Publications by authors named "Hiroyuki Okamoto"

228 Publications

Development of a physical geometric phantom for deformable image registration credentialing of radiotherapy centers for a clinical trial.

J Appl Clin Med Phys 2021 Jul 22;22(7):255-265. Epub 2021 Jun 22.

Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto, Japan.

Purpose: This study aimed to develop a physical geometric phantom for the deformable image registration (DIR) credentialing of radiotherapy centers for a clinical trial and tested the feasibility of the proposed phantom at multiple domestic and international institutions.

Methods And Materials: The phantom reproduced tumor shrinkage, rectum shape change, and body shrinkage using several physical phantoms with custom inserts. We tested the feasibility of the proposed phantom using 5 DIR patterns at 17 domestic and 2 international institutions (21 datasets). Eight institutions used the MIM software (MIM Software Inc, Cleveland, OH); seven used Velocity (Varian Medical Systems, Palo Alto, CA), and six used RayStation (RaySearch Laboratories, Stockholm, Sweden). The DIR accuracy was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance (HD).

Results: The mean and one standard deviation (SD) values (range) of DSC were 0.909 ± 0.088 (0.434-0.984) and 0.909 ± 0.048 (0.726-0.972) for tumor and rectum proxies, respectively. The mean and one SD values (range) of the HD value were 5.02 ± 3.32 (1.53-20.35) and 5.79 ± 3.47 (1.22-21.48) (mm) for the tumor and rectum proxies, respectively. In three patterns evaluating the DIR accuracy within the entire phantom, 61.9% of the data had more than a DSC of 0.8 in both tumor and rectum proxies. In two patterns evaluating the DIR accuracy by focusing on tumor and rectum proxies, all data had more than a DSC of 0.8 in both tumor and rectum proxies.

Conclusions: The wide range of DIR performance highlights the importance of optimizing the DIR process. Thus, the proposed method has considerable potential as an evaluation tool for DIR credentialing and quality assurance.
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http://dx.doi.org/10.1002/acm2.13319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292683PMC
July 2021

Successful diagnosis and treatment of pulmonary aspergillosis-related malignant catatonia using propofol and quetiapine: A case report.

Medicine (Baltimore) 2021 May;100(19):e25967

Department of Emergency Medicine, Sapporo Medical University Hospital, Sapporo-shi.

Introduction: Malignant catatonia (MC) is a movement disorder syndrome characterized by immobility, rigidity, and consciousness disorders that develops in association with mental and physical diseases. It is often fatal due to hyperthermia, rhabdomyolysis, and acute kidney injury. Its clinical symptoms are similar to those of another disorder, neuroleptic malignant syndrome (NMS), and it is often difficult to distinguish between the 2 disorders.

Patient Concerns: An Asian woman in her 60s with history of schizophrenia. She was admitted to our hospital because of symptoms such as fever, unconsciousness, and muscle rigidity. Blood tests showed kidney injury and high creatinine kinase levels.

Diagnoses: At the time of admission, she had been diagnosed with NMS complicated by pulmonary aspergillosis and was undergoing treatment although there was no improvement.

Interventions: Subsequently, the administration of propofol, a gamma-aminobutyric acid A agonist, markedly improved the symptoms, and the diagnosis was corrected to MC. At the beginning of her hospitalization, she received dantrolene, bromocriptine, amantadine, and L-3,4-dihydroxyphenylalanine as treatment for NMS, but her symptoms did not improve. With propofol, which is used for sedation, her catatonic symptoms improved markedly. Quetiapine administration further improved the symptoms, and it eventually resolved completely.

Outcomes: The patient's MC was in remission. Prolonged intensive care management resulted in a decline in activities of daily living, and she required rehabilitation at another hospital.

Conclusion: This is the first report of MC with suspected involvement of pulmonary aspergillosis. MC differs from NMS, in that it is treated more effectively with gamma-aminobutyric acid A agonists. Although benzodiazepines are the first choice for the diagnosis and treatment of MC, they are ineffective for majority of patients with schizophrenia. However, even in such cases, propofol and quetiapine are effective, and they facilitate diagnosis and treatment.
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http://dx.doi.org/10.1097/MD.0000000000025967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133261PMC
May 2021

Initial Experience of Intentional Internal High-Dose Policy Volumetric Modulated Arc Therapy of Neck Lymph Node Metastases ≥ 2 cm in Patients With Head and Neck Squamous Cell Carcinoma.

Front Oncol 2021 27;11:651409. Epub 2021 Apr 27.

Department of Radiation Therapy in National Cancer Center Hospital, Tokyo, Japan.

Background And Purpose: Most locoregional recurrences after definitive radiotherapy for head and neck squamous cell carcinoma (HNSCC) develop "in-field." Dose escalation while sparing organs at risk can be a good solution for improving local control without increasing adverse effects. This study investigated the safety and effectiveness of volumetric modulated arc therapy (VMAT) using intentionally internal high-dose policy (IIHDP) to treat neck lymph node metastases (NLNM) ≥ 2 cm in HNSCC patients.

Materials And Methods: We analyzed 71 NLNM from 51 HNSCC patients who had received definitive radiotherapy to treat NLNM ≥ 2 cm using the VMAT technique in our institution between February 2017 and August 2019. Thirty-seven NLNM from 25 patients were treated using IIHDP VMAT (group A), and 34 NLNM from 27 patients were treated with homogeneous-dose distribution policy (HDDP) VMAT (group B). One patient with three NLNM had one lymph node assigned to group A and the other two to group B. Adverse events and local recurrence-free survival (LRFS) was compared between the two groups.

Results: In the median follow-up period of 527 days, there were no significant differences between the groups in terms of dermatitis or mucositis ≥ grade 2/3, but LRFS was significantly longer in group A (p = 0.007). In the Cox regression analysis after adjustment for the propensity score, group A also showed an apparently superior LFRS.

Conclusion: Our initial experience of IIHDP VMAT suggested that IIHDP VMAT to treat HNSCC neck lymph node metastases measuring ≥ 2 cm was feasible and possibly led to better local control than HDDP VMAT.
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http://dx.doi.org/10.3389/fonc.2021.651409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112241PMC
April 2021

Neutron flux evaluation model provided in the accelerator-based boron neutron capture therapy system employing a solid-state lithium target.

Sci Rep 2021 Apr 13;11(1):8090. Epub 2021 Apr 13.

Division of Research and Development for Boron Neutron Capture Therapy, National Cancer Center Exploratory Oncology Research & Clinical Trial Center, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.

An accelerator-based boron neutron capture therapy (BNCT) system employing a solid-state Li target can achieve sufficient neutron flux for treatment although the neutron flux is reduced over the lifetime of its target. In this study, the reduction was examined in the five targets, and a model was then established to represent the neutron flux. In each target, a reduction in neutron flux was observed based on the integrated proton charge on the target, and its reduction reached 28% after the integrated proton charge of 2.52 × 10 mC was delivered to the target in the system. The calculated neutron flux acquired by the model was compared to the measured neutron flux based on an integrated proton charge, and the mean discrepancies were less than 0.1% in all the targets investigated. These discrepancies were comparable among the five targets examined. Thus, the reduction of the neutron flux can be represented by the model. Additionally, by adequately revising the model, it may be applicable to other BNCT systems employing a Li target, thus furthering research in this direction. Therefore, the established model will play an important role in the accelerator-based BNCT system with a solid-state Li target in controlling neutron delivery and understanding the neutron output characteristics.
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http://dx.doi.org/10.1038/s41598-021-87627-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044165PMC
April 2021

Blunt traumatic iliac vein injury without pelvic fracture - A case report.

Trauma Case Rep 2021 Apr 10;32:100412. Epub 2021 Feb 10.

Emergency and Critical Care Medical Center, Teine Keijinkai Hospital, 1-jo 12-chome, Maeda, Teine-ku, Sapporo 006-8555, Japan.

A 48-year-old man fell asleep while driving a 4-t truck, hit an 11-t truck from behind, and was injured. Contrast-enhanced computed tomography revealed retroperitoneal hematoma and extravasation of contrast medium in the left common iliac vein. No obvious pelvic fracture was observed. The patient showed no hemodynamic deterioration, so conservative management was selected. Computed tomography images obtained 2 days after injury showed that the hematoma around the left common iliac vein had shrunk and no clear vein thrombus was observed. No findings suggestive of deep vein thrombosis or pulmonary embolism were seen after the start of gait training. Iliac vein injury without pelvic fracture due to blunt trauma is particularly rare. This rare injury was attributed to sudden extension of the hip and force in the direction of the long axis of the common iliac vein. Conservative management is the recommended first choice for isolated iliac vein injury with stable hemodynamics.
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http://dx.doi.org/10.1016/j.tcr.2021.100412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900575PMC
April 2021

Non-surgical treatment of tetanus infection associated with breast cancer skin ulcer: a case report and literature review.

BMC Infect Dis 2021 Jan 7;21(1):37. Epub 2021 Jan 7.

Department of Emergency Medicine, Sapporo Medical University, Minami 1-jo, Nishi 16-chome, 291, Chuo-ku, Sapporo-shi, Hokkaido, 060-8543, Japan.

Background: Previous studies have reported poor prognosis in cases of tetanus that develops after bacteria enters via breast cancer-related skin ulcers that are not treated with surgical debridement. Herein, we review the literature concerning this presentation and report the first case of complete remission from tetanus without surgical debridement of the skin ulcer.

Case Presentation: An Asian woman aged over 60 years had a history of skin ulcer caused by breast cancer. She was diagnosed with tetanus due to trismus and opisthotonus. Based on the suspicion that the skin ulcer was the portal of entry for tetanus bacteria, we considered several debridement and thoracic surgical options for tetanus treatment. However, debridement was not performed as the surgery was considered high risk and the patient did not consent to it. The patient received treatment with anti-tetanus globulin and metronidazole; sound insulation and shielding were also performed in a dark room. Subsequently, the patient's symptoms improved, and sound insulation and deep sedation management were completed on 19th day of hospitalization. With no symptom recurrence, the patient was discharged on Day 54. To date, over 3 years after treatment, no evidence of tetanus recurrence has been observed. The case was characterized by a lack of autonomic hyperactivity. The tetanus severity was likely representative of the low amount of toxin that the patient was exposed to.

Conclusion: This case involved moderate severity tetanus originating from a chronic skin ulcer related to breast cancer. The patient survived without undergoing extensive debridement. No evidence of tetanus relapse was observed during the follow-up period, likely due to vaccination that might have restored the patient's active immunity. Debridement is not always necessary for tetanus complicated by breast cancer skin ulcers. Furthermore, appropriate toxoid vaccination is critical for preventing the onset and recurrence of tetanus in these patients.
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http://dx.doi.org/10.1186/s12879-020-05739-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792315PMC
January 2021

A dosimetric and centeredness comparison of the conventional and novel endobronchial applicators: A preliminary study.

Brachytherapy 2021 Mar-Apr;20(2):467-477. Epub 2021 Jan 19.

Department of Radiation Oncology, National Cancer Center Hospital, Chuo City, Tokyo, Japan.

Purpose: This study compared the applicator position relative to the tracheal wall and dosimetric parameters between conventional and novel applicators among patients receiving endobronchial brachytherapy (EBBT) for intratracheal tumors.

Methods And Materials: Data from 7 patients who received EBBT for intratracheal tumors were retrospectively analyzed; 4 and 3 patients were treated with conventional (2-wing) or novel (5-wing) applicators, respectively. Applicator centrality was evaluated using the distance between the center of the trachea and main bronchus (TMB) lumen and path of source (L). Dosimetric parameters, including plans normalized to D of the TMB = 45 Gy (normalized plan), were compared between the applicators.

Results: The mean and maximum values of L in cases of the 2-wing applicator group were approximately 5.0 mm and 10.0 mm, respectively. In the novel applicator group, the corresponding values were approximately 3.0 and 6.0 mm, respectively. In the normalized plan of the 2-wing applicator group, the ranges of median V of clinical target volume (CTV) and D of the TMB in all cases were 23.0-91.9% and 66.3-153.1 Gy, respectively. In the 5-wing applicator group, the corresponding values were 69.2-83.8% and 60.4-84.5 Gy, respectively.

Conclusions: In the 5-wing applicator group, the range was narrow in all dose-volume parameters except for D of the TMB. Compared to the conventional applicator, the 5-wing applicator can give a stable dose to the CTV and can reduce the maximum dose of the TMB. This suggests that stable EBBT can be given to any patient using the 5-wing applicator.
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http://dx.doi.org/10.1016/j.brachy.2020.11.005DOI Listing
January 2021

Dosimetric effect of the intestinal gas of online adaptive stereotactic body radiotherapy on target and critical organs without online electron density correction for pancreatic cancer.

Br J Radiol 2021 Mar 5;94(1119):20200239. Epub 2021 Feb 5.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Objective: This study aimed to assess the dosimetric effect of intestinal gas of stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) on target and critical organs for pancreatic cancer without online electron density correction (EDC).

Methods: Thirty pancreatic cancer patients who underwent online SMART were selected for this study. The treatment time of each stage and the total treatment time were recorded and analyzed. The concerned dose-volume parameters of target and organs-at-risk (OAR) were compared with and without an intestinal gas EDC using the Wilcoxon-signed rank test. Analysis items with value < 0.05 were considered statistically significant. The relationships between dosimetric differences and intestinal gas volume variations were investigated using the Spearman test.

Results: The average treatment time was 82 min, and the average EDC time was 8 min, which accounted for 10% of the overall treatment time. There were no significant differences in CTV (GTV), PTV, bowel, stomach, duodenum, and skin ( > 0.05) with respect to dose volume parameters. For the of gastrointestinal organs ( = 0.03), the mean dose of the liver ( = 0.002) and kidneys ( = 0.03 and = 0.04 for the left and right kidneys, respectively), there may be a risk of slight overestimation compared with EDC, and for the of the spinal cord ( = 0.02), there may be a risk of slight underestimation compared with EDC. A weak correlation for in the PTV and in the duodenum was observed.

Conclusion: For patients with similar inter-fractional intestinal gas distribution, EDC had little dosimetric effects on the of all GI organs and dose volume parameters of target in most plans.

Advances In Knowledge: By omitting the EDC of intestinal gas, the online SMART treatment time can be shortened.
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http://dx.doi.org/10.1259/bjr.20200239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011255PMC
March 2021

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.

BMC Urol 2020 Dec 14;20(1):196. Epub 2020 Dec 14.

Department of Radiation Therapy, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, Japan.

Background: In definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation.

Case Presentation: We report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation.

Conclusions: Our report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.
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http://dx.doi.org/10.1186/s12894-020-00767-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737272PMC
December 2020

Transvaginal artificial ascites infusion as a spacer in gynecological brachytherapy: a novel technique.

J Contemp Brachytherapy 2020 Oct 30;12(5):487-491. Epub 2020 Oct 30.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

This is a first paper to report on artificial ascites infusion via vaginal wall for pelvic interstitial brachytherapy. Artificial ascites is commonly used for treating liver tumors, with radiofrequency ablation and percutaneous artificial ascites infusion through the abdominal wall for pelvic brachytherapy has been previously reported by our group. However, the trans-abdominal needle approach under ultrasound guidance is unreliable due to poor visualization resulting in fluid injection into the abdominal wall or mesenterium and the rate of successful artificial ascites infusion was low. Target tumor of the vaginal cuff brachytherapy is usually adjacent to the intestine, and transvaginal artificial ascites infusion under trans-rectal ultrasonography is considered as a rational and simpler method to create a space between target volume and organs at risk, such as intestines or sigmoid colon, by increased visualization of the needle compared to trans-abdominal approach. Here, we report a practical experience of transvaginal artificial ascites infusion.
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http://dx.doi.org/10.5114/jcb.2020.100382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701932PMC
October 2020

Source position measurement by Cherenkov emission imaging from applicators for high-dose-rate brachytherapy.

Med Phys 2021 Jan 7;48(1):488-499. Epub 2020 Dec 7.

Graduate School of Medicine, Nagoya University, 1-1-20 Daiko-minami, Higashi-ku, Nagoya, Aichi, 461-8673, Japan.

Purpose: We developed a novel and simple method to measure the source positions in applicators directly for high-dose-rate (HDR) brachytherapy based on Cherenkov emission imaging, and evaluated the performance.

Methods: The light emission from plastic applicators used in cervical cancer treatments, irradiated by an Ir γ-ray source, was captured using a charge-coupled device camera. Moreover, we attached plastics of different shapes, including tapes, tubes, and plates to a metal applicator, to use as screens for the Cherenkov imaging. We determined the source positions and dwell intervals from the light profiles along with the applicator and compared these with preset values and dummy marker measurements.

Results: The source positions and dwell intervals measured from the light images were comparable to the dummy marker measurements and preset values. The distance from the applicator tip to the first source positions agreed with the dummy marker measurements within 0.2 mm for the plastic tandem. The dwell intervals measured using the Cherenkov method agreed with the preset values within 0.6 mm. The distances measured with three plastic types on the metal applicator also agreed with the dummy marker measurements within 0.2 mm. The dwell intervals measured using the plastic tape agreed with the preset values within 0.7 mm.

Conclusions: The proposed method should be suitable for rapid and easy quality assurance (QA) investigations in HDR brachytherapy, as it enables source position using a single image. The method allows for real-time, filmless measurements of the source positions to be obtained and is useful for rapid feedback in QA procedures.
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http://dx.doi.org/10.1002/mp.14606DOI Listing
January 2021

Imbalance toward TFH 1 cells playing a role in aberrant B cell differentiation in systemic sclerosis.

Rheumatology (Oxford) 2021 03;60(3):1553-1562

Department of Dermatology, Kansai Medical University, Hirakata, Japan.

Objective: SSc is a connective tissue disease with multisystem disorder induced by the inflammation and fibrosis following T and B cell abnormalities. Follicular helper CD4+ T (TFH) cells play a crucial role in the formation of germinal centres and specialize in interacting to aid B cell differentiation. We aimed to investigate TFH cells and their subsets to evaluate their involvement with B cell alteration in SSc.

Method: Circulating TFH cells (cTFH), B cells and their subsets were assessed by flow cytometry. The concentration of serum cytokines was measured by cytokine array assay. Immunohistochemistry and IF were performed to evaluate the migration of TFH cells in SSc skin lesions.

Results: The proportion of cTFH cells did not differ from controls, but their subsets were imbalanced in SSc patients. The frequency of TFH 1 was increased and correlated with ACA titre, serum IgM or CRP levels of patients, and cytokine concentrations of IL-21 and IL-6 that induce B cell differentiation in SSc. cTFH cells from SSc showed activated phenotype with expressing higher cytokine levels compared with controls. The frequency of TFH 17 was also increased, but was not correlated with a high level of Th17 cytokines in patients' sera. Furthermore, infiltration of TFH cells was found in skin lesion of SSc patients.

Conclusion: We here describe an imbalance of cTFH toward TFH 1 that may induce B cell alteration through IL-21 and IL-6 pathways and promote inflammation, contributing to the pathogenesis of SSc disease.
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http://dx.doi.org/10.1093/rheumatology/keaa669DOI Listing
March 2021

Advantages and challenges for noninvasive atrial fibrillation ablation.

J Interv Card Electrophysiol 2020 Oct 26. Epub 2020 Oct 26.

Cardiac Arrhythmia Service, Brigham and Women's Hospital, Boston, MA, USA.

Purpose: Although catheter ablation is an effective therapy for atrial fibrillation (AF), risks remain and improved efficacy is desired. Stereotactic radiotherapy is a well-established therapy used to noninvasively treat malignancies with precision. We sought to evaluate stereotactic arrhythmia radioablation (STAR) as a therapeutic option for treating AF.

Methods And Results: Three cancer patients with drug refractory AF were enrolled. Planning software using 3-D CT of the left atrium was used to design a desired ablation volume encompassing antral circumferential pulmonary vein isolation, roof and floor lines to create a "box" lesion set. After planning, patients were treated in the radioablation suite. STAR was able to deliver the intended radiation dose to the target in all 3 patients. No complications were observed over a follow-up period of 24 months. One patient with paroxysmal AF died from deterioration of cancer. The autopsy revealed evidence of fibroblasts and fibrogenesis in the region of atrial tissues targeted with radioablation. In one of these patients, left atrial posterior wall electrograms recorded from the esophagus before and 3 months after STAR indicated successful electrical isolation.

Conclusions: This is the first report of non-invasive radioablation of the left atrium with demonstration of successful electrical isolation. Although STAR may be safe and effective in delivering ablative energy to the left atrium, further evaluation is warranted regarding effectiveness.
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http://dx.doi.org/10.1007/s10840-020-00904-wDOI Listing
October 2020

Radiation protection in radiological imaging: a survey of imaging modalities used in Japanese institutions for verifying applicator placements in high-dose-rate brachytherapy.

J Radiat Res 2021 Jan;62(1):58-66

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku Fukuoka, Fukuoka, 812-8582, Japan.

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was $\le$75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed.
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http://dx.doi.org/10.1093/jrr/rraa088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779356PMC
January 2021

Configuration analysis of the injection position and shape of the gel spacer in gynecologic brachytherapy.

Brachytherapy 2021 Jan-Feb;20(1):95-103. Epub 2020 Oct 1.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Purpose: In this single-institution retrospective study, configuration analysis was performed to determine the optimal location and volume of hyaluronic acid gel spacer injection into the rectovaginal or vesicovaginal septum for effective dose reduction (DR) to the organs at risk (OARs), the rectum and bladder.

Methods And Materials: 70 and 50 intracavitary brachytherapy treatment plans used only vaginal cylinders with gel spacers for the rectal and bladder sides, respectively, whereas 28 did not use spacers. Correlation analysis was performed between the geometrical parameters and injection position of the gel spacers and the 2-cm covering doses of the OARs for each treatment.

Results: A higher DR was predicted for hyaluronic acid gel spacer injection within ±5 mm and ±2.5 mm in the lateral-medial direction from the midpoint on the rectal and bladder sides, and ±10 mm in the cranial-caudal direction from the midpoint on the rectal side. There were correlations between 2-cm covering doses and the gel spacer parameters: the volume on the rectal (p = 0.02) and bladder (p = 0.04) sides; the craniocaudal length on the rectal side (p << 0.05); and ventrodorsad thickness on each OAR (p << 0.05) sides. There was no significant difference in the DR between a volume of ∼10 cm and that of a higher volume (p >> 0.05).

Conclusions: A gel spacer volume of ∼10 cm provides sufficient OAR DR if its gravity point is on the midpoint between the cylinder applicator and OAR, and its craniocaudal length covers the active length of the cylinder applicator.
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http://dx.doi.org/10.1016/j.brachy.2020.08.021DOI Listing
October 2020

[Introduction of Quality Indicators into Radiotherapy Departments in Japan].

Igaku Butsuri 2020 ;40(3):75-87

Department of Radiation Oncology, National Cancer Center Hospital.

This study investigates the quality indicators (QIs) of medical care that are expected to be introduced to radiotherapy departments in Japan and evaluates whether the QIs reflect the characteristics of the treatment facilities. For this purpose, a questionnaire survey was administered to radiotherapy treatment facilities in Japan. A consensus of early QI candidates was obtained from the panel members. The characteristics identified in the candidate QIs were subdivided into 140 items covering 27 domains of medical-care contents in radiotherapy departments. These 140 items were compiled into a questionnaire, which was administered to 15 treatment facilities in Japan. The primary results indicated that 36 items in five domains are useful QI contents. The secondary findings indicated that the provision of advanced radiotherapy to several patients, the waiting time, and the radiotherapy initiated depend on the manpower of the departmental staff.
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http://dx.doi.org/10.11323/jjmp.40.3_75DOI Listing
November 2020

An overview of the medical-physics-related verification system for radiotherapy multicenter clinical trials by the Medical Physics Working Group in the Japan Clinical Oncology Group-Radiation Therapy Study Group.

J Radiat Res 2020 Nov;61(6):999-1008

Department of Radiation Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.

The Japan Clinical Oncology Group-Radiation Therapy Study Group (JCOG-RTSG) has initiated several multicenter clinical trials for high-precision radiotherapy, which are presently ongoing. When conducting multi-center clinical trials, a large difference in physical quantities, such as the absolute doses to the target and the organ at risk, as well as the irradiation localization accuracy, affects the treatment outcome. Therefore, the differences in the various physical quantities used in different institutions must be within an acceptable range for conducting multicenter clinical trials, and this must be verified with medical physics consideration. In 2011, Japan's first Medical Physics Working Group (MPWG) in the JCOG-RTSG was established to perform this medical-physics-related verification for multicenter clinical trials. We have developed an auditing method to verify the accuracy of the absolute dose and the irradiation localization. Subsequently, we credentialed the participating institutions in the JCOG multicenter clinical trials that were using stereotactic body radiotherapy (SBRT) for lungs, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for several disease sites, and proton beam therapy (PT) for the liver. From the verification results, accuracies of the absolute dose and the irradiation localization among the participating institutions of the multicenter clinical trial were assured, and the JCOG clinical trials could be initiated.
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http://dx.doi.org/10.1093/jrr/rraa089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674673PMC
November 2020

Patient Health Questionnaire-9 predicts the functional outcome of stroke patients in convalescent rehabilitation ward.

Brain Behav 2020 12 20;10(12):e01856. Epub 2020 Sep 20.

Department of Neurosurgery, Suiseikai Kajikawa Hospital, Hiroshima, Japan.

Introduction: Poststroke depression (PSD) negatively affects the functional outcome of stroke patients. Patient Health Questionnaire-9 (PHQ-9) is a validated screening tool for detecting PSD. This study investigated the relationship between PHQ-9 score and functional outcomes in stroke patients in a convalescent rehabilitation ward by evaluating functional independence measure (FIM) gain scores and the proportion of patients discharged.

Methods: In this retrospective study conducted from January 2017 to September 2019, consecutive stroke patients who were admitted to the convalescent rehabilitation ward and could answer PHQ-9 were assessed. The association between PHQ-9 scores at the time of admission to the convalescent rehabilitation ward and outcomes (FIM gain score and the proportion of patients discharged) was statistically analyzed.

Results: Among the 215 patients enrolled in the study, 62 (28.8%) were assessed as having depression, in whom PHQ-9 scores were 5 or above. Multivariate analysis revealed that the PHQ-9 score on admission to the convalescent rehabilitation ward was a significant independent factor influencing the FIM gain score (p = .009). In addition, a multivariate analysis revealed that the PHQ-9 score at the time of admission to the convalescent rehabilitation ward was a significant independent factor influencing the inability to discharge a patient (odds ratio 1.24, 95% confidence interval 1.12-1.39, p < .001).

Conclusions: The PHQ-9 score is a useful tool for predicting patient functional outcome, admission to the facility, and screening for poststroke depression.
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http://dx.doi.org/10.1002/brb3.1856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749590PMC
December 2020

Population pharmacokinetics of vedolizumab in Asian and non-Asian patients with ulcerative colitis and Crohn's disease.

Intest Res 2021 Jan 10;19(1):95-105. Epub 2020 Jul 10.

Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.

Background/aims: Vedolizumab is indicated for moderately-to-severely active ulcerative colitis (UC) and Crohn's disease (CD). Because multiple factors may result in different pharmacokinetics and clinical efficacies, understanding determinants of vedolizumab clearance may enhance dose and treatment strategies. The aim was to characterize vedolizumab pharmacokinetics in Asian and non-Asian UC and CD patients.

Methods: Population pharmacokinetic analysis for repeated measures, using data from 5 studies, was conducted using nonlinear mixed-effects modeling. A Bayesian estimation approach in NONMEM 7.3 was utilized to leverage the predominantly sparse data available for this analysis with results from a prior population pharmacokinetic analysis of vedolizumab.

Results: Vedolizumab pharmacokinetics were described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half life of vedolizumab was 24.7 days for anti-vedolizumab antibody (AVA)-negative patients and 18.1 days for AVA-positive patients; linear clearance (CLL) was 0.165 L/day for AVA-negative patients and 0.246 L/day for AVA-positive patients; central (Vc) and peripheral compartment volumes of distribution were 3.16 L and 1.84 L, respectively. Interindividual variabilities (percent coefficient of variation) were 30.8% for CLL and 19% for Vc; interoccasion variability on CLL was 20.3%; residual variance was 17.8%. For albumin, body weight and AVA, only extreme values were identified as potentially clinically important predictors of CLL. The effect of race (Asian/non-Asian) and diagnosis (UC/CD) on CLL was negligible and likely not of clinical importance.

Conclusions: Pharmacokinetic parameters were similar in Asian and non-Asian patients with moderately-to-severely active UC and CD. This analysis supports use of vedolizumab flat-fixed dosing in these patients. (Clinicaltrials.gov Identifiers: NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2). CCT 101; NCT02039505 and CCT-001; NCT02038920).
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http://dx.doi.org/10.5217/ir.2019.09167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873400PMC
January 2021

Autoimmune Pulmonary Alveolar Proteinosis Complicated with Sarcoidosis: the Clinical Course and Serum Levels of Anti-granulocyte-macrophage colony-stimulating Factor Autoantibody.

Intern Med 2020 Oct 30;59(20):2539-2546. Epub 2020 Jun 30.

Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Japan.

Autoimmune pulmonary alveolar proteinosis (APAP) is caused by macrophage dysfunction due to anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody. We experienced 2 cases of APAP complicated with sarcoidosis in a 42-year-old woman and a 51-year-old man (age at the sarcoidosis diagnosis). APAP preceded sarcoidosis in the woman, and both diseases were diagnosed simultaneously in the man. Sarcoidosis lesions were observed in the lung, skin, and eyes, and the pathological findings of APAP were not marked at the diagnosis of sarcoidosis in either case. Low-grade positive serum anti-GM-CSF autoantibody was suspected to be correlated with the occurrence of sarcoidosis and resolution of APAP.
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http://dx.doi.org/10.2169/internalmedicine.3853-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662056PMC
October 2020

How Much Was the Elective Lymph Node Region Covered in Involved-Field Radiation Therapy for Locally Advanced Pancreatic Cancer? Evaluation of Overlap Between Gross Target Volume and Celiac Artery-Superior Mesenteric Artery Lymph Node Regions.

Adv Radiat Oncol 2020 May-Jun;5(3):377-387. Epub 2019 Sep 13.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Purpose: The purpose of this study was to investigate the overlaps between gross target volume (GTV) and the celiac artery (CA) and superior mesenteric artery (SMA) lymph node regions and to examine the dose incidentally irradiated to the CA and SMA lymph node regions by involved-field radiation therapy (IFRT) for locally advanced pancreatic cancer (LAPC).

Methods And Materials: Fifty-nine patients who had LAPC without distant metastasis were included. They received IFRT at 50.4 Gy in 28 fractions with 3-dimensional conformal radiation therapy. We calculated the percentages of overlap of GTV in the CA and SMA lymph node regions and examined what cases tend to have an overlap. We also investigated the dose metrics of CA and SMA lymph node regions by IFRT and the frequency of CA or SMA lymph node metastasis after IFRT.

Results: The median GTV volume was 52.2 mL. Median overlap percentages in the CA and SMA lymph node regions were 39.2% and 28.6%, respectively. There was a significant correlation between GTV volume and SMA overlap percentage ( < .001). Although the SMA overlap percentage was higher in the pancreas head ( = .028), the CA overlap percentage was higher in the pancreas body or tail ( = .002). Median mean dose, D95, and minimum dose in the CA lymph node region were 50.1 Gy, 48.7 Gy, and 45.9 Gy, respectively, and those in the SMA lymph node region 49.9 Gy, 47.3 Gy, and 39.2 Gy, respectively. CA lymph node metastases after IFRT were detected in 4 patients (6.8%).

Conclusions: An overlap between GTV and CA-SMA lymph node regions was detected in many patients, and the CA and SMA lymph node regions were irradiated incidentally even by IFRT. Prophylactic lymph node regions might not be necessary in radiation therapy planning of LAPC.
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http://dx.doi.org/10.1016/j.adro.2019.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278027PMC
September 2019

Stereotactic body radiation therapy for early-stage non-small-cell lung cancer in octogenarians and older: an alternative treatment.

J Radiat Res 2020 Jul;61(4):586-593

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Surgery is the standard modality for early-stage I-II non-small-cell lung cancer (NSCLC). Generally, patients who are >80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients >80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients >80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80-94). The median follow-up period and OS was 39.8 months (range, 10-101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0-1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were >80 years old.
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http://dx.doi.org/10.1093/jrr/rraa027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336556PMC
July 2020

Mastocytosis with sudden recurrence of rash after a 13-year interval.

J Dermatol 2020 Jul 9;47(7):e271-e272. Epub 2020 Apr 9.

Department of Dermatology, Kansai Medical University, Hirakata, Japan.

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http://dx.doi.org/10.1111/1346-8138.15347DOI Listing
July 2020

[Summary of the Report of Task Group 100 of the AAPM: Application of Risk Analysis Methods to Radiation Therapy Quality Management].

Igaku Butsuri 2020 ;40(1):28-34

Department of Radiation Oncology, National Cancer Center Hospital.

In 2016, the American Association of Physicists in Medicine (AAPM) has published a report of task group (TG) 100 with a completely new concept, entitled "application of risk analysis methods to radiation therapy quality management." TG-100 proposed implementation of risk analysis in radiotherapy to prevent harmful radiotherapy accidents. In addition, it enables us to conduct efficient and effective quality management in not only advanced radiotherapy such as intensity-modulated radiotherapy and image-guided radiotherapy but also new technology in radiotherapy. It should be noted that treatment process in modern radiotherapy is absolutely more complex and it needs skillful staff and adequate resources. TG-100 methodology could identify weakness in radiotherapy procedure through assessment of failure modes that could occur in overall treatment processes. All staff in radiotherapy have to explore quality management in radiotherapy safety.
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http://dx.doi.org/10.11323/jjmp.40.1_28DOI Listing
September 2020

Prediction of Independent Gait in Acute Stroke Patients with Hemiplegia Using the Ability for Basic Movement Scale II Score.

Eur Neurol 2020 25;83(1):49-55. Epub 2020 Mar 25.

Department of Neurosurgery, Suiseikai Kajikawa Hospital, Hiroshima, Japan.

Introduction: Since independent gait is an important factor for home discharge, early prediction of independent gait after stroke is essential. The revised version of the Ability for Basic Movement Scale II (ABMS II) has been developed and validated for assessment of basic movements poststroke.

Objective: The purpose of this study was to investigate the predictive value of the ABMS II score for independent gait in acute stroke patients with hemiplegia.

Methods: We included 67 patients with first stroke and a unilateral lesion who were admitted to the stroke care unit. We evaluated the gait on the 14th and 90th days from admission.

Results: The ABMS II score was significantly higher in patients with independent gait on both the 14th and 90th days from admission. On receiver operating characteristic curve analysis, a minimum score of 26 points was predictive of independent gait on the 14th day from admission. Similarly, a score of 15 points was predictive of independent gait on the 90th day from admission.

Conclusions: The ABMS II score is a useful predictor of independent gait in acute stroke patients with hemiplegia.
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http://dx.doi.org/10.1159/000506421DOI Listing
November 2020

High-throughput analysis revealed the unique immunoglobulin gene rearrangements in plasmacytoma-like post-transplant lymphoproliferative disorder.

Br J Haematol 2020 05 19;189(4):e164-e168. Epub 2020 Mar 19.

Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

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http://dx.doi.org/10.1111/bjh.16583DOI Listing
May 2020

Exploring the imbalance of circulating follicular helper CD4 T cells in sarcoidosis patients.

J Dermatol Sci 2020 Mar 8;97(3):216-224. Epub 2020 Feb 8.

Department of Dermatology, Kansai Medical University, Osaka, Japan.

Background: Sarcoidosis is a systemic granulomatous disease characterized by the combination of Th1 and Th17 responses. Recently, several arguments have suggested a potential involvement of B cells as well as T cells in the pathogenesis of sarcoidosis. Follicular helper CD4 T (T) cells are specialized in interacting with and helping B cells, and play a crucial role in the formation of germinal centers.

Objective: We sought to explore the status of T cells and investigate their possible pathogenic role in sarcoidosis.

Methods: T cells and B cells in peripheral blood were examined by flow cytometry, and serum samples were studied by cytokine arrays. Immunohistochemistry was performed to check for the presence of T cells in sarcoidosis skin lesions. Gene expression in isolated T cells was analyzed by quantitative RT-PCR.

Results: The proportion of circulating T cells was decreased. CD4CXCR5 T cells were observed in cutaneous lesions in sarcoidosis. Gene expression in circulating T cells and serum cytokine concentrations related to Th17 were increased in sarcoidosis patients. Gene expressions of B cell differentiation cytokines in T cells were not altered in sarcoidosis patients.

Conclusion: We herein describe a decrease of circulating T cells and their migration to affected tissues. Circulating T cells are one of the potential cell types capable of producing IL-17 and enhancing Th17 responses, and may promote the chronic inflammation. We could not demonstrate a direct linkage between the imbalance of T cells and abnormal B cell differentiation in sarcoidosis.
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http://dx.doi.org/10.1016/j.jdermsci.2020.02.002DOI Listing
March 2020

Characteristics and clinical significance of augmentation spectra in solar urticaria.

J Dermatol 2020 Apr 21;47(4):369-377. Epub 2020 Jan 21.

Department of Dermatology, Kansai Medical University, Osaka, Japan.

Solar urticaria has unique spectra, such as inhibition and augmentation. The clinical significance of these spectra, especially augmentation, is not well understood. Reported cases of solar urticaria with augmentation spectra are extremely rare in the published English-language work. The purposes of this study were to evaluate the clinical features of solar urticaria with augmentation spectra and to elucidate the mechanisms and clinical importance of the spectra. We experienced 11 cases (five females, six males; mean age, 40.1 years; range, 1-74) of solar urticaria with augmentation spectra from April 2007 to July 2019. Augmentation spectra were UV-B in three cases, UV-A in two, visible light in four, UV-A and UV-B in one, and UV-A and visible light in one. Augmentation spectra were observed before action spectra in four cases, after in six, and before and after in one. Injection of sera irradiated with action spectra and augmentation spectra in vitro induced stronger immediate reactions than those of only action spectrum-irradiated sera in four of five cases. The results of injection tests suggested that augmentation spectra enhance the production of urticaria-forming factor. Clinically, we observed severe urticarial reactions in four cases, including anaphylaxis in three and moderate urticarial reactions in three. These results suggest that augmentation spectra are not as rare as previously thought and that they are associated with the severity of solar urticaria. Therefore, phototesting for both augmentation and action spectra should be performed to provide appropriate guidance for patients with solar urticaria.
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http://dx.doi.org/10.1111/1346-8138.15234DOI Listing
April 2020
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