高壓氧治療放射性出血性膀胱炎的系統性回顧及統合分析，一項隨機、對照、III 期試驗

Systematic Review and Meta-analysis of Hyperbaric Oxygen Therapy for Radiation-Induced Hemorrhagic Cystitis, A Randomized, Controlled, Phase III Trial

李幸儒(Hsing-Ju Li)

指導教授 ： 成佳憲

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2022年)

https://doi.org/10.6342/NTU202203482

摘要

背景:
癌症放射線治療引起的急性副作用通常在暴露後數週內發生，而慢性副作用發生在放射線治療後數月至數年。慢性放射性膀胱炎是一種慢性進行性疾病，在骨盆腔區域（例如:前列腺癌、直腸癌或婦科癌症)放射治療後有 5-15% 的患者會發生，造成一系列泌尿道症狀，包含常見血尿、尿失禁、排尿困難、急尿、頻尿、骨盆腔疼痛等。目前較非侵入性的治療選項包含藥物治療、高壓氧治療(HBOT)，及侵入性的膀胱內藥物灌注及雷射或電燒灼，至今尚未有明確的治療對於症狀有顯著改善。
高壓氧治療 (HBOT) 是公認放射性膀胱炎的治療選擇之一。高壓氧治療在高壓艙內讓病患經由頭上所戴的氧氣面罩吸百分之百氧氣，是一種間斷性、高濃度而短時間的氧氣呼吸治療法，以物理的現象來增加血液中氧氣濃度以提昇組織內的含氧量，提高血中及患部組織含氧度，減少缺氧組織的傷害，並可促進傷口癒合。高壓氧治療也有併發症包括氣壓傷性耳炎、視力障礙和感覺異常。
方法:
本研究進行系統性回顧及統合分析，搜尋發表在Embase、Pubmed、Web of Science 三個資料庫的文獻，以「radiation cystitis」和「hyperbaric oxygen therapy」為搜索關鍵字。預計以放射線膀胱炎血尿改善程度作為primary endpoint，比較標準治療(例如:保守治療)與高壓氧治療的差別。
結果:
本研究共有251 篇文獻進入初步審閱。排除重複文獻的75 篇，不適當主題的92 篇，摘要內容偏離主題的47 篇，及排除其他原因(包括非骨盆腔癌症或未使用高壓氧治療之病人)的27 篇，最後有11 篇文章納入此統合分析(包括隨機對照試驗2 篇，回顧性研究7 篇，前瞻性研究2 篇)。7 篇回溯性研究和2 篇前瞻性研究總共包含 449 名受試者進行薈萃分析。高壓氧治療有62%之病患血尿症狀完全改善(95% CI 0.57-0.66,P<0.0001,I2=38.3%)。
結論:
針對放射性膀胱炎患者的薈萃分析顯示高壓氧治療有顯著的改善血尿，未來需要有較多患者和長期追蹤的前瞻性隨機對照研究來驗證高壓氧治療放射性膀胱炎的療效。

關鍵字

放射性膀胱炎 ； 高壓氧治療 ； 血尿 ； 系統性回顧 ； 薈萃分析

並列摘要

Background
Acute side effects of cancer radiotherapy occur within weeks of radiation exposure, while chronic side effects have a latent period of months to years. Radiation cystitis is a chronic inflammatory disease in 5-10% of patients with radiation therapy to pelvic region (such as prostate, rectum, or gynecology malignancy). Radiation cystitis causes a series of symptoms, including hematuria, urinary incontinence, voiding difficulty, urgency, frequency, pelvic pain, etc. The current non-invasive treatments include drug treatment and hyperbaric oxygen therapy (HBOT), while invasive treatments include intravesicle drug infusion and laser or electric cauterization. There is limited evidence for an optimal treatment with a significant improvement of these symptoms.
One of the optional treatments for radiation cystitis is HBOT, which is performed in a hyperbaric chamber, allowing patients to inhale 100% oxygen through an oxygen mask worn on the head. It is an intermittent, high-concentration, and short-term oxygen inhalation therapy. HBOT mainly uses the physical phenomena to increase the oxygen concentration in the blood, elevate the oxygen content in the tissue, reduce the damage of hypoxic tissue, and promote wound healing.
Methods
This study utilized systematic review and meta-analysis. With “radiation cystitis” and “hyperbaric oxygen” as the key words, which were searched in the databases of Embase, Pubmed, and Web of Science. The primary endpoint of the present study is improvement of hematuria related to radiation cystitis for the comparison between standard treatments (e.g. conservative treatment) and HBOT.
Results
A total of 251 studies were included for the initial review. Seventy-five duplicated papers, 92 with inappropriate titles, 47 with the deviated subjects from the abstract, and 27 with other reasons (e.g. patients with malignancies outside pelvis or without the use of HBOT) were excluded. Finally, 11 articles were included for the meta-analysis. Seven were retrospective studies, 2 were prospective studies, and 2 were randomized controlled trials. Seven retrospective studies and 2 prospective studies included a total of 449 patients for the meta-analysis. Sixty-two percent of patients with HBOT had complete remission of hematuria symptoms (95% CI 0.57-0.66, P<0.0001, I2 = 38.3%)
Conclusion
A significant hematuria improvement of HBOT was shown in this meta-analysis for patients with radiation cystitis. Prospective randomized controlled studies with large number of patients and long-term follow-up are needed to validate the effect of HBOT on radiation cystitis in the future.

並列關鍵字

Radiation cystitis ； Hyperbaric oxygen therapy ； Hematuria ； Systematic review ； Meta-analysis

參考文獻

Cardinal, J., Slade, A., McFarland, M., Keihani, S., Hotaling, J. N., Myers, J. B. (2018). Scoping Review and Meta-analysis of Hyperbaric Oxygen Therapy for Radiation-Induced Hemorrhagic Cystitis [Review]. Current Urology Reports, 19(6). https://doi.org/10.1007/s11934-018-0790-3

Cheng, C., Foo, K. T. (1992). Management of severe chronic radiation cystitis. Ann Acad Med Singap, 21(3), 368-371. https://www.ncbi.nlm.nih.gov/pubmed/1416787

Chong, K. T., Hampson, N. B., Corman, J. M. (2005). Early hyperbaric oxygen therapy improves outcome for radiation-induced hemorrhagic cystitis. Urology, 65(4), 649-653. https://doi.org/10.1016/j.urology.2004.10.050

Chong, V., Rice, M. (2016). The effectiveness of hyperbaric oxygen therapy (HBOT) in radiation-induced haemorrhagic cystitis. New Zealand Medical Journal, 129(1446), 79-83. https://www.ncbi.nlm.nih.gov/pubmed/27906922

De Oliveira, T. M. R., Romao, A. J. C., Guerreiro, F. M. G., Lopes, T. M. M. (2015). Hyperbaric oxygen therapy for refractory radiation-induced hemorrhagic cystitis. International Journal of Urology, 22(10), 962-966. https://doi.org/10.1111/iju.12857