Publications by authors named "Munetoshi Hinata"

12 Publications

  • Page 1 of 1

Detecting immunotherapy-sensitive subtype in gastric cancer using histologic image-based deep learning.

Sci Rep 2021 11 22;11(1):22636. Epub 2021 Nov 22.

Department of Pathology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Immune checkpoint inhibitor (ICI) therapy is widely used but effective only in a subset of gastric cancers. Epstein-Barr virus (EBV)-positive and microsatellite instability (MSI) / mismatch repair deficient (dMMR) tumors have been reported to be highly responsive to ICIs. However, detecting these subtypes requires costly techniques, such as immunohistochemistry and molecular testing. In the present study, we constructed a histology-based deep learning model that aimed to screen this immunotherapy-sensitive subgroup efficiently. We processed whole slide images of 408 cases of gastric adenocarcinoma, including 108 EBV, 58 MSI/dMMR, and 242 other subtypes. Many images generated by data augmentation of the learning set were used for training convolutional neural networks to establish an automatic detection platform for EBV and MSI/dMMR subtypes, and the test sets of images were used to verify the learning outcome. Our model detected the subgroup (EBV + MSI/dMMR tumors) with high accuracy in test cases with an area under the curve of 0.947 (0.901-0.992). This result was slightly better than when EBV and MSI/dMMR tumors were detected separately. In an external validation cohort including 244 gastric cancers from The Cancer Genome Atlas database, our model showed a favorable result for detecting the "EBV + MSI/dMMR" subgroup with an AUC of 0.870 (0.809-0.931). In addition, a visualization of the trained neural network highlighted intraepithelial lymphocytosis as the ground for prediction, suggesting that this feature is a discriminative characteristic shared by EBV and MSI/dMMR tumors. Histology-based deep learning models are expected to be used for detecting EBV and MSI/dMMR gastric cancers as economical and less time-consuming alternatives, which may help to effectively stratify patients who respond to ICIs.
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http://dx.doi.org/10.1038/s41598-021-02168-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608814PMC
November 2021

A case of difficult-to-diagnose non-invasive papillary squamous cell carcinoma of the uterine cervix infected with human papilloma virus 6: A diagnostic pitfall.

Clin Case Rep 2021 Oct 4;9(10):e04905. Epub 2021 Oct 4.

Department of Obstetrics and Gynecology Graduate School of Medicine The University of Tokyo Tokyo Japan.

We encountered HPV6-positive cervical papillary squamous cancer (PSCC) that was difficult to diagnose. The case was initially diagnosed and treated for condyloma. To the best of our knowledge, this is the first report of HPV6 infection in PSCC.
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http://dx.doi.org/10.1002/ccr3.4905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489388PMC
October 2021

Cerebral toxoplasmosis complicating lymphoplasmacytic lymphoma in partial remission.

J Infect Chemother 2022 Feb 25;28(2):279-282. Epub 2021 Sep 25.

Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan. Electronic address:

Toxoplasma gondii can develop toxoplasmic encephalitis (TE) in immunodeficient conditions such as AIDS and after organ transplantation. While some cases of TE with malignant lymphoma were reported, these cases occurred immediately after chemotherapy or when their diseases were active. Here we report the first Case of TE that occurred in patient who was in partial remission (PR) of lymphoplasmacytic lymphoma (LPL) for two years. A 76-year-old man was referred to our institute because of disturbance of consciousness, right arm weakness and paresthesia. A computed tomography (CT) scan detected multiple nodules in his brain. Magnetic resonance imaging (MRI) of the head detected multiple gadolinium-enhancing parenchymal lesions with hyperintense signals on T2-and diffusion-weighted images, located in both cerebral and cerebellar hemispheres. Blood test and cerebrospinal fluid (CSF) findings were unremarkable. His rapidly deteriorating consciousness precluded a chance of brain biopsy. Considering the limited efficacy of antimicrobials and the imaging findings that could be compatible with the diagnosis of malignant lymphoma, we suspected central nerve system (CNS) recurrence of LPL. Although chemotherapy was initiated, he died of respiratory failure just after chemotherapy. A pathological autopsy showed his cause of death was TE. To our knowledge, this is the first case of TE in long-term PR of malignant lymphoma. TE should be suspected when patients with malignant lymphoma present unexplained neurologic symptoms regardless of their treatment efficacy of lymphoma. (226/250 words).
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http://dx.doi.org/10.1016/j.jiac.2021.09.005DOI Listing
February 2022

Rectal neuroendocrine tumor with extracapsular lymph node metastasis: a case report.

Clin J Gastroenterol 2021 Oct 24;14(5):1426-1430. Epub 2021 May 24.

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

The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor in patients with colorectal carcinoma. However, there is no English literature on neuroendocrine tumor (NET) with EX. We report a patient with rectal NET with extracapsular metastasis of a regional lymph node that was considered to be EX. A 51-year-old Japanese woman with diabetes was referred to our hospital for further examination of a submucosal tumor in the lower rectum. She was diagnosed as having rectal NET by immunohistochemical analysis of a biopsy, and underwent laparoscopic low anterior resection with lymph node dissection and covering ileostomy. Pathological findings of the resected specimen showed that the primary tumor was NET-G1 without any lymphatic or venous invasion. A single metastatic deposit was found near the capsule of a NET-negative regional lymph node. She has been free from recurrence for nine months without adjuvant treatments. Extracapsular metastasis of NET on a dissected lymph node in our case was considered to correspond to EX as defined for colorectal carcinoma. This rare case suggests that NET can disseminate to form EX in a similar manner to colorectal carcinoma.
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http://dx.doi.org/10.1007/s12328-021-01447-xDOI Listing
October 2021

Exosomes of Epstein-Barr Virus-Associated Gastric Carcinoma Suppress Dendritic Cell Maturation.

Microorganisms 2020 Nov 12;8(11). Epub 2020 Nov 12.

Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

The Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is characterized by the infiltration of lymphocytes and a unique tumor microenvironment. Exosomes from cancer cells are essential for intercellular communication. The aims of this study were to investigate the secretion of EBVaGC exosomes and their physiological effect on dendritic cell maturation in vitro and to characterize dendritic cells (DCs) in EBVaGC in vivo. Western blotting analysis of CD63 and CD81 of exosomes from EBV-infected gastric cancer cell lines indicated an increase in exosome secretion. The fraction of monocyte-derived DCs positive for the maturation marker CD86 was significantly suppressed when incubated with exosomes from EBV-infected gastric cancer cell lines. Immunohistochemical analysis of GC tissues expressing DC markers (S100, Langerin, CD1a, CD83, CD86, and BDCA-2) indicated that the density of DCs was generally higher in EBVaGC than in EBV-negative GC, although the numbers of CD83- and CD86-positive DCs were decreased in the group with high numbers of CD1a-positive DCs. A low number of CD83-positive DCs was marginally correlated with worse prognosis of EBVaGC in patients. EBVaGC is a tumor with abundant DCs, including immature and mature DCs. Moreover, the maturation of DCs is suppressed by exosomes from EBV-infected epithelial cells.
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http://dx.doi.org/10.3390/microorganisms8111776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697542PMC
November 2020

Retro-odontoid Pseudotumor: Two Cases of Intradural Ganglion Cysts Arising From the Odontoid Process with Syringobulbia.

World Neurosurg 2020 12 20;144:148-153. Epub 2020 Aug 20.

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

Background: Ganglion cysts mostly occur in the knuckles and wrists, but they rarely present in the odontoid process and can cause neurological symptoms by compressing the spinal cord. They are mostly localized in the epidural space, but may very rarely appear in the intradural space. There are no reports of cases of intradural ganglion cyst involving syringobulbia.

Case Description: We report the presentation and management of 2 cases of an intradural ganglion cyst of the odontoid process. Several treatment options for ganglion cysts of the odontoid process have been reported, such as rest and use of a neck collar, posterior decompression and fusion, and transoral anterior decompression. Because our 2 cases progressed rapidly and had severe neurological symptoms, surgical treatment was performed for rapid decompression and definitive pathological diagnosis. The mass was resected as much as possible using the lateral occipital fossa approach, and the operation was completed without dissection of the brain stem or manipulation of the syringobulbia. Postoperatively, neurological symptoms promptly improved, and the syringobulbia reduced.

Conclusions: For intradural ganglion cysts with syringobulbia, we suggest relief of the compression by resection of the mass and treatment of the syringobulbia in 2 stages, if necessary, to avoid the risk of damage to the brainstem.
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http://dx.doi.org/10.1016/j.wneu.2020.08.120DOI Listing
December 2020

Renal Effects after Pembrolizumab Treatment for Non-small Cell Lung Carcinoma.

Intern Med 2020 Apr 6;59(7):977-981. Epub 2019 Dec 6.

Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Japan.

Immune checkpoint inhibitors (CPIs), including pembrolizumab, are becoming common oncological treatments. CPIs have been associated with a significant risk of developing immune-related adverse events (irAEs), such as nephritis and interstitial nephritis. However, the occurrence of glomerulonephritis has only rarely been reported. We herein present the case of a 75-year-old woman with non-small cell lung carcinoma (NSCLC) who developed proteinuria and microscopic hematuria during treatment with pembrolizumab. Renal biopsy revealed tubulointerstitial nephritis and IgA nephropathy. Considering that a urinalysis showed no abnormality before treatment, the condition might have been induced by pembrolizumab. In this report, we focus on the correct diagnosis and management of renal irAEs, which remain controversial.
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http://dx.doi.org/10.2169/internalmedicine.3928-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184094PMC
April 2020

A case of primary breast angiosarcoma with multiple discontinuous small lesions.

Surg Case Rep 2019 Oct 25;5(1):157. Epub 2019 Oct 25.

Department of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Angiosarcoma of the breast is rare. It carries a poor prognosis because of its high risk of local recurrence and distant metastases. Presently, there are still no established systemic therapies. Thus, the main treatment strategy for breast angiosarcoma is complete resection. This underscores the importance of closely monitoring the spread of the tumor lesion, particularly for multifocal angiosarcoma, and to plan an optimal operative procedure. We herein present the successful surgical treatment of a rare case of multifocal primary breast angiosarcoma.

Case Presentation: A 43-year-old woman visited our hospital with a growing lump on her right breast accompanied by pain. Clinical and radiological examinations revealed a well-circumscribed 40-mm-diameter tumor at the inner lower quadrant of her right breast. Histological examination of a needle biopsy specimen revealed angiosarcoma. Based on a precise evaluation of the tumor by contrast-enhanced MRI and contrast-enhanced CT scan, a wide local excision with sufficient margins was performed. In the resected specimen, three discontinuous small lesions of angiosarcoma were observed around the main tumor. Therefore, total mastectomy was additionally performed. Pathological examination revealed two other small nodules of angiosarcoma in the remnant right breast, which appeared to be close but not continuous to the defective part of the initial resection. Postoperative follow-up at 1 year showed no signs of recurrence or distant metastasis. Multifocal primary breast angiosarcoma is extremely rare with only two previous reports describing its multifocality.

Conclusions: Owing to its rarity, a standardized surgical treatment for breast angiosarcoma remains controversial. Our case suggests that primary breast angiosarcoma may occasionally present with multifocal tumor. Thus, it is important to keep in mind the multifocality of breast angiosarcoma when assessing its spread by diagnostic imaging and when planning the surgical strategy.
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http://dx.doi.org/10.1186/s40792-019-0704-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814660PMC
October 2019

Tocilizumab for focal segmental glomerulosclerosis secondary to multicentric Castleman's disease.

Ann Hematol 2019 Aug 13;98(8):1995-1997. Epub 2019 Feb 13.

Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.

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http://dx.doi.org/10.1007/s00277-019-03616-yDOI Listing
August 2019

Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy.

Circ Heart Fail 2018 04;11(4):e004660

Department of Pediatrics (Y.N., R.I., H.T., S.K., K.S., H.A., T.S., Y.H., A.O.), Department of Pathology (K.I., M.H.), Department of Cardiovascular Medicine (N.T.), and Department of Developmental Medical Sciences (M.S.), Graduate School of Medicine, The University of Tokyo, Japan.

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004660DOI Listing
April 2018

A case of delayed exacerbation of interstitial lung disease after discontinuation of temsirolimus.

Respir Med Case Rep 2017 11;22:158-163. Epub 2017 Aug 11.

Department of Respiratory Medicine, The University of Tokyo Hospital, Japan.

Temsirolimus is an inhibitor of mammalian target of rapamycin and interstitial lung disease (ILD) is known to be one of the adverse events associated with temsirolimus, which usually improves rapidly after discontinuation of the drug and rarely worsens thereafter. Herein, we report a case of delayed exacerbation of ILD after discontinuation of temsirolimus for metastatic renal cell carcinoma in an 86-year-old male with chronic ILD. The patient developed gradually worsening dyspnea five weeks after an initiation of temsirolimus and was admitted to our facility. On his admission, although a pulmonary function test revealed a decreased diffusion capacity, there was no obvious progression of ILD on HRCT scan. His dyspnea once improved after discontinuation of temsirolimus, but it recurred and acute exacerbation of ILD was diagnosed 40 days after his last administration of temsirolimus. He received high-dose steroid therapy, however, he deteriorated and died. Histopathological examination of the lungs at autopsy revealed overlapping diffuse alveolar damage with chronic interstitial changes. In the present case, since there were no specific factors that could have caused acute exacerbation of ILD except for temsirolimus, it was considered to contribute to the exacerbation of underlying ILD. In conclusion, physicians should be aware of the possibility of temsirolimus-induced ILD not only while the medication is administered, but also even after it is discontinued. It is important to carefully interview the patient and to recognize the value of physiological tests, such as respiratory function tests and blood gas analysis, as well as imaging findings on HRCT.
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http://dx.doi.org/10.1016/j.rmcr.2017.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558510PMC
August 2017
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