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Objective Crohn's disease (CD) is a chronic inflammatory bowel disease that is associated with malnutrition. Sarcopenia is a malnutrition condition characterized by skeletal muscle loss that impairs the physical function. We investigated the clinical characteristics of patients with CD with sarcopenia and sarcopenic obesity (sarcopenic-o). Methods The body composition of patients with CD was evaluated using a bioelectrical impedance analysis. The clinical characteristics of patients with sarcopenia and sarcopenic-o were analyzed, and a predictive model for sarcopenia was developed. Patients: Patients with CD recruited from 2019 to 2021 were included. Results Among the 104 patients, 35 (33.7%) and 10 (9.6%) had sarcopenia and sarcopenic-o, respectively. In the sarcopenia group, the skeletal muscle index (SMI) and body mass index (BMI) were lower than those in the control group (SMI, 6.3 kg/m 2 vs. 7.7 kg/m 2 , p<0.01; BMI, 18.8 kg/m 2 vs. 22.6 kg/m 2 , p<0.01), whereas the Crohn's disease activity index (CDAI) was higher than in the control group (114.2 vs. 42.0, p<0.01). The predictive models of sarcopenia using the BMI and CDAI revealed high performance with areas under the receiver operating characteristic curve (AUC) of 0.87 and 0.72, respectively, and high specificity (0.94) and sensitivity (0.71), respectively. Sarcopenic-o patients could not be screened using the BMI (25 kg/m 2 ), and the SMI and body fat percentage were negatively correlated in patients with sarcopenia (p<0.01). Conclusion Sarcopenia and sarcopenic-o are relatively common conditions among patients with CD. Sarcopenia can be predicted using the clinical parameters of BMI and CDAI. Sarcopenic-o can be a severe form of sarcopenia.

Objectives: There are limited reports on the safety of gastrointestinal endoscopic procedures in individuals taking edoxaban, one of the direct oral anticoagulants. We clarified the incidence of delayed bleeding in patients who were on edoxaban in the perioperative period of gastrointestinal endoscopic procedures with a high risk of bleeding., Methods: This was an investigator-initiated, single-center, open-label, prospective, single-arm study. Patients on warfarin or edoxaban undergoing endoscopy with a high risk of bleeding were enrolled from June 2018 to September 2021. Warfarin was replaced with edoxaban in patients on warfarin. Patients taking other direct oral anticoagulants, and antiplatelet drugs, were excluded. The primary endpoint was severe delayed bleeding (Common Terminology Criteria for Adverse Events [CTCAE] grades III-V) and the secondary endpoints included thromboembolism, all adverse events, any delayed bleeding (CTCAE grades I or II), and hospital stay durations., Results: Twenty-one patients on edoxaban underwent high-risk endoscopy. Three cases (14%) experienced CTCAE grade III delayed bleeding, requiring endoscopic hemostasis. No CTCAE grade I-II delayed bleeding or thromboembolic events occurred. Cholangitis and aspiration pneumonia (conservatively treated) occurred during the hospital stay. The median length of hospital stay was 8 days (range 3-24 days). Patients with delayed bleeding had higher systolic blood pressure at admission and longer hospital stays., Conclusions: The delayed bleeding incidence in high-risk endoscopic procedures for patients on edoxaban was acceptable. Higher blood pressure may be associated with increased risk, but further research is needed., Competing Interests: Ken‐ichi Mizuno received honoraria from Daiichi‐Sankyo, Takeda Pharmaceutical, Olympus, Fujifilm, Miyarisan Pharmaceutical, and Nipro. Shuji Terai received research grants from Interstem, ASKA Pharmaceutical, Tsumura, CHIOME Bioscience, BioMimetics Sympathies, Nihon Pharmaceutical, Sysmex, Tosoh, Rohto, Stemrim, Shionogi, Kowa, Gilead Sciences, Abbott, AbbVie, Sumitomo Pharma, Takeda Pharmaceutical, Nippon Kayaku, Otsuka Pharmaceutical, Eisai, EA Pharma, and Asahi Kasei Pharma, and honoraria from Diichi‐Sankyo, Takeda Pharmaceutical, ASKA Pharmaceutical, Gilead Sciences, MSD, and Otsuka Pharmaceutical. The other authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Ulcerative colitis-associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability-high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies., Competing Interests: SO received research funding from Denka Co., Ltd. TW received remuneration and research funding from Denka Co., Ltd. All other authors declare that they have no competing interests., (Copyright: © Shimada et al.)

Purpose: Gastric neoplasia is a common manifestation of familial adenomatous polyposis (FAP). This study aimed to elucidate the clinical characteristics, endoscopic features including fundic gland polyposis (FGPsis), and treatment outcomes of gastric neoplasms (GNs) in patients with FAP., Materials and Methods: A total of 35 patients diagnosed with FAP, including nine patients from four pedigrees who underwent esophagogastroduodenoscopy (EGD), were investigated regarding patient characteristics, GN morphology, and treatment outcomes., Results: Twenty-one patients (60.0%) had 38 GNs; 33 (86.8%) and 5 (13.2%) were histologically diagnosed with adenocarcinoma and adenoma, respectively. There were no specific patient characteristics related to GNs. Nodule-type GNs were more prevalent in patients with FGP than without (52.2% vs. 0.0%, P=0.002) in the upper body of the stomach. Conversely, depressed-type GNs were fewer in patients with FGPsis than in those without (13.0% vs. 73.3%, P<0.001). Slightly elevated-type GNs were observed in both groups (34.8% vs. 20.0%, P=0.538). Even within pedigrees, the background gastric mucosa and types of GNs varied. In total, 24 GNs were treated with endoscopic submucosal dissection (ESD) and eight with endoscopic mucosal resection (EMR). EMR was selected for GNs with FGPsis because of the technical difficulty of ESD, resulting in a lower en bloc resection rate (62.5% vs. 100%, P=0.014)., Conclusions: Our study indicates the necessity of routine EGD surveillance in patients diagnosed with FAP. Notably, the morphology and location of GNs differed between patients with and without FGPsis. Endoscopic treatment and outcomes require more attention in cases of FGPsis., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2022. Korean Gastric Cancer Association.)

Mesenteric hematoma is an uncommon condition caused by focal bleeding in the mesenteric vessels. Hematomas are related to trauma, pancreatitis, arteriopathy, and the use of antithrombotic agents. Although hematomas cause intestinal stenosis by compressing the adjacent small bowel, duodenal stenosis due to hematoma is rare. Therefore, the treatment indications for cases of hematoma with stenosis have not been established. We herein report a case with a large mesenteric hematoma that caused duodenal stenosis by compressing the third portion of the duodenum. Stenosis was successfully ameliorated after long-term use of a double elementary diet tube.

The dextran sodium sulfate (DSS)-induced colitis mouse model has been widely utilized for human colitis research. While its mechanism involves a response to double-strand deoxyribonucleic acid (DNA) damage, ataxia telangiectasia mutated (Atm)-checkpoint kinase 2 (Chk2) pathway activation related to such response remains unreported. Recently, we reported that cyclin D1-binding protein 1 ( Ccndbp1 ) activates the pathway reflecting DNA damage in its knockout mice. Thus, this study aimed to examine the contribution of Ccndbp1 and the Atm-Chk2 pathway in DSS-induced colitis. We assessed the effect of DSS-induced colitis on colon length, disease activity index, and histological score and on the Atm-Chk2 pathway and the subsequent apoptosis in Ccndbp1 -knockout mice. DSS-induced colitis showed distal colon-dominant Atm and Chk2 phosphorylation, increase in TdT-mediated dUTP-biotin nick end labeling and cleaved caspase 3-positive cells, and histological score increase, causing disease activity index elevation and colon length shortening. These changes were significantly ameliorated in Ccndbp1 -knockout mice. In conclusion, Ccndbp1 contributed to Atm-Chk2 pathway activation in the DSS-induced colitis mouse model, causing inflammation and apoptosis of mucosal cells in the colon.

Gastric cancer is a Lynch syndrome (LS)-associated tumor, with the cumulative lifetime risk in LS patients estimated to be 5.8-13%. Hence, surveillance for gastric cancer is important for LS patients, especially in those with a family history of gastric cancer or of Asian descent. We report a very rare case of a LS patient who showed gastric metastasis from jejunal adenocarcinoma curatively resected 8 years prior. A 79-year-old female was diagnosed with a synchronous gastric submucosal tumor (SMT) and right-sided colon cancer. She was referred to our hospital as she and her family had histories of LS-associated tumors. She underwent curative intent surgery for the tumors. Postoperative histopathological examination revealed the gastric SMT was an adenocarcinoma completely covered by non-neoplastic gastric mucosa. Immunohistochemical analyses showed the gastric SMT had the same expression pattern for CDX2, cytokeratins 7 and 20 as the jejunal adenocarcinoma. Thirty-four months after surgery the patient is alive without recurrence or any other LS-associated tumors. To the best of our knowledge, this is the first report of gastric metastasis from small bowel adenocarcinoma in a LS patient. Awareness of this case may be important for gastric cancer surveillance in LS patients., (© 2022. Japanese Society of Gastroenterology.)

The incidence of gastric tube carcinoma (GTC) after esophagectomy for esophageal carcinoma has increased in recent years. Surgical removal of the reconstructed gastric tube is associated with high mortality, and endoscopic submucosal dissection (ESD) is a promising alternative. There are limited reports of ESD for GTC. This study investigated the efficacy and safety of ESD in GTC. This single-center retrospective study examined patients who underwent ESD for GTC after esophagectomy at our institution between 2003 and 2018. The curability of GTC with ESD was evaluated histologically according to the Japanese Gastric Cancer Treatment Guidelines. Patient characteristics and procedural and long-term outcomes were analyzed. Overall, 31 patients (29 men and 2 women; median age, 73 years) with 45 GTC lesions underwent ESD. The mean period between primary esophagectomy and the diagnosis of GTC was 10.6 years. Bleeding during ESD was noted in two patients (6.5%). No other adverse or fatal events such as perforation were noted. Complete resection and curative resection were documented in 80.6% and 48.4% of cases, respectively. The 3-year and 5-year overall survival rates were 67.6% and 47.7%, respectively. The 3-year and 5-year disease-specific survival rates were 100% and 92.9%, respectively. One patient died of GTC, and fourteen patients died of other diseases, including primary carcinoma in five cases. ESD was safe and provided good long-term outcomes in patients with GTC. Regular long-term gastroscopy is required for the early detection of GTC. Patients with GTC after esophagectomy for esophageal carcinoma have a high risk of other primary carcinomas or comorbidities after ESD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Satoru Hashimoto et al.)

The Pacific oyster (Crassostrea gigas) is an important species in oyster farming worldwide, including in Japan. Hiroshima Bay is one of the most important oyster farming areas in Japan. We investigated the occurrence of antifouling biocides used worldwide including diuron, Irgarol 1051 (Irgarol), and 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), which have been detected at sub-ppb levels in seawater in Japan, and estimated their no observed effect concentrations (NOECs). In recent years, the spat settlement of Pacific oysters has become poor, which presents a challenge for oyster aquaculture in Hiroshima Bay; hence, we conducted embryotoxicity and larva settlement tests using Pacific oysters. Compared to diuron and Irgarol, DCOIT exhibited a higher toxicity toward oyster embryos, and the minimum 24-h NOEC toxicity value for the oyster embryos was <3 ng/L. The highest concentrations of diuron, Irgarol, and DCOIT in the environmental seawater in the Seto Inland Sea were 27.6, 3.2, and 24 ng/L, respectively. Considering the NOECs, the environmental concentrations of these biocides suggest that the ecological risks posed by diuron and Irgarol are low, whereas those posed by DCOIT are high. However, the rate of detection of DCOIT was low because it degraded rapidly in the seawater before treatment for chemical analysis, except in the case of the treatment on the research vessel., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective Esophageal diverticulum is rare, and the concomitance of esophageal motility disorders (EMDs) and the efficacy of novel endoscopic treatment have not been investigated in Japan. Methods An examination including high-resolution manometry (HRM) was performed for patients with both EMDs and epiphrenic diverticulum. EMD-related epiphrenic diverticulum and Zenker's diverticulum were treated using salvage peroral endoscopic myotomy (s-POEM) and endoscopic diverticulotomy, respectively. Results Six cases of epiphrenic diverticulum were diagnosed in this study. Among 125 patients with achalasia and spastic disorders, concomitant epiphrenic diverticulum was observed in 4 (3.2%). Of these, three showed a normal lower esophageal sphincter pressure on HRM, although gastroscopy and esophagography revealed typical findings of an impaired lower esophageal sphincter relaxation. These four patients were successfully treated with s-POEM, and the Eckardt score improved from 6.3 to 0.25 at 32.5 (range: 13-56) months of follow-up, with equivalent treatment efficacy to that observed for achalasia and spastic disorders without epiphrenic diverticulum. In contrast, the two remaining cases of epiphrenic diverticulum had normal esophageal motility. Six cases of Zenker's diverticulum were diagnosed, and endoscopic diverticulotomy was successfully performed in all. The dysphagia score decreased from 2.8 to 0.17 at 14.8 (range: 2-36) months of follow-up. Overall, 12 endoscopic treatments were performed for esophageal diverticulum; no adverse events were observed. Conclusion In epiphrenic diverticulum patients, concomitant EMDs are not rare and should be carefully diagnosed. A normal lower esophageal sphincter pressure on HRM does not always mean a normal lower esophageal sphincter relaxation. S-POEM and endoscopic diverticulotomy are effective minimally invasive treatment options for EMD-related epiphrenic diverticulum and Zenker's diverticulum.

Objectives: Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota., Methods: Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double-ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method., Results: All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2-3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α-diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae , in the diverted colon decreased after autologous FMT., Conclusions: This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment., Competing Interests: Miyarisan Pharmaceutical Co. Ltd. supported this study in the analysis of the microbiota., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

We herein report a rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd-Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread., (© 2021. The Author(s).)

A 40-year-old man with slightly depressed (0-IIc) type gastric cancer of the pyloric anterior gastric area underwent pre-operative screening for tetralogy of Fallot and endoscopic submucosal dissection (ESD) and was tested for Helicobacter pylori antigens and antibodies. Both tests were negative. He did not have a history of eradication. Pathological diagnosis of ESD showed a well-differentiated adenocarcinoma. The tumor was CD10-positive, MUC5AC-negative, and MUC6-confocal positive; it showed differentiation with gastrointestinal phenotype. Moreover, the tumor cells were lysozyme-positive, resembling Paneth cells. Mucosal glands exhibited intestinal metaplasia on the anal side of the tumor lesion. On the oral side of the tumor, metaplasia was non-existent, with normal pyloric glands present in the mucosal layer. The patient was not infected with H. pylori ; however, intestinal metaplasia existed around the early gastric cancer. This suggested that the intestinal metaplasia occurred due to bile reflux, and the gastric neoplasia arose with the metaplasia without an H. pylori infection. This case may potentially help explain gastric cancer development in the absence of H. pylori infection., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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.

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors disclose the following: Shuji Terai received research funding from 10.13039/100016567Miyarisan Pharmaceutical Co., Ltd. Asami Matsumoto, Ayaka Minemura, Kentaro Oka and Motomichi Takahashi are employees of Miyarisan Pharmaceutical Co., Ltd.The remaining authors disclose no conflicts. Please note that all Biochemical and Biophysical Research Communications authors are required to report the following potential conflicts of interest with each submission. If applicable to your manuscript, please provide the necessary declaration in the box above.(1)All third-party financial support for the work in the submitted manuscript.(2)All financial relationships with any entities that could be viewed as relevant to the general area of the submitted manuscript.(3)All sources of revenue with relevance to the submitted work who made payments to you, or to your institution on your behalf, in the 36 months prior to submission.(4)Any other interactions with the sponsor of outside of the submitted work should also be reported. (5) Any relevant patents or copyrights (planned, pending, or issued).(6)Any other relationships or affiliations that may be perceived by readers to have influenced, or give the appearance of potentially influencing, what you wrote in the submitted work. As a general guideline, it is usually better to disclose a relationship than not., (© 2020 The Authors.)

An asymptomatic epiphrenic diverticulum (ED) was diagnosed in a man undergoing annual esophagogastroduodenoscopy (EGD) at another hospital 40 years before he presented to our hospital at age 63 years for his annual EGD. However, because substantial food retention was found in the ED, we could not confirm a lesion. After the retained food was removed endoscopically, a second EGD showed a reddish, flat lesion with an elevated mass within the ED. Endoscopic ultrasonography indicated that the elevated mass was deep in the submucosal layer. An esophagram showed that the ED was approximately 80 mm in diameter, which is considered large. An endoscopic biopsy of the lesion confirmed squamous cell carcinoma. Total esophagectomy was performed. Microscopic examination revealed well-differentiated to moderately differentiated squamous cell carcinoma invading the adventitia at the elevated lesion. The final pathological stage was pT3N0M0. There was no evidence of recurrence for 3 years during the quarterly follow-up examinations. To our knowledge, this case involved the longest asymptomatic term (40 years) since the ED was detected. A review of 18 reported cases of carcinoma in an ED indicated that advanced cancer has a poor prognosis. Periodic follow-up of ED patients is essential for early diagnosis.

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., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Myotonic dystrophy is a progressive disorder mainly affecting the voluntary muscles. We herein report a rare case of myotonic dystrophy complicated with high-resolution manometry-defined achalasia, the pathology of which is absent relaxation of the smooth muscles of lower esophageal sphincter (LES). In the present case, achalasia was considered a complication of myotonic dystrophy instead of sporadic achalasia, as on performing high-resolution manometry, the finding of an impaired LES relaxation (myotonic phase) changed to a totally emaciated LES function (muscle weakness phase) as myotonic dystrophy progressed.

Background and Aim: Functional gastrointestinal disorders are the most common disorders in gastroenterology and are currently considered as gut-brain interaction disorders with multiple related factors including motility disturbance. However, high-resolution manometry (HRM) had revealed a new disease concept known as minor esophageal motility disorders. This study aimed to investigate the correlation between functional esophageal disorders (FEDs) and minor esophageal motility disorders., Methods: Functional esophageal disorders were diagnosed using upper endoscopy, pH monitoring, and HRM, to exclude achalasia, esophago-gastric junction outflow obstruction, and other major esophageal motility disorders. FEDs with or without minor esophageal motility disorders were compared using the Chicago classification., Results: Twelve healthy volunteers also subjected to HRM showed no minor esophageal motility disorders. Of the 40 patients with FEDs, 15 (37.5%) were diagnosed with minor esophageal motility disorders. Characteristics were not different between patients with and without minor esophageal motility disorders (sex: P = 0.609, age: P = 0.054, body mass index: P = 0.137, and presence of psychiatric disorders: P = 0.404). The type and location of symptoms were not related to the comorbidity rate of minor esophageal motility disorders (P = 0.744 and 0.094). No patients with FEDs developed major esophageal motility disorders., Conclusions: Minor esophageal motility disorders were frequently observed in FEDs, but the causal relationship between esophageal symptoms remains unclear. The disease concepts of FEDs and minor esophageal motility disorders are considered to overlap and are both independent of major esophageal motility disorders., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and study aims  Several previous reports indicate that endoscopic injection of triamcinolone acetonide (TA) after widespread endoscopic submucosal dissection (ESD) is effective for preventing esophageal stricture. We investigated the efficacy of injecting TA in two sessions for preventing stricture formation post-ESD. Patients and methods  Sixty-six consecutive patients with widespread mucosal defects that affected more than three-fourths of the circumference of the esophagus were included. The study group (n = 40) received TA injections over two sessions: immediately after and 14 days after ESD. The control group (n = 26) did not receive a TA injection. This study was performed retrospectively against historical controls. The primary endpoint of this study was frequency of stricture after TA injection. The secondary endpoint was number of required endoscopic balloon dilations (EBDs) after TA injection. Results  The post-ESD stricture rate among patients who had subcircumferential mucosal defects was 45.7 % in the study group (16/35 patients), which was significantly lower than the rate of 73.9 % in the control group (17/23 patients; P  = 0.031). The number of EBD procedures required was significantly lower in the study group (median 0, range 0 - 7) than in the control group (median 4, range 0 - 20; P  < 0.001). There was no significant difference between the study and control groups among the patients who had full circumferential mucosal defects. Conclusion  This study showed that performing two sessions of TA injection is an effective and safe treatment for prevention of esophageal stricture following subcircumferential ESD.

Esophageal diverticula are rare conditions that cause esophageal symptoms, such as dysphagia, regurgitation, and chest pain. They are classified according to their location and characteristic pathophysiology into three types: epiphrenic diverticulum, Zenker's diverticulum, and Rokitansky diverticulum. The former two disorders take the form of protrusions, and symptomatic cases require interventional treatment. However, the esophageal anatomy presents distinct challenges to surgical resection of the diverticulum, particularly when it is located closer to the oral orifice. Since the condition itself is not malignant, minimally invasive endoscopic approaches have been developed with a focus on alleviation of symptoms. Several types of endoscopic devices and techniques are currently employed, including peroral endoscopic myotomy (POEM). However, the use of minimally invasive endoscopic approaches, like POEM, has allowed the development of new disorder called iatrogenic esophageal diverticula. In this paper, we review the pathophysiology of each type of diverticulum and the current state-of-the-art treatment based on our experience., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

Background: Esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (MM) and submucosa up to 200 µm (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., Competing Interests: None., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Aim: Achalasia is an esophageal motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation. On high-resolution manometry (HRM), impaired LES relaxation is defined by elevated integrated relaxation pressure (IRP). However, a new category of achalasia within the normal IRP range has been suggested., Methods: HRM was performed using a Starlet device and an IRP threshold of 26 mmHg. Peroral endoscopic myotomy (POEM) was performed for cases of achalasia diagnosed using established methods. During POEM, the histology of the LES was assessed. Follow-up was performed 2 months post-operatively., Results: Forty-one patients with achalasia (18 women, mean age 53 ± 18.6 years) were included. Among them, 27 were placed in the IRP > 26 mmHg subgroup (impaired LES relaxation on HRM) and 14 in the IRP ≤ 26 mmHg subgroup (normal LES relaxation on HRM). In the IRP ≤ 26 mmHg subgroup, patients were older, had longer symptom duration, and had more esophageal dilation. The IRP ≤ 26 mmHg subgroup had the same symptom severity as the higher IRP subgroup and POEM significantly improved symptoms and IRP, although four patients still had severe LES fibrosis., Conclusions: The clinical presentation of achalasia has a gap between a HRM-defined impaired LES relaxation, with aging or disease progression considered reasons for a lowered LES pressure. POEM can be a feasible treatment option, even for cases of achalasia with a normal IRP. However, patients with severe LES fibrosis need more attention for the therapeutic indication.

High-resolution manometry (HRM) and peroral endoscopic myotomy (POEM) have contributed significantly to the field of esophageal motility disorders in recent years. The development of HRM has categorized various esophageal motility disorders with a focus on a diverse range of manometric anomalies. Additionally, the Chicago classification criteria is widely used for manometric diagnosis. Moreover, POEM was introduced as a minimally invasive radical therapy for achalasia and shows promise for other spastic esophageal motility disorders as well. POEM has also enabled a transluminal endoscopic approach for determining the histology of the esophageal muscle layer, which is expected to assist in elucidating the etiology of disorders associated with esophageal motility. The purpose of this review is to update the diagnosis, pathology, and treatment of esophageal motility disorders, with a focus on the recent advances in this field.

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 ΔDCI with the circumferential mucosal defect ratio {P < 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P < 0.01, r = -0.601), and the number of stricture resolutions (P < 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., (© The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests.

Background and Aims: The safety and efficacy of endoscopic submucosal dissection (ESD) in elderly patients remain unclear. The aim of this study is to clarify the short- and long-term outcomes of colorectal ESD in elderly patients., Patients and Methods: A total of 482 consecutive patients with 501 colorectal lesions treated with ESD from February 2005 to December 2013 were retrospectively reviewed. Patients were divided into two groups: an elderly group (≥ 75 years of age) and a non-elderly group (< 75 years of age). Short-term outcomes of interest were procedure time, complication rate, hospital stay, en bloc resection rate, and non-curative resection rate. Long-term outcomes of interest were disease-specific survival, and overall survival rates in the elderly group (51 patients) and non-elderly group (92 patients) were also analyzed., Results: No significant differences were observed between the groups with respect to short-term outcomes. Two patients in each group required emergency surgery. Of the patients who underwent non-curative resection, 7/12 (58%) in the elderly group and 15/23 (65%) in the non-elderly group underwent additional surgery. The 5-year disease-specific survival rates in the elderly and non-elderly groups were both 100%, and the corresponding 5-year overall survival rates were 86.3 and 93.5%, respectively (p = 0.026)., Conclusions: Short-term outcomes after colorectal ESD were equivalent in both groups, and all patients showed favorable long-term outcomes. Considering the benign prognosis of lesions resected with ESD, preoperative screening of comorbidities is essential to improve overall survival.

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., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background and Aims: In patients with amyotrophic lateral sclerosis (ALS), percutaneous endoscopic gastrostomy (PEG) placement under sedation often causes apnea or hypoventilation. The aim of the present study was to assess whether unsedated PEG placement in ALS patients using ultrathin endoscopy (UTE) via the transoral route can improve safety., Methods: Between 2003 and 2013, PEG placement was identified and reviewed in 45 patients with ALS. PEG was performed in 14 patients using transoral UTE without sedation (UTE group), 17 patients using conventional normal-diameter esophagogastroduodenoscopy (C-EGD) without sedation (unsedated C-EGD group) and 14 patients using C-EGD with sedation (sedated C-EGD group). We compared the clinical features, cardiopulmonary data before and during PEG placement, and complications related to PEG placement among the three groups., Results: There were no significant differences in age, male/female ratio, forced vital capacity, blood pressure, oxygen saturation before and during PEG, or major complications among the three groups. No minor complications were observed in the UTE group, whereas apnea and/or hypoventilation were observed in the sedated C-EGD group and aspiration pneumonia was observed in the unsedated C-EGD group., Conclusions: Unsedated PEG placement using transoral UTE in ALS patients is a safe method.

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., Competing Interests: The authors declare that there are no competing interests regarding the publication of this manuscript.

The specific induction of genes in response to distinct environmental stress is vital for all eukaryotes. To study the mechanisms that result in selective gene responses, we examined the role of the fission yeast Tup1 family repressors in chromatin regulation. We found that chromatin structure around a cAMP-responsive element (CRE)-like sequence in ade6-M26 that is bound by Atf1.Pcr1 transcriptional activation was altered in response to osmotic stress but not to heat and oxidative stresses. Such chromatin structure alteration occurred later than the Atf1 phosphorylation but correlated well with stress-induced transcriptional activation at ade6-M26. This chromatin structure alteration required components for the stress-activated protein kinase (SAPK) cascade and both subunits of the M26-binding CREB/ATF-type protein Atf1.Pcr1. Cation stress and glucose starvation selectively caused chromatin structure alteration around CRE-like sequences in cta3(+) and fbp1(+) promoters, respectively, in correlation with transcriptional activation. However, the tup11Delta tup12Delta double deletion mutants lost the selectivity of stress responses of chromatin structure and transcriptional regulation of cta3(+) and fbp1(+). These data indicate that the Tup1-like repressors regulate the chromatin structure to ensure the specificity of gene activation in response to particular stresses. Such a role for these proteins may serve as a paradigm for the regulation of stress response in higher eukaryotes.