatic tail. Imaging modalities revealed that the tumor was hypovascular and gradually enhanced with calcification, but was without cystic lesions. EUS revealed the tumor had a clear boundary with a low echoic mass. EUS-FNA was performed and spindle-shaped cells that were immunopositive for S-100 and negative for c-kit, CD34, and desmin were detected, resulting in a diagnosis of schwannoma. Laparoscopic distal pancreatectomy with splenectomy was safely performed without recurrence for a year. Conclusions: Schwannoma is very rare; however, characteristics of the tumor, such as calcification, can help the diagnosis and, if possible, EUS-FNA should be performed for an appropriate treatment decision.

DOI： 10.1089/pancan.2018.0002

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Duodenal gastrointestinal stromal tumors (GISTs) are extremely rare disease entities, and the extraluminal type is difficult to diagnose. These tumors have been misdiagnosed as pancreatic tumors; hence, pancreaticoduodenectomy has been performed, although partial duodenectomy can be performed if accurately diagnosed. Developing a diagnostic methodology including endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) has allowed us to diagnose the tumor directly through the duodenum. Here, we present a case of a 50-year-old woman with a 27-mm diameter tumor in the pancreatic uncus on computed tomography scan. EUS showed a well-defined hypoechoic mass in the pancreatic uncus that connected to the duodenal proper muscular layer and was followed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Histological examination showed spindle-shaped tumor cells positively stained for c-kit. Based on these findings, the tumor was finally diagnosed as a duodenal GIST of the extraluminal type, and the patient underwent successful mass resection with partial resection of the duodenum. This case suggests that EUS and EUS-FNA are effective for diagnosing the extraluminal type of duodenal GISTs, which is difficult to differentiate from pancreatic head tumor, and for performing the correct surgical procedure.

DOI： 10.4253/wjge.v9.i12.583

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

Development of an effective, safe, and convenient method for gene delivery to the pancreas is a critical step toward gene therapy for pancreatic diseases. Therefore, we tested the possibility of applying the principle of hydrodynamic gene delivery for successful gene transfer to pancreas using rats as a model. The established procedure involves the insertion of a catheter into the superior mesenteric vein with temporary blood flow occlusion at the portal vein and hydrodynamic injection of DNA solution. We demonstrated that our procedure achieved efficient pancreas-specific gene expression that was 2,000-fold higher than that seen in the pancreas after the systemic hydrodynamic gene delivery. In addition, the level of gene expression achieved in the pancreas by the pancreas-specific gene delivery was comparable to the level in the liver achieved by a liver-specific hydrodynamic gene delivery. The optimal level of reporter gene expression in the pancreas requires an injection volume equivalent to 2.0% body weight with flow rate of 1 mL/s and plasmid DNA concentration at 5 mu g/mL. With the exception of transient expansion of intercellular spaces and elevation of serum amylase levels, which recovered within 3 days, no permanent tissue damage was observed. These results suggest that pancreas-targeted hydrodynamic gene delivery is an effective and safe method for gene delivery to the pancreas and clinically applicable.

DOI： 10.1016/j.omtn.2017.08.009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Hemorrhage is one of the serious adverse events of endoscopic sphincterotomy (EST). However, the risk factors for delayed hemorrhage after EST have not been clarified. The aim of this study was to examine the risk factors for delayed hemorrhage after EST.
Consecutive patients who underwent EST between January 2011 and December 2015 were analyzed retrospectively. The incidence, treatment outcomes, and risk factors for delayed hemorrhage were evaluated. Delayed hemorrhage was defined as symptomatic hemorrhage occurring 24 h after an endoscopic procedure.
After analyzing 1113 patients who underwent EST, delayed hemorrhage was seen to occur in 30 (2.7%) patients. The median period before presentation of delayed hemorrhage was 2 days (range 1-6) after EST, and its severity was mild in four, moderate in 20, and severe in six patients. All patients with delayed hemorrhage received successful endoscopic hemostasis. Univariate analysis showed that delayed hemorrhage occurred more frequently in patients with hemodialysis (p = 0.013), heparin replacement of antithrombotic agents (p = 0.012), or early hemorrhage occurring just after EST (p &lt; 0.001). Among these, hemodialysis (OR 6.44, 95% CI 1.67-24.8; p = 0.007), heparin replacement (OR 3.76, 95% CI 1.42-9.98; p = 0.008), and early hemorrhage (OR 4.35, 95% CI 1.90-9.96; p &lt; 0.001) proved to be independent risk factors for delayed hemorrhage on multivariate analysis.
The incidence of delayed hemorrhage after EST was 2.7%. Hemodialysis, heparin replacement, and early hemorrhage were the risk factors for delayed hemorrhage.

DOI： 10.1007/s00535-017-1347-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press  

The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 ± 0.5 and 1.0 ± 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation ofΔDCI with the circumferential mucosal defect ratio [P &lt
0.01, standardized regression coefficient (r) = -0.65], the number of stricture preventions (P &lt
0.01, r = -0.601), and the number of stricture resolutions (P &lt
0.01, r=-0.77). This HRMstudy showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.

DOI： 10.1093/dote/dox057

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 +/- 0.5 and 1.0 +/- 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation of Delta DCI with the circumferential mucosal defect ratio {P &lt; 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P &lt; 0.01, r = -0.601), and the number of stricture resolutions (P &lt; 0.01, r=-0.77). This HRM study showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.

DOI： 10.1093/dote/dox057

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

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

Background: Endoscopic submucosal dissection (ESD) and peroral endoscopic myotomy (POEM) are recently developed techniques that have the potential to significantly improve clinical outcomes. However, training opportunities on these techniques remain limited. To address this issue, we developed a novel ex-vivo ESD/POEM training model. Our aim in this paper is to describe the model and provide preliminary evidence of promising feasibility to improve access to ESD/POEM training. Methods: The model was developed using polyvinyl alcohol hydrogel, which can easily be modified to reproduce the stiffness of the different intestinal layers, namely the mucosa, submucosa, and muscle layer. Results: A training workshop, using our ex-vivo model, was held for 28 residents. Satisfaction and feasibility in using the ex-vivo model for endoscopic training were evaluated by using a self-report questionnaire. All participants were satisfied with their training experience (100% satisfaction rate), with 27 of the 28 participants reporting that the model was feasible in replicating all components of the ESD/POEM technique (96.4% feasibility rate). Conclusions: Based on this feedback, we propose that our non-biomaterial model has the feasibility to provide an effective endoscopy education tool and a satisfactory training experience.

DOI： 10.21037/atm.2017.01.27

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

AIM
To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus.
METHODS
Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples.
RESULTS
In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 +/- 7.9 in the epithelium and 2.3 +/- 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 +/- 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 +/- 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE.
CONCLUSION
Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs.

DOI： 10.3748/wjg.v23.i13.2414

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

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Language：English   Publisher：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0043-100691

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Alpha-fetoprotein (AFP)-L3 was originally reported as a hepatocellular carcinoma (HCC)-specific tumor marker, and recent accumulation of evidence has revealed that AFP-L3 frequency predicts the biological malignancy potential of HCC. However, AFP-L3 elevation from undetectable levels after curative treatment could not be discussed due to the difficulties of calculating AFP-L3 concentrations when serum AFP levels were low. Here, as a novel method, we used highly sensitive AFP-L3 frequency to predict HCC recurrence after curative treatment. Our cases illustrate that recognizing elevation of AFP-L3 from undetectable levels led to the early detection of recurrent HCC due to more careful surveillance.

DOI： 10.1159/000462969

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：GEORG THIEME VERLAG KG  

Background and study aims Short-type single-balloon enteroscope (short SBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is a promising alternative treatment in post-surgical altered anatomy. However, it is technically demanding, and factors affecting its technical difficulty have not yet been clarified. This study aimed to examine the procedural success rate of short SBE-assisted ERCP and the potential factors affecting procedural failure.
Patients and methods A total of 117 consecutive patients (203 procedures) with surgically altered anatomy underwent ERCP using prototype short SBEs. The procedural success rate of short SBE-assisted ERCP and the potential factors affecting procedural failure were examined retrospectively.
Results The enteroscopy success rate and procedural success rate were 92.6% (95% confidence interval [CI] 88.1%-95.8%) and 81.8 % (95% CI 75.8%-86.8 %), respectively. Multivariate analyses indicated that pancreatic indication (odds ratio [OR] 4.35, 95% CI 1.67-11.4), first ERCP attempt (OR 6.03, 95% CI 2.17-16.8), and no transparent hood (OR 4.61, 95% CI 1.48-14.3) were potential risk factors for procedural failure.
Conclusions Short SBE-assisted ERCP was effective in post-surgical altered anatomy. This large case series suggested the potential factors affecting procedural failure.

DOI： 10.1055/s-0042-118301

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Pancreatic metastasis from colorectal cancer is rare, and there have been only a few reports of its preoperative diagnosis by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with immunohistochemical staining. We herein describe the case of a 77-year-old woman in whom a solitary mass in the pancreatic tail was detected 11 years after rectal cancer resection. The patient also had a history of pulmonary tumor resection. We performed EUS-FNA and a histopathological examination showed adenocarcinoma with CD20+, CD7-, and CDX2+ (similar to her rectal cancer). EUS-FNA enabled a histopathological examination, including immunohistochemical staining, which helped to confirm the diagnosis of pancreatic and pulmonary metastasis from rectal cancer.

DOI： 10.2169/internalmedicine.56.7213

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Mesenchymal stem cell (MSC) therapies have been used in clinical trials in various fields. These cells are easily expanded, show low immunogenicity, can be acquired from medical waste, and have multiple functions, suggesting their potential applications in a variety of diseases, including liver disease and inflammatory bowel disease. MSCs help prepare the microenvironment, in response to inflammatory cytokines, by producing immunoregulatory factors that modulate the progression of inflammation by affecting dendritic cells, B cells, T cells, and macrophages. MSCs also produce a large amount of cytokines, chemokines, and growth factors, including exosomes that stimulate angiogenesis, prevent apoptosis, block oxidation reactions, promote remodeling of the extracellular matrix, and induce differentiation of tissue stem cells. According to ClinicalTrials.gov, more than 680 clinical trials using MSCs are registered for cell therapy of many fields including liver diseases (more than 40 trials) and inflammatory bowel diseases (more than 20 trials). In this report, we introduce background and clinical studies of MSCs in liver disease and inflammatory bowel diseases.

DOI： 10.1186/s41232-017-0045-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORP  

Background. Dentures and dental instruments are frequently encountered ingested foreign bodies. The aim of the present study was to assess the safety and efficacy of endoscopically removing ingested dental objects. Methods. Twenty-nine consecutive patients with 29 dental objects who were treated at the Niigata University Medical and Dental Hospital from August 2009 to December 2015 were retrospectively reviewed. Characteristics of the patients and the ingested dental objects, the clinical features and findings of radiological imaging tests, and outcomes of endoscopic removal were analyzed. Results. Patients' mean age was 62.9 + 21.0 years. The ingested dental objects included 23 dentures (13 crowns, 4 bridges, 4 partial dentures, and 2 other dentures) and 6 dental instruments. Twenty-seven upper gastrointestinal endoscopies and 2 colonoscopies were performed, and their success rates were 92.6% and 100%, respectively. There were 2 cases of removal failure; one case involved an impacted partial denture in the cervical esophagus, and this case required surgical removal. Conclusions. Endoscopic removal of ingested dentures and dental instruments is associated with a favorable success rate and acceptable complications. The immediate intervention and appropriate selection of devices are essential for managing ingested dental objects.

DOI： 10.1155/2016/3537147

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.113.603

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Other Link： http://search.jamas.or.jp/link/ui/2016226796

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DOI： 10.1016/j.gie.2015.02.037

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

Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a useful and relatively safe tool for the diagnosis and staging of pancreatic cancer. However, there have recently been several reports of tumor seeding after EUS-FNA of adenocarcinomas. A 78-year-old man was admitted to our hospital due to upper gastric pain. Examinations revealed a 20 mm mass in the pancreatic body, for which EUS-FNA was performed. The cytology of the lesion was adenocarcinoma, and the stage of the cancer was T3N0M0. The patient underwent surgery with curative intent, followed by adjuvant chemotherapy with S-1. An enlarging gastric submucosal tumor was found on gastroscopy at 28 mo after surgery accompanied by a rising level of CA19-9. Biopsy result was adenocarcinoma, consistent with a pancreatic primary tumor. Tumor seeding after EUS-FNA was strongly suspected. The patient underwent surgical resection of the gastric tumor with curative intent. The pathological result of the resected gastric specimen was adenocarcinoma with a perfectly matched mucin special stain result with the previously resected pancreatic cancer. This is the first case report of tumor seeding after EUS-FNA which was surgically resected and inspected pathologically.

DOI： 10.3748/wjg.v21.i27.8458

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

BackgroundAdequate needle size and tissue acquisition techniques for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) need further elucidation. Moreover, the actual negative pressure and suction forces of FNA needles remain unknown. We evaluated the suction forces of 19-gauge, 22-gauge, and 25-gauge conventional FNA needles and side hole aspiration needles using conventional negative pressure and the slow pull technique.
MethodsUsing a manometer, we determined the mean (SD) negative pressure and suction force for needle gauge, aspiration volume, and aspiration technique. We also evaluated the time to reach the maximum negative pressure.
ResultsSuction force was comparatively higher in the 19-gauge needle when 50ml of negative pressure was applied. Suction force using the slow pull method was very weak at 5% of pressure found with conventional methods. With the use of a 20-ml syringe, the time to reach the maximum negative pressure was 4s in the 19-gauge needle, 11s in the 22-gauge needle, and 80s in the 25-gauge needle.
ConclusionsBench-top testing showed that suction force increases with a larger gauge needle and larger aspiration volume. The slow pull method produces a very weak suction force. The time to reach the maximum negative pressure was longest in the 25-gauge needle.

DOI： 10.1002/jhbp.201

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Language：English   Publisher：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0034-1377388

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

Aim We recently reported that endoscopic papillary balloon dilation (EPBD) might suppress biliary bacterial contamination better than endoscopic sphincterotomy (EST) in patients with small bile duct stones (diameter 8mm). In the present study, we evaluated immediate and long-term outcomes of endoscopic papillary balloon dilation with regard to stone size. Methods We allocated 474 patients alternately to the two procedures. The patients were classified according to stone diameter (8mm or &gt;8mm) and outcomes (i.e. complete stone removal, early complications, and late complications) were compared. The predictive risk factors for late complications were also investigated. Results In patients with small stones, complete stone removal rate and early complication rate were similar between the two procedures; the incidence of pancreatitis was higher after EPBD, although the difference was not significant. Late complication rate and stone recurrence rate were significantly lower after EPBD than after EST (5.3% vs 17.3%, P=0.009; 4.4% vs 12.7%; P=0.048, respectively). In patients with large stones who underwent EPBD complete stone removal rate and late complication rate were lower, but the incidence of pancreatitis was higher. However, these differences were not statistically significant. Multivariate analysis showed that the increased risk of bactobilia following EPBD for large stones or EST, and the gallbladder with stones insitu were independent risk factors for late complications. Conclusions EPBD produced significantly better long-term outcomes than EST in patients with small bile duct stones.

DOI： 10.1111/j.1443-1661.2012.01393.x

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Undifferentiated-type early gastric adenocarcinomas are generally classified into two groups: pure undifferentiated-type adenocarcinomas, which naturally develop as undifferentiated-type without a glandular component; and mixed differentiated/undifferentiated-type adenocarcinomas, which are associated with some vestigial glandular component and presumably develop from differentiated-type adenocarcinoma. The differences in phenotypic expression between these two groups were examined using mucin core protein and CDX2.
A total of 210 lesions of undifferentiated-type early gastric adenocarcinoma less than 25 mm in diameter were classified into four categories (gastric type, gastrointestinal type, intestinal type, and null type) based on their MUC5AC, MUC6, MUC2, and CDX2 immunoprofiles.
Gastric type was significantly (p &lt; 0.01) decreased and gastrointestinal type was significantly (p &lt; 0.01) increased both in pure undifferentiated-type adenocarcinomas and in mixed differentiated/undifferentiated-type adenocarcinomas when CDX2 was applied to mucin core protein. In the pure undifferentiated-type adenocarcinomas, gastric type decreased and gastrointestinal type increased as tumor size increased (p &lt; 0.05). In contrast, in the mixed differentiated/undifferentiated-type adenocarcinomas, gastrointestinal type was most common even in small-sized (a parts per thousand currency sign10 mm) carcinomas and was generally stable regardless of tumor size. In submucosal carcinomas, gastrointestinal type decreased and gastric type and intestinal type increased during carcinoma invasion from the intramucosal to submucosal parts (p &lt; 0.05). The positivity rates for all phenotypic markers, especially gastric markers, tended to decrease during submucosal invasion.
CDX2 is a sensitive marker for assessing intestinal phenotypic expression, and it is likely that there are two different pathways of tumor progression in undifferentiated-type adenocarcinoma of the stomach, according to phenotypic expression.

DOI： 10.1007/s10120-012-0172-3

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Trousseau症候群は、Trousseauによって1865年に報告された、悪性腫瘍に合併する血栓症である。その脳卒中症状は、重篤な神経症状を呈し、直接的に生命予後に関与しうる傍悪性腫瘍症候群の一つとして認識されている。今回、胆管細胞癌に脳卒中症状を呈するTrousseau症候群を合併し死亡した2例を経験したので報告する。症例1は90歳、男性、症例2は58歳、女性でいずれの症例も生活習慣病の危険因子を有し、40mm前後の肝腫瘍で初診、各種画像検査、胆汁細胞診、組織診にて胆管細胞癌の診断となった。経過中、腫瘍の急激な増大、胆道出血を合併し、本症候群を発症しやすい状況であった。担癌患者では、病態が急速に進行する場合、凝固線溶系の異常値などに留意し、抗凝固療法の開始を含む対応が本症候群の発症を予防し、原病に対する治療介入の機会を増やしうる方法論であると考え、報告する。(著者抄録)

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DOI： 10.1016/j.gie.2017.03.161

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

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経乳頭的膵管生検および膵液細胞診の現状について概説した。経乳頭的膵管生検は膵管内腫瘤や主膵管と交通のある嚢胞性病変などでは良い適応であるが、単独では癌陽性率が十分でない。膵液細胞診は膵管ブラッシング細胞診、ガイドワイヤ擦過細胞診、膵管洗浄細胞診、ENPD留置下膵液細胞診など、さまざまな方法が行われており、複数の検体採取法の併用も有用である。また、診断の補助として膵液を利用した遺伝子診断も行われている。当センターでのIPMNもしくは膵管内腫瘤に対する生検の癌陽性率は67%で、偶発症は認めなかった。また、膵管狭窄に対するENPD留置下膵液細胞診は、感度33%、特異度100%、正診率72%であり、偶発症は膵炎を4.7%に認めるのみであった。EUS-FNAによりその役割は変化してきているが、必要な症例も依然として存在する。しかしながら偶発症として膵炎の危険性があるため、診断に対する利益を踏まえたうえで施行することが肝要である。(著者抄録)

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慢性膵炎は、膵石や膵管狭窄により膵管および膵組織の内圧上昇をきたし、疼痛や急性増悪、仮性嚢胞を生じる。慢性膵炎の治療としては、外科手術のほか内視鏡治療および体外衝撃波結石破砕術(ESWL)が行われており、膵石、膵管狭窄、仮性嚢胞などの病態に応じて治療法を選択する。膵石に対する治療はESWLが中心に位置するが、小結石、浮遊結石、X線透過性膵石には内視鏡的膵石除去術も有効である。膵石に主膵管狭窄を伴う場合にはESWLに加えて内視鏡治療の併用が必要となる。主膵管狭窄には内視鏡的拡張術のほか膵管ステント留置術(EPS)がある。仮性嚢胞の治療として内視鏡的嚢胞ドレナージ術が行われている。ESWL無効あるいは内視鏡治療にて狭窄突破やドレナージに難渋する例や再発を繰り返す例があり、病態によって外科手術を考慮することも必要である。(著者抄録)

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症例は70歳、男性。上腹部痛にて発症し、腫瘍マーカー、上部消化管内視鏡検査(GIF)、腹部CTにて、3型胃癌、多発性肝転移、癌性腹膜炎と診断。当科入院後、S-1 100mg/bodyを14日間内服、docetaxel(DOC)40mg/m2を1日目に点滴静注するS-1+DOC併用療法を施行。GIF,CT上腫瘍は著明に縮小し、腫瘍マーカーは正常化した。有害事象として、grade 3の白血球・好中球減少を認めたためG-CSF投与を行い、S-1,DOCをそれぞれ減量し治療を継続した。その他は比較的軽微であり、外来化学療法が可能であった。21コース終了現在、奏効を維持している。(著者抄録)

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