今日の臨床サポート

下咽頭悪性腫瘍

著者: 篠﨑剛 国立がん研究センター東病院 頭頸部外科

監修: 森山寛 東京慈恵会医科大学附属病院

著者校正済:2022/08/31
現在監修レビュー中
参考ガイドライン:
  1. 日本頭頸部癌学会編 頭頸部癌診療ガイドライン 2022年版
患者向け説明資料

概要・推奨   

  1. 初発症状として頸部腫瘤、嚥下障害、嚥下痛、声のかすれ、耳痛などが多い。
  1. 局所病変と全身状態に応じて根治と機能温存を目指した治療方針を検討する必要がある。
  1. 重複癌の評価も必要である。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
篠﨑剛 : 特に申告事項無し[2022年]
監修:森山寛 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 2022年のガイドライン改訂では前回改訂のような病期分類の変更はない。一方で診断、治療の技術は進歩しており、下咽頭という限定した臓器のみではなく腫瘍の特性に応じた治療が選択されるようになっている。2019年保険収載となった経口的切除についてのクリニカルクエスチョンが追加された。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 下咽頭癌は、比較的まれな疾患である。この癌の発生のピークは、男女ともに50~60歳の年齢である。男性に多く認められる。
  1. 過度のアルコール使用および喫煙が、下咽頭癌に対する危険因子である。
  1. 下咽頭は梨状陥凹・輪状後部・咽頭後壁の3つの亜部位に分類される。梨状陥凹の癌が最も多い。
  1. 輪状後部癌は、貧血(特に鉄欠乏性貧血)を持つ女性に多く発症する。
  1. 病理組織型では扁平上皮癌が大部分を占める。
  1. 食道癌や頭頸部癌、肺癌の重複がしばしば認められる[1]
問診・診察のポイント  
  1. 初発症状として頸部腫瘤、嚥下障害、嚥下痛、声のかすれ、耳痛などが多い。

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文献 

Toru Ugumori, Manabu Muto, Ryuichi Hayashi, Tomomasa Hayashi, Seiji Kishimoto
Prospective study of early detection of pharyngeal superficial carcinoma with the narrowband imaging laryngoscope.
Head Neck. 2009 Feb;31(2):189-94. doi: 10.1002/hed.20943.
Abstract/Text BACKGROUND: The newly developed narrowband imaging (NBI) gastrointestinal endoscope makes possible the detection of superficial carcinoma in the oropharynx and hypopharynx, which is difficult with the conventional laryngoscope. Here, we investigated whether the combined use of laryngoscope with NBI allows the detection of superficial carcinoma in this region.
METHODS: A total of 51 superficial, histologically confirmed lesions in 29 patients were studied. The quality of visualization of superficial carcinoma in the oropharynx and hypopharynx using the NBI-equipped laryngoscope was evaluated in comparison with the results by conventional laryngoscopy.
RESULTS: The NBI laryngoscope provided better detection of the irregular microvascular pattern of carcinoma than the conventional laryngoscope (p <.05) and better visualization of the demarcation line (p <.05), and thus significantly better visualization of the lesions.
CONCLUSION: The NBI laryngoscope may play an important role in the diagnosis and treatment of superficial carcinoma in the oropharynx and hypopharynx.

PMID 18853451
Young Min Park, Da Hee Kim, Min Seok Kang, Jae Yol Lim, Eun Chang Choi, Yoon Woo Koh, Se-Heon Kim
The First Human Trial of Transoral Robotic Surgery Using a Single-Port Robotic System in the Treatment of Laryngo-Pharyngeal Cancer.
Ann Surg Oncol. 2019 Dec;26(13):4472-4480. doi: 10.1245/s10434-019-07802-0. Epub 2019 Sep 9.
Abstract/Text BACKGROUND: This study aimed to evaluate the feasibility and safety of the DaVinci SP system for performing transoral robotic surgery (TORS) in patients with head and neck cancer.
METHODS: From October 2018 to April 2019, the medical records of 41 patients who underwent TORS using the DaVinci SP system were retrospectively reviewed.
RESULTS: During TORS, three robotic arms could be used to perform a geometric resection of the lesion in a narrow working space. The mean total operation time was 60 min, and the average time required to set up the robotic system was 10 min or less. All patients successfully underwent TORS. All robotic arms were inserted through a single port, which widened the working space around the patient's head and allowed the operative assistant an easy approach to the patient during the operation. The joggle joint of the robotic arms aided easy manipulation within the confined working space. The joggle joints of the endoscopic arm were controlled through the navigation system, which was very helpful in securing superior visualization of the surgical site, especially in the area of the larynx and the hypopharynx.
CONCLUSION: The study confirmed that the DaVinci SP system provided technical advantages above the Si and Xi systems for performing TORS. It was especially helpful in ensuring proper visualization of the surgical field and in performing precise surgery during surgery to the tongue base or the hypopharyngeal lesion.

PMID 31502020
Ichiro Tateya, Manabu Muto, Shuko Morita, Shin'ichi Miyamoto, Tomomasa Hayashi, Makiko Funakoshi, Ikuo Aoyama, Hirokazu Higuchi, Shigeru Hirano, Morimasa Kitamura, Seiji Ishikawa, Yo Kishimoto, Mami Morita, Juichi Ito
Endoscopic laryngo-pharyngeal surgery for superficial laryngo-pharyngeal cancer.
Surg Endosc. 2016 Jan;30(1):323-9. doi: 10.1007/s00464-015-4213-y. Epub 2015 Apr 28.
Abstract/Text BACKGROUND AND STUDY AIMS: Narrow band imaging (NBI) combined with magnifying endoscopy enables us to detect superficial laryngo-pharyngeal cancers, which are difficult to detect by standard endoscopy. Endoscopic laryngo-pharyngeal surgery (ELPS) is a technique developed to treat such lesions and the purpose of this study is to evaluate the usefulness of ELPS for superficial laryngo-pharyngeal cancer.
PATIENTS AND METHODS: Seventy five consecutive patients with 104 fresh superficial laryngo-pharyngeal cancers are included in this study. Under general anesthesia, a specially-designed curved laryngoscope was inserted to create a working space in the pharyngeal lumen. A magnifying endoscope was inserted transorally to visualize the field and a head & neck surgeon dissected the lesion using the combination of the orally-inserted curved grasping forceps and electrosurgical needle knife in both hands. The safely, functional outcomes, and oncologic outcomes of ELPS were evaluated retrospectively.
RESULTS: Median operation time per lesion was 35 min. Post-operative bleeding occurred in 3 cases and temporal subcutaneous emphysema occurred in 10 cases. No vocal fold impairment occurred after surgery. The median fasting period was 2 days and all patients except one have a normal diet with no limitations. Local recurrence occurred in 1 case, and the 3-year overall survival rate and the 3-year disease specific survival rate was 90% and 100%, respectively.
CONCLUSIONS: ELPS is a hybrid of head and neck surgery and gastrointestinal endoscopic treatment, and enjoys the merit of both procedures. ELPS makes it possible to perform minimally-invasive surgery, preserving both the swallowing and phonation functions.

PMID 25917165
Gregory S Weinstein, Bert W O'Malley, J Scott Magnuson, William R Carroll, Kerry D Olsen, Lixia Daio, Eric J Moore, F Christopher Holsinger
Transoral robotic surgery: a multicenter study to assess feasibility, safety, and surgical margins.
Laryngoscope. 2012 Aug;122(8):1701-7. doi: 10.1002/lary.23294. Epub 2012 Jul 2.
Abstract/Text OBJECTIVES/HYPOTHESIS: Our objective was to determine the safety, feasibility, and the adequacy of surgical margins for transoral robotic surgery (TORS), by reviewing the early results from independent institutional review board-approved clinical trials in three separate institutions.
STUDY DESIGN: Pooled Data from Independent Prospective Clinical Trials.
METHODS: One hundred ninety-two patients were initially screened, but inadequate exposure did not permit TORS in 13 (6.7%). For two additional patients, TORS was begun but intraoperatively converted to an open procedure. Thus, the intent-to-treat population was 177 patients (average age, 59 years; 81% male), predominantly comprised of tumors arising in the oropharynx (139, 78%) and larynx (26, 15%). TORS was performed for 161 (91%) patients with malignant disease: 153 (95%) with squamous cell carcinoma (T1 [50, 32.7%], T2 [74, 48.4%], T3 [21, 13.7%], T4 [8, 5.2%]), six patients (3.72%) with salivary gland tumors, and two patients with carcinoma in situ. The average follow-up was 345 days.
RESULTS: There was no intraoperative mortality or death in the immediate postoperative period. Average estimated blood loss was 83 mL; no patient required transfusion. The rate of positive margins was 4.3%. Twenty-nine patients (16%) experienced 34 serious adverse events that required hospitalization or intervention (grade 3) or were considered life threatening (grade 4, 2.3%). Tracheostomy was performed in 12.4% of all patients (22/177), but only 2.3% had a tracheostomy at last follow-up. For all patients undergoing TORS without previous therapy, the percutaneous endoscopic gastrostomy dependency rate was 5.0%. The average hospital stay was 4.2 days.
CONCLUSIONS: Based on this multicenter study, TORS appears to be safe, feasible, and as such play an important role in the multidisciplinary management of head and neck cancer.

Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
PMID 22752997
Ciaran Lane, Rasheda Rabbani, Janice Linton, S Mark Taylor, Norbert Viallet
Systematic review and meta-analysis of transoral laser microsurgery in hypopharyngeal carcinoma.
Laryngoscope Investig Otolaryngol. 2020 Feb;5(1):66-73. doi: 10.1002/lio2.351. Epub 2020 Jan 14.
Abstract/Text BACKGROUND: Transoral laser microsurgery has been suggested as an alternative treatment modality for hypopharyngeal carcinoma. The purpose of this study is to systematically review the oncologic and functional outcomes of patients with hypopharyngeal carcinoma when treated with primary transoral laser microsurgery.
METHODS: A comprehensive literature search was performed using PRISMA methodology on OVID MEDLINE and EMBASE. Meta-analysis was completed for oncological outcomes.
RESULTS: Six studies reported quality of life outcomes five reported oncologic outcomes. A median of 95% (range 0.83-0.98) patients achieving gastrostomy independence, a median of 3% (range 0%-6%) were tracheostomy dependent, and a median of 97% (Range 0.89-1.0) were able to preserve their larynx. Pooled five-year overall survival was 54% (CI, 0.50-0.58, I2 = 29%), pooled disease-specific survival was 72% (CI, 0.68-0.77, I2 = 46%), and pooled local control rate was 78% (CI, 0.72-0.85, I2 = 69%).
CONCLUSION: Systematic review supports improvements in functional outcomes and oncologic outcomes with transoral laser microsurgery.

© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals, Inc. on behalf of The Triological Society.
PMID 32128432
Armando De Virgilio, Oreste Iocca, Luca Malvezzi, Pasquale Di Maio, Raul Pellini, Fabio Ferreli, Giovanni Cugini, Giovanni Colombo, Giuseppe Spriano
The Emerging Role of Robotic Surgery among Minimally Invasive Surgical Approaches in the Treatment of Hypopharyngeal Carcinoma: Systematic Review and Meta-Analysis.
J Clin Med. 2019 Feb 18;8(2). doi: 10.3390/jcm8020256. Epub 2019 Feb 18.
Abstract/Text The aim of this systematic review with meta-analysis was to investigate the available literature on transoral approaches in the treatment of hypopharyngeal squamous cell carcinoma, with a special focus on transoral robotic surgery (TORS). A systematic review was conducted according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) check-list, and 15 studies were included. Five of the included studies evaluated TORS, while ten studies focused on transoral laser microsurgery (TLM) for the treatment of early or advanced stage hypopharyngeal cancer. Overall, survival rates of TLM and TORS studies, analyzed together in the cumulative meta-analysis, were 66.4% (95% confidence interval (CI) 54.3%⁻76.7%) at 36+ months of follow up. The TORS subgroup showed a higher cumulative survival rate (85.5%, 95% CI 55.8%⁻96.5%) compared to TLM (58.5%, 95% CI 46.6%⁻69.6%). Cumulative data showed that 29.3% (95% CI 24.0%⁻35.3%) of deaths were attributable to cancer. The results were similar between TLM and TORS studies. The larynx function preservation cumulative rate was 94.3% (95% CI 91.8%⁻96.1%). The results were similar among the two subgroups. The present review supports the use of transoral approaches in the treatment of hypopharyngeal cancer. TORS is oncologically sound and provides excellent functional results with low complication rates.

PMID 30781660
Jean-Pierre Pignon, Aurélie le Maître, Emilie Maillard, Jean Bourhis, MACH-NC Collaborative Group
Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients.
Radiother Oncol. 2009 Jul;92(1):4-14. doi: 10.1016/j.radonc.2009.04.014. Epub 2009 May 14.
Abstract/Text BACKGROUND: Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the results limited the conclusions and prompted us to confirm the results on a more complete database by adding the randomised trials conducted between 1994 and 2000.
METHODS: The updated IPD meta-analysis included trials comparing loco-regional treatment to loco-regional treatment+chemotherapy in HNSCC patients and conducted between 1965 and 2000. The log-rank-test, stratified by trial, was used to compare treatments. The hazard ratios of death were calculated.
RESULTS: Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The hazard ratio of death was 0.88 (p<0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction (p<0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. Both direct (6 trials) and indirect comparisons showed a more pronounced benefit of the concomitant chemotherapy as compared to induction chemotherapy. For the 50 concomitant trials, the hazard ratio was 0.81 (p<0.0001) and the absolute benefit 6.5% at 5 years. There was a decreasing effect of chemotherapy with age (p=0.003, test for trend).
CONCLUSION: The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.

PMID 19446902
Takeshi Shinozaki, Ryuichi Hayashi, Wataru Okano, Toshifumi Tomioka, Takuya Higashino
Treatment results of 99 patients undergoing open partial hypopharyngectomy with larynx preservation.
Jpn J Clin Oncol. 2019 Oct 1;49(10):919-923. doi: 10.1093/jjco/hyz091.
Abstract/Text OBJECTIVE: Hypopharyngeal cancers frequently go undetected until advanced stages. However, recent advances in endoscopic technology have enabled earlier detection of hypopharyngeal cancer. We evaluated the effectiveness of larynx-preserving surgery for hypopharyngeal cancer.
METHODS: We retrospectively analyzed 99 patients with hypopharyngeal squamous cell carcinoma who underwent partial hypopharyngectomy with larynx preservation between September 1992 and December 2009 at the National Cancer Center Hospital East. Of these, 91 patients underwent larynx-preserving surgery as initial treatment; eight patients underwent salvage surgery for recurrent disease after previous radiotherapy. Also, 9 of our patients had undergone previous radiotherapy in the head and neck for a different cancer. Before surgery, the TNM stage and tumor location was recorded. Free-flap reconstruction was performed in 60 patients, while the hypopharyngeal mucosa was closed without a free flap in 39 patients.
RESULTS: The 5-year overall survival rate in our cohort was 66.9%, and 59 patients are currently alive without recurrence. Thirty-three patients died due to primary recurrence (n = 5), regional recurrence (n = 10), distant metastasis (n = 9), postoperative death (n = 1), and unrelated disease (n = 8). Laryngeal function could not be preserved in 19 patients, 2 of whom had undergone previous radiotherapy, and 7 of whom had undergone both previous radiotherapy and other salvage surgeries.
CONCLUSION: Partial hypopharyngectomy can preserve laryngeal function in patients with pharyngeal cancer with careful patient selection.

© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PMID 31242294
Tong Jin, Xuezhong Li, Dapeng Lei, Dayu Liu, Qiuan Yang, Guojun Li, Xinliang Pan
Preservation of laryngeal function improves outcomes of patients with hypopharyngeal carcinoma.
Eur Arch Otorhinolaryngol. 2015 Jul;272(7):1785-91. doi: 10.1007/s00405-014-3115-2. Epub 2014 Jun 10.
Abstract/Text This study compares clinical characteristics and survival between patients with and without laryngeal function (LF) preservation during surgical treatment for hypopharyngeal carcinoma. We retrospectively reviewed 485 cases of hypopharyngeal carcinoma treated at a single institution for analysis. There were 337 cases with and 148 cases without LF preservation after surgery. Preservation of LF was complete in 237 patients and partial in 100 patients. There were significant statistical differences between the preservation group and the group without preservation in T-stage (P < 0.001), overall staging (P < 0.001), and tumor sites (P < 0.001) except the N-stage (P = 0.240). The patients with LF preservation had significantly better overall survival (log-rank, P = 0.005) and a lower risk of death than those without LF preservation (HR 0.62, 95% CI 0.43-0.97), after multivariable adjustment. Treatment with surgery in combination with radiotherapy is still the favorable choice for patients with hypopharyngeal carcinoma. The maximal restoration of pharyngoesophageal continuity and function improves survival for patients whose tumors are excised completely for the preservation of LF and laryngeal and pharyngeal reconstruction.

PMID 24913624

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