記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Auris Nasus Larynx  

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive cancer-related disease with a dismal clinical course. The patient in this report was a 43-year-old man with metastatic salivary duct carcinoma arising from the parotid gland. Combined androgen blockade therapy was administered started as first-line treatment, but failed after 5 months, followed by docetaxel plus carboplatin therapy as second-line treatment, which failed after 3 months. Genomic profiling revealed a BRAF V600E mutation, and combined BRAF and MEK inhibitor therapy was started as third-line treatment. The cancer remained stable during the first 10 months of third-line treatment, but treatment was subsequently discontinued due to the onset of symptoms of fatigue, myalgia and arthritis. Twenty days after the onset of these symptoms and interruption of third-line treatment, the patient was urgently admitted to hospital with respiratory distress and severe thrombocytopenia. CT images at the time of admission led our radiologist to the possibility of PTTM, but the patient died the day after admission and autopsy findings indicated that PTTM was the cause of death. This report describes a very informative case of PTTM with sequential imaging and detailed autopsy findings were available and provides a literature review.

DOI： 10.1016/j.anl.2024.07.002

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Annals of Esophagus  

Background: Preoperative docetaxel, cisplatin, and 5-fluorouracil (DCF) has become the standard treatment for resectable esophageal squamous cell carcinoma (ESCC) based on the results of the JCOG1109 trial. However, preoperative DCF is associated with a high frequency of febrile neutropenia (FN), especially in elderly patients with risk factors for FN. The utility of primary prophylactic pegfilgrastim on day 3 of preoperative DCF for preventing FN was demonstrated in a Phase II study, but it did not report comparison data in elderly ESCC patients. We aimed to evaluate the utility of primary prophylactic pegfilgrastim in these patients. Methods: We retrospectively evaluated the clinical utility of primary prophylactic pegfilgrastim on day 3 of preoperative DCF in elderly patients with resectable ESCC. The patients were divided into a day 3 pegfilgrastim group (D3PG) and a no pegfilgrastim group (NPG). The incidence of FN and grade ≥3 neutropenia, histopathological effects, and relapse-free survival (RFS) were compared between the groups. Results: Thirty patients were enrolled in each group. FN was observed in 3.3% of patients in the D3PG and 26.6% of those in the NPG (P=0.02), and grade ≥3 neutropenia was observed in 10% and 70%, respectively (P<0.001). The pathological complete response rate was 24.1% in the D3PG and 33.3% in the NPG (P=0.44); the respective 3-year RFS rates were 70.1% and 57.1% (P=0.30). The relative dose intensity was 0.914 in the D3PG and 0.850 in the NPG for docetaxel (P=0.01), 0.858 and 0.844, respectively, for cisplatin (P=0.45), and 0.916 and 0.846 for 5-fluorouracil (P=0.01). Conclusions: Primary prophylactic pegfilgrastim on day 3 of preoperative DCF significantly reduced the risks of FN and grade ≥3 neutropenia in elderly patients with ESCC. There was no significant difference between the groups in histological effects or RFS.

DOI： 10.21037/aoe-24-20

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastrointestinal Cancer  

Background: Nivolumab monotherapy is the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) after failure of platinum-based chemotherapy without anti-PD-1 antibody. Fixed dosing with 240 mg every 2 weeks was approved initially, followed by fixed dosing with 480 mg every 4 weeks based on pharmacokinetics data. However, information on the comparative efficacy and safety of the two doses remains limited. Methods: We compared progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and the incidence of adverse events (AEs) between the two doses in 117 patients who received second-line (n = 85) or later-line (n = 32) nivolumab monotherapy at our institution between January 2016 and December 2021. Results: In the second-line group, patient characteristics for the 240 mg and 480 mg groups were as follows (240 mg vs. 480 mg): performance status (PS) 0/1/2 was 34/61/5% vs. 54/42/4%, and prior fluoropyrimidine plus platinum therapy (FP) was 81.3% vs. 42.3%. In the later-line group, the characteristics were: PS 0/1/2 was 28/60/12% vs. 14/86/0%, and prior FP was 60.0% vs. 42.8%. ORR was 11.9 vs. 24.0% in the second-line group (p = 0.19) and 0 vs. 14.3% in the later-line group (p = 0.22). Median PFS was 1.7 vs. 4.1 months on second-line (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.35–1.01, p = 0.056) and 1.4 vs. 1.8 months on later-line (HR 0.58, 95% CI 0.23–1.46, p = 0.25); AEs of any grade were observed in 58.3 vs. 69.7%, respectively. Conclusions: The efficacy and safety of the two doses of nivolumab monotherapy were comparable in patients with advanced ESCC.

DOI： 10.1007/s12029-024-01092-w

Scopus

PubMed

記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

記述言語：日本語   出版者・発行元：Journal of Clinical Oncology  

Background: Docetaxel and cisplatin, 5-FU (DCF) therapy has established as the standard neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC) based on the results of the JCOG1109 study. If patients showed recurrence of ESCC after neoadjuvant DCF therapy, platinum-containing regimens were used as palliative treatment in the clinical practice. However, there were no data of correlation between histopathological response by neoadjuvant DCF therapy and clinical efficacy of palliative platinum-containing regimens for recurrent ESCC. Methods: We retrospectively reviewed patients with ESCC who received neoadjuvant DCF therapy and R0 resection between Feb 2014 to June 2022 in our hospital. We evaluated histopathological response by neoadjuvant DCF therapy based on the Japanese Classification of Esophageal Cancer 12^th (Grade 0: ineffective, Grade 1: slightly effective, Grade 2: moderately effective, Grade 3: markedly effective [pT0]) and objective response rate (ORR), progression-free survival (PFS) during platinum-containing regimens as clinical efficacy outcomes. We analyzed the correlation between histopathological response and ORR, PFS using Fisher’s exact tests and the log-rank tests. In addition, we analyzed clinical factors related to clinical efficacy of palliative chemotherapy using Cox proportional hazards models. Results: In this study, 398 patients received neoadjuvant DCF therapy and we identified 88 eligible patients with recurrence. Among 88 patients, 33 patients initially received palliative chemotherapy and analyzed. Patients’ characteristics were followed; Male/Female: 26 (78.8%)/7 (21.2%), median age (range): 64 (46–76) years, PS 0/1/2: 1 2(36.4%)/17 (51.5%), 4 (12.1%). Histopathological response 0/1/2/3 were in 1 (3.0%)/23 (69.7%)/7 (21.2%)/2 (6.1%) patients, respectively. Among these 33 patients, 23 patients received platinum-containing regimens. In the patients who received palliative chemotherapy, the ORR were 34.8% (8/23) in histopathological response 0/1 group and 44.4% (4/9) in histopathological response 2/3 group, with no statistical difference (p = 0.696). The median PFS was 2.43 (95%CI: 2.33–2.53) months in histopathological response 0/1 group and 4.04 (95%CI: 0-10.77) months in histopathological 2/3 group (HR[95%CI]: 1.121 [0.413-3.043]). Multivariate analysis using Cox proportional hazards models revealed chemotherapy-free-interval (CFI), 6 months (HR[95%CI]: 3.594 [1.027–12.580]) was independent prognostic factor, whereas histopathological response didn’t show the significance (HR[95%CI]: 0.723 [0.195–2.678]). Conclusions: Histopathological response by neoadjuvant DCF therapy did not affect the efficacy of platinum-containing regimens for recurrent ESCC, while CFI might be the prognostic factors. Research Sponsor: None.

DOI： 10.1200/JCO.2024.42.3_suppl.272

Scopus

記述言語：日本語   出版者・発行元：Journal of Clinical Oncology  

Background: Although nivolumab plus ipilimumab (Nivo+Ipi) is strongly recommended as 1st-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC), tumor proportion score (TPS) should be considered. Despite the efficacy, patients who received Nivo+Ipi often experienced serious immune related adverse events (irAEs). However, there are few data on safety and short-term efficacy of Nivo+Ipi in real world. Methods: We retrospectively collected data of pts who received Nivo+Ipi for advanced ESCC between May 2022 to July 2023 in the National Cancer Center Hospital. We evaluated adverse events by CTCAE v5.0 and multivariate analysis using a logistic regression model. estimated overall response rate (ORR) by RECIST v1.1 and progression-free survival (PFS). Results: Thirty pts were subjects in this study. The characteristics were as follows: median age (range): 63.5 (36-80) years, male/female: 24/6, metastatic/recurrent: 3/27, ECOG PS 0/1≤: 16/14, PD-L1 TPS 1%≤: 17, number of organs with metastases 1/2≤: 13/17, treatment-line 1st/2nd≤ 6/24 Median follow-up time was 5.0 months (mo) (reverse Kaplan-Meier, 95%CI; 3.0-8.3 mo). Any grade and grade 3≤ irAEs were observed in 12 (40.0%) and in 5 pts (17.9%), respectively. In grade 3≤ irAEs, AST/ALT elevation (n=2, 7.1%), adrenal insufficiency (n=1, 3.6%), pneumonitis (n=1, 3.6%), myositis (n=1, 3.6%), encephalopathy (n=1, 3.6%), stevens-Johnson syndrome (n=1, 3.6%) were reported. The pts who received systemic steroid therapy was 8 pts (28.6%). Two pts received high-dose steroid with methyl-prednisolone, 1 g/body for 3 days, four pts needed steroid therapy with prednisolone, 1-2 mg/kg and two pts added mycophenolate mofetil. No treatment-related deaths were reported. For the pts who received Nivo+Ipi as a first-line treatment (n=6), 3 pts (50%) achieved partial response and 2 pts (33.3%) had stable disease. 6-mo PFS rate of the 1st line pts was 63%. For the pts who received Nivo+Ipi in later-line, the ORR and the median PFS were 33.3% and 2.6 mo (95%CI; 1.4-3.9 mo), respectively. Fifteen pts received subsequent systemic therapy, which consisted of taxane (12 pts), fluoropyrimidine plus platinum (2 pts) and 1 pt continued Nivo+Ipi beyond progression. Conclusions: Our study may demonstrate a consistent incident of irAEs in pts who received Nivo+Ipi in the real world, compared to the results of the CheckMate 648. Despite of the short time of follow-up period, 1st-line treatment with Nivo+Ipi appeared to be more efficacious than Nivo+Ipi used as a later-line treatment.

DOI： 10.1200/JCO.2024.42.3_suppl.329

Scopus

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

症例は77歳男性。EBウイルス小分子RNA陽性T2N2M0ステージIII鼻咽頭扁平上皮癌(NPSCC)と診断され、根治的化学放射線療法(CRT)が開始された。CRT後の画像診断では完全寛解と判定されたが、14ヵ月後の内視鏡検査で潰瘍を伴う表在性局所再発が検出された。組織病理学的検査ではNPSCCの再燃であり、造影CTで鼻咽頭後壁に13×11mm大の病変を認め、PET-MRIでは病変部にFDG集積がみられ、リンパ節転移や遠隔転移はなかった。患者からmaxillary swingアプローチを介した鼻咽頭切除の同意が得られなかったため、光免疫療法(PIT)を行うこととした。セツキシマブサロタロカンナトリウム640mg/m2を静注投与し、グレード2のインフュージョンリアクションに対してデキサメタゾンとクロルフェニラミンを投与、その後、120ルクスの照明器具を備えた暗室管理とした。さらに光力学療法半導体レーザーを用いたレーザー照射を行い、エピネフリン含浸ガーゼを鼻腔に留置し、Hardy鼻腔用二弁鏡を下鼻甲介と鼻中隔の間に挿入した。PIT施行後7日目に退院となり、4週以上の皮膚および眼部への日光曝露回避を指導した。4週後には病変の完全消退を認め、7ヵ月後、遅発性有害事象や再発なく生存中である。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Auris Nasus Larynx  

Photoimmunotherapy for head and neck cancer (HNC-PIT) is a newly developed locoregional treatment targeting the epidermal growth factor. This treatment consists in administering cetuximab sarotalocan sodium that conjugates cetuximab with the dye IRdye700DX, which is activated by near-infrared ray illumination at 690 nm. HNC-PIT has been conditionally approved in Japan in September 2020 for the treatment of unresectable locally advanced or unresectable locoregionally recurrent HNC. However, its outcomes on the local recurrence of the nasopharyngeal squamous cell carcinoma (NPSCC) remain undetermined. In this report, we assessed the effects of HNC-PIT assisted by transnasal endoscopy on the local recurrence of NPSCC. A 77-year-old male presented with a local recurrence of NPSCC. The initial diagnosis revealed a squamous cell carcinoma, T2N2M0 stage III, positive for Epstein-Barr virus-encoded small RNA by in situ hybridization, which was treated with concurrent chemoradiotherapy (CRT). However, local recurrence was detected 14 months after CRT. We performed HNC-PIT under transnasal endoscopy. Seven months have passed since the HNC-PIT treatment, and the patient is alive without delayed adverse events and evidence of recurrence. Local recurrence of NPSCC, which is difficult to treat with minimally invasive surgery, is considered a potential candidate for HNC-PIT.

DOI： 10.1016/j.anl.2022.06.004

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PubMed

記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

切除可能局所進行食道扁平上皮癌患者のうち、高齢および腎・心の機能障害が理由となってシスプラチン(CDDP)を含む術前治療には不適格とされる症例に対し、術前にFOLFOX(オキサリプラチン、ロイコボリン、5-フルオロウラシル)治療を実施することの安全性と短期有効性を評価した。75歳以上または腎か心の機能障害がみられた上記の癌患者で、2019～2021年に当施設で術前FOLFOX治療を行った35名(男性25名、年齢65～89歳)を後方視的に解析した。本集団のうち75歳以上の高齢者は69%を占め、腎機能障害は74%に、心機能障害は17%にみられていた。5-フルオロウラシルの相対用量強度(RDI)はボーラス投与で70.2%、持続静注投与で87.1%であり、オキサリプラチンのRDIは85.2%であった。グレード3以上の有害事象で最も多かったものは好中球減少(60%)と白血球減少(29%)であった。また発熱性好中球減少症とグレード3の肺炎が2名(6%)ずつで発生した。31名では手術が実施され、R0切除達成率は87%、組織学的に遺残腫瘍の証拠が示されなかった率は16%となった。治療関連死は発生しなかった。冒頭に述べた症例への術前FOLFOXは管理可能な安全性プロファイルを示し、短期有効性は良好であることが明らかになった。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Esophagus  

Background: The standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (LAESCC) in Japan is docetaxel, cisplatin (CDDP), and 5-fluorouracil. However, patients with renal or cardiac dysfunction and elderly patients are ineligible for a CDDP-containing regimen because of toxicities. Oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) therapy has less renal toxicity than CDDP-containing regimens and does not require hydration. However, there are limited data on preoperative FOLFOX therapy in these patients. Methods: This retrospective study analyzed patients with resectable LAESCC who were aged ≥ 75 years or had renal or cardiac dysfunction and received preoperative FOLFOX between 2019 and 2021. FOLFOX was administered every 2 weeks for 3 or 4 cycles and was followed by surgery. Adverse events associated with chemotherapy, the complete resection (R0) rate, relative dose intensity (RDI), and histopathological response were evaluated. Results: Thirty-five patients were eligible. Median age was 77 (range 65–89) years; 68.6% were aged ≥ 75 years, 74.3% had renal dysfunction, and 17.1% had cardiac dysfunction. The RDI was 70.2% and 87.1% for bolus and continuous intravenous 5-fluorouracil, respectively and 85.2% for oxaliplatin. The most common grade ≥ 3 adverse events were neutropenia (60.0%) and leucopenia (28.6%). Two patients (5.7%) had febrile neutropenia and grade 3 pneumonia. Thirty-one patients underwent surgery. The R0 resection rate was 87.1%, and there was no histopathological evidence of residual tumor in 16.1%. There were no treatment-related deaths. Conclusions: Preoperative FOLFOX had a manageable safety profile and showed favorable short-term efficacy in patients with resectable LAESCC who were ineligible for CDDP-containing treatment.

DOI： 10.1007/s10388-022-00951-4

Scopus

PubMed

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

平衡障害がみられる65歳以上の患者を対象に、前庭リハビリテーション(VR)と杖の使用が歩行機能と平衡機能を改善する効果を調査した。2018年7月からの4ヵ月間に浮動性めまいの症状がみられ当科を受診した65歳以上の患者21名(女性14名、年齢65～92歳)を組み入れた。組み入れ基準としては、めまいが3ヵ月間以上みられており、かつ、めまいの問診票(Dizziness Handicap Inventory日本語版)のスコアが26以上であることとした。VR(X1パラダイムとBrandt-Daroff法、自宅で1日2回)を2ヵ月間施行してもらい、その期間の前後で歩行機能を定量評価した。VR施行前の評価では、杖を使用しても歩幅または歩行速度に差は生じなかった。VR後には杖使用によって歩幅が50.5cmから52.0cmへと有意に広がったが(p=0.039)、歩行速度は変化しなかった。杖を使用する条件でVR前後を比較した場合、歩幅は49.9cmから52.0cmへと有意に広がり、歩行速度も90.5cm/sから96.1cm/sへと有意に速くなった(いずれもp=0.005)。こうした結果からVRと杖使用は歩行機能を改善するよう相乗的に作用すると考えられた。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Adults over the age of 65 years with balance disorders are at about twice the risk of falls, compared with those without balance disorders. Falls contribute to about 74% of the proximal femoral fractures commonly seen in the elderly. Since balance disorders are more prevalent in older adults than in younger adults, it is important to deal with balance disorders in older adults to prevent falls and the resulting deterioration in their ADL (activity of daily living). In this study, we investigated the effects of vestibular rehabilitation (VR) and cane use on improving gait and balance in patients aged over 65 years with balance disorder. METHODS: Patients aged over 65 years presenting to the Department of Otolaryngology at St. Marianna University School of Medicine between July 1 and November 1, 2018, with symptoms of dizziness for ≥ 3 months and a Japanese translation of the Dizziness Handicap Inventory score of ≥ 26 were included in the study. We quantitatively analyzed their gait before and after VR, and with and without the use of a cane. RESULTS: A total of 21 patients participated in the study (14 women; mean age 73.9 ± 6.9 years). Before VR, using a cane made no difference to step length or walking speed. After VR, using a cane increased step length from 50.5 cm (95% confidence interval [CI], 47.4-53.7 cm) to 52.0 cm (95% CI, 48.9-55.1 cm) (p = 0.039). There was no change in walking speed. A comparison of walking assessment results while using a cane before and after VR showed that step length increased from 49.9 cm (95% CI, 46.6-53.2 cm) to 52.0 cm (95% CI, 48.9-55.1 cm) (p = 0.005), and walking speed increased from 90.5 cm/s (95% CI, 82.7-98.4 cm/s) to 96.1 cm/s (95% CI, 88.3-103.9 cm/s) (p = 0.005). CONCLUSIONS: Walking speed and step length with the use of a cane significantly improved following VR. VR and cane use may act synergistically to improve walking.

DOI： 10.1016/j.anl.2020.10.010

PubMed

記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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83歳女性で、頭痛、咽頭痛、呼吸困難を主訴とした。咽喉頭内視鏡検査で左披裂部に発赤・腫脹・粘膜疹、喉頭蓋左側に粘膜疹、左梨状陥凹に唾液貯留を認め、声帯は両側とも副正中位に固定していたが、気道は確保されていた。白血球数上昇を認め急性咽喉頭炎に伴う喉頭浮腫と診断し、ピペラシリン/タゾバクタムで治療を開始し、ステロイド漸減療法も併用した。第5病日にウイルス抗体価検査にて血清水痘・帯状疱疹ウイルス(VZV)IgG≧128倍、血清VZV IgM 5.68倍が判明し、VZV再活性化に伴う両側声帯麻痺の診断でアシクロビル点滴投与を開始した。髄液中細胞数の増加を認め、無菌性髄膜炎の可能性も否定できなかった。第20病日に嚥下造影検査にて早期咽頭流入を認め、前咽頭期型の誤嚥と考え胃瘻を造設した。声帯麻痺と嚥下障害は改善傾向で第50病日に退院し、第120病日に右声帯が、第140病日に左声帯がほぼ正常まで改善した。胃瘻は第122病日に閉鎖した。

記述言語：英語   出版者・発行元：聖マリアンナ医科大学医学会  

気管切開を実施した患者の転帰と気管孔閉鎖を調査した。2010年4月～2015年5月に気管切開を施行された患者204例(男性120例、女性84例、平均64.7歳)を対象とした。患者を原疾患により6つのカテゴリーに分類し、頭頸部疾患は79例、脳神経疾患は45例、心血管疾患は22例、消化器疾患は19例、呼吸器疾患は15例、他の疾患は24例であった。気道切開実施後の転帰は、退院81例(39.7%)、転院89例(43.6%)、死亡34例(16.7%)であった。頭頸部疾患患者は退院時の孔閉鎖の割合が最も高かった。孔閉鎖までの期間の中央値は頭頸部疾患患者が非頭頸部疾患患者よりも有意に短かった。一方、脳神経疾患患者はリハビリテーション病院への転院時に気管孔開口の割合が最も高かった。死亡率は心血管疾患(50.0%、22例中11例)、消化器疾患(36.8%、19例中7例)、呼吸器疾患(26.7%、15例中4例)の気管切開患者で高かった。

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52歳男性で、右難聴、めまいを主訴とした。飲酒して就寝した翌日に主訴を認め、右突発性難聴の診断で紹介受診し、純音聴力検査では右高度感音難聴を呈した。眼振所見では仰臥位から頭を25°回転した位置に眼振停止点を持つ持続性方向交代性向地性眼振を認め、患側が右のlight cupulaと考えられた。その後、右難聴は緩やかに改善したが、眼振所見はlight cupulaの状態から麻痺性眼振と思われる左向き定方向性眼振を経て、最終的にクプラ結石症と考えられる持続性方向交代性背地性眼振に変化したため、体軸を中心として回転する運動療法を行うも効果はなく、背地性眼振が持続した。これらの病態は、突発性難聴により引き起こされた難聴を伴わない迷路障害より高度な内リンパ内の恒常性の混乱によるものと推察された。

J-GLOBAL

J-GLOBAL

記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

J-GLOBAL

J-GLOBAL

J-GLOBAL

J-GLOBAL

J-GLOBAL

J-GLOBAL

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語