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洪健華 雙極電刀攝護腺刮除術前,短期使用5-alpha還原酶抑制劑:對於較大體積攝護腺血管影響及手術失血量降低之評估 2018/10/1 下午 03:19:03 0
原 文 題  目 Short-term pretreatment with a dual 5α-reductase inhibitor before bipolar transurethral resection of the prostate (B-TURP): evaluation of prostate vascularity and decreased surgical blood loss in large prostates
作  者 Busetto GM, Giovannone R, Antonini G, Rossi A, Del Giudice F, Tricarico S, Ragonesi G, Gentile V, De Berardinis E
出  處 BJU Int. 2015 Jul;116(1):117-23.
出版日期 Jul, 2015
評 論

攝護腺肥大,除了在尿道旁的移行區(transitional zone)間質以及腺泡組織(stromal and acinar)增生外,血管增加也是重要的特色。5-alpha還原酶抑制劑可以造成攝護腺上皮細胞凋亡,導致腺體積減少。根據MTOPS以及combAT的大規模研究,對於中重度下泌尿道症狀,以及有較高疾病進展風險的男性病患,歐洲泌尿科醫學會以及台灣泌尿科醫學會的診療指引,都建議給予甲型腎上腺受體阻斷劑與5-alpha還原酶抑制劑的合併治療。然而,臨床上當病人對於藥物反應不佳,或發生尿滯留、反覆泌尿道感染、膀胱結石、腎功能損傷、血尿等併發症時,病患仍需要接受手術治療。隨著手術器械和手術技巧的進步,對精益求精的泌尿科醫師來說,更不容許發生手術併發症,例如出血或是急迫性尿失禁。因此,使用5α 還原酶抑制劑是否能幫助泌尿科醫師在手術前降低手術相關的併發症,例如出血,是個有趣的議題。

本研究將259位病人隨機分成兩組,手術前短期給予八周的藥物治療,一組接受安慰劑治療,一組接受0.5mg dutasteride,評估能否降低術中失血量。所有病人一律在手術前一小時以及手術後48小時抽血。除了測量血色素(hemoglobin)以及血比容(hematocrit)之外,本篇另一個特點,是為了評估攝護腺的血管新生和生成,測量了VEGF(vascular endothelial growth factor,刺激內皮細胞,影響血管生成),以及MVD ( Microvessel density, 本研究是利用CD34,一種糖基化的跨膜蛋白,會表現在大多數內皮細胞)來評估5-alpha還原酶抑制劑對血管生成的影響。

結果發現,藥物治療後,兩組攝護腺體積沒有明顯差異,安慰劑組的平均攝護腺體積為60ml,治療組為61ml。治療組DHT以及PSA明顯較低,而血清總睪固酮及並沒有顯著差異。平均手術時間也沒有統計上差異,安慰劑組為50分鐘,治療組為48分鐘。比較手術(雙極電刀刮除術)前後的血色素以及血比容差異,在小攝護腺體積組別(小於50 ml),安慰劑組比治療組,平均血色素下降為2.41g/dL比1.92 g/dL, p= 0.454;然而血比容為2.22% 比1.95%,無統計上顯著性。在攝護腺體積大於50ml的組別,則有顯著的差異性。(安慰劑組ΔHb 3.86對比治療組ΔHb2.05 g/dL ;安慰劑組ΔHt 4.98% 對比治療組2.64%)。同樣地,VEGF 以及MVD 也只有在攝護腺體積大於50ml的病患方面,才有顯著的降低。

本研究結論認為,對於大體積(>50ml)的攝護腺,術前給予短期八週dutasteride可以顯著降低手術之失血。雖然學理上,這是合理結果,但是從結果分析來看,兩組相差的血色素變化不到1g/dL, 文章也未探討是否因此減少輸血的機率。儘管統計上有顯著性,對臨床醫師來說是否有實際意義仍有待思考。不過文章嘗試探討5-alpha 還原酶抑制劑對於攝護腺肥大手術的影響。是個值得參考的切入點,期待未來有更多研究來分析此類治療對於術後併發症的影響,甚至更大體積的攝護腺(例如>80ml)是否更有助益、或是對於雷射手術的病患相關研究。

abstract

Objective
To investigate if short-term treatment with dutasteride (8 weeks) before bipolar transurethral resection of the prostate (B-TURP) can reduce intraoperative bleeding, as dutasteride a dual 5α-reductase inhibitor (5-ARI) blocks the conversion of testosterone into its active form dihydrotestosterone (DHT), and reduces prostate volume and prostate-specific antigen (PSA) levels, while increasing urinary flow rate.

Patients and Methods
In all, 259 patients were enrolled and randomised to two groups: Group A, receiving placebo and Group B, receiving dutasteride (0.5 mg daily for 8 weeks). Blood samples were taken before and after B-TURP for serum chemistry evaluation. In particular we evaluated blood parameters associated with blood loss [haemoglobin (Hb) and haematocrit (Ht)] and prostate vascularity [vascular endothelial growth factor (VEGF) immunoreactivity and microvessel density (MVD) using cluster of differentiation 34 (CD34) immunoreactivity].

Results
Total testosterone, DHT, PSA level and prostate volume were evaluated and with the exception of DHT and PSA level there was no statistically significant differences between the groups. When comparing changes in Hb and Ht between Group A and Group B before and after B-TURP, there was a statistically significant difference only in patients with large prostates of ≥50 mL (ΔHb 3.86 vs 2.05 g/dL and ΔHt 4.98 vs 2.64%, in Groups A and B, respectively). There was no significant difference in MVD and VEGF index in prostates of <50 mL, conversely in large prostates the difference become statistically significant.

Conclusions
Dutasteride was able to reduce operative and perioperative bleeding only in patients with large prostates (≥50 mL) that underwent B-TURP. Our findings are confirmed by Hb and Ht values reported before and after the B-TURP and reductions in the molecular markers for VEGF and CD34 in the dutasteride-treated specimens.

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