摘要
研究背景：口腔及口咽癌患者罹患阻塞型睡眠呼吸中止症較一般健康族群高，根據腫瘤發生的位置以及治療方式的不同，已接受檢查者，阻塞型睡眠呼吸中止症盛行率可達12%到92%。接受皮瓣重建手術會使呼吸道更為狹窄，因此加重了睡眠呼吸中止的嚴重程度，。罹患阻塞型睡眠呼吸中止症若未發現治療，長期可能增加心、腦血管、代謝疾病的發生率及死亡率。睡眠時呼吸中止或淺呼吸，會引發打鼾、覺醒、血氧降低及二氧化碳上升等情形，影響睡眠而造成白天疲勞、嗜睡、注意力與記憶力下降等症狀影響生活品質，其中缺氧的情況可能會影響癌症的預後。若能早期發現睡眠呼吸中止嚴重度的變化，有助於及早介入治療及照護。
研究目的：旨在瞭解口腔及口咽癌患者術前、術後一周及術後六個月阻塞型睡眠呼吸中止症嚴重程度的變化，以及影響阻塞型睡眠呼吸中止症之相關因素。
研究方法：本研究為前瞻性世代研究，對象為南部某醫學中心門診口腔及口咽癌患者，採立意取樣法，納入條件為(1) 初診斷為口腔及口咽癌，診斷碼為ICD-O-3：C00-C06、C09-C10、C14；(2) 預計接受游離皮瓣重建手術治療；(3)年滿20歲(含)以上；(4) 有能力及意願提供書面知情同意，以及配合研究執行。排除條件為(1)合併其他癌症的病人；(2)已確認診斷有睡眠呼吸障礙者、嚴重精神疾病且無法配合受測者。在手術前、手術後一周及手術後六個月施行多頻道睡眠生理檢查，評估阻塞型睡眠呼吸中止症嚴重程度變化。
研究結果：本研究共納入15位口腔及口咽癌患者，阻塞型睡眠呼吸中止症數值在術前發生率為80%，在術後一周明顯變嚴重，其發生率為92.3%，術後六個月比術前嚴重，但比起術後一周有較趨緩情況，其發生率為91.7%。手術前頸圍(r=.517, p=.048)與AHI呈顯著正相關；手術後一周年齡(r= -.650, p=.016)與AHI呈顯著負相關；手術後六個月身體質量指數(r=.623, p=.03)與AHI呈顯著正相關，治療歷程(p=.022)與AHI達到顯著差異。
結論與建議：本研究發現口腔及口咽癌患者在接受游離皮瓣重建手術後，無論是手術後一周亦或是手術後六個月，阻塞型睡眠呼吸中止症程度皆比手術前更為嚴重，其相關因素包括：年齡、頸圍、身體質量指數及癌症治療歷程。因此臨床醫療人員應培養評估阻塞型睡眠呼吸中止症危險因子及臨床症狀之能力，提升對口腔及口咽癌患者睡眠困擾主訴之敏感度，方能夠提供個別化及適切性之醫療照護。

SUMMARY
Little was known about the association between obstructive sleep apnea (OSA) and oral and oropharynx cancers (OOCs). To clarify the impact of free flap reconstruction on OSA, we performed a pilot study to investigate the change of OSA severity in patients with OOC before and after flap reconstruction surgery. The purpose of this study was to describe the long-term trend on OSA of patients with OOC, and to understand the related factors. The study design was prospective cohort study. This study recruited 15 patients who were newly diagnosed with OOCs and expected to receive free flap reconstruction surgery. For each participant, polysomnography tests were performed repeatedly at the time of pre-operative, post-operative 1-week, and post-operative 6-month periods. Our study showed that OOCs patients with free flap reconstruction surgery had significantly increased AHI level during post-operative 1-week period. The OSA severity became partial remission after 6 months. We recommend that the head and neck cancer team should pay attention to the OSA issues in OOCs patients with free flap reconstruction surgery.

參考文獻
台灣癌症防治網(2018)‧認識頭頸癌‧取自http://web.tccf.org.tw/lib/project/books/book01.php
衛生福利部國民健康署(2018)‧105年癌症登記年報‧取自http://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=269&pid=80840
衛生福利部統計處 (2017)‧106年國人死因統計結果‧取自https://www.mohw.gov.tw/cp-3795-41794-1.html
陳濘宏(2005)‧阻塞型睡眠呼吸中止症‧台灣醫學，9(3)，361-366。
郭秋香、馬素華、張玉坤、林鴻銓(2011)‧阻塞型睡眠呼吸中止症候群主要危險因子探討‧長庚護理，22(1)，26-37。
曾良鵬(2014)‧口腔癌可以手術嗎?‧高醫醫訊，34(6)，10-11。
葉世彬(2005)‧睡眠呼吸生理與相關疾病介紹‧台灣醫界，48(3)，25-30。
葉世彬(2013)‧睡眠疾患手冊：醫生VS病人最需要的一本書(二版)‧台北：合記。
葛應欽(1995)‧台灣之口腔癌與嚼檳榔、吸菸、酒精消耗間的關聯性 ‧口腔病理學及口腔內科學雜誌，24。
劉勝義(2011)‧睡眠醫學實務‧台北：合記。
American Joint Committee on Cancer. (2012). AJCC cancer staging atlas. In C. C. Compton, D. R. Byrd, J. Garcia-Aguilar, S. H. Kurtzman, A. Olawaiye & M. K. Washington (Eds.), A companion to the seventh editions of the AJCC cancer staging manual and handbook. Retrieved from http://link.springer.com/book/10.1007/978-1-4614-2080-4/page/1
Ancoli-Israel S., & Aayalon L. (2006). Diagnosis and treatment of sleep disorders in older adults. American Journal of Geriatric Psychiatry, 14, 95-103.
Aurora, R. N., Collop, N. A., Jacobowitz, O., Thomas, S. M., Quan, S. F., & Aronsky, A. J. (2015). Quality measures for the care of adult patients with obstructive sleep apnea. Journal of Clinical Sleep Medicine, 11(3), 357–383.
Basoglu, O. K., Keskin, B., Tasbakan, M. S., & Gurgun, C. (2015). Effect of Semirecumbent Sleep Position on Severity of Obstructive Sleep Apnea in Patients With Heart Failure. Journal of cardiac failure, 21(10), 842–847. https://doi.org/10.1016/j.cardfail.2015.06.004
Berry, R. B., Brooks, R., Gamaldo, C., Harding, S. M., Lloyd, R. M., Quan, S. F., Troester, M. T., & Vaughn, B. V. (2014). The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. (Version 2.1). Darien, IL: American Academy of Sleep Medicine.
Bruce, E. B., Kerstin, M. S., Shiyu S. Overview of treatment for head and neck cancer. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on March 20, 2018.)
Buysse, D. J., Reynolds, C. F., 3rd., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989). The pittsburgh sleep quality index: A new instrument for psychiatric practice and research. Psychiatry Research, 28(2), 193－213.
Cartwright R. D. (1984). Effect of sleep position on sleep apnea severity. Sleep, 7(2), 110–114. https://doi.org/10.1093/sleep/7.2.110
Cartwright, R. D., Diaz, F., & Lloyd, S. (1991). The effects of sleep posture and sleep stage on apnea frequency. Sleep, 14(4), 351–353. https://doi.org/10.1093/sleep/14.4.351
Cheng, C. H., Huang, Y. C., & Jih, K. S. (2003). Anthropometric measurements and sleep-related features in relation to obstructive sleep apnea syndrome. Thoracic Medicine, 18(3), 187-193. doi:10.29806/TM.200306.0001
Colin, S. P., Kerstin, M. S., Overview of the diagnosis and staging of head and neck cancer. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on March 20, 2018.)
Davi, M., Carbonare, L., Giustina, A., Ferrari, M., Frigo, A., Lo Cascio, V., & Francia, G. (2008). Sleep apnoea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease, European Journal of Endocrinology, 159(5), 533-540.
Devins, G. M., Otto, K. J., Irish, J. C., & Rodin, G. M. . (2010). Head and neck cancer. In J.C. Holland (Ed.), Psycho-oncology. New York: Oxford University Press.
Epstein, L. J., Kristo, D., Strollo, P. J., Jr., Friedman, N., Malhotra, A., Patil, S. P., Ramar, K., ... Weinstein, M. D. (2009). Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. Journal of Clinical Sleep Medicine, 5(3), 263-276.
Franklin, K. A., & Lindberg, E. (2015). Obstructive sleep apnea is a common disorder in the population—a review on the epidemiology of sleep apnea. Journal of Thoracic Disease, 7(8), 1311–1322.
Gaines, J., Vgontzas, A. N., Fernandez-Mendoza, J., Calhoun, S. L., He, F., Liao, D., … Bixler, E. O. (2016). Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents. American Journal of Physiology - Endocrinology and Metabolism, 311(5), E851–E858. http://doi.org/10.1152/ajpendo.00249.2016
Global Burden of Disease Cancer Collaboration, Fitzmaurice C., Allen C., ……Naghavi , M. (2017) Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncology , 3(4):524-548.
Grunstein, R. R., Ho, K.Y., Sullivan, C.E. (1991) Sleep apnea in acromegaly. Annals of internal medicine, 115(7), 527-32.
Huang, L. W., Hsu, J. Y., Chang, C. J., Wang, H. C., Cheng, S. L., Lin, C. H.,...Yu, C. J. (2016). Predictive factors warrant screening for obstructive sleep apnea in COPD: A Taiwan national survey. International Journal of Obstructive Pulmonary Disease, 11, 665-673.
Huyett, P., Kim, S., Johnson , J.T., Soose, R.J.(2017). Obstructive sleep apnea in the irradiated head and neck cancer patient. The Laryngoscope, 127(11), 2673-2677.
Johns, M. W. (1971). Methods of assessing human sleep. Archives of Internal Medicine, 127(3), 484－492
Kathryn, L., Maria, C., Christine, M., Marylin, D. (2004). Impaired sleep and rhythms in persons with cancer. Sleep Medicine Reviews, 8 (3), 199 – 212.
Kingman, P. S. Overview of obstructive sleep apnea in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on November 01, 2017.)
Lin, S. L. (1992). Perception of sleep quality/quantity and fear in critically ill patients with respiratory failure using mechanical ventilator support. Unpublished masters thesis, University of Washington.
Lin, H. C., Friedman, M., Chang, H. W., Fang, F. M., Lin, M. C., & Su, M. C. (2014). Impact of head and neck radiotherapy for patients with nasopharyngeal carcinoma on sleep-related breathing disorders. JAMA otolaryngology head & neck surgery, 140(12), 1166–1172. https://doi.org/10.1001/jamaoto.2014.2953
Loth, A., Michel, J., Giorgi, R., Santini, L., Rey, M., Elbaum, J.M., …… Fakhry, N. (2017).Prevalence of obstructive sleep apnoea syndrome following ropharyngeal cancer treatment: A prospective cohort study. Clinical Otolaryngology, 42(6), 1281-1288. https://doi.org/10.1111/coa.12869
Lacko, M., Braakhuis, B. J., Sturgis, E. M., Boedeker, C. C., Suarez, C.,Rinaldo, A., Ferlito, A., Takes, R. P. (2014). Genetic susceptibility to head and neck squamous cell carcinoma. International Journal of Radiation Oncology Biology Physics, 89(1), 38-48.
Mason, M., Cates, C. J., Smith, I. (2015) Effects of opioid, hypnotic and sedating medications on sleep‐disordered breathing in adults with obstructive sleep apnoea. Cochrane Database of Systematic Reviews, 7, 1465-1858.
Militsakh, O., Chi, A., Alberg, A., Cannick, G., Ford, M., Carpenter, M., Miller, P., Sutkowski, N., & Day, T. (2010). Head and neck cancer prevention. In W. M. Koch (Ed.), Eerly diagnosis and treatment of cancer: head and neck cancer. Philadelphia: Saunders.
Ohayon, E.M. Wickwire, M. Hirshkowitz, S.M. Albert, A. Avidan, F.J. Daly et al,. (2017). National Sleep Foundation's sleep quality recommendations: First report. Sleep Health, 3(1), 6-19.
Park, J. G., Ramar, K., & Olson, E. J. (2011). Updates on definition, consequences, and management of obstructive sleep apnea. Mayo Clinic Proceedings, 86(6), 549–555.
Parrott, A. C., & Hindmarch, I. (1978). Factor analysis of asleep evaluation questionnaire. Psychological Medicine, 8(2), 325-329.
Payne, R. J., Hier, M. P., Kost, K. M., Black, M. J., Zeitouni, A. G., Frenkiel, S., & ...Kimoff, R. J. (2005). High prevalence of obstructive sleep apnea among patients with head and neck cancer. Journal of Otolaryngology, 34(5), 304-311.
Paul, E. P., Terry, Y, Jodi, H. B., Mari, P., Erika, W. H., Khin, M. H. (2013) Increased prevalence of sleep-disordered breathing in adults, American Journal of Epidemiology, 177(9), 1006–1014. https://doi.org/10.1093/aje/kws342.
Peppard, P. E., Young, T., Palta, M., Dempsey, J., Skatrud, J. (2000) Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA, 284(23), 3015–3021. doi:10.1001/jama.284.23.3015.
Rosenow, F., McCarthy, V., Caruso, A. C. (1998) Sleep apnoea in endocrine diseases. Journal of sleep research, 7(1), 3-11.
Sergio, T., Rogerio, S. S., Jose , A. T., Lia, R. A. B.(2010)Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic sleep study. Sleep Medicine, 11(5), 441-446.

Shih, J. W., Chiang, W. F., Wu, A., Wu, M. H., Wang, L. Y., Yu, Y. L., … Kung, H. J. (2017). Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression. Nature communications, 8, 15874. doi:10.1038/ncomms15874
Shuman, A. G., Duffy, S. A., Ronis, D. L., Garetz, S. L., McLean, S. A., Fowler, K. E., & Terrell, J. E. (2010). Predictors of poor sleep quality among head and neck cancer patients. The Laryngoscope, 120(6), 1166–1172. http://doi.org/10.1002/lary.20924
Siegel, R. L., Miller, K. D., Jemal, A. (2017) Cancer Statistics, 2017. CA: a cancer Journal for Clinicians, 67(1),7-30.
Simpson, T., Lee, E. R., & Cameron, C. (1996). Relationships among sleep dimensions and factors that impair sleep after cardiac surgery. Research in Nursing & Health, 19, 213-223.
Snyder-Halpern, R., & Verran, J. A. (1987). Instrumentation to describe subjective sleep characteristics in healthy subjects. Research in Nursing and Health, 10(3), 155-163.
Steffen, A. Graefe, H., Gehrking, E., Konig, I. R., & Wollenberg, B. (2009). Sleep apnoea in patients after treatment of head neck cancer. Acta Oto-Laryngologica, 129(11), 1300-1305.
WHO. (2018). Cancer prevention. Geneva: World Health Organization. Retrieved from http://www.who.int/cancer/prevention/en/
Young, T., Palat, M., Dempsey, J., Skatrud, J., Weber, S., & Badr, S. (1993). The occurrence of sleep-disordered breathing among middleaged adults. New England Journal of Medicine, 328, 1230-1235.
Young, T., Shahar, E., Nieto, F. J., Redline, S.,Newman, A. B., Gottlieb, D. J.,Walsleben, J. A., Finn, L., Enright, P. (2002). Predictors of sleep-disordered breathing in community-dwelling adults: The sleep heart health study. Archives of internal medicine, 162(8), 893-900.
Young, T., Skatrud, J., Peppard, P. E. (2004) Risk factors for obstructive sleep apnea in adults. JAMA, 291(16), 2013–2016. doi:10.1001/jama.291.16.2013.