Prolyl Isomerase Pin1 Expression in the Spinal Motor Neurons of Patients With Sporadic Amyotrophic Lateral Sclerosis

Haruhisa Kato,Makiko Naito,Tomoko Saito,Takuto Hideyama,Yasuhiro Suzuki,Takashi Kimura,Shin Kwak,Hitoshi Aizawa 대한신경과학회 2022 Journal of Clinical Neurology Vol.18 No.4

Background and Purpose Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Selective deficiency of edited adenosine deaminase acting on RNA 2 (ADAR2), a key molecule in the acquisition of Ca2+ resistance in motor neurons, has been reported in sporadic ALS (sALS) spinal motor neurons. Since ADAR2 activity is positively regulated by prolyl isomerase Protein never in mitosis gene A interacting-1 (Pin1), a known phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, we investigated Pin1 expression in spinal motor neurons in sALS. Methods Specimens of the spinal cord were obtained from the lumbar region in eight sALS patients and age-matched five controls after postmortem examinations. The specimens were double stained with anti-Pin1 and anti-TAR DNA-binding protein of 43 kDa (TDP-43) antibodies, and examined under a fluorescence microscope. Results This study analyzed 254 and 422 spinal motor neurons from 8 sALS patients and 5 control subjects, respectively. The frequency of motor neurons with high cytoplasmic Pin1 expression from the spinal cord did not differ significantly between sALS specimens without cytoplasmic TDP-43 inclusions and control specimens. However, in sALS specimens, neurons for which the Pin1 immunoluminescence intensity in the cytoplasm was at least twice that in the background were more common in specimens with cytoplasmic TDP-43 inclusions (p<0.05 in χ2 test). Conclusions In sALS, neurons with higher expression levels of Pin1 levels had more TDP-43 inclusions. Despite the feedback mechanism between Pin1 and ADAR2 being unclear, since Pin1 positively regulates ADAR2, our results suggest that higher Pin1 expression levels in motor neurons with TDP-43 pathology from sALS patients represent a compensatory mechanism

Preclinical Efficacy and Clinical Feasibility of a Novel Aerosol- Exposure Protection Mask for Esophagogastroduodenoscopy

Mai Ego Makiguchi,Seiichiro Abe,Yutaka Okagawa,Satoru Nonaka,Haruhisa Suzuki,Shigetaka Yoshinaga,Ichiro Oda,Okamoto Ryuta,Yutaka Saito 대한소화기내시경학회 2022 Clinical Endoscopy Vol.55 No.2

Background/Aims: This study aimed to assess the efficacy of a novel aerosol-exposure protection (AP) mask in preventingcoronavirus disease in healthcare professionals during upper gastrointestinal endoscopy and to evaluate its clinical feasibility. Methods: In Study 1, three healthy volunteers volitionally coughed with and without the AP mask in a cleanroom. Microparticleswere visualized and counted with a specific measurement system and compared with and without the AP mask. In Study 2,30 patients underwent endoscopic resection with the AP mask covering the face, and the SpO2 was measured throughout theprocedure. Results: In Study 1, the median number of microparticles in volunteers 1, 2, and 3 with and without the AP mask was 8.5 and 110.0,7.0 and 51.5, and 8.0 and 95.0, respectively (p<0.01). Using the AP mask, microparticles were reduced by approximately 92%. Themedian distances of microparticle scattering without the AP mask were 60, 0, and 68 in volunteers 1, 2, and 3, respectively. In Study 2,the mean SpO2 was 96.3%, and desaturation occurred in three patients. Conclusion: The AP mask could provide protection from aerosol exposure and can be safely used for endoscopy in clinical practice.

Metachronous Gastric Cancer Following Curative Endoscopic Resection of Early Gastric Cancer

Seiichiro Abe,Ichiro Oda,Takeyoshi Minagawa,Masau Sekiguchi,Satoru Nonaka,Haruhisa Suzuki,Shigetaka Yoshinaga,Amit Bhatt,Yutaka Saito 대한소화기내시경학회 2018 Clinical Endoscopy Vol.51 No.3

This review article summarizes knowledge about metachronous gastric cancer (MGC) occurring after curative endoscopic resection (ER)of early gastric cancer (EGC), treatment outcomes of patients who developed MGC, and efficacy of Helicobacter pylori eradication toprevent MGC. The incidence of MGC following curative ER increases over time and is higher than in patients undergoing gastrectomy. Increasing age and multifocal EGC are independent risk factors for developing MGC. An MGC following curative ER is usually a small(<20 mm) and differentiated intramucosal cancer. Most MGC lesions are found at an early stage on semiannual or annual surveillanceendoscopy and are successfully treated by further ER, with excellent long-term outcomes. Eradication of H. pylori may reduce the riskof MGC following ER of EGC, but further prospective studies with long-term outcomes are required. Surveillance endoscopy followinggastric ER should be continued indefinitely, due to the risk of MGC even after successful H. pylori eradication. Risk stratification andtailored endoscopic surveillance schedules need to be developed.

Endoscopic Resection of Undifferentiated Early Gastric Cancer

Seiichiro Abe,Yuichiro Hirai,Mai Ego Makiguchi,Masau Sekiguchi,Satoru Nonaka,Haruhisa Suzuki,Shigetaka Yoshinaga,Yutaka Saito 대한위암학회 2023 Journal of gastric cancer Vol.23 No.1

Endoscopic resection (ER) is widely performed for early gastric cancer (EGC) with a negligible risk of lymph node metastasis (LNM) in Eastern Asian countries. In particular, endoscopic submucosal dissection (ESD) leads to a high en bloc resection rate, enabling accurate pathological evaluation. As undifferentiated EGC (UD-EGC) is known to result in a higher incidence of LNM and infiltrative growth than differentiated EGC (D-EGC), the indications for ER are limited compared with those for D-EGC. Previously, clinical staging as intramucosal UD-EGC ≤2 cm, without ulceration, was presented as ‘weakly recommended’ or ‘expanded indications’ for ER in the guidelines of the United States, Europe, Korea, and Japan. Based on promising long-term outcomes from a prospective multicenter study by the Japan Clinical Oncology Group (JCOG) 1009/1010, the status of this indication has expanded and is now considered ‘absolute indications’ in the latest Japanese guidelines published in 2021. In this study, which comprised 275 patients with UD-EGC (cT1a, ≤2 cm, without ulceration) treated with ESD, the 5-year overall survival (OS) was 99.3% (95% confidence interval, 97.1%–99.8%), which was higher than the threshold 5-year OS (89.9%). Currently, the levels of evidence grades and recommendations for ER of UD-EGC differ among Japan, Korea, and Western countries. Therefore, a further discussion is warranted to generalize the indications for ER of UD-EGC in countries besides Japan.

Complications of endoscopic resection in the upper gastrointestinal tract

Takeshi Uozumi,Seiichiro Abe,Mai Ego Makiguchi,Satoru Nonaka,Haruhisa Suzuki,Shigetaka Yoshinaga,Yutaka Saito 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.4

Endoscopic resection (ER) is widely utilized as a minimally invasive treatment for upper gastrointestinal tumors; however, complications could occur during and after the procedure. Post-ER mucosal defect leads to delayed perforation and bleeding; therefore, endoscopic closure methods (endoscopic hand-suturing, the endoloop and endoclip closure method, and over-the-scope clip method) and tissue shielding methods (polyglycolic acid sheets and fibrin glue) are developed to prevent these complications. During duodenal ER, complete closure of the mucosal defect significantly reduces delayed bleeding and should be performed. An extensive mucosal defect that comprises three-quarters of the circumference in the esophagus, gastric antrum, or cardia is a significant risk factor for post-ER stricture. Steroid therapy is considered the first-line option for the prevention of esophageal stricture, but its efficacy for gastric stricture remains unclear. Methods for the prevention and management of ER-related complications in the esophagus, stomach, and duodenum differ according to the organ; therefore, endoscopists should be familiar with ways of preventing and managing organ-specific complications.

Efficacy of Current Traction Techniques for Endoscopic Submucosal Dissection

Seiichiro Abe,Shih Yea Sylvia Wu,Mai Ego,Hiroyuki Takamaru,Masau Sekiguchi,Masayoshi Yamada,Satoru Nonaka,Taku Sakamoto,Haruhisa Suzuki,Shigetaka Yoshinaga,Takahisa Matsuda,Ichiro Oda,Yutaka Saito 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.6

This systematic review aimed to assess the efficacy of the current approach to tissue traction during the endoscopic submucosal dissection (ESD) of superficial esophageal cancer, early gastric cancer, and colorectal neoplasms. We performed a systematic electronic literature search of articles published in PubMed and selected comparative studies to investigate the treatment outcomes of tractionassisted versus conventional ESD. Using the keywords, we retrieved 381 articles, including five eligible articles on the esophagus, 13 on the stomach, and 12 on the colorectum. A total of seven randomized controlled trials and 23 retrospective studies were identified. Clip line traction and submucosal tunneling were effective in reducing the procedural time during esophageal ESD. The efficacy of traction methods in gastric ESD varied in terms of the devices and strategies used depending on the lesion location and degree of submucosal fibrosis. Several prospective and retrospective studies utilized traction devices without the need to reinsert the colonoscope. When pocket creation is included, the traction devices and methods effectively shorten the procedural time during colorectal ESD. Although the efficacy is dependent on the organ and tumor locations, several traction techniques have been demonstrated to be efficacious in facilitating ESD by maintaining satisfactory traction during dissection.