Faculty Profiles - NISHIO Naoki

Papers - NISHIO Naoki

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＜Editors' Choice＞ Long-term outcomes of lateral skull base reconstruction with a free omental flap and facial nerve reconstruction. Reviewed International journal Open Access

Miki Kambe, Kazunobu Hashikawa, Keisuke Takanari, Shunjiro Yagi, Kazuhiro Toriyama, Katsumi Ebisawa, Naoki Nishio, Takashi Maruo, Nobuaki Mukoyama, Yasushi Fujimoto, Masazumi Fujii, Kiyoshi Saito, Masakatsu Takahashi, Yuzuru Kamei

Nagoya journal of medical science Vol. 85 ( 2 ) page： 255 - 264 2023.5

Language：English Publishing type：Research paper (scientific journal)

In lateral skull base reconstruction, it is necessary to seal the defect in the lateral skull base, fill the dead space, and, sometimes, reconstruct the facial nerve. However, this procedure is difficult to perform with a standard musculocutaneous flap. Therefore, for such cases, an omental flap is used in our hospital because of its flexibility. In this study, we report our experience with the procedure (lateral skull base reconstruction with a free omental flap) and its long-term outcome and facial nerve reconstruction, with special focus on facial nerve recovery. This study is a technical note and a retrospective review. It was conducted in Nagoya University Hospital. Overall, 16 patients (12 women and 4 men; mean age: 55.1 years) underwent lateral skull base reconstruction with a free omental flap after subtotal temporal bone resection or lateral temporal bone resection during 2005-2017. The main outcome measures were postoperative complications and facial nerve recovery: Yanagihara score and House-Brackmann grading system. Complications included partial necrosis and minor cerebrospinal fluid leakage in 2 patients. Facial nerve recovery could be observed more than 12 months after surgery, with a mean Yanagihara score of 19.6 and House-Brackmann grade of 3.60. The free omental flap is a reliable method for lateral skull base reconstruction, especially in cases where facial nerve reconstruction is needed. To the best of our knowledge, this is the first report on facial nerve recovery after lateral skull base reconstruction.

DOI： 10.18999/nagjms.85.2.255

Open Access

Web of Science

PubMed

喉頭摘出者に対する術前の自己音声の保存の重要性について「Save the Voiceプロジェクト」

西尾直樹, 向山宣昭, 横井紗矢香, 重山真由, 和田明久, 三谷壮平, 藤本保志, 曾根三千彦

日本耳鼻咽喉科頭頸部外科学会会報 Vol. 126 ( 4 ) page： 591 - 591 2023.4

喉頭摘出者に対する術前の自己音声の保存の重要性について「Save the Voiceプロジェクト」

西尾直樹, 向山宣昭, 横井紗矢香, 重山真由, 和田明久, 三谷壮平, 藤本保志, 曾根三千彦

日本耳鼻咽喉科頭頸部外科学会会報 Vol. 126 ( 4 ) page： 591 - 591 2023.4

Safety and Clinical Benefits of Laryngeal Closure in Patients with Amyotrophic Lateral Sclerosis. Reviewed International journal

Sayaka Yokoi, Naoki Nishio, Takashi Maruo, Mariko Hiramatsu, Nobuaki Mukoyama, Hidenori Tsuzuki, Akihisa Wada, Naoki Atsuta, Daisuke Ito, Takashi Tsuboi, Gen Sobue, Masahisa Katsuno, Yasushi Fujimoto, Michihiko Sone

Dysphagia Vol. 38 ( 1 ) page： 211 - 219 2023.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

This study evaluated the safety of laryngeal closure and post-surgical changes in swallowing function of patients with amyotrophic lateral sclerosis (ALS) and proposed an appropriate surgical strategy for patients with ALS. Clinical and surgical data of 26 consecutive patients with ALS who underwent laryngeal closure at Nagoya University Hospital in Japan between 2003 and 2020 were retrospectively analyzed. Changes in swallowing functions were evaluated before and approximately 1 month post-surgery using Neuromuscular Disease Swallowing Status Scale (NdSSS), and Functional Oral Intake Scale (FOIS). The median operation time was 126 min (range, 51-163 min), and the median intraoperative blood loss was 20 mL (range, 0-88 mL). Among the 26 ALS patients who underwent laryngeal closure, grade 1 (mild) complications occurred in three patients (12%); however, no severe complications were observed. After surgery, 25 patients (96%) maintained the swallowing function and only one patient (4%) had deteriorating NdSSS and FOIS scores. No patients were referred to our hospital due to severe aspiration pneumonia after the surgery. Two patients did not require a feeding tube after the surgery and returned to oral intake. Laryngeal closure may be a safe surgical procedure for preventing chronic aspiration and may also maintain swallowing function of patients with ALS. Further multicenter prospective studies using the gold standard videofluoroscopic swallowing examination are required to support our findings.

DOI： 10.1007/s00455-022-10454-0

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PubMed

Surgical Strategy for Squamous Cell Carcinoma of the External Auditory Canal: Management of Locally Advanced Cases with Skull Base Involvement. Reviewed International journal

Seiya Goto, Naoki Nishio, Kenichiro Iwami, Tadao Yoshida, Takashi Maruo, Nobuaki Mukoyama, Hidenori Tsuzuki, Sayaka Yokoi, Akihisa Wada, Mariko Hiramatsu, Yuichiro Hayashi, Yuzuru Kamei, Masazumi Fujii, Michihiko Sone, Yasushi Fujimoto

Journal of neurological surgery. Part B, Skull base Vol. 84 ( 01 ) page： 69 - 78 2023.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Objective Surgical indications for advanced-stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) are highly dependent on the skull base surgery team. The aim of this study was to evaluate the surgical outcomes in patients with SCC of the EAC and to clarify the surgical indication of far advanced cases using the T4 subclassification. Methods Patients with SCC of the EAC who underwent curative treatment from 2002 to 2021 at our hospital were retrospectively reviewed. Clinical and surgical results, including operative data, overall survival (OS), and disease-specific survival (DSS), were analyzed. To clarify the surgical indication for advanced-stage tumors, we proposed the T4 subclassification. Results In the 46 patients included in the study, 8 patients had T1 tumors, 10 had T2 tumor, 5 had T3 tumors, and 23 had T4 tumors. The 5-year DSS with T1, T2, T3, and T4 tumors were 100, 85.7, 100, and 61.7%, respectively. No prognostic impacts for margin status were found between the 5-year OS and DSS ( p = 0.23 and 0.13, respectively). Patients with far-advanced-stage (T4b) tumors were significantly associated with shorter DSS than those with early-stage (T1/T2) and advanced-stage (T3/T4a) tumors ( p = 0.007 and 0.03, respectively). Conclusion The present study focused on patients with SCC of the EAC at a university hospital over a period of 20 years, especially with skull base involvement, and a T4 subclassification was proposed. Complete tumor resection in an en bloc fashion could help achieve a good survival rate even in patients with locally advanced tumors.

DOI： 10.1055/a-1733-2585

Web of Science

PubMed

New, safe and simple endoscopic cricopharyngeal myotomy with a curved rigid laryngoscope: A case report. Reviewed International journal Open Access

Takashi Maruo, Yasushi Fujimoto, Sayaka Yokoi, Mayu Shigeyama, Naoki Nishio, Mariko Hiramatsu, Michihiko Sone

Molecular and clinical oncology Vol. 18 ( 2 ) page： 10 - 10 2023.2

Language：English Publishing type：Research paper (scientific journal)

Endoscopic cricopharyngeal myotomy (ECPM) is a safe and minimally invasive technique that is used to treat patients whose esophageal inlet fails to open because of specific diseases, such as Wallenberg's syndrome and neuromuscular diseases. The present study described the performance of a new, safe and simple ECPM using a curved rigid laryngoscope, which is used for endoscopic laryngopharyngeal surgery for patients with dysphagia due to pharyngeal residue after swallowing. The patient was an 80-year-old woman with laryngeal palsy caused by lower cranial nerve palsy after cranial base schwannoma surgery. ECPM was performed with a curved rigid laryngoscope. The postoperative course was good; postoperative rehabilitation eliminated the residue after swallowing a thickened solution and mealtimes were shorter than before surgery. This procedure allows the hypopharynx to be widely expanded and it is possible to develop a wider surgical field than when using a direct laryngoscope. In addition, this procedure appears to be relatively easy to perform if the surgeon is familiar with the curved rigid laryngoscope technique.

DOI： 10.3892/mco.2023.2606

Open Access

Web of Science

PubMed

頭頸部外科手術の基盤となる技術スキルに対する認識若手医師と熟達医との違い

三谷壮平, 西尾直樹, 松木崇, 木谷卓史, 佐藤恵里子, 坂本佳代, 細川裕貴, 鵜久森徹, 脇坂浩之, 羽藤直人

頭頸部外科 Vol. 32 ( 3 ) page： 257 - 263 2023.2

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(NPO)日本頭頸部外科学会

頭頸部外科手術の基盤となる技術スキルに対する認識について多施設アンケート調査を行った。先行研究の7つのカテゴリーに分類されている60個の技術スキルを用いて,若手医師69名と熟達医15名の回答を比較した。若手医師は,熟達医よりも技術スキル全体を重要と評価しており(P=0.027),熟達医が重要視しているスキルだけでなく,全ての技術スキルに対して気を配っていることが示唆された。熟達医は,「カウンタートラクション」が全カテゴリー中最も難易度が高いと評価していたが,若手医師は自身のスキルに7カテゴリー中3番目に高い自信を持っていた。このような認識の乖離が,技術伝承のひとつの障壁になっている可能性がある。(著者抄録)

喉頭摘出後代用音声の進歩音声合成スマートフォンアプリを用いた新しい代用音声 Reviewed

飴矢美里, 勢井洋史, 三谷壮平, 西尾直樹, 羽藤直人

喉頭 Vol. 34 ( 2 ) page： 51 - 57 2022.12

喉頭摘出後代用音声の進歩音声合成スマートフォンアプリを用いた新しい代用音声 Open Access

飴矢美里, 勢井洋史, 三谷壮平, 西尾直樹, 羽藤直人

喉頭 Vol. 34 ( 2 ) page： 51 - 57 2022.12

Factors for differential outcome across cancers in clinical molecular-targeted fluorescence imaging. Reviewed International coauthorship International journal

Quan Zhou, Nynke S van den Berg, Wenying Kang, Jacqueline Pei, Naoki Nishio, Stan van Keulen, Myrthe A Engelen, Yu-Jin Lee, Marisa Hom, Johana C M Vega Leonel, Zachary Hart, Hannes Vogel, Romain Cayrol, Brock A Martin, Mark Roesner, Glenn Shields, Natalie Lui, Melanie Hayden Gephart, Roan C Raymundo, Grace Yi, Monica Granucci, Gerald A Grant, Gordon Li, Eben L Rosenthal

Journal of nuclear medicine : official publication, Society of Nuclear Medicine Vol. 63 ( 11 ) page： 1693 - 1700 2022.11

Language：English Publishing type：Research paper (scientific journal)

Clinical imaging performance using a fluorescent antibody was compared across three cancers to elucidate physical and biological factors contributing to differential translation of epidermal growth factor receptor (EGFR) expression to macroscopic fluorescence in tumors. Methods: Thirty-one patients with high-grade glioma (HGG, n = 5), head-and-neck squamous cell carcinoma (HNSCC, n = 23) or lung adenocarcinoma (LAC, n = 3) were systemically infused with 50 mg panitumumab-IRDye800, 1 - 3 days prior to surgery. Intraoperative open-field fluorescent images of the surgical field were acquired, where imaging device settings and operating room lighting conditions were tested on tissue-mimicking phantoms. Fluorescence contrast and margin size were measured on resected specimen surface. Antibody distribution and EGFR immunoreactivity were characterized in macroscopic and microscopic histological structures. Integrity of the blood-brain barrier (BBB) was examined via tight junction protein (claudin-5) expression with immunohistochemistry. Stepwise multivariate linear regression of biological variables was performed to identify independent predictors of panitumumab-IRDye800 concentration in tissue. Results: Optimally acquired at the lowest gain for tumor detection with ambient light, intraoperative fluorescence imaging enhanced tissue-size dependent tumor contrast by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Tissue surface fluorescence target-to-background ratio correlated with margin size and identified 78 - 97% of at-risk resection margins ex vivo. In 4 µm-thick tissue sections, fluorescence detected tumor with 0.85 - 0.89 areas under the receiver operating characteristic curves. Preferential breakdown of BBB in HGG improved tumor specificity of intratumoral antibody distribution relative to that of EGFR (96% vs 80%) despite its reduced concentration (3.9 ng/mg tissue) compared to HNSCC (8.1 ng/mg) and LAC (6.3 ng/mg). Cellular EGFR expression, tumor cell density, plasma antibody concentration and delivery barrier were independently associated with local intratumoral panitumumab-IRDye800 concentration with 0.62 goodness-of-fit of prediction. Conclusion: In multi-cancer clinical imaging of receptor-ligand based molecular probe, plasma antibody concentration, delivery barrier, as well as intratumoral EGFR expression driven by cellular biomarker expression and tumor cell density, led to heterogeneous intratumoral antibody accumulation and spatial distribution while tumor size, resection margin, and intraoperative imaging settings substantially influenced macroscopic tumor contrast.

DOI： 10.2967/jnumed.121.263674

Web of Science

PubMed

Primary laryngeal cryptococcosis mimicking laryngeal malignancy: a case report. Reviewed International journal Open Access

Kazuya Tonai, Naoki Nishio, Sayaka Yokoi, Masumi Kobayashi, Michihiko Sone

Nagoya journal of medical science Vol. 84 ( 4 ) page： 900 - 905 2022.11

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Primary laryngeal cryptococcosis is an extremely rare infection and presents with non-specific symptoms such as hoarseness or sore throat, resulting in delayed diagnosis. Here, we report the patient of a 56-year-old female patient with primary laryngeal cryptococcosis, who was being treated with oral and inhaled steroids for rheumatoid arthritis and bronchial asthma. The patient suffered from prolonged hoarseness and sore throat, and endoscopic biopsy was performed several times under local anesthesia, demonstrating only inflammatory cell infiltration. Considering the possibility of laryngeal malignancy, a third biopsy was performed by endoscopic laryngomicrosurgery under general anesthesia. Intraoperative frozen section revealed non-neoplastic laryngeal mucosa with erosion and severe inflammatory cell infiltration. However, we could not confirm the definite diagnosis of the lesion in the intraoperative consultation. Postoperative histopathological examination revealed a small number of yeast-type fungi and a definitive diagnosis was established by special stains including Alcian blue stain. Finally, the patient was diagnosed as primary laryngeal cryptococcosis. Daily oral administration of fluconazole (400 mg/day) was performed for 6 months according to the treatment protocol for pulmonary cryptococcosis. The symptoms gradually improved, and endoscopy revealed no recurrence 6 months post-treatment. Clinicians should consider the possibility of laryngeal cryptococcosis when severe inflammation is found in the larynx and discuss the disease history and pathological results with pathologists more closely.

DOI： 10.18999/nagjms.84.4.900

Open Access

Web of Science

PubMed

Fluorescent molecular imaging can improve intraoperative sentinel margin detection in oral squamous cell carcinoma. Reviewed International coauthorship International journal

Giri Krishnan, Nynke S van den Berg, Naoki Nishio, Shrey Kapoor, Jaqueline Pei, Laura Freeman, Yu-Jin Lee, Stan van Keulen, Shayan Fakurnejad, James Condon, Fred Back, Brock Martin, Eben L Rosenthal

Journal of nuclear medicine : official publication, Society of Nuclear Medicine Vol. 63 ( 8 ) page： 1162 - 1168 2022.8

Language：English Publishing type：Research paper (scientific journal)

Rationale: In head and neck cancer, a major limitation of current intraoperative margin analysis is the ability to detect areas most likely to be positive based on specimen palpation, especially for larger specimens where sampling error limits detection of positive margins. This study aims to prospectively examine the clinical value of fluorescent molecular imaging to accurately identify "the sentinel margin," the point on a specimen where tumour lies closest to the resected edge in real-time during frozen section analysis. Methods: Eighteen patients with oral squamous cell carcinoma were enrolled into a prospective clinical trial and infused intravenously with 50mg of panitumumab-IRDye800CW 1-5 days prior to surgery. Resected specimens were imaged in a closed-field near-infrared optical imaging system in near-real time, and custom designed software was used to identify locations of highest fluorescence on deep and peripheral margins. The surgeon identified the sentinel margin blinded to optical specimen mapping, and then the regions of highest fluorescence were identified and marked for frozen analysis. Final pathology based on specimen reconstruction was used as reference standard. Results: Resected specimens were imaged in the operating room and fluorescence had a higher interobserver agreement with pathology (Cohen kappa value 0.96) than the surgeon (Cohen kappa values of 0.82) for the location of the closest margin. Plotting margin distance at the predicted sentinel margin location of each observer versus the actual closest margin distance at pathology demonstrated best correlation between fluorescence and pathology (R2 = 0.98), with surgeon (R2 = 0.75). Principal Conclusion: Fluorescence imaging can improve identification of the sentinel margin in head and neck cancer resections, holding promise for rapid identification of positive margins and improved oncological outcomes.

DOI： 10.2967/jnumed.121.262235

Web of Science

PubMed

Validation of a surgical training model containing indocyanine green for near-infrared fluorescence imaging. Reviewed International coauthorship International journal

Naoki Nishio, Sohei Mitani, Kayo Sakamoto, Gaku Morimoto, Sayaka Yokoi, Mayu Shigeyama, Akihisa Wada, Nobuaki Mukoyama, Eben L Rosenthal, Michihiko Sone

Laryngoscope investigative otolaryngology Vol. 7 ( 4 ) page： 1011 - 1017 2022.8

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Objective: To determine the efficacy of a surgical training model for fluorescence-guided cancer surgery and validate its utility to detect any residual tumors after tumor resection using electrocautery. Methods: We developed surgical training models containing indocyanine green (ICG) for near-infrared (NIR) fluorescence imaging using a root vegetable organic material (konjac). After the fluorescence assessment for the models, the surgical simulation for fluorescence-guided cancer surgery using electrocautery was performed. ICG-containing tumors were divided into two surgical groups: "Enucleation" (removal of the entire visible tumor) and "Complete resection" (removal of the tumor with an appropriate 5-mm surgical margin). Results: All 12 ICG-containing tumors were clearly visible from the normal view but not from the flipped view. The tumor resection time was significantly longer in the "Complete resection" group than in the "Enucleation" group (p < .001). The ICG-containing tumors showed a high tumor-to background ratio from the normal (average = 45.8) and flipped (average = 19.2) views, indicating that the models including ICG-containing tumors were useful for a surgical simulation in fluorescence-guided surgery. The average mean fluorescence intensity of the wound bed was significantly higher in the "Enucleation" group than in the "Complete resection" group (p < .01). No decrease in fluorescence signal was found in the wound bed even at 2 days postresection. Conclusion: Our surgical training model containing a fluorescent agent is safe, inexpensive, not harmful for humans, and easy to dispose after use. Our model would be beneficial for surgeons to learn NIR fluorescence imaging and to accelerate fluorescence-guided cancer surgery into clinical application.

DOI： 10.1002/lio2.858

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PubMed

近赤外光が導く新たな腫瘍切除トレーニングモデルの開発

西尾直樹, 三谷壮平, 坂本佳代, 重山真由, 横井紗矢香, 向山宣昭, 曾根三千彦

頭頸部癌 Vol. 48 ( 2 ) page： 196 - 196 2022.5

喉頭摘出者における音声変換技術を用いた自己音声の再獲得 Save the Voiceプロジェクト

西尾直樹, 向山宣昭, 横井紗矢香, 三谷壮平, 勢井洋史, 藤本保志, 曾根三千彦

日本耳鼻咽喉科頭頸部外科学会会報 Vol. 125 ( 4 ) page： 739 - 739 2022.4

頭頸部外科手術に必要な技術スキルに対する認識熟達医と若手医師とのギャップ

三谷壮平, 西尾直樹, 松木崇, 木谷卓史, 佐藤恵里子, 坂本佳代, 相原栞, 細川裕貴, 鵜久森徹, 脇坂浩之, 羽藤直人

日本耳鼻咽喉科頭頸部外科学会会報 Vol. 125 ( 4 ) page： 764 - 764 2022.4

Increased risk of thyroid dysfunction by PD-1 and CTLA-4 blockade in patients without thyroid autoantibodies at baseline. Reviewed International journal

Shintaro Iwama, Tomoko Kobayashi, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Masahiko Ando, Xin Zhou, Ayana Yamagami, Takeshi Onoue, Yohei Kawaguchi, Takashi Miyata, Mariko Sugiyama, Hiroshi Takagi, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Keiko Wakahara, Kenji Yokota, Masashi Kato, Naoki Nishio, Chie Tanaka, Kazushi Miyata, Atsushi Ogura, Takanori Ito, Tsunaki Sawada, Tomoya Shimokata, Kaoru Niimi, Fumiharu Ohka, Masatoshi Ishigami, Momokazu Gotoh, Naozumi Hashimoto, Ryuta Saito, Hitoshi Kiyoi, Hiroaki Kajiyama, Yuichi Ando, Hideharu Hibi, Michihiko Sone, Masashi Akiyama, Yasuhiro Kodera, Hiroshi Arima

The Journal of clinical endocrinology and metabolism Vol. 107 ( 4 ) page： E1620 - E1630 2022.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Previous studies showed that although the risk of thyroid dysfunction (thyroid immune-related adverse events [irAEs]) induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2-7% in patients negative for anti-thyroid-antibodies (ATAs) at baseline, it was much higher (30-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. METHODS: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab plus CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the last clinical visit. RESULTS: Of the 451 patients, 51 developed thyroid-irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) with CTLA-4-Ab, and 10 of 27 (37.0%) with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid-irAEs was significantly higher in patients who were positive versus negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs. 13/329 (4.0%), p < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs. 4/17 (23.5%), p < 0.05] treatments. The risk of thyroid-irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. CONCLUSIONS: This study showed that the incidence of thyroid-irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

DOI： 10.1210/clinem/dgab829

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PubMed

Management of bilateral locally advanced squamous cell carcinoma of the external auditory canal Reviewed

Nishio, N; Okazaki, Y; Wada, A; Tsuzuki, H; Kambe, M; Fujimoto, Y; Sone, M

ACTA OTO-LARYNGOLOGICA CASE REPORTS Vol. 7 ( 1 ) page： 8 - 13 2022.2

【二次出版】ANL Secondary Publication 耳鼻咽喉科医のための結紮縫合カリキュラムの開発

佐藤恵里子, 三谷壮平, 西尾直樹, 木谷卓史, 真田朋昌, 鵜久森徹, Holsinger F. Christopher, Baik Fred M., 羽藤直人

日本耳鼻咽喉科頭頸部外科学会会報 Vol. 124 ( 11 ) page： 1543 - 1544 2021.11

Clinical course of liver injury induced by immune checkpoint inhibitors in patients with advanced malignancies. Reviewed International journal

Takanori Ito, Masatoshi Ishigami, Takafumi Yamamoto, Kazuyuki Mizuno, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Takashi Honda, Hiroki Kawashima, Satoshi Yasuda, Hidenori Toyoda, Kenji Yokota, Tetsunari Hase, Naoki Nishio, Osamu Maeda, Masashi Kato, Naozumi Hashimoto, Hideharu Hibi, Yasuhiro Kodera, Michihiko Sone, Yuichi Ando, Masashi Akiyama, Yoshie Shimoyama, Mitsuhiro Fujishiro

Hepatology international Vol. 15 ( 5 ) page： 1278 - 1287 2021.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury. METHODS: We evaluated the characteristics and clinical course of immune-related liver injury in 1214 patients treated with ICIs for advanced malignancies except for hepatocellular carcinoma between August 2014 and May 2021. RESULTS: During the follow-up period (median, 252 days), 58 patients (4.8%) had an immune-related liver injury (≥ Grade 3). The liver-injury patterns were hepatocellular (n = 26, 44.8%), mixed (n = 11, 19.0%), or cholestatic (n = 21, 36.2%), and the median time to onset of liver injury was 39, 81, and 53 days, respectively; the hepatocellular pattern occurred earlier than the other types (p = 0.047). Corticosteroids were administered to 30 (51.7%) patients; while liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns, and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20. CONCLUSION: The incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differ according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

DOI： 10.1007/s12072-021-10238-y

Web of Science

PubMed

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Papers - NISHIO Naoki