Publications by authors named "Hiroyuki Matsubayashi"

208 Publications

Sharing genetic test results of germline pathogenic variants of hereditary cancer with relatives: A single-center cross-sectional study.

Jpn J Clin Oncol 2021 Jul 8. Epub 2021 Jul 8.

Graduate School of Health Management, Keio University, Tokyo, Japan.

Objective: This study aimed to determine whether Japanese cancer patients share test results of germline pathogenic variants of hereditary cancer with their relatives.

Methods: This single-center cross-sectional study enrolled 21 Japanese patients who received results of germline pathogenic variants of hereditary cancer at least 6 months prior.

Results: All patients shared their test results with at least one relative, with the following sharing rates: 85.7% for first-degree relatives, 10% for second-degree relatives and 8.3% for third-degree relatives. Patients most commonly shared the information with their children aged >18 years (86.7%), followed by their siblings (73.6%), spouses (64.7%) and parents (54.5%). Three categories were extracted from qualitative analysis: 'characteristics of my cancer', 'knowledge and caution about inheritability' and 'utilization of medical care.'

Conclusions: The rate of test result sharing with first-degree relatives was comparable with those in Europe and the USA. Patients with germline pathogenic variants also tended to share their test results more with their children and siblings than with their parents. Informing their relatives of the results was suggestive of the motivation to influence their relatives' health outcome and contribute to the well-being of their children and siblings.
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http://dx.doi.org/10.1093/jjco/hyab110DOI Listing
July 2021

Can regular follow-up imaging contribute to the determination of appropriate timing of surgery in patients with undiagnosed mucinous cystic neoplasm? A multicenter retrospective study.

Jpn J Clin Oncol 2021 Jul 2. Epub 2021 Jul 2.

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

Objective: Guidelines suggest that patients with undiagnosed pancreatic cystic lesions should be monitored despite a lack of evidence supporting surveillance for undiagnosed mucinous cystic neoplasms (MCNs). We aimed to investigate the pre- and post-operative clinical course of patients with MCN and the utility of follow-up for patients who were not diagnosed with MCN at initial examination.

Patients And Methods: This multicenter retrospective study enrolled 28 patients with resected pathology-proven MCN; 12 and 16 patients underwent surgery within and after 6 months from the initial examination (Groups A and B, respectively). Outcome measures included changes in imaging findings until surgery in Group B, pathological findings between both groups and differences in pathological findings between patients with and without regular follow-up imaging in Group B.

Results: In Group B, the median cyst size was 30 and 48 mm at the initial examination and immediately before surgery, respectively. The incidence of mural cysts, thickened walls and mural nodules were 25, 19 and 0%, respectively, at the initial examination and 69, 56 and 31%, respectively, immediately before surgery. There were no significant differences in the invasive carcinoma rates between Groups A and B (13 vs. 17%). Regular follow-up imaging was offered to Group B. Among these, invasive carcinoma was found in one patient exhibiting no recurrence. One patient without follow-up imaging had invasive carcinoma recurrence post-operatively.

Conclusions: MCNs increased in size, and typical imaging findings appeared over time. For undiagnosed MCN, regular follow-up examination contributed to the determination of the appropriate surgical timing.
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http://dx.doi.org/10.1093/jjco/hyab103DOI 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

Genomic profiling of multiple tissues in two patients with multiple endocrine neoplasia type 1.

Biomed Res 2021 ;42(2):89-94

Shizuoka Cancer Center.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor syndrome. This hereditary cancer is caused by germline variants in MEN1. Two patients with MEN1 were identified via whole exome sequencing and gene expression profile analysis, conducted for 5,063 patients with various types of cancers. We obtained multiple tumors from each patient; tumors derived from these two MEN1 patients had a loss of the normal MEN1 allele and frequently chromosomal copy number changes. Thus, we investigated whether structural variants were present in the MEN1 patient genomes. Whole-genome sequencing revealed no catastrophic rearrangements, and the tumor samples had very low somatic variants. The two patients had germline variants in MEN1 and some chromosomal copy number changes including on chromosome 11. The only pathogenic variant detected was the MEN1 germline variant, and chromosomal rearrangements led to tumorigenesis in somatic cells. Furthermore, the MEN1 tumor samples displayed a specific signature characterized by T:A>C:G transition. Studies of multiple tumors obtained from single patients are rare in hereditary cancer syndromes, and our results provide insights that the second hit of the tumor suppressor gene MEN1 may be caused by a gross genome rearrangement, not a small insertion and deletion, nor a change in epigenetic regulation.
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http://dx.doi.org/10.2220/biomedres.42.89DOI Listing
January 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

Detectability on Plain CT is an Effective Discriminator between Carcinoma and Benign Disorder for a Polyp >10 mm in the Gallbladder.

Diagnostics (Basel) 2021 Feb 25;11(3). Epub 2021 Feb 25.

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.

An appropriate diagnosis is required to avoid unnecessary surgery for gallbladder cholesterol polyps (GChPs) and to appropriately treat pedunculated gallbladder carcinomas (GCs). Generally, polyps >10 mm are regarded as surgical candidates. We retrospectively evaluated plain and contrast-enhanced (CE) computed tomography (CT) findings and histopathological features of 11 early GCs and 10 GChPs sized 10-30 mm to differentiate between GC and GChP >10 mm and determine their histopathological background. Patient characteristics, including polyp size, did not significantly differ between groups. All GCs and GChPs were detected on CE-CT; GCs were detected more often than GChPs on plain CT (73% vs 9%; < 0.01). Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for GCs were 73%, 90%, 89%, 75%, and 81%, respectively. On multivariate analysis, lesion detectability on plain CT was independently associated with GCs (odds ratio, 27.1; = 0.044). Histopathologically, GChPs consisted of adipose tissue. Although larger vessel areas in GCs than in GChPs was not significant (52,737 μm vs 31,906 μm; = 0.51), cell densities were significantly greater in GCs (0.015/μm vs 0.0080/μm; < 0.01). Among GPs larger than 10 mm, plain CT could contribute to differentiating GCs from GChPs.
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http://dx.doi.org/10.3390/diagnostics11030388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996218PMC
February 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

Comparing the 14-mm uncovered and 10-mm covered metal stents in patients with distal biliary obstruction caused by unresectable pancreatic cancer: a multicenter retrospective study.

Surg Endosc 2021 Feb 16. Epub 2021 Feb 16.

Department of Gastroenterological Internal Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.

Background: Endoscopic biliary drainage using metal stent (MSs) is an established palliative treatment for patients with unresectable malignant distal biliary obstruction (MDBO). However, a major drawback of MS is recurrent biliary obstruction (RBO). Uncovered MSs with a diameter of 14 mm (UMS-14) were developed to overcome this. We aimed to compare the clinical outcomes of UMS-14 with those of conventional covered MSs having a diameter of 10 mm (CMS-10).

Methods: Consecutive patients with MDBO caused by unresectable pancreatic cancer, who underwent UMS-14 or CMS-10 placement at two tertiary-care centers, were retrospectively examined according to the Tokyo Criteria 2014.

Results: Two hundred and thirty-eight patients who underwent UMS-14 (the UMS-14 group, n = 80) or CMS-10 (the CMS-10 group, n = 158) over a 62-month period were included. The technical and clinical success rates were similar between the two groups. RBO occurred in 20 (25%) and 59 (37%) patients of the UMS-14 and CMS-10 groups, respectively (p = 0.06). Median time till RBO was significantly longer in the UMS-14 group than in the CMS-10 group (not reached vs. 290 days, p = 0.04). Multivariate analysis revealed that CMS-10 placement was an independent risk factor for RBO (hazard ratio: 1.66, 95% confidence interval: 1.00-2.76). The incidence of early complications, including pancreatitis, and the overall survival (UMS-14 vs. CMS-10: 169 vs. 167 days, p = 0.83) were comparable between the two groups.

Conclusions: UMS-14 stents were safe and effective for treating patients with MDBO secondary to unresectable pancreatic cancer. The insertion of UMS-14 is recommended, because it is less likely to get occluded as compared to CMS-10.
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http://dx.doi.org/10.1007/s00464-021-08342-zDOI Listing
February 2021

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

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

Role of Tumor Mutation Burden Analysis in Detecting Lynch Syndrome in Precision Medicine: Analysis of 2,501 Japanese Cancer Patients.

Cancer Epidemiol Biomarkers Prev 2021 01 12;30(1):166-174. Epub 2020 Oct 12.

Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

Background: Tumor mutation burden (TMB) is the total exonic mutation count per megabase of tumor DNA. Recent advances in precision medicine occasionally detect Lynch syndrome (LS) by germline sequencing for mismatch-repair (g.) genes but not using TMB. The current study analyzes the utility of TMB in detecting LS.

Methods: Whole-exome sequencing (ion-semiconductor sequencing) was performed for somatic and germline DNA from 2,501 various cancer patients to detect TMB and g. sequencing. MMR IHC was conducted when high TMB (≥10) was detected in LS-related cancers with an additional condition of wild-type in colorectal cancers. Target sequencing and multiplex ligation-dependent probe amplification (MLPA) were further performed for g. genes in MMR-deficient cancers (TMB-based g. target sequencing). We compared universal sequencing and TMB-based target sequencing in their sensitivity for detecting LS.

Results: LS was detected in 16 (0.6%) of the 2,501 patients: 1.1% (9/826) of colorectal cancer patients, 16.2% (6/37) of endometrial cancer patients, and 14.3% (1/7) of small intestine cancer patients. TMB-based g. target sequencing (81.3%) showed superior sensitivity for detecting LS than universal g. sequencing (56.3%; = 0.127) but missed 3 LS patients (1 with a low-TMB cancer, 1 with a -mutant colorectal cancer, and 1 with an MMR-proficient cancer). Ion-semiconductor sequencing could detect single-nucleotide substitutions but not large deletions. -mutated cancers showed extremely high TMBs (48.4-749.2).

Conclusions: g. target sequencing, combined with TMB, somatic mutation, and MMR IHC is an effective strategy for detecting LS.

Impact: TMB can be a biomarker for detecting LS in precision medicine.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0694DOI Listing
January 2021

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

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

Ultrathin colonoscopy can improve complete preoperative colonoscopy for stenotic colorectal cancer: Prospective observational study.

Dig Endosc 2021 May 7;33(4):621-628. Epub 2020 Oct 7.

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

Objectives: Preoperative colonoscopy is often incomplete for stenotic colorectal cancers (CRC). This prospective observational study aimed to evaluate the ability of an ultrathin colonoscope (UTC) to inspect the whole colon by passing through the stenotic CRC.

Methods: All patients who underwent preoperative colonoscopy for stenotic CRCs at Shizuoka Cancer Center were examined for eligibility. If a standard colonoscope (PCF-H290ZI) could not pass because of a stenosis, the patients were recruited. All of the eligible patients were prospectively enrolled when informed consent could be obtained, and complete colonoscopy was attempted again using an UTC (PCF-PQ260L). Patients with stent placement and those requiring right hemicolectomy were not recruited. Primary endpoints were pass-through and cecal intubation rates. The detected synchronous neoplasias (adenomas and cancers) and their pathological findings after resection were evaluated.

Results: A total of 100 patients were enrolled between September 2017 and February 2019. The mean age was 65.6 ± 10.8 years, and 59% were male. The pass-through and cecal intubation rates were 67% (67/100) and 58% (58/100), respectively. Synchronous lesions located proximal to the stenoses were detected in 65.5% (38/58) of the complete colonoscopies, with a total of 86 lesions, including 18 advanced neoplasias with three invasive cancers.

Conclusion: When standard colonoscopy cannot pass through stenotic CRC, ultrathin colonoscopy can be considered as an option to inspect the whole colon proximal to the stenosis because treatment strategy can potentially be changed by detecting synchronous neoplasias proximal to the stenosis before surgery. (UMIN000028505).
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http://dx.doi.org/10.1111/den.13829DOI Listing
May 2021

Disclosure of secondary findings in exome sequencing of 2480 Japanese cancer patients.

Hum Genet 2021 Feb 24;140(2):321-331. Epub 2020 Jul 24.

Research Institute of Shizuoka Cancer Center, Shizuoka, Japan.

High-throughput sequencing has greatly contributed to precision medicine. However, challenges remain in reporting secondary findings (SFs) of germline pathogenic variants and managing the affected patients. The aim of this study was to examine the incidence of SFs in Japanese cancer patients using whole exome sequencing (WES) and to understand patient preferences regarding SF disclosure. WES was conducted for 2480 cancer patients. Genomic data were screened and classified for variants of 59 genes listed by the American College of Medical Genetics and Genomics SF v2.0 and for an additional 13 hereditary cancer-related genes. Majority of the participants (68.9%; 1709/2480) opted for disclosure of their SFs. Thirty-two pathogenic or likely pathogenic variants, including BRCA1 (7 patients), BRCA2 (4), CHEK2 (4), PTEN (3), MLH1 (3), SDHB (2), MSH6 (1), NF1 (1), EXT2 (1), NF1 (1), NTRK1 (1), MYH7 (3), MYL2 (1), TNNT2 (1), LDLR (2), FBN1 (1), and KCNH2 (1) were recognized in 36 patients (1.5%). Twenty-eight (77.8%) patients underwent genetic counseling and received their SF results. Eighteen (64.3%) patients underwent clinical management for SFs. Genetic validation tests were administered significantly more frequently to patients with than without a SF-related personal history (P = 0.025). This was a first attempt at a large-scale systematic exome analysis in Japan; nevertheless, many cancer patients opted for disclosure of SFs and accepted or considered clinical management.
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http://dx.doi.org/10.1007/s00439-020-02207-6DOI Listing
February 2021

United European Gastroenterology guideline: How to manage immunoglobulin G4-related digestive diseases.

United European Gastroenterol J 2020 07;8(6):635-636

Department of Endoscopy, Yokohama City Hospital, Kanagawa, Japan.

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http://dx.doi.org/10.1177/2050640620927846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437082PMC
July 2020

Effectiveness of suction valve button removal in retrieving resected colon polyps for better histological assessment: Propensity score matching analysis.

Dig Endosc 2021 Mar 27;33(3):433-440. Epub 2020 Sep 27.

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

Background And Aim: Fragmentation of endoscopically resected colorectal polyps during retrieval is one of the limitations for appropriate pathological diagnosis; however, little is known about steps to reduce it. We aimed to evaluate the effect of removing the suction valve button, which is one of the intricate parts of the endoscope, during polyp suction retrieval for fragmentation and pathological diagnosis.

Methods: We retrospectively reviewed the polyps retrieved by suctioning. We used the propensity score matching method to adjust for difference between the button-attached and button-removed groups. Outcomes of fragmentation, pathological diagnosis of non-neoplastic polypectomy (NNP), and pathological cut-end among neoplastic lesions were evaluated.

Results: On the basis of propensity score matching, 322 pairs of cases were selected for analysis. After matching, the difference in the variables between the two groups was closely balanced. The fragmentation rate was significantly different between the groups (button-attached 36.6% vs. button-removed 22.4%, P < 0.001). No significant difference in the NNP rate was observed between the two groups (button-attached 8.4% vs. button-removed 9.9%). The rate of unclear cut-end was lower in the button-removed group than in the button-attached group (16.2% vs. 9.1%, P = 0.010). In the multivariate analysis, button removal was independently associated with reductions of fragmentation (odds ratio [OR] 0.508, P < 0.001) and unclear cut-end (OR 0.503, P = 0.009). Also, NNP was associated with smaller lesion size (OR 0.364, P < 0.001), but not with button removal.

Conclusions: Suction valve button removal during polyp suction retrieval was an effective method to decrease the rates of fragmentation and histological unclear margins.
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http://dx.doi.org/10.1111/den.13779DOI Listing
March 2021

Diagnostic performance for T1 cancer in colorectal lesions ≥10 mm by optical characterization using magnifying narrow-band imaging combined with magnifying chromoendoscopy; implications for optimized stratification by Japan Narrow-band Imaging Expert Team classification.

Dig Endosc 2021 Mar 19;33(3):425-432. Epub 2020 Aug 19.

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

Background: Magnifying narrow-band imaging (M-NBI) and magnifying chromoendoscopy (M-CE) enable accurate diagnosis of T1 colorectal cancer, but the diagnostic yields from combined M-NBI and CE have not been fully analyzed. We aimed to evaluate the diagnostic yield of combining Japan NBI Expert Team (JNET) classification using M-NBI and M-CE.

Methods: Superficial colorectal lesions ≥10 mm removed at a Japanese tertiary cancer center between February 2016 and December 2018 were included. We analyzed the relationship between JNET classification, M-CE findings, and histological results based on prospectively collected endoscopic and pathologic data.

Results: A total of 1573 lesions, including 56 superficial submucosal invasive cancers, 160 deep submucosal invasive cancers, and 81 advanced cancers (≥T2) were analyzed. The probability of deeply invasive cancer (95% confidence interval) was 1.8% (1.1-2.8), 30.1% (25.4-35.1), and 96.6% (91.5-99.1) in JNET Types 2A, 2B, and 3, respectively. The probability of deeply invasive cancer in JNET Type 2B lesions with non-V, VL, and VH pit pattern was 4.3%, 16.6%, 76.0%, respectively (P < 0.001).

Conclusions: Our study showed the stratification by M-NBI using JNET classification and the effect of additional M-CE for JNET Type 2B lesions.
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http://dx.doi.org/10.1111/den.13766DOI Listing
March 2021

Efficacy and safety of cold-snare endoscopic mucosal resection for colorectal adenomas 10 to 14 mm in size: a prospective observational study.

Gastrointest Endosc 2020 12 26;92(6):1239-1246. Epub 2020 May 26.

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

Background And Aims: Cold-snare endoscopic mucosal resection (CS-EMR) has been adapted in a piecemeal fashion as a safe and effective procedure for resection of colorectal polyps ≥10 mm. However, few data are available on en bloc CS-EMR for adenomas of 10 to 14 mm. Thus, this study evaluated the efficacy and safety of CS-EMR for these colorectal adenomas.

Methods: In this single-arm, prospective, observational study, patients with at least 1 slightly elevated and sessile colorectal adenoma measuring 10 to 14 mm were recruited to undergo CS-EMR. The primary outcome was histological complete resection rate by CS-EMR, which was defined as en bloc resection, with a pathologically negative vertical margin and no neoplastic tissue obtained from 4 quadrants of the mucosal defect margin. Secondary outcomes were en bloc resection rate by CS-EMR, failure rate of CS-EMR, and the incidence of adverse events.

Results: A total of 80 polyps from 72 patients were included. CS-EMR failed in 11 lesions (13.7%), all of which were resected using a high-frequency electric current. The rates of en bloc resection and histologic complete resection by CS-EMR were 82.5% (66 of 80) and 63.8% (51 of 80), respectively. No bleeding occurred during the CS-EMR procedure, and there was no delayed bleeding or perforation at the site where CS-EMR was performed.

Conclusions: CS-EMR can be safely performed in an en bloc fashion for some colorectal adenomas measuring 10 to 14 mm. However, there is room for improvement regarding the resectability and evaluation of the vertical margin after CS-EMR. (Clinical trial registration number: UMIN000031248.).
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http://dx.doi.org/10.1016/j.gie.2020.05.019DOI Listing
December 2020

Present Status of Endoscopic Submucosal Dissection for Non-Ampullary Duodenal Epithelial Tumors.

Clin Endosc 2020 Nov 15;53(6):652-658. Epub 2020 Jan 15.

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

Prediction of histology by endoscopic examination is important in the clinical management of non-ampullary duodenal epithelial tumors (NADETs), including adenoma and adenocarcinoma. The use of a simple scoring system based on the findings of white-light endoscopy or magnified endoscopy with narrow-band imaging is useful to differentiate between Vienna category 3 (C3) and C4/5 lesions. Less invasive endoscopic resection procedures, such as cold snare polypectomy, are quick to perform and convenient for small (<10 mm) C3 lesions. Neoplasms with higher grade histology, such as C4/5 lesions, should be treated by endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or surgery. Although EMR often requires piecemeal resection, the complication rate is acceptable. Excellent complete resection rates could be achieved by ESD; however, it remains a challenging method considering the high risk of complications. Shielding or closure of the ulcer after ESD is effective at decreasing the risk of delayed bleeding and perforation. Laparoscopic endoscopic cooperative surgery is an ideal treatment with a high rate of en bloc resection and a low rate of complications, although it is limited to high-volume centers. Patients with NADETs could benefit from a multidisciplinary approach to stratify the optimal treatment based on endoscopic diagnoses.
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http://dx.doi.org/10.5946/ce.2019.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719431PMC
November 2020

Multiple Carcinomas and Intraepithelial Neoplasms in a Case of Familial Pancreatic Cancer: Rapid Morphological Changes in the Pancreatic Cyst and Pathological Lesions Undetected by Clinical Images.

Intern Med 2020 Apr 9;59(8):1041-1046. Epub 2020 Jan 9.

Division of Endoscopy, Shizuoka Cancer Center, Japan.

A 69-year-old woman with a family history of pancreatic cancer was referred because of imaging changes of a pancreas cyst. Magnetic resonance cholangiopancreatography showed a faintly dilated main pancreatic duct and a pancreas body cyst that had changed rapidly over the past year. Computed tomography demonstrated an emerging enhancing lesion in the pancreatic cyst. Endoscopic ultrasonography revealed an irregular-margined, heterogeneous-echoic pancreatic mass, without findings of early chronic pancreatitis. She underwent distal pancreatectomy. A histologic examination of the resected specimen revealed invasive adenocarcinoma with numerous multicentric foci of pancreatic intraepithelial neoplasia (PanIN), including high-grade PanIN, apparently separate from the main cancer.
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http://dx.doi.org/10.2169/internalmedicine.3882-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205531PMC
April 2020

Steroid Therapy and Steroid Response in Autoimmune Pancreatitis.

Int J Mol Sci 2019 Dec 30;21(1). Epub 2019 Dec 30.

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

Autoimmune pancreatitis (AIP), a unique subtype of pancreatitis, is often accompanied by systemic inflammatory disorders. AIP is classified into two distinct subtypes on the basis of the histological subtype: immunoglobulin G4 (IgG4)-related lymphoplasmacytic sclerosing pancreatitis (type 1) and idiopathic duct-centric pancreatitis (type 2). Type 1 AIP is often accompanied by systemic lesions, biliary strictures, hepatic inflammatory pseudotumors, interstitial pneumonia and nephritis, dacryoadenitis, and sialadenitis. Type 2 AIP is associated with inflammatory bowel diseases in approximately 30% of cases. Standard therapy for AIP is oral corticosteroid administration. Steroid treatment is generally indicated for symptomatic cases and is exceptionally applied for cases with diagnostic difficulty (diagnostic steroid trial) after a negative workup for malignancy. More than 90% of patients respond to steroid treatment within 1 month, and most within 2 weeks. The steroid response can be confirmed on clinical images (computed tomography, ultrasonography, endoscopic ultrasonography, magnetic resonance imaging, and F-fluorodeoxyglucose-positron emission tomography). Hence, the steroid response is included as an optional diagnostic item of AIP. Steroid treatment results in normalization of serological markers, including IgG4. Short- and long-term corticosteroid treatment may induce adverse events, including chronic glycometabolism, obesity, an immunocompromised status against infection, cataracts, glaucoma, osteoporosis, and myopathy. AIP is common in old age and is often associated with diabetes mellitus (33-78%). Thus, there is an argument for corticosteroid therapy in diabetes patients with no symptoms. With low-dose steroid treatment or treatment withdrawal, there is a high incidence of AIP recurrence (24-52%). Therefore, there is a need for long-term steroid maintenance therapy and/or steroid-sparing agents (immunomodulators and rituximab). Corticosteroids play a critical role in the diagnosis and treatment of AIP.
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http://dx.doi.org/10.3390/ijms21010257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981453PMC
December 2019

A risk-prediction model for en bloc resection failure or perforation during endoscopic submucosal dissection of colorectal neoplasms.

Dig Endosc 2020 Sep 6;32(6):932-939. Epub 2020 Feb 6.

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

Objectives: Technical difficulties in colorectal endoscopic submucosal dissections (ESD) result in en bloc resection failure or perforation. This study aimed to develop and validate a risk score for predicting en bloc resection failure or perforation in ESD of colorectal neoplasms.

Methods: This single-center observational study included 1133 colorectal neoplasms treated with ESD in a Japanese tertiary cancer center. With a derivation set (n = 716), we performed multiple logistic regression to identify significant risk factors for en bloc resection failure or perforation. Based on odds ratios, we developed a risk score, ranging from 0 to 10: 0-1 'low risk' (LR); 2-4 'moderate risk' (MR); and 5-10 'high risk' (HR). An independent validation set comprised prospectively enrolled subjects (n = 417) that underwent ESDs from January 2014 to August 2016. The performance of the risk score for predicting en bloc resection failure or perforation for each risk tier was evaluated.

Results: The baseline incidences of en bloc resection failure or perforation were 14.5% and 5.5% in the derivation and validation sets, respectively. We identified the following significant risk factors: endoscopist experience, tumor location, morphology, scope operability, underlying fold, and fold convergence. In the validation set, the incidences of en bloc resection failure or perforation were 0% in the LR tier (n = 62; 14.8%), 2.3% in the MR tier (n = 293; 70.4%), and 25.8% in the HR tier (n = 62; 14.8%) (P < 0.001, Cochran-Armitage trend test).

Conclusions: A risk scoring system, which was developed and prospectively validated, can successfully estimate the incidence of en bloc resection failure or perforation.
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http://dx.doi.org/10.1111/den.13619DOI Listing
September 2020

An Intra-abdominal Solid-cystic Desmoid That Emerged after Distal Gastrectomy.

Intern Med 2019 15;58(24):3525-3529. Epub 2019 Dec 15.

Division of Endoscopy, Shizuoka Cancer Center, Japan.

Desmoid is a locally aggressive fibroblastic neoplasm, typically showing a heterogeneous solid mass, and its pathogenesis is multifactorial, including surgical scars. We herein report a rare case of an intra-abdominal desmoid, consisting of solid and cystic components covered with epithelial linings, that emerged after distal gastrectomy. The preoperative diagnosis was inconclusive, so laparotomy was performed. Histopathology of the solid component showed proliferating spindle cells, which were positive for beta-catenin in their nuclei. Clinicians need to bear in mind that desmoids can appear in a solid-cystic form, and immunostaining of beta-catenin should be applied for tumors that emerge around postoperative wounds.
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http://dx.doi.org/10.2169/internalmedicine.3252-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949453PMC
March 2020

Rare Images of a Peripancreatic Ganglioneuroma.

Intern Med 2020 04 13;59(7):1005-1006. Epub 2019 Dec 13.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan.

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http://dx.doi.org/10.2169/internalmedicine.3826-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184096PMC
April 2020

Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers.

Diagnostics (Basel) 2019 Oct 31;9(4). Epub 2019 Oct 31.

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.

A family history of pancreatic cancer (PC) is a risk factor of PC, and risk levels increase as affected families grow in number and/or develop PC at younger ages. Familial pancreatic cancer (FPC) is defined as a client having at least two PC cases in a first degree relatives. In the narrow sense, FPC does not include some inherited cancer syndromes that are known to increase the risks of PC, such as Peutz-Jeghers syndrome (PJS), hereditary pancreatitis (HP), hereditary breast ovarian cancer syndrome (HBOC), and so on. FPC accounts for 5%-10% of total PC diagnoses and is marked by several features in genetic, epidemiological, and clinicopathological findings that are similar to or distinct from conventional PC. Recent advances in genetic medicine have led to an increased ability to identify germline variants of cancer-associated genes. To date, high-risk individuals (HRIs) in many developed countries, including FPC kindreds and inherited cancer syndromes, are screened clinically to detect and treat early-stage PC. This article highlights the concept of FPC and the most recent data on its detection.
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http://dx.doi.org/10.3390/diagnostics9040169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963266PMC
October 2019