Publications by authors named "Osamu Ishikawa"

538 Publications

Neuroendovascular training using multisource video-recording system in a hybrid operating room.

World Neurosurg 2021 Jul 13. Epub 2021 Jul 13.

Department of Neurosurgery, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan 113-8655.

Background: Increasing restrictions over trainees' working hours and the recent coronavirus disease 2019 pandemic warrant new educational methods of surgical skills.

Objective: We assessed a novel video-recording system for neuroendovascular skill education, developed with the installation of a hybrid operating room (OR) at our institution.

Methods: A single-plane angiography unit with a large flat display (Flexvion, Philips Medical Systems) was installed in our OR. All media sources in the OR, including live fluoroscopy and ceiling-mounted camcorders, were connected to a video switcher. This video switcher laid up to eight video images into one big image, which was transferred to the large display and the professional-use blue-ray recorder. The recording was performed continuously during the procedure. This recording system was evaluated retrospectively with a questionnaire administered to the five trainees.

Results: Using this system, 68 interventional procedures were recorded. Among the potential merits, the trainees assigned the highest value to the simultaneous recording of the operator's hand motions and the fluoroscopy images. Among the potential limitations of the system, the prolonged time and the increased volume of the video data bothered the trainees the most. The recorded video looked like a live demonstration.

Conclusion: Our "selfie" video recording system was useful for skill training of neuroendovascular interventions.
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http://dx.doi.org/10.1016/j.wneu.2021.07.029DOI Listing
July 2021

Clinical course and background of eight patients who discontinued secukinumab after achieving a score of 0 on the psoriasis area and severity index.

J Dermatol 2021 May 18. Epub 2021 May 18.

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

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http://dx.doi.org/10.1111/1346-8138.15948DOI Listing
May 2021

Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress.

J Dermatol 2021 Jul 11;48(7):1052-1061. Epub 2021 Apr 11.

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Oxidative stress has been reported to play an important role in the pathogenesis of skin fibrosis in systemic sclerosis (SSc). We previously identified that botulinum toxin (BTX) injection suppresses pressure ulcer formation in a cutaneous ischemia-reperfusion injury mouse model by regulation of oxidative stress. However, the therapeutic possibility of BTX administration for preventing skin fibrosis in SSc is unclear. The objective of this study was to investigate the effect of BTX-B on skin fibrosis in a murine model of SSc and determine the underlying mechanism. We found that BTX-B injection significantly reduced dermal thickness and inflammatory cell infiltration in bleomycin-induced skin fibrosis lesion in mice. We also identified that the oxidative stress signal detected through bioluminescence in OKD48 mice after bleomycin injection in the skin was significantly decreased by BTX-B. Additionally, mRNA levels of oxidative stress associated factors (NOX2, HO-1, Trx2) were significantly decreased by BTX-B. Apoptotic cells in the lesional skin of bleomycin-treated mice were significantly reduced by BTX-B. Oxidant-induced intracellular accumulation of reactive oxygen species in SSc fibroblasts was also inhibited by BTX-B. In conclusion, BTX-B might improve bleomycin-induced skin fibrosis via the suppression of oxidative stress and inflammatory cells in the skin. BTX-B injection may have a therapeutic effect on skin fibrosis in SSc.
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http://dx.doi.org/10.1111/1346-8138.15888DOI Listing
July 2021

Rotational Angiography-Based Gamma Knife Radiosurgery for Brain Arteriovenous Malformations: Preliminary Therapeutic Outcomes of the Novel Method.

Neurosurgery 2021 Jun;89(1):60-69

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan.

Background: High-definition vascular imaging is desirable for treatment planning in Gamma Knife radiosurgery (GKRS; Elekta AB) for brain arteriovenous malformations (BAVMs). Currently, rotational angiography (RA) provides the clearest 3-dimensional visualization of niduses with high spatial resolution; however, its efficacy for GKRS has not been clarified. At our institution, RA has been integrated into GKRS (RA-GKRS) for better treatment planning and outcomes since 2015.

Objective: To evaluate RA-GKRS outcomes of BAVMs and compare them with conventional GKRS (c-GKRS) outcomes.

Methods: We retrospectively analyzed the radiosurgical outcomes of 50 BAVMs treated with RA-GKRS compared with the 306 BAVMs treated with c-GKRS. Considering possible differences in the baseline characteristics, we also created propensity score-matched cohorts and compared the radiosurgical outcomes between them to ensure comparability.

Results: The obliteration time was shorter in the RA-GKRS group (cumulative rate, 88% vs 65% at 4 yr [P = .001]). Multivariate Cox proportional hazards analysis demonstrated that the RA-GKRS group (hazard ratio 2.38, 95% CI 1.58-3.60; P = .001) had a better obliteration rate. The cumulative 4-yr post-GKRS hemorrhage rates were 4.0% and 2.6% in the RA-GKRS and c-GKRS groups, respectively (P = .558). There was a trend toward early post-GKRS signal change in the RA-GKRS group compared with the c-GKRS group (cumulative rate, 38% vs 29% at 2 yr; P = .118). Those results were also confirmed in the matched cohort analyses.

Conclusion: The integration of RA into GKRS is promising and may provide earlier nidus obliteration.
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http://dx.doi.org/10.1093/neuros/nyab066DOI Listing
June 2021

Survey of actual conditions of erythema marginatum as a prodromal symptom in Japanese patients with hereditary angioedema.

World Allergy Organ J 2021 Feb 6;14(2):100511. Epub 2021 Feb 6.

Department of Nephrology, Internal Medicine, Saiyu Soka Hospital, Soka City, Saitama, Japan.

Background: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1-INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1-INH (HAEnC1-INH). The mutations of factor XII, plasminogen, angiopoietin 1, and kininogen 1 genes may be the cause of HAEnC1-INH. Nevertheless, other causative molecules (HAE-unknown) may be involved. The Japanese therapeutic environment for HAE has been improving owing to the self-subcutaneous injection of icatibant, which was approved for the treatment of acute attack and enables early therapy. Erythema marginatum (EM) is a visible prodromal symptom which occasionally occurs prior to an angioedema attack; hence, recognizing the risk of an acute attack is important for early treatment. However, the detailed characteristics of EM remain unclear. In this study, we first investigated the clinical manifestations of EM in Japanese patients with HAE.

Methods: A 20-point survey was developed and distributed to 40 physicians to gather clinical data on EM from patients with HAE.

Results: Data on 68 patients with HAE (58 patients with HAE-1/2 and 10 patients with HAE-unknown) were collected. Of the patients with HAE-1/2, 53.4% experienced EM, whereas 43.1% did not. The forearm was the most frequent area of EM (64.5%), followed by the abdomen (29.0%) and upper arm and precordium (19.3%). Of the HAE-1/2 patients with EM, 41.9% always had angioedema following EM, while 29.0% always had colocalization of EM with angioedema. Moreover, 3.2% showed a correlation between the awareness of EM and severity of an angioedema attack. In 60.9% of HAE-1/2 patients with EM, the interval between the awareness of EM and appearance of angioedema was <3 h. Of the patients with HAE-unknown, 30.0% also experienced EM.

Conclusion: We confirmed that more than one-half of Japanese patients with HAE-1/2 and one-third of those with HAE-unknown develop EM as the prodromal symptom of an angioedema attack. Physicians should communicate the significance of EM to patients with HAE to prepare them for possible imminent attacks.
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http://dx.doi.org/10.1016/j.waojou.2021.100511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872976PMC
February 2021

Embolization of dural arteriovenous fistula during twin pregnancy - A case report and literature review.

Interv Neuroradiol 2021 Jan 28:1591019921991396. Epub 2021 Jan 28.

Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Several literature reviews have suggested that pregnancy may trigger the formation of dural arteriovenous fistulae (DAVF). However, few case reports have described DAVF discovered during pregnancy, and treatment strategies remain largely unknown. A 28-year-old primigravid woman without any medical history of note presented to our hospital for natural twin conception. She started to feel left-sided pulsatile tinnitus in 23 weeks of gestation. Magnetic resonance imaging of the head raised suspicion of left cavernous sinus DAVF with leptomeningeal venous drainage. Considering the risk of intracerebral hemorrhage due to the increased cardiac output in the third trimester of a twin pregnancy, we performed transarterial embolization for the DAVF, which was successfully achieved without complications in 28 weeks of gestation. Tinnitus resolved immediately after the procedure, and the postoperative course proved uneventful. Both fetuses were safely delivered by cesarean section on 37 1/7 weeks of gestation.

Conclusions: We encountered a case of cavernous sinus DAVF during a twin pregnancy. This case suggests that hemodynamic shift due to pregnancy has potential to cause higher shunt flow in an arteriovenous fistula. The timing of treatment should be determined in consideration of the hemodynamic change in the course of pregnancy. If X-ray exposures and iodine contrast media are appropriately managed, endovascular intervention is one treatment option, even during pregnancy.
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http://dx.doi.org/10.1177/1591019921991396DOI Listing
January 2021

A case of coexisting Bowen's disease and cutaneous pseudolymphoma.

Eur J Dermatol 2020 Dec;30(6):744-746

Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan.

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http://dx.doi.org/10.1684/ejd.2020.3912DOI Listing
December 2020

Outcomes of stereotactic radiosurgery for hemorrhagic arteriovenous malformations with or without prior resection or embolization.

J Neurosurg 2020 Dec 4:1-9. Epub 2020 Dec 4.

Departments of1Neurosurgery and.

Objective: The major concern about ruptured arteriovenous malformations (rAVMs) is recurrent hemorrhage, which tends to preclude stereotactic radiosurgery (SRS) as a therapeutic modality for these brain malformations. In this study, the authors aimed to clarify the role of SRS for rAVM as a stand-alone modality and an adjunct for a remnant nidus after surgery or embolization.

Methods: Data on 410 consecutive patients with rAVMs treated with SRS were analyzed. The patients were classified into groups, according to prior interventions: SRS-alone, surgery and SRS (Surg-SRS), and embolization and SRS (Embol-SRS) groups. The outcomes of the SRS-alone group were analyzed in comparison with those of the other two groups.

Results: The obliteration rate was higher in the Surg-SRS group than in the SRS-alone group (5-year cumulative rate 97% vs 79%, p < 0.001), whereas no significant difference was observed between the Embol-SRS and SRS-alone groups. Prior resection (HR 1.78, 95% CI 1.30-2.43, p < 0.001), a maximum AVM diameter ≤ 20 mm (HR 1.81, 95% CI 1.43-2.30, p < 0.001), and a prescription dose ≥ 20 Gy (HR 2.04, 95% CI 1.28-3.27, p = 0.003) were associated with a better obliteration rate, as demonstrated by multivariate Cox proportional hazards analyses. In the SRS-alone group, the annual post-SRS hemorrhage rates were 1.5% within 5 years and 0.2% thereafter and the 10-year significant neurological event-free rate was 95%; no intergroup difference was observed in either outcome. The exclusive performance of SRS (SRS alone) was not a risk for post-SRS hemorrhage or for significant neurological events based on multivariate analyses. These results were also confirmed with propensity score-matched analyses.

Conclusions: The treatment strategy for rAVMs should be tailored with due consideration of multiple factors associated with the patients. Stand-alone SRS is effective for hemorrhagic AVMs, and the risk of post-SRS hemorrhage was low. SRS can also be favorably used for residual AVMs after initial interventions, especially after failed resection.
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http://dx.doi.org/10.3171/2020.7.JNS201502DOI Listing
December 2020

Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial.

Allergy 2021 06 23;76(6):1789-1799. Epub 2020 Dec 23.

Hiroshima University, Hiroshima, Japan.

Background: With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long-term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once-daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients.

Methods: APeX-J is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run-in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert-confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert-confirmed attacks/month between screening and randomization) to receive once-daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert-confirmed angioedema attacks during dosing in the 24-week treatment period.

Results: Nineteen patients were randomized to receive once-daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment-emergent adverse events (TEAEs) in berotralstat-treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%).

Conclusions: Orally administered, once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.
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http://dx.doi.org/10.1111/all.14670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247297PMC
June 2021

Preliminary study of eye tracking to investigate the differences in gaze behaviors depending on the experience of neuroendovascular therapy.

Surg Neurol Int 2020 21;11:351. Epub 2020 Oct 21.

Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Background: Neuroendovascular therapy is now the choice for the management of many neurovascular pathologies, and physicians with endovascular skills are in high demand. In addition to the traditional method of practicing hand movements to learn skills, a new strategy of practicing eye movements to learn skills is also attracting attention. This preliminary study explored the differences in gaze behavior depending on experience with endovascular procedures to be facilitated in future skill training in neuroendovascular therapy.

Methods: Four physicians with experience of 3-412 neuroendovascular procedures wore eye-tracking devices during coil embolization of swine cervical arteries. Gaze metrics with direct correlations to the expertise of endovascular procedures were explored.

Results: Gaze metrics with a positive direct correlation to experience included the proportion of fixation durations (PFD) in the screen area and the native images. Those with a negative direct correlation included the PFD in the off-screen area and the roadmap images and the average fixation durations in the off-screen and coil areas. During the parent artery occlusion procedure with detachable coils, more experienced operators preferred to look at native images rather than roadmap images and that less experienced operators tended to look down at their hands more frequently.

Conclusion: This preliminary study demonstrated the feasibility of eye tracking to identify the differences in gaze behavior depending on the experience of endovascular procedures and may guide future eye-tracking studies in neuroendovascular therapy.
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http://dx.doi.org/10.25259/SNI_543_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656012PMC
October 2020

Neurosurgical versus endovascular treatment of spinal dural arteriovenous fistulas: a multicenter study of 195 patients.

J Neurosurg Spine 2020 Nov 13:1-8. Epub 2020 Nov 13.

8Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital, Tokyo.

Objective: The purpose of the present study was to compare the treatment success rates of primary neurosurgical and endovascular treatments in patients with spinal dural arteriovenous fistulas (dAVFs).

Methods: Data from 199 consecutive patients with thoracic and lumbosacral spinal dAVFs were collected from 18 centers. Angiographic and clinical findings, the rate of initial treatment failure or recurrence by procedures, risk factors for treatment failure, complications, and neurological outcomes were statistically analyzed.

Results: Spinal dAVFs were frequently detected in the thoracic region (81%), fed by a single feeder (86%), and shunted into an intradural vein via the dura mater. The fistulous connection between the feeder(s) and intradural vein was located at a single spinal level in 195 patients (98%) and at 2 independent levels in 4 patients (2%). Among the neurosurgical (n = 145), and endovascular (n = 50) treatment groups of single dAVFs (n = 195), the rate of initial treatment failure or recurrence was significantly higher in the index endovascular treatment group (0.68% and 36%). A multivariate analysis identified endovascular treatment as an independent risk factor with significantly higher odds of initial treatment failure or recurrence (OR 69; 95% CI 8.7-546). The rate of complications did not significantly differ between the two treatment groups (4.1% for neurosurgical vs 4.0% for endovascular treatment). With a median follow-up of 26 months, improvements of ≥ 1 point in the modified Rankin Scale (mRS) score and Aminoff-Logue gait and Aminoff-Logue micturition grades were observed in 111 (56%), 121 (61%), and 79 (40%) patients, respectively. Independent risk factors for lack of improvement in the Aminoff-Logue gait grades were multiple treatments due to initial treatment failure or recurrence (OR 3.1) and symptom duration (OR 1.02).

Conclusions: Based on data obtained from the largest and most recently assessed multicenter cohort, the present study shows that primary neurosurgery is superior to endovascular treatment for the complete obliteration of spinal dAVFs by a single procedure.
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http://dx.doi.org/10.3171/2020.6.SPINE20309DOI Listing
November 2020

Suppression of neuropeptide by botulinum toxin improves imiquimod-induced psoriasis-like dermatitis via the regulation of neuroimmune system.

J Dermatol Sci 2021 Jan 6;101(1):58-68. Epub 2020 Nov 6.

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan. Electronic address:

Background: Psoriasis is a multifactorial disease arises from a complex interaction of genetics, immune system, and environmental aspects. IL-23/Th17 immune axis has been considered as a primary modulator in psoriasis. In addition, several findings imply that nervous system may take a part in the pathogenesis of psoriasis, suggesting that nervous system, through its neuropeptide, may interact with immune system and lead to the formation of psoriasis.

Objective: We aimed to ascertain the role of neuropeptides secreted from neurons in the pathogenesis of psoriasis in vivo.

Methods: The release of neuropeptide was inhibited by injecting Botulinum toxin B (BTX-B) on Imiquimod (IMQ)-induced psoriasis-like dermatitis mice model. Quantification of skin dermatitis, infiltrating inflammatory cells, and the production of cytokines at the lesional skin area were performed by PSI score, immunostaining, and real-time PCR. We also tested the effect of selective CGRP antagonist (CGRP) on psoriasis-like dermatitis in IMQ-treated mice.

Results: BTX-B injection significantly suppressed PSI score and reduced the number of CD4 T cells, CD11c dendritic cells, and the production of IL-17A/F in the lesional skin. The expressions of PGP9.5 nerve fibers and neuropeptides (SP, CGRP) were also significantly reduced following BTX-B injection. Additionally, CGRP antagonist also suppressed the development of IMQ-induced psoriasis-like dermatitis in mice.

Conclusion: The suppression of neuropeptide secretion in the skin by BTX injection might inhibit nerve elongation, the infiltration of immune cells, as well as IL-17 production, resulting in the improvement of psoriasis. Neuropeptide inhibitor could also be applied to the treatment of psoriasis.
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http://dx.doi.org/10.1016/j.jdermsci.2020.11.003DOI Listing
January 2021

The clinical impact of splenic artery ligation on the occurrence of digestive varices after pancreaticoduodenectomy with combined portal vein resection: a retrospective study in two institutes.

Langenbecks Arch Surg 2020 Oct 15. Epub 2020 Oct 15.

Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan.

Purpose: Pancreaticoduodenectomy (PD) concomitant with portal vein resection (PVR) often develops into digestive varices with an occurrence rate of 30-50%, and the variceal bleeding is sometimes untreatable and results in fatality. Against this issue, splenic artery (SpA) ligation during PD-PVR is emerging as an easy and effective prophylactic surgical option. The aim of this study was to investigate the significance of SpA ligation in the development of digestive varices in patients undergoing PD-PVR.

Method: We retrospectively investigated 97 patients with PDAC who received PD-PVR in two hospitals. Vascular reconstruction of the splenic vein (SpV) was not performed in either hospital. We assessed the occurrence rate of digestive varices in these patients in association with the performance of SpA ligation.

Results: The occurrence rate of digestive varices was 23%. SpA ligation was the only significant decreasing factor for the development of digestive varices (odds ratio 0.3, p = 0.035). Although SpV resection was not a significant risk factor for the development of digestive varices in all patients, SpV resection was a significant risk factor for the development of digestive varices in patients without SpA ligation, as demonstrated in previous reports. SpA ligation did not increase surgical complications or impair pancreatic function.

Conclusion: PD-PVR surgery was accompanied by a 23% incidence of digestive varices, and SpA ligation significantly decreased the development of digestive varices without causing clinically significant complications.

Trial Registration: No. 18196 (Osaka International Cancer Institute) and no. 19006 (National Hospital Organization Osaka National Hospital).
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http://dx.doi.org/10.1007/s00423-020-02010-xDOI Listing
October 2020

Characteristics of Japanese patients with eosinophilic fasciitis: A brief multicenter study.

J Dermatol 2020 Dec 29;47(12):1391-1394. Epub 2020 Aug 29.

Department of Dermatology, Kumamoto University, Kumamoto, Japan.

Eosinophilic fasciitis is a relatively rare cutaneous fibrotic condition affecting the deep fascia of the extremities, with or without peripheral blood eosinophilia. To examine the characteristics of Japanese patients with eosinophilic fasciitis, we conducted a brief, multicenter, retrospective survey at seven university hospitals. In total, 31 patients were identified as having eosinophilic fasciitis, among whom 30 patients fulfilled the Japanese diagnostic criteria. The male : female ratio was 2.3:1, and the mean age was 47.7 years. Three of the patients were under 20 years old. The possible triggering factors included muscle training, sports, walking or sitting for a long time, physical work, insect bite and drug. Co-occurrence of morphea was observed in nine cases (29%), and malignancies were associated in three (two hematological malignancies and one internal malignancy). Immunological abnormalities in the serum showed positive antinuclear antibody, positive rheumatoid factor, increased aldolase levels and increased immunoglobulin G levels. The patients were treated with either monotherapy or combination therapy by oral prednisolone (20-80 mg/day), methotrexate (6-10 mg/week), cyclosporin (100-150 mg/day), mizoribine, infliximab and phototherapy. Methylprednisolone pulse therapy was performed in six cases. By contrast, spontaneous improvement due to resting only was observed in two cases, and skin hardening was improved by withdrawal of the anticancer drug in one case. This study suggests several characteristics of Japanese patients with eosinophilic fasciitis, namely male predominance, rare pediatric occurrence, immunological abnormalities and coexistence with morphea. Systemic prednisolone is the first-line therapy, but pulse therapy is occasionally required for severe cases. The triggering events of physical stress are not so frequent as have previously been reported, and various factors or even unknown factors may be associated with the induction of eosinophilic fasciitis.
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http://dx.doi.org/10.1111/1346-8138.15561DOI Listing
December 2020

Expression of long interspersed nuclear elements-1 as a surrogate marker for global genomic hypomethylation of malignant skin tumors.

J Dermatol Sci 2020 Sep 3;99(3):213-215. Epub 2020 Aug 3.

Department of Dermatology, Gunma University Graduate School of Medicine, Japan.

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http://dx.doi.org/10.1016/j.jdermsci.2020.07.008DOI Listing
September 2020

Stent-Assisted Coil Embolization of a Basilar Artery Dissecting Aneurysm Involved in Skull Base Chordoma Before Endoscopic Transsphenoidal Transclival Resection.

World Neurosurg 2020 11 11;143:466-470. Epub 2020 Aug 11.

Department of Neurosurgery, The University of Tokyo, Tokyo, Japan.

Background: Skull base chordomas will occasionally penetrate the clival dura mater and extend into the prepontine cistern, involving the basilar artery. Few reports have described cases of skull base chordoma accompanying a dissecting aneurysm of the basilar artery, and the treatment strategies have remained largely unknown.

Case Description: A 28-year-old man was referred to our hospital with a complaint of severe headache. A skull base chordoma involving a basilar artery dissecting aneurysm was diagnosed. We initially performed endovascular surgery for the dissecting aneurysm after dual antiplatelet therapy before surgical resection of the tumor, which was successfully achieved without complications. Follow-up angiography 3 months after endovascular surgery disclosed obliteration of the dissecting aneurysm. We then stopped the dual antiplatelet therapy, and performed judicious resection using an endoscopic transclival approach. The residual tumor was treated with radiosurgery. At the last follow-up examination, the patient was stable, and the tumor remained sufficiently controlled.

Conclusions: We have reported a case of a dissecting aneurysm of the basilar artery with clival chordoma. Our findings suggest that chordoma with intradural vascular encasement has the potential to invade the vessel wall. To avoid rupture of those critical vascular structures, treatment strategies that minimize stress on the involved arteries and offer safe and sufficient surgical resection should be considered.
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http://dx.doi.org/10.1016/j.wneu.2020.08.054DOI Listing
November 2020

Clinical features of anti-transcription intermediary factor 1γ (TIF1γ)-positive dermatomyositis with internal malignancy and investigation of the involvement of TIF1γ expression in tumors in the pathogenesis of cancer-associated dermatomyositis.

J Dermatol 2020 Dec 30;47(12):1395-1402. Epub 2020 Jul 30.

Departments of, Department of, Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibody (Ab) is significantly associated with internal malignancies in adult patients with dermatomyositis (DM). Although pathogenesis of cancer-associated DM is unknown, TIF1γ overexpression in tumors has been considered to be critical for the development of DM. The objective of this study was to investigate clinical characteristics of patients with anti-TIF1γ Ab-positive DM and elucidate risk factors that are potentially associated with internal malignancy. In addition, we compared the expression of TIF1γ in tumor tissues of patients with anti-TIF1γ Ab-positive DM, anti-TIF1γ Ab-negative DM and without DM in order to investigate the pathogenesis of cancer-associated DM. We analyzed 77 Japanese patients with DM, and found 19 patients to be positive for anti-TIF1γ Ab. Patients with anti-TIF1γ Ab-positive DM were older and presented heliotrope rash and flagellate erythema more frequently than patients without anti-TIF1γ Ab (P < 0.05). Interstitial lung disease (ILD) and rapidly progressive ILD, as well as palmar violaceous erythema, were less frequent in patients with anti-TIF1γ Ab than in patients without. Furthermore, internal malignancy and dysphagia were significantly more frequent in the anti-TIF1γ Ab-positive group (P < 0.01). Male sex and dysphagia were significantly associated with internal malignancy in patients with anti-TIF1γ Ab-positive DM (P < 0.01 and <0.05, respectively). Using immunohistochemistry, we examined the TIF1γ expression in tumors of 11 patients with cancer-associated DM (anti-TIF1γ Ab-positive, nine; anti-TIF1γ Ab-negative, two) and 25 patients without DM. TIF1γ was highly expressed in all tumors, and there was no significant difference in TIF1γ expression between patients with and without DM. Furthermore, TIF1γ expressions in tumors were similar irrespective of the presence of anti-TIF1γ Ab. These results suggest that anti-TIF1γ antibody may not be simply induced by overexpression of TIF1γ in tumors in patients with DM, but that other mechanisms may exist.
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http://dx.doi.org/10.1111/1346-8138.15526DOI Listing
December 2020

Peculiar Characteristics of Arteriovenous Malformations Arising in the Galenic Region.

Diagnostics (Basel) 2020 Jul 15;10(7). Epub 2020 Jul 15.

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo 1138655, Japan.

Arteriovenous malformations (AVM) are congenital vascular lesions fed by arterial feeders originating from branches of the internal carotid artery (ICA) or vertebrobasilar artery. We experienced unique AVMs arising in the midline Galenic region, receiving blood supply from the ICA/vertebral artery systems and the external carotid artery system. We retrospectively reviewed data on eight patients who had an AVM arising in the Galenic region and were treated in the University of Tokyo Hospital between 1990 and 2019. The median age at diagnosis was 62 years. Three cases (38%) presented with obstructive hydrocephalus due to aqueduct obstruction caused by an engorged vein of Galen. In all cases, feeders from dural arteries were present and the vein of Galen was the primary drainer. All patients underwent stereotactic radiosurgery. Five patients were followed for > two years; nidus obliteration was confirmed in one, and > 75% shrinkage was confirmed in three, while one patient died due to hemorrhage. Altogether, AVMs arising in the Galenic region are rare and exhibit several peculiar characteristics including the presence of dural feeders, an older age at presentation and presentation with obstructive hydrocephalus.
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http://dx.doi.org/10.3390/diagnostics10070481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400176PMC
July 2020

Fatal case of toxic epidermal necrolysis due to apalutamide used as a novel prostate cancer drug.

J Dermatol 2020 Oct 14;47(10):e359-e360. Epub 2020 Jul 14.

Department of, Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.

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http://dx.doi.org/10.1111/1346-8138.15510DOI Listing
October 2020

Atypical Hidradenitis Suppurativa on the Leg in a Psoriatic Patient.

Indian J Dermatol 2020 May-Jun;65(3):231-232

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan E-mail:

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http://dx.doi.org/10.4103/ijd.IJD_20_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292468PMC
June 2020

Clinical implications of the serum CA19-9 level in "biological borderline resectability" and "biological downstaging" in the setting of preoperative chemoradiation therapy for pancreatic cancer.

Pancreatology 2020 Jul 6;20(5):919-928. Epub 2020 Jun 6.

Department of Surgery, Osaka International Cancer Institute, Japan.

Background: Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and "biological downstaging" in chemoradiation therapy (CRT) for pancreatic cancer (PC).

Methods: A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. "Biological downstaging" was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor).

Results: The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986).

Conclusions: Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated "biological downstaging" in b-BR in the preoperative CRT strategy.
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http://dx.doi.org/10.1016/j.pan.2020.05.020DOI Listing
July 2020

S-shaped distal access catheter supported microcatheter navigation into the lenticulostriate artery feeders of brain arteriovenous malformations.

Interv Neuroradiol 2020 Dec 19;26(6):725-732. Epub 2020 Jun 19.

Department of Neurosurgery, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Background: Although the embolization of lenticulostriate artery feeders is often warranted in the treatment of brain arteriovenous malformations, it is technically challenging due to steep and repeated angulations. Here, we describe our novel technique of navigating a flow-guided microcatheter into lenticulostriate artery feeders using the strong support provided by an S-shaped distal access catheter.

Methods: We reviewed our retrospective cohort of brain arteriovenous malformations, in which lenticulostriate artery feeders were attempted to embolize.

Result: During the study period, endovascular embolization was performed in 25 arteriovenous malformations cases. Of these, eight lenticulostriate artery feeders were present in six cases (24%). In two cases, lenticulostriate artery feeder catheterization was avoided from the beginning due to the small diameters of the feeders. After all, microcatheter navigation for lenticulostriate artery feeders were attempted in four cases with six lenticulostriate artery feeders. In all the six feeders, the S-shaped distal access catheter was successful in supporting the microcatheter to advance distally to the lenticulostriate artery feeders, even if other approaches were unsuccessful. Of the six catheterized lenticulostriate artery feeders, four were embolized. Symptomatic infarction in the lenticulostriate artery territory and mild vasospasm occurred in two cases each, but they did not result in permanent neurological deficits.

Conclusion: Although some potential complications need to be considered, the S-shaped distal access catheter technique appears to be an effective alternative approach to gaining access to difficult feeders of arteriovenous malformations.
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http://dx.doi.org/10.1177/1591019920935275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724592PMC
December 2020

Initial predictors of skin thickness progression in patients with diffuse cutaneous systemic sclerosis: Results from a multicentre prospective cohort in Japan.

Mod Rheumatol 2021 Mar 20;31(2):386-393. Epub 2020 Jul 20.

Department of Molecular Pathology of Skin, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.

Objective: To identify initial parameters that predict worsening of skin thickening in patients with diffuse cutaneous systemic sclerosis (dcSSc) using a multicentre, prospective, observational cohort in Japan.

Methods: A total of 171 patients with dcSSc were selected from a prospective cohort database based on the following criteria: dcSSc, modified Rodnan total skin thickness score (mRSS) ≥7, disease duration <60 months, and valid mRSS data at one year. Worsening of skin thickness was defined as an increase in mRSS ≥3 points and an increase ≥25% from baseline to one year. Initial demographic and clinical parameters useful for predicting the progression of skin thickness were identified using univariate and multivariable analysis, and prediction models of skin thickening progression were built based on combinations of independent predictive parameters.

Results: Only 23 patients (13.5%) experienced worsening mRSSs at one year. Short disease duration, low mRSS, absence of nailfold bleeding, arthritis, and a high erythrocyte sedimentation rate at diagnosis were identified as predictors of subsequent worsening of the mRSS even after adjusting for the treatment. Assessment of the best predictive model revealed that patients with a disease duration ≤12 months and mRSS ≤19 had a risk of mRSS worsening within one year, with a sensitivity of 73.9% and specificity of 81.1%.

Conclusion: Identification of predictors of subsequent worsening of skin thickness in dcSSc patients is useful for identifying patients who require intensive treatment with potential disease-modifying agents and for improving clinical trial design by characterizing eligible progressors in the Japanese population.
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http://dx.doi.org/10.1080/14397595.2020.1784548DOI Listing
March 2021

A predictive score for identification of rupture site in subarachnoid haemorrhage with multiple intracranial aneurysm.

Br J Neurosurg 2021 Apr 8;35(2):145-150. Epub 2020 Jun 8.

Department of Neurosurgery, Showa General Hospital, Tokyo, Japan.

Purpose: The rigid method of identifying the rupture site in cases of subarachnoid haemorrhage (SAH) with multiple intracranial aneurysms (MIAs) is still unclear. Here we present a reliable method by using a combination of six predictors.

Materials And Methods: Concerning the 48 SAH patients with MIAs who visited the Showa General Hospital during the period from January 2005 to March 2016, several predictors of rupture site such as the aneurysm-related morphologic features (size, aspect ratio, shape, bleb), aneurysm location, and the distribution of SAH were investigated. Compared with other coexisting aneurysms in each predictor, each aneurysm was categorized into 'suspicion' or 'non-suspicion', and we analyzed the association between 'suspicion' and rupture.

Results: In the first analysis, all variables were associated with rupture and included in the multivariate logistic regression analysis. The presence of bleb (OR, 20.7; CI, 2.3-186;  = .007) and the aneurysm location (OR, 23.5; CI, 5.2-106;  < .001) were significantly associated with rupture in multivariate logistic regression analysis. Based on the results, a predictive score for rupture was created and calculated for each aneurysm, and the aneurysm with highest predictive score in each patient was categorized into 'suspicion'. 'Suspicion' in the predictive score was significantly associated with rupture (OR, 412.5; CI, 52.2-16384;  < .001). The sensitivity (0.90), specificity (0.98) and the accuracy (0.94) of identifying the rupture site by the predictive score were quite satisfactory.

Conclusion: Our results suggest that the predictive score may be an excellent parameter to identify the rupture site in cases of SAH with MIAs.
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http://dx.doi.org/10.1080/02688697.2020.1775783DOI Listing
April 2021

Pseudofailure of Ventriculoperitoneal Shunt due to Drug-Resistant Constipation, Dramatically Responsive to Rectal Tube Placement: Pitfall Case Series of Avoidable Shunt Revision.

World Neurosurg 2020 09 24;141:131-136. Epub 2020 May 24.

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan.

Background: Ventriculoperitoneal shunt placement is a common standard treatment for hydrocephalus, and these shunts function appropriately in the presence of a pressure gradient between the ventricular and abdominal cavities.

Case Description: We encountered 2 cases of shunt malfunction that was due to an increase in intra-abdominal pressure, mainly caused by constipation and excessive accumulation of enteric gas. Although aggressive bowel regimens were implemented, this management failed in both patients. Careful physical examination revealed unusually elevated tonus of the anus sphincter muscle, and a fecal incontinence catheter was inserted into the rectum. Following this procedure, constipation rapidly improved together with a marked reduction in enteric gas, leading to a normalization of ventricular size on imaging and neurologic improvements. Both patients were able to avoid unnecessary surgical exploration or shunt revision.

Conclusions: Constipation is one of the differential diagnoses of ventriculoperitoneal shunt malfunction, and bowel regimens are the first-line treatment. However, some cases can prove resistant to medical therapy, and mechanical tube placement can provide an alternative or additional solution. Before proceeding to surgical exploration, the intra-abdominal environment should be properly assessed and every option should be explored to address underlying causes of shunt failure to avoid unnecessary intervention.
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http://dx.doi.org/10.1016/j.wneu.2020.05.169DOI Listing
September 2020

Demographic and clinical characteristics of cytomegalovirus reactivation in dermatomyositis.

J Dermatol 2020 Aug 26;47(8):876-881. Epub 2020 May 26.

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Dermatomyositis (DM) patients are known to have various infectious complications, such as cytomegalovirus (CMV) reactivation, due to immune dysfunction caused by DM itself and immunosuppressants used for treatment. Although CMV reactivation has been known to be a major cause of mortality in immunocompromised hosts, there has not been sufficient study of CMV reactivation in DM patients. The objective of this study was to examine the frequency of CMV reactivation in DM patients and to investigate risk factors potentially associated with development of CMV reactivation. We analyzed 52 Japanese DM patients, and CMV reactivation was observed in 21 (40.4%). The mean duration from the initiation of prednisolone (PSL) to the diagnosis of CMV reactivation was 6.1 ± 0.5 weeks. The total amount of oral PSL before the diagnosis of CMV reactivation was 2000.3 ± 169.3 mg. Using a univariate analysis, we found that the prevalence of interstitial lung disease and the frequency of diabetes mellitus complications in DM patients with CMV reactivation was significantly higher than that in DM patients without CMV. We identified that low lymphocytes (<900/μL) in DM patients was significantly associated with developing CMV reactivation. The use of immunosuppressants, including tacrolimus, cyclosporin and/or i.v. cyclophosphamide, was significantly associated with CMV reactivation in DM patients. Using a multivariate analysis, low lymphocytes at the time of DM diagnosis was found to be a risk factor for CMV reactivation. In addition, there was a tendency for diabetes mellitus to be a risk factor for CMV reactivation in DM patients. There was no difference in the prognosis for those with or without CMV reactivation in this study. These results suggest that in the DM patients with risk factors such as low lymphocytes and diabetes mellitus complications, regularly monitoring CMV reactivation and adequate treatment with antiviral agents may be necessary to prevent a poor prognosis.
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http://dx.doi.org/10.1111/1346-8138.15409DOI Listing
August 2020

The synchronized gene expression of retrotransposons and type I interferon in dermatomyositis.

J Am Acad Dermatol 2021 Apr 19;84(4):1103-1105. Epub 2020 May 19.

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

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http://dx.doi.org/10.1016/j.jaad.2020.05.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234944PMC
April 2021