Publications by authors named "Masaya Mori"

62 Publications

Hepatitis C virus relapse after successful treatment with direct-acting antivirals, followed by sarcomatous changes in hepatocellular carcinoma: a case report.

J Med Case Rep 2020 May 27;14(1):62. Epub 2020 May 27.

Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan.

Background: Combination therapy of interferon and ribavirin has traditionally been used to eradicate hepatitis C virus. The sustained virologic response achieved with interferon-related therapy is persistent, and late relapses after achieving sustained virologic response at 24 weeks using this therapy are reportedly rare (< 1%). In 2014, interferon-free therapy with direct-acting antivirals was developed, and the rate of sustained virologic response was improved. However, the persistence thereof remains uncertain, and the appropriate follow-up period for hepatitis C virus-positive patients is under discussion.

Case Presentation: A 74-year-old Japanese man who had hepatitis C virus-related hepatocellular carcinoma and was successfully treated with radiofrequency ablation four times underwent direct-acting antiviral therapy with daclatasvir and asunaprevir; sustained virologic response at 24 weeks was confirmed. However, although he had no high risk factors for reinfection, hepatitis C virus ribonucleic acid was detected again 6 months after achieving sustained virologic response at 24 weeks. Moreover, he developed active hepatitis with an increased viral load. Five months after development of hepatitis, recurrent hepatocellular carcinoma emerged in segment II, where we had performed radiofrequency ablation 17 months previously. The recurrent hepatocellular carcinoma enlarged quite rapidly and induced multiple peritoneal disseminations and lung metastases. He died 3 months after the abrupt recurrence. A sarcomatous change in the hepatocellular carcinoma was identified during the autopsy.

Conclusions: Although sustained virologic response at 24 weeks has generally been regarded to denote complete eradication of hepatitis C virus, we present a patient in whom hepatitis C virus recurred 6 months after achieving sustained virologic response at 24 weeks with direct-acting antiviral therapy. In addition, a sarcomatous change in hepatocellular carcinoma emerged 5 months after active hepatitis developed due to late hepatitis C virus relapse in this case. The sarcomatous change in hepatocellular carcinoma is generally thought to be related to anticancer therapies, such as radiofrequency ablation. However, in this case, late viral relapse and active hepatitis in addition to the previous radiofrequency ablation could have been the trigger. There may be a need for follow-up of hepatitis C virus ribonucleic acid beyond sustained virologic response at 24 weeks with direct-acting antiviral therapy, owing to the possibility of late viral relapse and tumorigenesis.
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http://dx.doi.org/10.1186/s13256-020-02392-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251811PMC
May 2020

4-Bromo-1,8-naphthalimide derivatives as fluorogenic substrates for live cell imaging of glutathione S-transferase (GST) activity.

Talanta 2019 Nov 15;204:633-640. Epub 2019 Jun 15.

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

Fluorogenic substrates are used to visualize the activity of cancer-associated enzymes and to interpret biological events. Certain types of glutathione S-transferase (GST), such as Pi class GST (referred to as GSTP1), are more highly expressed in a wide variety of human cancer tissues compared to their corresponding normal tissues. Pi class GST is thus a cancer cell molecular marker and potential target for overcoming resistance to chemotherapy. Here, we report that 4-bromo-1,8-naphthalimide (BrNaph) is a practical fluorogenic GST substrate. We have found that HE-BrNaph, an N-hydroxyethyl derivative, shows remarkable fluorescence enhancement upon GST-catalyzed SAr replacement of the bromo group with a glutathionyl group. This substitution was highly selective and occurred only in the presence of GSH/GSTs; no non-enzymatic reaction was observed. We demonstrated that HE-BrNaph allows visualization of GST activity in living cells and enables to distinguish cancer cells from normal cells. Further, various N-substitutions in BrNaph retain susceptibility to enzymatic activity and isozyme selectivity, suggesting the applicability of BrNaph derivatives. Thus, BrNaph and its derivatives are GST substrates useful for fluorescence imaging and the intracellular detection of GSTP1 activity in living cells.
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http://dx.doi.org/10.1016/j.talanta.2019.06.059DOI Listing
November 2019

A highly selective fluorogenic substrate for imaging glutathione S-transferase P1: development and cellular applicability in epigenetic studies.

Chem Commun (Camb) 2019 Jul;55(56):8122-8125

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

Pi-class glutathione S-transferase (GSTP1) is a molecular marker enzyme whose expression level is altered in various malignant tumour tissues. Herein, we report the first highly selective fluorogenic GSTP1 substrate, Ps-TG, and its membrane-permeable derivative Ps-TAc, for specific visualization of intracellular GSTP1 activity in cancer cells or epigenetically regulated GSTP1 expression.
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http://dx.doi.org/10.1039/c9cc03064fDOI Listing
July 2019

A case of adenomyoepithelioma with myoepithelial carcinoma of the breast.

Clin Case Rep 2019 May 30;7(5):930-934. Epub 2019 Mar 30.

Department of Breast and Endocrine Surgery Mitsui Memorial Hospital Tokyo Japan.

Adenomyoepithelioma with myoepithelial carcinoma of the breast is rare and diagnosed with histology and immunohistochemistry. We present a case of malignant transformation over 10 years, with ultrasonographic findings, highlighting the importance of an early excisional biopsy. Conservative surgery and radiation therapy were performed. There was no recurrence for 2 years.
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http://dx.doi.org/10.1002/ccr3.2100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509899PMC
May 2019

The hepatic capsular arteries: imaging features and clinical significance.

Abdom Radiol (NY) 2019 08;44(8):2729-2739

Department of Clinical Anatomy, Tokyo Medical & Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan.

Background: Although the anatomical features of the hepatic capsular arteries have been previously reported, the radiological and clinical importance of these arteries has not been well documented.

Imaging Findings: We injected barium sulfate into the intra- and extra-hepatic arteries in cadavers to investigate the hepatic capsular arteries. The web-like hepatic capsular arteries derived from the capsular branch of the peripheral hepatic arteries are called isolated arteries. There were anastomoses between the intra- and extra-hepatic arteries (inferior phrenic artery, superior falciform ligament artery, and cystic artery) through the hepatic capsular arteries.

Clinical Significance: We reviewed the radiology database and assessed clinical cases. When the hepatic artery is occluded, the collateral vessels, such as the inferior phrenic artery and the superior falciform ligament artery, develop via the hepatic capsular arteries at the right triangular ligament and falciform ligament, respectively. Bleeding from capsular arteries causes extensions of the subcapsular hematoma.

Conclusion: The hepatic capsular arteries spread along the hepatic surface and constitute the vascular network throughout the liver. These arteries play an important role in collateral circulation in various clinical situations, as well as subcapsular hematoma.
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http://dx.doi.org/10.1007/s00261-019-02021-3DOI Listing
August 2019

Nivolumab-induced myocardial necrosis in a patient with lung cancer: A case report.

Respir Med Case Rep 2019 15;27:100839. Epub 2019 Apr 15.

Division of Thoracic Surgery, Mitsui Memorial Hospital, Kanda-Izumicho 1, Chiyoda, Tokyo, 101-8643, Japan.

A 74-year-old man with lung adenocarcinoma recurrence was admitted to our hospital because of dyspnea 7 days after receiving initial immunotherapy with nivolumab. Electrocardiography revealed ST-segment elevation in V1-6 and echocardiography showed a markedly reduced left ventricular ejection fraction of 9% and akinesis of the anteroseptal wall and apex. He died from acute heart failure 3 days after admission. Microscopically, multiple small foci of myocardial necrosis with few inflammatory cells were scattered in both ventricles. Obstruction of the coronary artery was not identified. We believed that the cause of death was acute heart failure possibly due to nivolumab-induced myocardial necrosis.
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http://dx.doi.org/10.1016/j.rmcr.2019.100839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476808PMC
April 2019

Rapidly progressive miliary brain metastasis of lung cancer after EGFR tyrosine kinase inhibitor discontinuation: An autopsy report.

Neuropathology 2019 Apr 13;39(2):147-155. Epub 2019 Mar 13.

Department of Pathology, Mitsui Memorial Hospital, Tokyo, Japan.

Miliary brain metastasis is a rare type of brain metastasis, in which carcinoma cells disseminate to numerous foci confined to Virchow-Robin/subpial spaces. Symptoms usually progress within several months, and magnetic resonance imaging (MRI) shows multiple small contrast-enhancing lesions. We report an autopsy case of a patient who rapidly deteriorated within a week due to miliary brain metastasis after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) discontinuation, without contrast-enhancing lesions on MRI. A 74-year-old woman was diagnosed with stage IV lung adenocarcinoma with EGFR L868R mutation 2 years before presentation. Gefitinib, an EGFR-TKI was started. After 7 months, multiple new punctate contrast-enhancing lesions in the cerebral cortex appeared. After switching to another EGFR-TKI, erlotinib, these lesions disappeared. One year later, erlotinib was discontinued because of disease progression in the lung and docetaxel was initiated. Sixteen days later, cognitive decline appeared which rapidly progressed to bedridden state in 4 days. MRI showed multiple cortical small fluid-attenuated inversion recovery high intensity lesions which lacked contrast enhancement. The patient exhibited a state of akinetic mutism within a few days, and died 52 days after the appearance of neurological symptoms. The rapid progression indicated disease flare after EGFR-TKI discontinuation. Autopsy revealed numerous foci of metastasis in the cerebral cortex, basal ganglia, thalamus, and cerebellum, in which cancer cells were mostly confined to the Virchow-Robin/subpial spaces. These pathological findings were compatible with previous reports of miliary brain metastasis. Recent reports suggest that early disseminated cancer cells can survive for a long time and even remain after chemotherapy in supportive niches, and Virchow-Robin spaces are the niches in the brain. Our case suggests that these cancer cells may rapidly proliferate as a withdrawal burst after discontinuation of molecular targeted drugs, and show pathological findings of miliary brain metastasis.
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http://dx.doi.org/10.1111/neup.12542DOI Listing
April 2019

Acute Bilateral Oculomotor Nerve Palsy in an Adult Patient with Neisseria meningitidis.

Intern Med 2019 Jun 1;58(11):1639-1642. Epub 2019 Feb 1.

Department of Cardiology, Komaki City Hospital, Japan.

A 69-year-old woman was admitted to our hospital with a fever, dizziness, and headache caused by Neisseria meningitidis. After ceftriaxone was administered, she suddenly developed bilateral oculomotor nerve palsy. Intra-orbital magnetic resonance imaging using appropriate sequences revealed that her bilateral third intracranial nerves were enlarged and enhanced. She achieved complete recovery by two months after additional short-term treatment with intravenous immunoglobulin and methylprednisolone. Although intracranial nerve disorders that result from bacterial meningitis are most frequently reported in children, it is noteworthy that it can also cause focal intracranial nerve inflammation with ophthalmoparesis in N. meningitidis infection in adults.
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http://dx.doi.org/10.2169/internalmedicine.2098-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599925PMC
June 2019

Granulomatosis with Polyangiitis Localized in the Greater Omentum.

Case Rep Surg 2018 28;2018:6145903. Epub 2018 Feb 28.

Department of Pathology, Mitsui Memorial Hospital, Tokyo, Japan.

Granulomatosis with polyangiitis (GPA) is known as anti-neutrophil cytoplasmic antibody- (ANCA-) associated small vessel vasculitis and typically manifests as pulmonary-renal syndrome, but the disease is not limited to pulmonary or renal systems. The inflammation can involve whole body organs. In addition, the ANCA titer does not always become positive. Here, we describe the case of a 91-year-old man who presented with umbilical pain and fever of unknown origin. Only the increased computed tomography value of the greater omentum suggested intra-abdominal inflammation; however, serological examinations, including the ANCA level, could not reveal the focus or cause of symptoms. Finally, the histopathological examination of specimens surgically excised from the greater omentum demonstrated GPA limited to the greater omentum. This report reminds physicians to consider GPA in the differential diagnosis of acute abdominal pain or fever of unknown origin.
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http://dx.doi.org/10.1155/2018/6145903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851328PMC
February 2018

Pancreaticoduodenectomy for an Ampullary Region Carcinoma Occurred in Annular Pancreas Coexistent with Replaced Common Hepatic Artery.

Case Rep Med 2018 20;2018:3258141. Epub 2018 Feb 20.

Department of Pathology, Mitsui Memorial Hospital, 1 Kanda Izumicho, Chiyoda-ku, Tokyo 101-8643, Japan.

Introduction: Annular pancreas is a rare congenital abnormality characterized by a ring of pancreatic tissue surrounding the descending portion of the duodenum. Annular pancreas coexisting with replaced common hepatic artery which is also a rare anatomical variation has not been reported previously.

Case Presentation: A 53-year-old man visited our hospital complaining of epigastric pain. Based on radiological examinations, he was diagnosed as having pancreatitis, annular pancreas, and hepatomesenteric trunk. One month later, obstructive jaundice developed. Endoscopic examination revealed ampullary region carcinoma. We performed pancreaticoduodenectomy using the "artery-first" approach.

Discussion: Both annular pancreas and common hepatic artery anomaly are rare. High-quality preoperative imaging and awareness of such rare conditions are necessary for operative safety. Although the embryological relationship between these anomalies is uncertain, the present case may suggest some relevance between the two.

Conclusion: The "artery-first" approach may be a useful method for pancreaticoduodenectomy in patients who have an anatomical abnormality.
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http://dx.doi.org/10.1155/2018/3258141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838470PMC
February 2018

Pulmonary Tumor Thrombotic Microangiopathy due to Advanced Gastric Cancer with Virchow's Node Metastasis.

Int Heart J 2018 Mar 5;59(2):443-447. Epub 2018 Mar 5.

Division of Cardiology, Mitsui Memorial Hospital.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related complication characterized by severe progressive pulmonary hypertension. Antemortem diagnosis is difficult owing to the rapid progression of the condition, especially when the patient has no known malignancies and initially presents with pulmonary hypertension. Here we report a case of PTTM due to occult gastric cancer with metastasis in the left supraclavicular lymph node, also known as Virchow's node. Enlarged Virchow's node is an important indicator of advanced gastric cancer. In patients with progressive pulmonary hypertension of unknown origin, enlarged Virchow's node can be an important indicator for the diagnosis of PTTM.
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http://dx.doi.org/10.1536/ihj.17-249DOI Listing
March 2018

A case of herpes simplex virus pneumonia detected by sputum cytodiagnosis.

Clin Case Rep 2018 01 7;6(1):165-169. Epub 2017 Dec 7.

Department of Pathology Mitsui Memorial Hospital Tokyo Japan.

A sputum test is noninvasive and simple. It contributed to correct diagnosis of a patient with severe acute respiratory failure. We again point out the usefulness of sputum cytodiagnosis for differentiating severe pneumonia.
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http://dx.doi.org/10.1002/ccr3.1309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771873PMC
January 2018

Fluorescein diacetate (FDA) and its analogue as substrates for Pi-class glutathione S-transferase (GSTP1) and their biological application.

Talanta 2018 Mar 5;179:845-852. Epub 2017 Dec 5.

Laboratory of Molecular and Chemical Biology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address:

Pi class glutathione S-transferase (GSTP1) is highly expressed in various cancerous cells and pre-neoplastic legions, where it is involved in apoptotic resistance or metabolism of several anti-tumour chemotherapeutics. Therefore, GSTP1 is a marker of malignant and pre-malignant cells and is a promising target for visualization and drug development. Here we demonstrate that fluorescein diacetate (FDA), a fluorescent probe used for vital staining, is a fluorescently activated by esterolytic activity of human GSTP1 (hGSTP1) selectively among various cytosolic GSTs. Fluorescence activation of FDA susceptible to GST inhibitors was observed in MCF7 cells exogenously overexpressing hGSTP1, but not in cells overexpressing hGSTA1 or hGSTM1. Inhibitor-sensitive fluorescence activation was also observed in several cancer cell lines endogenously expressing GSTP1, suggesting that GSTP1 is involved in FDA esterolysis in these cells. Among the FDA derivatives examined, FOMe-Ac, the acetyl ester of fluorescein O-methyl ether, was found to be a potential reporter for GSH-dependent GSTP1 activity as well as for carboxylesterase activity. Since GSTP1 is highly expressed in various types of cancer cells compared to their normal counterparts, improving the fluorogenic substrates to be more selective to the esterolysis activity of GSTP1 rather than carboxylesterases should lead to development of tools for detecting GSTP1-overexpressing cancer cells and investigating the biological functions of GSTP1.
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http://dx.doi.org/10.1016/j.talanta.2017.12.010DOI Listing
March 2018

The protective role of YAP1 on ER stress-induced cell death in vascular smooth muscle cells.

Eur J Pharmacol 2017 Nov 23;815:470-477. Epub 2017 Sep 23.

Department of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine-ku, Sapporo 006-8590, Japan. Electronic address:

Apoptosis of vascular smooth muscle cells (VSMCs) has been implicated in the progression of atherosclerosis, especially in vascular remodelling and plaque rupture. Although it is known that Yes-associated protein 1 (YAP1) is a critical molecule that regulates cell proliferation, differentiation and apoptosis, the role of YAP1 in VSMCs apoptosis remains unknown. In this study, we investigated whether YAP1 modulates VSMC apoptosis induced by endoplasmic reticulum (ER) stress. In cultured VSMC, tunicamycin caused cell death accompanied by an increase in caspase-3 processing and C/EBP homologous protein (CHOP) expression. YAP1 protein expression was downregulated by tunicamycin and the phosphorylation of YAP1 at the Ser127 site was significantly increased by tunicamycin. Tunicamycin further decreased cell viability followed by an increase in caspase-3 processing in the absence of YAP1 when compared with treatment only with tunicamycin or siYAP1. On the other hand, overexpression of a constitutively active YAP1 (YAP1-5SA), which lacks five serine phosphorylation sites, significantly prevented the caspase-3 processing and restored the decrease in cell viability induced by tunicamycin. Overexpression of YAP1-5SA significantly inhibited tunicamycin-induced caspase-8 processing without affecting phosphorylation of p-38 and Akt. Furthermore, the overexpression of YAP1-5SA significantly restored the decrease in ANKRD1 expression induced by tunicamycin. The inhibition of tunicamycin-induced caspase-3 cleavage by YAP1-5SA was markedly attenuated in ANKRD1-knockdown cells. These results demonstrate that ER stress can alter intracellular YAP1 protein expression in VSMCs and that YAP1 is protective against VSMC apoptosis induced by ER stress through inhibiting caspase8/3 activation mediated in part by upregulation of ANKRD1.
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http://dx.doi.org/10.1016/j.ejphar.2017.09.033DOI Listing
November 2017

[How Long Are Unstained Sections Available for Immunostaining? -A Study of Antigenicity Preservation Time-].

Rinsho Byori 2016 11;64(11):1215-1219

It is well known that the antigenicity of unstained sections put on a slide glass decreases when the slides are stored at room temperature. Several methods have been reported to prevent reduced antigenicity, such as storing in a dark place at 4°C, covering sections with paraffin or a sheet, and storing in a deep freezer at -80°C. The aim of the present study is to determine how long unstained sections can be stored in a refriger- ator (ie, 1 week, 2 weeks, 1 month and 2 months). Each section was well stained and equal to the day 0 section for CD3, CD20, bcl-2, bcl-6, ER, PgR, HER2, Ki-67, chromogranin-A, synaptophysin, CK5, CK7, CK20, and TTF-1. In conclusion, unstained sections can be used for immunostaining after at least 2 months of storage, and preparing several control sections and storing them in a refrigerator is useful for minimizing control block loss. [Original].
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November 2016

Histopathological characteristics of renal changes in human renin-angiotensinogen double transgenic rats.

J Toxicol Pathol 2016 Apr 12;29(2):125-9. Epub 2015 Dec 12.

Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.

The human renin-angiotensinogen double transgenic rat (dTGR) is a model of hypertension. The aim of this short report was to describe the histopathological characteristics of the renal changes in this rat strain in detail. Seven to nine-week-old male dTGRs were euthanized, and their kidneys were histopathologically examined. At the time of sacrifice, the average systolic blood pressure of the dTGRs was 258 mmHg, while that of age-matched, normal Sprague-Dawley rats was 135 mmHg. In the kidney, histopathological changes were observed mainly in blood vessels, tubules and glomeruli. In blood vessels, changes including medial hypertrophy, intimal thickening, hyaline change and/or fibrinoid necrosis were observed in arteries and arterioles. In tubules, changes including tubular basophilia were observed radially, mainly around interlobular arteries with lesions. In glomeruli, changes including hyaline droplet accumulation in podocytes, which was accompanied by increased expression of desmin, were observed. These changes were similar to those reported in other hypertension models, such as the spontaneously hypertensive rat (SHR). We hope that this short report will be helpful in histopathological examination of renal changes in this or other hypertension models.
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http://dx.doi.org/10.1293/tox.2015-0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866003PMC
April 2016

[A Surgical Case of Intrapulmonary Bronchogenic Cyst Treated by Left Lower Lobectomy for Hemopneumothorax and Repeated Hemoptysis].

Kyobu Geka 2015 Aug;68(9):764-7

Department of Thoracic Surgery, Mitsui Memorial Hospital, Tokyo, Japan.

A 79-year-old female visited a hospital because of high fever and computed tomography(CT)showed a cystic lesion with fluid accumulation in her left lung. She had hemoptysis and left chest pain 3 days after antibiotic therapy was started. Chest CT demonstrated the cystic lesion rupturing and causing hemopneumothorax. Then she was referred to our department and thoracic drainage was performed. However, a week after the drainage, she had hemoptysis and chest pain again, and the left lower lobectomy was performed. Histopathological findings showed the cystic lesion was intrapulmonary bronchogenic cyst. We describe a rare case of the hemopneumothorax due to the hemorrhage in the bronchogenic cyst.
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August 2015

Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis.

Blood Purif 2015 ;40(2):146-54

Background: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown.

Methods: This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-β2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS.

Results: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with ‘Amyloid (1+) and Calcification >1 mm' and ‘Amyloid (2+) and Calcification >1 mm' (vs. ‘Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with ‘Amyloid (2+) and Calcification >1 mm' (OR: 24.3).

Conclusions: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.
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http://dx.doi.org/10.1159/000381938DOI Listing
July 2016

Complete Surgical Resection of a Leiomyosarcoma Arising from the Inferior Vena Cava.

Case Rep Med 2015 18;2015:342148. Epub 2015 Jun 18.

Division of Pathology, Mitsui Memorial Hospital, Kanda-Izumi-cho 1, Chiyoda-ku, Tokyo 101-8643, Japan.

A 76-year-old Japanese man was referred to our hospital with chief complaint of right hypochondoralgia. Abdominal ultrasound showed a retroperitoneal tumor in the suprarenal region of the right kidney. Computed tomography revealed an enhanced lobular tumor with irregular, circumscribed, and indistinct border. Ultrasound-guided biopsy was performed. The tumor consisted of spindle-shaped cells with a giant nucleus and multinuclear cells. The diagnosis was leiomyosarcoma by immunohistochemical staining. The patient underwent surgery accessed by a right eighth intercostal thoracoabdominal incision. The tumor was completely resected, accompanied by removal of the posterosuperior segment of the right hepatic lobe, right adrenal gland, and a portion of the inferior vena cava (IVC). The histopathologic diagnosis was leiomyosarcoma arising from the IVC. We present a rare case of a successfully managed leiomyosarcoma of the IVC. This case suggests the importance of curative surgical resection of the tumor due to low efficacy of adjuvant chemotherapy for leiomyosarcoma.
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http://dx.doi.org/10.1155/2015/342148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488522PMC
July 2015

DSR-71167, a novel mineralocorticoid receptor antagonist with carbonic anhydrase inhibitory activity, separates urinary sodium excretion and serum potassium elevation in rats.

J Pharmacol Exp Ther 2015 Jul 28;354(1):2-9. Epub 2015 Apr 28.

Drug Research Division, Sumitomo Dainippon Pharma., Co., Ltd., Osaka, Japan.

Mineralocorticoid receptor (MR) antagonists, such as spironolactone (SPI) and eplerenone (EPL), are useful for treating hypertension and heart failure. However, these two agents have the serious side effect of hyperkalemia. We hypothesized that adding the ability to inhibit carbonic anhydrase (CA) would reduce the risk of hyperkalemia associated with MR antagonists. We investigated the profiles of DSR-71167 [2-([(2,2-difluoroethyl)amino]methyl)-2'-fluoro-N-(3-methoxy-4-sulfamoylphenyl)biphenyl-4-carboxamide hydrochloride; an MR antagonist with weak CA inhibitory activity] with regard to antimineralocorticoid actions by examining relationships between the urinary excretion of sodium (index of antimineralocorticoid action) in deoxycorticosterone acetate-treated rats and elevation of serum levels of potassium in potassium-loaded rats compared with a DSR-71167 derivative without CA inhibition (2-(hydroxymethyl)-N-[4-(methylsulfonyl)phenyl]-2'-(trifluoromethyl)biphenyl-4-carboxamide), SPI, and EPL. DSR-71167 dose-dependently increased urinary excretion of sodium in deoxycorticosterone acetate-treated rats without elevating serum levels of potassium in potassium-loaded rats. 2-(Hydroxymethyl)-N-[4-(methylsulfonyl)phenyl]-2'-(trifluoromethyl)biphenyl-4-carboxamide, SPI, and EPL elevated serum levels of potassium significantly in potassium-loaded rats at doses that increased MR inhibitory activity. We confirmed that DSR-71167 significantly increases urinary bicarbonate and decreases blood bicarbonate, as pharmacodynamic markers of CA inhibition, in intact rats. Chronic DSR-71167 administration showed antihypertensive effects in high salt-loaded Dahl hypertensive rats. These results demonstrate that DSR-71167 is a novel type of MR antagonist, with CA inhibitory activity, which is expected to become a safer MR antagonist with a low potential risk for hyperkalemia.
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http://dx.doi.org/10.1124/jpet.114.221341DOI Listing
July 2015

A Case of Granulocyte-Colony Stimulating Factor-Producing Spindle Cell Carcinoma of the Breast.

Clin Breast Cancer 2015 Aug 21;15(4):e213-7. Epub 2015 Feb 21.

Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.clbc.2015.02.003DOI Listing
August 2015

Giant polypoid tumor expressing on the pyloric ring.

Case Rep Med 2015 22;2015:986971. Epub 2015 Jan 22.

Division of Pathology, Mitsui Memorial Hospital, Kanda-Izumi-cho 1, Chiyoda-ku, Tokyo 101-8643, Japan.

A 66-year-old Japanese man was referred to our hospital because of suspected duodenal cancer. Upper gastric endoscopy revealed a giant polypoid-type tumor that extended from the duodenum bulb to the pyloric ring. A computed tomography scan revealed a slightly enhanced lobular tumor protruding into the duodenum bulb. Positron emission tomography showed an accumulation of (18)F-fluorodeoxyglucose in the area extending from the antrum of the stomach to the duodenum bulb. Since an endoscopic ultrasound test suggested that the tumor might invade the muscular tunic, indications of endoscopic mucosal resection were not favored, and the tumor was curatively removed via distal gastrectomy. The histopathologic diagnosis was papillary adenocarcinoma, and the invasion depth was the mucosal layer without vascular invasion, which was different from the preoperative diagnosis. Our case suggests the difficulties in precise diagnosis of the invasion depth of the giant polypoid cancer.
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http://dx.doi.org/10.1155/2015/986971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320937PMC
February 2015

An analysis of initial and follow-up CT findings in intramural hematoma, aortic double-lumen dissection, and mixed type lesions.

Acta Radiol 2015 Sep 26;56(9):1091-9. Epub 2014 Sep 26.

Mitsui Memorial Hospital, Tokyo, Japan.

Background: Although the clinical presentation of intramural hematoma (IMH) and aortic double-lumen dissection (AD) is similar, the imaging results and subsequent clinical course of the two lesions differ.

Purpose: To compare the clinical and radiological findings of IMH, AD, and mixed type lesions.

Material And Methods: Forty-two patients with IMH, 38 with AD, and 10 with mixed type lesions were imaged with post-contrast-enhanced CT. The most proximal ulcer-like lesions and entry tears and the distal ends of the IMH and AD were evaluated. The interval change of the intramural hematoma, ulcer-like lesion, and false lumen was observed. The pathological findings of the aorta were evaluated in 15 patients.

Results: The most proximal ulcer-like lesion and entry tear were located in the arch to the descending aorta in 27 (64.2%) of the 42 patients with IMH and in 24 (63.1%) of the 38 patients with AD. The distal extension was located at the iliac arteries in six (14.3%) patients with IMH and in 31 (81.6%) patients with AD (P < 0.001). The intramural hematomas regressed in 29 (93.5%) of 31 patients, and the ulcer-like lesion progressed in 14 (70%) of 20 patients with IMH. The clinical features of the mixed type lesions resembled those of AD, rather than IMH. The intramural hematoma or dissection was observed within the outer media in all lesion types on histopathology.

Conclusion: There is a distinct difference between IMH and AD in distal extension; however, the locations of the lesions are pathologically the same in the media of the aorta.
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http://dx.doi.org/10.1177/0284185114549824DOI Listing
September 2015

Sclerosing rhabdomyosarcoma of a chest wall in an adult: a case report and review of the literature.

Ann Thorac Cardiovasc Surg 2014 3;20 Suppl:642-5. Epub 2013 Oct 3.

Department of Thoracic Surgery, Pathology, Mitsui Memorial Hospital, Chiyoda-ku, Tokyo, Japan.

Sclerosing rhabdomyosarcoma (SRMS) is a newly recognized and rare variant of rhabdomyosarcoma. This soft tissue tumor has not yet been reported as a thoracic lesion. We report a case of a 26-year-old woman who presented with a large chest wall tumor. The tumor originated from the right anterior chest wall and protruded into the intra- and extrapleural cavity. A transcutaneous needle biopsy revealed spindle cells in an abundant hyalinized and fibrous stroma. Although the tumor was considered as a malignant soft-tissue neoplasm, a definitive diagnosis could not be established. A wide excision of the chest wall including the second, third and fourth rib and a part of sternum was performed. Histologically, cytoplasmic cross-striations were found in a portion of the tumor cells. The tumor cells were positive for muscle markers, and the tumor was diagnosed as rhabdomyosarcoma consistent with a sclerosing type of rhabdomyosarcoma. Eighteen months after the complete resection, the patient has pleural disseminations but is alive and undergoing chemotherapy. This case highlights the histologic features of a rare form of rhabdomyosarcoma, and emphasizes the importance of awareness of its existence and the utility of skeletal muscle markers in distinguishing sclerosing rhabdomyosarcoma from its mimics.
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http://dx.doi.org/10.5761/atcs.cr.13-00030DOI Listing
October 2015

High-grade lung adenocarcinoma with fetal lung-like morphology: clinicopathologic, immunohistochemical, and molecular analyses of 17 cases.

Am J Surg Pathol 2013 Jun;37(6):924-32

Department of Pathology and Clinical Laboratories, Thoracic Surgery Division, National Cancer Center Hospital, Japan.

Low-grade lung adenocarcinoma of fetal lung type, which is well characterized by its unique clinicopathologic and molecular features, is recognized as a distinct variant of lung cancer. In contrast, high-grade lung adenocarcinoma with fetal lung-like morphology (HG-LAFM) has not been studied widely. To characterize this subset better, we analyzed 17 high-grade adenocarcinomas with at least focal component resembling a developing epithelium in the pseudoglandular phase of the fetal lung. These rare (ca. 0.4%) carcinomas occurred predominantly in elderly men with a heavy smoking history, who showed elevated serum α-fetoprotein in 4 of 5 cases tested. Histologic examination revealed a fetal lung-like component as a focal finding accounting for 5% to 60% of the total tumor volume. It was invariably admixed with tissues having a morphology not resembling that of a fetal lung. A coexisting non-fetal lung-like element was quite heterogenous in appearance, showing various growth patterns. However, clear-cell (88%), hepatoid (29%), and large cell neuroendocrine carcinoma (24%) histology seemed overrepresented. HG-LAFM was characterized immunohistochemically by frequent expression of α-fetoprotein (41%), glypican-3 (88%), SALL-4 (59%), neuroendocrine markers (82%), CDX-2 (35%), and p53 (65%). HG-LAFM was molecularly heterogenous in that EGFR or KRAS mutation was observed in 22% of cases tested for both. Our data indicate that HG-LAFMs might form a coherent subgroup of lung adenocarcinomas. However, the uniformly focal nature of the fetal lung-like element, widely diverse coexisting non-fetal lung-like histology, and inhomogenous molecular profiles lead us to believe that HG-LAFM is best regarded as a morphologic pattern showing characteristic association with several clinicopathologic parameters rather than a specific tumor entity.
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http://dx.doi.org/10.1097/PAS.0b013e31827e1e83DOI Listing
June 2013

Pulmonary resection of lung cancer in a patient with partial anomalous pulmonary venous connection.

Ann Thorac Surg 2013 May;95(5):1799-801

Department of Thoracic Surgery and Pathology, Mitsui Memorial Hospital, Tokyo, Japan.

We report a case of a 64-year-old man in whom a partial anomalous pulmonary venous connection (PAPVC) was found before right lower lobectomy for lung cancer. In addition to lung cancer, there was a right superior pulmonary vein that drained into the superior vena cava (SVC). There was a concern of right ventricular heart failure resulting from increased left-to-right shunt flow after lobectomy. Therefore cardiac catheterization was performed to calculate the pulmonary-to-systemic flow rate in the presence of blocked blood flow to the lower lobe pulmonary artery. As a result, we successfully performed lobectomy without correcting the PAPVC.
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http://dx.doi.org/10.1016/j.athoracsur.2012.10.033DOI Listing
May 2013

A case of more than 20 years survival with glioblastoma, and development of cavernous angioma as a delayed complication of radiotherapy.

Neuropathology 2013 Oct 13;33(5):576-81. Epub 2013 Feb 13.

Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan; Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.

Glioblastoma (GBM) is the most common malignant CNS neoplasm, the prognosis of which remains poor even after multidisciplinary treatment. The 5-year overall survival rate of GBM is less than 10% and has remained unchanged for more than 50 years. Because GBM patients rarely survive over a decade, only very few cases of delayed complications caused by therapy have been reported. Here, we report the case of a 24-year-old man who is still alive 21 years after surgical resection and chemoradiotherapy for GBM. This patient developed a cavernous angioma 19 years after the initial surgery as a delayed complication of radiotherapy. The diagnosis of the initial tumor was confirmed by histopathological review, which indicated that the tumor had immunohistochemical and genetic profiles consistent with GBM. Long-term survival in the case of this GBM patient likely resulted from a combination of factors, including hypermethylation of the MGMT (O(6)-methyl guanine methyl transferase) CpG island, young age at diagnosis, good performance status, and complete surgical resection of the tumor. To the best of our knowledge, this case report describes one of the longest-surviving GBM patients and is the first on radiation-induced cavernous angioma in a GBM patient.
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http://dx.doi.org/10.1111/neup.12022DOI Listing
October 2013

Asymptomatic insulinoma: a case report and autopsy series.

Diabetes Res Clin Pract 2012 Dec 17;98(3):445-51. Epub 2012 Oct 17.

Division of Diabetic Metabolic Internal Medicine, Mitsui Memorial Hospital, Tokyo, Japan.

Aims: We investigated the prevalence and characterization of asymptomatic pancreatic tumors in response to our experience of asymptomatic insulinoma.

Methods: A patient with a moderately low glucose level and pancreatic incidentaloma detected by CT was examined. Pancreas specimens from 423 autopsy cases were also pathologically examined systematically by hematoxylin-eosin staining.

Results: The examined patient showed no profile characteristic of insulinoma by fasting or loading tests, however, ASVS led to diagnosis of insulin-producing tumor. The tumor was resected with the pancreatic body and tail and revealed to be 10 mm in diameter, with 98.5% of the cells positive for insulin. Pathological evaluation confirmed a well-differentiated endocrine pancreatic tumor, which was suggestive of an incidentally detected asymptomatic insulinoma. Microscopic evaluations of pancreatic specimens from 423 autopsy cases revealed pancreatic monotonous lesions in 6 cases (1.42%). In 4 autopsy specimens large enough for immuno-histochemical evaluation, the lesions were positive for glucagon but negative for insulin.

Conclusions: As concerns the present study, retrospective immunohistochemical investigation in autopsy cases revealed the presence of asymptomatic glucagonoma but no asymptomatic insulinoma. Advances in diagnostic imaging, however, might raise the probability of detecting early asymptomatic stages of insulinoma incidentally. ASVS appears to be sensitive even for asymptomatic incidental insulinomas.
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http://dx.doi.org/10.1016/j.diabres.2012.08.007DOI Listing
December 2012

Unusual presentation of localized gastric mucosa-associated lymphoid tissue lymphoma mimicking poorly differentiated gastric adenocarcinoma.

Case Rep Gastroenterol 2012 Jan 25;6(1):47-51. Epub 2012 Jan 25.

Department of Internal Medicine, University of Pittsburgh Medical Center, Presbyterian Shadyside, Pittsburgh, Pa., USA.

The risk of misdiagnosing neoplastic cells typically infiltrating an epithelium forming a lymphoepithelial lesion as poorly differentiated gastric cancer in endoscopic biopsies, particularly in low-grade mucosa-associated lymphoid tissue (MALT) lymphomas, is described. A 76-year-old woman was referred for management of a poorly differentiated gastric adenocarcinoma. Diagnostic endoscopy in our unit showed a 2 cm raised, submucosal lesion with central erosion in the upper body of the stomach, but repeat biopsies of the lesion were interpreted as inflamed gastric mucosa and negative for malignancy. Systematic gastric biopsies to rule out any foci of MALT lymphoma changes were also negative. Therefore, endoscopic submucosal dissection was performed to obtain an accurate specimen. Histology revealed centrocyte-like cells and a lymphoepithelial lesion invading into the mucosa with obliteration of the gastric glands, which was initially interpreted as poorly differentiated adenocarcinoma.
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http://dx.doi.org/10.1159/000336322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304077PMC
January 2012