Department of Urology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Urology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
J Pediatr Urol. 2020 Dec;16(6):807-814. doi: 10.1016/j.jpurol.2020.08.005. Epub 2020 Aug 14.
Although the consequences of testicular torsion (TT) have been recognized for centuries, little progress has been made to improve outcomes beyond those seen with timely scrotal exploration. Even with testicular salvage, ischemia/reperfusion injury cause significant atrophy and functional impairment. Recent efforts have sought to identify adjuvant pharmacological or surgical interventions that may attenuate these consequences. In this review, we assess the evidence supporting clinical use of these nascent interventions.
We conducted a review of the literature published from 2000 to 2020, using the search terms "torsion", "testicular", "reperfusion", "ischemia", and "injury". Clinical and laboratory research focused on adjuvant pharmacological and surgical techniques mitigating torsion-associated injury in animal models and humans were identified. We recorded intervention timing/dose/route, and outcome timing/category through biomarkers of reperfusion injury, histology, and hormonal/reproductive function.
Fifty-four FDA-approved agents, plus 52 herbal/investigational drugs, were reported in animal TT models. In every study, the investigated agents showed beneficial effects on measured endpoints compared to controls. Despite these universally promising animal findings, no pharmacological trials in humans were reported. Surgical techniques studied in animal models included decompression (tunica albuginea incision, TAI), "ischemic conditioning", and hypothermia. Only three human studies on surgical adjuvant maneuvers have been reported, all involving TAI; these showed potential benefit, but the level of evidence is low.
There is preliminary evidence that adjuvant treatments may mitigate the effects of ischemia/reperfusion injury. However, the pool of investigated pharmacological agents is wide, yet remarkably shallow; most compounds have been reported in a single animal study. To advance this field, a mechanism-based approach should be used to select promising agents that can be tested systematically. This will determine treatment parameters that maximize safety, efficacy, and tolerability. Only then is it possible to move toward human trials. Adjuvant surgical methods such as TAI show promise in humans but require more robust clinical evaluation.
尽管睾丸扭转（TT）的后果已经被认识了几个世纪，但除了及时进行阴囊探查外，在改善预后方面几乎没有取得任何进展。即使进行了睾丸保留，缺血/再灌注损伤也会导致显著的萎缩和功能障碍。最近的研究努力旨在确定可能减轻这些后果的辅助药理学或手术干预措施。在这篇综述中，我们评估了支持这些新兴干预措施临床应用的证据。
我们对 2000 年至 2020 年期间发表的文献进行了综述，使用的检索词包括“扭转”、“睾丸”、“再灌注”、“缺血”和“损伤”。在动物模型和人类中，确定了侧重于减轻与扭转相关损伤的辅助药理学和手术技术的临床和实验室研究。我们通过再灌注损伤的生物标志物、组织学和激素/生殖功能，记录了干预的时间/剂量/途径，以及结果的时间/类别。
在动物 TT 模型中，报道了 54 种 FDA 批准的药物，外加 52 种草药/研究药物。在每项研究中，与对照组相比，研究药物对测量终点都显示出有益的效果。尽管这些动物研究结果普遍很有前景，但没有报道人类的药理学试验。在动物模型中研究的手术技术包括减压（白膜切开术，TAI）、“缺血预处理”和低温。只有三项关于手术辅助操作的人类研究报告，均涉及 TAI；这些研究显示出潜在的益处，但证据水平较低。
有初步证据表明辅助治疗可能减轻缺血/再灌注损伤的影响。然而，被研究的药物种类繁多，但深度却很有限；大多数化合物仅在一项动物研究中被报道。为了推进这一领域，应该采用基于机制的方法来选择有希望的药物，以便系统地进行测试。这将确定最大限度地提高安全性、疗效和耐受性的治疗参数。只有这样，才有可能进行人体试验。TAI 等辅助手术方法在人类中显示出前景，但需要更严格的临床评估。
