記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Tonsillectomy with steroid pulse therapy (TSP) and tonsillectomy monotherapy (T) have improved the prognosis of patients with immunoglobulin A nephropathy (IgAN). However, a consensus has not been reached on the best treatment for these patients. This study aimed to compare the efficacies of TSP and T. METHODS: Data of patients with IgAN who received TSP or T were retrospectively analyzed. The exclusion criterion was a serum creatinine level > 1.5 mg/dL. The clinical remission and renal survival rates were compared. RESULTS: Patients were divided into groups based on the treatment method: the TSP (n = 82) and T groups (n = 41). No significant differences were observed in patient characteristics, except for the observation period (TSP: 60 months, T: 113 months). The log-rank test revealed that the clinical remission rate was significantly higher in the TSP group than in the T group (p < 0.05). The superiority of TSP was also observed in the urinary protein excretion (> / = or < 1 g/day) of the two subgroups. According to the Cox proportional-hazards model, the treatment method and daily urinary protein extraction were independent factors affecting clinical remission. The 10-year renal survival rates in the TSP and T groups were 100% and 92.5%, respectively. The log-rank test revealed a tendency for a higher renal survival rate in the TSP group than in the T group (p = 0.09). CONCLUSION: The clinical remission rate was significantly higher with TSP than with T, regardless of urinary protein levels. TSP tended to have a better renal survival rate than T.

DOI： 10.1007/s10157-024-02527-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In CD70-expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27-positive lymphocytes infiltrate around tumor cells. NPC patients with CD27-positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27-positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70-positive NPC with CD27-positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27-targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.

DOI： 10.1111/cas.16079

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Sialendoscopy is a procedure used to remove salivary stones intraorally using a sialendoscope. In this study, we identified treatment outcomes of sialendoscopic surgery and identified predictive factors for successful stone removal by sialendoscopy alone. METHODS: We assembled the medical records of 144 patients who underwent sialendoscopic surgery for submandibular gland sialolithiasis at the Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, from October 2010 to November 2021, and collected patient backgrounds, medical condition, perioperative factors including operation method and complications, postoperative course, and stone constituents from a clinical laboratory testing company. RESULTS: Submandibular gland stones were successfully removed using sialendoscopy in 58 patients (40%). In multivariate analysis, location, major axis, and mobility of the stones were independent factors for successful removal. In receiver operating characteristic analysis, <7.5 mm of a major axis may be used as a measuring standard for successful removal. Removal of parenchymal stones is prone to involve prolonged operation times, increased postoperative complications, and development of retained stones. The stones mainly consisted of calcium phosphate and protein, with content percentages ranging from 0 to 98% (median 37%) and from 0 to 100% (median 63%), respectively. The percentage of calcium phosphate was negatively correlated with the number of floating stones and successful stone removal. CONCLUSION: Sialendoscopy is an aesthetically attractive treatment for sialolithiasis that avoids cervical incisions. The present results showed not only known but also new predictive factors for the successful removal of stones (<7.5 mm) and percentage of calcium phosphate. Moreover, our results suggest that careful consideration is required regarding the indication of sialendoscopic surgery in patients with parenchymal stones.

DOI： 10.1016/j.anl.2023.01.006

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記述言語：英語  

Immune checkpoint inhibitors (ICIs) are a novel treatment option for treating head and neck squamous cell carcinoma (HNSCC). Among the immune-related adverse effects, cerebral infarction (CI) is a rare but fatal complication, and it has been reported in various cancers, except HNSCC. Herein, we describe three cases of patients diagnosed with HNSCC who experienced CI following ICI treatment. In addition, we conducted a comprehensive literature review on ICI-related thrombosis. Three patients with recurrent HNSCC were treated with nivolumab. Two patients had a history of CI, or heart disease, and were concurrently prescribed antithrombotic medications during nivolumab treatment. The number of nivolumab administrations varied from 1-25 before the onset of CI. All patients experienced worsening of neurological symptoms due to CI, irrespective of antithrombotic treatment, and they ultimately succumbed to the disease within 16-222 days following their initial ICI administration. ICIs may cause thromboembolisms, leading to CI. Based on our review of the literature, a history of thromboembolism or heart disease could be a risk factor for ICI-related thrombosis.

DOI： 10.7759/cureus.47406

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語  

A 15-year-old girl presented with a 3-year-history of continuous outflow of saliva from a pharyngocutaneous fistula, located at 5 mm superior to her tracheal stoma. She was diagnosed with Miller-Dieker syndrome at birth. At 2 years of age, pediatric surgeons at our institution carried out laryngotracheal separation to prevent aspiration pneumonia. At the age of 12 years, she developed continuous saliva discharge from the fistula. We performed central-part laryngectomy and resection of the pharyngocutaneous fistula, which relieved her from the continuous saliva discharge. Central-part laryngectomy is less invasive and easier to perform than total laryngectomy. We hereby present a case and retrospective analysis of 12 patients, who underwent central-part laryngectomy.

DOI： 10.1016/j.anl.2022.04.011

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記述言語：英語  

Upper airway infections caused by anaerobic bacteria, including pharyngitis and tonsillitis, are a common cause of septic thrombosis (Lemierre's syndrome). Although otitis media rarely progresses to systemic infection, an abscess surrounding the middle ear can affect the central nervous system. Trueperella bernardiae was originally considered a non-pathogenic aerobic bacterium but has subsequently been reported to cause bacteremia and brain abscesses. Here, we report a case of otitis media caused by T. bernardiae complicated by meningitis, subdural empyema, and septic pulmonary emboli in an immunocompetent patient.

DOI： 10.7759/cureus.42977

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be beneficial for the treatment of aggressive tumors. Because transcription factors are difficult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identified Brachyury-derived epitopes that elicit antigen-specific and tumor-reactive CD4+ T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the efficacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also confirmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer.

DOI： 10.1007/s00262-023-03460-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The engagement of CD27 on lymphocytes with its ligand, CD70, on tumors is believed to mediate tumor immune evasion and the elevation of serum soluble CD27 (sCD27) levels in patients with CD70-positive malignancies. We previously showed that CD70 is expressed in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), an Epstein-Barr virus (EBV)-related malignancy. However, little is known about serum sCD27 expression and its association with the clinical characteristics of, and the CD27/CD70 interaction in, ENKL. In the present study, we show that serum sCD27 is significantly elevated in the sera of patients with ENKL. The levels of serum sCD27 provided excellent diagnostic accuracy for discriminating patients with ENKL from healthy subjects, correlated positively with the levels of other diagnostic markers (lactate dehydrogenase, soluble interleukin-2 receptor, and EBV-DNA), and decreased significantly following treatment. Elevated serum sCD27 levels also correlated significantly with advanced clinical stage and tended to correspond with shorter survival, in patients with ENKL. Immunohistochemistry indicated that CD27-positive tumor-infiltrating immune cells exist adjacent to CD70-positive lymphoma cells. In addition, serum sCD27 levels in patients with CD70-positive ENKL were significantly higher than those in patients with CD70-negative ENKL, suggesting that the intra-tumoral CD27/CD70 interaction boosts the release of sCD27 in serum. Furthermore, the EBV-encoded oncoprotein latent membrane protein 1 upregulated CD70 expression in ENKL cells. Our results suggest that sCD27 may serve as a novel diagnostic biomarker and also may serve as a tool for evaluating the applicability of CD27/CD70-targeted therapies by predicting intra-tumoral CD70 expression and CD27/CD70 interaction in ENKL.

DOI： 10.1007/s00262-023-03394-7

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Homeobox B7 (HOXB7) is a master regulatory gene that regulates cell proliferation and activates oncogenic pathways. Overexpression of HOXB7 correlates with aggressive behavior and poor prognosis in patients with cancer. However, the expression and role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we observed that most samples from patients with oropharyngeal cancer and HNSCC expressed HOXB7. As no direct inhibitor has been reported, we identified a potent peptide epitope to target HOXB7-expressing tumors through immune cells. A novel HOXB7-derived peptide epitope (HOXB78-25 ) elicited antigen-specific and tumor-reactive promiscuous CD4+ T cell responses. These CD4+ T cells produced γ-interferon (IFN-γ) and had the direct ability to kill tumors through granzyme B. Notably, downregulation of HOXB7 using siRNA enhanced human leukocyte antigen class II expression on tumor cells by decreasing the phosphorylation of MAPK. Mitogen-activated protein kinase inhibition augmented IFN-γ production by HOXB7-reactive CD4+ T cell responses without decreasing the expression of HOXB7. These results suggest that combining HOXB7 peptide-based vaccine with MAPK inhibitors could be an effective immunological strategy for cancer treatment.

DOI： 10.1111/cas.15619

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To evaluate the efficacy and safety of Alternating Chemoradiotherapy (ACRT) using cisplatin and 5-Fluorouracil (5-FU) in patients with nasopharyngeal carcinoma. METHODS: This was a retrospective study in which patients' clinical records were reviewed to identify patients with a new diagnosis of nasopharyngeal carcinoma at our institution between January 2005 and January 2019. Thirty-seven eligible patients were identified; of these, the clinical details of 27 patients treated with ACRT were evaluated. Patient outcomes, including overall survival and progression-free survival, and adverse events were assessed. RESULTS: Of these initial 37 patients, 1, 10, 13, 10, and 3 were staged as I, II, III, IVA, and IVB, respectively, as defined by the 8th edition of the TNM classification system. Twenty-seven patients received ACRT comprising sequential administration of chemotherapy, radiotherapy (wide field), chemotherapy, radiotherapy (shrinking field), and chemotherapy. The 5-year overall survival and progression-free survival rates were 83.7% and 88.9%, respectively. Treatment compliance was 93%, which is comparable to that of previous reports. CONCLUSION: ACRT using cisplating and 5-fluorouracil was well tolerated with acceptable efficacy. LEVEL OF EVIDENCE: IVa.

DOI： 10.1016/j.bjorl.2022.12.004

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen-derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor-specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1140-162 , which effectively activated TWIST1-specific CD4+ T-cells. In a short-term culture system, we detected more TWIST1-specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1-reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.

DOI： 10.1111/cas.15429

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A combination therapy with immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has become the first-line treatment for recurrent or metastatic head and neck squamous carcinoma (HNSCC). Although steroids are often used as anti-emetic medications during chemotherapy, their adverse effects on immune-combined chemotherapy are unclear in HNSCC. METHODS: The effects of dexamethasone on tumor growth and immune cell population were evaluated in a mouse HNSCC model treated with PD-1 blockade combined with cisplatin. The effect of various doses of dexamethasone on cell proliferation, survival, surface markers, IFN-γ production, and antitumor effects in antigen-specific T cells was examined in vitro. The recovery of T cell dysfunction by IL-2 was assessed in vitro and in vivo. RESULTS: In a mouse HNSCC model, dexamethasone showed limited antitumor effects on immunochemotherapy. Dexamethasone decreased the number of T cells and inhibited T cell differentiation into effector and central memory T cells. In the in vitro assessment, dexamethasone induced cell death, limited proliferation, and reduced the reactivity against HNSCC cell lines of antigen-specific T cells in a dose-dependent manner. The expression of inhibitory receptors on T cells was not affected by steroids. This inhibition was recovered by IL-2 and IL-2/anti-IL-2 complexes (IL-2 Cx) in vitro and in vivo, respectively. CONCLUSION: Our preclinical data indicate that dexamethasone diminishes the antitumor effects of immunochemotherapy in patients with HNSCC. IL-2 Cx recovered the inhibition of antitumor immunity by steroids and might be a potent immune adjuvant for patients who require steroids during PD-1 blockade and chemotherapy.

DOI： 10.1016/j.tranon.2022.101358

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー感染症学会  

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fibroblast growth factor receptor 1 (FGFR1) is overexpressed in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Being associated with poor prognosis, FGFR1 is a potential therapeutic target for aggressive tumors. T cell-based cancer immunotherapy has played a central role in novel cancer treatments. However, the potential of antitumor immunotherapy targeting FGFR1 has not been investigated. Here, we showed that FGFR-tyrosine kinase inhibitors (TKIs) augmented antitumor effects of immune checkpoint inhibitors in an HNSCC mouse model and upregulated tumoral MHC class I and MHC class II expression in vivo and in vitro. This upregulation was associated with the mitogen-activated protein kinase signaling pathway, which is a crucial pathway for cancer development through FGFR signaling. Moreover, we identified an FGFR1-derived peptide epitope (FGFR1305-319) that could elicit antigen-reactive and multiple HLA-restricted CD4+ T cell responses. These T cells showed direct cytotoxicity against tumor cells that expressed FGFR1. Notably, FGFR-TKIs augmented antitumor effects of FGFR1-reactive T cells against human HNSCC cells. These results indicate that the combination of FGFR-TKIs with immunotherapy, such as an FGFR1-targeting peptide vaccine or immune checkpoint inhibitor, could be a novel and robust immunologic approach for treating patients with FGFR1-expressing cancer cells.

DOI： 10.1080/2162402X.2021.2021619

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 20-month-old male patient presented with a tumor on his tongue. The tumor was detected at birth with an initial size of 5 mm; thereafter, it gradually grew larger. The patient had no symptoms, but he frequently touched the tumor, as he grew older. The authors performed a tumor resection under general anesthesia, and the histopathological diagnosis confirmed that it was an accessory tongue, with the same components as that of a normal tongue. An accessory tongue regularly grows bigger as a patient grows older, resulting in dysphagia and articulation disorder. Younger patients should get accessory tongues surgically resected as soon as they are old enough to receive general anesthesia.

DOI： 10.1016/j.anl.2020.08.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Identification of immunogenic tumor antigens, their corresponding T cell epitopes and the selection of effective adjuvants are prerequisites for developing effective cancer immunotherapies such as therapeutic vaccines. Murine double minute 2 (MDM2) is an E3 ubiquitin-protein ligase that negatively regulates tumor suppressor p53. Because MDM2 overexpression serves as a poor prognosis factor in various types of tumors, it would be beneficial to develop MDM2-targeted cancer vaccines. In this report, we identified an MDM2-derived peptide epitope (MDM232-46) that elicited antigen-specific and tumor-reactive CD4+ T cell responses. These CD4+ T cells directly killed tumor cells via granzyme B. MDM2 is expressed in head and neck cancer patients with poor prognosis, and the T cells that recognize this MDM2 peptide were present in these patients. Notably, Nutlin-3 (MDM2-p53 blocker), inhibited tumor cell proliferation, was shown to augment antitumor T cell responses by increasing MDM2 expression, HLA-class I and HLA-DR through class II transactivator (CIITA). These results suggest that the use of this MDM2 peptide as a therapeutic vaccine combined with MDM2 inhibitors could represent an effective immunologic strategy to treat cancer.

DOI： 10.1007/s00262-021-02940-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocytosis, and its receptor, CD47, is overexpressed in various cancer types. Based on our findings that breast cancer patients with highly expressed CD47 have poor survival, we evaluated the therapeutic efficacy and underlying mechanisms of combination therapy with the STING ligand cGAMP and an antagonistic anti-CD47 mAb using E0771 mouse breast cancer cells. Anti-CD47 mAb monotherapy did not suppress tumor growth in our setting, whereas cGAMP and anti-CD47 mAb combination therapy inhibited tumor growth. The combination therapy enhanced phagocytosis of tumor cells and induced systemic anti-tumor immune responses, which rely on STING and type I IFN signaling. Taken together, our findings indicate that coadministration of cGAMP and an antagonistic anti-CD47 mAb may be promising for effective cancer immunotherapy.

DOI： 10.1084/jem.20200792

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Stimulator of interferon genes (STING) contributes to anti-tumor immunity by activating antigen-presenting cells and inducing mobilization of tumor-specific T cells. A role for tumor-migrating neutrophils in the anti-tumor effect of STING-activating therapy has not been defined. We used mouse tumor transplantation models for assessing neutrophil migration into the tumor triggered by intratumoral treatment with STING agonist, 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Intratumoral STING activation with cGAMP enhanced neutrophil migration into the tumor in an NF-κB/CXCL1/2-dependent manner. Blocking the neutrophil migration by anti-CXCR2 monoclonal antibody impaired T cell activation in tumor-draining lymph nodes (dLNs) and efficacy of intratumoral cGAMP treatment. Moreover, the intratumoral cGAMP treatment did not show any anti-tumor effect in type I interferon (IFN) signal-impaired mice in spite of enhanced neutrophil accumulation in the tumor. These results suggest that both neutrophil migration and type I interferon (IFN) induction by intratumoral cGAMP treatment were critical for T-cell activation of dLNs and the anti-tumor effect. In addition, we also performed in vitro analysis showing enhanced cytotoxicity of neutrophils by IFN-β1. Extrinsic STING activation triggers anti-tumor immune responses by recruiting and activating neutrophils in the tumor via two signaling pathways, CXCL1/2 and type I IFNs.

DOI： 10.1007/s00262-021-02864-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent studies have revealed that tumor cells decrease their immunogenicity by epigenetically repressing the expression of highly immunogenic antigens to survive in immunocompetent hosts. We hypothesized that these epigenetically hidden "stealth" antigens should be favorable targets for cancer immunotherapy due to their high immunogenicity. To identify these stealth antigens, we treated human lung cell line A549 with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5Aza) and its prodrug guadecitabine for 3 d in vitro and screened it using cDNA microarray analysis. We found that the gene encoding sperm equatorial segment protein 1 (SPESP1) was re-expressed in cell lines including solid tumors and leukemias treated with 5Aza, although SPESP1 was not detected in untreated tumor cell lines. Using normal human tissue cDNA panels, we demonstrated that SPESP1 was not detected in normal human tissue except for testis and placenta. Moreover, we found using immunohistochemistry SPESP1 re-expression in xenografts in BALB/c-nu/nu mice that received 5Aza treatment. To assess the antigenicity of SPESP1, we stimulated human CD4+ T-cells with a SPESP1-derived peptide designed using a computer algorithm. After repetitive stimulation, SPESP1-specific helper T-cells were obtained; these cells produced interferon-γ against HLA-matched tumor cell lines treated with 5Aza. We also detected SPESP1 expression in freshly collected tumor cells derived from patients with acute myeloid leukemia or lung cancer. In conclusion, SPESP1 can be classified as a stealth antigen, a molecule encoded by a gene that is epigenetically silenced in tumor cells but serves as a highly immunogenic antigen suitable for cancer immunotherapy.

DOI： 10.1111/cas.14973

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Early life respiratory insults, such as viral infections or hyperoxia, often increase asthma susceptibility later in life. The mechanisms underlying this increased susceptibility are not fully understood. IL-33 has been shown to be critically involved in allergic airway diseases. IL-33 expression in the neonatal lung can be increased by various respiratory insults associated with asthma development. Therefore, we investigated whether and how early life increases in IL-33 impact allergic airway responses later in life. Using a novel IL-33 transgenic mouse model, in which full-length IL-33 was inducible overexpressed in lung epithelial cells, we transiently upregulated lung IL-33 expression in neonatal mice for one week. After resting for 4-6 weeks, mice were intranasally exposed to a single-dose of recombinant IL-33 or the airborne allergen Alternaria. Alternatively, mice were exposed to Alternaria and ovalbumin multiple times for one month. We found that a transient increase in IL-33 expression during the neonatal period promoted IL-5 and IL-13 production when mice were later exposed to a single-dose of IL-33 or Alternaria in adulthood. However, increased IL-33 expression during the neonatal period did not affect airway inflammation, type 2 cytokine production, lung mucus production, or antigen-specific antibody responses when adult mice were exposed to Alternaria and ovalbumin multiple times. These results suggest that transient increased IL-33 expression early in life may have differential effects on allergic airway responses in later life, preferentially affecting allergen-induced acute type 2 cytokine production.

DOI： 10.1371/journal.pone.0252199

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Placenta-specific 1 (PLAC1) is expressed primarily in placental trophoblasts but not in normal tissues and is a targetable candidate for cancer immunotherapy because it is a cancer testis antigen known to be up-regulated in various tumors. Although peptide epitopes capable of stimulating CD8 T cells have been previously described, there have been no reports of PLAC1 CD4 helper T lymphocyte (HTL) epitopes and the expression of this antigen in head and neck squamous cell carcinoma (HNSCC). Here, we show that PLAC1 is highly expressed in 74.5% of oropharyngeal and 51.9% of oral cavity tumors from HNSCC patients and in several HNSCC established cell lines. We also identified an HTL peptide epitope (PLAC131-50) capable of eliciting effective antigen-specific and tumor-reactive T cell responses. Notably, this peptide behaves as a promiscuous epitope capable of stimulating T cells in the context of more than one human leukocyte antigen (HLA)-DR allele and induces PLAC1-specific CD4 T cells that kill PLAC1-positive HNSCC cell lines in an HLA-DR-restricted manner. Furthermore, T-cells reactive to PLAC131-50 peptide were detected in the peripheral blood of HNSCC patients. These findings suggest that PLAC1 represents a potential target antigen for HTL based immunotherapy in HNSCC.

DOI： 10.1080/2162402X.2020.1856545

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.xocr.2020.100250

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Colorectal cancer (CRC) patients with metastatic lesions have low 5-year survival rates. During metastasis, cancer cells often obtain unique characteristics such as epithelial-mesenchymal transition (EMT). Vimentin a biomarker contributes to EMT by changing cell shape and motility. Since abnormal phosphorylation is a hallmark of malignancy, targeting phosphorylated vimentin is a feasible approach for the treatment of metastatic tumors while sparing non-tumor cells. Recent evidence has revealed that both CD8 cytotoxic T lymphocytes (CTLs) and also CD4 helper T lymphocytes (HTLs) can distinguish post-translationally modified antigens from normal antigens. Here, we showed that the expression of phosphorylated vimentin was upregulated in metastatic sites of CRC. We also showed that a chemotherapeutic reagent augmented the expression of phosphorylated vimentin. The novel phosphorylated helper peptide epitopes from vimentin could elicit a sufficient T cell response. Notably, precursor lymphocytes that specifically reacted to these phosphorylated vimentin-derived peptides were detected in CRC patients. These results suggest that immunotherapy targeting phosphorylated vimentin could be promising for metastatic CRC patients.

DOI： 10.1007/s00262-020-02524-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although cisplatin (CDDP) has been used as a major chemotherapeutic drug for head and neck squamous cell carcinoma (HNSCC), its impact on T-cell functions is controversial. Therefore, we investigated the immunologic effects of CDDP and antitumor effects by combination therapy of CDDP with a ligand for stimulator of interferon genes, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Direct impacts of CDDP on T-cell functions were addressed by comparing T-cell functions between human subjects treated and untreated with CDDP. The immune responses and the efficacy of combination therapy using CDDP and cGAMP were assessed using BALB/c mice inoculated with mouse squamous cell carcinoma (SCC) cell lines. CDDP inhibited T-cell proliferation in a dose-dependent manner. T-cell functions of CDDP-treated HNSCC patients were comparable to those of healthy donors and CDDP-untreated HNSCC patients. In the mice bearing SCC cell lines, combination therapy using CDDP and cGAMP enhanced the gene expressions of CXCL9 and CXCL10 in the tumor tissues and inhibited tumor growth. The antitumor effect was cancelled by anti-CXCR3 monoclonal antibody. These findings suggest that the combination therapy using CDDP and an immunomodulating drug like cGAMP would be a rational cancer immunotherapy for patients with HNSCC.

DOI： 10.1016/j.bbrc.2019.11.107

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) originates from squamous epithelium of the upper aerodigestive tract and is the most common malignancy in the head and neck region. Among HNSCCs, oropharynx squamous cell carcinoma (OSCC) has a unique profile and is associated with human papillomavirus infection. Recently, anti-programmed cell death-1 monoclonal antibody has yielded good clinical responses in recurrent and/or metastatic HNSCC patients. Therefore, programmed death-ligand 1 (PD-L1) may be a favorable target molecule for cancer immunotherapy. Although PD-L1-expressing malignant cells could be targeted by PD-L1-specific CD8+ cytotoxic T lymphocytes, it remains unclear whether CD4+ helper T lymphocytes (HTLs) recognize and kill tumor cells in a PD-L1-specific manner. METHODS: The expression levels of PD-L1 and HLA-DR were evaluated using immunohistochemical analyses. MHC class II-binding peptides for PD-L1 were designed based on computer algorithm analyses and added into in vitro culture of HTLs with antigen-presenting cells to evaluate their stimulatory activity. RESULTS: We found that seven of 24 cases of OSCC showed positive for both PD-L1 and HLA-DR and that PD-L1241-265 peptide efficiently activates HTLs, which showed not only cytokine production but also cytotoxicity against tumor cells in a PD-L1-dependent manner. Also, an adoptive transfer of the PD-L1-specific HTLs significantly inhibited growth of PD-L1-expressing human tumor cell lines in an immunodeficient mouse model. Importantly, T cell responses specific for the PD-L1241-265 peptide were detected in the HNSCC patients. CONCLUSIONS: The cancer immunotherapy targeting PD-L1 as a helper T-cell antigen would be a rational strategy for HNSCC patients.

DOI： 10.1186/s12967-019-1957-5

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Nasal natural killer/T-cell lymphoma (NNKTL) is closely associated with Epstein-Barr virus (EBV) and is characterized by poor prognosis, resulting from rapid progression of lesions in the affected organs. Recent data have shown that NNKTL is associated with the aberrant expression of cyclin-dependent kinase 1 (CDK1) and its downstream target survivin, but little is known about the functional roles of CDK1 and survivin in NNKTL. In the current study, we show that knockdown of the EBV-encoded oncoprotein latent membrane protein 1 (LMP1) induces downregulation of CDK1 and survivin in NNKTL cells. Immunohistochemistry detected CDK1 and survivin expression in LMP1-positive cells of NNKTL biopsy specimens. Inhibition of CDK1 and survivin in NNKTL cells with several inhibitors led to a dose-dependent decrease in cell proliferation. In addition, the Sp1 inhibitor mithramycin, which can downregulate both CDK1 and survivin, significantly suppressed the growth of established NNKTL in a murine xenograft model. Our results suggest that LMP1 upregulation of CDK1 and survivin may be essential for NNKTL progression. Furthermore, targeting CDK1 and survivin with Sp1 inhibitors such as mithramycin may be an effective approach to treat NNKTL, which is considered to be a treatment-refractory lymphoma.

DOI： 10.1038/s41374-018-0182-9

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The human T cell receptor is capable of distinguishing between normal and post-translationally modified peptides. Because aberrant phosphorylation of cellular proteins is a hallmark of malignant transformation, the expression of the phosphorylated epitope could be an ideal antigen to combat cancer without damaging normal tissues. p53 activates transcription factors to suppress tumors by upregulating growth arrest and apoptosis-related genes. In response to DNA damage, p53 is phosphorylated at multiple sites including Ser33 and Ser37. Here, we identified phosphorylated peptide epitopes from p53 that could elicit effective T helper responses. These epitope peptides, p5322-41/Phospho-S33 and p5322-41/Phospho-S37, induced T helper responses against tumor cells expressing the phosphorylated p53 protein. Moreover, chemotherapeutic agents augmented the responses of such CD4 T cells via upregulation of phosphorylated p53. The upregulation of phosphorylated p53 expression by chemotherapy was confirmed in in vitro and xenograft models. We evaluated phosphorylated p53 expression in the clinical samples of oropharyngeal squamous cell carcinoma and revealed that 13/24 cases (54%) were positive for phosphorylated p53. Importantly, the lymphocytes specific for the phosphorylated p53 peptide epitopes were observed in the head and neck squamous cell cancer (HNSCC) patients. These results reveal that a combination of phosphorylated p53 peptides and chemotherapy could be a novel immunologic approach to treat HNSCC patients.

DOI： 10.1080/2162402X.2018.1466771

PubMed

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Despite recent advances in treatment for melanoma patients through using immune checkpoint inhibitors, these monotherapies have limitations and additional treatments have been explored. Type I IFNs have been used to treat melanoma and possess immunomodulatory effects including enhancement of T-cell infiltration. T-cell plays a critical role in immune checkpoint therapies via restoration of effector functions and tumor infiltration by T-cells predicts longer survival in a variety of cancer types. Moreover, tumor-infiltrating T-cells are associated with the expression of chemokines such as CCL5 and CXCR3 ligands in tumor tissues. We therefore investigated whether intratumoral injection of IFN-β induces the expression of CCL5 and CXCR3 ligands in melanoma cells and has additional antitumor effects when combined with anti-PD-L1 mAb treatment. IFN-β treatment enhanced CD8+ T-cell infiltration into tumors and CCL5 and CXCR3 ligand expression. In vivo studies using a mouse model showed that monotherapy with IFN-β, but not with anti-PD-L1 mAb, inhibited tumor growth in comparison to control. However, the therapeutic efficacy of IFN-β was significantly enhanced by the addition of anti-PD-L1 mAb. This antitumor response of combination therapy was abrogated by anti-CD8 mAb and IFN-β augmented the neoantigen-specific T-cell response of anti-PD-L1 mAb. Our findings suggest that IFN-β induces the expression of CCL5 and CXCR3 ligands in melanoma, which could play a role in T-cell recruitment, and enhances the efficacy of anti-PD-L1 mAb treatment in a CD8-dependent manner.

DOI： 10.1016/j.bbrc.2017.06.072

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive neoplasm with poor therapeutic responses and prognosis. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays an important role in immune evasion of tumor cells through T-cell exhaustion. The aim of the present study was to examine the expression of PD-L1 and PD-1 molecules in NNKTL. We detected the expression of PD-L1 in biopsy samples from all of the NNKTL patients studied. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells infiltrated the tumor tissues in 36% of patients. Most significantly, soluble PD-L1 (sPD-L1) was present in sera of NNKTL patients at higher levels as compared to healthy individuals and the levels of serum sPD-L1 in patients positively correlated with the expression of PD-L1 in lymphoma cells of tumor tissues. In addition, the high-sPD-L1 group of patients showed significantly worse prognosis than the low-sPD-L1 group. Furthermore, we confirmed that membrane and soluble PD-L1 was expressed on the surface and in the culture supernatant, respectively, of NNKTL cell lines. The expression of PD-L1 was observed in tumor tissues and sera from a murine xenograft model inoculated with an NNKTL cell line. Our results suggest that sPD-L1 could be a prognostic predictor for NNKTL and open up the possibility of immunotherapy of this lymphoma using PD-1/PD-L1 axis inhibitors.

DOI： 10.1007/s00262-017-1987-x

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Stimulator of IFN genes (STING) spontaneously contributes to anti-tumor immunity by inducing type I interferons (IFNs) following sensing of tumor-derived genomic DNAs in the tumor-bearing host. Although direct injection of STING ligands such as cyclic diguanylate monophosphate (c-di-GMP) and cyclic [G(2',5')pA(3',5')p] (cGAMP) into the tumor microenvironment exerts anti-tumor effects through strong induction of type I IFNs and activation of innate and adaptive immunity, the precise events caused by STING in the tumor microenvironment remain to be elucidated. We describe here our finding that a CD45+ CD11bmid Ly6C+ cell subset transiently accumulated in mouse tumor microenvironment of 4T1 breast cancer, squamous cell carcinomas, CT26 colon cancer, or B16F10 melanoma tissue after intratumoral injection of cGAMP. The accumulated cells displayed a macrophage (M ) phenotype since the cells were positive for F4/80 and MHC class II and negative for Ly6G. Intratumoral cGAMP treatment did not induce Mφ accumulation in STING-deficient mice. Depletion of CD8+ T cell using anti-CD8 mAb impaired the anti-tumor effects of cGAMP treatment. Depletion of the Mφ using clodronate liposomes impaired the anti-tumor effects of cGAMP treatment. Functional analysis indicated that the STING-triggered tumor-migrating Mφ exhibited phagocytic activity, production of tumor necrosis factor alpha TNFα), and high expression levels of T cell-recruiting chemokines, Cxcl10 and Cxcl11, IFN-induced molecules, MX dynamin-like GTPase 1 (Mx1) and 2'-5' oligoadenylate synthetase-like 1 (Oasl1), nitric oxide synthase 2 (Nos2), and interferon beta 1 (Ifnb1). These results indicate that the STING-triggered tumor-migrating Mφ participate in the anti-tumor effects of STING-activating compounds.

DOI： 10.1007/s00262-017-1975-1

PubMed

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記述言語：英語   出版者・発行元：日本がん免疫学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tumor immune escape has been a major problem for developing effective immunotherapy. The human leukocyte antigen G (HLA-G) is a non-classical MHC class I molecule whose primary function is to protect the fetus from the mother's immune system. While HLA-G is hardly found in normal adult tissues, various tumor cells are known to express it, aiding their escape from the immune system. Thus, HLA-G is an attractive immunotherapy target. CD4(+) helper T lymphocytes (HTLs) play an important role in the immune reaction against tumors by assisting in the generation and persistence of CD8(+) cytotoxic T lymphocytes (CTLs) or by displaying direct antitumor effects. We report here that HLA-G expression in breast cancer significantly correlates with a poor prognosis. Also, we describe that the MHC class II-binding peptide HLA-G26-40 was effective in eliciting tumor-reactive CD4(+) T cell responses. Furthermore, treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine increased HLA-G expression in tumors and subsequently enhanced recognition by HLA-G26-40-specific HTLs. These findings predict that a combination immunotherapy targeting HLA-G together with a DNA methyltransferase inhibitor could be useful against some cancers.

DOI： 10.1080/2162402X.2016.1169356

PubMed

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掲載種別：研究論文（学術雑誌）  

Sjögren's syndrome (SS) is an autoimmune disease with glandular and extraglandular manifestations. In terms of pulmonary and cardiac involvement, pleural and pericardial effusion are rare. Moreover, pleural effusion accompanied by pericardial effusion is very rare. We report a case of primary SS (pSS) presenting as pleural effusion, pericardial effusion and ascites. A 58-year-old woman was admitted to our hospital with a 2-week history of dyspnea. Bilateral pleural effusion, pericardial effusion and ascites were detected. Primary SS was diagnosed, based on xerophthalmia, xerostomia, positive results for the Shirmer test and anti-SS-A antibody, and abnormal salivary gland sialography. Pleural and pericardial effusions were attributed to autoimmunological inflammation and ascites was thought to be due to hyperinflammation-induced severe hypoalbuminemia. Treatment with highdose corticosteroid was proved successful.

Scopus

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/art.34418

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated the relationship between nasopharyngeal flora of pediatric patients and antibiotic consumption in a local community in Japan between 2000 and 2009 retrospectively. There was a clear relationship between the lower annual consumption rate of cephalosporins and the lower annual prevalence of non-susceptible strains of Streptococcus pneumoniae (SP). High prevalence of BLNAR (β-lactamase nonproducing ampicillin-resistant Haemophilus influenzae) has been one of the bacteriological features of Japan.

DOI： 10.1159/000324789

PubMed

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本鼻科学会  

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：日本がん免疫学会  

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記述言語：日本語   出版者・発行元：日本がん免疫学会  

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本鼻科学会  

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

食道異物は近年の内視鏡器具の進歩により、内視鏡下に摘出可能な症例が増加している。渉猟し得た限りで内視鏡下の異物摘出後に遺残が判明し、外切開にて遺残異物を摘出した報告はない。今回われわれは内視鏡下に半分を摘出し得たものの、残存した食道腔外殻付きアマエビ異物に対して頸部外切開を必要とした症例を経験したので報告する。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J01054&link_issn=&doc_id=20150624450007&doc_link_id=%2Fea4broes%2F2015%2F006603%2F007%2F0226-0231%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fea4broes%2F2015%2F006603%2F007%2F0226-0231%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

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記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

36歳男。先行する体幹失調、それに続くめまい発作(視界が左右に揺れ歩行困難)を繰り返していた。入院時、左右方向に無秩序に生じる異常眼球運動を常時認め、各種検査や画像検査で異常はなく、注視眼振検査で水平方向が主体ではあるが無秩序に生じる急速眼球運動(opsoclonus様)と、それに先行する失調症状からopsoclonus-myoclonus syndrome(OMS)が疑われた。特発性のOMSと考えステロイドパルス療法(メチルプレドニゾロン点滴3日間)を計2コース実施し、いずれのクールでも2日目の点滴終了後に異常眼球運動の停止を認め、2クール終了後1年3ヵ月時点まで明らかな再発は認めてない。ステロイドパルス療法による異常眼球運動停止後のENG検査では、追跡眼球運動検査で左指標追跡時saccadic ataxic patternを示し、視運動性眼振検査で触発不良、温刺激検査でvisual suppressionの異常を認めたこと等から、潜在的な小脳の機能不全が示唆された。また、ステロイドパルス療法にて異常眼球運動が消失したことから、何らかの自己免疫的機序が発症に寄与した可能性が示唆された。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J00580&link_issn=&doc_id=20140808240003&doc_link_id=10.5631%2Fjibirin.107.603&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.107.603&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

症例は27歳男性で、自殺企図により包丁で右頸部を刺傷し、近医救急搬送となった。搬送時には出血は止まっていたが、著明な頸部腫脹が認められたため、再出血の可能性が高いと判断され、当院へ救急搬送された。CTでは右総頸動脈分岐部付近に造影剤の漏出を認め、緊急で全身麻酔下に手術を施行した。手術所見では右総頸動脈は4/5周にわたり断裂を認め、断裂部末梢の血流は保存されていたため、血管吻合は行わず、頸動脈損傷部の上下を3重結紮した。術後経過は良好で、術後23日目に後遺症なく退院した。なお、入院中に精神科を受診したが、うつ病などの気分障害による希死念慮はみられず、急性アルコール中毒による衝動的自殺行為と診断された。本症例では血腫により総頸動脈損傷部が圧迫止血され、手術までの時間が確保できたため救命することができたと考えられた。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00580&link_issn=&doc_id=20130802250013&doc_link_id=10.5631%2Fjibirin.106.747&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.106.747&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

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記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

73歳男。咽頭痛を主訴とした。入院時咽頭内視鏡所見にて喉頭蓋の喉頭面から一部声門下の気管にかかる広範な白色病変を認めたが、鼻腔、口腔、咽頭内に異常所見はなかった。当初は原因不明の喉頭炎として治療を開始したが、入院後の問診の結果、咽頭痛出現前に有機リン酸系殺虫剤散布していたことが判明し、誤吸入を原因とする化学熱傷と考えた。有機リン中毒の症状や肺水腫は止めず、入院2日後(誤吸入9日後)に白色病変は改善傾向となり、入院4日後に退院となった。退院後、近医における胸部X線では異常所見は認めなかった。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2012&ichushi_jid=J00580&link_issn=&doc_id=20120904380010&doc_link_id=10.5631%2Fjibirin.105.859&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.105.859&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

71歳男性。38歳時にオスラー病による鼻出血のため著者らの施設へ紹介となった。KTPレーザーによる粘膜焼灼術を20年間に22回行ったが、今回、鼻出血の回数ならびに出血量のコントロールが困難となり、入院となった。所見では左外鼻孔は度重なる鼻粘膜焼灼処置により狭小化し、鼻中隔には穿孔が認められた。鼻中隔穿孔を伴う中等症オスラー病と診断され、鼻粘膜皮膚移植術を施行したところ、鼻出血の頻度は激減し、術後16ヵ月経過現在、QOLの大幅な改善が得られた。

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記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

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記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

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記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

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