Publications by authors named "Masanori Sato"

115 Publications

Reduced impact of viral load of HHV-6 in liquor on severity of AESD due to exanthema subitum: A case report and literature review.

Brain Dev 2021 May 7. Epub 2021 May 7.

Department of Neurology, Nagano Children's Hospital, Azumino, Japan. Electronic address:

Background: The most common causative pathogen of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was reported as HHV-6. Although excitotoxic injury with delayed neuronal death is considered to be a possible pathogenesis of AESD, the detailed pathophysiology remains unclear.

Case Presentation: We present a twelve-month-old girl with AESD due to HHV-6 primary infection. She was successfully treated for AESD including targeted temperature management and the administration of vitamin B1, B6, and L-carnitine. Although the viral load of HHV-6 in her liquor was high (12,000 copies/mL), she fully recovered without antiviral agent use.

Discussion: There has been no study focusing on the HHV-6 viral load in patients with AESD, and only a few case reports have been published. We reviewed the clinical features and viral load in the liquor of our case and four reported infants with AESD due to HHV-6 primary infection who had real-time PCR tests results. Viral loads in the three patients with a poor prognosis were 31.5, negative, and 3,390 copies/mL, respectively. On the other hand, the copy numbers of HHV-6 DNA in the two patients with no sequelae were 12,000 and 106 copies/mL, respectively, and our case had the highest viral load among the five summarized patients.
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http://dx.doi.org/10.1016/j.braindev.2021.04.008DOI Listing
May 2021

MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model.

Sci Rep 2021 Feb 11;11(1):3599. Epub 2021 Feb 11.

Department of Medical Oncology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.

Non-alcoholic steatohepatitis (NASH)-related HCC is associated with oxidative stress. However, the mechanisms underlying the development of NASH-related HCC is unclear. MUTYH is one of the enzymes that is involved in repair of oxidative DNA damage. The aim of this study was to investigate the association between MUTYH and NASH-related hepatocarcinogenesis. MUTYH wild-type (Mutyh), heterozygous (Mutyh), and MUTYH-null (Mutyh) mice were fed a high-fat high-cholesterol (HFHC) diet or HFHC + high iron diet (20 mice per group) for 9 months. Five of 20 Mutyh mice fed an HFHC + high iron diet developed liver tumors, and they developed more liver tumors than other groups (especially vs. Mutyh fed an HFHC diet, P = 0.0168). Immunohistochemical analysis revealed significantly higher accumulation of oxidative stress markers in mice fed an HFHC + high iron diet. The gene expression profiles in the non-tumorous hepatic tissues were compared between wild-type mice that developed no liver tumors and MUTYH-null mice that developed liver tumors. Gene Set Enrichment Analysis identified the involvement of the Wnt/β-catenin signaling pathway and increased expression of c-Myc in MUTYH-null liver. These findings suggest that MUTYH deficiency is associated with hepatocarcinogenesis in patients with NASH with hepatic iron accumulation.
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http://dx.doi.org/10.1038/s41598-021-83138-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878918PMC
February 2021

Epitokous metamorphosis, reproductive swimming, and early development of the estuarine polychaete, Southern, 1921 (Annelida, Nereididae) on the east coast of the Malay Peninsula.

Zookeys 2021 18;1011:1-24. Epub 2021 Jan 18.

Research Field in Science, Science and Engineering Area, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan.

The reproductive and developmental characteristics of the nereidid polychaete, Southern, 1921, commonly recorded in tropical estuaries in the Indo-West Pacific, were examined from Malaysia (the mangrove area of Kuala Ibai, Terengganu) and Thailand (the Lower Songkhla Lagoon) on the east coast of the Malay Peninsula. Epitokous metamorphosis of fully mature males and females and their reproductive swimming behaviour were recorded based on ten Malaysian epitokous specimens, which were collected at night during spring tides in a period of January 2018 to March 2019. Six Thailand epitokes were obtained in February and March 2006 by the laboratory rearing of immature worms. Epitokous metamorphosis is characterised by the enlargement of eyes in both sexes, division of the body into three parts and modification of parapodia with additional lobes in the mid-body of males, and replacement of atokous chaetae in the mid-body by epitokous natatory chaetae, completely in males and incompletely in females. The diameter of coelomic unfertilised eggs in females was 100-140 µm. After fertilisation, each egg formed a jelly layer, inside which embryonic development progressed. Trochophores hatched out of the jelly layer, entering a short free-swimming larval phase followed by demersal life at the early stage of 3-chaetiger nectochaeta one day after fertilisation. Then, the larvae entered benthic life as juveniles, crawling on the bottom, at the late stage of 3-chaetiger nectochaeta two days after fertilisation. The results indicate that has an annual life cycle, which is usually completed within an estuary with limited larval dispersal ability.
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http://dx.doi.org/10.3897/zookeys.1011.59780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835201PMC
January 2021

Discovery of benzo[f]pyrido[4,3-b][1,4]oxazepin-10-one derivatives as orally available bromodomain and extra-terminal domain (BET) inhibitors with efficacy in an in vivo psoriatic animal model.

Bioorg Med Chem 2021 Mar 25;34:116015. Epub 2021 Jan 25.

Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. Electronic address:

Bromodomain and extra-terminal domain (BET) protein plays an important role in epigenetic regulation, and the regulation of disruption contributes to the pathogenesis of cancer and inflammatory disease. With the goal of discovering novel BET inhibitors, especially BRD4 inhibitors, we designed and synthesized several compounds starting from our previously reported pyrido-benzodiazepinone derivative 4 to enhance BRD4 inhibitory activity while avoiding hERG inhibition. Molecular docking studies and structure-activity relationship studies led to the identification of 9-fluorobenzo[f]pyrido[4,3-b][1,4]oxazepin-10-one derivative 43, which exhibited potent BRD4 inhibitory activity with excellent potency in imiquimod-induced psoriasis model mice.
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http://dx.doi.org/10.1016/j.bmc.2021.116015DOI Listing
March 2021

Survival benefit of conversion surgery after intensive chemotherapy for unresectable metastatic gastric cancer: a propensity score-matching analysis.

J Cancer Res Clin Oncol 2021 Aug 3;147(8):2385-2396. Epub 2021 Feb 3.

Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan.

Purpose: The clinical benefit of conversion surgery (CS) for unresectable gastric cancer (GC), whereby unresectable GC responds to chemotherapy and subsequently receives curative-intent surgery, remains unclear. Here, we aimed to clarify the clinical value of CS.

Methods: In this retrospective cohort study, we analyzed 175 unresectable GC, who received triple combined chemotherapy between 2004 and 2019. We divided patients into two groups: those who underwent CS and those receiving chemotherapy only (CS and C groups, respectively). Propensity score matching was used to minimize confounding bias.

Results: Of 175 cases, 61 (34.9%) underwent CS. R0 resection was obtained in 85.2%. After matching, 44 pairs were selected; there were no significant differences in baseline covariants. Group CS had a significantly better median overall survival (OS) (18.8 vs. 46.0 months, p < 0.001), and prolonged progression-free survival (7.4 vs. 25.8 months, p < 0.001). Subgroup analysis of OS showed a favorable trend for CS for almost all subgroups. Multivariate analysis revealed that good ECOG performance status and CS were associated with a longer OS.

Conclusion: The survival benefit of CS was consistently demonstrated in the univariate and multivariate analysis, even in the matched cohort. Additional large-scale trials are needed for further validation.
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http://dx.doi.org/10.1007/s00432-021-03516-7DOI Listing
August 2021

Case series of three patients with hereditary diffuse gastric cancer in a single family: Three case reports and review of literature.

World J Gastroenterol 2020 Nov;26(42):6689-6697

Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan.

Background: Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome often associated with germline mutations in the gene. However, the frequency of mutations is low in patients with HDGC in East Asian countries. Herein, we report three cases of HDGC harboring a missense variant, c.1679C>G, from a single Japanese family.

Case Summary: A 26-year-old female (Case 1) and a 51-year-old male (father of Case 1), who had a strong family history of gastric cancer, were diagnosed with advanced diffuse gastric cancer. After genetic counselling, a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa. Genetic analysis revealed a c.1679C>G variant in all three patients.

Conclusion: It is important for individuals suspected of having HDGC to be actively offered genetics evaluation. This report will contribute to an increased awareness of HDGC.
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http://dx.doi.org/10.3748/wjg.v26.i42.6689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673959PMC
November 2020

Vermiculite as a culture substrate greatly improves the viability of frozen cultures of ectomycorrhizal basidiomycetes.

Fungal Biol 2020 08 12;124(8):742-751. Epub 2020 Jun 12.

Fungus/Mushroom Resource and Research Center (FMRC), Faculty of Agriculture, Tottori University, 4-101 Koyama-Minami, Tottori, 680-8553, Japan.

We assessed a new cryopreservation protocol that uses vermiculite as a culture substrate, called the vermiculite protocol (VP), by assessing the viability, recovery time of hyphae after revival, and colony diameter of cryosensitive ectomycorrhizal basidiomycete strains after storage for 2 weeks or 1 year in a vapour-phase liquid nitrogen tank. Twelve difficult-to-preserve strains of nine species (Amanita citrina, A. pantherina, A. rubescens, A. spissa, Kobayasia nipponica, Lactarius akahatsu, L. hatsudake, Sarcodon aspratus, and Tricholoma flavovirens) that did not achieve good revival after cryopreservation with our previous Homolka's perlite protocol and modified perlite protocol (MPP) experiments were used to assess the new methodology. Vermiculite and liquid medium were put into a cryotube and inoculated with an agar plug containing mycelia. The cryotube was cultured for various incubation times. After adequate mycelial growth, a mixture of cryoprotectants (5% dimethyl sulfoxide and 10% trehalose [5D10T] or 5% glycerol and 10% trehalose [5G10T]) was placed into the cryotube. The cryotube was frozen in a freezing container in a -80 °C freezer and then stored in vapour-phase liquid nitrogen. In the recovery test, 10 of 12 strains showed 100% revival after 2 weeks of storage in the 5G10T cryoprotectant, and all 12 strains showed 100% revival after 2 weeks of storage in the 5D10T cryoprotectant. Furthermore, all strains were viable after 1 year of storage in a vapour-phase liquid nitrogen tank. Thus, the VP is applicable to a wide range of ectomycorrhizal basidiomycete cultures, including highly cryosensitive strains.
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http://dx.doi.org/10.1016/j.funbio.2020.05.002DOI Listing
August 2020

International Survey on Determinants of Antibiotic Duration and Discontinuation in Pediatric Critically Ill Patients.

Pediatr Crit Care Med 2020 09;21(9):e696-e706

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.

Objectives: We hypothesized that antibiotic use in PICUs is based on criteria not always supported by evidence. We aimed to describe determinants of empiric antibiotic use in PICUs in eight different countries.

Design: Cross-sectional survey.

Setting: PICUs in Canada, the United States, France, Italy, Saudi Arabia, Japan, Thailand, and Brazil.

Subjects: Pediatric intensivists.

Interventions: None.

Measurements And Main Results: We used literature review and focus groups to develop the survey and its clinical scenarios (pneumonia, septic shock, meningitis, and intra-abdominal infections) in which cultures were unreliable due to antibiotic pretreatment. Data analyses included descriptive statistics and linear regression with bootstrapped SEs. Overall response rate was 39% (482/1,251), with individual country response rates ranging from 25% to 76%. Respondents in all countries prolonged antibiotic duration based on patient characteristics, disease severity, pathogens, and radiologic findings (from a median increase of 1.8 d [95% CI, 0.5-4.0 d] to 9.5 d [95% CI, 8.5-10.5 d]). Younger age, severe disease, and ventilator-associated pneumonia prolonged antibiotic treatment duration despite a lack of evidence for such practices. No variables were reported to shorten treatment duration for all countries. Importantly, more than 39% of respondents would use greater than or equal to 7 days of antibiotics for patients with a positive viral polymerase chain reaction test in all scenarios, except in France for pneumonia (29%), septic shock (13%), and meningitis (6%). The use of elevated levels of inflammatory markers to prolong antibiotic treatment duration varied among different countries.

Conclusions: Antibiotic-related decisions are complex and may be influenced by cultural and contextual factors. Evidence-based criteria are necessary to guide antibiotic duration and ensure the rational use of antibiotics in PICUs.
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http://dx.doi.org/10.1097/PCC.0000000000002397DOI Listing
September 2020

[Introduction of Medical Physics Course in Komazawa University].

Igaku Butsuri 2020;40(2):68-70

Graduate Division of Health Sciences, Komazawa University.

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http://dx.doi.org/10.11323/jjmp.40.2_68DOI Listing
September 2020

Proton magnetic resonance spectroscopy of lung cancer .

Radiol Case Rep 2020 Jul 22;15(7):1099-1102. Epub 2020 May 22.

Thoracic Surgery, Gunma Prefectural Cancer Center, Ota, Gunma, Japan.

Proton magnetic resonance spectroscopy (H-MRS) has demonstrated that , lung cancer has higher lactate and choline signals than those of normal tissues. The detection of these metabolites in lung cancer by H-MRS would be useful for clinical diagnoses of lung cancer. We report the detection of lactate and choline in lung cancer by H-MRS in a 41-year-old Asian man who was diagnosed with pT4N0M0 ⅢA stage, right upper lobe lung adenocarcinoma. A lactate-lipid peak was observed near 1.33 ppm in the spectrum of lung cancer at TE  =  30 ms, and it was inverted at TE  =  135 ms, indicating that a lactate signal is contained in the lactate-lipid peak. A choline peak was also observed near 3.2 ppm in the spectrum with fat suppression at TE  =  135 ms. An accumulation of similar cases will help determine the appropriate applications of H-MRS for lung cancer.
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http://dx.doi.org/10.1016/j.radcr.2020.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256246PMC
July 2020

Parechovirus-A3 encephalitis presenting with focal seizure mimicking herpes simplex virus infection.

J Infect Chemother 2020 Jul 20;26(7):736-740. Epub 2020 Mar 20.

Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan. Electronic address:

Background: Febrile neonates and young infants presenting with seizure require immediate evaluation and treatment. Herein we experienced two young infants with parechovirus-A3 (PeV-A3) encephalitis, initially presented with focal seizure suspecting herpes simplex virus (HSV) encephalitis.

Cases: We have experienced 2 infantile cases, initially presented with focal seizure. At presentation, HSV encephalitis was strongly suspected and empiric acyclovir therapy was started; however, serum and/or cerebrospinal fluid (CSF) PCR for HSV were negative. Instead, serum and/or CSF PCR for parechovirus-A was positive. PeV-A3 infection was confirmed by genetic sequence analyses. Both cases required multiple anticonvulsant therapy and intensive care for intractable seizure. Diffusion-weighted imaging of brain magnetic resonance imaging (MRI) showed distinct findings; high-intensity lesions in the gray matter of parietal and occipital lobes in Case 1, and bilateral decreased diffusion of the deep white matter and corpus callosum in Case 2. We have followed two cases more than four years; Case 1 developed epilepsy, has been on an anticonvulsant to control her seizure. Case 2 has significant neurodevelopmental delay, unable to stand or communicate with language.

Conclusions: PeV-A3 encephalitis needs to be in differential diagnosis when neonates and young infants present with focal seizure, mimicking HSV encephalitis. Special attention may be necessary in patients with PeV-A3 encephalitis given it could present with intractable seizure with high morbidity in a long-term.
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http://dx.doi.org/10.1016/j.jiac.2020.02.003DOI Listing
July 2020

Insufficiency of prosthetic posterolateral overlap related to recurrence after laparoscopic transabdominal preperitoneal inguinal hernioplasty, as assessed by video review.

BMC Surg 2020 Feb 10;20(1):27. Epub 2020 Feb 10.

Department of Surgery, Shimada Municipal Hospital, 1200-5 Noda, Shimada, Shizuoka, Japan.

Background: Technical factors leading to hernia recurrence after transabdominal preperitoneal repair include insufficient dissection, inadequate prosthetic overlap and prosthetic size, improper fixation and folding, or crinkling of the prosthesis. However, determining intraoperatively if a case will develop recurrent hernias due to these factors remains unclear.

Methods: Five surgeons blind-reviewed operation videos of primary laparoscopic hernioplasty in 13 lesions that went on to develop recurrent hernias (i.e., future recurrence), as well as 28 control lesions, to assess twelve items of surgical techniques. Since we changed a surgical policy of covering myopectineal orifice (MPO) in April 2003, we analyzed the data for the earlier and later periods. The data was analyzed with hierarchical clustering to obtain a gross grouping. The differences of the ratings between the future recurrent and control lesions were then analyzed and the association of the techniques with the hernia recurrence rate, the size of the prosthesis, and the hernia type across hernia recurrence were explored.

Results: The lesions were grouped based on the time series, and its boundary was approximated when we changed our surgical policy. This policy change caused ratings to progress from 34% satisfactory, to 79% satisfactory. The recurrence rate decreased to 0.7% (5/678), compared with 6.2% (10/161) before the policy was implemented (p < 0.001). With univariate analysis, the ratings of posterior prosthesis overlap to the MPO in the recurrent lesions were significantly lower than controls in the later period (p = 0.019). Although various types of recurrences were noted in the earlier period, only primary indirect and recurrent indirect hernias were observed in the later period (p = 0.006).

Conclusions: Fully covering the MPO with mesh is essential for preventing direct recurrence hernias. Additional hernia recurrence prevention can be obtained by giving appropriate attention to prosthesis overlap posterior to the MPO in a large indirect hernia.
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http://dx.doi.org/10.1186/s12893-020-0690-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011534PMC
February 2020

Management of Multiple Arteriovenous Malformations of the Small Bowel.

Case Rep Med 2019 11;2019:2046857. Epub 2019 Dec 11.

Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan.

A 62-year-old Japanese female was referred to our hospital with gastrointestinal bleeding. Although small-bowel bleeding was suspected, no bleeding source was identified by enhanced computed tomography (CT), video capsule endoscopy (VCE), and double-balloon enteroscopy (DBE). Five years later, the patient had recurrent intermittent bloody stools with a significant decrease in hemoglobin levels. Although no active bleeding was observed on antegrade DBE, we detected a pulsatile submucosal uplift accompanied by a small red patch on the top of the uplift in the jejunum. Arteriovenous malformation (AVM) was suspected as the cause of small-bowel bleeding. Multiple-phase CT showed a number of small vascular ectasias during the arterial phase in the jejunum, and we confirmed the presence of multiple AVMs in the jejunum by selective angiography. To identify the location of the lesions and determine the minimal surgical margins, we performed intraoperative selective angiography with indocyanine green (ICG) injection. This technique allowed us to clearly observe the region and perform segmental small-bowel resection with minimal surgical margin. The patient reported that she has had no gastrointestinal bleeding at the two years follow-up visit.
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http://dx.doi.org/10.1155/2019/2046857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927056PMC
December 2019

Utility of Scanning Electron Microscopy Elemental Analysis Using the 'NanoSuit' Correlative Light and Electron Microscopy Method in the Diagnosis of Lanthanum Phosphate Deposition in the Esophagogastroduodenal Mucosa.

Diagnostics (Basel) 2019 Dec 18;10(1). Epub 2019 Dec 18.

Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.

Background: We have recently developed the correlative light and electron microscopy of hematoxylin and eosin (H&E)-stained glass slides using the 'NanoSuit' method. The aim of this study is to explore the utility of the new NanoSuit-correlative light and electron microscopy method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy elemental analysis for the diagnosis of lanthanum phosphate deposition in the H&E-stained glass slides.

Methods: Nine H&E-stained glass slides of the upper gastrointestinal tract mucosa containing the brown pigmented areas by light microscopic observation, which were suspected as lanthanum phosphate deposition, were observed and analyzed by scanning electron microscopy-energy dispersive X-ray spectroscopy using the NanoSuit-correlative light and electron microscopy method.

Results: In all nine slides, the new NanoSuit-correlative light and electron microscopy method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy revealed the accumulation of both lanthanum and phosphorus in the tissue area corresponding to the brown pigment deposition. In addition to the existence of lanthanum phosphate in the stomach and duodenum, known target organs, we observed deposition in the esophagus for the first time. Furthermore, we observed lanthanum phosphate deposition in the background mucosa of stomach containing primary adenocarcinoma.

Conclusions: Scanning electron microscopy-energy dispersive X-ray spectroscopy analysis using the NanoSuit-correlative light and electron microscopy method is useful for the diagnosis of lanthanum phosphate deposition in the H&E-stained glass slides. Lanthanum phosphate deposition occurs not only in the stomach and duodenum but also in the esophagus.
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http://dx.doi.org/10.3390/diagnostics10010001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167806PMC
December 2019

Comparison of mild encephalopathy with reversible splenial lesion with and without acute focal bacterial nephritis.

Brain Dev 2020 Jan 4;42(1):56-63. Epub 2019 Oct 4.

Division of Neurology, Nagano Children's Hospital, Azumino, Japan; Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address:

Objective: Clinically mild encephalitis/encephalopathy with a reversible lesion (MERS) is characterized by reversible lesions with transiently-reduced diffusion in the splenium of the corpus callosum on magnetic resonance imaging. Recently, cases of MERS with accompanying acute focal bacterial nephritis (AFBN) have been reported in children. This study aimed to clarify the clinical features of MERS with AFBN.

Methods: A retrospective study of patients with MERS was conducted at Nagano Children's Hospital, Japan, from April 2013 to March 2018. The clinical signs and laboratory findings of MERS patients with AFBN (AFBN group) and without AFBN (non-AFBN group) were measured and compared.

Results: Of 12 patients diagnosed as having MERS, 3 were also found to have AFBN. Seven of the 9 patients without AFBN were associated with infectious agents, including rotavirus and influenza viruses. No patient received steroids or intravenous immunoglobulin therapy, and none displayed neurological sequelae. Serum C-reactive protein (CRP) levels were significantly higher in the AFBN group than in the non-AFBN group (14.7 mg/dL versus 0.8 mg/dL, P = 0.009). AFBN group patients were also significantly older (97 months versus 27 months, P = 0.018) and experienced significantly less frequent seizures (33% versus 100%, P = 0.045). The mean duration of neurological symptoms was significantly longer in the AFBN group than in the non-AFBN group (4 days versus 1.7 days, P = 0.013).

Conclusions: Pediatric patients with AFBN often present with non-specific findings, such as fever and abdominal pain. Pediatricians should be aware of the possibility of AFBN in the clinical setting of MERS, particularly when the patient exhibits inexplicably high CRP.
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http://dx.doi.org/10.1016/j.braindev.2019.08.008DOI Listing
January 2020

Large Intraosseous Schwannoma in Petrous Apex Presenting with Intratumoral Hemorrhage.

World Neurosurg 2019 Nov 31;131:53-57. Epub 2019 Jul 31.

Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Background: Intracranial schwannomas are rarely confined to the skull. We here report a large schwannoma localized in the petrous apex that presented with intratumoral hemorrhage.

Case Description: A 35-year-old woman with mild hearing disturbance and ear fullness underwent computed tomography scan and magnetic resonance imaging, which demonstrated a tumor accompanied with intratumoral hematoma in the right petrous apex. Bone marrow was totally destroyed, but the bone cortex was relatively preserved. Pathologic specimen showed that the tumor was composed of proliferation of elongated neoplastic cells and positive for S-100 protein. It showed a nuclear palisading pattern, compatible with schwannoma. The lack of any cranial nerve signs and relative preservation of canals through which cranial nerves pass suggested the neurilemma cells surrounded vessels or mismigrated fetal neurilemma cells in the petrous apex as origin of the tumor. Benign nature of the tumor and total disappearance of the symptoms, supposedly due to the spontaneous absorption of the hematoma, made the patient choose a wait-and-watch approach. Magnetic resonance imaging studied 7 years after the diagnosis showed significant decrease of the tumor volume and disappearance of the hematoma.

Conclusions: Although it is a large intraosseous schwannoma in the petrous apex, it has a benign nature, its size is reduced due to the hematoma absorption, and the patient is asymptomatic. We observed the patients for 7 years after the diagnosis.
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http://dx.doi.org/10.1016/j.wneu.2019.07.179DOI Listing
November 2019

New record of an estuarine polychaete, (Annelida, Nereididae) on the eastern coast of Peninsular Malaysia.

Zookeys 2019 18;831:81-94. Epub 2019 Mar 18.

Department of Earth and Environmental Sciences, Graduate School of Engineering and Science, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan Kagoshima University Kagoshima Japan.

An estuarine species of Nereididae (Annelida), (Southern, 1921) has been newly recorded on the eastern coast of Peninsular Malaysia located in the South China Sea based on 23 specimens collected from three estuaries (Tumpat, Kelantan Delta, Kelantan; Setiu Lagoon, Terengganu; Kuala Ibai, Terengganu). The morphological characteristics of the Malaysian specimens agree well with those of the previous original description and the redescription of based on Indian, Myanmar and Singapore specimens. The number of paragnaths in all groups on the proboscis of our Malaysian specimens is within the range of the intraspecific variation of as shown in the previous descriptions. An identification key to species of the species complex, which includes two morphologically similar species, is provided.
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http://dx.doi.org/10.3897/zookeys.831.28588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503610PMC
March 2019

Experimental study of humidity effect on charge measurement of reference ionization chambers in clinical high-energy photon beams.

Med Phys 2019 Sep 9;46(9):4177-4183. Epub 2019 Jul 9.

Graduate Division of Health Sciences, Komazawa University, Tokyo, 1548525, Japan.

Purpose: In the practice code of dosimetry, humidity effect is assumed to be constant as far as the measurements are performed in the relative humidity (RH) range of (20-80)%; thus, the humidity effect can be ignored with a dose uncertainty of 0.15%. This assumption is based on the previous experimental results by Niatel and Guiho. Rogers and Ross calculated the stopping power ratio of humid air and dry air for high-energy electron beams by using a Monte Carlo code. They demonstrate that the W value, the mean energy required to create an ion pair in air, is independent of the beam quality when the air is dry, and that the traditional humidity correction can be used also for high-energy photon and electron beams; however, this was only a computational study. In the present study, we measured the humidity correction of Farmer-type ionization chambers in high-energy photon beams and determined the W values of humid air using the calculated energy deposition of humid air with a Monte Carlo code. Furthermore, we proposed an analytical expression to determine a practical humidity correction for an ionization chamber as a function of absolute humidity.

Method: Experiments were carried out using a clinical linear accelerator (linac, Elekta Precise) at the National Metrology Institute of Japan (NMIJ). A shield box was constructed downstream of the linac and connected to an air processor, which maintained the temperature around 22°C and controlled the humidity in the range of (10-70)% inside the box. We prepared two Farmer-type ionization chambers: PTW 30013 and Exradin A19. Each ionization chamber was placed inside the box and irradiated with 6-, 10-, and 15-MV high-energy photon beams from the clinical linac. The energy deposition to the humid air inside the ionization chamber was calculated using the Electron Gamma Shower Version 5 (EGS5) code system.

Results: Stabilization for the humidity of the ionization chamber was completed within 3 h. The polarity and ion recombination corrections did not show any change in the humidity range studied. The measured humidity correction and the evaluated W values of humid air in high-energy photon beams were in good agreement with those by Rogers in TG-21 and by Niatel in the range of RH (10-70)%.

Conclusion: Humidity correction of ionization chambers in high-energy photon beams from the clinical linac was determined experimentally. Using the analytical expression for the energy depositions by EGS5, the analytical expression for the W values was also derived.
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http://dx.doi.org/10.1002/mp.13665DOI Listing
September 2019

Gene Mutations in During Long-Term Preservation by Repeated Subculturing.

Biopreserv Biobank 2019 Oct 2;17(5):395-400. Epub 2019 Apr 2.

NITE Biological Resource Center (NBRC), National Institute of Technology and Evaluation (NITE), Tokyo, Japan.

Subculturing is frequently used for the preservation of basidiomycetes. In this study, to assess and verify the risks of repeated subculturing on the long-term preservation of strains of culture collections, we performed single nucleotide polymorphism (SNP) analysis in genes encoding enzymes of the mevalonate pathway, 1,3-β-glucan synthesis, lignin degradation, and the tricarboxylic acid (TCA) cycle of mycelia before and after preserving for a 4-year period by the subculturing 30 times every 45 days of NBRC 8346. As a result of analyzing 60 genes of the strain, SNPs were found in 18 genes, and 14 of them were found in the exon region. Nonsynonymous coding SNPs were found in two genes (, ) encoding enzymes of mevalonate pathway and five genes (, , , , ) encoding enzymes of lignin degradation after subculturing of NBRC 8346.
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http://dx.doi.org/10.1089/bio.2018.0149DOI Listing
October 2019

Preoperative FOLFOX in resectable locally advanced rectal cancer can be a safe and promising strategy: the R-NAC-01 study.

Surg Today 2019 Aug 5;49(8):712-720. Epub 2019 Mar 5.

Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.

Purpose: The aim of this study was to assess the safety of rectal surgery after 5-fluorouracil-leucovorin-oxaliplatin chemotherapy (FOLFOX6).

Methods: This was a prospective, multicenter study in 11 Japanese hospitals. We included patients with rectal cancer who received 4 courses of modified FOLFOX6 (mFOLFOX6) before rectal surgery and examined the postoperative complication rate, the clinicopathological response, and the rate of chemotherapy-related adverse events (UMIN 000012559).

Results: The study population included 36 men and 5 women. The average age of the patients was 60.8 years and the average body mass index was 23.1 kg/m. After 4 courses of chemotherapy, grade 2 peripheral nerve disorder and other grade 3 adverse events were seen in 3 patients each (7.3%). Twenty-eight (73.7%) and 8 (21.1%) patients underwent low anterior resection and abdominoperineal resection, respectively. The pelvic nerves were preserved in 35 patients. Surgical morbidity (grade ≥ 3) occurred in 4 patients (10.5%). Anastomotic leakage occurred after surgery in 2 patients (7.1%). No patients achieved pathologically complete remission. However, downstaging of the clinical stage and N stage was seen in 17 (41.5%) and 22 (53.7%) patients, respectively.

Conclusions: Surgery after four courses of mFOLFOX6 chemotherapy can be a safe and promising strategy for patients with locally advanced rectal cancer.
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http://dx.doi.org/10.1007/s00595-019-01788-8DOI Listing
August 2019

Acquisition of Quasi-Monochromatic Dual-Energy in a Microfocus X-ray Generator and Development of Applied Technology.

Diagnostics (Basel) 2019 Mar 4;9(1). Epub 2019 Mar 4.

Department of Radiological Sciences, Faculty of Health Sciences, Komazawa University, Setagaya-ku, Tokyo 154-8525, Japan.

In regenerative medicine, evaluation of bone mineral density using a microfocus X-ray generator could eventually be used to determine the degree of bone tissue regeneration. To evaluate bone mineral density against regenerated bone material, two low-energy X-rays are necessary. Herein, the acquisition of quasi-monochromatic, dual-energy soft X-ray and the subsequent medical application were examined using the K-absorption edges of two types of metal filters (i.e., zirconium and tin) in a microfocus X-ray generator. Investigation of the optimal tube voltage and filter thickness to form a quasi-monochromatic energy spectrum with a single filter revealed that a filter thickness of 0.3 mm results in an optimal monochromatization state. When a dual filter was used, the required filter thickness was 0.3 mm for tin and 0.2 mm for zirconium at a tube voltage of 35 kV. For the medical application, we measured quasi-monochromatic, dual-energy X-rays to evaluate the measurement accuracy of bone mineral density. Using aluminum as a simulated bone sample, a relative error of ≤5% was consistent within the aluminum thickness range of 1⁻3 mm. These data suggest that a bone mineral density indicator of recycled bone material can be easily obtained with the quasi-monochromatic X-ray technique using a microfocus X-ray generator.
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http://dx.doi.org/10.3390/diagnostics9010027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468472PMC
March 2019

A modified perlite protocol with a mixed dimethyl sulfoxide and trehalose cryoprotectant improves the viability of frozen cultures of ectomycorrhizal basidiomycetes.

Mycologia 2019 Jan-Feb;111(1):161-176. Epub 2019 Feb 4.

c Fungus/Mushroom Resource and Research Center, Faculty of Agriculture , Tottori University , 4-101 Koyama-Minami, Tottori 680-8553 , Japan.

Homolka's perlite protocol (HPP) was evaluated for cryopreservation of a wide range of ectomycorrhizal basidiomycete cultures, then a modified perlite protocol (MPP), in which cryoprotectant was added just before freezing rather than during the culturing process, was applied to cryosensitive strains that failed to survive when HPP was used. Further modifications of MPP with various cryoprotectants were explored to improve the cryopreservation of hard-to-preserve strains. The efficacy of HPP was assessed in 111 strains of 38 species of basidiomycetes of various cryosensitivities. After freezing strains using HPP, the viability and colony diameter of the strains were examined after 2 wk, 6 mo, and 1 y of storage at -80 C. Of the 111 strains tested, 91 survived after 1 y of storage with high viability of 80% or more, whereas the remaining 20 strains exhibited low and unstable viability. For those selected cryosensitive strains that did not survive well when HPP was used, MPP was applied with a mixture of cryoprotectants, dimethyl sulfoxide (DMSO), glycerol, and trehalose, at different concentrations and combinations. Toxicity testing of the cryoprotectants in the nonfrozen state revealed that 12% (v/v) glycerol was highly toxic for six strains (four species), whereas DMSO (5% and 10% [v/v]) was less toxic than glycerol. The viability of the cryosensitive strains after freezing demonstrated that DMSO was more efficient than glycerol, and trehalose enhanced the cryoprotective effects of both glycerol and DMSO when MPP was used for cryopreservation. Our comparative analysis of MPP with various combinations and concentrations of cryoprotectants revealed that a mixture of 5% DMSO and 10% trehalose was the most effective cryoprotectant, and that using MPP with this cryoprotectant was applicable to many cryosensitive strains.
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http://dx.doi.org/10.1080/00275514.2018.1520035DOI Listing
May 2019

Concentrations of various forms of vitamin B in ginkgo seed poisoning.

Brain Dev 2019 Mar 23;41(3):292-295. Epub 2018 Oct 23.

Department of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.

A 2-year-old girl required medical attention for a sudden onset of repetitive tonic-clonic convulsions after ingesting 20-30 ginkgo seeds. Concentrations of the major forms of circulating vitamin B, pyridoxal-5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid, as well as the known ginkgo seed toxin 4'-O-methylpyridoxine (MPN) were measured in the serum and cerebrospinal fluid (CSF). PLP is an active form of vitamin B and necessary for γ-aminobutyric acid (GABA) production. High MPN concentrations were observed in both the serum and CSF. As the PLP to PL ratio was markedly decreased in serum and CSF examinations, we suspected the ratio to be important in GABA production. This case report provides novel information on the metabolism of vitamin B in humans as a result of ginkgo seed poisoning.
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http://dx.doi.org/10.1016/j.braindev.2018.10.007DOI Listing
March 2019

Unknown mass on chest radiography: Morgagni hernia identified on ultrasonography.

Pediatr Int 2018 09;60(9):904-905

Department of Pediatric Intensive Care, Nagano Children's Hospital, Azumino City, Nagano, Japan.

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http://dx.doi.org/10.1111/ped.13644DOI Listing
September 2018

An intronic single nucleotide polymorphism in the MUTYH gene is associated with increased risk for HCV-induced hepatocellular carcinoma.

Free Radic Biol Med 2018 12 13;129:88-96. Epub 2018 Sep 13.

Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address:

Background & Aims: The role of base excision repair genes in human hepatocarcinogenesis has not yet been explored. Here, we investigated relationships between variants of these genes and the risk of developing hepatocellular carcinoma (HCC).

Methods: Nineteen tagging SNPs in base excision repair genes (including MUTYH, OGG1 and MTH1) were genotyped using iPLEX assays; one significant SNP was found and confirmed in Japanese patients with chronic hepatitis C (CHC) (n = 38 HCC and 55 controls). The effects of modifying the intronic variants were determined by luciferase assays. MUTYH-null mice were used to examine the involvement of oxidative stress and DNA repair enzymes in hepatocarcinogenesis.

Results: Significant associations were found for a single intron SNP (rs3219487) in the MUTYH gene. The risk of developing HCC in patients with A/A or G/A genotypes was higher than in those with the G/G genotype (OR = 9.27, 95% CI = 2.39 -32.1, P = 0.0005). MUTYH mRNA levels in both peripheral mononuclear cells were significantly lower in G/A or A/A genotyped subjects (P = 0.0157 and 0.0108, respectively). We found that -2000 in the MUTYH promoter region is involved in enhanced expression of MUTYH by insertion of a major allele sequence of rs3219487. Liver tumors were observed in MUTYH-null mice after 12 months´ high iron diet, but no tumors developed when dietary anti-oxidant (N-Acetyl-L-cysteine) was also provided.

Conclusions: CHC patients with the rs3219487 adenine allele had a significantly increased risk of developing HCC. MUTYH-null mice with iron-associated oxidative stress were susceptible to development of liver tumors unless prevented by dietary anti-oxidants.
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http://dx.doi.org/10.1016/j.freeradbiomed.2018.09.010DOI Listing
December 2018

Increased Duodenal Iron Absorption through Upregulation of Ferroportin 1 due to the Decrement in Serum Hepcidin in Patients with Chronic Hepatitis C.

Can J Gastroenterol Hepatol 2018 14;2018:2154361. Epub 2018 Aug 14.

Department of Medical Oncology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-Ku, Sapporo 060-8543, Japan.

Hepatic iron accumulation is generally increased in the chronic hepatitis C (CHC) liver; however, the precise mechanism of such accumulation remains unclear. We evaluated iron absorption from the gastrointestinal tract of patients with CHC and control participants. We measured the expression of a panel of molecules associated with duodenal iron absorption and serum hepcidin levels to determine the mechanism of iron accumulation in the CHC liver. We enrolled 24 patients with CHC and 9 patients with chronic gastritis without infection or an iron metabolism disorder as control participants. An oral iron absorption test (OIAT) was administered which involved a dosage of 100 mg of sodium ferrous citrate. Serum level of hepcidin-25 was measured by liquid chromatography-tandem mass spectrometry. Ferroportin 1 (FPN) mRNA was measured by RT-PCR and FPN protein was analyzed by western blot. Samples were obtained from duodenum biopsy tissue from each CHC patient and control participant. Caco-2/TC7 cells were incubated in Costar transwells (0.4 m pores). The OIAT showed significantly greater iron absorption in CHC patients than control participants. Serum hepcidin-25 in the CHC group was significantly lower than in the control group. Compared with control participants, duodenal FPN mRNA expression in CHC patients was significantly upregulated. The FPN mRNA levels and protein levels increased significantly in Caco-2/TC7 cell monolayers cultured in transwells with hepcidin. Lower serum hepcidin-25 levels might upregulate not only FPN protein expression but also mRNA expression in the duodenum and cause iron accumulation in patients with CHC.
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http://dx.doi.org/10.1155/2018/2154361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112088PMC
February 2019

Neoadjuvant chemotherapy with docetaxel, nedaplatin, and fluorouracil for resectable esophageal cancer: A phase II study.

Cancer Sci 2018 Nov 25;109(11):3554-3563. Epub 2018 Sep 25.

Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Cisplatin plus 5-fluorouracil is regarded as standard neoadjuvant chemotherapy for esophageal squamous cell carcinoma (ESCC) in Japan, but the prognosis remains poor. We have previously described how definitive chemoradiotherapy with docetaxel, nedaplatin, and 5-fluorouracil (DNF) led to a very high response rate and promising survival times. We therefore undertook a phase II trial to evaluate the feasibility and efficacy of neoadjuvant DNF. The study included patients with clinical stage Ib-III ESCC. Chemotherapy consisted of i.v. docetaxel (30 mg/m ) and nedaplatin (50 mg/m ) on days 1 and 8, and a continuous infusion of 5-fluorouracil (400 mg/m /day) on days 1-5 and 8-12, every 3 weeks. After three courses of chemotherapy, esophagectomy was carried out. The primary end-point was the completion rate of the protocol treatment. Twenty-eight patients were enrolled (cStage Ib/II/III, 2/3/23) and all received at least two cycles of chemotherapy. Twenty-five patients underwent surgery, all of whom achieved an R0 resection, leading to a completion rate of 89.3%. The overall response rate was 87.0%. A pathological complete response was confirmed in eight (32.0%) cases. Grade 3/4 adverse events included leukopenia (32.1%), neutropenia (39.3%), febrile neutropenia (10.7%), thrombocytopenia (10.7%), and diarrhea (14.3%), but were manageable. Treatment-related deaths and major surgical complications did not occur. Estimated 2-year progression-free and overall survival rates were 70.4% and 77.2%, respectively. Thus, DNF therapy was well tolerated and deemed feasible, with a strong tumor response in a neoadjuvant setting for ESCC. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014305).
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http://dx.doi.org/10.1111/cas.13772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215867PMC
November 2018

Neonatal renovascular hypertension.

Pediatr Int 2018 May;60(5):501

Department of Pediatric Intensive Care, Nagano Children's Hospital, Azumino City, Nagano, Japan.

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http://dx.doi.org/10.1111/ped.13549DOI Listing
May 2018

Design and development of a nonrigid phantom for the quantitative evaluation of DIR-based mapping of simulated pulmonary ventilation.

Med Phys 2018 May 28. Epub 2018 May 28.

Radiological Sciences, Graduate Division of Health Sciences, Komazawa University, Tokyo, 154-8525, Japan.

Purpose: The validation of deformable image registration (DIR)-based pulmonary ventilation mapping is time consuming and prone to inaccuracies and is also affected by deformation parameters. In this study, we developed a nonrigid phantom as a quality assurance (QA) tool that simulates ventilation to evaluate DIR-based images quantitatively.

Methods: The phantom consists of an acrylic cylinder filled with polyurethane foam designed to simulate pulmonic alveoli. A polyurethane membrane is attached to the inferior end of the phantom to simulate the diaphragm. In addition, tracheobronchial-tree-shaped polyurethane tubes are inserted through the foam and converge outside the phantom to simulate the trachea. Solid polyurethane is also used to model arteries, which closely follow the model airways. Two three-dimensional (3D) CT scans were performed during exhalation and inhalation phases using xenon (Xe) gas as the inhaled contrast agent. The exhalation 3D-CT image is deformed to an inhalation 3D-CT image using our in-house program based on the NiftyReg open-source package. The target registration error (TRE) between the two images was calculated for 16 landmarks located in the simulated lung volume. The DIR-based ventilation image was generated using Jacobian determinant (JD) metrics. Subsequently, differences in the Hounsfield unit (HU) values between the two images were measured. The correlation coefficient between the JD and HU differences was calculated. In addition, three 4D-CT scans are performed to evaluate the reproducibility of the phantom motion and Xe gas distribution.

Results: The phantom exhibited a variety of displacements for each landmark (range: 1-20 mm). The reproducibility analysis indicated that the location differences were <1 mm for all landmarks, and the HU variation in the Xe gas distribution was close to zero. The mean TRE in the evaluation of spatial accuracy according to the DIR software was 1.47 ± 0.71 mm (maximum: 2.6 mm). The relationship between the JD and HU differences had a large correlation (R = -0.71) for the DIR software.

Conclusion: The phantom implemented new features, namely, deformation and simulated ventilation. To assess the accuracy of the DIR-based mapping of the simulated pulmonary ventilation, the phantom allows for simulation of Xe gas wash-in and wash-out. The phantom may be an effective QA tool, because the DIR algorithm can be quickly changed and its accuracy evaluated with a high degree of precision.
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http://dx.doi.org/10.1002/mp.13017DOI Listing
May 2018

A multi-institutional study of independent calculation verification in inhomogeneous media using a simple and effective method of heterogeneity correction integrated with the Clarkson method.

J Radiat Res 2018 Jul;59(4):490-500

Radiological Sciences, Graduate Division of Health Sciences, Komazawa University, Tokyo, Japan.

In inhomogeneous media, there is often a large systematic difference in the dose between the conventional Clarkson algorithm (C-Clarkson) for independent calculation verification and the superposition-based algorithms of treatment planning systems (TPSs). These treatment site-dependent differences increase the complexity of the radiotherapy planning secondary check. We developed a simple and effective method of heterogeneity correction integrated with the Clarkson algorithm (L-Clarkson) to account for the effects of heterogeneity in the lateral dimension, and performed a multi-institutional study to evaluate the effectiveness of the method. In the method, a 2D image reconstructed from computed tomography (CT) images is divided according to lines extending from the reference point to the edge of the multileaf collimator (MLC) or jaw collimator for each pie sector, and the radiological path length (RPL) of each line is calculated on the 2D image to obtain a tissue maximum ratio and phantom scatter factor, allowing the dose to be calculated. A total of 261 plans (1237 beams) for conventional breast and lung treatments and lung stereotactic body radiotherapy were collected from four institutions. Disagreements in dose between the on-site TPSs and a verification program using the C-Clarkson and L-Clarkson algorithms were compared. Systematic differences with the L-Clarkson method were within 1% for all sites, while the C-Clarkson method resulted in systematic differences of 1-5%. The L-Clarkson method showed smaller variations. This heterogeneity correction integrated with the Clarkson algorithm would provide a simple evaluation within the range of -5% to +5% for a radiotherapy plan secondary check.
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http://dx.doi.org/10.1093/jrr/rry039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054244PMC
July 2018
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