Publications by authors named "Kenichiro Imai"

185 Publications

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Gastrointest Endosc 2021 Aug;94(2):434-435

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

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http://dx.doi.org/10.1016/j.gie.2021.04.011DOI Listing
August 2021

Anything you don't know is invisible to your eyes: Educational interventions for serrated polyps can increase their detection.

Authors:
Kenichiro Imai

Dig Endosc 2021 Jul 14. Epub 2021 Jul 14.

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

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http://dx.doi.org/10.1111/den.14071DOI Listing
July 2021

Ten-year progression of a diminutive rectosigmoid polyp left in situ at the index colonoscopy.

Dig Endosc 2021 Jul 6. Epub 2021 Jul 6.

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

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http://dx.doi.org/10.1111/den.14075DOI Listing
July 2021

Features of post-endoscopic submucosal dissection electrocoagulation syndrome for early gastric neoplasm.

J Gastroenterol Hepatol 2021 Jun 15. Epub 2021 Jun 15.

Division of Endoscopy, Shizuoka Cancer Center, Nagaizumi, Japan.

Background And Aim: Post-endoscopic submucosal dissection electrocoagulation syndrome (PECS) has become a common adverse event after colorectal endoscopic submucosal dissection (ESD) and esophageal ESD. However, little is known about PECS after gastric ESD. Therefore, this study aimed to investigate the clinical features of PECS after gastric ESD.

Methods: Patients who underwent ESD for gastric cancer or adenoma between January 2016 and December 2017 were retrospectively investigated. PECS was clinically diagnosed based on the presence of upper abdominal pain and localized abdominal tenderness with a temperature of >37.5°C, without perforation. We analyzed the clinical features of PECS.

Results: A total of 637 ESD cases were enrolled; PECS occurred in 32 patients (5.0%), all of whom were diagnosed on postoperative Day 1. Among PECS cases, unplanned prolongation of hospitalization or fasting period was observed in 15 patients (47%). As a result, the median durations of hospitalization and fasting period were significantly longer in PECS cases (P = 0.008 and P < 0.001, respectively); however, the mean differences were less than a day. Additionally, all PECS cases recovered with conservative treatment.

Conclusions: PECS is considered a common adverse event after gastric ESD. More than half of patients with PECS could start diets and be discharged as well as those without PECS.
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http://dx.doi.org/10.1111/jgh.15583DOI Listing
June 2021

Tip-in Endoscopic Mucosal Resection for 15- to 25-mm Colorectal Adenomas: A Single-Center, Randomized Controlled Trial (STAR Trial).

Am J Gastroenterol 2021 Jul;116(7):1398-1405

Division of Endoscopy, Shizuoka Cancer Center, Nagaizumi-cho, Suntogun, Shizuoka, Japan.

Introduction: One-piece endoscopic mucosal resection (EMR) for lesions >15 mm is still unsatisfactory, and attempted 1-piece EMR for lesions >25 mm can increase perforation risk. Therefore, modifications to ensure 1-piece EMR of 15- to 25-mm lesions would be beneficial. The aim of this study was to investigate whether Tip-in EMR, which anchors the snare tip within the submucosal layer, increases en bloc resection for 15- to 25-mm colorectal lesions compared with EMR.

Methods: In this prospective randomized controlled trial, patients with nonpolypoid colorectal neoplasms of 15-25 mm in size were recruited and randomly assigned in a 1:1 ratio to undergo Tip-in EMR or standard EMR, stratified by age, sex, tumor size category, and tumor location. The primary endpoint was the odds ratio of en bloc resection adjusted by location and size category. Adverse events and procedure time were also evaluated.

Results: We analyzed 41 lesions in the Tip-in EMR group and 41 lesions in the EMR group. En bloc resection was achieved in 37 (90.2%) patients undergoing Tip-in EMR and 30 (73.1%) who had EMR. The adjusted odds ratio of en bloc resection in Tip-in EMR vs EMR was 3.46 (95% confidence interval: 1.06-13.6, P = 0.040). The Tip-in EMR and EMR groups did not differ significantly in adverse event rates (0% vs 4.8%) or median procedure times (7 vs 5 minutes).

Discussion: In this single-center randomized controlled trial, we found that Tip-in EMR significantly improved the en bloc resection rate for nonpolypoid lesions 15-25 mm in size, with no increase in adverse events or procedure time.
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http://dx.doi.org/10.14309/ajg.0000000000001320DOI Listing
July 2021

Unsupervised colonoscopic depth estimation by domain translations with a Lambertian-reflection keeping auxiliary task.

Int J Comput Assist Radiol Surg 2021 Jun 17;16(6):989-1001. Epub 2021 May 17.

Graduate School of Informatics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.

Purpose: A three-dimensional (3D) structure extraction technique viewed from a two-dimensional image is essential for the development of a computer-aided diagnosis (CAD) system for colonoscopy. However, a straightforward application of existing depth-estimation methods to colonoscopic images is impossible or inappropriate due to several limitations of colonoscopes. In particular, the absence of ground-truth depth for colonoscopic images hinders the application of supervised machine learning methods. To circumvent these difficulties, we developed an unsupervised and accurate depth-estimation method.

Method: We propose a novel unsupervised depth-estimation method by introducing a Lambertian-reflection model as an auxiliary task to domain translation between real and virtual colonoscopic images. This auxiliary task contributes to accurate depth estimation by maintaining the Lambertian-reflection assumption. In our experiments, we qualitatively evaluate the proposed method by comparing it with state-of-the-art unsupervised methods. Furthermore, we present two quantitative evaluations of the proposed method using a measuring device, as well as a new 3D reconstruction technique and measured polyp sizes.

Results: Our proposed method achieved accurate depth estimation with an average estimation error of less than 1 mm for regions close to the colonoscope in both of two types of quantitative evaluations. Qualitative evaluation showed that the introduced auxiliary task reduces the effects of specular reflections and colon wall textures on depth estimation and our proposed method achieved smooth depth estimation without noise, thus validating the proposed method.

Conclusions: We developed an accurate depth-estimation method with a new type of unsupervised domain translation with the auxiliary task. This method is useful for analysis of colonoscopic images and for the development of a CAD system since it can extract accurate 3D information.
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http://dx.doi.org/10.1007/s11548-021-02398-xDOI Listing
June 2021

[A Case of HER2 Positive Unresectable Gastric Cancer Leading to Conversion Therapy with Chemotherapy].

Gan To Kagaku Ryoho 2021 Apr;48(4):593-595

Dept. of Surgery, Tokyo Metropolitan Health and Medical Corporation Toshima Hospital.

A 72‒year‒old man visited our hospital with a chief complaint of epigastralgia. Upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer at the body of the stomach. Following an investigation, he was diagnosed with human epidermal growth factor receptor 2‒positive gastric cancer with invasion to the pancreas as well as the paraaortic lymph node, and multiple liver metastases were also observed. The cancer was judged to be cT4a, N2M1(H1 LYM: No. 16), cStage Ⅳ and thus was considered suitable for chemotherapy. We performed capecitabine plus cisplatin plus trastuzumab therapy. After 3 courses, the primary lesion and swollen lymph nodes decreased in size. After 20 chemotherapy courses, the primary lesion relapsed, so conversion surgery was performed. The patient underwent total gastrectomy, distal pancreatectomy, and partial resection of the liver. We planned to perform adjuvant chemotherapy, but the patient declined it because of anorexia. At 18 months after the operation, recurrence of the tumor was detected at the celiac artery. Chemotherapy was performed as follows: capecitabine plus trastuzumab 10 courses, ramucirumab plus paclitaxel, irinotecan, and nivolumab. However, the patient eventually died 71 months after the first visit.
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April 2021

Risk Stratification Score Improves Sensitivity for Advanced Colorectal Neoplasia in Colorectal Cancer Screening: The Oshima Study Workgroup.

Clin Transl Gastroenterol 2021 Mar;12(3):e00319

Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan.

Introduction: Noninvasive colorectal cancer (CRC) screening methods with higher sensitivity for advanced colorectal neoplasia (ACN) than the fecal immunochemical test (FIT) alone are warranted. This study aimed to elucidate the diagnostic performance of a risk stratification score calculated using baseline individual characteristics and its combination with FIT for detecting ACN.

Methods: This cross-sectional analysis of data from a prospective cohort in Izu Oshima, Japan, included asymptomatic individuals age 40-79 years who underwent both 2-day quantitative FIT and screening colonoscopy. The 8-point risk score, calculated based on age, sex, CRC family history, body mass index, and smoking history, was assessed. Colonoscopy results were used as reference.

Results: Overall, 1,191 individuals were included, and 112 had ACN. The sensitivity and specificity of the 1-/2-day FIT (cutoff: 50-200 ng Hb/mL) for ACN were 17.9%-33.9% (4.9%-22.0% for right-sided ACN) and 91.8%-97.6%, respectively. The risk score's c-statistic for ACN was 0.66, and combining the score (cutoff: 5 points) with 1-/2-day FIT (cutoff: 50-200 ng Hb/mL) yielded a sensitivity and specificity for ACN of 46.4%-56.3% (43.9%-48.8% for right-sided ACN) and 76.6%-80.8%, respectively. The specificity of the risk score and FIT combination for all adenomatous lesions was 82.4%-86.4%.

Discussion: The 8-point risk score remarkably increased the sensitivity for ACN, particularly for right-sided ACN. Although the specificity decreased, it was still maintained at a relatively high level. The risk score and FIT combination has the potential to become a viable noninvasive CRC screening option.
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http://dx.doi.org/10.14309/ctg.0000000000000319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925133PMC
March 2021

[Two Cases of Metastatic Colorectal Cancer Treated with TAS-102 plus Bevacizumab].

Gan To Kagaku Ryoho 2021 Mar;48(3):419-421

Dept. of Surgery, Tokyo Metropolitan Health and Medical Corporation Toshima Hospital.

Trifluridine/tipiracil (TAS-102) is an important chemotherapeutic agent recommended by the Japanese guidelines as third- or fourth-line treatment for colorectal cancer. Some studies have reported that administration of TAS-102 concomitant with bevacizumab prolongs progression-free and overall survival in colorectal cancer. We describe 2 patients treated with a chemotherapeutic regimen comprising TAS-102 concomitant with bevacizumab for recurrent colorectal cancer. No adverse events ≥Grade 3(except for hematotoxicity)were observed in these patients. The patient received several courses of chemotherapy with adjustments of the dose and dosing intervals to prevent neutropenia. Combination therapy using TAS-102 and bevacizumab is a feasible Late-line chemotherapeutic regimen for colorectal cancer.
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March 2021

Long-term outcomes of salvage endoscopic submucosal dissection for local failure after chemoradiotherapy for esophageal squamous cell carcinoma.

Jpn J Clin Oncol 2021 Jul;51(7):1036-1043

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

Background: Salvage endoscopic submucosal dissection is considered a minimally invasive treatment for local failure after chemoradiotherapy for esophageal squamous cell carcinoma. However, the long-term outcomes have not been fully evaluated. This study investigated the short-term and long-term outcomes of salvage endoscopic submucosal dissection.

Methods: Patients who underwent endoscopic submucosal dissection for local recurrence or residual tumor after chemoradiotherapy from January 2006 to December 2017 were retrospectively investigated. Follow-up included endoscopic examination and computed tomography at least once every 6 months after salvage endoscopic submucosal dissection. Risk factors for disease recurrence after salvage endoscopic submucosal dissection were assessed using the Cox hazards model.

Results: A total of 30 patients (33 cases of esophageal squamous cell carcinoma: local recurrence, n = 27; residual tumor, n = 6) were included. The median endoscopic submucosal dissection procedure time was 40 min (interquartile range [IQR], 33-58.5 min). En bloc resection was achieved in 31 (94%) of 33 esophageal squamous cell carcinoma cases. One patient with intraoperative perforation did not require surgical intervention and recovered with conservative treatment. A total of 16 patients (53%) had disease recurrence at a median follow-up of 51 months (IQR, 33-81 months). The 3-year overall, disease-specific, recurrence-free and local recurrence-free survival rates were 75%, 82%, 58% and 90%, respectively. The positive vertical margin, submucosal invasion in the endoscopic submucosal dissection specimen and piecemeal resection were significantly associated with disease recurrence after salvage endoscopic submucosal dissection.

Conclusions: Salvage endoscopic submucosal dissection is a feasible treatment for local failure after chemoradiotherapy for esophageal squamous cell carcinoma with acceptable long-term outcomes. However, for cases with positive vertical margins and submucosal invasion in the endoscopic submucosal dissection specimen, salvage endoscopic submucosal dissection outcomes were insufficient and additional treatment might be required.
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http://dx.doi.org/10.1093/jjco/hyab027DOI Listing
July 2021

Comparison of five-phase computed tomography images of type 1 autoimmune pancreatitis and pancreatic cancer: Emphasis on cases with atypical images.

Pancreatology 2021 Apr 16;21(3):666-675. Epub 2021 Feb 16.

Endoscopy, Shizuoka, Japan.

Background/objectives: International consensus diagnostic criteria (ICDC) include characteristic images of autoimmune pancreatitis (AIP); however, reports on atypical cases are increasing. The aims of this study were to compare CT findings between AIP and pancreatic cancer (PC), and to analyze type 1 AIPs showing atypical images.

Methods: Five-phase CT images were compared between 80 type 1-AIP lesions and 80 size- and location-matched PCs in the case-control study. Atypical AIPs were diagnosed based on the four ICDC items.

Results: ICDC items were recognized in most AIP lesions; pancreatic enlargement (87.7%), narrowing of the main pancreatic duct (98.8%), delayed enhancement (100%), and no marked upstream-duct dilation (97.5%). CT values of AIPs increased rapidly until the pancreatic phase and decreased afterward, while those of PCs gradually increased until the delayed phase (P < 0.0001). Atypical images were recognized in 14.8% of AIPs, commonly without pancreatic enlargement (18.5 mm) and sometimes mimicking intraductal neoplasms. The CT values and their ratios were different between atypical AIPs and size-matched PCs most significantly in the pancreatic phase, but similar in the delayed phase.

Conclusions: Ordinary type 1 AIPs can be diagnosed with the ICDC, but atypical AIPs represented a small fraction. "Delayed enhancement" is characteristic to ordinary AIPs, however, "pancreatic-phase enhancement" is more diagnostic for atypical AIPs.
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http://dx.doi.org/10.1016/j.pan.2021.01.016DOI Listing
April 2021

Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy.

Autophagy 2021 Jan 26:1-26. Epub 2021 Jan 26.

Ubiquitin Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Macroautophagy/autophagy is an intracellular degradation process that delivers cytosolic materials and/or damaged organelles to lysosomes. synthesis of the autophagosome membrane occurs within a phosphatidylinositol-3-phosphate-rich region of the endoplasmic reticulum, and subsequent expansion is critical for cargo encapsulation. This process is complex, especially in mammals, with many regulatory factors. In this study, by utilizing PRKN (parkin RBR E3 ubiquitin protein ligase)-mediated mitochondria autophagy (mitophagy)-inducing conditions in conjunction with chemical crosslinking and mass spectrometry, we identified human BCAS3 (BCAS3 microtubule associated cell migration factor) and C16orf70 (chromosome 16 open reading frame 70) as novel proteins that associate with the autophagosome formation site during both non-selective and selective autophagy. We demonstrate that BCAS3 and C16orf70 form a complex and that their association with the phagophore assembly site requires both proteins. structural modeling, mutational analyses in cells and phosphoinositide-binding assays indicate that the WD40 repeat domain in human BCAS3 directly binds phosphatidylinositol-3-phosphate. Furthermore, overexpression of the BCAS3-C16orf70 complex affects the recruitment of several core autophagy proteins to the phagophore assembly site. This study demonstrates regulatory roles for human BCAS3 and C16orf70 in autophagic activity.
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http://dx.doi.org/10.1080/15548627.2021.1874133DOI Listing
January 2021

[Two Cases of Advanced Gastric Cancer Diagnosed as Pathological Complete Response after Preoperative Chemotherapy with S-1 and Oxaliplatin].

Gan To Kagaku Ryoho 2020 Dec;47(13):2171-2173

Dept. of Surgery, Tokyo Metropolitan Health and Medical Treatment Corporation Toshima Hospital.

We herein report 2 cases of gastric cancer treated by S-1 and oxaliplatin combination therapy before later undergoing gastrectomy. The pathological results of both cases demonstrated complete response. Case 1 had a giant tumor which was suspected to have invaded the pancreas. Case 2 was associated with extensive lymph node metastasis. Based on the findings of these 2 cases, preoperative chemotherapy with S-1 and oxaliplatin for advanced gastric cancer shows sufficient efficacy.
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December 2020

[A Case Report of Sigmoid Colon Cancer with Para-Aortic Lymph Node Metastases and Multiple Liver Metastases Resected after FOLFOX Therapy].

Gan To Kagaku Ryoho 2020 Dec;47(13):2077-2079

Dept. of Surgery, Tokyo Metropolitan Health and Medical Corporation Toshima Hospital.

The patient, a male in his 70s, visited our hospital with a chief complaint of general fatigue and weight loss. Upon a detailed examination, he was diagnosed with sigmoid colon cancer, para-aortic lymph node metastases, and multiple liver metastases, for which he was hospitalized due to a poor performance status(PS). FOLFOX therapy was administered as the symptoms caused by the primary lesion were not recognized and his general condition was considered to be poor and thus he was deemed to be inoperable. After completing 2 courses of the chemotherapy, although his PS improved, laparoscopic sigmoidectomy was carried out with colonic stent placement due to the occurrence of an intestinal obstruction as a result of an enlargement of the primary lesion. Following surgery, 2 courses of FOLFOX therapy and 4 courses of FOLFOX plus bevacizumab therapy were administered and he is alive at 5 months after the operation without progression.
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December 2020

White light and/or magnifying endoscopy with narrow band imaging for superficial nonampullary duodenal epithelial tumors.

Scand J Gastroenterol 2021 Feb 8;56(2):211-218. Epub 2021 Jan 8.

Division of Endoscopy, Shizuoka Cancer Center, Nagaizumi, Shizuoka, Japan.

Background And Aim: A reliable optical diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) to guide optimal treatment strategy is lacking. The aim of this study was to simulate the treatment outcomes based on optical diagnosis using white light imaging (WLI) or magnifying endoscopy with narrow band imaging (MNBI) and to evaluate the method to extract optimal lesions suitable for cold snare polypectomy (CSP) or not.

Methods: We created a decision tree model using WLI and MNBI diagnosis for ideal treatment for SNADETs. Optical diagnoses of Vienna category 3 lesions (C3), category 4/5 (C4/5) were defined based on the WLI scoring system or the MNBI pattern diagnosis. Ideal treatments were CSP for C3 < 10mm, and endoscopic mucosal resection, endoscopic submucosal dissection or surgery for lesions ≥10mm or C4/5. Ideal treatment results based on optical diagnosis were analyzed according to actual pathological results.

Results: A total of 218 lesions with pre-operative diagnosis of SNADETs were included for analysis. Percentage of ideal treatment for C3 < 10mm based on WLI or MNBI or both was 88%, 83% and 97%. When WLI and MNBI diagnoses predicted the same histology, the specificity, positive predictive value and accuracy were significantly higher than those of WLI or MNBI alone ( < .05).

Conclusions: A decision tree model using lesion diameter, WLI scoring and MNBI pattern diagnosis is hypothetically useful to select ideal lesions for CSP among SNADETs. Optical diagnosis using both WLI and MNBI is more useful than WLI or MNBI alone.
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http://dx.doi.org/10.1080/00365521.2020.1866062DOI Listing
February 2021

Continuous warfarin administration versus heparin bridging therapy in post colorectal polypectomy haemorrhage: a study protocol for a multicentre randomised controlled trial (WHICH study).

Trials 2021 Jan 7;22(1):33. Epub 2021 Jan 7.

Department of Gastroenterology and Hepatology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan.

Background: Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding.

Methods: We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events.

Discussion: The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy.

Trial Registration: UMIN-CTR UMIN000023720 . Registered on 22 August 2016.
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http://dx.doi.org/10.1186/s13063-020-04975-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791998PMC
January 2021

Mitochondrial sorting and assembly machinery operates by β-barrel switching.

Nature 2021 02 6;590(7844):163-169. Epub 2021 Jan 6.

Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kyoto, Japan.

The mitochondrial outer membrane contains so-called β-barrel proteins, which allow communication between the cytosol and the mitochondrial interior. Insertion of β-barrel proteins into the outer membrane is mediated by the multisubunit mitochondrial sorting and assembly machinery (SAM, also known as TOB). Here we use cryo-electron microscopy to determine the structures of two different forms of the yeast SAM complex at a resolution of 2.8-3.2 Å. The dimeric complex contains two copies of the β-barrel channel protein Sam50-Sam50a and Sam50b-with partially open lateral gates. The peripheral membrane proteins Sam35 and Sam37 cap the Sam50 channels from the cytosolic side, and are crucial for the structural and functional integrity of the dimeric complex. In the second complex, Sam50b is replaced by the β-barrel protein Mdm10. In cooperation with Sam50a, Sam37 recruits and traps Mdm10 by penetrating the interior of its laterally closed β-barrel from the cytosolic side. The substrate-loaded SAM complex contains one each of Sam50, Sam35 and Sam37, but neither Mdm10 nor a second Sam50, suggesting that Mdm10 and Sam50b function as placeholders for a β-barrel substrate released from Sam50a. Our proposed mechanism for dynamic switching of β-barrel subunits and substrate explains how entire precursor proteins can fold in association with the mitochondrial machinery for β-barrel assembly.
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http://dx.doi.org/10.1038/s41586-020-03113-7DOI Listing
February 2021

Discrepancy between endoscopic and pathological ulcerative findings in clinical intramucosal early gastric cancer.

Gastric Cancer 2021 May 5;24(3):691-700. Epub 2021 Jan 5.

Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.

Background: Ulcerative finding (UL) is one of the factors that define the indication and curability of endoscopic resection (ER) in early gastric cancer (EGC). Discrepancies between endoscopic UL (cUL) and pathological UL (pUL) sometimes occur in clinical practice. The aim of this study was to investigate the discrepancy rate in UL diagnosis and the risk factors associated with such discrepancies.

Methods: Patients with clinical intramucosal (cT1a) EGC who underwent ER or surgery between September 2002 and December 2017 were analyzed. The proportion of cUL-negative (cUL0) lesions that were identified as pUL-positive (pUL1) and that of cUL-positive (cUL1) lesions that were identified as pUL-negative (pUL0) were calculated. Logistic regression analysis was performed to estimate the associations between discrepancy in UL diagnosis and clinical variables of the lesion, such as the size, histology, location, and macroscopic type.

Results: In total, 5382 lesions were evaluated; 5.5% of cUL0 lesions (256/4619) were identified as pUL1, while 38.7% of cUL1 lesions (295/763) were pUL0. Multivariate analysis indicated that in cUL1 lesions, tumor location in the lower third of the stomach (odds ratio 3.11, 95% confidence interval 1.90-5.08) was identified as an independent risk factor for overestimation.

Conclusions: Endoscopic diagnosis of UL in cT1a EGC was overestimated in 38.7% of lesions, especially for lesions located in the lower third of the stomach. This discrepancy should be considered in the management of cT1a EGC with UL.
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http://dx.doi.org/10.1007/s10120-020-01150-9DOI Listing
May 2021

Bile aspiration during EUS-guided hepaticogastrostomy is associated with lower risk of postprocedural adverse events: a retrospective single-center study.

Surg Endosc 2021 Jan 4. Epub 2021 Jan 4.

Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.

Background: In endoscopic retrograde cholangiopancreatography (ERCP), reduction of pressure inside of the bile duct by bile aspiration is a well-known method to lower the rate of adverse events (AEs) including cholangitis. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) has been introduced as an alternative to ERCP. The use of self-expandable metallic stents is recommended in EUS-HGS to reduce bile leak; however, other methods to reduce the rate of AEs including bile leak, abdominal pain, fever, and sepsis, have not been elucidated yet. This study investigated whether bile aspiration during EUS-HGS decreased the rate of postprocedural AEs.

Methods: Consecutive patients who underwent EUS-HGS between July 2016 and April 2020 were retrospectively evaluated in this study. EUS-HGS was performed at a tertiary cancer center. Patient characteristics, site of biliary obstruction, the quantity of bile aspirated during EUS-HGS, type of stent, whether or not antegrade stenting (AS) was performed, procedure time, and AEs were assessed based on a prospectively recorded institutional endoscopy database. Logistic regression analysis was performed to identify factors affecting postprocedural AEs.

Results: Ninety-six patients were included in the study. EUS-guided HGS with and without AS was performed in 45 and 51 patients, respectively. Bile was aspirated in 71 patients (74%). The quantity of bile aspirated was 0-10 mL and > 10 mL in 40 and 56 patients, respectively. AEs including fever, abdominal pain, postprocedural cholangitis, sepsis, acute pancreatitis, and bleeding occurred in 45 patients (47%). The AE rates were 65% (26/40) and 34% (19/56), for 0-10 mL and > 10 mL bile, respectively (p = 0.004). Using multivariate analysis, the only independent factor affecting the occurrence of AEs was found to be an aspirated bile amount of 0-10 mL (odds ratio: 4.16; 95% CI 1.6-10.8).

Conclusions: Bile aspiration of more than 10 mL during EUS-HGS contributes to reducing the rate of postprocedural AEs.
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http://dx.doi.org/10.1007/s00464-020-08189-wDOI Listing
January 2021

Small-Dose Endoscopic Tattooing Using a Novel Needle for Localization Prior to Laparoscopic Surgery of Colorectal Cancer.

Dig Dis Sci 2021 Jan 2. Epub 2021 Jan 2.

Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-Gun, Shizuoka, 411-8777, Japan.

Backgrounds: Endoscopic tattooing failure by deep mural injection or tattoo leakage-induced massive staining causes localization errors or decreased laparoscopic visualization. To overcome these, we developed a novel tattoo needle with comparatively shorter needle (length, 2.5 mm) and minimal-caliber catheter (volume, 0.3 mL).

Aims: The single-center, prospective observational study aimed to determine the efficacy and safety of a small-doze endoscopic tattooing prior to laparoscopic surgery for colorectal cancer, using the needle.

Methods: Patients with colorectal cancer indicated for laparoscopic surgery were recruited. With the novel needle, a single tattoo was created at the anterior wall close to the lesion. During laparoscopic surgery, surgeons assessed the tattoo visibility, tattoo leakage, and the disturbance of laparoscopic view by tattoo leakage. The primary endpoint was an accurate localization by visible tattoo. Secondary endpoints were adverse events related to tattooing, the need for intraoperative endoscopy, and tattoo leakage.

Results: A total of 383 tattoos in 358 patients were analyzed. Accurate tumor localization rate was 96.6% (95% confidence interval [CI]: 94.3-98.0%). No adverse events occurred. Intraoperative colonoscopy was performed in 7 (1.8%) patients with invisible tattoo. Tattoo leakage was found in 4.2% (95%CI: 2.6-6.7%), and leakage disturbed the laparoscopic view of the surgical plane in 0.7% (95%CI: 0.3-2.3%).

Conclusions: Prior to laparoscopic surgery for colorectal cancer, our endoscopic tattooing with a standardized protocol using a novel needle is considered a simple, highly reliable localization technique with an extremely safe profile, which would be valuable to reduce physician's efforts and redundant medical resources. Trial registration number UMIN000021012. Date of registration: June 2016.
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http://dx.doi.org/10.1007/s10620-020-06757-7DOI Listing
January 2021

Tools for the Recognition of Sorting Signals and the Prediction of Subcellular Localization of Proteins From Their Amino Acid Sequences.

Front Genet 2020 25;11:607812. Epub 2020 Nov 25.

The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

At the time of translation, nascent proteins are thought to be sorted into their final subcellular localization sites, based on the part of their amino acid sequences (i.e., sorting or targeting signals). Thus, it is interesting to computationally recognize these signals from the amino acid sequences of any given proteins and to predict their final subcellular localization with such information, supplemented with additional information (e.g., -mer frequency). This field has a long history and many prediction tools have been released. Even in this era of proteomic atlas at the single-cell level, researchers continue to develop new algorithms, aiming at accessing the impact of disease-causing mutations/cell type-specific alternative splicing, for example. In this article, we overview the entire field and discuss its future direction.
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http://dx.doi.org/10.3389/fgene.2020.607812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723863PMC
November 2020

Structural snapshot of the mitochondrial protein import gate.

FEBS J 2020 Dec 10. Epub 2020 Dec 10.

Faculty of Life Sciences, Kyoto Sangyo University, Japan.

The translocase of the outer mitochondrial membrane (TOM) complex is the main entry gate for most mitochondrial proteins. The TOM complex is a multisubunit membrane protein complex consisting of a β-barrel protein Tom40 and six α-helical transmembrane (TM) proteins, receptor subunits Tom20, Tom22, and Tom70, and regulatory subunits Tom5, Tom6, and Tom7. Although nearly 30 years have passed since the main components of the TOM complex were identified and characterized, the structural details of the TOM complex remained poorly understood until recently. Thanks to the rapid development of the cryoelectron microscopy (EM) technology, high-resolution structures of the yeast TOM complex have become available. The identified structures showed a symmetric dimer containing five different subunits including Tom22. Biochemical and mutational analyses based on the TOM complex structure revealed the presence of different translocation paths within the Tom40 import channel for different classes of translocating precursor proteins. Previous studies including our cross-linking analyses indicated that the TOM complex in intact mitochondria is present as a mixture of the trimeric complex containing Tom22. Furthermore, the dimeric complex lacking Tom22, and the trimer and dimer may handle different sets of mitochondrial precursor proteins for translocation across the outer membrane. In this Structural Snapshot, we will discuss possible rearrangement of the subunit interactions upon dynamic conversion of the TOM complex between the different subunit assembly states, the Tom22-containing core dimer and trimer.
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http://dx.doi.org/10.1111/febs.15661DOI Listing
December 2020

Current Challenges and Opportunities in Designing Protein-Protein Interaction Targeted Drugs.

Adv Appl Bioinform Chem 2020 12;13:11-25. Epub 2020 Nov 12.

Department of Biological Sciences, Purdue University, West Lafayette, IN 47906, USA.

It has been noticed that the efficiency of drug development has been decreasing in the past few decades. To overcome the situation, protein-protein interactions (PPIs) have been identified as new drug targets as early as 2000. PPIs are more abundant in human cells than single proteins and play numerous important roles in cellular processes including diseases. However, PPIs have very different physicochemical features from the conventional drug targets, which make targeting PPIs challenging. Therefore, as of now, only a small number of PPI inhibitors have been approved or progressed to a stage of clinical trial. In this article, we first overview previous works that analyzed differences between PPIs with PPI targeting ligands and conventional drugs with their binding pockets. Then, we constructed an up-to-date list of PPI targeting drugs that have been approved or are currently under clinical trial and have bound drug-target structures available. Using the dataset, we analyzed the PPIs and their ligands using several scores of druggability. Druggability scores showed that PPI sites and their drugs targeting PPIs are less druggable than conventional binding pockets and drugs, which also indicates that PPI drugs do not follow the conventional rules for drug design, such as Lipinski's rule of five. Our analyses suggest that developing a new rule would be beneficial for guiding PPI-drug discovery.
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http://dx.doi.org/10.2147/AABC.S235542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669531PMC
November 2020

Type 1 Autoimmune Pancreatitis Extending along the Main Pancreatic Duct: IgG4-related Pancreatic Periductitis.

Intern Med 2021 Mar 30;60(5):739-744. Epub 2020 Sep 30.

Division of Endoscopy, Shizuoka Cancer Center, Japan.

We herein report a unique form of autoimmune pancreatitis (AIP) spreading along the main pancreatic duct (MPD). A 70-year-old man was referred for a small lesion at the pancreatic neck, accompanying an adjacent cyst and dilated upstream MPD. Four years earlier, health checkup images had shown a pancreatic cyst but no mass lesion. Endoscopic ultrasonography showed a contrast-enhanced, tumorous lesion, mainly occupying the MPD. With a preoperative diagnosis of ductal neoplasms mainly spreading in the MPD, Whipple's resection was performed. The resected specimens showed MPD periductitis with IgG4-related pathology, indicating type 1 AIP. Clinicians should practice caution concerning the various AIP forms.
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http://dx.doi.org/10.2169/internalmedicine.5754-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990648PMC
March 2021

Artificial Intelligence System to Determine Risk of T1 Colorectal Cancer Metastasis to Lymph Node.

Gastroenterology 2021 03 24;160(4):1075-1084.e2. Epub 2020 Sep 24.

Graduate School of Informatics, Nagoya University, Nagoya, Japan.

Background & Aims: In accordance with guidelines, most patients with T1 colorectal cancers (CRC) undergo surgical resection with lymph node dissection, despite the low incidence (∼10%) of metastasis to lymph nodes. To reduce unnecessary surgical resections, we used artificial intelligence to build a model to identify T1 colorectal tumors at risk for metastasis to lymph node and validated the model in a separate set of patients.

Methods: We collected data from 3134 patients with T1 CRC treated at 6 hospitals in Japan from April 1997 through September 2017 (training cohort). We developed a machine-learning artificial neural network (ANN) using data on patients' age and sex, as well as tumor size, location, morphology, lymphatic and vascular invasion, and histologic grade. We then conducted the external validation on the ANN model using independent 939 patients at another hospital during the same period (validation cohort). We calculated areas under the receiver operator characteristics curves (AUCs) for the ability of the model and US guidelines to identify patients with lymph node metastases.

Results: Lymph node metastases were found in 319 (10.2%) of 3134 patients in the training cohort and 79 (8.4%) of /939 patients in the validation cohort. In the validation cohort, the ANN model identified patients with lymph node metastases with an AUC of 0.83, whereas the guidelines identified patients with lymph node metastases with an AUC of 0.73 (P < .001). When the analysis was limited to patients with initial endoscopic resection (n = 517), the ANN model identified patients with lymph node metastases with an AUC of 0.84 and the guidelines identified these patients with an AUC of 0.77 (P = .005).

Conclusions: The ANN model outperformed guidelines in identifying patients with T1 CRCs who had lymph node metastases. This model might be used to determine which patients require additional surgery after endoscopic resection of T1 CRCs. UMIN Clinical Trials Registry no: UMIN000038609.
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http://dx.doi.org/10.1053/j.gastro.2020.09.027DOI Listing
March 2021

Tip-in endoscopic mucosal resection: Simple, efficacious trick for endoscopic mucosal resections of large colorectal polyps.

Dig Endosc 2021 Jan 27;33(1):203. Epub 2020 Oct 27.

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

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http://dx.doi.org/10.1111/den.13846DOI Listing
January 2021

Macroscopic on-site evaluation of biopsy specimens for accurate pathological diagnosis during EUS-guided fine needle biopsy using 22-G Franseen needle.

Endosc Ultrasound 2020 Nov-Dec;9(6):385-391

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

Background And Objectives: Measuring a visible core length during macroscopic on-site evaluation (MOSE) can be useful for accurate diagnoses during an EUS-guided fine needle biopsy (EUS-FNB). We aimed to estimate visible core cutoff lengths predictive of a correct diagnosis when using 22-gauge Franseen needles for biopsies from pancreatic masses.

Materials And Methods: We assessed 77 consecutive patients who underwent EUS-FNB using 22-gauge Franseen needles for pancreatic masses between March 2018 and October 2018. At least two needle passes were performed in all patients, irrespective of the findings on MOSE. The endoscopists measured the visible cores using a ruler during MOSE. The first two passes were analyzed on a per pass basis, and the correlation between visible core lengths and diagnostic accuracy was evaluated.

Results: We evaluated 150 needle passes of 75 patients. The accuracy per pass was 92% (138/150). The median length of the visible cores was 15 (range: 0-60) mm and they were significantly longer in the correct diagnosis group than in the incorrect diagnosis group. The accuracy correlated positively with the visible core length. Receiver-operating characteristic curve analysis of the visible core length for accuracy demonstrated an optimal cutoff value of 10 mm. On multivariate logistic regression, visible core lengths >10 mm independently affected the correct diagnosis (odds ratio: 5.1, P= 0.02).

Conclusions: Visible cores exceeding 10 mm may be useful for correct diagnosis while using a 22-gauge Franseen needle for EUS-FNB from pancreatic masses.
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http://dx.doi.org/10.4103/eus.eus_49_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811705PMC
September 2020
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