Publications by authors named "Shigeo Hara"

125 Publications

Fascioliasis Presenting With Migrating Liver Masses.

Am J Trop Med Hyg 2021 Jul 12. Epub 2021 Jul 12.

2Department of Pathology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.

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http://dx.doi.org/10.4269/ajtmh.21-0539DOI Listing
July 2021

Gastrointestinal perforation following dabrafenib and trametinib administration in non-small cell lung carcinoma with BRAF V600E mutation: a case report and literature review.

Invest New Drugs 2021 May 23. Epub 2021 May 23.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-Ku, Kobe, 650-0047, Japan.

Gastrointestinal perforation related to mitogen-activated protein kinase kinase (MEK) inhibitors has been reported previously; however, there has been no case report of such a condition in patients with non-small cell lung cancer (NSCLC). Herein, we report a case of small intestinal perforation secondary to dabrafenib and trametinib administration, but not related to tumor regression. A 62-year-old man with non-small cell lung cancer harboring BRAF V600E mutation was treated with dabrafenib and trametinib. Four months after the initiation of treatment, a small intestinal perforation was diagnosed. Dabrafenib and trametinib rechallenge was performed after gastrointestinal perforation. The patient responded well to therapy and did not experience recurrence of gastrointestinal perforation. To the best of our knowledge, this is the first report of gastrointestinal perforation in a patient with NSCLC treated with a MEK inhibitor. The mechanism and risk factors of trametinib-induced perforation are currently unknown. Physicians should be aware of such severe gastrointestinal side effects of trametinib.
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http://dx.doi.org/10.1007/s10637-021-01135-0DOI Listing
May 2021

Discordant Immune Marker Expression Between Preoperatively Biopsied and Matched Surgically Resected Specimens in Patients With Oral Squamous Cell Carcinoma.

Cureus 2021 Apr 11;13(4):e14423. Epub 2021 Apr 11.

Department of Otolaryngology, Head and Neck Surgery, Kobe City Medical Center General Hospital, Kobe, JPN.

Programmed cell death ligand 1 (PD-L1) expression and tumor-associated immune cell (TAIC) density can be the biomarkers of survival outcome and for predicting the efficacy of immune checkpoint inhibitors in oral squamous cell carcinoma (OSCC), but whether single biopsy accurately reflects the values of these parameters in resected specimens is unclear. To clarify this, we evaluated the concordance of immune marker expression (PD-L1, PD-1, CD3, CD4, CD8, and CD68) between 39 paired biopsied and surgically resected specimens obtained from patients with OSCC at Kobe City Medical Center General Hospital between July 2011 and January 2016. Immune marker expression was assessed using immunohistochemistry. PD-L1 expression was consistent between the biopsied and surgically resected specimens in only 76.9% of cases. TAIC density was significantly lower in biopsied than in surgically resected specimens. There was considerable discordance in immune marker expression between biopsied and surgically resected specimens. We should take into consideration that PD-L1 positivity and TAIC density would be underestimated by single small biopsies compared to the estimations by surgically resected specimens.
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http://dx.doi.org/10.7759/cureus.14423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112876PMC
April 2021

Reversible renal-limited thrombotic microangiopathy due to gemcitabine-dexamethasone-cisplatin therapy: a case report.

BMC Nephrol 2021 May 12;22(1):175. Epub 2021 May 12.

Department of Hematology, Kobe City Medical Center General Hospital, 2-1-1 Minami-machi, Minatojima, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.

Background: Gemcitabine and cisplatin are chemotherapeutic agents used for treating multiple cancers, and these agents are sometimes used in combination. Drug-induced thrombotic microangiopathy (TMA) is a rare but potentially fatal complication. It typically presents as a systemic disease with the classical triad of hemolytic anemia, thrombocytopenia, and organ damage. In contrast to systemic TMA, cases of renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad, have been reported with relatively good prognosis. Most cases of renal-limited TMA are associated with calcineurin inhibitors, and cases of drug-induced renal-limited TMA due to gemcitabine-dexamethasone-cisplatin therapy have been rarely reported.

Case Presentation: A 43-year-old woman with lymphoma developed acute kidney injury with marked proteinuria, microhematuria, and abnormal urinary casts after receiving one cycle of gemcitabine-dexamethasone-cisplatin therapy. Although she did not show hemolytic anemia and thrombocytopenia, renal biopsy showed diffuse injury to the glomerular endothelial cells, supporting the diagnosis of renal-limited TMA. Her condition improved only with the cessation of gemcitabine and cisplatin treatment. She received another chemotherapy without gemcitabine and platinum agents, and no recurrence of renal-limited TMA was observed.

Conclusions: Drug-induced TMA occurs early after gemcitabine and cisplatin use in renal-limited form and is reversible when detected and managed in a timely manner. Urinalysis, which is simple and inexpensive and can be easily performed, is a beneficial screening tool for early-onset drug-induced TMA among patients who receive gemcitabine-dexamethasone-cisplatin therapy.
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http://dx.doi.org/10.1186/s12882-021-02386-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114690PMC
May 2021

[Surgical Excision of Calcified Amorphous Tumors on Mitral and Aortic Valves:Report of a Case].

Kyobu Geka 2021 Feb;74(2):134-137

Department of Cardiovascular Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.

Calcified amorphous tumor (CAT) is a nonneoplastic cardiac tumor that can be located in any of the four cardiac chambers, but is predominantly detected on the mitral valve. We report a rare case of CAT originating from the mitral and aortic valves. A 69-year-old woman with end-stage renal disease, hypertension, and diabetes mellitus was referred to our hospital for the evaluation of cardiac masses found incidentally on screening transthoracic echocardiography. She had no symptoms, including fever and neurological deficits, and her blood cultures were negative. Echocardiography revealed mobile masses arising from the mitral and aortic valves. We performed surgical excision and histopathologically diagnosed the masses with cardiac CATs. Mobile and pedunculated CAT frequently causes systemic embolization, and thus, complete surgical excision is recommended in such a case.
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February 2021

Dramatic response to encorafenib in a patient with Erdheim-Chester disease harboring the BRAF mutation.

Am J Hematol 2021 Aug 26;96(8):E295-E298. Epub 2021 May 26.

Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.

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http://dx.doi.org/10.1002/ajh.26232DOI Listing
August 2021

TAFRO syndrome presenting as intrahepatic cholangitis on autopsy.

Clin Case Rep 2021 Apr 3;9(4):2254-2258. Epub 2021 Mar 3.

Department of Pathology Kobe City Medical Center General Hospital Kobe Japan.

Elevation of ALP is an abnormal feature in TAFRO syndrome, but the cause is unknown. This article is the first report that histologically showed intrahepatic cholangitis may be the cause of ALP elevation in TAFRO syndrome.
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http://dx.doi.org/10.1002/ccr3.4005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077398PMC
April 2021

Moyamoya disease with refractory hypertension associated with peripheral arterial stenosis in the renal parenchyma.

CEN Case Rep 2021 Apr 7. Epub 2021 Apr 7.

Department of Nephrology, Hyogo Prefectural Kobe Children's Hospital, 1-6-7 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.

Moyamoya disease (MMD) has long been known to be associated with hypertension. While renal artery stenosis (RAS) is considered one of the causes of hypertension with MMD, most hypertension causes remain unexplained. A boy with MMD was diagnosed with renovascular hypertension (RVH) due to left-sided RAS by angiography. Although nephrectomy on the affected side for unilateral RVH was performed, hypertension poorly improved. Histopathological examination of the resected specimens revealed that the vascular lumen not only of the renal artery but also of peripheral vessels in the renal parenchyma was narrowed. He developed end-stage renal disease caused by multiple wasp stings and received a kidney transplant from a living donor with his remaining right kidney resected. His hypertension improved dramatically just after the operation. In histopathological findings, the narrowed vascular lumen was also observed in the resected right renal parenchyma similar to that in the left kidney. In our case, these pathological findings were the same as those of major vessels previously reported in MMD patients. Immunohistochemical staining with anti-renin antibody on bilateral intrinsic kidneys was strongly revealed in the Juxtaglomerular apparatus. He has been normotensive with the minimum amount of amlodipine since transplantation and resection of his intrinsic right kidney. This is the first report to show the possibility that peripheral arterial stenosis in the renal parenchyma due to MMD would result in refractory hypertension. If MMD patients have hypertension of unknown origin without significant RAS, it should be considered that the etiology may be peripheral arterial stenosis in the renal parenchyma.
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http://dx.doi.org/10.1007/s13730-021-00594-xDOI Listing
April 2021

Anti-glomerular Basement Membrane Disease with Antiphospholipid Syndrome.

Intern Med 2021 Jul 22;60(14):2255-2260. Epub 2021 Feb 22.

Department of Nephrology, Nagasaki University Hospital, Japan.

A 48-year-old woman presented with a fever, microscopic hematuria, proteinuria, and rapid deterioration of the renal function. Pulmonary alveolar hemorrhaging and a high level of anti-glomerular basement membrane (GBM) antibodies (700 IU/mL) were observed. Based on her medical history and positive findings of serum lupus anticoagulant, anti-phospholipid antibody syndrome (APS) was suspected. A renal biopsy revealed cellular crescentic glomerulonephritis with thrombosis, suggesting anti-GBM disease with catastrophic APS. The patient was treated with pulse steroid therapy, plasma exchange, hemodialysis, and intravenous cyclophosphamide pulse therapy. To our knowledge, this is the first report of a patient with anti-GBM disease and APS.
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http://dx.doi.org/10.2169/internalmedicine.4943-20DOI Listing
July 2021

Chest wall pseudotumor: a case of non-tuberculous mycobacterial infection.

BMC Infect Dis 2021 Feb 19;21(1):196. Epub 2021 Feb 19.

The Department of General Thoracic Surgery, Kobe City Medical Centre General Hospital, 2-2-1, Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.

Background: Non-tuberculous mycobacterial (NTM) infections are increasing worldwide, making them an international public health problem. Surgical management is often indicated for localized infectious disease; however, most surgeons are unaware of the potential risks of transmission during surgery.

Case Presentation: An 88-year-old Asian female was referred to our hospital for a tumor in the right lateral thoracic region. One month prior, she had a feeling of fullness and complained of localized pain and warmth in the right lateral thoracic wall. Pain and warmth gradually resolved without intervention; however, the fullness was getting worse. Computed tomography (CT) scan showed a mass of approximately 65 × 30 mm with an osteolytic change, involving the right 8th rib. Based on the rapid growth rate and CT findings, we strongly suspected a malignant chest wall tumor, and en bloc tumor resection with the 8th rib was performed. When the specimen was cut, a large amount of viscous pus was drained and its culture showed growth of Mycobacterium avium. Microscopically, the non-caseating epithelioid cell granuloma extended into the rib, infiltrating the bone cortex. On follow-up 1 month after discharge, there were no signs of infection or other adverse events associated with the surgery.

Conclusions: Herein, we report about a patient with a mass diagnosed as an NTM abscess involving the rib cage, which was confused with a malignant tumor and eventually diagnosed following surgical excision. This report emphasizes the need to be aware of the possibility of NTM infection and take appropriate precautions if the patient has a rapidly growing mass in the chest wall.
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http://dx.doi.org/10.1186/s12879-021-05843-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893767PMC
February 2021

Underwater endoscopic mucosal resection for complete R0 removal of colorectal polyp in a patient with ulcerative colitis.

Endoscopy 2021 Feb 16. Epub 2021 Feb 16.

Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.

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http://dx.doi.org/10.1055/a-1346-8769DOI Listing
February 2021

Dissociated response and clinical benefit in patients treated with nivolumab monotherapy.

Invest New Drugs 2021 Aug 10;39(4):1170-1178. Epub 2021 Feb 10.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.

Immune checkpoint inhibitors (ICIs) are effective for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, an unconventional response pattern is sometimes encountered. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with ICI treatment. In this study, we examined the characteristics and treatment outcomes of DR in previously treated NSCLC patients, receiving nivolumab monotherapy. We conducted a retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab. We assessed the tumor response of each organ using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at the first radiologic evaluation. We investigated treatment outcome and compared overall survival using the Kaplan-Meier Method and log-rank tests. Further, we conducted the same analysis in patients who had previously received chemotherapy or tyrosine kinase inhibitor therapy in our hospital. Between April 2016 and September 2018, 107 patients who received nivolumab fulfilled the inclusion criteria. Of them, 5 (5%) patients showed a DR. There were no specific differences in characteristics between DR and non-DR cases. Patients showing DR had significantly longer overall survival than those showing concordant progressive disease (46.9 vs. 8.2 months, p = 0.038). The frequencies of DR in the ICI, chemotherapy, and tyrosine kinase inhibitor-treated cohorts were 5%, 1%, and 4%, respectively. DR was uncommon, but this presented a distinctive pattern of nivolumab response. Some patients might benefit from continuing nivolumab therapy and may achieve a longer overall survival.
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http://dx.doi.org/10.1007/s10637-021-01077-7DOI Listing
August 2021

Extraglomerular Vascular Involvement of Glomerulopathy with Fibronectin Deposits.

Intern Med 2021 Jul 8;60(13):2103-2107. Epub 2021 Feb 8.

Department of Nephrology, Kyoto Prefectural University of Medicine, Japan.

Glomerulopathy with fibronectin deposits (GFND) is a rare hereditary kidney disease with autosomal dominant inheritance. A 21-year-old woman who had been diagnosed with GFND 10 years ago was admitted for investigation of a rapid decline in her renal function, hemolytic anemia, and cardiac dysfunction. A renal biopsy showed GFND accompanied by extraglomerular vascular lesions. Comprehensive treatments against hypertension and anemia improved the renal function. Although there have been few reports of vascular lesions in GFND, we suspect that endothelial hyperpermeability resulting from hypertension caused the fibronectin deposition and narrowing of the extraglomerular vascular lumens, thereby accelerating hypertension and inducing hemolytic anemia.
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http://dx.doi.org/10.2169/internalmedicine.6558-20DOI Listing
July 2021

A Splint-to-CT Data Registration Strategy for Maxillary Navigation Surgery.

Case Rep Dent 2020 4;2020:8871148. Epub 2020 Dec 4.

Department of Oral and Maxillofacial Surgery, Kobe City Medical Center General Hospital, Kobe, Hyogo 650-0047, Japan.

Computer-assisted navigation plays an important role in modern craniomaxillofacial surgery. Although headpins and skull posts are widely used for the fixation of the reference frame, they require the use of invasive procedures. Headbands are easily displaced intraoperatively, thus reducing the accuracy of the surgical outcome. This study reported the utility of a novel splint integrated with a reference frame and registration markers for maxillary navigation surgery. A maxillary splint with a 10 cm resin handle was fabricated before surgery, to fix the reference frame to the splint. The splint was set after the incorporation of fiducial gutta-percha markers into both the splint and resin handle for marker-based pair-point registration. A computed tomography (CT) scan was acquired for preoperative CT-based planning. A marker-based pair-point registration procedure can be completed easily and noninvasively using this custom-made integrated splint, and maxillary navigation surgery can be performed with high accuracy. This method also provides maximum convenience for the surgeon, as the splint does not require reregistration, and can be removed temporarily when required. The splint-to-CT data registration strategy has potential applicability not only for maxillary surgery but also for otolaryngologic surgery, neurosurgery, and surgical repair after craniofacial trauma.
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http://dx.doi.org/10.1155/2020/8871148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787847PMC
December 2020

Extensive leukoencephalopathy associated with idiopathic capillary leak syndrome: report of a case with neuropathology.

Neurol Sci 2021 May 7;42(5):2095-2098. Epub 2021 Jan 7.

Department of Neurology, Kobe City Medical Center General Hospital, 650-0047, 2-1-1 Minatojima-Minamimachi, Chuou-ku, Kobe, Hyogo, Japan.

Introduction: Idiopathic systemic capillary leak syndrome (ISCLS) is a rare cryptogenic disorder characterized by recurrent hemoconcentration, hypoalbuminemia, edema, and hypotension due to extravascular fluid leakage. This is the first report that details uncommon extensive leukoencephalopathy caused by ISCLS upon a neuropathological investigation.

Case Report: A 68-year-old female had recurrent episodes of hemoconcentration, hypoalbuminemia, and generalized edema and was diagnosed with ISCLS. After 9 years, brain magnetic resonance imaging (MRI) incidentally revealed extensive leukoencephalopathy without neurological deficits. Thorough examinations ruled out other disorders, and the cerebral involvement due to ISCLS was finally diagnosed. Three years later, she developed an acute-onset coma and status epilepticus together with hypotension and hemoconcentration, which were compatible with ISCLS recurrence. Electroencephalogram and MRI were correlated with a seizure arising from the left hemisphere. Extensive leukoencephalopathy did not show notable changes for 3 years. Although treatment for ISCLS recurrence temporally improved hemoconcentration and consciousness, consciousness worsened again by marked edema of the left hemisphere, and she died of cerebral herniation. A brain autopsy revealed straggly perivascular plasma leakage around the small vessels of the deep white matter, which supported that the leukoencephalopathy was caused by ISCLS. Widespread myelin pallor and decreased axonal density with sparse astrogliosis and microgliosis were observed in the cerebral white matter and corresponded with a chronic change in the MRI.

Conclusion: Current radiological and pathological observations revealed that frequent perivascular leakages could cause chronic leukoencephalopathy, were linked with the development of systemic capillary leakage in ISCLS, and provided insights into the mysterious pathophysiology.
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http://dx.doi.org/10.1007/s10072-020-05000-5DOI Listing
May 2021

Calcified amorphous tumor presenting with rapid growth in the ascending aorta.

J Vasc Surg Cases Innov Tech 2020 Dec 2;6(4):671-673. Epub 2020 Sep 2.

Department of Cardiovascular Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.

A calcified amorphous tumor (CAT) is a rare, non-neoplastic cardiac mass frequently located in cardiac chambers, especially the mitral valve or annulus. Here, we report an exceedingly rare case of CAT as an atypical mobile mass in the ascending aorta in a 62-year-old man who was on hemodialysis for 11 years. The CAT grew rapidly within 3 months. We resected the mass, and he was discharged with no complications. This report shows that the CAT can grow rapidly, even in the aorta, and provides important information on the progression of this rare disease and its clinical features.
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http://dx.doi.org/10.1016/j.jvscit.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683222PMC
December 2020

Comparison of the 2018 and 2003 International Society of Nephrology/Renal Pathology Society classification in terms of renal prognosis in patients of lupus nephritis: a retrospective cohort study.

Arthritis Res Ther 2020 11 4;22(1):260. Epub 2020 Nov 4.

Department of Nephrology, Fujita Health University School of Medicine, 1-98, Kutsukakecho Dengakugakubo, Toyoake City, Aichi, 470-1192, Japan.

Background: Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003.

Methods: We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR).

Results: A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11-1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models.

Conclusion: This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.
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http://dx.doi.org/10.1186/s13075-020-02358-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640657PMC
November 2020

Clinical significance of tumor-associated immune cells in patients with oral squamous cell carcinoma.

Head Neck 2021 02 7;43(2):534-543. Epub 2020 Oct 7.

Department of Otolaryngology, Head and Neck Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.

Background: The expression of PD-L1 in tumor cells and infiltration of tumor-associated immune cells (TAICs) might reflect the tumor biology of head and neck cancer. We aimed to characterize their prognostic roles in oral squamous cell carcinomas (OSCCs).

Methods: We enrolled 103 OSCC patients who underwent definitive surgery. Immune expression levels of PD-L1, PD-1, CD3, CD4, CD8, and CD68 were assessed in surgically resected specimens. We evaluated the effects of immune marker expression and localization on survival outcomes.

Results: Multivariate analysis results adjusted by the pathological stage, resection margin, and extracapsular extension showed that a high number of PD-1 TAICs and intratumoral CD68 TAICs were independent positive and negative prognostic markers (hazard ratio: 0.20 and 4.15, respectively; P = .02 and .01, respectively).

Conclusion: PD-1 TAICs in the tumor microenvironment and CD68 TAICs in the intratumoral area could act as novel biomarkers for predicting overall survival outcomes in OSCC patients.
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http://dx.doi.org/10.1002/hed.26498DOI Listing
February 2021

FAT1 biallelic truncating mutation causes a non-syndromic proteinuria in a child.

CEN Case Rep 2021 02 9;10(1):100-105. Epub 2020 Sep 9.

Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo, Kobe, Hyogo, 6500017, Japan.

The identification of monogenic causes in patients with proteinuria has revealed that the encoded proteins functionally participate in distinct cellular tasks and signaling pathways in the slit diaphragms of the glomerular basement membrane. FAT1 is a member of a small family of vertebrate-cadherin-like genes, which is a crucial component in slit diaphragms and has a vital role in tubular regeneration. Only 5 cases with glomerulonephritis having FAT1 gene biallelic variants have been reported. However, only one had the biallelic truncating variant, and others had missense variants. Therefore, we need further evidence of this gene being responsible for steroid-resistant nephrotic syndrome (SRNS) or glomerulonephritis. Here we describe a 5-year-old boy in who proteinuria was detected at the age of 3 years without any extrarenal symptom. The pathological findings were examined, and targeted exome sequencing was performed. We also conducted reviews for all previously-reported cases of glomerulonephritis possessing FAT1 biallelic gene variants. We found two novel truncating variants in FAT1 (NM_005245.3), c.12867dup in exon 10, and, c.5480_5483del in exon 25. Our case showed mild proteinuria compared to previously-reported cases who showed SRNS and extrarenal symptoms that might have been because the latter variant in our patient was located on out of cadherin domains; however, our follow up period is short and we further need careful follow up. Our findings corroborate the evidence that individuals with FAT1-truncating variants can show isolated mild proteinuria. Further studies are needed to investigate the genotype-phenotype correlation in this disease. Therefore, our case will provide vital information regarding this rare condition.
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http://dx.doi.org/10.1007/s13730-020-00529-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829294PMC
February 2021

A case report of adult-onset COQ8B nephropathy presenting focal segmental glomerulosclerosis with granular swollen podocytes.

BMC Nephrol 2020 08 28;21(1):376. Epub 2020 Aug 28.

Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Background: Primary coenzyme Q10 (CoQ10) deficiency of genetic origin is one of a few treatable focal segmental glomerulosclerosis (FSGS). Renal morphologic evidence for COQ8B mutation and CoQ10 deficiencies of other gene mutations is assessed using electron microscopy with marked increase of abnormal-shaped mitochondria in podocytes. However, light microscopic morphologic features of deficiencies other than FSGS have not been reported.

Case Presentation: A 30-year-old woman was admitted to our hospital because proteinuria was found during four consecutive medical checkups. She had no medical history or family history of proteinuria and severe renal dysfunction. The swollen podocytes were stained to the same extent as mitochondria-rich proximal tubular cells under both Masson's trichrome and hematoxylin-eosin staining, whereas no mitochondrial abnormalities were detected under the first electron microscopic views. As proteinuria and estimated glomerular filtration rate (eGFR) deteriorated after pregnancy, we reevaluated the additional electron microscopic views and detected mitochondrial abnormalities. Genetic testing revealed COQ8B mutation (c.532C > T, p.R178W); therefore, we diagnosed COQ8B nephropathy. CoQ10 supplementation improved proteinuria and stopped eGFR reduction.

Conclusions: This is the first report of granular swollen podocytes due to mitochondrial diseases detected under light microscopy. We propose that this finding can be the clue for the diagnosis of both COQ8B nephropathy and the other CoQ10 deficiencies.
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http://dx.doi.org/10.1186/s12882-020-02040-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456044PMC
August 2020

Adrenal Corticomedullary Mixed Tumor Associated With the -G388R Variant.

J Endocr Soc 2020 Sep 21;4(9):bvaa101. Epub 2020 Jul 21.

Department of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan.

Adrenal corticomedullary mixed tumors (CMMTs) are extremely rare; with only 20 cases being reported to date, the pathogenesis has remained elusive. A 31-year-old woman developed gestational hypertension with psychiatric disturbances persistent to postpartum and was diagnosed with pheochromocytoma, for which adrenalectomy was performed. Histological findings showed mixed adrenocortical adenoma and pheochromocytoma. Double immunostaining of inhibin and INSM1 (insulinoma-associated protein 1) showed that the 2 tumor components had distinct functional properties. Exome analysis of peripheral leukocytes and tumor (singular, as anatomically it is only 1 mass) revealed a homozygous germline -G388R variant. As a readout of the variant, serine phosphorylation of signal transducer and activator of transcription 3 (STAT3) was detected only in the nucleus of adrenocortical adenoma component but not in the pheochromocytoma component. No tyrosine phosphorylation of STAT3 was detected. We report a case of CMMT with the germline -G388R variant. Although additional studies are required, our immunohistochemical analysis suggests that the variant may play a role in the development of the adrenocortical component within the pheochromocytoma, leading to CMMT.
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http://dx.doi.org/10.1210/jendso/bvaa101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417000PMC
September 2020

Tension pneumoperitoneum caused by intestinal perforation from underlying colon cancer: a case report.

J Med Case Rep 2020 Jul 22;14(1):112. Epub 2020 Jul 22.

Emergency Department, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, Japan.

Background: Tension pneumoperitoneum, a form of abdominal compartment syndrome, is an important clinical condition. Increased pressure in the intraperitoneal cavity leads to respiratory and circulatory instability. Most of the reported cases include complications due to active air infusion into the peritoneal cavity or trauma; however, few reports are available on tension pneumoperitoneum caused by perforation from colon cancer. We present a case of a patient with tension pneumoperitoneum caused by gastrointestinal perforation owing to colon cancer.

Case Presentation: A 63-year-old Japanese man with altered mental state was brought to our emergency department. He was in shock, and an abdominal radiograph suggested gastrointestinal perforation. Despite rapid fluid infusion and inotropic support, his condition deteriorated. His abdomen was tensely distended; abdominal computed tomography showed significant intra-abdominal gas. Following immediate needle decompression, his circulatory status improved. Emergent laparotomy revealed an approximately 10-cm tumor (adenocarcinoma) in the colon, which caused the perforation.

Conclusions: A perforated wall or the surrounding omental fat that acts as a one-way valve could lead to tension pneumoperitoneum without active air infusion. Although tension pneumoperitoneum is a life-threatening condition, it is reversible if prompt diagnosis and immediate decompression are performed. Physicians should always consider this condition as one of the causes of shock or cardiopulmonary arrest, even without an apparent medical history of active air infusion or trauma.
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http://dx.doi.org/10.1186/s13256-020-02437-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374859PMC
July 2020

Anti-transcriptional intermediary factor 1-γ antibody-positive dermatomyositis induced by nivolumab for lung adenocarcinoma: A case report.

Invest New Drugs 2021 Feb 10;39(1):251-255. Epub 2020 Jul 10.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.

Immune checkpoint inhibitors can induce immune-related adverse events (irAEs) in different organs. Dermatomyositis is a rare form of systemic irAE. Although dermatomyositis-specific antibodies, especially anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibodies, have been detected in a few cases of immune checkpoint inhibitor-associated dermatomyositis, their titers before immunotherapy have not been examined. We hereby report the first irAE case of dermatomyositis accompanied by seroconversion of anti-TIF1-γ antibody following nivolumab treatment for advanced lung adenocarcinoma. A 64-year-old Japanese male with an advanced lung adenocarcinoma (cT4N2M1a stage IVA) received nivolumab as third-line therapy. Skin rashes appeared two days later, and were treated with a topical steroid as just drug eruptions. 7 weeks later, he was emergently admitted because of high serum creatine kinase level. Clinical examination showed deteriorated rashes along with slightly weakened proximal muscles. Muscle biopsy revealed myopathic changes consistent with dermatomyositis. Anti-TIF1-γ antibody was positive, which was found to be within normal range before nivolumab administration. He was diagnosed with dermatomyositis and treated with systemic corticosteroids, tacrolimus, and intravenous immunoglobulin. However, these drugs showed limited effectiveness against the progression of muscle weakness. He died of respiratory failure due to lung cancer and muscle weakness progression 6 months after the admission. In conclusion, our case demonstrates that the development of dermatomyositis was causally related to immune activation by nivolumab. Given the potential exacerbation of autoimmune paraneoplastic disorders in cancer patients receiving immunotherapy, clinicians should be aware of early manifestations of systemic irAEs that require prompt diagnosis and intervention.
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http://dx.doi.org/10.1007/s10637-020-00974-7DOI Listing
February 2021

Histological changes of a kidney in a recipient who received an allograft from a patient with Fabry disease.

J Nephrol 2020 08 13;33(4):657-659. Epub 2020 Jun 13.

Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

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http://dx.doi.org/10.1007/s40620-020-00782-5DOI Listing
August 2020

A case of anal intraepithelial neoplasia resected by endoscopic submucosal dissection after magnifying narrow-band imaging evaluation.

Gastrointest Endosc 2020 Dec 9;92(6):1271-1272. Epub 2020 Jun 9.

Department of Gastroenterology, Kobe City Medical Centre General Hospital, Kobe, Japan.

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http://dx.doi.org/10.1016/j.gie.2020.06.005DOI Listing
December 2020

Complement activation is associated with crescent formation in IgA nephropathy.

Virchows Arch 2020 Oct 16;477(4):565-572. Epub 2020 Apr 16.

Department of Diagnostic Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, Japan.

IgA nephropathy (IgAN) is common chronic glomerulonephritis with variable prognosis, ranging from minor urinary abnormalities to end-stage renal disease. The revised Oxford classification of IgAN explains that cellular/fibrocellular crescents are associated with poor renal prognosis, proposing an extension to the MEST-C score. C3 immunofluorescent staining follows a distribution similar to IgA staining. Therefore, complement activation was reported to play a pivotal role in IgAN pathogenesis. This study included 132 IgAN patients diagnosed by renal biopsies. The clinical parameters at the time of the biopsies were obtained from patient data records. We classified the patients into C ≥ 1 and C0 groups, and compared clinical, light microscopic, and immunofluorescent features. In the C ≥ 1 group, 2 (1.5%) and 31 (23.5%) patients were assigned to C2 and C1, respectively. The remaining 99 patients (75%) were classified as C0. The C ≥ 1 group had lower average age and rate of hypertension, and higher score of urinary occult blood and E score. The C ≥ 1 group had significantly higher average immunofluorescence scores for IgA, C5b-9, mannose-associated serine protease (MASP) 1/3, MASP2, properdin, factor B, and kappa. The steroid use rate was significantly higher in the C ≥ 1 group. During the follow-up period of 2.90 years on average, the rate of renal dysfunction was not significantly different between groups. Crescent formation in IgAN was associated with activation of the lectin and alternative pathways. The C ≥ 1 group had significantly increased use of steroids, which probably caused comparable renal function during the follow-up period.
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http://dx.doi.org/10.1007/s00428-020-02800-0DOI Listing
October 2020

Fibrillary Glomerulopathy with a High Level of Myeloperoxidase-ANCA: A Case Report.

Case Rep Nephrol 2020 23;2020:6343521. Epub 2020 Mar 23.

Department of Internal Medicine, Suwa Central Hospital, Chino, Nagano 391-8503, Japan.

An elderly woman was admitted with the chief complaint of gross hematuria. Laboratory values indicated a high myeloperoxidase-ANCA level. In renal histological examination, 40% of the glomeruli showed crescent formation, but immunofluorescence staining showed positivity for IgG, C3, and C1q. Furthermore, the deposition of fibrils in the glomerulus was noted on electron microscopy, and immunohistochemical staining showed strong positivity for DNA-J heat shock protein family member B9 (DNAJB9). Crescent formation is a common feature of fibrillary glomerulonephritis (FGN). Thus, in ANCA-positive crescentic glomerulonephritis, immunohistochemical assessments for immunoglobulins and DNAJB9, as well as electron microscopy, are important to correctly diagnose FGN.
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http://dx.doi.org/10.1155/2020/6343521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128069PMC
March 2020
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