Publications by authors named "Seiichi Hirota"

295 Publications

Histomorphological changes in the ileal mucosa in secondary amyloidosis.

QJM 2021 Jun 15. Epub 2021 Jun 15.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya.

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http://dx.doi.org/10.1093/qjmed/hcab168DOI Listing
June 2021

Automated classification of coronary atherosclerotic plaque in optical frequency domain imaging based on deep learning.

Atherosclerosis 2021 Jun 7;328:100-105. Epub 2021 Jun 7.

Division of Cardiology, Department of Medicine II, Kansai Medical University, Hirakata, Japan.

Background And Aims: We developed a deep learning (DL) model for automated atherosclerotic plaque categorization using optical frequency domain imaging (OFDI) and performed quantitative and visual evaluations.

Methods: A total of 1103 histological cross-sections from 45 autopsy hearts were examined to compare the ex vivo OFDI scans. The images were segmented and annotated considering four histological categories: pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), and healed erosion/rupture (HER). The DL model was developed based on pyramid scene parsing network (PSPNet). Given an input image, a convolutional neural network (ResNet50) was used as an encoder to generate feature maps of the last convolutional layer.

Results: For the quantitative evaluation, the mean F-score and IoU values, which are used to evaluate how close the predicted results are to the ground truth, were used. The validation and test dataset had F-score and IoU values of 0.63, 0.49, and 0.66, 0.52, respectively. For the section-level diagnostic accuracy, the areas under the receiver-operating characteristic curve produced by the DL model for FC, PIT, FA, and HER were 0.91, 0.85, 0.86, and 0.86, respectively, and were comparable to those of an expert observer.

Conclusions: DL semantic segmentation of coronary plaques in OFDI images was used as a tool to automatically categorize atherosclerotic plaques using histological findings as the gold standard. The proposed method can support interventional cardiologists in understanding histological properties of plaques.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.06.003DOI Listing
June 2021

Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with .

Pathogens 2021 Apr 6;10(4). Epub 2021 Apr 6.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan.

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma-carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. () is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. was detected in SSA/Ps by fluorescence in situ hybridization using a -targeted probe, and expression of β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for . Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of -positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to -negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-catenin translocation and enhanced expression in Caco2 cells. may play a role in the proliferation of SSA/P lesions through promotion of β-catenin nuclear translocation and REG Iα expression.
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http://dx.doi.org/10.3390/pathogens10040434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067346PMC
April 2021

Pathological Complete Remission of Liver Metastases Correlates With Elimination of Tumor-infiltrating Tregs in Gastric Cancer.

Anticancer Res 2021 Mar;41(3):1571-1577

Department of Gastroenterological Surgery, Hyogo College of Medicine, Nishinomiya, Japan.

Background/aim: Tumor-infiltrating Foxp3 regulatory T-cells (Ti-Tregs) promote tumor progression and contribute to poor prognosis in gastric cancer, but the relationship between Ti-Tregs and response to chemotherapy for liver metastases from gastric cancer (LMGC) is unclear. We estimated the correlation between pathological response to chemotherapy and Ti-Tregs in LMGC.

Patients And Methods: Ti-Tregs were analyzed with immunohistochemistry as CD3 Foxp3 cells in patients with synchronous LMGC.

Results: Of 53 patients with LMGC, 49 received chemotherapy as initial treatment and 10 underwent R0 resection. LMGC disappeared pathologically in 5 resected cases despite radiologically residual disease. Ti-Tregs were found frequently in residual LMGC and primary lesions but rarely in tumor scar tissue. There was no relationship between frequency of CD8 cells and pathological response.

Conclusion: Marked reduction in Ti-Tregs correlates with pathological complete remission of LMGC. Ti-Tregs may be a biomarker to predict the effects of chemotherapy when used in combination with radiological findings.
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http://dx.doi.org/10.21873/anticanres.14917DOI Listing
March 2021

Potential problems of partial resection for colitis-associated cancer in a patient with ulcerative colitis: case report.

J Surg Case Rep 2021 Mar 22;2021(3):rjab086. Epub 2021 Mar 22.

Department of Inflammatory Bowel Disease Surgery, Hyogo College of Medicine, Hyogo, Japan.

Total proctocolectomy and an ileal pouch-anal anastomosis are recommended as the standard procedure for ulcerative colitis (UC)-colitis-associated cancer (CAC). However, several studies have reported the partial colectomy and endoscopic resection of UC-CAC in recent years. We present a surgical case of UC-CAC that was detected at a site that had not been diagnosed preoperatively, and we report potential problems of partial colectomy and endoscopic resection through this case. Considerations of synchronous and metachronous cancer/dysplasia are important before partial resection is planned for CAC in UC. Moreover, it should be noted that endoscopic resection at the anal site can be a risk factor for pouch surgery failure due to fibrosis after resection.
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http://dx.doi.org/10.1093/jscr/rjab086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984846PMC
March 2021

CT Findings of Primary Renal Angiosarcoma.

Case Rep Oncol 2021 Jan-Apr;14(1):212-216. Epub 2021 Mar 1.

Department of Radiology, Hyogo College of Medicine, Nishinomiya, Japan.

Primary angiosarcomas of the kidney are very rare but highly aggressive tumors showing poor prognosis. We present a case of primary renal angiosarcoma occurring in a 60-year-old man with left flank pain. CT images depicted a huge exophytic mass (14 cm in diameter) in the left kidney, exhibiting central extensive hemorrhage or necrosis without contrast enhancement. The mass showed centripetal peripheral nodular enhancement on dynamic contrast-enhanced CT images. We suggest its inclusion in the differential diagnosis of cases of hemorrhagic renal tumors with prominent vasculature.
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http://dx.doi.org/10.1159/000512015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983682PMC
March 2021

Pathological findings after third- and second-generation everolimus-eluting stent implantations in coronary arteries from autopsy cases and an atherosclerotic porcine model.

Sci Rep 2021 Mar 18;11(1):6281. Epub 2021 Mar 18.

Division of Human Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

Pathological changes after third-generation drug-eluting stent implantation remain unclear. We compared the tissue responses of coronary arteries after the implantation of third-generation abluminal biodegradable-polymer everolimus-eluting stent (3rd EES) and second-generation durable-polymer EES (2nd EES) using autopsy specimens and an atherosclerotic porcine model. We compared the histology of stented coronary arteries obtained by autopsy performed 1-10 months after 3rd EES (n (number of cases) = 4, stent-implanted period of 3-7 months) and 2nd EES (n (number of cases) = 9, stent-implanted period of 1-10 months) implantations. The ratio of covered stent struts was higher with 3rd EESs than with 2nd EESs (3rd; 0.824 ± 0.032 vs. 2nd; 0.736 ± 0.022, p = 0.035). Low-density lipoprotein receptor knockout minipigs were stented with 3rd or 2nd EES in the coronary arteries and the stented regions were investigated. The fibrin deposition around the 2nd EES was more prominent. Additionally, higher density of smooth muscle cells was confirmed after the 3rd EES implantation. Pathological examination after the 3rd EES demonstrated a combination of less fibrin deposition and more rapid acquisition of well-developed neointima as compared to the 2nd EES at autopsy and the atherosclerotic porcine model.
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http://dx.doi.org/10.1038/s41598-021-85740-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973802PMC
March 2021

A case of planar-type gastrointestinal stromal tumor of the transverse colon with perforation.

Clin J Gastroenterol 2021 Mar 16. Epub 2021 Mar 16.

Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the human gastrointestinal tract. They usually develop in the stomach and small intestine, but extremely rarely in the colon. Although most GISTs form a mass, some cases showing a flatly proliferating lesion called planar-type GIST have been reported in the sigmoid colon and small intestine. Those are often associated with diverticular lesion and/or perforation. We present here a case of planar-type GIST of the transverse colon with perforation. A 49-year-old Japanese woman abruptly complained of abdominal pain, and was clinically diagnosed as perforation of the transverse colon. Partial resection of the transverse colon including the perforated site was done, and no apparent mass lesion was present. Histology showed that spindle cells flatly proliferated around the perforated area and replaced the layers from submucosa to subserosa. Immunohistochemistry revealed that the spindle cells were KIT-, DOG1- and CD34-positive. Codons 557 and 558 of exon 11 of the c-kit gene were heterozygously deleted at the lesional tissue but not at the normal mucosal tissue. Planar-type GIST of the transverse colon has not been reported yet, and the literature search for the similar cases was done.
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http://dx.doi.org/10.1007/s12328-021-01385-8DOI Listing
March 2021

Diffuse cutaneous mastocytosis: Identification of KIT mutation and long-term follow-up with serum tryptase level.

J Dermatol 2021 May 31;48(5):672-675. Epub 2021 Jan 31.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

Diffuse cutaneous mastocytosis (DCM) is the least common subtype of cutaneous mastocytotis and is generally more severe than other subtypes. We herein report a case of DCM with the consequence of a long-term follow-up. A 4-month-old boy visited with a 3-month history of diffuse erythema that gradually worsened. Darier's sign was positive. The plasma histamine level was 4.95 ng/mL, and the serum tryptase and c-Kit (CD117) levels were 33.3 and 27.4 ng/mL, respectively. Histopathology of the biopsied specimen showed dermal papillary edema and infiltration of mast cells identified by c-Kit and toluidine blue staining. Amplification and direct sequencing of genomic DNA extracted from the skin biopsy specimen revealed the presence of a deletion of codon 419 in exon 8 (c.1255_1257delGAC [p. Asp419del]). There was no evidence of systemic infiltration of mast cells in this case, and we started topical corticosteroid and oral antihistamine with the diagnosis of DCM. Diffuse erythema subsided constantly with age in parallel with chronological decline of serum tryptase level, and it is no longer apparent presently at the age of 7 years, leaving only faint brown spots. Blister formation did not occur throughout the course. Our case indicates that spontaneous resolution can be expected even in DCM after a long period of time, and that serum tryptase level serves as a good surrogate marker to monitor the clinical course.
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http://dx.doi.org/10.1111/1346-8138.15764DOI Listing
May 2021

Severity of liver fibrosis using shear wave elastography is influenced by hepatic necroinflammation in chronic hepatitis patients, but not in cirrhotic patients.

Hepatol Res 2021 Apr 25;51(4):436-444. Epub 2021 Feb 25.

Ultrasound Imaging Center, Hyogo College of Medicine Hospital, Nishinomiya, Japan.

Aim: Shear wave elastography (SWE) in patients with chronic liver diseases is a noninvasive useful method for the diagnosis of liver fibrosis severity, which can be an alternative to liver biopsy. However, the liver stiffness measurement using SWE can be affected by various factors including hepatic inflammation, extrahepatic cholestasis, heart failure, and underlying liver diseases. The aim of this study is to clarify the correlation between liver stiffness using SWE and hepatic necroinflammation serologically and pathologically.

Methods: A total of 843 patients with chronic liver disease who received liver biopsy were analyzed. Liver stiffness measurement using transient elastography (TE) and virtual touch quantification (VTQ) were carried out on the same day as the liver biopsy. The correlation between SWE and hepatic inflammation was analyzed serologically and pathologically.

Results: The liver stiffness values increased significantly with the progression of liver fibrosis and inflammation (overall p < 0.001). In patients with F0-1, F2, and F3, TE and VTQ values of A2 or A3 were significantly higher than those of A0 or A1 (p value, all <0.05), but not in patients with F4. The median alanine aminotransferase (ALT) values increased significantly with the progression of liver inflammation (p < 0.001). Moreover, TE and VTQ in patients with ALT ≥70 IU/L were significantly higher than those in patients with ALT <70 IU/L (p < 0.01), but not in patients with F4.

Conclusion: Shear wave elastography can be affected by hepatic necroinflammation in F0-F3 fibrosis, but not in F4.
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http://dx.doi.org/10.1111/hepr.13617DOI Listing
April 2021

[A case of Endocrine Active Retroperitoneal Ganglioneuroma, Difficult to Differentiate From Adrenal Pheochromocytoma].

Hinyokika Kiyo 2020 Dec;66(12):439-442

The Department of Surgical Pathology, Hyogo College of Medicine.

A 66-year-old woman who had been receiving medication for hypertension and hyperlipidemia was referred to our hospital for evaluation of a left adrenal tumor (12×8 mm) that was incidentally detected on computed tomography. Her 24-hour urinary catecholamine level was elevated, and metaiodobenzylguanidine (MIBG) scintigraphy revealed increased uptake in the area around the left adrenal gland, necessitating laparoscopic adrenalectomy for preoperative diagnosis of left adrenal pheochromocytoma. Intraoperatively, we detected a para-aortic tumor behind the adrenal gland, and this lesion was excised together with the adrenal gland. However, manipulation of the para-aortic tumor led to elevation in the blood pressure to 170 mmHg. Histopathological examination of the resected specimens revealed an adrenocortical adenoma and a para-aortic ganglioneuroma, consisting of ganglion cells, nerve fibers, and Schwann cells. The patient's blood pressure normalized immediately postoperatively, and MIBG scintigraphy revealed a negative result. Endocrine active ganglioneuromas are rare, and to our knowledge, currently only 8 cases (including ours) have been reported in the Japanese and English literature.
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http://dx.doi.org/10.14989/ActaUrolJap_66_12_439DOI Listing
December 2020

A New Ultrasonographic "Fluttering Sign" for Hepatic Hemangioma.

Ultrasound Med Biol 2021 Apr 5;47(4):941-946. Epub 2021 Jan 5.

Division of Hepatobiliary and Pancreatic Disease, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

The aim of the study described here was to clarify the diagnostic value of the fluttering sign, a new sign that characterizes hepatic hemangiomas in gray-scale ultrasonography (US). It refers to a phenomenon in which the speckled echogenicity inside the hemangioma changes continuously and seems to be moving. A total of 172 hemangiomas diagnosed with contrast-enhanced US were evaluated. The fluttering sign was found in 123 of 172 hemangiomas (71.5%). Its prevalence was significantly higher than that of the marginal strong echo (89/172, 51.7%, p < 0.001), posterior acoustic enhancement (103/172, 59.9%, p = 0.031) and chameleon sign (100/172, 58.1%, p = 0.013). In addition, the fluttering sign was observed significantly more frequently in mixed or hypo-echoic tumors than in hyper-echoic tumors (p < 0.001), relatively large tumors (p < 0.001) and tumors that were less than 5 cm from the body surface (p = 0.015). The fluttering sign in gray-scale US has great potential to be a new complementary sign for the diagnosis of hemangioma.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.12.004DOI Listing
April 2021

Adverse Oncologic Outcomes of Adenocarcinoma of the Anal Canal in Patients With Crohn's Disease.

Dis Colon Rectum 2021 04;64(4):409-419

Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo, Japan.

Background: Anal lesions in cases of Crohn's disease can give rise to adenocarcinoma of the anal canal; however, the oncologic outcomes in these patients have not yet been thoroughly investigated.

Objective: This study aimed to clarify the influence of Crohn's disease on the oncologic outcomes in patients with adenocarcinoma of the anal canal.

Design: This was a retrospective observational study from a prospectively collected database.

Settings: The study was conducted at a single institution.

Patients: This study included 102 patients with adenocarcinoma of the anal canal, including 34 (33.3%) with Crohn's disease-associated lesions and 68 (66.7%) with non-Crohn's disease-associated lesions.

Main Outcome Measures: Prognostic factors were detected using a Cox regression analysis, and the oncologic outcomes were calculated using the Kaplan-Meier method.

Results: Crohn's disease-associated patients were significantly younger (45 vs 62 y; p < 0.001), had a high incidence of external/anal gland-type disease (61.8% vs 5.9%, p < 0.001) and had large tumors (7.1 ± 3.0 vs 4.7 ± 2.3 cm; p = 0.03) in comparison with non-Crohn's disease-associated patients. A Cox regression analysis showed that an advanced clinical T stage (T3 or T4; tumor size ≥5 cm) was an independent risk factor for 5-year local recurrence-free survival (HR = 3.49; p = 0.04), disease-free survival (HR = 2.82; p = 0.008), and overall survival (HR = 2.92; p = 0.006), and Crohn's disease association was an independent prognostic factor for local recurrence-free survival (HR = 2.29; p = 0.04) and overall survival (HR = 2.86; p = 0.04). The oncologic outcomes of patients who had the 2 abovementioned negative factors (cT3,4 Crohn's disease-associated patients) were significantly poorer than those of T3,4 non-Crohn's disease-associated patients (5-year local recurrence-free survival: 32.5% vs 70.4%, p = 0.001; disease-free survival: 15.9% vs 40.7%, p = 0.04; overall survival: 25.8% vs 71.0%, p = 0.007).

Limitations: This was a single-arm, retrospective study.

Conclusions: Significantly poorer oncologic outcomes were confirmed in Crohn's disease-associated patients with large tumors. Thus, it is important to perform careful surveillance of anal lesions in patients with Crohn's disease while taking these facts into consideration. See Video Abstract at http://links.lww.com/DCR/B449.

Resultados Oncolgicos Adversos Del Adenocarcinoma Del Canal Anal En Pacientes Con Enfermedad De Crohn: ANTECEDENTES:Las lesiones anales en casos de enfermedad de Crohn pueden dar lugar a un adenocarcinoma del canal anal; sin embargo, los resultados oncológicos en estos pacientes aún no se han investigado a fondo.OBJETIVOS:Este estudio tuvo como objetivo aclarar la influencia de la enfermedad de Crohn en los resultados oncológicos en pacientes con adenocarcinoma del canal anal.DISEÑO:Estudio observacional retrospectivo de una base de datos recopilada prospectivamente.ENTORNO CLINICO:El estudio se realizó en una sola institución.PACIENTES:Este estudio incluyó 102 pacientes con adenocarcinoma del canal anal, incluidos 34 (33,3%) con lesiones asociadas a la enfermedad de Crohn y 68 (66,7%) con lesiones no asociadas a la enfermedad de Crohn.PRINCIPALES MEDIDAS DE VOLARACION:Los factores pronósticos se detectaron mediante un análisis de regresión de Cox y los resultados oncológicos se calcularon utilizando el método de Kaplan-Meier.RESULTADOS:Los pacientes asociados a la enfermedad de Crohn eran significativamente más jóvenes (45 versus a 62 años, p <0,001), tenían una alta incidencia de enfermedad de tipo glandular externo/ anal (61,8% versus a 5,9%, p <0,001) y tumores grandes (7,1 ± 3,0 cm versus a 4,7 ± 2,3 cm, p = 0,03) en comparación con los pacientes no asociados a la enfermedad de Crohn. Un análisis de regresión de Cox mostró que un estadío clínico T avanzado (T3,4; tamaño del tumor ≥5 cm) era un factor de riesgo independiente para la supervivencia sin recidiva local (SLF) a 5 años (índice de riesgo [HR]: 3,49, p = 0,04), supervivencia libre de enfermedad (SSE) (HR: 2,82, p = 0,008) y supervivencia general (SG) (HR: 2,92, p = 0,006), y la enfermedad de Crohn asociada fue un factor pronóstico independiente para la SLF (HR: 2,29, p = 0,04) y SG (HR: 2,86, p = 0,04). Los resultados oncológicos de los pacientes que tenían los dos factores negativos mencionados anteriormente (pacientes asociados con la enfermedad de Crohn cT3,4) fueron significativamente peores que los de los pacientes no asociados con la enfermedad de Crohn con T3,4 (LFS a 5 años: 32,5% versus a 70,4 %, p = 0,001; SSE: 15,9% versus a 40,7%, p = 0,04; SG: 25,8% versus a 71,0%, p = 0,007).LIMITACIONES:Un estudio retrospectivo de un solo brazo.CONCLUSIONES:Se confirmaron resultados oncológicos significativamente peores en pacientes asociados con la enfermedad de Crohn con tumores grandes. Por lo tanto, es importante realizar una vigilancia cuidadosa de las lesiones anales en pacientes con enfermedad de Crohn. Consulte Video Resumen en http://links.lww.com/DCR/B449.
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http://dx.doi.org/10.1097/DCR.0000000000001874DOI Listing
April 2021

Diagnostic accuracy of optical coherence tomography for the identification of in-stent fibroatheroma following stent implantation: an ex vivo histological validation study.

Int J Cardiovasc Imaging 2021 May 4;37(5):1503-1509. Epub 2021 Jan 4.

Division of Cardiology, Department of Medicine II, Kansai Medical University, Hirakata, Osaka, 5731010, Japan.

The accurate identification of in-stent fibroatheroma by in vivo imaging is clinically important to preventing the late catch-up phenomenon after stent deployment. This study investigated the diagnostic accuracy of optical coherence tomography (OCT) for the detection of "in-stent fibroatheroma" following stent implantation. Fifty stented coronary arteries from the 31 autopsy hearts were examined to compare OCT and histological image findings. A histological in-stent fibroatheroma was defined as a neointima containing an acellular necrotic core generated by macrophage infiltration. OCT-derived in-stent fibroatheroma comprised a heterogeneous pattern with an invisible stent strut behind the low-signal-intensity region. A total of 122 matched OCT and histology cross-sections were evaluated. Using histological findings as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value for OCT-derived in-stent fibroatheroma were 100%, 99%, 80%, and 100%, respectively. The only histological finding underlying the false-positive diagnosis of OCT-derived in-stent fibroatheroma was foam cell accumulation without a necrotic core on the neointimal surface. No false-negative diagnosis of OCT for in-stent fibroatheroma was apparent in this analysis. This study demonstrated the potential capability of OCT based on stent strut visualization behind low-signal-intensity regions to discriminate in-stent fibroatheroma from other neointimal tissues.
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http://dx.doi.org/10.1007/s10554-020-02125-8DOI Listing
May 2021

Interobserver variability in assessments of atherosclerotic lesion type via optical frequency domain imaging.

J Cardiol 2021 May 28;77(5):465-470. Epub 2020 Nov 28.

Division of Cardiology, Department of Medicine II, Kansai Medical University, Hirakata, Japan.

Background: To date, there have been no data available regarding the diagnostic performance of optical frequency domain imaging (OFDI) for in vivo histological classification of atherosclerotic lesions. This study investigated whether OFDI can be used to diagnose and classify histological atherosclerotic lesions in the coronary artery by ex vivo histological examinations.

Methods: Three-hundred-fifteen histological cross-sections from 21 autopsy hearts were matched with the OFDI images. Histological cross-sections were classified into six categories: adaptive intimal thickening (AIT), pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), calcified nodule, and healed erosion/rupture. The five observers with different years of experience in the interpretation of OFDI provided a single diagnosis for the OFDI scans of each cross-section according to the aforementioned six histological categories. The diagnostic accuracy and interobserver variability of lesion types for each OFDI observer were determined using histology as the gold standard.

Results: The overall agreement rates between OFDI and histopathologic diagnosis for OFDI observers 1-5 were 81%, 70%, 68%, 61%, and 50% (κ values of 0.75, 0.61, 0.58, 0.49, and 0.36), respectively. Although the diagnostic accuracy of OFDI for detecting AIT and FC was excellent for all five observers, the sensitivity, and positive predictive values of OFDI for detecting PIT and FA were low in proportion to years of experience.

Conclusion: The diagnostic accuracy of atherosclerotic tissue properties from OFDI scans correlated with the observers' years of experience, especially when lesions contained lipid components.
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http://dx.doi.org/10.1016/j.jjcc.2020.11.009DOI Listing
May 2021

Endoscopic findings in a patient with epigastric pain.

Gut 2020 Oct 14. Epub 2020 Oct 14.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

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http://dx.doi.org/10.1136/gutjnl-2020-322332DOI Listing
October 2020

Use of segmental colorectal lavage cytology during surveillance colonoscopy for detecting dysplastic and cancer cells in patients with ulcerative colitis.

Int J Clin Exp Pathol 2020 1;13(8):2035-2040. Epub 2020 Aug 1.

Department of Surgical Pathology, Hyogo College of Medicine Nishinomiya, Japan.

Purpose: To examine whether segmental colorectal lavage cytology (CRLC) during surveillance colonoscopy was useful for detecting dysplastic and cancer cells in ulcerative colitis (UC) patients.

Methods: We examined whether CRLC can detect dysplastic and cancer cells in total colectomy materials of 39 UC patients. After washing the luminal surface of dissected colorectal tissues with saline, the fluid was collected. We also examined whether segmental CRLC during surveillance colonoscopy can detect dysplastic and cancer cells in 45 UC patients. Fluid was collected after washing segmental colorectum including the suspicious region. Cytological specimens were stained with Papanicolaou and immunocytochemically stained with anti-p53 antibody.

Results: Although cancer and dysplastic cells were found by CRLC in 9 and 4 UC patients receiving total colectomy respectively, histology revealed 9 cancer lesions but only 2 dysplastic foci. In segmental CRLC, cancer cells were detected in 2 UC patients and dysplastic cells in 4 UC patients. Biopsy revealed 2 cases with colon cancer lesions but only 2 cases with dysplastic foci.

Conclusions: Segmental CRLC is a less-invasive and effective method in detecting dysplastic and cancer cells in UC patients during surveillance colonoscopy. It could be used as a complementary method for colonoscopy-directed biopsy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476949PMC
August 2020

Toxoplasmic Encephalitis Followed by Primary EBV-Associated Post-Transplant Lymphoproliferative Disorder of the Central Nervous System in a Patient Undergoing Allogeneic Hematopoietic Stem Cell Transplant: A Case Report.

Transplant Proc 2020 Nov 29;52(9):2858-2860. Epub 2020 Aug 29.

Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

Toxoplasmic encephalitis (TE) and post-transplant lymphoproliferative disorder of the central nervous system (CNS-PTLD) are major complications after allogeneic hematopoietic stem cell transplant (allo-SCT); both are fatal without timely diagnosis and disease-specific treatment. Differential diagnosis of TE and CNS-PTLD can be challenging because brain biopsy, a gold standard for diagnosis, is sometimes not possible, owing to poor patient condition after allo-SCT. Here, we describe a case of isolated CNS-PTLD arising during the therapeutic course of TE. A 51-year-old man was admitted with mental abnormalities and fever on Day 106 after allo-SCT to treat myelodysplastic syndrome. Magnetic resonance imaging (MRI) revealed multiple nodular and ring-enhanced lesions in the brain, and the result of polymerase chain reaction (PCR) for Toxoplasma gondii in cerebrospinal fluid was positive; therefore, he was diagnosed with TE. Anti-Toxoplasma therapy led to clinical improvement, and the result of subsequent PCR was negative. However, he developed left-sided hemiplegia on Day 306. Head MRI revealed a new lesion and a growing lesion, presenting as ring-enhanced nodules. Brain biopsy was performed, and a pathologic diagnosis of Epstein-Barr virus-associated CNS-PTLD was made. There was no evidence of TE. He was treated successfully by reducing immunosuppressants, followed by rituximab administration and a donor lymphocyte infusion, resulting in complete remission. While T.gondii-specific PCR has great value for diagnosis of TE, CNS-PTLD can be diagnosed only by brain biopsy; hence, brain biopsy may be warranted in cases of suspected PTLD.
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http://dx.doi.org/10.1016/j.transproceed.2020.08.002DOI Listing
November 2020

Epithelioid glioblastoma with microglia features: potential for novel therapy.

Brain Pathol 2020 11 6;30(6):1119-1133. Epub 2020 Aug 6.

Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan.

Epithelioid glioblastoma (E-GBM) was recently designated as a subtype of glioblastoma (GBM) by the World Health Organization (2016). E-GBM is an aggressive and rare variant of GBM that primarily occurs in children and young adults. Although most characterized cases of E-GBM harbor a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600 (BRAF-V600E), in addition to telomerase reverse transcriptase promoter mutations and homozygous CDKN2A/B deletions, the origins and cellular nature of E-GBM remain uncertain. Here, we present a case of E-GBM that exhibits antigenic and functional traits suggestive of microglia. Although no epithelial [e.g., CKAE1/3, epithelial membrane antigen (EMA)] or glial (e.g., GFAP, Olig2) markers were detected by immunohistochemical staining, the microglial markers CD68 and Iba1 were readily apparent. Furthermore, isolated E-GBM-derived tumor cells expressed microglial/macrophage-related genes including cytokines, chemokines, MHC class II antigens, lysozyme and the critical functional receptor, CSF-1R. Isolated E-GBM-derived tumor cells were also capable of phagocytosis and cytokine production. Treating E-GBM-derived tumor cells with the BRAF-V600E inhibitor, PLX4032 (vemurafenib), resulted in a dose-dependent reduction in cell viability that was amplified by addition of the CSF-1R inhibitor, BLZ945. The present case provides insight into the cellular nature of E-GBM and introduces several possibilities for effective targeted therapy for these patients.
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http://dx.doi.org/10.1111/bpa.12887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754497PMC
November 2020

Tumor-associated macrophage-derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma.

Cancer Sci 2020 Aug 6;111(8):2895-2906. Epub 2020 Jul 6.

Department of Respiratory Medicine and Hematology, Hyogo College of Medicine, Nishinomiya, Japan.

Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive malignant neoplasm. Due to the difficulty of achieving curative surgical resection in most patients with MPM, a combination chemotherapy of cisplatin and pemetrexed has been the only approved regimen proven to improve the prognosis of MPM. However, the median overall survival time is at most 12 mo even with this regimen. There has been therefore a pressing need to develop a novel chemotherapeutic strategy to bring about a better outcome for MPM. We found that expression of interleukin-1 receptor (IL-1R) was upregulated in MPM cells compared with normal mesothelial cells. We also investigated the biological significance of the interaction between pro-inflammatory cytokine IL-1β and the IL-1R in MPM cells. Stimulation by IL-1β promoted MPM cells to form spheroids along with upregulating a cancer stem cell marker CD26. We also identified tumor-associated macrophages (TAMs) as the major source of IL-1β in the MPM microenvironment. Both high mobility group box 1 derived from MPM cells and the asbestos-activated inflammasome in TAMs induced the production of IL-1β, which resulted in enhancement of the malignant potential of MPM. We further performed immunohistochemical analysis using clinical MPM samples obtained from patients who were treated with the combination of platinum plus pemetrexed, and found that the overexpression of IL-1R tended to correlate with poor overall survival. In conclusion, the interaction between MPM cells and TAMs through a IL-1β/IL-1R signal could be a promising candidate as the target for novel treatment of MPM (Hyogo College of Medicine clinical trial registration number: 2973).
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http://dx.doi.org/10.1111/cas.14523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419052PMC
August 2020

A case of planar-type GIST of the sigmoid colon showing diverticular structure with perforation.

World J Surg Oncol 2020 Jun 11;18(1):125. Epub 2020 Jun 11.

Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.

Background: Gastrointestinal stromal tumors (GISTs) generally form well-defined mass lesions. However, some cases of the flatly distributed and muscularis propria-replacing GISTs have been reported so far. We experienced an additional case of planar-type GIST of the sigmoid colon accompanied by a diverticulum with perforation.

Case Presentation: A 68-year-old Japanese male with sudden onset of abdominal pain was clinically diagnosed with gastrointestinal perforation, and an emergency abdominal operation was performed. A diverticulum with rupture was found in the sigmoid colon, but no apparent tumor was observed. Histological examination revealed bland spindle cells flatly proliferating and diffusely replacing the muscularis propria at the diverticular structure. The spindle cells were positive for KIT, DOG1, and CD34. Mutational analysis of the c-kit gene revealed that the lesion had a heterozygous deletion of 2 amino acids at codons 557 and 558 of exon 11. The mutation was not observed in the normal mucosa of the surrounding tissue.

Conclusion: We diagnosed this case as an unusual planar-type GIST. Some similar cases have been reported in the sigmoid colon and other sites. We discuss the mechanism of development of the planar-type GISTs associated with the diverticulum.
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http://dx.doi.org/10.1186/s12957-020-01906-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291680PMC
June 2020

Tangential Signal Dropout Mimicking the Appearance of Lipid-rich Plaques and Macrophage Infiltration on Optical Frequency Domain Imaging.

EuroIntervention 2020 Apr 28. Epub 2020 Apr 28.

Division of Cardiology, Department of Medicine II, Kansai Medical University, Hirakata, Japan.

Aims: This study evaluated the optical frequency domain imaging (OFDI) artifact of tangential signal dropout (TSD), which mimics the appearance of lipid-rich plaque and macrophage (Mø) infiltration.

Methods And Results: A total of 1,019 histological cross-sections from 23 autopsy hearts were matched with the corresponding OFDI images. Of those, 232 OFDI cross-sections that contained signal-poor regions with diffuse borders were classified as lipid-rich plaques. The angle θ was calculated between the OFDI beam that strikes the edge of the luminal surface of the low-intensity region and that which strikes the surface line of the low-intensity region. On histological evaluation, 182 (78%) cross-sections were classified as histologically lipidic/Mø infiltration, while the remaining 50 (22%) cross-sections as histologically non-lipidic/Mø infiltration. The angle θ was significantly smaller in the non-lipidic/Mø infiltration group than in the lipidic/Mø infiltration group (12±6° versus 37±14°, p<0.001). Receiver operating curve analysis revealed that the optimal cutoff value of the incident angle for predicting TSD was 23° with area under the curve 0.98.

Conclusions: When the OFDI imaging beam strikes the tissue at an angle q<23°, TSD artifact could occur. To eliminate image misinterpretation, our findings suggest that the OFDI catheter geometry should be considered for the accurate diagnosis of lipid-rich plaques and Mø infiltration.
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http://dx.doi.org/10.4244/EIJ-D-20-00014DOI Listing
April 2020

Phosphorylated STAT3 expression linked to methylation is associated with proliferative ability of gastric mucosa in patients with early gastric cancer.

Oncol Lett 2020 May 16;19(5):3542-3550. Epub 2020 Mar 16.

Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine Hospital, Nishinomiya, Hyogo 663-8501, Japan.

Gastric cancers (GCs) may develop in the gastric mucosa after elimination of () using eradication therapy. Cytokine signaling is a key mechanism underlying GC development and progression, and STAT3 signaling may serve a central role in gastritis-associated tumorigenesis. In the present study, () methylation was examined, as an activator of phosphorylated (p-)STAT3 expression in the non-neoplastic gastric mucosa (non-NGM) of patients with early GC. The methylation status of the gene promoter was analyzed using methylation-specific PCR in the non-NGM of patients with or without early GC. Expression levels of p-STAT3 and Ki67 were investigated immunohistochemically in non-NGM with early GC before and after eradication. In non-NGM, promoter methylation was detected in 17/51 patients (33.3%) with early GC. In those patients, the non-NGM labeling indices of both Ki67 and p-STAT3 were significantly higher compared with that in patients with early GC without methylation. A significant correlation between Ki67 and p-STAT3 expression levels was demonstrated in the non-NGM of patients with early GC. In patients with early GC without methylation, the labeling indices of both Ki67 and p-STAT3 in non-NGM were significantly reduced after eradication, whereas no such change was observed in patients with early GC with methylation. methylation is associated with continuous p-STAT3 overexpression and enhanced epithelial cell proliferation in non-NGM of patients with early GC.
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http://dx.doi.org/10.3892/ol.2020.11462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115067PMC
May 2020

Association Between FOXP3/CD8 Lymphocyte Ratios and Tumor Infiltrating Lymphocyte Levels in Different Breast Cancer Subtypes.

Anticancer Res 2020 Apr;40(4):2141-2150

Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Japan

Background/aim: Patients with non-luminal breast cancer subtypes with high levels of tumor infiltrating lymphocytes (TILs) have better prognosis than those with luminal subtype. We evaluated the role of TILs according to the subtype.

Materials And Methods: An immunohistochemical analysis of 139 breast cancer cases was conducted to calculate the FOXP3+/CD8+ T cell ratios and their relationships with TILs and disease-free survival (DFS) were evaluated.

Results: FOXP3+/CD8+ T cell ratios were significantly associated with TIL levels only in luminal breast cancers (p=0.0001). Low FOXP3+/CD8+ T cell ratio was significantly associated with longer DFS (p=0.017). All luminal subtype patients with high TIL levels had high FOXP3+/CD8+ T cell ratios compared to only half of non-luminal subtype patients with high TIL levels.

Conclusion: High FOXP3+/CD8+ T cell ratios in breast cancers may partly explain the worse prognosis of luminal breast cancers, but not that of non-luminal breast cancers with high TIL levels.
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http://dx.doi.org/10.21873/anticanres.14173DOI Listing
April 2020

Multiple gastrointestinal stromal tumors caused by a novel germline KIT gene mutation (Asp820Gly): a case report and literature review.

Gastric Cancer 2020 07 7;23(4):760-764. Epub 2020 Mar 7.

Department of Surgical Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract; most of them have gain-of-function mutations of the KIT gene. There have been rare cases of families with multiple GISTs, that had autosomal dominant germline KIT mutations. Here, we present a case of multiple GISTs caused by a novel germline KIT mutation. Intraoperatively, the main tumor was present in the body of the stomach, and multiple small nodules were detected mainly in the upper and middle part of the gastric wall; several nodules were also present in the small bowel wall. The main tumor and surrounding nodules were resected. DNA sequencing of the tumor tissue, adjacent normal mucosal tissue, and peripheral blood leukocytes revealed that the patient had germline Asp820Gly mutation in exon 17 of the KIT gene. This is the first case with germline Asp820Gly mutation in exon 17 of the KIT gene.
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http://dx.doi.org/10.1007/s10120-020-01055-7DOI Listing
July 2020

Treatment strategy in a patient showing borderline features between plasmablastic lymphoma and plasmablastic myeloma harboring a 17p deletion.

Ann Hematol 2020 Jun 3;99(6):1405-1407. Epub 2020 Mar 3.

Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

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http://dx.doi.org/10.1007/s00277-020-03975-xDOI Listing
June 2020

Expression of p16 in nodular fasciitis: an implication for self-limited and inflammatory nature of the lesion.

Int J Clin Exp Pathol 2019 1;12(3):1029-1034. Epub 2019 Mar 1.

Department of Surgical Pathology, Hyogo College of Medicine 1-1 Mukogawa-cho, Nishinomiya-city, Hyogo 663-8501, Japan.

Nodular fasciitis (NF) is a self-limited tumorous lesion occurring in the upper as well as lower extremities. NF is composed of a proliferation of "primary culture"-like myofibroblastic cells with nuclear atypia and large nucleoli, thus mimicking sarcoma. NF harbors a promoter-swapping fusion gene containing the entire coding region of gene. Therefore, NF is a tumor with a fusion oncogene but self-limited. In order to explore why NF is self-limited, we examined whether myofibroblastic cells in NF express p16 protein, a gene product of gene and an inhibitor of cyclin-dependent kinase 4 (CDK4) as well as one of the hallmarks of cellular senescence. We immunohistochemically demonstrated strong and diffuse expression of p16 in myofibroblastic cells in 11 out of 15 cases of NF, and strong but partial expression in the remaining 4 of the cases. We also showed that 15 out of 15 cases of NF were immunohistochemically negative or only showed focal and faint immunopositivity for CDK4, murine double minute 2 (MDM2), and TP53 proteins. Furthermore, there were no significant changes in the copy number of and genes, and no significant mutations in and genes in 1 case of NF selected. These data suggest a possible involvement in cell cycle arrest and presumed cellular senescence by p16 in myofibroblastic cells in NF. This may explain the self-limited as well as inflammatory nature of NF as a senescence-associated secretory phenotype.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945175PMC
March 2019

Hypermethylation of Corticotropin Releasing Hormone Receptor-2 Gene in Ulcerative Colitis Associated Colorectal Cancer.

In Vivo 2020 Jan-Feb;34(1):57-63

Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.

Background/aim: The difficulty of early diagnosis of colitis associated colorectal cancer (CACRC) due to colonic mucosal changes in long-standing ulcerative colitis (UC) patients is often experienced in daily clinical practice. Noninvasive objective monitoring for cancer development is advantageous for optimizing treatment strategies in UC patients. We aimed to examine the epigenetic alterations occurring in CACRC, focusing on DNA hypermethylation of CpG islands.

Materials And Methods: The level of DNA methylation in CpG cites was compared between CACRC and the counterpart non-tumorous mucosa using Infinium HumanMethylation 450K BeadChip.

Results: Our subjects included 3 males and 3 females (median age, 49.5 years). The 450K CpG site DNA methylation microarray revealed that the difference in β value (level of hypermethylation) was the highest for corcicotropin releasing hormone receptor 2 (CRHR2) between CACRC and counterpart non-tumorous mucosa.

Conclusion: Detection of hypermethylation of CRHR2 may be promising for cancer screening in UC patients.
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http://dx.doi.org/10.21873/invivo.11745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984071PMC
June 2020