Publications by authors named "Asuka Araki"

46 Publications

Low Fecal Calprotectin Predicts Histological Healing in Patients with Ulcerative Colitis with Endoscopic Remission and Leads to Prolonged Clinical Remission.

Inflamm Bowel Dis 2022 May 18. Epub 2022 May 18.

Inflammatory Bowel Disease Center, Shimane University Hospital, Izumo, Shimane, Japan.

Background: Consensus regarding the cutoff value of fecal calprotectin (FC) for predicting histological healing (HH) in ulcerative colitis (UC) is lacking. This study aimed to determine an optimal FC cutoff value for predicting HH in patients with UC with clinical and endoscopic remission. Furthermore, FC's predictability for prolonged clinical remission (CR) was investigated.

Methods: Patients with UC in clinical and endoscopic remission, defined as a partial Mayo score (PMS) ≤ 2 points and a Mayo endoscopic subscore 0-1, were prospectively enrolled. Biopsy samples were evaluated by Geboes score (GS), with HH defined as a GS < 2.0. Patients were followed for 2 years or until relapse, defined as a PMS > 2 or medication escalation.

Results: Seventy-six patients with UC were included. The median FC value in patients with HH (n = 40) was 56.2 µg/g, significantly lower than that in those with histological activity (118.1 µg/g; P < .01). The area under the curve (AUC) in a receiver operating characteristic (ROC) curve analysis to predict HH for FC was 0.71 (95% confidence interval [CI], 0.59-0.83), with an optimal cutoff value of 82.7 µg/g (73% sensitivity; 64% specificity; P < .01). Of 74 patients observed for 2 years, 54 (73%) had prolonged CR. In the ROC curve analysis, the AUC to predict prolonged CR for FC was 0.79 (95% CI, 0.68-0.90), equivalent to that for HH (0.73; 95% CI, 0.64-0.86; P = .40). The optimal FC cutoff value to predict prolonged CR was 84.6 µg/g (72% sensitivity; 85% specificity; P < .01).

Conclusions: Fecal calprotectin < 82 µg/g predicts HH in patients with UC with clinical and endoscopic remission. Low FC leads to prolonged CR, equivalent to HH.
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http://dx.doi.org/10.1093/ibd/izac095DOI Listing
May 2022

Oxaliplatin-related Portal Hypertension Complicated with Esophageal Varices and Refractory Massive Ascites - Case Report.

Intern Med 2022 Apr 2. Epub 2022 Apr 2.

Department of Internal Medicine II, Shimane University Faculty of Medicine, Japan.

Oxaliplatin, widely used as a chemotherapy drug for colorectal cancer, is known to cause various adverse reactions. In particular, special attention for the development of portal hypertension associated with porto-sinusoidal vascular disease is necessary, as it is a serious adverse life-threating reaction, although rare. We herein report a case of oxaliplatin-related portal hypertension that developed several years after oxaliplatin administration and led to esophageal varices and refractory massive ascites. Clinical physicians should be aware of the possibility of oxaliplatin-induced portal hypertension and its possible development over a long period after discontinuation of the drug.
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http://dx.doi.org/10.2169/internalmedicine.9266-21DOI Listing
April 2022

A Case of Successful Control of Hypercalcemia with Sorafenib, Evocalcet, and Denosumab Combination Therapy for Recurrent Parathyroid Carcinoma.

Intern Med 2022 Apr 2. Epub 2022 Apr 2.

Internal Medicine 1, Shimane University Faculty of Medicine, Japan.

Parathyroid carcinoma (PC) is a rare type of endocrine cancer. Recurrence and metastasis are common after surgery, and refractory hypercalcemia often leads to a poor prognosis. However, there are currently no specific strategies for PC recurrence. We herein report a 61-year-old Japanese man with metastatic PC who was treated with sorafenib, a multikinase inhibitor. In this case, the serum calcium level was under control for 10 months after the initiation of sorafenib. This case suggests that combination therapy with sorafenib, evocalcet, and denosumab may be an alternative, stronger management option for refractory hypercalcemia in recurrent PC.
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http://dx.doi.org/10.2169/internalmedicine.9261-21DOI Listing
April 2022

Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study.

Clin Gastroenterol Hepatol 2022 Jan 17. Epub 2022 Jan 17.

Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Background & Aims: There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage.

Methods: This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients.

Results: The median follow-up period was 4.6 years (range, 0.3-21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52-3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02-7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02-5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality.

Conclusions: Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.
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http://dx.doi.org/10.1016/j.cgh.2022.01.002DOI Listing
January 2022

Open partial nephrectomy of a left-to-right crossed fused renal ectopia with clear cell renal cell carcinoma: Case report and review of the literature.

Urol Case Rep 2022 Mar 4;41:101964. Epub 2021 Dec 4.

Department of Urology, Shimane University Faculty of Medicine, Japan.

Crossed fused renal ectopia (CFRE) is a rare congenital renal abnormality. It is usually diagnosed incidentally by imaging. Herein we report a 53-year-old patient with renal cell carcinoma of CFRE. He was successfully treated with an open partial nephrectomy and was discharged without any complications. Furthermore, we review similar cases of CFRE to identify the clinical features and surgical technique.
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http://dx.doi.org/10.1016/j.eucr.2021.101964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661463PMC
March 2022

Intestinal-type gastric dysplasia in Helicobacter pylori-naïve patients.

Virchows Arch 2022 Apr 17;480(4):783-792. Epub 2021 Nov 17.

Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan.

Gastric dysplasia and gastric cancer in Helicobacter pylori (Hp)-naïve patients usually exhibit a gastric phenotype, reflecting gastric mucosa without intestinal metaplasia (IM). We showed that intestinal-type gastric dysplasia (IGD) rarely occurs in the Hp-naïve stomach. In the last 10 years, we treated 1760 gastric dysplasia and gastric cancer patients, with 3.6% (63/1760) being Hp-naïve. Among these, ten were diagnosed with 14 IGDs and enrolled in this retrospective analysis. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We analyzed their endoscopic and microscopic features and patient demographics. Five men and five women aged 64 ± 21 years were included. WLE showed the depressed lesions mimicking a benign raised erosion in the prepyloric compartment. Multiple growths were confirmed in 30% (3/10) of patients. NBIME showed a near-regular microstructure and capillaries in 50% (7/14) of lesions with a gastritis-like appearance. Histologically, background mucosa was non-atrophic pyloric gland tissue, but 40.0% of samples (4/10) contained sporadic IM. Most of the lesions (8/14) were low-grade dysplasia, and others had a high-grade component, with one progressing to intramucosal carcinoma. The neoplastic surface was widely covered with foveolar epithelium in 57.1% (8/14). Immunohistochemically, neoplastic cells expressed CDX2 in all patients (14/14), MUC2 and CD10 in 92.9% (13/14), MUC5AC in 14% (2/14), and no expression of MUC6, showing an intestinal phenotype. Ki-67 was overexpressed with a mean labeling index of 58.3 ± 38.5%, and p-53 was overexpressed in 92.9% (13/14), regardless of the dysplastic grade. The IGD rarely occurs in Hp-naïve patients with distinctive clinicopathologic characteristics.
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http://dx.doi.org/10.1007/s00428-021-03237-9DOI Listing
April 2022

Palm Pustules Induced by Pemetrexed.

J Thorac Oncol 2021 09 6;16(9):1589-1591. Epub 2021 Jul 6.

Division of Medical Oncology & Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan.

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http://dx.doi.org/10.1016/j.jtho.2021.06.021DOI Listing
September 2021

Sporadic foveolar-type gastric adenoma with a raspberry-like appearance in Helicobacter pylori-naïve patients.

Virchows Arch 2021 Oct 27;479(4):687-695. Epub 2021 May 27.

Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan.

Sporadic foveolar-type gastric adenoma (FGA) has been described as an extremely rare polyp that is whitish and flatly elevated. However, we recently found that sporadic FGA with a raspberry-like appearance (FGA-RA) is not rare in Helicobacter pylori (H. pylori)-naïve gastric mucosa. We endoscopically or surgically treated 647 patients with gastric epithelial neoplasms in the last 5 years, with 7.7% (50/647) being H. pylori-naïve. Among these, 43 FGA-RAs were diagnosed based on histologic and endoscopic features in 34 patients, who were all enrolled in this retrospective study. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We subsequently analyzed their endoscopic and microscopic features and patient characteristics. The patients were 22 males and 12 females aged 57±23 years (mean±2SD). WLE showed raspberry-like small polyps mimicking gastric hyperplastic polyps in the oxyntic gastric compartment (body/fundus). Multiple growths were confirmed in 20.6% (7/34) of the patients. NBIME revealed irregularly shaped papillary/gyrus-like microstructures with abnormal capillaries. Histologically, all lesions were intraepithelial neoplasms, and most of lesions (62.8%, 27/43) exhibited low-grade dysplasia. Immunohistochemically, neoplastic cells featured strong and diffuse MUC5AC expression, negative or very low MUC6 expression, and negative MUC2/CD10 expression. They also showed Ki-67 hyperexpression with a mean labeling index of 59.4±48.7%. The coexistence of fundic gland polyps in the background mucosa was significantly higher in multiple FGA-RA cases than in solitary cases (100% vs. 55.5%, P< 0.05). FGA-RA is a newly suggested histologic variant of sporadic FGA whose occurrence is not rare in daily endoscopic practice.
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http://dx.doi.org/10.1007/s00428-021-03124-3DOI Listing
October 2021

ERCC1 Is a Predictive Biomarker for Non-small Cell Lung Cancer But Is Antibody-dependent.

Anticancer Res 2021 May;41(5):2653-2660

Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine, Izumo, Japan.

Background/aim: To predict the efficacy of platinum-containing chemotherapy, ERCC1 expression levels were investigated. Studies have shown changes in the performance of anti-ERCC1 antibodies; therefore, predicting chemotherapy efficacy by immunohistochemical assessment of ERCC1 is controversial.

Patients And Methods: Twenty-eight patients who received platinum-containing chemotherapy and underwent computed tomography evaluation 6-9 weeks after therapy initiation were retrospectively identified. The tumor samples were evaluated in 2012 and 2018 using the latest anti-ERCC1 antibodies available at those times.

Results: In 2012, the ERCC1 H-score was significantly higher in patients with disease progression than in patients without disease progression (p=0.019). Although the same trend was shown in 2018, there were some inconsistent results between the 2012 and 2018 samples.

Conclusion: Patients with tumors showing low ERCC1 expression had a better disease control rate on platinum-containing chemotherapy. However, since the performance of the antibody changed over time, standardized technology to evaluate ERCC1 expression is needed.
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http://dx.doi.org/10.21873/anticanres.15046DOI Listing
May 2021

Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration.

Cells 2021 01 14;10(1). Epub 2021 Jan 14.

Department of Neurology, Shimane University Faculty of Medicine, 89-1 Enya Cho, Izumo 693-8501, Japan.

Ataxia and Male Sterility (AMS) is a mutant mouse strain that contains a missense mutation in the coding region of , a gene that encodes a deglutamylase. AMS mice exhibit early cerebellar Purkinje cell degeneration and an ataxic phenotype in an autosomal recessive manner. To understand the underlying mechanism, we generated neuronal stem cell (NSC) lines from wild-type (NMW7), mutation heterozygous (NME), and mutation homozygous (NMO1) mouse brains. The NNA1 levels were decreased, and the glutamylated tubulin levels were increased in NMO1 cultures as well as in the cerebellum of AMS mice at both 15 and 30 days of age. However, total β-tubulin protein levels were not altered in the AMS cerebellum. In NMO1 neurosphere cultures, β-tubulin protein levels were increased without changes at the transcriptional level. NMO1 grew faster than other NSC lines, and some of the neurospheres were attached to the plate after 3 days. Immunostaining revealed that SOX2 and nestin levels were decreased in NMO1 neurospheres and that the neuronal differentiation potentials were reduced in NMO1 cells compared to NME or NMW7 cells. These results demonstrate that the AMS mutation decreased the NNA1 levels and increased glutamylation in the cerebellum of AMS mice. The observed changes in glutamylation might alter NSC properties and the neuron maturation process, leading to Purkinje cell death in AMS mice.
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http://dx.doi.org/10.3390/cells10010155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830091PMC
January 2021

Identification of Molecular Basis for Objective Discrimination of Breast Cancer Cells (MCF-7) from Normal Human Mammary Epithelial Cells by Raman Microspectroscopy and Multivariate Curve Resolution Analysis.

Int J Mol Sci 2021 Jan 14;22(2). Epub 2021 Jan 14.

Raman Project Center for Medical and Biological Applications, Shimane University, Matsue 690-8504, Japan.

Raman spectroscopy (RS), a non-invasive and label-free method, has been suggested to improve accuracy of cytological and even histopathological diagnosis. To our knowledge, this novel technique tends to be employed without concrete knowledge of molecular changes in cells. Therefore, identification of Raman spectral markers for objective diagnosis is necessary for universal adoption of RS. As a model study, we investigated human mammary epithelial cells (HMEpC) and breast cancer cells (MCF-7) by RS and employed various multivariate analyses (MA) including principal components analysis (PCA), linear discriminant analysis (LDA), and support vector machine (SVM) to estimate diagnostic accuracy. Furthermore, to elucidate the underlying molecular changes in cancer cells, we utilized multivariate curve resolution analysis-alternating least squares (MCR-ALS) with non-negative constraints to extract physically meaningful spectra from complex cellular data. Unsupervised PCA and supervised MA, such as LDA and SVM, classified HMEpC and MCF-7 fairly well with high accuracy but without revealing molecular basis. Employing MCR-ALS analysis we identified five pure biomolecular spectra comprising DNA, proteins and three independent unsaturated lipid components. Relative abundance of lipid 1 seems to be strictly regulated between the two groups of cells and could be the basis for excellent discrimination by chemometrics-assisted RS. It was unambiguously assigned to linoleate rich glyceride and therefore serves as a Raman spectral marker for reliable diagnosis. This study successfully identified Raman spectral markers and demonstrated the potential of RS to become an excellent cytodiagnostic tool that can both accurately and objectively discriminates breast cancer from normal cells.
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http://dx.doi.org/10.3390/ijms22020800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830327PMC
January 2021

Immunohistochemical expression of filaggrin is decreased in proton pump inhibitor non-responders compared with proton pump inhibitor responders of eosinophilic esophagitis.

Esophagus 2021 04 9;18(2):362-371. Epub 2020 Sep 9.

Organ Pathology Unit, Department of Pathology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.

Background: Eosinophilic esophagitis (EoE) is an allergic gastrointestinal disease that features eosinophilic infiltration of esophageal mucosa, but the role of barrier dysfunction of the epithelium in its pathogenesis remains to be elucidated. Clinically, EoE is divided into proton pump inhibitor-non-responders (PPI-NR) and PPI-responders (PPI-R). Our main aims were to investigate the differences of expression of epidermal differential complex (EDC) proteins and desmoglein that are considered to play important roles in formation of the epidermal skin barrier between these two conditions and to seek the usefulness of the differences in pathological diagnosis. Conventional histopathological findings and allergic background were also compared.

Methods: Twenty-nine PPI-NR and 44 PPI-R were recruited, and 35 reflux esophagitis patients were also enrolled. After clinical information and histopathological findings were reviewed, immunohistochemical expression of EDC proteins (filaggrin, loricrin, and involucrin) and desmoglein in all three groups were examined and semi-quantitatively scored.

Results: Regarding allergic conditions, the prevalence of asthma was significantly higher in PPI-NR than in PPI-R. Other allergic conditions showed no differences. Histopathological findings did not exhibit the statistical difference between PPI-NR and PPI-R. However, immunostaining score of filaggrin in PPI-NR was significantly lower than in PPI-R, although the expressions of involucrin, loricrin and desmoglein demonstrated no differences.

Conclusions: The results suggest a role of reduced filaggrin expression in the difference of effectiveness of PPI treatment between PPI-NR and PPI-R. Moreover, immunohistochemical determination of filaggrin expression in EoE patients could be informative in the clinical decision of how to treat the patients.
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http://dx.doi.org/10.1007/s10388-020-00781-2DOI Listing
April 2021

Diagnosis of a small Leydig cell tumor by dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging.

Radiol Case Rep 2020 Jul 1;15(7):875-878. Epub 2020 May 1.

Department of Radiology, Shimane University Faculty of Medicine, P.O. Box 00693-8501, 89-1 Enya Izumo, Japan.

Leydig cell tumors are usually small and resemble normal ovarian stroma, so they are often difficult to localize. Here, we present a rare case in 39-year-old woman which dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging findings showed some differences between a Leydig cell tumor and normal ovarian stroma. Combining these 2 MRI techniques may be useful for diagnosing a Leydig cell tumor.
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http://dx.doi.org/10.1016/j.radcr.2020.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200933PMC
July 2020

A case of cellular variants of Sclerosing epithelioid fibrosarcoma resembling Plasmacytoma/Myeloma: Diagnostic difficulty in the fine needle aspiration.

Int J Surg Case Rep 2020 7;68:228-233. Epub 2020 Mar 7.

Department of Organ Pathology, Shimane University School of Medicine, Japan.

Introduction: Sclerosing epithelioid sarcoma (SEF) is a rare fibroblastic sarcoma. It is classically composed of cords of epithelioid cells embedded in a hyalinized stroma; however, cases of cellular variants also exist. A cellular variants of SEF can mimic Plasmacytoma/Myeloma (PM) and myoepithelioma. Hence, accurate diagnosis of SEF is important for cytologists and pathologists.

Presentation Of Case: We present the case of a 75-year-old female patient diagnosed with a cellular variant of SEF occurring in the erector spinal muscle. Immunostaining of MUC4 and fluorescence in situ hybridization of EWSR1 (break-apart signal) were used for diagnosis.

Conclusion: The cellular variants of SEF presented diagnostic difficulties in fine needle aspiration. Moreover, it could not be distinguished from PM.
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http://dx.doi.org/10.1016/j.ijscr.2020.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078455PMC
March 2020

Eosinophilic Granulomatosis with Polyangiitis Initially Diagnosed as Eosinophilic Gastroenteritis.

Intern Med 2020 Apr 26;59(8):1029-1033. Epub 2019 Dec 26.

Department of Internal Medicine II, Shimane University Faculty of Medicine, Japan.

We herein report two cases of eosinophilic granulomatosis with polyangiitis (EGPA) initially diagnosed as eosinophilic gastroenteritis (EGE) based solely on endoscopic biopsy results. One year after the EGE diagnosis, one patient presented with multiple purpura, and skin biopsy findings resulted in a change of the diagnosis to EGPA. In another patient, multiple skin and colonic ulcerations emerged eight years after the diagnosis of EGE, at which time histological examinations of endoscopic biopsy specimens revealed vasculitis, and the diagnosis was changed to EGPA. Physicians should be aware of the possible existence of EGPA in cases diagnosed as EGE.
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http://dx.doi.org/10.2169/internalmedicine.3391-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205524PMC
April 2020

Tenosynovial Giant Cell Tumor, Localized Type With Extensive Chondroid Metaplasia: A Case Report With Immunohistochemical and Molecular Genetic Analysis.

Int J Surg Pathol 2020 Jun 26;28(4):447-453. Epub 2019 Nov 26.

Shimane University, Izumo, Shimane, Japan.

Tenosynovial giant cell tumor (TSGCT) of localized type is a common disease occurring mostly in the hands. Diagnosis of this tumor is relatively easy to render with hematoxylin-eosin-stained sections as compared with that of TSGCT of diffuse type. However, very rare cases with chondroid metaplasia that have recently been reported mainly in diffuse type can make pathological differentiation from soft tissue cartilaginous tumors extremely difficult. In this article, the authors present the second reported case of TSGCT of localized type showing extensive chondroid metaplasia. Pathological interpretation was difficult without utilizing immunohistochemistry and fluorescence in situ hybridization. One must be careful not to misdiagnose this lesion as cartilaginous tumors of soft tissue, and we suspect at least some chondroblastoma-like chondroma could be reclassified as TSGCT of localized type with extensive chondroid metaplasia. Morphological, immunohistochemical, and molecular genetic characteristics are presented and discussed.
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http://dx.doi.org/10.1177/1066896919889672DOI Listing
June 2020

Gastric foveolar-type adenomas endoscopically showing a raspberry-like appearance in the -uninfected stomach.

Endosc Int Open 2019 Jun 12;7(6):E784-E791. Epub 2019 Jun 12.

Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan.

Foveolar-type adenoma is described as a very rare tumor that occurs in individuals without (HP) infection and diagnosed as adenocarcinoma in the Japanese Classification of Gastric Carcinoma (JCGC). However, we have frequently encountered patients with foveolar-type adenoma that endoscopically resembles a hyperplastic polyp, suggesting that it has just been overlooked to date. Here, we analyzed clinicopathological characteristics of a special subtype of foveolar-type adenoma showing specific endoscopic findings. From a total of 212 patients with gastric cancer resected during a 22-month period, we enrolled 14 (6.6 %) diagnosed with foveolar-type adenoma (adenocarcinoma in JCGC). HP infection status was determined by eradication history, HP serum IgG antibody level, urea breath test, and endoscopic and histological findings. All lesions were observed using white-light endoscopy and narrow-band imaging with magnification endoscopy (NBIME). Endoscopically resected lesions were histologically examined. None of 14 patients had a current or past history of HP infection. All lesions were visualized on non-atrophic gastric mucosa as small reddish protrusions with fine granular surface, showing a raspberry-like appearance. NBIME showed papillary or gyrus-like microstructures with irregular capillary. Lesions were histologically diagnosed as foveolar-type adenoma showing MUC5AC-positive gastric mucin phenotype. Ki-67 was overexpressed (median labeling index 69.9 %, range 28.4 - 92.1 %), though all lesions were an intraepithelial tumor without stromal invasion. p53 over-staining was not seen in any. Raspberry-like lesions on non-atrophic gastric mucosa in HP-uninfected individuals should be evaluated for the possibility of a special subtype of foveolar-type adenoma.
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http://dx.doi.org/10.1055/a-0854-3818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561766PMC
June 2019

Xp11.2 translocation renal cell carcinoma with SFPQ/PSF-TFE3 fusion gene: A case report with unusual histopathologic findings.

Pathol Res Pract 2019 Sep 26;215(9):152479. Epub 2019 May 26.

Department of Organ Pathology, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan.

Xp11.2 translocation renal cell carcinoma (Xp11tRCC) is a subtype of renal cell carcinoma (RCC) characterized by chromosomal rearrangement of the region harboring the transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3). Xp11tRCCs comprises 20% to 40% of RCCs of children and adolescents and is generally associated with good prognosis. However in adult, the incidence of this tumor is relatively low (1% to 4%), suggesting a more aggressive course. TFE3 gene is fused by translocation to numerous partner genes, and definitive molecular characteristics can be difficult to verify. In this case report, we presented a case of Xp11tRCC with the SFPQ/PSF-TFE3 chimeric gene. The fusion gene was detected by 5'-rapid amplification of cDNA ends (5'RACE). The tumor was found to be in an advanced stage with multiple lymph node metastases. The histological characteristics of the tumor were different from those of XP11tRCC with other more frequently detected fusion genes.
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http://dx.doi.org/10.1016/j.prp.2019.152479DOI Listing
September 2019

Is Asymptomatic Esophageal Eosinophilia the Same Disease Entity as Eosinophilic Esophagitis?

Clin Gastroenterol Hepatol 2019 06 23;17(7):1405-1407. Epub 2018 Aug 23.

Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane, Japan.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder that is characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Its prevalence has been increasing rapidly in both Western and Asian countries. In Japan, most of the cases of esophageal eosinophilia (EE) are found in an upper endoscopy examination for gastric cancer screening performed during a comprehensive health check-up. Indeed, we frequently encounter patients with asymptomatic EE showing typical endoscopic findings, such as linear furrows, as well as histologic findings compatible with EoE. However, the current clinical guidelines for EoE diagnosis include symptoms related to esophageal dysfunction, thus patients without symptoms do not fulfill the diagnostic criteria. The clinical characteristics remain to be fully elucidated, thus we aimed to clarify clinical features of asymptomatic EE as compared with those of EoE.
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http://dx.doi.org/10.1016/j.cgh.2018.08.048DOI Listing
June 2019

Successful Food-Elimination Diet in an Adult with Eosinophilic Gastroenteritis.

ACG Case Rep J 2018 23;5:e38. Epub 2018 May 23.

Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Izumo, Japan.

We successfully treated a 22-year-old woman with eosinophilic gastroenteritis (EGE) using a multiple food-elimination diet. The patient was diagnosed with EGE based on histopathological findings and initially treated with oral prednisolone. The symptoms immediately improved, although they recurred when prednisolone was tapered to a low dose. We then treated her with a multiple food-elimination diet, including milk, soy, eggs, wheat, nuts, seafood, and rice. During dietary treatment, we identified dairy products and eggs as causative foods of the symptoms, and we ceased prednisolone. Similar to eosinophilic esophagitis, an elimination diet may be effective for adult patients with EGE.
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http://dx.doi.org/10.14309/crj.2018.38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968151PMC
May 2018

Acute suppurative thyroiditis caused by thyroid papillary carcinoma in the right thyroid lobe of a healthy woman.

Thyroid Res 2018 15;11. Epub 2018 May 15.

1Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501 Japan.

Background: The thyroid gland is resistant to microbial infection, because of its organ characteristics such as encapsulation, iodine content, and rich blood supply. Therefore, acute suppurative thyroiditis (AST), as a bacterial infection of the thyroid gland, is rarely seen. AST typically takes places on the left side the neck region in children, because of the coincidence of the left piriform sinus fistula, as a most common route of infection. AST is also usually seen in immunocompromised hosts. Herein, we report a rare case of AST in the right thyroid lobe of adult woman without any immunocompromised condition.

Case Presentation: A 59-year-old woman was introduced to our hospital for the further examination with fever, sore throat, and right anterior neck swelling. The patient appeared not to be immunodeficient. Neck ultrasonography showed a 47-mm, hypoechoic, heterogeneous nodule with ill-defined margins and irregular form, suggesting a right thyroid malignant nodule. Fine needle aspiration (FNA) biopsy specimen revealed numerous number of neutrophils in the background without nuclear atypia. Based on the clinical course and cytology, AST was confirmed to be diagnosed. Complete response was obtained by an intravenous administration of antimicrobial agents within a week. Image findings such as CT scan did not show any piriform sinus fistula. Four months later, neck ultrasonography showed a significant decrease in size of the nodule in the right thyroid gland to 27 mm, but the lesion still resembled a malignant nodule. So, FNA was repeated again and cytological examination confirmed papillary thyroid carcinoma (PTC). The patient subsequently underwent total thyroidectomy and bilateral level D1 lymph node dissection. Histological findings revealed a 20-mm PTC in the right lobe with sternothyroid muscle invasion of the tumor.

Conclusions: This report represents a rare case of AST associated with PTC on the right side of thyroid gland, found in a healthy adult woman. The reason why AST coincided with malignant thyroid tumor is unclear. We have to take it into our account that malignant tumor may exist in the background when AST is identified on the right side of thyroid gland with a healthy subject.
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http://dx.doi.org/10.1186/s13044-018-0049-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952856PMC
May 2018

Co-localization of cystatin C and prosaposin in cultured neurons and in anterior horn neurons with amyotrophic lateral sclerosis.

J Neurol Sci 2018 Jan 20;384:67-74. Epub 2017 Nov 20.

Departments of Internal Medicine III, Shimane University Faculty of Medicine, Japan.

Cystatin C (CST3) is a cysteine protease inhibitor that regulates lysosomal enzyme activity and is reported to be involved in the process of neurodegeneration. In the present study, we investigated whether CST3 interacts with other proteins and affects neurodegeneration in vitro and under disease conditions. We intended to identify any protein that interacts with CST3 by using a yeast two-hybrid system, and found prosaposin (PSAP) as a candidate protein. The binding of CST3 and PSAP was confirmed using an immunoprecipitation-based in vitro assay. An enzyme activity assay revealed that PSAP ameliorated CST3-mediated inhibition of cathepsin B activity. To investigate further, CST3 and PSAP were co-expressed in HeLa cells and in a human neuronal cell line (A1). Subsequent immunocytochemical studies demonstrated that they were co-localized mainly in the lysosomes. In spinal motor neurons of autopsy cases, both proteins showed a granular staining pattern. However, the staining intensities of CST3 and PSAP decreased in Bunina body-positive motor neurons of patients with amyotrophic lateral sclerosis (ALS). Further analysis with immunofluorescence staining revealed that CST3 was immunopositive in the inclusions of ALS motor neurons, where it was closely associated, and sometimes co-localized, with PSAP. CST3 immunoreactivity is recognized as a marker for Bunina bodies in ALS, suggesting that PSAP might also be included in Bunina bodies. The interaction of CST3 and PSAP may alter their functions, leading to motor neuron degeneration in ALS.
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http://dx.doi.org/10.1016/j.jns.2017.11.023DOI Listing
January 2018

CNS high-grade neuroepithelial tumor with BCOR internal tandem duplication: a comparison with its counterparts in the kidney and soft tissue.

Brain Pathol 2018 09 28;28(5):710-720. Epub 2017 Dec 28.

Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Central nervous system high-grade neuroepithelial tumors with BCOR alteration (CNS HGNET-BCOR) are a recently reported rare entity, identified as a small fraction of tumors previously institutionally diagnosed as so-called CNS primitive neuroectodermal tumors. Their genetic characteristic is a somatic internal tandem duplication in the 3' end of BCOR (BCOR ITD), which has also been found in clear cell sarcomas of the kidney (CCSK) and soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and these BCOR ITD-positive tumors have been reported to share similar pathological features. In this study, we performed a clinicopathological and molecular analysis of six cases of CNS HGNET-BCOR, and compared them with their counterparts in the kidney and soft tissue. Although these tumors had histologically similar structural patterns and characteristic monotonous nuclei with fine chromatin, CNS HGNET-BCOR exhibited glial cell morphology, ependymoma-like perivascular pseudorosettes and palisading necrosis, whereas these features were not evident in CCSK or URCS/PMMTI. Immunohistochemically, diffuse staining of Olig2 with a mixture of varying degrees of intensity, and only focal staining of GFAP, S-100 protein and synaptophysin were observed in CNS HGNET-BCOR, whereas these common neuroepithelial markers were negative in CCSK and URCS/PMMTI. Therefore, although CNS HGNET-BCOR, CCSK and URCS/PMMTI may constitute a group of BCOR ITD-positive tumors, only CNS HGNET-BCOR has histological features suggestive of glial differentiation. In conclusion, we think CNS HGNET-BCOR are a certain type of neuroepithelial tumor relatively close to glioma, not CCSK or URCS/PMMTI occurring in the CNS.
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http://dx.doi.org/10.1111/bpa.12585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028450PMC
September 2018

A Combined Deposition of Lanthanum and β2-Microglobulin-Related Amyloid in the Gastroduodenal Mucosa of Hemodialysis-Dependent Patients: An Immunohistochemical, Electron Microscopic, and Energy Dispersive X-Ray Spectrometric Analysis.

Int J Surg Pathol 2017 Dec 4;25(8):674-683. Epub 2017 Jul 4.

1 Shimane University, Izumo, Shimane, Japan.

Lanthanum carbonate (LC) is a new type of phosphate adsorbent used to treat patients with hyperphosphatemia caused by chronic kidney diseases. Recent studies have pointed out that lanthanum deposition can be found in the cytoplasm of histiocytes in the gastroduodenal mucosa of these patients. On the other hand, it is well known that patients on long-term hemodialysis can develop deposition of β2-microglobulin-related amyloid (Aβ2M) mainly around joints. However, involvement of the gastrointestinal tract by hemodialysis-associated amyloidosis has been thought to be rare, and therefore only Aβ2M, if any, has been reported to accumulate in the vascular walls of the submucosa and muscularis propria. Thus, in contrast to AA amyloid, biopsy from gastrointestinal mucosa has long been considered to have little significance in detecting amyloid. We present unusual histologic findings on biopsy specimens taken from the gastroduodenal mucosa of 7 hemodialysis-dependent patients taking LC for more than a year. These findings were due to a combined deposition of lanthanum and β2-microglobulin-related amyloid in the cytoplasm of histiocytes. The deposition of amyloid was confirmed by conventional histochemistry, immunohistochemistry, and transmission electron microscopy, and that of lanthanum by transmission electron microscopy and scanning electron microscopy/energy dispersive X-ray spectrometry. This is the first report of such a peculiar combined deposition of lanthanum and amyloid in the gastroduodenal mucosa of hemodialysis patients. Although the exact mechanism of combination and pathogenesis is unclear, we believe that histologic examination of the gastrointestinal mucosa should be considered in the careful follow-up and observation of hemodialysis patients taking LC.
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http://dx.doi.org/10.1177/1066896917718623DOI Listing
December 2017

Celiac disease in non-clinical populations of Japan.

J Gastroenterol 2018 Feb 7;53(2):208-214. Epub 2017 Apr 7.

Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.

Background: Celiac disease is a chronic autoimmune enteropathy caused by gluten ingestion. While its prevalence in Western countries is reported to be as high as 1%, the prevalence has not been evaluated in a large-scale study of a Japanese population. The aim of our study was to clarify the possible presence of celiac disease in a Japanese non-clinical population as well as in patients showing symptoms suggestive of the disease.

Methods: Serum samples were collected from 2008 non-clinical adults and 47 patients with chronic unexplained abdominal symptoms between April 2014 and June 2016. The anti-tissue transglutaminase (TTG) immunoglobulin A antibody titer was determined as a screening test for celiac disease in all subjects, and individuals with a value of >2 U/mL subsequently underwent testing for the presence of serum endomysial IgA antibody (EMA) as confirmation. Those testing positive for EMA or with a high concentration (>10 U/mL) of TTG were further investigated by histopathological examinations of duodenal mucosal biopsy specimens and HLA typing tests.

Results: Of the 2008 non-clinical adults from whom serum samples were collected, 161 tested positive for TTG, and all tested negative for EMA. Four subjects who had a high TTG titer were invited to undergo confirmatory testing, and the histopathological results confirmed the presence of celiac disease in only a single case (0.05%). Of the 47 symptomatic patients, one (2.1%) was found to have a high TTG titer and was diagnosed with celiac disease based on duodenal histopathological findings.

Conclusion: The presence of celiac disease in a non-clinical Japanese population was low at 0.05% and was rarely found in patients with unexplained chronic abdominal symptoms.
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http://dx.doi.org/10.1007/s00535-017-1339-9DOI Listing
February 2018

Telomerase activation in posterior fossa group A ependymomas is associated with dismal prognosis and chromosome 1q gain.

Neuro Oncol 2017 Sep;19(9):1183-1194

Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Austria; Neuromed Campus, Kepler University Hospital, Linz, Austria; Institute of Neurology, Medical University of Vienna, Austria; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neuropathology, University Hospital Heidelberg, Germany; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neurosurgery, Medical University of Vienna, Austria; Department of Radiotherapy, Medical University of Vienna, Austria.

Background: Ependymomas account for up to 10% of childhood CNS tumors and have a high rate of tumor recurrence despite gross total resection. Recently, classification into molecular ependymoma subgroups has been established, but the mechanisms underlying the aggressiveness of certain subtypes remain widely enigmatic. The aim of this study was to dissect the clinical and biological role of telomerase reactivation, a frequent mechanism of cancer cells to evade cellular senescence, in pediatric ependymoma.

Methods: We determined telomerase enzymatic activity, hTERT mRNA expression, promoter methylation, and the rs2853669 single nucleotide polymorphism located in the hTERT promoter in a well-characterized cohort of pediatric intracranial ependymomas.

Results: In posterior fossa ependymoma group A (PF-EPN-A) tumors, telomerase activity varied and was significantly associated with dismal overall survival, whereas telomerase reactivation was present in all supratentorial RelA fusion-positive (ST-EPN-RELA) ependymomas. In silico analysis of methylation patterns showed that only these two subgroups harbor hypermethylated hTERT promoters suggesting telomerase reactivation via epigenetic mechanisms. Furthermore, chromosome 1q gain, a well-known negative prognostic factor, was strongly associated with telomerase reactivation in PF-EPN-A. Additional in silico analyses of gene expression data confirmed this finding and further showed enrichment of the E-twenty-six factor, Myc, and E2F target genes in 1q gained ependymomas. Additionally, 1q gained tumors showed elevated expression of ETV3, an E-twenty-six factor gene located on chromosome 1q.

Conclusion: Taken together we describe a subgroup-specific impact of telomerase reactivation on disease progression in pediatric ependymoma and provide preliminary evidence for the involved molecular mechanisms.
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http://dx.doi.org/10.1093/neuonc/nox027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570194PMC
September 2017

A Case Report of Bilateral Sarcomatoid Carcinoma of Adrenal Glands With Adrenal Insufficiency.

Int J Surg Pathol 2016 Dec 27;24(8):743-748. Epub 2016 Jun 27.

Shimane University School of Medicine, Shimane, Japan.

Adrenocortical carcinomas are relatively rare, but they are considered to be highly aggressive malignant tumors. Sarcomatoid carcinomas represent an even more aggressive type. Bilateral malignant adrenal tumors are extraordinary rare, except for those that represent metastatic spread from a primary neoplasm. Here we report a case of a 69-year-old woman who presented symptoms that raised strong suspicions of adrenal insufficiency. Bilateral adrenal masses, identified in the imaging study, were responsible for the clinical manifestation and surgically resected. Surgical specimens of the bilateral adrenal tumors shared histological features compatible with sarcomatoid carcinoma. It was very difficult to confirm that the sarcomatoid carcinomas were derived from the cortex of the adrenal glands, but careful morphological observation and the panel of antibodies used for immunohistochemistry made the diagnosis possible. This is the first report of sarcomatoid carcinomas involving both adrenal glands. It should be emphasized that sarcomatoid carcinoma can arise bilaterally from even functionally impaired adrenal glands.
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http://dx.doi.org/10.1177/1066896916657589DOI Listing
December 2016

Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma.

Acta Neuropathol Commun 2016 08 22;4(1):88. Epub 2016 Aug 22.

Institute of Neurology, Medical University of Vienna, Vienna, Austria.

Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers are needed to improve patient outcome. To date, the most promising candidate marker is chromosome 1q gain, which has been associated in independent studies with adverse outcome. Furthermore, gene expression and methylation profiles revealed distinct molecular subgroups in the supratentorial and posterior fossa (PF) compartment and Laminin alpha-2 (LAMA2) and Neural Epidermal Growth Factor Like-2 (NELL2) were suggested as surrogate markers for the two PF subgroups PF-EPN-A and PF-EPN-B. PF-EPN-A tumors were also characterized by tenascin-C (TNC) expression and tenascin-C has been suggested as candidate gene on 9q, involved in tumor progression. Therefore, we have analyzed the status of chromosome 1q, TNC, LAMA2, and NELL2 expression in a series of pediatric PF ependymomas in terms of their frequency, associations among themselves, and clinical parameters, as well as their prognostic impact. We confirm the negative prognostic impact of 1q gain and TNC expression and could classify PF ependymomas by these two markers into three molecular subgroups. Tumors with combined 1q gain and TNC expression had the poorest, tumors without 1q gain and TNC expression had a favorable and TNC positive 1q non-gained cases had an intermediate outcome. We found also differences in age and tumor grade in the three subgroups and thus, provide evidence that PF pediatric ependymomas can be divided by chromosome 1q status and TNC expression in three molecular subgroups with distinct clinico-pathological features. These analyses require only few amounts of tumor tissue, are broadly available in the routine clinical neuropathological setting and thus, could be used in further therapy trials to optimize treatment of ependymoma patients.
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http://dx.doi.org/10.1186/s40478-016-0349-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994287PMC
August 2016

Interpretation of postmortem head computed tomography for non-traumatic in-hospital deaths by non-radiologists: a preliminary study.

Springerplus 2016 4;5(1):978. Epub 2016 Jul 4.

Department of Organ Pathology, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501 Japan.

Purpose: Postmortem computed tomography (PMCT) has recently become important to clarify the cause of death in forensic medicine. It has also been proven to be useful for in-hospital deaths to a certain extent when interpreted by radiologists. However, accuracy of the interpretations of PMCT by non-radiologists remains to be elucidated. Nevertheless, they are often required to write death certificates based on the findings of PMCT in the absence of radiologists in Japan. We compared the interpretations of postmortem head CT (PMCT-H) by non-radiologists with the autopsy findings.

Methods: This study included 13 patients who underwent both brain dissection at autopsy and PMCT between June 2011 and December 2014. All cases were non-traumatic in-hospital deaths. Interpretation of PMCT was performed by the clinicians in charge of the patients, not by radiology experts.

Results: The patients were first examined with PMCT and then autopsies were performed. Ten out of 13 cases were confirmed to have no lesions in the cranial cavity by both PMCT-H and autopsy. Two cases were diagnosed with intracranial hemorrhage (intracerebral and/or subarachnoid hemorrhage) and one with recurrent malignant lymphoma by both the clinicians and the pathologists. Intracranial hemorrhages were thought to be the direct causes of mortality of the two patients, and recurrent malignant lymphoma was considered to be one of the cardinal findings of the cancer death. There were no discrepancies between PMCT-H and autopsy findings.

Conclusions: The interpretations of PMCT-H by non-radiologists were completely the same as the autopsy findings regarding the non-traumatic in-hospital deaths in this study. It is premature to draw a definitive conclusion at present, but PMCT-H might be as effective as autopsy not only for those lesions described above but also for no remarkable changes in the brain. There has been no report on such a comparison. We believe further verification of the validity of interpretation of PMCT by non-radiologists is worthwhile in terms of death certificates made out in the absence of radiology experts and pathologists.
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http://dx.doi.org/10.1186/s40064-016-2653-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932004PMC
July 2016
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