Details of a Researcher - Nishio, Hiroshi

Meningitis caused by Listeria monocytogenes in a locally advanced cervical cancer patient with pyometra: A case report

Matoba Y., Nishio H., Sekiguchi K., Uno S., Masuda K., Hiramatsu M., Takahashi M., Oishi M., Uwamino Y., Uchida S., Daté Y., Morisada T., Banno K., Nakahara J., Aoki D.

Gynecologic Oncology Reports （Gynecologic Oncology Reports) 37 2021.08

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Locally advanced cervical cancer occasionally induces pyometra, but there have been no reports of meningitis where pyometra is the cause of infection. Here, we report a case of Listeria monocytogenes meningitis related to pyometra during concurrent chemoradiotherapy (CCRT) in a cervical cancer patient. The patient, a 77-year-old woman, was diagnosed with Stage IIB (FIGO 2018) cervical adenocarcinoma, and CCRT was initiated. Pyometra was exacerbated during CCRT, and after her first brachytherapy, she presented at our hospital with fever and decreased consciousness level. After admission to the Intensive Care Unit, the patient lost consciousness and experienced frequent seizures; tracheal intubation was required. Whole-body computed tomography revealed pyometra; therefore, transvaginal removal of the abscess was performed. Laboratory tests and vital signs indicated septic shock, and meropenem was administered. L. monocytogenes was detected in the abscess from the uterine cavity and the blood cultures on the third day of hospitalization. A lumbar puncture was performed on the same day to investigate whether the patient had meningitis. A FilmArray meningitis/encephalitis panel test of the spinal fluid revealed L. monocytogenes. After the diagnosis of meningitis with L. monocytogenes, ampicillin and gentamicin were started, and the blood test results gradually improved. Five months after the initial episode, her consciousness recovered, however she still received mechanical ventilatory support. L. monocytogenes infections can occur in patients undergoing chemotherapy, even without the use of steroids or immunosuppressive agents. In cases with pyometra, intrauterine manipulation can increase the risk of severe infection.
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Evaluating the importance of routine drainage following laparoscopic pelvic lymph node dissection for gynecological malignancies

Sakai K., Nakamura M., Yamagami W., Chiyoda T., Kobayashi Y., Nishio H., Hayashi S., Nomura H., Kataoka F., Tominaga E., Banno K., Aoki D.

International Journal of Gynecology and Obstetrics （International Journal of Gynecology and Obstetrics) 153 （ 3 ） 438 - 442 2021.06

ISSN 00207292

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Objective: To determine the efficacy of drainage following pelvic lymph node (PLN) dissection, especially for cases involving laparoscopic surgery. Methods: In this retrospective study, 368 patients with malignant gynecological tumors who underwent systemic PLN dissection at Keio University Hospital between January 2012 and October 2018 were enrolled. Drainage tubes were placed in the retroperitoneal fossa in all patients. Medical records were used for data collection. Results: Laparoscopy was performed on 81 patients, and laparotomy was performed on 287 patients. In the laparoscopy group, tubes were removed 1 day post surgery. In the laparotomy group, tubes were removed 1 day post surgery in 167 patients and 4 days post surgery in 120 patients. Compared with the laparotomy group, we determined the laparoscopy group to have a significantly lower prevalence of lymphocyst (6.2% vs 20.2%, p = 0.002) but a similar prevalence of lymphedema (4.9% vs 5.2%), and symptomatic lymphocyst (2.5% vs 4.5%). The two laparotomy groups did not differ significantly with respect to the prevalence of lymphedema (4.8% vs 5.8%), lymphocyst (20.4% vs 20.0%), or symptomatic lymphocyst (4.2% vs 5.0%). Conclusion: Our results suggest that routine drainage should be omitted, especially in cases involving laparoscopic surgery.
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Current status of cancer immunotherapy for gynecologic malignancies

Nishio H., Iwata T., Aoki D.

Japanese Journal of Clinical Oncology （Japanese Journal of Clinical Oncology) 51 （ 2 ） 167 - 172 2021.02

ISSN 03682811

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Recent cancer immunotherapy development with immune checkpoint inhibitors has shown durable clinical responses in a wide variety of tumor types. These drugs targeting programmed cell death 1, its ligand programmed death ligand 1 and cytotoxic T cell lymphocyte-associated antigen 4 have revolutionized the field of cancer treatment. It is of significant interest in optimizing the immunotherapy for cancer patients beyond the conventional treatments such as surgery, chemotherapy and radiation. Many clinical trials evaluating the safety and efficacy of various combined regimens with immune checkpoint inhibitors have been reported and are in progress. Among gynecologic malignancy, endometrial cancers have distinct subtypes with microsatellite instability-high status and polymerase ɛ mutation. These types have been shown to immunogenic tumors and appropriated candidate for immune checkpoint inhibitors. Also, recurrent cervical cancer showed a promising objective response with single anti-PD1 Ab treatment. Despite their definite outcome and considerable potential of immunotherapy, not all patients received a survival benefit and further understanding of human tumor immunology is essential to improve this type of therapy. In this review, we have summarized the updated results of clinical trials of cancer immunotherapy for gynecologic malignancies and discussed the future perspectives.
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Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy

Ohno A., Iwata T., Katoh Y., Taniguchi S., Tanaka K., Nishio H., Nakamura M., Morisada T., Chen G., Saito M., Yaguchi T., Kawakami Y., Aoki D.

Gynecologic Oncology （Gynecologic Oncology) 159 （ 2 ） 329 - 334 2020.11

ISSN 00908258

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Objectives: To (i) identify correlations between selected immunogenic factors and clinicopathological characteristics, (ii) determine whether intratumoral abundance of various specific tumor-infiltrating lymphocytes (TILs) is a prognostic indicator in women with Stage II and III cervical cancer who undergo treatment with cisplatin-based concurrent chemoradiotherapy (CCRT), and (iii) investigate subtypes of FOXP3+ T cells in 15 fresh samples of cervical cancer. Methods: In this retrospective study, intratumoral lesions in colposcopic biopsies from 55 women with advanced cervical cancer who subsequently underwent CCRT at our institution were subjected to automatic immunological staining using the following six mouse monoclonal antibodies: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD206, and anti-FOXP3. Associations between the findings on automatic scoring of the number of each type of TIL in each specimen and various clinicopathological characteristics were analyzed, as were associations between the abundance of various specific types of TIL and survival. Subtypes of FOXP3+ TILs in 15 additional fresh tumor samples were also investigated using flow cytometry. Results: Infiltration with CD8+ TILs was associated with pelvic lymph node metastasis. Abundant infiltration by CD3+, CD4+, CD8+, CD206+, and FOXP3+ TILs were statistically significant indicators of better progression-free and overall survival. Regarding subtypes of FOXP3+ TILs, non-Tregs (Fr-III) were found in all samples tested for this. Conclusions: The abundance of various specific intratumoral TILs may be prognostic indicators in patients with advanced cervical cancer undergoing CCRT.
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Impact of the COVID-19 epidemic at a high-volume facility in gynecological oncology in Tokyo, Japan: A single-center experience

Nogami Y., Kobayashi Y., Tsuji K., Yokota M., Nishio H., Nakamura M., Yamagami W., Morisada T., Tominaga E., Banno K., Aoki D.

Journal of Ovarian Research （Journal of Ovarian Research) 13 （ 1 ） 2020.09

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Background: The number of cases of novel coronavirus disease 2019 (COVID-19) in Japan have risen since the first case was reported on January 24, 2020, and 6225 infections have been reported as of June 30, 2020. On April 8, 2020, our hospital began screening patients via pre-admission reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and chest computed tomography (CT). Although no patients exhibited apparent pneumonia, treatment delay or changes in treatment plans were required for a few patients based on the results of screening tests. During an emerging infectious disease pandemic, the likelihood of being infected, as well as the disease itself, affects clinical decision making in several ways. We summarized and presented our experience. Case presentation: After the introduction of pre-admission screening, RT-PCR and CT were performed in 200 and 76 patients, respectively, as of June 30, 2020. The treatment of five patients, including two patients with cervical cancer, two patients with ovarian tumors, and one patient with ovarian cancer, was affected by the results. Two asymptomatic RT-PCR-positive patients did not develop COVID-19, but their treatment was delayed until the confirmation of negative results. The other three patients were RT-PCR-negative, but abnormal CT findings suggested the possibility of COVID-19, which delayed treatment. The patients receiving first-line preoperative chemotherapy for ovarian cancer had clinically evident exacerbations because of the treatment delay. Conclusion: During the epidemic phase of an emerging infectious disease, we found that COVID-19 has several other effects besides its incidence. The postponing treatment was the most common, therefore, treatment of ovarian tumors and ovarian cancer was considered to be the most likely to be affected among gynecological diseases. Protocols that allow for easy over-diagnosis can be disadvantageous, mainly because of treatment delays, and therefore, the protocols must be developed in light of the local infection situation.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Investigating cancer-immunoescape mechanism and effective immunotherapy for ovarian cancer

Nishio, Hiroshi

科学研究費補助金研究成果報告書 2015
ヒト卵巣がんにおけるNF-κB経路の恒常的活性化による免疫抑制とNF-κB阻害剤によるその解除

Nishio, Hiroshi

（慶應義塾大学大学院医学研究科) 2014
ヒト卵巣がんにおけるNF-κB経路の恒常的活性化による免疫抑制とNF-κB阻害剤によるその解除

Nishio, Hiroshi

（慶應義塾大学大学院医学研究科) 2014
ヒト卵巣がんにおけるNF-κB経路の恒常的活性化による免疫抑制とNF-κB阻害剤によるその解除

Nishio, Hiroshi

（慶應義塾大学大学院医学研究科) 2014
Analysis of immune escape mechanism in cervical cancer that aims at immunotherapeutic application

Nishio, Hiroshi

科学研究費補助金研究成果報告書 2009

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

卵巣がんにおける腫瘍浸潤T細胞の免疫不応状態の克服による複合的免疫療法の開発

2022.04

-

2025.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(C), Principal investigator
婦人科がんにおける新規免疫チェックポイントの機能解析と複合的免疫療法の開発

2019.04

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2022.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator
卵巣癌における免疫原性遺伝子変異による内在性腫瘍抗原の導出と新規免疫療法の開発

2016.04

-

2017.03

JSPS, No Setting
卵巣癌における癌免疫逃避機構の解明及び効果的な免疫治療法の開発

2013.04

-

2015.03

JSPS, Grant-in-Aid for Scientific Research, Principal investigator
婦人科がんにおける免疫逃避機構の解明及び新規治療法の開発

2011.04

-

2012.03

JSPS, Grant-in-Aid for Scientific Research, No Setting