一、研究計畫之背景：
接受義乳重建並接受放射治療的乳癌病患，相較於僅接受義乳重建的病患，面臨較高的併發症與不良後果風險。高壓氧治療（Hyperbaric Oxygen Therapy）為放射線相關併發症的已知治療選項之一。本研究旨在探討若在症狀尚未進展至影響生活品質或導致重建失敗前即早期介入高壓氧，是否能減緩這些併發症的發生。
二、研究設計：
本研究為一項前瞻性、小規模觀察性臨床研究，設計依據為文獻中針對放射線延遲性副作用中高壓氧之研究。所有受試者均接受兩階段義乳重建手術，並在第二階段手術前完成研究納入。是否接受高壓氧由病人自行決定。高壓氧治療至少進行15次，最多達20次。於第二階段手術中取得皮膚與莢膜組織進行分析。問卷評估於高壓氧後3個月、第二階段手術後3個月與6個月進行。主要終點為檢體分析(包含組織學分析及RNA sequencing)，次要終點包括重大併發症、病人問卷回報結果與臨床評估。
三、研究結果：
本研究共納入 7 位患者（HBOT 組 4 例；非 HBOT 組 3 例），皆無需再次手術或重建失敗。組織學上，放射線治療後皮膚在兩組間無顯著差異，但 HBOT 組表皮厚度有增加趨勢。在莢膜組織中，HBOT 與膠原纖維排列較分散及 α-SMA 表現降低相關，CD68 與 Vimentin 亦呈下降趨勢，顯示巨噬細胞浸潤及成纖維母細胞活性減弱。RNA 定序顯示，皮膚樣本有 244 個差異表現基因（DEGs），莢膜樣本則有 980 個，並富集於免疫及肌肉骨骼相關途徑，顯示 HBOT 可減緩放射治療後的慢性發炎與因缺氧誘發肌成纖維母細胞活化所導致的纖維化。問卷評估（包括BR23與LENT-SOMA）反映出的病人自述結果受個別臨床條件影響甚鉅，無法作為具代表性的依據。同樣地，臨床對莢膜攣縮的評估，如Baker分級與Paris Breast Center之美觀評估，也缺乏一致性與代表性。
四、結論：
接受高壓氧治療的病患在莢膜攣縮方面，無論於組織學評估或RNA定序結果中皆顯示出改善。然而，病患自填問卷及臨床評估的結果並未呈現一致或具代表性的趨勢，可能與樣本數不足、病人臨床狀況高度異質，以及追蹤時間較短等因素有關。雖然本研究結果尚不足以作為具統計代表性的依據，但在組織學與分子層次所觀察到的改善趨勢，為未來相關研究提供了有價值的參考方向。

Introduction:
Breast cancer patients who undergo implant-based reconstruction followed by radiotherapy face an increased risk of complications and adverse outcomes compared to those who receive implant reconstruction alone. Hyperbaric oxygen therapy (HBOT) is a recognized treatment option for managing radiation-induced complications. This study aimed to investigate whether the early application of HBOT—before symptoms progress to a level that affects quality of life or leads to reconstruction failure—could help mitigate these complications.
Study Design:
Based on a review of the literature regarding HBOT for delayed radiation-related side effects, we conducted a prospective, small-scale observational clinical study. All patients underwent two-stage implant-based breast reconstruction and were enrolled prior to the second-stage procedure. The decision to receive HBOT was made by the patients. HBOT was administered for a minimum of 15 sessions, up to 20 sessions. Skin and capsule specimens were collected during the second-stage operation. Questionnaires were administered at three times: three months after HBOT, and three and six months after the second-stage operation. The primary endpoint was specimens’ evaluation, including histologic examination and RNA sequencing. Secondary endpoints included major complications, patient-reported outcomes, and clinical assessments.
Results:
Seven patients were included (HBOT, n=4; non-HBOT, n=3), with no reoperations or reconstructive failures. Histologically, irradiated skin showed no group differences, though epidermal thickness tended to be greater with HBOT. In capsule tissue, HBOT was associated with more dispersed collagen fibers and reduced α-SMA, with lower CD68 and Vimentin suggesting decreased macrophage and fibroblast activity. RNA sequencing identified 244 DEGs in skin versus 980 in capsule, with enrichment in immune and musculoskeletal pathways, consistent with attenuation of chronic inflammation and key fibrotic processes driven by hypoxia-induced myofibroblast activation following radiotherapy.
However, patient-reported outcomes, as assessed by the BR23 and LENT-SOMA questionnaires, were heavily influenced by individual clinical conditions and did not provide representative or consistent trends. Similarly, clinical evaluations of capsular contracture—including the Baker classification and aesthetic assessment using the Paris Breast Center (PBC) scale—also lacked consistency and generalizability.
Conclusion:
Patients who received hyperbaric oxygen therapy (HBOT) demonstrated improvements in capsular contracture, as evidenced by both histological evaluation and RNA sequencing results. However, patient-reported outcomes and clinical assessments did not exhibit consistent or representative trends. This discrepancy may be attributed to the limited sample size, high heterogeneity in clinical conditions, and relatively short follow-up period. Although the findings of this study are not yet sufficient to serve as statistically representative evidence, the observed improvements at the histological and molecular levels offer a meaningful direction for future research.

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