van Lieshout Laura A M, Steenbeek Miranda P, De Hullu Joanne A, Vos M Caroline, Houterman Saskia, Wilkinson Jack, Piek Jurgen Mj
Department of Obstetrics and Gynaecology, Catharina Cancer Institute, Catharina Hospital, Michelangelolaan 2, Eindhoven, Netherlands, 5623EJ.
Cochrane Database Syst Rev. 2019 Aug 28;8(8):CD012858. doi: 10.1002/14651858.CD012858.pub2.
Ovarian cancer has the highest mortality rate of all gynaecological malignancies with an overall five-year survival rate of 30% to 40%. In the past two decades it has become apparent and more commonly accepted that a majority of ovarian cancers originate in the fallopian tube epithelium and not from the ovary itself. This paradigm shift introduced new possibilities for ovarian cancer prevention. Salpingectomy during a hysterectomy for benign gynaecological indications (also known as opportunistic salpingectomy) might reduce the overall incidence of ovarian cancer. Aside from efficacy, safety is of utmost importance, especially due to the preventive nature of opportunistic salpingectomy. Most important are safety in the form of surgical adverse events and postoperative hormonal status. Therefore, we compared the benefits and risks of hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy.
To assess the effect and safety of hysterectomy with opportunistic salpingectomy versus hysterectomy without salpingectomy for ovarian cancer prevention in women undergoing hysterectomy for benign gynaecological indications; outcomes of interest include the incidence of epithelial ovarian cancer, surgery-related adverse events and postoperative ovarian reserve.
The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two clinical trial registers were searched in January 2019 together with reference checking and contact with study authors.
We intended to include both randomised controlled trials (RCTs) and non-RCTs that compared ovarian cancer incidence after hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For assessment of surgical and hormonal safety, we included RCTs that compared hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications.
We used standard methodological procedures recommended by Cochrane. The primary review outcomes were ovarian cancer incidence, intraoperative and short-term postoperative complication rate and postoperative hormonal status. Secondary outcomes were total surgical time, estimated blood loss, conversion rate to open surgery (applicable only to laparoscopic and vaginal approaches), duration of hospital admission, menopause-related symptoms and quality of life.
We included seven RCTs (350 women analysed). The evidence was of very low to low quality: the main limitations being a low number of included women and surgery-related adverse events, substantial loss to follow-up and a large variety in outcome measures and timing of measurements.No studies reported ovarian cancer incidence after hysterectomy with opportunistic salpingectomy compared to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For surgery-related adverse events, there were insufficient data to assess whether there was any difference in both intraoperative (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.11 to 3.94; 5 studies, 286 participants; very low-quality evidence) and short-term postoperative (OR 0.13, 95% CI 0.01 to 2.14; 3 studies, 152 participants; very low-quality evidence) complication rates between hysterectomy with opportunistic salpingectomy and hysterectomy without opportunistic salpingectomy because the number of surgery-related adverse events was very low. For postoperative hormonal status, the results were compatible with no difference, or with a reduction in anti-Müllerian hormone (AMH) that would not be clinically relevant (mean difference (MD) -0.94, 95% CI -1.89 to 0.01; I = 0%; 5 studies, 283 participants; low-quality evidence). A reduction in AMH would be unfavourable, but due to wide CIs, the postoperative change in AMH can still vary from a substantial decrease to even a slight increase.
AUTHORS' CONCLUSIONS: There were no eligible studies reporting on one of our primary outcomes - the incidence of ovarian cancer specifically after hysterectomy with or without opportunistic salpingectomy. However, outside the scope of this review there is a growing body of evidence for the effectiveness of opportunistic salpingectomy itself during other interventions or as a sterilisation technique, strongly suggesting a protective effect. In our meta-analyses, we found insufficient data to assess whether there was any difference in surgical adverse events, with a very low number of events in women undergoing hysterectomy with and without opportunistic salpingectomy. For postoperative hormonal status we found no evidence of a difference between the groups. The maximum difference in time to menopause, calculated from the lower limit of the 95% CI and the natural average AMH decline, would be approximately 20 months, which we consider to be not clinically relevant. However, the results should be interpreted with caution and even more so in very young women for whom a difference in postoperative hormonal status is potentially more clinically relevant. Therefore, there is a need for research on the long-term effects of opportunistic salpingectomy during hysterectomy, particularly in younger women, as results are currently limited to six months postoperatively. This limit is especially important as AMH, the most frequently used marker for ovarian reserve, recovers over the course of several months following an initial sharp decline after surgery. In light of the available evidence, addition of opportunistic salpingectomy should be discussed with each woman undergoing a hysterectomy for benign indication, with provision of a clear overview of benefits and risks.
卵巢癌是所有妇科恶性肿瘤中死亡率最高的,总体五年生存率为30%至40%。在过去二十年中,越来越明显且更普遍地被接受的是,大多数卵巢癌起源于输卵管上皮,而非卵巢本身。这种范式转变为卵巢癌的预防带来了新的可能性。在因良性妇科指征进行子宫切除术时切除输卵管(也称为机会性输卵管切除术)可能会降低卵巢癌的总体发病率。除了疗效外,安全性至关重要,特别是考虑到机会性输卵管切除术的预防性本质。最重要的是手术不良事件形式的安全性和术后激素状态。因此,我们比较了子宫切除术加机会性输卵管切除术与单纯子宫切除术的益处和风险。
评估在因良性妇科指征接受子宫切除术的女性中,子宫切除术加机会性输卵管切除术与未行输卵管切除术的子宫切除术在预防卵巢癌方面的效果和安全性;感兴趣的结局包括上皮性卵巢癌的发病率、手术相关不良事件和术后卵巢储备。
2019年1月检索了Cochrane妇科与生育(CGF)小组试验注册库、CENTRAL、MEDLINE、Embase、PsycINFO、CINAHL以及两个临床试验注册库,并进行了参考文献核对和与研究作者的联系。
我们打算纳入随机对照试验(RCT)和非RCT,这些研究比较了因良性妇科指征接受子宫切除术的女性中,子宫切除术加机会性输卵管切除术与未行机会性输卵管切除术的子宫切除术后卵巢癌的发病率。为了评估手术和激素安全性,我们纳入了在因良性妇科指征接受子宫切除术的女性中,比较子宫切除术加机会性输卵管切除术与未行机会性输卵管切除术的子宫切除术的RCT。
我们采用了Cochrane推荐的标准方法程序。主要综述结局为卵巢癌发病率、术中和术后短期并发症发生率以及术后激素状态。次要结局为总手术时间、估计失血量、转为开腹手术的比率(仅适用于腹腔镜和阴道入路)、住院时间、绝经相关症状和生活质量。
我们纳入了7项RCT(共分析350名女性)。证据质量极低至低:主要局限性在于纳入女性数量少且手术相关不良事件少、大量失访以及结局测量和测量时间差异很大。没有研究报告在因良性妇科指征接受子宫切除术的女性中,子宫切除术加机会性输卵管切除术与未行机会性输卵管切除术的子宫切除术后卵巢癌的发病率。对于手术相关不良事件,由于手术相关不良事件数量非常少,没有足够的数据来评估子宫切除术加机会性输卵管切除术与未行机会性输卵管切除术的子宫切除术在术中(比值比(OR)0.66,95%置信区间(CI)0.11至3.94;5项研究,286名参与者;极低质量证据)和术后短期(OR 0.13,95%CI 0.01至2.14;3项研究,152名参与者;极低质量证据)并发症发生率上是否存在差异。对于术后激素状态,结果显示无差异,或抗苗勒管激素(AMH)降低但在临床上无相关性(平均差(MD)-0.94,95%CI -1.89至0.01;I² = 0%;5项研究,283名参与者;低质量证据)。AMH降低是不利的,但由于置信区间宽,术后AMH的变化仍可能从大幅下降到甚至略有增加。
没有符合条件的研究报告我们的主要结局之一——特别是子宫切除术加或未加机会性输卵管切除术后卵巢癌的发病率。然而,在本综述范围之外,越来越多的证据表明机会性输卵管切除术本身在其他干预措施中或作为绝育技术是有效的,强烈提示其具有保护作用。在我们的荟萃分析中,我们发现没有足够的数据来评估手术不良事件是否存在差异,因为接受子宫切除术加或未加机会性输卵管切除术的女性中不良事件数量非常少。对于术后激素状态,我们没有发现两组之间存在差异的证据。根据95%CI下限和AMH自然平均下降计算得出的绝经时间最大差异约为20个月,我们认为这在临床上无相关性。然而,结果应谨慎解释,对于非常年轻的女性尤其如此,因为术后激素状态的差异在她们中可能更具临床相关性。因此,有必要研究子宫切除术中机会性输卵管切除术的长期影响,特别是在年轻女性中,因为目前结果仅限于术后六个月。这一限制尤为重要,因为AMH是最常用的卵巢储备标志物,在手术后最初急剧下降后的几个月内会恢复。鉴于现有证据,应与每位因良性指征接受子宫切除术的女性讨论是否增加机会性输卵管切除术,并清楚地概述益处和风险。