Publications by authors named "Hiroyuki Ono"

308 Publications

Factors influencing plasma coproporphyrin-I concentration as biomarker of OATP1B activity in patients with rheumatoid arthritis.

Clin Pharmacol Ther 2021 Jul 28. Epub 2021 Jul 28.

Department of Clinical Pharmacy, Oita University Hospital, 5-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan.

Organic anion transporting polypeptides (OATP)1B are drug transporters mainly expressed in the sinusoidal membrane. In previous reports, genetic factor, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) which is one of the uremic toxins, inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) decreased OATP1B1 activity in vitro, but in vivo effects of these factors have not been elucidated. Plasma coproporphyrin-I (CP-I) is spotlighted as a highly accurate endogenous substrate of OATP1B. This study focused on patients with rheumatoid arthritis (RA) and evaluated the influence of several factors comprising gene polymorphisms, uremic toxins and inflammatory cytokines on OATP1B activity using plasma CP-I concentration. Thirty-seven outpatients with RA who satisfied the selection criteria were analyzed at the time of recruitment (baseline) and at the next visit. OATP1B1*15 carriers tended to have higher CP-I concentration compared to non-carriers. Plasma CP-I correlated positively with CMPF concentration, but did not correlate with IL-6 or TNF-α concentration. Multiple logistic regression analysis by stepwise selection identified plasma CMPF concentration and OATP1B1*15 allele as significant factors independently affecting plasma CP-I concentration at baseline and at the next visit, respectively. In conclusion, the present results suggest that inflammatory cytokines do not have clinically significant effects on OATP1B activity, whereas the effects of genetic polymorphisms and uremic toxins should be considered.
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http://dx.doi.org/10.1002/cpt.2375DOI Listing
July 2021

Response.

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

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

Association of CYP3A5 polymorphisms and parathyroid hormone with blood level of tacrolimus in patients with end-stage renal disease.

Clin Transl Sci 2021 May 31. Epub 2021 May 31.

Department of Clinical Pharmacy, Oita University Hospital, Oita, Japan.

Because tacrolimus is predominantly metabolized by CYP3A, the blood concentration/dose (C/D) ratio is affected by CYP3A5 polymorphism. Parathyroid hormone (PTH) expression increases in secondary hyperparathyroidism, which is frequently associated with end-stage renal disease. Recently, PTH has been shown to downregulate CYP3A expression at mRNA level. In this study, we examined the influence of CYP3A5 polymorphism on and association of serum intact-PTH (iPTH) level with blood tacrolimus concentration in patients with end-stage renal disease just before kidney transplantation. Forty-eight patients who satisfied the selection criteria were analyzed. Subjects were classified into two phenotype subgroups: CYP3A5 expressor (CYP3A5*1/*1 and *1/*3; n = 15) and CYP3A5 nonexpressor (CYP3A5*3/*3; n = 33). The blood tacrolimus C/D (per body weight) ratio was significantly lower in CYP3A5 expressors than that in CYP3A5 nonexpressors. A significant positive correlation was found between tacrolimus C/D and iPTH concentrations (r = 0.305, p = 0.035), and the correlation coefficient was higher after excluding 20 patients co-administered CYP3A inhibitor or inducer (r = 0.428, p = 0.023). A multiple logistic regression analysis by stepwise selection identified CYP3A5 polymorphism and serum iPTH level as significant factors associated with tacrolimus C/D. These results may suggest the importance of dose design considering not only the CYP3A5 phenotype but also serum iPTH level when using tacrolimus in patients who undergo renal transplantation.
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http://dx.doi.org/10.1111/cts.13065DOI Listing
May 2021

Glucocorticoid-dependent Tubulointerstitial Nephritis with IgM-positive Plasma Cells Presenting with Intracellular Crystalline Inclusions within the Rough Endoplasmic Reticulum.

Intern Med 2021 Apr 12. Epub 2021 Apr 12.

Department of Nephrology, Tokushima University Graduate School of Biomedical Science, Japan.

Tubulointerstitial nephritis (TIN) with IgM-positive plasma cells (IgMPC-TIN) is an autoimmune kidney disease characterized by IgM/CD138-double-positive plasma cell infiltration in the tubulointerstitium. A 50-year-old man developed IgMPC-TIN and presented with crystalline inclusions in the rough endoplasmic reticulum. Intracellular crystal formation is a rare finding in paraprotein-related kidney diseases, but this case showed no pathogenic monoclonal immunoglobulin. Prednisolone (PSL, 30 mg) improved the TIN, but PSL tapering resulted in the recurrence of TIN. Combination therapy with 15 mg PSL and 150 mg mizoribine ultimately stabilized TIN. This case offers original evidence concerning the pathophysiology and treatment strategy of IgMPC-TIN.
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http://dx.doi.org/10.2169/internalmedicine.7118-21DOI Listing
April 2021

Surgically treated gastric cancer in Japan: 2011 annual report of the national clinical database gastric cancer registry.

Gastric Cancer 2021 May 3;24(3):545-566. Epub 2021 Apr 3.

Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Background: The National Clinical Database (NCD) nationwide registry program of gastric cancer started in 2018. The purpose of this study was to report the treatment results of the NCD registry in the form of treatment results of the real world in Japan.

Methods: Patients' characteristics, tumor features, treatments, and outcomes were collected using a web-based data entry system. We analyzed the initial NCD database for data on surgically treated gastric cancer patients in 2011.

Results: A total of 30,257 patients with malignant gastric tumors were enrolled by the NCD registry program from 501 hospitals in all 47 prefectures. Of these, the status of data entry was not approved in 8.8% of the registered data, and follow-up information was missing in 1.2% of the approved cases. Excluding 1777 cases, which were not resected for primary gastric cancer, 25,306 resected cases included 44.4% of stomach surgeries recorded in the NCD. The 5 year survival rate of the resected cases was 71.3% and the operative mortality rate was 0.41%. The stage-specific 5 year survival rates were as follows: 89.6% for stage IA, 83.8% for stage IB, 77.3% for stage IIA, 69.1% for stage IIB, 58.7% for stage IIIA, 44.1% for stage IIIB, 30.1% for stage IIIC, and 13.4% for stage IV.

Conclusions: The NCD gastric cancer registry program demonstrated validity for database construction. The gastric cancer registry is expected to become a nationwide registry with the dissemination of data entry system and method in the NCD.
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http://dx.doi.org/10.1007/s10120-021-01178-5DOI Listing
May 2021

Incidence and treatment outcomes of metachronous gastric cancer occurring after curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer: Japan Clinical Oncology Group study-post hoc analysis of JCOG1009/1010.

Gastric Cancer 2021 Sep 31;24(5):1123-1130. Epub 2021 Mar 31.

Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Background And Aims: A drawback of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is the development of metachronous gastric cancer (MGC). While MGC after ESD for differentiated-type (D-) EGC was well understood, little is known about MGC occurring after ESD for undifferentiated-type (UD-) EGC, because ESD had not been indicated. We evaluated the incidence and treatment outcomes of MGC after ESD of UD-EGC.

Methods: This study is a post hoc analysis of JCOG1009/1010, a multicenter trial to evaluate the efficacy and safety of ESD for UD-EGC. The patients who underwent curative ESD of index solitary UD-EGC were analyzed. Surveillance endoscopy was performed biannually for the first 3 years and thereafter annually. We assessed the time to MGC occurrence after ESD, lesion characteristics, and treatment outcomes of MGC. Time to MGC occurrence was estimated by cumulative incidence function, with death and total gastrectomy as competing risks.

Results: A total of 198 patients were included in this study. During a median follow-up period of 5.8 years, 4 patients (2%) developed MGC. Median time to MGC occurrence was 4.5 years (range: 3.1-5.4). Five-year cumulative incidence of MGC was 1.0% (95% CI: 0.2-3.3%). Two MGCs were histologically D-EGC, and the remaining two were UD-EGC. The median tumor size of MGCs was 1.0 cm (range: 0.7-1.7), and the depth of invasion (M/SM1/SM2) was 2/1/1, respectively. Three patients achieved curative resection with repeated ESD.

Conclusions: MGC does not occur commonly after curative ESD of UD-EGC, and repeated ESD could contribute to stomach preservation.
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http://dx.doi.org/10.1007/s10120-021-01183-8DOI Listing
September 2021

Sensitive, wide-range and high-throughput quantification of cyclosporine in whole blood using ultra-performance liquid chromatography coupled to tandem mass spectrometry and comparison with an antibody-conjugated magnetic immunoassay.

Biomed Chromatogr 2021 Aug 19;35(8):e5128. Epub 2021 Apr 19.

Department of Clinical Pharmacy, Oita University Hospital, Yufu, Oita, Japan.

Because either trough or peak concentration at 2 h after administration is measured in routine therapeutic drug monitoring for cyclosporine A (CyA), a quantification method with a wide-range calibration curve capable of simultaneously measuring both concentrations is required. We developed a sensitive, wide-range and high-throughput quantification method for CyA in whole blood using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and compared patients' blood CyA levels measured by UPLC-MS/MS and antibody-conjugated magnetic immunoassay (ACMIA). Whole blood samples were prepared by solid-phase extraction using Oasis HLB μElution plate. The UPLC-MS/MS assay showed excellent linearity over a wide calibration range of 5-2500 ng/mL. Within-batch accuracy and precision as well as batch-to-batch accuracy and precision fulfilled the criteria of US Food and Drug Administration guidelines. The blood CyA concentrations measured by the UPLC-MS/MS assay correlated strongly with those measured by ACMIA. A Bland-Altman plot showed a fixed error between CyA concentrations measured by the two methods, and the concentrations measured by the UPLC-MS/MS method were consistently lower than those measured by ACMIA. We have succeeded to develop a sensitive, wide-range and high-throughput quantification method for CyA in whole blood using UPLC-MS/MS.
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http://dx.doi.org/10.1002/bmc.5128DOI Listing
August 2021

Effect of S-1 on blood levels of phenobarbital and phenytoin: A case report.

Clin Case Rep 2021 Mar 4;9(3):1514-1517. Epub 2021 Feb 4.

Department of Clinical Pharmacy Oita University Hospital, Yufu-shi Oita Japan.

Drug-drug interaction of fluorinated pyrimidine anticancer agents with phenytoin is well known, but interaction with phenobarbital is limited. We describe a case showing increases in plasma phenobarbital as well as phenytoin concentrations during preoperative S-1 (tegafur/gimeracil/oteracil) and radiation therapy for rectal cancer.
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http://dx.doi.org/10.1002/ccr3.3813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981613PMC
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

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

Diagnostic yield of conventional endoscopy with endoscopic ultrasonography for submucosal invasion of superficial esophageal squamous cell carcinoma: a post hoc analysis of multicenter prospective confirmatory study (JCOG0508).

Esophagus 2021 Jul 28;18(3):604-611. Epub 2021 Jan 28.

Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Background: Endoscopic ultrasonography (EUS) is reportedly the reliable modality to predict the depth of esophageal squamous cell carcinoma (ESCC), however, most previous studies are retrospective or single-centered. We aimed to evaluate the diagnostic ability of conventional endoscopy and EUS using the data from a multicenter prospective study of endoscopic resection (ER) followed by chemoradiotherapy for cSM1-2N0M0 ESCC (JCOG0508).

Methods: All lesions were evaluated as cSM cancer with both conventional endoscopy and EUS before enrollment and judged as cSM1 or cSM2 in real time. We compared the clinical and pathological diagnoses for tumor depth and assessed the positive predictive value (PPV) for pSM (pSM/cSM) as the primary endpoint. We also investigated the clinical factors affecting the pathological depth of SM.

Results: 175 lesions were examined, and clinical diagnosis was SM1 in 114 and SM2 in 61 lesions. The pathological diagnoses of the epithelium, lamina propria mucosa, muscularis mucosae, SM1, and SM2 were 3, 31, 55, 17, and 69. The PPV for pSM was 49.1% (86/175) in all lesions, 34.2% (39/114) in cSM1 lesions, and 77.0% (47/61) in cSM2 lesions. Multivariable analysis demonstrated that cSM2 (vs. cSM1, OR 6.79) was an independent clinical factor associated with pSM.

Conclusions: While the accurate depth diagnosis in cSM ESCC was difficult to make, the clinical diagnosis of SM2 with both conventional endoscopy and EUS was significantly associated with pSM. Furthermore, diagnostic ER could be recommended to confirm the pathological diagnosis especially in cSM1 lesions with both conventional endoscopy and EUS.
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http://dx.doi.org/10.1007/s10388-021-00815-3DOI Listing
July 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

Case Report: Efficacy of Reduced Doses of Asfotase Alfa Replacement Therapy in an Infant With Hypophosphatasia Who Lacked Severe Clinical Symptoms.

Front Endocrinol (Lausanne) 2020 18;11:590455. Epub 2020 Dec 18.

Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Background: Hypophosphatasia is a rare bone disease characterized by impaired bone mineralization and low alkaline phosphatase activity. Here, we describe the course of bone-targeted enzyme replacement therapy with asfotase alpha for a female infant patient with hypophosphatasia who lacked apparent severe clinical symptoms.

Case Presentation: The patient exhibited low serum alkaline phosphatase (60 U/L; age-matched reference range, 520-1,580) in a routine laboratory test at birth. Further examinations revealed skeletal demineralization and rachitic changes, as well as elevated levels of serum calcium (2.80 mmol/L; reference range, 2.25-2.75 mmol/L) and ionic phosphate (3.17 mmol/L; reference range, 1.62-2.48 mmol/L), which are typical features in patients with hypophosphatasia. Sequencing analysis of the tissue-nonspecific alkaline phosphatase () gene identified two pathogenic mutations: c.406C>T, p.Arg136Cys and c.979T>C, p.Phe327Leu. Thus, the patient was diagnosed with hypophosphatasia. At the age of 37 days, she began enzyme replacement therapy using asfotase alpha at the standard dose of 6 mg/kg/week. Initial therapy from the age of 37 days to the age of 58 days substantially improved rickets signs in the patient; it also provided immediate normalization of serum calcium and ionic phosphate levels. However, serum ionic phosphate returned to a high level (2.72 mmol/L), which was presumed to be a side effect of asfotase alpha. Thus, the patient's asfotase alfa treatment was reduced to 2 mg/kg/week, which allowed her to maintain normal or near normal skeletal features thereafter, along with lowered serum ionic phosphate levels. Because the patient exhibited slight distal metaphyseal demineralization in the knee at the age of 2 years and 6 months, her asfotase alfa treatment was increased to 2.4 mg/kg/week. No signs of deterioration in bone mineralization were observed thereafter. At the age of 3 years, the patient's motor and psychological development both appeared normal, compared with children of similar age.

Conclusion: This is the first report in which reduced doses of asfotase alfa were administered to an infant patient with hypophosphatasia who lacked apparent severe clinical symptoms. The results demonstrate the potential feasibility of a tailored therapeutic option based on clinical severity in patients with hypophosphatasia.
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http://dx.doi.org/10.3389/fendo.2020.590455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775725PMC
June 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

A nonrandomized, single-arm confirmatory trial of expanded endoscopic submucosal dissection indication for undifferentiated early gastric cancer: Japan Clinical Oncology Group study (JCOG1009/1010).

Gastric Cancer 2021 Mar 8;24(2):479-491. Epub 2020 Nov 8.

Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Background: While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC.

Methods: The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC.

Results: Three hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1-99.8).

Conclusions: ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.
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http://dx.doi.org/10.1007/s10120-020-01134-9DOI Listing
March 2021

Clinical characteristics associated with 1-year tolvaptan efficacy in autosomal dominant polycystic kidney disease with a wide range of kidney functions.

J Med Invest 2020 ;67(3.4):315-320

Department of Nephrology, Graduate School of Biomedical Science, Tokushima University, Tokushima, Japan.

Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR). We enrolled 24 patients with eGFR 35.3 (28.0-65.5) ml / min / 1.73m2 and evaluated treatment effect as ΔΔeGFR (ml / min / 1.73m2 / year) or ΔΔtotal kidney volume (TKV) (% / year) that was calculated as post-treatment annual change - pre-treatment annual change. Pre ΔeGFR was significantly low in eGFR responders, defined as ΔΔeGFR > 0 ml / min / 1.73m2 / year. In eGFR responders, pre ΔeGFR, post ΔeGFR, eGFR, TKV, and proteinuria were significantly correlated with ΔΔeGFR. In TKV responders defined as ΔΔTKV > 5 % / year, we identified hypertension history, proteinuria, TKV, and post ΔTKV as significantly correlated factors with ΔΔTKV. In conclusion, pre ΔeGFR may be a predictive factor of therapeutic efficacy on kidney function. Tolvaptan may have greater efficacy in early-stage ADPKD with rapid GFR decline or with well-controlled blood pressure. J. Med. Invest. 67 : 315-320, August, 2020.
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http://dx.doi.org/10.2152/jmi.67.315DOI Listing
January 2020

Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer (second edition).

Dig Endosc 2021 Jan 9;33(1):4-20. Epub 2020 Dec 9.

Japan Gastroenterological Endoscopy Society, Tokyo, Japan.

In response to the rapid and wide acceptance and use of endoscopic treatments for early gastric cancer, the Japan Gastroenterological Endoscopy Society, in collaboration with the Japanese Gastric Cancer Association, produced "Guidelines for Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection for Early Gastric Cancer" in 2014, as a set of basic guidelines in accordance with the principles of evidence-based medicine. At the time, a number of statements had to be established by consensus (the lowest evidence level), as evidence levels remained low for many specific areas in this field. However, in recent years, the number of well-designed clinical studies has been increasing. Based on new findings, we have issued the revised second edition of the above guidelines that cover the present state of knowledge. These guidelines are divided into the following seven categories: indications, preoperative diagnosis, techniques, evaluation of curability, complications, long-term postoperative surveillance, and histology.
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http://dx.doi.org/10.1111/den.13883DOI 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

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

Insulin resistant diabetes mellitus in SHORT syndrome: case report and literature review.

Endocr J 2021 Jan 3;68(1):111-117. Epub 2020 Sep 3.

Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.

SHORT syndrome is a rare developmental disorder frequently associated with growth failure and insulin resistant diabetes mellitus (IRDM). Since GH has a diabetogenic effect, GH therapy has been regarded as a contraindication. We observed a Brazilian girl with SHORT syndrome who received GH therapy from 4 6/12 years of age for SGA short stature. GH dosage was increased from 0.23 to 0.36 mg/kg/week, but statural response to GH therapy remained poor. Her blood HbA1c level, though it remained 5.5-6.0% in childhood, began to elevate with puberty and increased to 9.2% at 10 6/12 years of age, despite the discontinuation of GH therapy at 9 11/12 years of age. Laboratory studies indicated antibody-negative IRDM. She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%. Whole exome sequencing revealed a de novo heterozygous pathogenic variant (c.1945C>T:p.(Arg649Trp)) in PIK3R1 known as the sole causative gene for SHORT syndrome. Subsequent literature review for patients with molecularly confirmed SHORT syndrome revealed the development of IRDM in 10 of 15 GH-untreated patients aged ≥12 years but in none of three GH-treated and six GH-untreated patients aged ≤10 years. These findings imply a critical role of pubertal development and/or advanced age rather than GH therapy in the development of IRDM, and a usefulness of SGLT2 inhibitor in the treatment of IRDM.
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http://dx.doi.org/10.1507/endocrj.EJ20-0291DOI Listing
January 2021
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