Search

Competing Interests: Conflict of interest None.

Objectives: This study was designed to investigate the effects of a completely passive isokinetic cycle (PIC) exercise with electromyostimulation (EMS) on improving muscle strength and the changes in kinesthesia during daily activities., Methods: Twenty-nine sedentary females were divided into three groups. The EMS anterior and whole groups performed the PIC exercise without EMS 3 times a week for 3 weeks, followed by a 1-week break, and then performed it with EMS applied to the anterior and entire thigh muscles, respectively, 3 times a week for 3 weeks. The control group did not perform any training., Results: The PIC exercise with EMS significantly increased the 30s chair stand test scores by 12-16% and the maximum isometric knee extension and flexion torques by 38-68% in both EMS-applied groups. The participants found its exercise easy and felt more comfortable with daily physical activities. The exercise without EMS did not show similar improvements. Muscle soreness was significantly greater in the EMS anterior group than in the EMS whole group; however, it was not severe., Conclusions: The PIC exercise with EMS resulted in significant increases in muscle strength, facilitating a perceived ease of daily physical activities, while minimizing difficulties, effort, and notable muscle soreness., (Copyright: © 2023 Hylonome Publications.)

Aims/introduction: The mechanisms underlying the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on aortic endothelial dysfunction in diet-induced obesity are not clearly understood. This study investigated whether SGLT2 inhibition by luseogliflozin improved free fatty acid (FFA)-induced endothelial dysfunction in high-fat diet (HFD)-induced obese mice., Materials and Methods: Mice were fed a control diet or high-fat diet for 8 weeks, and then each diet with or without luseogliflozin was provided for an additional 8 weeks under free or paired feeding. Afterward, the thoracic aortas were removed and utilized for the experiments., Results: Luseogliflozin treatment decreased body weight, fasting blood glucose, insulin, and total cholesterol in HFD-fed mice only under paired feeding but not under free feeding. Endothelial-dependent vasodilation under FFA exposure conditions was significantly lower in HFD-fed mice than in control diet-fed mice, and luseogliflozin treatment ameliorated FFA-induced endothelial dysfunction. Reactive oxygen species (ROS) production induced by FFA was significantly increased in HFD-induced obese mice. Luseogliflozin treatment increased the expression of superoxide dismutase 2 (SOD2), an antioxidative molecule, and reduced FFA-induced ROS production in the thoracic aorta. Superoxide dismutase reversed FFA-induced endothelial dysfunction in HFD-fed mice., Conclusions: It was shown that caloric restriction is important for the effect of luseogliflozin on metabolic parameters and endothelial dysfunction. Furthermore, SGLT2 inhibition by luseogliflozin possibly ameliorates FFA-induced endothelial dysfunction by increasing SOD2 expression and decreasing reactive oxygen species production in the thoracic aorta., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Delayed bleeding (DB) rarely occurs after cold snare polypectomy (CSP) for colorectal polyps, but no large-scale studies have investigated this. The present study evaluated the rate, characteristics, and risk factors of DB of CSP., Methods: We conducted a multicenter retrospective study at 10 Japanese institutions. A total of 18,007 patients underwent CSP for colorectal polyps ≤ 10 mm in size from March 2015 to September 2019, and cases of DB (DB group) were analyzed for the rate, antithrombotic drugs, polyp size, morphology, location, and risk factors. As a control, 269 non-bleeding cases (non-DB group) with 606 polyps who underwent CSP at the same 10 facilities in the 2-week study period were extracted., Results: We analyzed 26 DB cases with 28 lesions, and the total DB rate was 0.14% (26/18,007). The DB group had significantly higher rates of using antiplatelets (42.3% vs. 13.0%, p < 0.001) and anticoagulants (19.2% vs. 2.6%, p = 0.002), and significantly higher rates of polyp size ≥ 5 mm (67.9% vs. 45.2%, p = 0.015), rectal lesion (25.0% vs. 6.6%, p = 0.003), and polypoid lesion (89.3% vs. 55.3%, p < 0.001) than the non-DB group. A multivariate analysis (odds ratio; 95% confidence interval) for patient characteristics showed antiplatelet use (4.521; 1.817-11.249, p = 0.001) and anticoagulant use (7.866; 20.63-29.988, p = 0.003) as independent risk factors for DB. Polyp size ≥ 5 mm (3.251; 1.417-7.463, p = 0.005), rectal lesion (3.674; 1.426-9.465, p = 0.007), and polypoid lesion (7.087; 20.81-24.132, p = 0.002) were also risk factors for lesion characteristics., Conclusions: The rate of DB was 0.14% and antithrombotic drug use, polyp size, location, and morphology were related to it., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Previous reports have shown favorable performance of artificial intelligence (AI) systems for diagnosing esophageal squamous cell carcinoma (ESCC) compared with endoscopists. However, these findings don't reflect performance in clinical situations, as endoscopists classify lesions based on both magnified and non-magnified videos, while AI systems often use only a few magnified narrow band imaging (NBI) still images. We evaluated the performance of the AI system in simulated clinical situations. We used 25,048 images from 1433 superficial ESCC and 4746 images from 410 noncancerous esophagi to construct our AI system. For the validation dataset, we took NBI videos of suspected superficial ESCCs. The AI system diagnosis used one magnified still image taken from each video, while 19 endoscopists used whole videos. We used 147 videos and still images including 83 superficial ESCC and 64 non-ESCC lesions. The accuracy, sensitivity and specificity for the classification of ESCC were, respectively, 80.9% [95% CI 73.6-87.0], 85.5% [76.1-92.3], and 75.0% [62.6-85.0] for the AI system and 69.2% [66.4-72.1], 67.5% [61.4-73.6], and 71.5% [61.9-81.0] for the endoscopists. The AI system correctly classified all ESCCs invading the muscularis mucosa or submucosa and 96.8% of lesions ≥ 20 mm, whereas even the experts diagnosed some of them as non-ESCCs. Our AI system showed higher accuracy for classifying ESCC and non-ESCC than endoscopists. It may provide valuable diagnostic support to endoscopists., (© 2022. The Author(s).)

Background: Both insulin resistance and postprandial glucose spikes are known for their potential to induce vascular endothelial dysfunction in individuals with metabolic syndrome. However, these factors are inextricable, and therefore, their relative contributions to inducing endothelial dysfunction remain elusive. In this study, we aimed to disentangle the effects of these factors and clarify whether bardoxolone methyl (CDDO-Me), a novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator, protects against glucose spike-induced endothelial dysfunction., Methods: We induced glucose spikes twice daily for a duration of 1 week to rats fed a standard/control diet (CD) and Western-type diet (WTD). Endothelium-dependent relaxation (EDR) was evaluated using isolated thoracic aortas. Gene expression and dihydroethidium (DHE)-fluorescence studies were carried out; the effect of CDDO-Me on aortic endothelial dysfunction in vivo was also evaluated., Results: Neither WTD-induced insulin resistance nor pure glucose spikes significantly deteriorated EDR. However, under high-glucose (20 mM) conditions, the EDR of thoracic aortas of WTD-fed rats subjected to glucose spikes was significantly impaired. In this group of rats, we observed significantly enhanced DHE fluorescence as a marker of reactive oxygen species, upregulation of an oxidative stress-related gene (NOX2), and downregulation of an antioxidant gene (SOD2) in the thoracic aortas. As expected, treatment of the thoracic aorta of this group of rats with antioxidant agents significantly improved EDR. We also noted that pretreatment of aortas from the same group with CDDO-Me attenuated endothelial dysfunction, accompanied by a correction of the redox imbalance, as observed in gene expression and DHE fluorescence studies., Conclusions: For the first time, we showed that insulin resistance and glucose spikes exert a synergistic effect on aortic endothelial dysfunction. Furthermore, our study reveals that CDDO-Me ameliorates endothelial dysfunction caused by glucose spikes in a rat model of metabolic syndrome., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: High-grade dysplasia (HGD) and T1 lesions are accidentally resected by cold snare polypectomy (CSP) and the characteristics, and follow-up of them has not been reported. In this study, we analyzed the histopathological findings and recurrence of them., Methods: This was a multicenter retrospective-cohort study. We collected HGD and T1 lesions of ≤ 10 mm resected by CSP among 15 520 patients receiving CSP from 2014 to 2019 at nine related institutions, and we extracted only cases receiving definite follow-up colonoscopy after CSP of HGD and T1 lesions. We analyzed these tumor's characteristics and therapeutic results such as R0 resection and local recurrence and risk factors of recurrence., Results: We collected 103 patients (0.63%) and extracted 80 lesions in 74 patients receiving follow-up colonoscopy for CSP scar. Mean age was 68.4 ± 12.0, and male rate was 68.9% (51/80). The mean tumor size (mm) was 6.6 ± 2.5, and the rate of polypoid morphology and rectum location was 77.5% and 25.0%. The rate of magnified observation was 53.8%. The rates of en bloc resection and R0 resection were 92.5% and 37.5%. The local recurrence rate was 6.3% (5/80, median follow-up period: 24.0 months). The recurrence developed within 3 months after CSP for four out of five recurrent cases. Comparing five recurrent lesions to 75 non-recurrent lesions, a positive horizontal margin was a significant risk factor (60.0% vs 10.7%, P < 0.001)., Conclusions: High-grade dysplasia and T1 resected by CSP were analyzed, and the local recurrence rate of them was substantially high., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and study aims  This study evaluated the technical aspects of colorectal endoscopic submucosal dissection (ESD) with the Clutch Cutter (CC) (Fujifilm Co., Tokyo, Japan), a scissor-type knife, and the S-O clip (SO) as a traction clip, and compared the safety and efficacy to ESD using a needle-type knife. Patients and methods  This was a single-center retrospective study. In Study 1, we evaluated 125 ESD patients: 60 using the SO and CC (SO group) and 65 using the CC (CC group). In Study 2, we evaluated 185 ESD patients: the CC group (N = 65) and 120 using the Flush knife BT-S (Flush group) (Fujifilm Co., Tokyo, Japan). In both studies, the clinicopathological features and therapeutic outcomes were compared using a propensity score-matched analysis. Results  In 36 pairs of matched patients in Study 1, the rates of en bloc resection, R0 resection, perforation, and postoperative bleeding (POB) were 97.2 %, 88.9 %, 2.8 %, and 0 %, respectively, for the SO group and 100 %, 91.7 %, 0 %, and 0 % for the CC group (not significant). The mean procedure time for the SO group among less-experienced endoscopists was significantly shorter than in the CC group (42 vs. 65 minutes, P  = 0.036). In 49 pairs of matched patients in Study 2, the rates of en bloc resection, R0 resection, perforation, and POB were 100 %, 95.8 %, 0 %, and 0 %, respectively, for the CC group and 98.0 %, 95.8 %, 0 %, and 2.0 % for the Flush group (not significant). The mean procedure time in the CC group among less-experienced endoscopists was significantly shorter than in the Flush group (52 vs. 67 minutes, P  = 0.038). Conclusions  CC and the combined use of CC and SO reduced colorectal ESD procedure time among less-experienced endoscopists., Competing Interests: Competing interests Drs. Yoshida (J162001222) and Naito (J162003400, J162003294) received a research grant from Fujifilm Medical Co., Ltd. Dr. Itoh (J082003006) was affiliated with a department that was partially funded by Fujifilm Medical Co., Ltd., (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: The balance between pro-atherogenic and anti-atherogenic factors is very crucial in the development of atherosclerotic lesions. Although the expression of the six-transmembrane epithelial antigen of the prostate 4 (STEAP4) in myeloid cells is known to be atheroprotective, there is not a single study reporting on the status of STEAP4 expression in circulating monocytes in the early stages of diet-induced obesity or in events of glycemic excursions., Methods: We induced glycemic spikes twice daily for a 1-week duration to rats fed on regular chow and western diet, and analyzed gene expression changes in the peripheral blood mononuclear cells (PBMCs). We also conducted experiments on RAW 264.7 cells to gain insight into some of our in vivo findings., Results: Diet-induced obesity and glycemic excursions independently caused a significant increase in STEAP4 mRNA expression in PBMCs. This was also accompanied by an induction of a substantial number of pro-inflammatory cytokines, chemokines, and chemokine receptors. However, the combined effect of western diet and hyperglycemic spikes was subtle and non-additive. In the in vitro setting, either glucose spikes, persistent hyperglycemia, or a combination of palmitic acid and insulin resulted in a parallel increase in expression of STEAP4 and pro-inflammatory genes. This was, however, significantly abrogated with 4-octyl itaconate or attenuated by inhibitors of p38MAPK and NF-kB., Conclusions: STEAP4 expression in mononuclear cells is induced by increasing inflammation or oxidative stress. The observed increase in STEAP4 expression in circulating monocytes due to visceral obesity or glycemic excursions is a compensatory response., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00542-1., Competing Interests: Conflict of interestAll authors declare no conflict of interest., (© The Japan Diabetes Society 2021, corrected publication 2021.)

Purpose: For rectal neuroendocrine tumors (NETs) ≤ 10 mm, endoscopic resection is a standard treatment. However, there is no consensus whether additional surgery should be performed for patients at risk of lymph node metastasis (LNM) after endoscopic resection. The purpose of this study was to analyze the results of endoscopic resection and additional surgery of rectal NETs, thereby clarify the characteristics of cases with LNM., Methods: This study was a multicenter retrospective cohort study conducted at 12 Japanese institutions. A total of 132 NETs ≤ 10 mm were analyzed regarding various therapeutic results. A comparative analysis was performed by dividing the cases into two groups that underwent additional surgery or not. Furthermore, the relationship between tumor size and LNM was examined., Results: The endoscopic treatments were 12 endoscopic mucosal resections (EMR), 58 endoscopic submucosal resections with ligation (ESMR-L), 29 precutting EMRs, and 33 endoscopic submucosal dissections (ESD). The R0 resection rates of EMR were 41.7%, and compared to this rate, other three treatments were 86.2% (p < 0.001), 86.2% (p = 0.005), and 97.0% (p < 0.001), respectively. There were 41 non-curative cases (31.1%), and 13 had undergone additional surgery. Then, LNM was observed in 4 of the 13 patients, with an overall rate of LNM of 3.0% (4/132). The rate of positive lymphatic invasion and the rate of LNM by tumor size ≤ 6 mm and 7-10 mm were 9.7 vs. 15.4% (p = 0.375) and 0 vs. 10.3% (p = 0.007)., Conclusions: A multicenter study revealed the priority of each endoscopic resection and the low rate of LNM for rectal NETs ≤ 6 mm.

Introduction: The number of colonoscopy (CS) for the elderly is increasing. There are only a few reports focusing on CS among the very elderly aged ≥ 90-y. We aimed to analyze the efficacy of CS and of colorectal cancer (CRC) for patients aged ≥ 90-y., Methods: We retrospectively analyzed consecutive patients aged ≥ 90-y receiving CS at eight institutions from October 2016 to September 2017. Bowel preparation, complications, and endoscopic diagnosis were analyzed. The non-elderly group aged between 50-y and 64-y and elderly group aged between 65-y and 79-y were compared to very-elderly group aged ≥ 90-y. Through propensity score matching of sex and CS indications (symptomatic or asymptomatic), the number of CRC and the treatment in each group were analyzed., Results: We analyzed 125 patients receiving 154 colonoscopies (0.9%) in the very-elderly group from among 16,968 cases. Among 92 cases who received bowel-cleansing solution, good preparations were achieved in 94.5%. The rate of CS-related complications was 1.3% (2/154). The rate of CRC in the very-elderly group was 27.2% (34/125), higher than the non-elderly group (7.2%, 9/125, p < 0.01) and elderly group (8.8%, 11/125, p < 0.01). Therapeutic interventions for CRC in the very-elderly group were performed in 73.5% (24/34) patients. The mean survival of 12 patients with CRC resection was 788 days., Conclusions: CS could be performed safely for the very elderly aged ≥ 90-y with careful considerations. CRC was confirmed to be more frequent in this group with over 70% of patients receiving appropriate therapeutic intervention.

Background: In general, basal insulin targets fasting plasma glucose (FPG) levels, and prandial insulin targets postprandial glucose (PPG) levels. However, the effects of basal insulin on PPG levels are controversial. We investigated the effect of basal insulin on postprandial hyperglycemia using a test meal at breakfast as well as compared differences between degludec and glargine., Methods: A total of 20 participants with type 2 diabetes were randomly assigned to degludec ( n  = 10) or glargine ( n  = 10). We initiated basal-bolus insulin therapy and titrated only basal insulin until FPG was < 6.1 mmol/L. We evaluated changes in post-breakfast glucose levels and changes in clinical parameters such as serum C-peptide (CPR), proinsulin (PI), and free fatty acids (FFA) levels between the pre- and post-titration periods. Differences between degludec and glargine in the post-titration period were also evaluated., Results: Post-breakfast glucose levels significantly decreased by 46.1% in the post-titration period compared with the pre-titration period ( n  = 20, p  < 0.001). These decreases correlated positively with decreases in the post-breakfast PI/CPR ratio ( r  = 0.692, p  < 0.001) and in fasting FFA levels ( r  = 0.720, p  < 0.001). There were no significant differences in post-breakfast glucose levels between degludec and glargine. However, the hypoglycemic rate with degludec was significantly lower than with glargine., Conclusion: Our results suggest that basal insulin with either degludec or glargine decreases the incidence of post-breakfast hyperglycemia accompanied by decreasing the post-breakfast PI/CPR ratio and fasting FFA levels in patients with type 2 diabetes., Competing Interests: Conflict of interestYoshihiko Nishio has received honoraria for scientific lectures from Eli Lilly Japan, Sanofi, and Novo Nordisk Pharma; and received grants/research support from Novo Nordisk Pharma. Kazuma Ogiso, Nobuyuki Koriyama, Takahiko Obo and Akinori Tokito have nothing to disclose., (© The Japan Diabetes Society 2020.)

Background: Local recurrence after cold snare polypectomy (CSP) of colorectal polyps has not been well analyzed. In this study, we analyzed the characteristics of local recurrence., Methods: We retrospectively reviewed consecutive lesions resected by CSP from 2014 to 2016 and lesions that were followed up at ≥ 10 months after CSP, were analyzed. Our indication for CSP was a benign tumor of < 15 mm in size. We analyzed local recurrence and its risk factors using multivariate analyses. In addition, we compared lesions of ≥ 10 mm and < 10 mm. Moreover, therapeutic methods for recurrence were analyzed., Results: Finally, we analyzed 554 cases out of 820 consecutive cases. The mean polyp size was 5.3 ± 2.8 mm and the en bloc resection and histopathological complete resection rates were 99.3% and 70.2%, respectively. The overall recurrence rate was 1.9% (mean follow-up period: 13.0 ± 4.0 months). Significant differences were observed between 11 recurrent lesions and 543 lesions without recurrence regarding polyp size (8.0 ± 3.7 mm vs. 5.2 ± 2.7 mm, p < 0.001), rate of sessile-serrated polyp (27.3% vs. 3.0%, p < 0.001), and histopathological positive margin (45.4% vs. 3.7%, p = 0.019). Multivariate analyses showed that a histopathological positive margin was the only significant risk factor for local recurrence (OR 16.600, 95% CI 3.707-74.331, p < 0.001). Regarding the comparison between 74 lesions of ≥ 10 mm and 480 lesions of < 10 mm, significant differences were observed in the en bloc resection rate (93.2% vs. 100%, p < 0.001), high-grade dysplasia rate (8.1% vs. 0.8%, p < 0.001), and histopathological complete resection rate (54.0% vs. 72.7%, p = 0.001). The recurrence rates of these two groups were 5.4% and 1.4%, respectively (p = 0.069). All recurrent cases could be resected with repeat CSP., Conclusions: The local recurrence rate after CSP for lesions of < 10 mm was 1.4%. CSP was not recommended for lesions of ≥ 10 mm due to high rates of recurrence and malignancy.

Background: Neurofibromatosis type 1 is characterized by multiple café au lait spots and cutaneous and plexiform neurofibromas, and is one of the most common autosomal dominant hereditary disorders caused by mutations of the neurofibromatosis type 1 tumor suppressor gene. Osteomalacia in neurofibromatosis type 1 is very rare and is characterized by later onset in adulthood. In humans, fibroblast growth factor 23, which is a causative factor of tumor-induced osteomalacia, is not only a paracrine and autocrine factor, but is also a physiological regulator of phosphate balance in normal serum., Case Presentation: Our patient was a 65-year-old Japanese woman whose neurofibromas began to appear when she was in elementary school. At age 28, she was diagnosed as having neurofibromatosis type 1. A spinal compression fracture and multiple rib fractures were identified in 2012 and 2017, respectively. Her laboratory findings revealed hypophosphatemia due to renal phosphate wasting and a high serum level of fibroblast growth factor 23. Neurofibromas located on the surface of her right forearm and left upper arm, in which a slight abnormal accumulation of tracers was observed on 111 indium-pentetreotide scintigraphy, were surgically removed, but there was no improvement in hypophosphatemia or serum fibroblast growth factor 23 after surgery. Therefore, we administered eldecalcitol, which also failed to produce improvement in abnormal data. Subsequent combination with dibasic calcium phosphate hydrate led to improvement in some of the abnormalities, including hypophosphatemia. Immunohistochemical staining using anti-human fibroblast growth factor 23 antibody revealed slightly positive results, however, only one out of three amplifications of the fibroblast growth factor 23 gene was observed by real-time polymerase chain reaction, and no clear fibroblast growth factor 23 gene expression in the resected neurofibromas could be confirmed., Conclusions: We here describe a first rare case of a 65-year-old woman with neurofibromatosis type 1 associated with hypophosphatemic osteomalacia in which a high serum fibroblast growth factor 23 level was confirmed.

Objectives: An endoscope with a light-emitting diode (LED) light source which has a 2-mm close-distance observation function without magnification, has been marketed, enabling linked color imaging (LCI) and blue laser imaging (BLI) for tumor detection and characterization. We analyzed the efficacy of a LED endoscope compared to a LASER endoscope., Methods: We retrospectively reviewed 272 lesions observed using the LED endoscopic system (Fujifilm Co., Tokyo, Japan) from May 2018 to September 2019. The Japanese NBI Classification was used for tumor characterization. We analyzed the diagnostic accuracy and confidence level. Sixty-one lesions observed with both the LED and magnified LASER endoscopes were also analyzed to compare the diagnostic accuracy. Regarding the tumor detectability, we calculated color difference values (CDVs) and brightness values (BVs) of white-light imaging, BLI, and LCI modes between the two endoscopes for each tumor., Results: The mean polyp size was 9.2 ± 11.3 mm. Histology showed 71 sessile serrated lesions, 193 adenoma and high-grade dysplasias, and 8 T1 cancers. The diagnostic accuracy of tumors ≥ 10 and < 10 mm was 72.0% and 92.9% (p < 0.001), respectively and the high confidence rate was 93.8%. The diagnostic accuracy of LED (77.0%) was a little higher than that of LASER without magnification (65.6%, p = 0.16) but was not inferior to that of LASER with magnification (82.0%, p = 0.50). The respective CDVs of LED and LASER endoscopes were 20.6 ± 11.2 and 21.6 ± 11.2 for LCI (p = 0.30), and the respective BVs were 210.0 ± 24.2 and 175.9 ± 21.1 (p < 0.001)., Conclusions: A LED endoscope with close-distance observation improved tumor detection and characterization due to high brightness.

Materials and Methods: This was a multicenter retrospective cohort study. The subjects were patients aged ≥20 years treated for chronic constipation from May 2018 to November 2019 at 12 related institutions. Patients were divided into ≤74 years and ≥75 years old. Elobixibat at 10 mg/day was prescribed for two weeks. We then analyzed the discontinuation due to ineffectiveness, change of spontaneous bowel movements (SBM), stool consistency, the time until the first SBM, adverse events, and effect-related factors., Results: There were 140 cases (61 males) evaluated, with an average age of 72.1 ± 13.6 years (≤74 years: 71 cases; ≥75 years: 69 cases). The discontinuation rate was 7.9%. The SBM (times/week) increased from 2.86 to 6.08 ( p < 0.001). The overall SBM improvement rate was 74.0% (≤74 years: 78.2% vs. ≥75 years: 68.9%, p = 0.31; male: 75.0% vs. female: 73.3%, p = 0.78). The overall improvement rate of stool consistency was 59.6% (≤74 years: 62.9%, ≥75 years: 56.1%, p = 0.42). The time until the first SBM (hours) for those ≤74 years and ≥75 years was 17.2 ± 14.3 and 11.2 ± 8.4 ( p = 0.04). Adverse event rates for those ≤74 years and ≥75 years were 28.2% and 10.1% ( p < 0.01). There were no significant effect-related factors for gender, age, and use of laxatives., Conclusions: Short-period elobixibat is shown to be effective also for the elderly and male., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Akira Tomie et al.)

Background: The prevalence of childhood-onset growth hormone (GH) deficiency (GHD) is estimated to be approximately 1 in 5000 or more, with the cause unknown in most cases (idiopathic isolated GHD). However, additional disorders of secretion of other pituitary hormones reportedly develop over time, with a frequency of 2-94% (median, 16%). Furthermore, median times to development of other anterior pituitary hormone deficiencies have been reported to be 6.4-9.4 years. On the other hand, adult patients affected by childhood-onset GHD reportedly develop impaired ventilation function due to reduced lung volumes and respiratory pressures, probably due to reductions in respiratory muscle strength. In addition, GH is known to play a role in stimulating the glomerular filtration rate (GFR), and the estimated GFR (eGFR) is decreased in patients with GHD., Case Presentation: This case involved a 65-year-old woman. Her short stature had been identified at around 3 years of age, but no effective treatments had been provided. The patient was mostly amenorrheic, and hair loss became apparent in her late 30s. She developed hyperuricemia, dyslipidemia, and hypertension at 45 years of age. In addition, the patient was diagnosed with hypothyroidism at 50 years of age. At 58 years of age, endocrinological examination showed impaired secretion of thyroid-stimulating hormone, luteinizing hormone/follicle-stimulating hormone, and growth hormone, and magnetic resonance imaging showed an empty sella turcica. However, secretion ability of adrenocorticotropic hormone was retained. At 63 years of age, respiratory function tests confirmed a markedly restricted ventilation disorder (vital capacity, 0.54 L; percentage predicted vital capacity, 26.9%). Renal function had also decreased (eGFR, 25.0 mL/min/1.73 m 2 ). Furthermore, she was diagnosed with hypothalamic secondary hypoadrenocorticism. The patient developed CO 2 narcosis at 65 years of age, and noninvasive positive pressure ventilation was started., Conclusions: The rare case of a 65-year-old woman with childhood-onset GHD with panhypopituitarism, including late-onset secondary hypoadrenocorticism in her 60s, associated with severely impaired respiratory function and renal dysfunction, was reported. In GHD patients with risk factors for progression from isolated GHD to combined pituitary hormone deficiency, such as empty sella turcica, lifelong endocrinological monitoring may be important.

Endoscopic submucosal dissection (ESD) for superficial gastrointestinal neoplasms has become widespread. However, certain aspects of the procedure remain difficult to manage, such as intraoperative bleeding and perforation. There are two kinds of scissor-type knife: the Clutch Cutter (Fujifilm Co., Tokyo, Japan) and the SB knife (Sumitomo Bakelite Co., Tokyo, Japan). These knives have different features from other types of ESD knives and enable the performance of all ESD procedures, including mucosal incision, submucosal dissection, and hemostasis. The standard approach with scissor-type knives involves first grabbing the tissue and then incising or dissecting it. Theoretically, perforation as a result of unintentional movement should never happen with scissor-type knives compared to needle- or blade-type knives, which may induce perforation through unintentional movement. Moreover, the rates of severe bleeding and self-completion of ESD with scissor-type knives by non-experts were reported to be significantly better than for other knives. Thus, scissor-type knives can resolve these problems and help to further standardize ESD globally. In this review, we summarize reports on the efficacy of such scissor-type knives for ESD of gastrointestinal tumors. We also present the pocket-creation method and the application of traction devices, such as dental floss and S-O clips (Zeon Medical Co., Tokyo, Japan) for improving the performance of ESD with a Clutch Cutter., (© 2019 Japan Gastroenterological Endoscopy Society.)

Backgrounds and Aims: Recently, direct oral anticoagulants (DOACs) have become widely used for preventing thromboembolism. However, postoperative hemorrhage (POH) is a major complication associated with endoscopic mucosal resection (EMR) for colorectal lesions. In this multicenter study, we analyzed the incidence of POH after EMR associated with DOACs and explored the associated risk factors., Materials and Methods: This study was a multicenter retrospective cohort study conducted at 8 Japanese institutions. A total of 2062 cases that underwent EMR for colorectal lesions at these 8 institutions from October 2016 to September 2017 were analyzed. The cases were divided into 4 groups: the DOAC group (63 cases), warfarin group (34 cases), antiplatelet group (185 cases), and no antithrombotics group (1780 cases). In all lesions of the DOAC and warfarin groups, endoscopic clipping was performed after EMR. The rate of POH in the DOAC group, patients' clinical characteristics, the risk factors of POH, and the rate of thromboembolism due to stopping DOACs were compared with other groups., Results: The rates of POH were 7.9% ∗ (5/63), 2.9% (1/34), 3.2% (6/185), and 0.6% ∗∗ (11/1780) in the DOAC, warfarin, antiplatelet, and no antithrombotics groups, respectively ( ∗ vs. ∗∗ , p < 0.001). Regarding risk factors, the tumor size with POH (mm) was significantly bigger than that without POH (16.2 ± 8.3 vs. 7.2 ± 4.9, p < 0.001). There were no significant differences in the rates of POH based on the type of DOAC. In addition, no thromboembolisms occurred due to stopping of DOAC treatment., Conclusions: Patients receiving DOACs had significantly higher rates of POH after EMR than those without antithrombotics., Competing Interests: All authors have no conflicts of interest to declare., (Copyright © 2019 Ritsu Yasuda et al.)

Background: We analyzed the efficacy of precutting endoscopic mucosal resection (EMR), which is a method of making a full or partial circumferential mucosal incision around a tumor with a snare tip for en bloc resection., Methods: We reviewed cases from 2011 to 2018 in which precutting EMR (n = 167) and standard EMR (n = 557) were performed for lesions of 10 - 30 mm. Precutting EMR was indicated for benign lesions of 20 - 30 mm or lesions of < 20 mm for which standard EMR was difficult. Through propensity score matching of the two groups, the therapeutic outcomes for 35 lesions of ≥ 20 mm and 98 lesions of < 20 mm in each group were analyzed., Results: In the two sizes of lesion, there were significant differences between the precutting and standard groups in the en bloc resection rate (≥ 20 mm 88.6 % vs. 48.5 %, P  < 0.001; < 20 mm 98.0 % vs. 85.7 %, P  = 0.004) and the histological complete resection rate (≥ 20 mm 71.4 % vs. 42.9 %, P  = 0.02; < 20 mm 87.8 % vs. 67.3 %, P  < 0.001)., Conclusion: Precutting EMR enabled high en bloc resection rates in cases involving difficult lesions., Competing Interests: Drs. Yoshida and Naito have received research grants from FUJIFILM Medical Co., Ltd., (© Georg Thieme Verlag KG Stuttgart · New York.)

There is a paucity of aggregated clinical trials on strategies of ameliorating endothelial dysfunction associated with Metabolic Syndrome (MS). We reviewed clinical trials conducted between 2008 and 2017, reporting on strategies of improving endothelial function in patients with MS. A comprehensive search of published articles by the Google Scholar and PubMed were carried out. Only studies involving non-invasive, objective measurement of endothelial function were included. Thirty (30) studies were selected for analysis, in which physical exercise training, diet modification, calcium channel blockers + alpha-lipoic acid, bezafibrate, allopurinol, mesoglycan, and l-arginine supplementation significantly improved Endothelial-Dependent Vasodilation (EDV) in patients with MS but without cardiovascular diseases. Large multicenter clinical trials are required to address the question of generalizability of these findings., (Copyright © 2019 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

A laser endoscopy system was developed in 2012. The system allows blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) to be performed as modes of narrow-band light observation; these modes have been reported to be useful for tumor detection and characterization. Furthermore, an innovative endoscopy system using four-light emitting diode (LED) multilight technology was released in 2016 to 2017 in some areas in which laser endoscopes have not been approved for use, including the United States and Europe. This system enables blue light imaging (this is also known as BLI) and LCI with an LED light source instead of a laser light source. Several reports have shown that these modes have improved tumor detection. In this paper, we review the efficacy of BLI and LCI with laser and LED endoscopes in tumor detection and characterization.

Background/aims: Settings of structure and color enhancement (CE) change view of white light imaging and a preset low enhancement setting is used regularly. The aim of this study was to investigate whether higher enhancement settings increased colorectal lesions' visibility with endoscopists' visibility scoring and objective color difference (CD) value., Methods: From April 2015 to September 2015, we analyzed 27 pictures and 100 videos of colorectal lesions. Combinations of structure enhancement (B3, A3, A5) and CE (CE 0, 1, 3) were evaluated and CD values of 2 corresponding modes (high enhancement: A5 + CE3, preset low enhancement: A3 + CE0) were calculated using marketed software. In the video, these 2 modes were evaluated. All pictures and movies were graded by 4 endoscopists using visibility scores: score 4 (excellent) to score 1 (poor)., Results: The scores of A3 + CE0 (2.74 ± 1.09) were significantly lower than those of all other higher enhancement settings such as B3 + CE1 (3.11 ± 1.08), A3 + CE1 (3.33 ± 0.91), and A5 + CE3 (3.56 ± 0.74; p < 0.001). The CD value of A5 + CE3 was significantly higher than A3 + CE0 (20.2 ± 6.9 vs. 12.9 ± 5.6, p < 0.001). In the video, the scores for A5 + CE3 were significantly higher than A3 + CE0 (3.27 ± 0.83 vs. 2.53 ± 1.05, p < 0.001)., Conclusions: Higher enhancement settings increased visibility of colorectal lesions., (© 2018 S. Karger AG, Basel.)

Introduction: Previous narrow-band imaging (NBI) was dark and reported not to be useful for polyp detection. In this study, we analyzed the efficacy of an additional 30-s observation of the right-sided colon with the recent bright high-resolution NBI., Methods: We enrolled patients undergoing colonoscopy from February 2015 to May 2017 in two institutions. All procedures were performed with the latest system (EVIS LUCERA ELITE, Olympus). The cecum and ascending colon were first observed with white light imaging (WLI) in both the NBI and WLI group. Then, the colonoscope was re-inserted, and the cecum and ascending colon were observed for an additional 30 s. In this second observation, NBI was performed for the first 130 patients in the NBI group and WLI for the next 130 in the WLI group. The number of adenoma and sessile serrated polyps (ASPs) in the second observation were examined in both groups. According to our initial pilot study, the sample size was estimated at 126., Results: In the first observation, the number of ASPs was 72 in the NBI group and 72 in the WLI group (p = 1.0). In the second observation, the number of ASPs was 23 in the NBI group and 10 in the WLI group (p = 0.02). The polyp and adenoma detection rates in the second observation were 16.2% and 12.3% in the NBI group and 7.7% (p = 0.03) and 6.2% (p = 0.09) in the WLI group., Conclusions: The additional 30-s observation with recent NBI decreased missed polyps in the right-sided colon.

Background and Aims: Various risk factors for lymph node metastasis (LNM) have been reported in colorectal T1 cancers. However, the factors available are insufficient for predicting LNM. We therefore investigated the utility of the new histological factor "pure well-differentiated adenocarcinoma" (PWDA) as a safe factor for predicting LNM in T1 and T2 cancers., Materials and Methods: We reviewed 115 T2 cancers and 202 T1 cancers in patients who underwent surgical resection in our center. We investigated the rates of LNM among various clinicopathological factors, including PWDA. PWDA was defined as a lesion comprising only well-differentiated adenocarcinoma. The consistency of the diagnosis of PWDA was evaluated among two pathologists. In addition, 72 T1 cancers with LNM from 8 related hospitals over 10 years (2008-2017) were also analyzed., Results: The rates of LNM and PWDA were 23.5% and 20.0%, respectively, in T2 cancers. Significant differences were noted between patients with and without LNM regarding lymphatic invasion (81.5% vs. 36.4%, p < 0.001), poor histology (51.9% vs. 19.3%, p = 0.008), and PWDA (3.7% vs. 25.0%, p = 0.015). The rates of LNM and PWDA were 8.4% and 36.1%, respectively, in T1 cancers. Regarding the 73 PWDA cases and 129 non-PWDA cases, the rates of LNM were 0.0% and 13.2%, respectively ( p < 0.001). Among the 97 cases with lymphatic or venous invasion, the rates of LNM in 29 PWDA cases and 68 non-PWDA were 0% and 14.7%, respectively ( p = 0.029). The agreement of the two pathologists for the diagnosis of PWDA was acceptable (kappa value > 0.5). A multicenter review showed no cases of PWDA among 72 T1 cancers with LNM., Conclusions: PWDA is considered to be a safe factor for LNM in T1 cancer.

Extreme hallux valgus has been documented to be related to lower functional ability and health-related quality of life. It also has a negative effect on foot structure and biomechanical characteristics, which in turn may affect muscle strength in the foot and ankle. Thus, the purposes of this study were to determine whether there is a difference of ankle muscle strength in varied hallux valgus deformities and to investigate correlations between hallux valgus angles and ankle muscle strength. Hallux valgus angles and ankle muscle strength data were collected from 31 middle-aged Japanese women. The hallux valgus angle was measured with a 3-dimensional foot scanner; ankle muscle strength was measured with a dynamometer. Results showed no differences in ankle muscle strength between normal and mild-to-moderate hallux valgus at both 60º/second and 120º/second (p > .05). Unexpectedly, women with mild-to-moderate hallux valgus had a greater value for inversion peak torque per body weight and eversion-to-inversion ratio than those with normal hallux valgus (p = .019 and p = .022) at 120º/second. Furthermore, hallux valgus was correlated with inversion peak torque and peak torque per body weight (r = 0.47; p = .012 and r = 0.50; p = .007) and associated with eversion-to-inversion strength ratio (r = -0.47; p = .012). The findings indicated that mild-to-moderate hallux valgus did not result in a decrease in ankle muscle strength. Conversely, mild-to-moderate hallux valgus had greater ankle inversion strength in middle-aged Japanese women. Further studies are needed to investigate ankle muscle strength in severe hallux valgus deformities., (Copyright © 2018 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims:  Severe fibrosis poses a challenge in colorectal endoscopic submucosal dissection (ESD). Recently, the pocket-creation method (PCM) has been developed for overcoming various difficulties of ESD. A specific tapered hood is used for adequate traction in the PCM, and endoscopic operability becomes stable in the pocket. In this study, we investigated the efficacy of the PCM in ESD for cases with severe fibrosis., Patients and Methods: We retrospectively reviewed 1000 consecutive colorectal ESD cases (April 2006 to January 2017). Since 2016, the PCM was performed in 58 cases. The indications for ESD included (1) tumors ≥ 20 mm in size diagnosed as intramucosal cancer or high-grade dysplasia and part of T1a cancer using magnifying endoscopic examinations and (2) tumors that appeared impossible to resect with endoscopic mucosal resection because of suspected fibrosis. We identified 120 cases with severe fibrosis and compared them to cases without severe fibrosis. Additionally, the 120 severe fibrosis cases were divided into the PCM and non-PCM groups. En bloc resection, procedure time, discontinuation, and complications were analyzed between these 2 groups., Results:  Among all 1000 ESDs, severe fibrosis and discontinuation rates were 12.0 % (120 cases) and 1.8 % (18 cases), respectively. Regarding the comparison between cases with severe fibrosis and with no severe fibrosis, there were significant differences about en bloc resection rate (78.3 % vs. 95.7 %, P  < 0.001), discontinuance rate (12.5 % vs. 0.3 %, P  < 0.001), and perforation rate (8.3 % vs. 2.6 %, P  = 0.001). Among the 120 cases with severe fibrosis, 21 and 99 cases were in the PCM and non-PCM groups, respectively. The PCM group had a higher en bloc resection rate (95.2 vs. 74.7, P  =  0.03), a shorter mean procedure time (min) (79.6 ± 26.5 vs. 118.8 ± 71.0, P  = 0.001), and no cases of discontinuation. An analysis of the interobserver agreement for the diagnosis of severe fibrosis among the 3 endoscopists showed kappa values of > 0.6., Conclusions:  In cases with severe fibrosis, the PCM with ESD improved en bloc resection rates and shortened the procedure time compared to the conventional non-PCM method. Additionally, the PCM reduced the discontinuation rate.

Background and Aims: Missed polyps are a pitfall of colonoscopy. In this study, we analyzed the efficacy of an additional 30 seconds observation using linked color imaging (LCI) for detecting adenoma and sessile serrated adenoma/polyp (SSA/P)., Materials and Methods: We enrolled patients undergoing colonoscopy from February to October 2017 in two institutions. In all patients, the cecum and ascending colon were observed with white light imaging (WLI) first. The colonoscope was inserted again, and the cecum and ascending colon were observed for an additional 30 seconds using either LCI or WLI. The method for the 30 sec observation was to insufflate the cecum and ascending colon sufficiently and observe them in a distant view, because the length of the second observation was determined to be precisely 30 sec. For the second observation, LCI was performed for the first 65 patients and WLI for the next 65. Adenoma and SSA/P detection rate (ASDR) in the second observation were examined in both groups. According to a pilot study, the sample size was estimated 65., Results: In the first observation, ASDR were 30.7% in the LCI group and 32.2% in the WLI group ( p = 0.85). For the second observation, 13 polyps were detected in the LCI group and 5 polyps in the WLI group ( p = 0.04). Additionally, ASDR for the second observation were 18.5% and 6.1%, respectively ( p = 0.03). There were no significant differences between the LCI and WLI groups with respect to morphology (ratio of polypoid) (38.5% versus 60.0%, p = 0.52) and histology (ratio of adenoma) (92.3% versus 100.0%, p = 0.91). Total adenoma and SSA/P number were 48 in the LCI group and 36 in the WLI group ( p = 0.02)., Conclusion: The 30 seconds additional observation with LCI improved the detection of adenoma and SSA/P in the right-sided colon.

Background: Most previous insulin infusion protocols are titrated for Westerners and are not simple to follow. In this study, we tested the efficacy and safety of our simple insulin infusion protocol utilizing lower insulin doses for Asians., Methods: A total of 152 patients with type 2 diabetes undergoing cardiothoracic surgery were included. After surgery, blood glucose (BG) was initially managed according to our algorithm protocol, and subsequently by the post-algorithm protocol. Insulin infusion rates in the algorithm protocol were titrated in two steps according to (1) current BG levels and (2) the difference between current and previous BG levels. In the post-algorithm protocol, insulin lispro was injected subcutaneously in addition to intravenous insulin infusion according to BG levels. The efficacy was assessed as achievement rates of two target BG ranges (140-199 and 80-199 mg/dL), and safety was assessed as hypoglycemia (< 70 mg/dL) and protocol error rates., Results: With the use of the algorithm protocol, 58.7% of 1749 BG measurements achieved a range of 140-199 mg/dL, and 95.9% achieved levels within the 80-199 mg/dL range. Hypoglycemia and protocol error rates were 0.47 and 0.51%, respectively. With the post-algorithm protocol, 48.7 and 98.3% of 898 BG measurements achieved each target range. Hypoglycemia and protocol error rates were 0.78 and 0.22%, respectively. Severe hypoglycemia (< 40 mg/dL) was not observed., Conclusions: Our insulin infusion protocol seems to be efficacious, safe, and widely feasible for Asian patients because of its simplicity and lower insulin dose., Competing Interests: All the authors declare that they have no conflict of interest.Yoshihiko Nishio has received honoraria for scientific lectures from Eli Lilly. Kazuma Ogiso, Nobuyuki Koriyama, Takahiko Obo, Akinori Tokito, and Takayuki Ueno have nothing to disclose.All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (National Hospital Organization Kagoshima Medical Center, Ethics Committee, date of approval: 6 February 2017, approval no. 28-71) and with the Helsinki Declaration of 1964 and later versions.

Obesity is considered a major influential factor of foot structure and function. It has been reported to result in detrimental alterations of foot structure indicators and a decrease in muscle strength, which can lower the quality of life and increase the morbidity of obesity. The purpose of the present study was to determine the effect of weight reduction on foot structure and the strength of the muscles that move the ankle in obese adults. A total of 33 obese Japanese participants (mean body mass index 28.49 ± 2.87 kg/m 2 ) without an exercise habit participated in a 12-week dietary modification program. Their foot structure indicators were measured using a 3-dimensional foot scanner, and the strength of the muscles that move the ankle was assessed using a dynamometer. After the dietary modification, the mean body weight reduction was 7.49 ± 4.10 kg (9.38%; 77.82 ± 13.26 kg before and 70.33 ± 11.37 kg after; p <.001). The wide foot indicators, including the forefoot girth, rearfoot width, and instep girth, had decreased significantly (p <.05), and the decreases correlated positively with the weight reduction. Regarding the strength of the muscles that move the ankle, except for dorsiflexion, all the measured peak torque values per body weight had increased significantly (p <.01). These results suggest that the weight reduction induced by a 12-week dietary modification results in thinner feet and increased strength of the muscles that move the ankle., (Copyright © 2017 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims:  Water drop adhesions (WDA) impair endoscopic view during gastrointestinal endoscopy. We developed a novel lens cleaner designed using two types of harmLess surfactants and it is reported to be useful for preventing lens cloudiness during colorectal ESD. In the current study, we examined the ability of it for preventing and removing WDA., Patients and Methods:  During laboratory experiments, the cleaner (Cleash; Fujifilm Co., Tokyo, Japan and Nagase Medicals Co., Hyogo, Japan) was applied to the endoscopic lens and an air/water device (AWD) (water 200 mL, dimethicone 1 mL, Cleash 1 mL). The endoscope was submerged in water 100 times for 5 cycles. Rates of WDA were calculated for various groups (lens and AWD with or without Cleash) and compared to a normal cleaner (SL cleaner). During clinical research, 30 colonoscopies and 30 esophagogastroduodenoscopies were analyzed. For the Cleash group, the cleaner was applied to both lens and AWD. The numbers of WDA and WDA with non-rapid removal were calculated, compared to those of the SL cleaner group., Results:  The mean WDA rate for the Cleash setting (lens: Cleash; AWD: Cleash) was 11.0 %, which was significantly lower than other settings (lens: SL cleaner; AWD: water, 31.0 %; P  < 0.001) (lens: Cleash; AWD: water, 19.0 %; P  < 0.001). Clinical research of colonoscopies indicated that the numbers of WDA (number/15 sec) and WDA with non-rapid removal were 0.38 and 0.17 for the Cleash group and 0.91 and 0.46 for the SL cleaner groups ( P  < 0.001, P  < 0.001). For esophagogastroduodenoscopies, the results were 0.47 and 0.24 for the Cleash group and 0.54 and 0.42 for the SL cleaner group ( P  = 0.72, P  = 0.018)., Conclusion:  A clear and beautiful image without WDA is useful not only for routine endoscopy but also, more importantly, for magnifying endoscopy and other endoscopic treatments. The use of Cleash to lens and AWD showed positive results for preventing and removing WDA during laboratory experiments and clinical research involving CS. Additionally, it also showed positive results for the removal of WDA during EGD.