Publications by authors named "Masanori Inoue"

71 Publications

Leucyl-tRNA synthetase deficiency systemically induces excessive autophagy in zebrafish.

Sci Rep 2021 Apr 16;11(1):8392. Epub 2021 Apr 16.

Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan.

Leucyl-tRNA synthetase (LARS) is an enzyme that catalyses the ligation of leucine with leucine tRNA. LARS is also essential to sensitize the intracellular leucine concentration to the mammalian target of rapamycin complex 1 (mTORC1) activation. Biallelic mutation in the LARS gene causes infantile liver failure syndrome type 1 (ILFS1), which is characterized by acute liver failure, anaemia, and neurological disorders, including microcephaly and seizures. However, the molecular mechanism underlying ILFS1 under LARS deficiency has been elusive. Here, we generated Lars deficient (larsb) zebrafish that showed progressive liver failure and anaemia, resulting in early lethality within 12 days post fertilization. The atg5-morpholino knockdown and bafilomycin treatment partially improved the size of the liver and survival rate in larsb zebrafish. These findings indicate the involvement of autophagy in the pathogenesis of larsb zebrafish. Indeed, excessive autophagy activation was observed in larsb zebrafish. Therefore, our data clarify a mechanistic link between LARS and autophagy in vivo. Furthermore, autophagy regulation by LARS could lead to development of new therapeutics for IFLS1.
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http://dx.doi.org/10.1038/s41598-021-87879-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052342PMC
April 2021

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model.

PLoS One 2021 22;16(3):e0248352. Epub 2021 Mar 22.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Hepatocellular carcinoma (HCC) is the fifth most common primary tumor and the third leading cause of cancer-related deaths worldwide. Rodent models of HCC have contributed to the advancement of studies investigating liver carcinogenesis, tumor-host interactions, and drug screening. However, their small size renders them unsuitable for surgical or clinical imaging studies, necessitating the development of larger-size HCC models. Here, we developed a xenograft model of human HCC in X-linked interleukin-2 receptor gamma chain gene (Il2rg)-targeted severe combined immunodeficient (SCID) pigs. HepG2 cell suspension in serum-free medium containing 50% membrane matrix was directly injected into the liver parenchyma of eight X-linked Il2rg-targeted SCID pigs (6.6-15.6 kg) via ultrasonography-guided percutaneous puncture. Tumor engraftment was evaluated weekly using ultrasonography, and cone-beam computed tomography was performed during arterial portography (CTAP) and hepatic arteriography (CTHA) to evaluate the hemodynamics of engrafted tumors. The engrafted tumors were histologically analyzed following necropsy and assessed for pathological similarities to human HCCs. Macroscopic tumor formation was observed in seven of the eight pigs (simple nodular tumors in three and multinodular tumors in four). Engrafted tumors were identified as low-echoic upon ultrasonography and as perfusion-defect nodules on the CTAP images. Meanwhile, CTHA showed that the tumors were hyperattenuating. Further, histopathological findings of the engrafted tumors were consistent with those of human HCC. In conclusion, the porcine model of human HCC, successfully generated herein, might help develop more effective therapeutic strategies for HCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248352PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984615PMC
March 2021

Vessel Occlusion using Hydrogel-Coated versus Nonhydrogel Embolization Coils in Peripheral Arterial Applications: A Prospective, Multicenter, Randomized Trial.

J Vasc Interv Radiol 2021 04 4;32(4):602-609.e1. Epub 2021 Mar 4.

Department of Radiology, Oita University Faculty of Medicine, Oita, Japan.

Purpose: To evaluate the safety and effectiveness of hydrogel-coated coils for vessel occlusion in the body trunk.

Materials And Methods: A total of 77 patients with various peripheral vascular lesions, treatable by embolization with coils, were randomized (hydrogel group, n = 38; nonhydrogel group, n = 39). In the hydrogel group, embolization of the target vessel was conducted using 0.018-inch hydrogel-coated coils (AZUR 18; Terumo Medical Corporation, Tokyo, Japan) with or without bare platinum coils. The nonhydrogel group received both bare platinum coils and fibered coils without the use of hydrogel-coated coils.

Results: Complete target vessel occlusion was accomplished in 36 patients in the hydrogel group and 37 patients in the nonhydrogel group. No major adverse events were observed in either group. The median number of coils/vessel diameter and the median total coil length/vessel diameter were significantly larger in the nonhydrogel group than in the hydrogel group (P = .005 and P = .004, respectively). The median embolization length was significantly longer in the nonhydrogel group (31.95 mm) than in the hydrogel group (23.43 mm) (P = .002). If no expansion was assumed, the median packing density in the hydrogel group was 44.9%, which was similar to that in the nonhydrogel group (46.5%) (P = .79). With full expansion assumed, the median packing density in the hydrogel group was 125.7%.

Conclusions: Hydrogel-coated coils can be safely used for peripheral vascular coil embolization, and hydrogel-coated and conventional coils in combination allow for a shorter embolization segment and shorter coil length.
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http://dx.doi.org/10.1016/j.jvir.2020.12.001DOI Listing
April 2021

Treatment effect prediction using CT after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

Eur Radiol 2021 Feb 10. Epub 2021 Feb 10.

Department of Radiology, Keio University School of Medicine, 35, Shinanomachi, Shinjyuku-ku, Tokyo, 160-8582, Japan.

Objective: To evaluate whether the change in computed tomography pulmonary angiography (CTPA) metrics after balloon pulmonary angioplasty (BPA) can predict treatment effect in chronic thromboembolic pulmonary hypertension (CTEPH) patients.

Methods: This study included 82 CTEPH patients who underwent both CTPA and right heart catheterization (RHC) before and at the scheduled time of 6 months after BPA. The diameters of the main pulmonary artery (dPA), ascending aorta (dAA), right atrium (dRA), right ventricular free wall thickness (dRVW), and right and left ventricles (dRV, dLV) were measured on CTPA. The correlation of the New York Heart Association functional class (NYHA FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) level, and calculated CT metrics with a decrease in mean pulmonary artery pressure (ΔmPAP) using RHC (used as the reference for BPA effect) was investigated. Using multiple regression analysis, independent variables were also identified.

Results: In univariate analysis, clinical indicators (NYHA FC, 6MWD, and BNP level) improved significantly after BPA and were significantly correlated with ΔmPAP (p < 0.01). In the univariate analysis of CTPA parameters, dPA, dRA, dPA/dAA ratio, dRVW, and dRV/dLV ratio decreased significantly and were significantly correlated with ΔmPAP (p < 0.01). Multivariate analysis demonstrated that decreased dPA (p = 0.001) and decreased dRA (p = 0.039) on CTPA were independent predictive factors of ΔmPAP.

Conclusions: Decreased dPA and dRA on CTPA could predict a decrease in mPAP after BPA, thus potentially eliminating unnecessary invasive catheterization.

Key Points: • The reduction in mean pulmonary artery pressure after balloon pulmonary angioplasty in CTEPH patients was significantly correlated with the clinical indices improvement and CTPA parameter decrease. • The decreased diameter of the main pulmonary artery and the decreased diameter of the right atrium on CTPA were independent predictors of mean pulmonary artery pressure reduction.
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http://dx.doi.org/10.1007/s00330-021-07711-5DOI Listing
February 2021

Propofol midazolam for sedation during radiofrequency ablation in patients with hepatocellular carcinoma.

JGH Open 2021 Feb 22;5(2):273-279. Epub 2020 Dec 22.

Departmetn of Anesthesiology, Graduate School of Medicine Chiba University Chiba Japan.

Background And Aim: Standardization of the sedation protocol during radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) is needed. This randomized, single-blind, investigator-initiated trial compared clinical outcomes during and after RFA using propofol and midazolam, respectively, in patients with HCC.

Methods: Few- and small-nodule HCC patients (≤3 nodules and ≤3 cm) were randomly assigned to either propofol or midazolam. Patient satisfaction was assessed using a 100-mm visual analog scale (VAS) (1 mm = not at all satisfied, 100 mm = completely satisfied). Sedation recovery rates 1, 2, 3, and 4 h after RFA were evaluated based on Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores; full recovery was defined as a MOAA/S score of 5.

Results: Between July 2013 and September 2017, 143 patients with HCC were enrolled, and 135 patients were randomly assigned to the treatment group. Compared with midazolam, propofol exhibited similar median procedural satisfaction (propofol: 73.1 mm, midazolam: 76.9 mm, = 0.574). Recovery rates 1 and 2 h after RFA were higher in the propofol group than in the midazolam group. Meanwhile, recovery rates observed 3 and 4 h after RFA were similar in the two groups. The safety profiles during and after RFA were almost identical in the two groups.

Conclusion: Patient satisfaction was almost identical in patients receiving propofol and midazolam sedation during RFA. Propofol sedation resulted in reduced recovery time compared with midazolam sedation in patients with HCC. The safety profiles of both propofol and midazolam sedation during and after RFA were acceptable.
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http://dx.doi.org/10.1002/jgh3.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857294PMC
February 2021

Successful Percutaneous Abscess Drainage and Irrigation for the Treatment of Infected Aortic Aneurysm Post-Thoracic Endovascular Aortic Repair.

CJC Open 2020 Nov 31;2(6):735-738. Epub 2020 Aug 31.

Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.

Infected aortic aneurysm (IAA) is a rare, life-threatening disease with rapid progression and a high mortality rate. An 84-year-old man developed IAA caused by urosepsis owing to extended-spectrum β-lactamase-producing infection. Considering surgical risk and perioperative mortality, the patient underwent computed tomography-guided percutaneous abscess drainage and continuous irrigation with optimal antibiotic therapy. We controlled his systemic inflammation without surgery; thus, he was discharged. Six months later, we confirmed that the abscess had almost disappeared in the follow-up computed tomography scan. Percutaneous abscess drainage and irrigation may be an effective therapeutic option for surgical high-risk patients with IAA.
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http://dx.doi.org/10.1016/j.cjco.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711014PMC
November 2020

Arteriovenous malformation on the sole of the foot treated successfully by embolization.

Radiol Case Rep 2020 Dec 12;15(12):2621-2626. Epub 2020 Oct 12.

Department of Diagnostic Radiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Arteriovenous malformations of the sole of the foot are rare and can cause disturbances in normal living activities. We report a case of a plantar arteriovenous malformation in a 24-year-old male with pain and difficulty in walking. The arteriovenous malformation was complex, with a large and poorly marginated nidus, so we considered that with surgical resection, walking disabilities would be inevitable. When surgical removal of vascular mass is difficult, embolization alone can be effective. Therefore, he was treated with 4 therapeutic embolization procedures. Transvenous approaches to the venous sac and direct punctures of the nidus was performed. The nidus was successfully eradicated by embolization using alcohol, resulting in the disappearance of associated symptoms. Appropriate imaging is essential for diagnosis and evaluation of treatment. We were successful in achieving improved quality of life and satisfaction for a rare and difficult case by percutaneous embolization and sclerotherapy.
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http://dx.doi.org/10.1016/j.radcr.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566210PMC
December 2020

Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials.

Liver Cancer 2020 Sep 22;9(5):596-612. Epub 2020 Jul 22.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden.

Aims: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs.

Methods: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC.

Results: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC.

Conclusions: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.
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http://dx.doi.org/10.1159/000508809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548915PMC
September 2020

Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma.

Liver Cancer 2020 Aug 5;9(4):382-396. Epub 2020 May 5.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: The present study aimed to assess the efficacy and safety of lenvatinib and verify the possibility of lenvatinib for the expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma (HCC) in real-world practice, primarily focusing on the population that was excluded in the REFLECT trial.

Methods: We retrospectively collected data on patients with advanced HCC who were administered lenvatinib in 7 institutions in Japan.

Results: Of 152 advanced HCC patients, 95 and 57 patients received lenvatinib in first-line and second- or later-line systemic therapies, respectively. The median progression-free survival in Child-Pugh class A patients was nearly equal between first- and second- or later-line therapies (5.2 months; 95% CI 3.7-6.9 for first line, 4.8 months; 95% CI 3.8-5.9 for second or later line, = 0.933). According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate of 27 patients (18%) who showed a high burden of intrahepatic lesions (i.e., main portal vein and/or bile duct invasion or 50% or higher liver occupation) at baseline radiological assessment was 41% and similar with that of other population. The present study included 20 patients (13%) with Child-Pugh class B. These patients observed high frequency rates of liver function-related adverse events due to lenvatinib. The 8-week dose intensity of lenvatinib had a strong correlation with liver function according to both the Child-Pugh and albumin - bilirubin scores.

Conclusion: Lenvatinib had potential benefits for patients with advanced HCC with second- or later-line therapies and a high burden of intrahepatic lesions. Dose modification should be paid increased attention among patients with poor liver function, such as Child-Pugh class B patients.
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http://dx.doi.org/10.1159/000507022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506220PMC
August 2020

Intrahepatic lymphatic channel sclerotic embolization for treatment of postoperative lymphatic ascites: a report of 3 cases.

Radiol Case Rep 2020 Nov 15;15(11):2353-2357. Epub 2020 Sep 15.

Respiratory Medicine, Hanoi French Hospital, Hanoi, Vietnam.

Postoperative hepatic lymphorrhea is extremely rare and there is no standard treatment for this condition. We report the cases of 3 men, 32-, 56-, and 37-year-old, with postoperative hepatic lymphorrhea, which was refractory to conservative treatment. Transhepatic lymphangiography allowed locating the lymphatic leak and treating it with hepatic lymphatic vessels injection of foam sclerotic agent. This technique seems efficient and safe.
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http://dx.doi.org/10.1016/j.radcr.2020.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501473PMC
November 2020

Fibro-adipose vascular anomaly (FAVA): three case reports with an emphasis on the mammalian target of rapamycin (mTOR) pathway.

Diagn Pathol 2020 Jul 25;15(1):98. Epub 2020 Jul 25.

Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.

Background: Fibro-adipose vascular anomaly (FAVA) is a new entity of vascular anomalies with somatic and mosaic gain-of-function mutations of the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). PIK3CA mutation excessively activates mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis. Histologically, FAVA is composed of intramuscular fibrous and adipose tissues with venous malformation (VM). Although sirolimus known as a mTOR inhibitor has good response to FAVA, expression pattern of the mTOR pathway was still unclear. Herein, we immunohistochemically investigated three novel FAVA patients with an emphasis on the mTOR pathway (p-S6K1, p-4EBP1 and p-AKT).

Case Presentation: Case 1: A 10-year-old female had complained of pain in the left thigh since she was 6-year-old. Under the clinical diagnosis of VM, she underwent surgical resection for the lesion. Case 2: A 29-year-old female patient had complained of discomfort and mild pain in the left shoulder since she was 18-year-old. After childbirth, she had severe ongoing pain and contracture of the shoulder. Under clinical diagnosis of VM, surgical resection was performed. Case 3: A 53-year-old female had complained of pain and knee restriction after surgical treatment of a knee tumor at the age of 31. Under the clinical diagnosis of atypical lipomatous tumor or high grade liposarcoma, surgical resection was performed. Histologically, all three patients presented with characteristic features of fibrous and adipose tissues with abnormal vessels within the skeletal muscle, leading to diagnosis of FAVA. Although VM has been reported as an important finding in FAVA, immunohistological findings demonstrated that abnormal vessels comprised complex of VM and lymphatic malformation (LM) in all cases. Furthermore, besides vascular malformation, abnormal fibrous and adipose tissues of FAVA expressed mTOR pathway components.

Conclusions: We presented three new cases of FAVA. Histological and immunohistochemical analyses revealed that VM and LM complex was an important finding in FAVA, and that the mTOR pathway components were expressed in abnormal fibrous tissue, adipose tissue and vascular malformation. These findings suggested that FAVA might be a mesenchymal malformation caused by PI3K/AKT/mTOR pathway.
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http://dx.doi.org/10.1186/s13000-020-01004-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382067PMC
July 2020

Chylothorax treated with targeted sclerotherapy by direct puncture of the lymphatic leakage site.

Radiol Case Rep 2020 Aug 29;15(8):1398-1402. Epub 2020 Jun 29.

Department of Radiology, Tokyo Metropolitan Bokutoh Hospital, 4-23-15 Kotobashi, Sumida-ku, Tokyo 130-8575, Japan.

We report a novel application of targeted sclerotherapy to eradicate high-output chylothorax. The patient underwent thoracic duct embolization; however, cannulation of the thoracic duct failed, and thoracic duct disruption was performed. Leakage continued; therefore, the leakage site in the mediastinum was punctured directly under fluoroscopic guidance and a drainage catheter was inserted, followed by sclerotherapy using OK-432. Finally, leakage stopped and chylothorax improved. This technique may be useful for refractory chylothorax in patients where thoracic duct embolization fails.
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http://dx.doi.org/10.1016/j.radcr.2020.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329934PMC
August 2020

Japanese clinical practice guidelines for vascular anomalies 2017.

Jpn J Radiol 2020 Apr;38(4):287-342

Division of Radiology, National Center for Child Health and Development, Tokyo, Japan.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.
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http://dx.doi.org/10.1007/s11604-019-00885-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150662PMC
April 2020

Japanese clinical practice guidelines for vascular anomalies 2017.

Pediatr Int 2020 Mar 22;62(3):257-304. Epub 2020 Mar 22.

Division of Radiology, National Center for Child Health and Development, Tokyo, Japan.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.
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http://dx.doi.org/10.1111/ped.14077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232443PMC
March 2020

Japanese Clinical Practice Guidelines for Vascular Anomalies 2017.

J Dermatol 2020 May 22;47(5):e138-e183. Epub 2020 Mar 22.

Division of Radiology, National Center for Child Health and Development, Tokyo, Japan.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety and systematizing treatment, employing evidence-based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQ) were decided based on the important clinical issues. For document retrieval, key words for published work searches were set for each CQ, and work published from 1980 to the end of September 2014 was searched in PubMed, Cochrane Library and Japana Centra Revuo Medicina databases. The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System technique. A total of 33 CQ were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.
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http://dx.doi.org/10.1111/1346-8138.15189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317503PMC
May 2020

Tyrosine pre-transfer RNA fragments are linked to p53-dependent neuronal cell death via PKM2.

Biochem Biophys Res Commun 2020 05 4;525(3):726-732. Epub 2020 Mar 4.

Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan. Electronic address:

Fragments of transfer RNA (tRNA), derived either from pre-tRNA or mature tRNA, have been discovered to play an essential role in the pathogenesis of various disorders such as neurodegenerative disease. CLP1 is an RNA kinase involved in tRNA biogenesis, and mutations in its encoding gene are responsible for pontocerebellar hypoplasia type-10. Mutation of the CLP1 gene results in the accumulation of tRNA fragments of several different kinds. These tRNA fragments are expected to be associated with the disease pathogenesis. However, it is still unclear which of the tRNA fragments arising from the CLP1 gene mutation has the greatest impact on the onset of neuronal disease. We found that 5' tRNA fragments derived from tyrosine pre-tRNA (5' Tyr-tRF) caused p53-dependent neuronal cell death predominantly more than other types of tRNA fragment. We also showed that 5' Tyr-tRF bound directly to pyruvate kinase M2 (PKM2). Injection of zebrafish embryos with PKM2 mRNA ameliorated the neuronal defects induced in zebrafish embryos by 5' Tyr-tRF. Our findings partially uncovered a mechanistic link between 5' Tyr-tRF and neuronal cell death that is regulated by PKM2.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.157DOI Listing
May 2020

The autophagy reaction in the human umbilical cord: a potential marker for estimating fetal nutrition and neonatal growth.

J Matern Fetal Neonatal Med 2020 Mar 3:1-5. Epub 2020 Mar 3.

Department of Pediatrics, Faculty of Medicine, Oita University Oita, Japan.

To assess the induction of autophagy in the human umbilical cord for physiological adaptation against starvation. The expression of autophagy-related proteins (LC3-II, p62) in umbilical cord tissues from 40 neonates was assessed by Western blotting. The correlation between the expression of autophagy-related proteins and maternal findings (height, weight, body mass index [BMI]), placental weight, neonatal findings (gestational age, height, weight, Apgar score at 1 min and 5 min), and the pH of the umbilical arterial blood were analyzed using Spearman's rank correlation coefficient test ( values of <.05 were considered significant). Venous blood findings (pH, pCO, glucose, total protein, albumin, and lactic acid) were also evaluated in 16 neonates admitted to the NICU. The expression of LC3-II was positively correlated with serum total protein ( = 0.564,  = .023). The p62 level was also correlated with maternal BMI ( = 0.376,  = .017), the neonatal Apgar score at 1 min ( = 0.331  = .037), total protein ( = 0.588,  = .017), and albumin ( = 0.552,  = .027) positively. A multiple linear regression analysis that included clinical parameters related to fetal nutrition and neonatal growth revealed that serum total protein was significantly associated with both LC3-II ( = .024) and p62 ( = .034) in the umbilical cord. The LC3-II or p62 expression in the umbilical cord may suggest the autophagy reaction for the homeostasis of protein or amino acid metabolism in the perinatal period.
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http://dx.doi.org/10.1080/14767058.2020.1730320DOI Listing
March 2020

CLP1 acts as the main RNA kinase in mice.

Biochem Biophys Res Commun 2020 Feb 17. Epub 2020 Feb 17.

Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan. Electronic address:

CLP1 plays an essential role in the protein complex involved in mRNA 3'-end formation and polyadenylation as well as in the tRNA splicing endonuclease (TSEN) complex involved in the splicing of precursor tRNAs. NOL9 localizes in the nucleolus of cells and plays an essential role in ribosomal RNA maturation. Both CLP1 and NOL9 are RNA kinases that phosphorylate the 5' end of RNAs. From the evidence that phosphorylation of the 5' end of a siRNA is essential for its efficient RNA cleavage, it was expected that CLP1 and NOL9 would be corresponding molecules. However, there had been no direct evidence that this is the case. In this study, murine NOL9 showed no apparent RNA kinase activity in cells or even in an RNA kinase assay using recombinant murine NOL9 protein. Although siRNA efficiency was decreased in CLP1 kinase-dead (Clp1) cells, it was not influenced by NOL9 overexpression. These findings indicate that in mouse cells it is CLP1 that mainly acts to phosphorylate the 5' end of RNAs in the siRNA pathway, with no apparent involvement of NOL9.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.066DOI Listing
February 2020

Interstitial Lymphatic Embolization with Balloon Assistance for Treatment of Chyluria.

J Vasc Interv Radiol 2020 03 29;31(3):523-526. Epub 2020 Jan 29.

Department of Respiratory Medicine, Hanoi French Hospital, 1 Phuong Mai St., Dong Da District, 10000 Hanoi, Vietnam.

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http://dx.doi.org/10.1016/j.jvir.2019.09.025DOI Listing
March 2020

Correction to: Current management strategies for visceral artery aneurysms: an overview.

Surg Today 2020 Mar;50(3):320

Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

The article Current management strategies for visceral artery aneurysms.
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http://dx.doi.org/10.1007/s00595-019-01947-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033054PMC
March 2020

Successful treatment of hepatic lymphorrhea by percutaneous transhepatic lymphangiography followed by sclerotherapy using OK-432.

Surg Case Rep 2019 Dec 23;5(1):203. Epub 2019 Dec 23.

Department of Surgery, Hiratsuka City Hospital, 1-19-1 Minamihara, Hiratsuka, Kanagawa, 254-0065, Japan.

Background: Conventional lymphangiography cannot detect leakage sites of hepatic lymphatic vessels. Percutaneous transhepatic lymphangiography can be used to visualize leakage sites, and once the leakage site has been confirmed, effective sclerotherapy can be performed.

Case Presentation: A rare case of intractable hepatic lymphorrhea due to injury of the hepatoduodenal ligament following pancreaticoduodenectomy is reported. Drainage of massive ascites from the drainage tube continued after surgery. Percutaneous transhepatic lymphangiography visualized the intrahepatic lymphatic vessels and the leakage site at the hepatic hilum. An 8-Fr drainage catheter was inserted adjacent to the leakage point under fluoroscopic computed tomography guidance. Repeated sclerotherapy using intraperitoneal administration of OK-432 (picibanil) through the catheter was performed, which exposed the leakage site, and control of the ascites was finally achieved.

Conclusions: To the best of our knowledge, this is the first successful case of detection of a leakage site using intrahepatic lymphangiography, followed by sclerotherapy using OK-432.
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http://dx.doi.org/10.1186/s40792-019-0761-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928181PMC
December 2019

Current management strategies for visceral artery aneurysms: an overview.

Surg Today 2020 Jan 16;50(1):38-49. Epub 2019 Oct 16.

Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Visceral artery aneurysms (VAAs) are rare and affect the celiac artery, superior mesenteric artery, and inferior mesenteric artery, and their branches. The natural history of VAAs is not well understood as they are often asymptomatic and found incidentally; however, they carry a risk of rupture that can result in death from hemorrhage in the peritoneal cavity, retroperitoneal space, or gastrointestinal tract. Recent advances in imaging technology and its availability allow us to diagnose all types of VAA. VAAs can be treated by open surgery, laparoscopic surgery, endovascular therapy, or a hybrid approach. However, there are still no specific indications for the treatment of VAAs, and the best strategy depends on the anatomical location of the aneurysm as well as the clinical presentation of the patient. This article reviews the literature on the etiology, clinical features, diagnosis, and anatomic characteristics of each type of VAA and discusses the current options for their treatment and management.
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http://dx.doi.org/10.1007/s00595-019-01898-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949316PMC
January 2020

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Invest New Drugs 2020 02 6;38(1):172-180. Epub 2019 Jun 6.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.
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http://dx.doi.org/10.1007/s10637-019-00801-8DOI Listing
February 2020

Intravascular Ultrasound-Guided Percutaneous Portal Vein Recanalization for Chronic Portal Vein Obstruction.

J Vasc Interv Radiol 2019 Oct 22;30(10):1628-1631.e1. Epub 2019 Apr 22.

Department of Radiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173 8606, Japan.

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http://dx.doi.org/10.1016/j.jvir.2018.12.009DOI Listing
October 2019

Transarterial chemoembolization as a substitute to radiofrequency ablation for treating Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma.

Oncotarget 2018 Apr 20;9(30):21560-21568. Epub 2018 Apr 20.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background And Aim: Transarterial chemoembolization (TACE) is the standard procedure for treating Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC). However, it is often carried out in the treatment of BCLC stage 0/A HCC for various reasons. This study aimed to elucidate the prognosis for BCLC stage 0/A HCC patients treated with TACE or with radiofrequency ablation (RFA).

Materials And Methods: The prognosis of 242 BCLC stage 0/A HCC patients within Milan criteria who underwent initially TACE or RFA were retrospectively analyzed using propensity score matching analysis.

Results: The analyses of baseline patient characteristics revealed that the maximum tumor size and the proportion of BCLC stage A patients were significantly higher in patients treated with TACE than in those treated with RFA (<0.001 and 0.047, respectively). After adjusting these factors using propensity score matching (1:3 matching), patients treated with TACE (n=32) and those treated with RFA (n=96) were further analyzed. The local recurrence rate was significantly higher in the TACE group than in the RFA group (<0.001). However, the overall survival (OS) in HCC patients treated with TACE was comparable to that in HCC patients treated with RFA (1 year, 93.5 vs. 95.8%; 3 years, 75.4 vs. 85.8%; 5 years, 61.8 vs. 70.7%; =0.196). Multivariate analyses followed by univariate analyses revealed that serum bilirubin level (=0.032), serum albumin level (=0.008), HBV-DNA (=0.013), and tumor number (=0.021) were independent predictors of OS.

Conclusion: TACE can substitute RFA at least in some patients with BCLC 0/A HCC.
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http://dx.doi.org/10.18632/oncotarget.25108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940395PMC
April 2018

Retroperitoneal hematoma volume is a good predictor of perioperative mortality after endovascular aneurysm repair for ruptured abdominal aortic aneurysm.

J Vasc Surg 2018 10;68(4):998-1006.e2

Department of Surgery, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan.

Objective: The objective of this study was to validate the usefulness of retroperitoneal hematoma volume as a predictor of perioperative mortality after endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA).

Methods: We retrospectively reviewed consecutive patients with rAAA who underwent the unified EVAR first protocol between 2012 and 2016 at any one of three participating institutions in Japan and were prospectively registered in a dedicated database. Only patients with preoperative computed tomography scans adequate for three-dimensional volumetric analysis were included. Volumetry was used to measure the retroperitoneal hematoma volume. To adjust for body size differences between patients, the retroperitoneal hematoma volume was divided by the abdominal cavity volume, and the predictive power of this ratio was validated using appropriate statistical methods.

Results: Of 114 patients with rAAA managed during the study period, 101 (88.6%) underwent EVAR, 9 (7.9%) underwent open surgical repair, and 4 (3.5%) did not undergo any repair. Finally, 82 of 101 patients treated with EVAR were included in the analysis. Within 30 days after EVAR, the mortality rates for the 82 patients included in the analysis and the 19 excluded patients were 24.4% and 31.6%, respectively, without statistically significant differences (P = .518). The retroperitoneal hematoma volume ratio was 3.59% ± 2.46% and 7.63% ± 3.45% in survivors and nonsurvivors, respectively (P < .001). Univariate analysis of other preoperative demographic and anatomic factors revealed that a Glasgow Aneurysm Score >85, systolic blood pressure <90 mm Hg, loss of consciousness, and mean minimum right external iliac artery diameter were statistically significant. Receiver operating characteristic curve analysis for the prediction of perioperative mortality revealed that retroperitoneal hematoma volume ratio was the best predictor of perioperative mortality in patients with rAAA of type >III in the Fitzgerald classification (area under the curve: retroperitoneal hematoma volume ratio, 0.880; Glasgow Aneurysm Score, 0.587; P < .001). Based on the Youden index, the optimal cutoff for the retroperitoneal hematoma volume ratio was 6.97%, providing a sensitivity of 0.833 and specificity of 0.860.

Conclusions: Our study suggests that retroperitoneal hematoma volume may be a good predictor of perioperative mortality after EVAR for rAAA, especially for patients with Fitzgerald classification >III and a best cutoff value of 6.97%.
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http://dx.doi.org/10.1016/j.jvs.2018.01.048DOI Listing
October 2018

Henoch-Schönlein Purpura Complicated by Hepatocellular Carcinoma.

Intern Med 2017 Nov 25;56(22):3041-3045. Epub 2017 Sep 25.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Japan.

Although Henoch-Schönlein purpura (HSP) is known to be accompanied by malignancies, cases with hepatobiliary cancer are extremely rare. A 62-year-old man with palpable purpura rapidly extending to both lower legs was admitted to our hospital. He was undergoing follow-up for cirrhosis caused by chronic hepatitis B virus infection and hepatocellular carcinoma (HCC). He had renal dysfunction with hematuria and proteinuria and abdominal pain. Based on the clinical presentation and skin biopsy findings, he was diagnosed with HSP. The administration of steroids resulted in the rapid improvement of the patient's symptoms and he was discharged 12 days after admission.
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http://dx.doi.org/10.2169/internalmedicine.8885-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725858PMC
November 2017

Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment.

Invest New Drugs 2018 04 11;36(2):332-339. Epub 2017 Sep 11.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child-Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child-Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand-foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child-Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child-Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.
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http://dx.doi.org/10.1007/s10637-017-0507-3DOI Listing
April 2018