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大学院医学系研究科（医学専攻等） 医学専攻 腫瘍制御医学系 臨床腫瘍学講座 |
職務経歴（学内） 【 表示 ／ 非表示 】
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2023年04月-継続中
秋田大学 大学院医学系研究科（医学専攻等） 医学専攻 腫瘍制御医学系 講師
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2019年04月-2023年03月
秋田大学 大学院医学系研究科（医学専攻等） 医学専攻 腫瘍制御医学系 助教
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2017年06月-2019年03月
秋田大学 医学部 寄附講座 寄附講座助教
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A diarylpentanoid curcumin analog exhibits improved radioprotective potential in the intestinal mucosa
Koji Fukuda, Yoshihiko Uehara, Eiko Nakata
International Journal of Radiation Biology 92 ( 7 ) 388 - 394 2017年03月
国内共著
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Fujita K.
Japanese Journal of Clinical Oncology ( Japanese Journal of Clinical Oncology ) 54 ( 11 ) 1165 - 1170 2024年11月
研究論文（学術雑誌）
BACKGROUND: The modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) are indicators of nutritional status in cancer patients; however, the effects of baseline mGPS and PNI on the duration of administration of the ghrelin receptor agonist anamorelin, which is used to treat cachexia in patients with cancer, are unclear. This study aimed to clarify the association of mGPS and PNI with the duration of oral anamorelin administration for patients who did not have beneficial effects from anamorelin. METHODS: The attending physician determined the duration of oral anamorelin administration based on discontinuation due to cancer progression, poor efficacy, adverse events, or death. RESULTS: The 12-week continuation rate of oral anamorelin was 30.4%. Univariate analysis revealed that an Eastern Cooperative Oncology Group performance status (ECOG-PS) of ≥2 (P < .001), concurrent chemotherapy (P = .002), albumin level (P = .005), C-reactive protein level (P = .013), and a mGPS of 2 (P = .014) were statistically significant predictors of the 12-week continuation rate of oral anamorelin. In the multivariate analysis, a mGPS of 2 remained a significant risk factor, and the ECOG-PS and concurrent chemotherapy had no effect on the association between the mGPS and 12-week continuation rate of oral anamorelin. CONCLUSION: Patients with a mGPS of 2, compared with mGPS of 0 or 1, are less likely to maintain oral anamorelin therapy, regardless of the ECOG-PS or concurrent chemotherapy. Therefore, it is necessary to consider initiating anamorelin administration at mGPS 0 or 1.
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PD-L1 expression in keratinocyte and infiltration of CD4 + T lymphocyte can predict a severe type of erythema multiforme major induced by the anti-PD-1 antibody, pembrolizumab.
Ryohei Kadoi, Taichi Yoshida, Mai Noto, Aya Toyoshima, Sino Fujii, Koji Fukuda, Kazuhiro Shimazu, Daiki Taguchi, Hanae Shinozaki, Naoki Kodama, Michihiro Kono, Hiroshi Nanjyo, Hiroyuki Shibata
International cancer conference journal 13 ( 3 ) 268 - 274 2024年07月
研究論文（学術雑誌）
UNLABELLED: Skin toxicity is the most common adverse event of treatment with immune check point inhibitors. Among them, erythema multiforme is a rare occurrence with a frequency of 4%, with most of the cases developing grade 1/2 disease. We experienced high grade erythema multiforme major developing with pembrolizumab treatment for anal canal cancer with extensive skin metastases. Steroid ointment was ineffective, and the skin lesions with blisters expanded to > 45% of the body surface area. The patient was at risk for symptom aggravation, and a pulse therapy with methylprednisolone and increasing the dose of oral prednisolone (1 mg/kg) were started. The skin lesions improved in 1.8 months. Unless urgent and appropriate treatments such as high dose steroid administration were conducted, the skin toxicities could not be controlled. The presence of CD4+ T cells and PD-L1+ keratinocytes in the skin biopsy might be a predictive marker of erythema multiforme major resistant to standard steroid treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-024-00676-4.
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Fujita K.
Investigational New Drugs ( Investigational New Drugs ) 42 ( 3 ) 252 - 260 2024年06月
研究論文（学術雑誌）
The aim of the present study was to determine whether the trough plasma concentrations (C0) of regorafenib and its metabolites, the N-oxide metabolite (M-2) and the desmethyl N-oxide metabolite (M-5), in 21 patients receiving regorafenib therapy were affected by albumin-bilirubin (ALBI) grade. Regorafenib was administered at dosages ranging from 40 to 160 mg once daily on a 3-week-on, 1-week-off cycle. C0 values of regorafenib and its major metabolites were measured by high-performance liquid chromatography on day 8 after treatment initiation. The C0 values of regorafenib and metabolites M-2 and M-5 were significantly lower in patients with ALBI grade 2 as compared with grade 1 (P = 0.023, 0.003 and 0.017, respectively). The total C0 of regorafenib and its metabolites was significantly higher in ALBI grade 1 patients relative to grade 2 (3.489 μg/mL vs. 1.48 μg/mL; P = 0.009). The median relative dose intensity (RDI) of patients categorized as ALBI grade 2 was significantly lower than that of grade 1 patients (21.9% vs. 62.9%; P = 0.006). In 15 colorectal cancer patients among the total 21 patients, patients with ALBI grade 2 (n = 9) had a significantly shorter median overall survival time than patients with grade 1 (n = 6; P = 0.013). Administering a low dose of regorafenib to patients with ALBI grade 2 reduces the RDI of regorafenib and lowers treatment efficacy, as an appropriate C0 of regorafenib is not maintained. Monitoring the C0 of regorafenib regularly is necessary to guide dose adjustment.
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Recent trends in bone metastasis treatments: A historical comparison using the new Katagiri score system.
Kenji Matsuda, Kazuhiro Shimazu, Hanae Shinozaki, Koji Fukuda, Taichi Yoshida, Daiki Taguchi, Kyoko Nomura, Hiroyuki Shibata
World journal of clinical cases 12 ( 15 ) 2499 - 2505 2024年05月
研究論文（学術雑誌）
BACKGROUND: Bone metastasis has various negative impacts. Activities of daily living (ADL) and quality of life (QOL) can be significantly decreased, survival may be impacted, and medical expenses may increase. It is estimated that at least 5% cancer patients might be suffering from bone metastases. In 2016, we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis. Since then, the therapeutic outcomes for patients have gradually improved. As life expectancy is a major determinant of surgical intervention, the strategy should be modified if the prolongation of survival is to be achieved. AIM: To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis. METHODS: For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023, parameters including the site and number of bone metastases, laboratory data, and survival time, were extracted from electronic medical records and the Katagiri score was calculated. The association with survival was determined for each factor. RESULTS: Data from 136 patients were obtained. The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0% in this study, which was 6% and an apparent improvement from 2014 when the scoring system was developed. Other factors significantly affecting survival included five or more bone metastases than less (P = 0.0080), and treatment with chemotherapy (P < 0.001), bone modifying agents (P = 0.0175) and immune checkpoint inhibitors (P = 0.0128). In recent years, advances in various treatment methods have extended the survival period for patients with advanced cancer. It is necessary not only to simply extend survival time, but also to maintain ADL and improve QOL. CONCLUSION: Various therapeutic interventions including surgical approach for bone metastasis, which is a disorder of locomotor organs, are increasingly required. Guidelines and scoring system for prognosis need to be revised promptly.
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A case of hereditary breast and ovarian cancer syndrome of initially presented as cancer of unknown primary with lymph node metastases unveiled by genetic analysis.
Juri Yamada, Koji Fukuda, Tae Sugawara, Kenichi Makino, Kazuhiro Shimazu, Taichi Yoshida, Daiki Taguchi, Hanae Shinozaki, Yukihiro Terada, Hiroshi Nanjo, Hiroyuki Shibata
International cancer conference journal 13 ( 2 ) 139 - 143 2024年04月
研究論文（学術雑誌）
Cancer of unknown primary (CUP) is a heterogeneous disease concept involving various malignant tumors. Understanding its pathophysiology is often difficult, together with its treatment. Here, we present a case of CUP with abdominal lymph node enlargement and elevated carbohydrate antigen 125 levels. It initially resembled a favorable prognosis type similar to ovarian cancer, but metastases were observed in cervical lymph nodes, indicating a somewhat atypical CUP compared to the typical ovarian cancer-like CUP. We identified a germline Breast Cancer 1 (BRCA1) p.L63* variant through a family history inquiry and BRCA analysis, indicating hereditary breast and ovarian cancer syndrome. The patient achieved near-complete remission with platinum-based therapy followed by poly (ADP-ribose) polymerase (PARP) inhibitor. The variant has shown sensitivity in both clinical and pathogenic reports in the ClinVar database of the National Institutes of Health. No clinical studies reported on the efficacy of PARP inhibitors specific to this variant, but our case demonstrated the sensitivity of platinum-based therapy followed by PARP inhibitor. Reports of CUP in hereditary breast and ovarian cancer syndrome are very rare, with only a single report in the literature.
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Clinical Course of a Rare Epstein-Barr Virus-Associated Smooth Muscle Tumor and Its Genomic Analysis
Miyahara J.
Case Reports in Oncology ( Case Reports in Oncology ) 16 ( 1 ) 577 - 584 2023年08月
Epstein-Barr virus (EBV) can rarely induce smooth muscle tumors (SMTs). A 20-year-old female patient underwent kidney transplantation for renal failure. Since then, she has been treated with immunosuppressants, including a calcineurin inhibitor, tacrolimus, and prednisolone, owing to the immunological rejection. Three years later, she developed large liver tumors (diameter >5 cm) and multiple small lung tumors that were identified as EBV-SMTs based on the results of liver biopsy/histopathology. No intervention was performed except for the addition of a mammalian target of the rapamycin inhibitor, everolimus, which inhibits both immune reaction and SMT growth. Finally, after 8 years, the transplanted kidney became nonfunctional, and immunosuppressant administration became unnecessary as urinary dialysis was started. Under these circumstances, SMT growth was observed despite the absence of immunosuppressant administration. Three months after the cessation of the immunosuppressants, EBV-SMTs in the liver and lungs shrank slightly. To the best of our knowledge, this is the first report on the genomic profile of this rare tumor. The clinical course of our patient indicates that EBV can induce SMTs, and immunological suppression of EBV may inhibit the activity of these tumors.
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Kiyomiya M.
Japanese journal of clinical oncology ( Japanese journal of clinical oncology ) 53 ( 3 ) 270 - 274 2023年03月
We report the sensitivity of immune checkpoint inhibitors for tumors developing in a patient bearing the MSH2 c.1808A > T (Asp603Val) variant belonging to a pedigree of Lynch syndrome. This variant was previously thought to be of unknown significance, but we recently found that this missense mutation was likely pathogenic. At that time, there were no active members with malignancies that could be treated with chemotherapy. Thereafter, an 81-year-old woman bearing this variant, who was a cousin of the proband of this family, had multiple lymph node metastases from her resected gastric cancer. An immune checkpoint inhibitor, pembrolizumab, an anti-PD-1 antibody, was used to treat these tumors. After 3 months of treatment, almost all tumors disappeared, and elevated CA19-9 levels normalized. She survives over 15 months safely. It was indicated that the tumors bearing this germline variant were sensitive to pembrolizumab. This observation suggests that an MSH2 c.1808A > T (Asp603Val) variant induces mismatch repair deficiency, resulting in sensitization to immune checkpoint inhibition.
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Mounai Y.
Case Reports in Oncology ( Case Reports in Oncology ) 16 ( 1 ) 21 - 29 2023年
Intimal sarcoma is an extremely rare mesenchymal tumor arising in the great vessels. To date, intimal sarcoma has not been reported in patients with Lynch syndrome (LS), even though this syndrome lacks DNA mismatch repair ability genetically and is prone to various malignancies. This patient was diagnosed with LS by the Revised Amsterdam Criteria II, and she suffered from intimal sarcoma in the left pulmonary artery. She had a germline missense variant of PMS2 (c.1399G>A, pV467I) which is classified as a variant of unknown significance. In her intimal sarcoma, PMS2 expression was decreased. Additionally, it exhibited microsatellite instability and a high tumor mutational burden (69 mutations/Mb) which are features of mismatch repair deficiency, although PMS2 (c.1399G>A, pV467I) missense is a variant of unknown significance. The metastatic lesions of intimal sarcoma in this patient responded heterogeneously to pembrolizumab, an immune checkpoint inhibitor. Cytotoxic agents and radiation were also effective for some metastatic lesions, but some lesions, including her liver metastases, were resistant. The hypermutable nature of the LS genotype might acquire resistance to an immune checkpoint inhibitor and other cytotoxic agents such as occurred with her liver metastases.
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Two Cases of ALK-Altered Cancers of Unknown Primary Diagnosed by Immunohistochemistry
Kato Y.
Case Reports in Oncology ( Case Reports in Oncology ) 15 ( 1 ) 21 - 26 2022年01月
Cancer of unknown primary (CUP) accounts for 5% of all malignancies. Patients with CUP may live averagely for 8 months after diagnosis, and thus, rapid and reasonable diagnosis is necessary. Among patients with CUP, anaplastic lymphoma kinase (ALK)-overexpressing CUPs, whose primary sites were confirmed to be the lungs (Lung-CUP) by using antibodies against cytokeratin 7, thyroid transcription factor-1, and Napsin A, along with clinical characteristics progressed rapidly and were very sensitive to the ALK inhibitor alectinib. The incidence of ALK alteration in Lung-CUP is 19%. Consequently, it is advised that Lung-CUP be examined by immunohistochemistry (IHC) with an anti-ALK antibody. Alternative examinations, such as a cancer genome test, require as much as 2 months to complete, whereas IHC can be completed within days. In this report, a rapid assessment by IHC led to alectinib treatment, which resulted in good outcomes in 2 cases of Lung-CUP. Alectinib was effective for ALK-altered Lung-CUPs.
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A novel Lynch syndrome pedigree bearing germ-line MSH2 missense mutation c.1808A>T (Asp603Val)
Sekine R.
Japanese Journal of Clinical Oncology ( Japanese Journal of Clinical Oncology ) 52 ( 1 ) 81 - 85 2022年01月