ACM  >> Vol. 9 No. 3 (March 2019)

    UAE在妇产科疾病治疗中的新评价
    To Re-Evaluate UAE in the Treatment of Gynecological and Obstetric Diseases

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作者:  

陈 星,赖筱琍,朱含笑,叶丽娅,梅双双:温州医科大学附属浙江省台州医院妇产科,浙江 临海;
糜若然:天津医科大学总医院妇产科,天津

关键词:
子宫动脉栓塞术妇产科疾病治疗并发症Uterine Artery Embolisation The Diseases of Obstetrics and Gynecology Treatment Complication

摘要:

UAE (uterine artery embolisation)是属于血管介入的新的微创治疗方法,目前广泛应用于妇产科疾病领域,均取得了不错的治疗效果。本综述评价了UAE在妇产科疾病领域的应用范围、适应症、预后结局,其对生育的影响,经济费用,尤其是并发症的介绍,对有生育要求的、再次生育及妊娠的影响。提出:临床医生在合理应用UAE时,更应充分评估其并发症及其对生育功能的影响。

UAE (uterine artery embolization) is a new minimally invasive alternative procedure to surgery with reduced morbidity and mortality, and preserves the patient’s future fertility potential, which is widely used as a management of various gynecologic and obstetric abnormalities and has ob-tained good therapeutic effects. This review evaluates the applied range, indications, prognosis in obstetrics and gynecology disease, influence on fertility, economic cost, especially the complications of these diseases, and influence on fertility and pregnancy again of UAE. In short words, UAE must be carefully and rationally used, and the complications should be seriously evaluated and considered, especially potential impacts on fertility and pregnancy in child-bearing period in women.

1. 引言

UAE (uterine artery embolisation)是属于血管介入的新的微创治疗方法,应用导管器材和栓塞材料直接超选择至子宫动脉附近,在不损伤正常组织的前提下,达到止血的目的 [1] ,对妇产科疾病进行治疗,现在已广泛应用于妇产科良性疾病及恶性疾病的治疗,均取得明显的疗效。但是因其存在并发症及远期副作用,值得临床医生高度关注,本文就其临床治疗及其并发症进行评价。

2. UAE用于妇产科疾病

2.1. 产后出血

UAE是妇产科放射介入学的核心技术,自1979年Brown [2] 首次报道用于产后出血的治疗,随着放射介入学的发展,有条件的医院开展UAE治疗难治性产后出血已成为主要的治疗手段。针对前置胎盘造成的产前及产后出血UAE作为保守治疗的方法之一 [3] [4] [5] ,保留子宫保留生育功能,是保守治疗的一个选择。

2.2. 子宫肌瘤

子宫肌瘤是育龄期女性常见的生殖系统良性肿瘤,1995年法国学者Ravina [6] 首次报道应用UAE治疗子宫肌瘤,并取得与手术切除相当的效果,国内1996年牛惠敏 [7] 开始将UAE用于子宫肌瘤的治疗,也取得了与手术效果相当的疗效,因此在过去的20年,多中心试验及小样本试验均认为UAE是治疗子宫肌瘤的保守和安全微创治疗的方法。UAE治疗子宫肌瘤的3个月和6个月 [8] [9] ,肌瘤体积分别减小50%和67%,在随访期间,肌瘤的体积减少60%~65%。随访8.7个月 [10] ,89%的患者月经改善,96%的患者盆腔痛及压迫症状改善,随访4.4个月及12.3个月,子宫平均体积减少34%、48%,子宫肌瘤体积减少50%、78%。此后前瞻性研究也得出相似的结论,包括月经过多(83%)及痛经(77%)症状均有改善,50岁闭经发生率41%,40岁以下闭经发生率3% [11] [12] [13] ,另一项临床研究随访3年后发现,2.82%的患者需再次子宫肌瘤剔除,9.79%的患者需子宫切除术,1.83%的患者需再次UAE,28.6% (365/1278)患者闭经,45岁以上患者约78.9%,15.6%在40~45岁之间,5%在40岁以下,目前尚没有明显的证据显示UAE与闭经之间存在因果关系 [14] [15] [16] 。但是,需要选择合适的患者及充分的告知。UAE的住院时间比子宫肌瘤剔除手术及子宫切除手术均缩短,能更快地恢复日常活动。2014年Cochrane [17] 文献综述包括7个随机试验,对照组试验,应用UAE及在随后的2~5年内,15%~32%的患者还需要手术干预,因此最终UAE及手术的费用也是常常需要考虑的问题。

2.3. 子宫腺肌病

子宫腺肌病作为育龄期女性常见的良性疾病,因其严重的症状——经量增多及经期腹痛加重,不能耐受,子宫切除是彻底治疗的手段,目前保守治疗的手段日益增多,包括长效孕激素LNG-曼月乐环的应用,使患者保守治疗有了另一个选择,然而个别患者也存在曼月乐治疗无效,子宫射频消融治疗无效的情况。2008年Bratby和Walker [18] 等的临床回顾性分析及随访结果认为,UAE作为子宫腺肌病的治疗方法,88%的患者6个月后部分或者全部月经改善,1年后是79%,此外81%和80%的患者月经改善和肿块相关症状改善,包括有明显的子宫体积减小。2018 [19] 年的研究对保守治疗的117例子宫腺肌病行UAE治疗后,回顾性的研究认为:采用量化的VAS (面部表情评分系统)、UFS-QoL (生活质量评分)评分系统对患者的症状进行评分,在12个月中VAS中位评分从58降到17 (P < 0.001),QoL评分从42升到88 (P < 0.001),认为总的成功率为(102/115) 89%,痛经缓解达到(94/104) 94%,血红蛋白上升达到(91/104) 88%,6 (5%)例切除子宫,3例中度并发症是腹股沟区的血肿,3例亚急性并发症:1例子宫内膜炎,2例输尿管感染,2例出现非计划妊娠。因此认为UAE治疗子宫腺肌症与子宫切除相比较,被认为是可以保留子宫,住院时间短,微创,恢复快速。因此,UAE被认为是可供选择的治疗子宫腺肌病的保守治疗方法。

2.4. 剖宫产疤痕妊娠(Cesarean Scar Pregnancy, CSP)

剖宫产疤痕处妊娠是少见的剖宫产远期并发症之一,是异位妊娠的特殊类型,发病率0.45%,极具危险,随着我国二胎政策的放开,前次剖宫产术后的育龄期女性再次妊娠面临的一个危险,如不能早期诊断及时处理,常导致难以控制的大出血危及生命而切除子宫。UAE的合理应用 [20] ,栓塞时局部使用MTX或者5-FU,超声监测下刮宫,可提高了刮宫的准确性,避免过多损伤子宫内膜,尽力保护育龄期女性的生育能力。国内的2016年一项Meta分析荟萃了11个研究725例CSP患者 [21] ,认为UAE + 刮宫比MTX + 刮宫,在住院日,失血量及β-hcg降低方面均具有优势,因此,对于CSP患者,UAE能否作为首选,还需要大规模的前瞻性试验进一步验证。

2.5. 宫颈妊娠(Cervical Ectopic Pregnancy, CP)

作为特殊类型的异位妊娠,宫颈妊娠是异位妊娠中发病率很低但很危险的妊娠类型。宫颈妊娠占妊娠数的1:1000~95000,在异位妊娠中发生率 < 1%,同剖宫产疤痕妊娠一样具有危险性的妊娠类型,因在治疗过程中,宫颈收缩欠佳引致致命大出血,常需要切除子宫,因大部分为个案报道,目前尚无治疗的指南,因此CP更倾向于个体化治疗,早期诊断及时处理是关键,UAE作为治疗的一个方法 [22] [23] [24] ,配合全身MTX,UAE后刮宫清除宫颈妊娠产物,减少出血,保留子宫。

2.6. 前置胎盘

在前置胎盘及胎盘植入的患者,在减少出血及保留子宫的治疗中,UAE治疗方法优于切除子宫。可以在娩出胎盘前,术中UAE,达到减少产后出血,保留子宫的目的 [25] [26] 。

2.7. 宫颈癌的治疗

对于晚期宫颈癌难治性的出血,中度-重度的出血及贫血,其他治疗方法无效时,作为姑息性治疗方法,可选择UAE,使得患者病情得到缓解,改善生活质量。局部巨块型宫颈癌的新辅助治疗,术前选择化疗,可予动脉插管化疗,可以缩小肿块,术中减少出血,达到减少手术病率的作用。对于巨块型出血的宫颈癌患者,可以选择UAE控制出血 [27] ,巨块缩小,为彻底根治术做准备 [28] 。

3. UAE的并发症和远期副作用

UAE在妇产科良、恶性疾病方面显示出巨大的优势及显著的治疗效果,在基层医院也得到了开展,而一些并发症的出现同样引起了临床医生的关注。

3.1. 栓塞综合征

国外文献报道约有15%的患者出现典型的栓塞后综合征 [29] ,症状有腰腹痛,原因可能与子宫肌瘤或者子宫腺肌症患者组织缺血有关,Bradley等 [30] 认为疼痛与栓塞剂型有关。也有学者认为与栓塞后动脉痉挛,引起供血器官或者组织缺血也可以引起腰腹痛。

3.2. 发热、感染及败血症

发热是因为组织缺血坏死产生吸收热,部分因为栓塞剂和造影剂所致。一般不超过38.0℃,少数可达38.5℃应区分术后的吸收热和坏死感染,及时使用抗生素控制感染。有报道因前置胎盘行UAE [31] ,术后出现高热等感染所致的败血症,需积极的后续处理,挽救患者的生命。

3.3. 肺栓塞 [32] [33]

UAE因其有创操作可使动脉内膜损伤,造成血栓形成,另一个原因是UAE后,下肢制动,影响下肢血液循环,可以导致下肢静脉血栓形成,血栓随着血液循环栓塞肺动脉,有报道剖宫产后因产后出血 [34] ,UAE后造成急性肺栓塞。

3.4. 对生殖器官的影响

育龄期女性,UAE在有效治疗的范围内,所有的治疗方法均应考虑生育及卵巢功能。

3.4.1. 对月经的影响

UAE的保守目的是最大限度的保留女性生殖器官,而部分患者出现阴道不规则流血,阴道分泌物增多,阴道排液增多,月经减少甚至闭经等,UAE可以使子宫动脉内膜损伤卵巢动脉内膜的损伤导致子宫性闭经、卵巢性闭经,子宫性闭经发生率0.1%~0.4%,卵巢性闭经少见 [35] [36] ,对于育龄期保留生育功能的女性,子宫性闭经主要由于UAE后子宫内膜萎缩及子宫腔粘连造成,宫腔镜检查可以明确诊断,而患者生育能力受损。而卵巢性闭经,子宫内膜正常,可以选择激素替代治疗,恢复月经及生育功能。大部分患者上述症状都是暂时的可逆的,予以中药调理或者激素治疗。部分子宫肌瘤UAE后,子宫肌瘤与子宫内膜瘘口形成,因此表现出血阴道异常排液。

3.4.2. 子宫内膜炎症及子宫积脓

UAE最严重的并发症是子宫切除术,文献报道子宫肌瘤栓塞术后,肌瘤坏死引起细菌的逆行性感染,导致子宫感染,个别患者可发展为脓毒血症及败血症需积极治疗,挽救患者生命 [31] 。

3.4.3. 子宫破裂

Takeda J,等报道1例31岁因宫颈妊娠行UAE,术后5天和25天MRI评估,发现子宫底部下段后壁局部血运减少,在35岁妊娠32周时因自发性子宫底部下段后壁破裂行剖宫产术 [37] ,因此UAE术后MRI检测子宫局部缺血可能预示再次妊娠可能有子宫破裂的风险。

3.4.4. 子宫梗死

少见及不可控制的并发症,因产后出血(疤痕妊娠,前置胎盘、胎盘植入)等行UAE后,由于栓塞剂的大小与性质,侧枝循环的建立,以及栓子本身的游动,患者出现发热、月经过多、白带量多,考虑子宫发生梗死,盆腔CT进一步明确诊断,需手术切除子宫或者子宫次全切除术,同时因部分膀胱梗死,还需要切除膀胱 [38] 。部分患者UAE后可影响腰骶干神经丛的血供,影响神经的功能,从而引起下肢肌无力 [39] 。

3.5. 膀胱和输尿管的影响 [40] [41]

异位栓塞可以导致膀胱和输尿管缺血损伤,局部坏死,因此,还需要保护功能的治疗。

3.6. 对肠道功能的影响

研究报道 [42] 1例35岁未生育,出血多的子宫肌瘤患者行UAE后,予以预防性应用头孢唑林抗生素,出现腹痛、腹胀症状,最初认为是栓塞并发症,随后出现呼吸急促及心率加快,炎症指标及血乳酸均增高,CT和腹部X平片提示结肠扩张,结肠镜检查显示:肌层下的粘膜溃疡,最后行部分结肠切除及回肠末端造口术,术中发现穿孔周围是中毒性巨结肠,由于术前未做病理检查,因此认为是抗生素引起的伪膜性结肠炎。

3.7. 神经、皮肤损伤

常见于髂内动脉栓塞术时,闭孔神经和坐骨神经的血供受到影响,从而影响其功能,轻度损伤可以给予药物和物理营养支持治疗获得缓解,重度损伤恢复较慢,有时难以恢复。皮肤病损多发生在使用化疗药的患者,局部皮肤的红肿破溃 [43] ,需要治疗,可以局部封闭或者50%的硫酸镁湿敷。

3.8. 远期并发症

对妊娠和生育的影响:UAE最严重的并发症是对育龄期女性生育功能的影响。

3.8.1. 对子宫的影响

随着UAE时间的延长,部分患者出现缓慢的月经减少甚至闭经,研究发现在45岁以上的患者发生率较高,检查时发现宫腔粘连,子宫内膜萎缩,为子宫性闭经的又一个因素,需要引起临床医生的警惕。对于有UAE 病史的女性,再次妊娠时,应严密观察,预防自发性子宫破裂。育龄期女性生育史第一次剖宫产疤痕妊娠第一次UAE栓塞后,再次切口妊娠还需要UAE比例增高。

3.8.2. 对卵巢的影响

Kim等 [44] 的研究发现UAE术后,对围绝经期大于40岁的女性,卵巢的AMH恢复比小于40岁的女性更困难,年轻女性卵巢功能相对容易恢复。而当卵巢血管的细小分支同时被栓塞,引起卵巢血供不足,缺血坏死,性激素检查发现卵巢性闭经,此种闭经,可以通过激素替代治疗恢复月经周期。

3.8.3. 对生殖的影响

Goldberg [45] 等的回顾性研究,纳入53例UAE后妊娠,139例腹腔镜子宫肌瘤剔除术后妊娠,评估UAE与腹腔镜治疗子宫肌瘤对生育的影响,发现,UAE比腹腔镜手术更易引起早产及先露异常。Homer and Saridogan [46] 的研究277例UAE后妊娠,与子宫肌瘤剔除术后比较,有较高的流产、剖宫产、及产后出血的比例。而其他的研究认为并发症的发生UAE与手术效果相当。Mohan et al. [47] 在2013年的综述文章中指出UAE后的妊娠与早产与普通人相当,流产的发生率与未治疗的子宫肌瘤接近。而2014年更新的Cochrane [17] 综述认为手术切除比UAE更能改善生育。因此对有生育要求的子宫肌瘤患者,UAE更应该慎重。

3.8.4. 对性功能的影响

有研究认为神经缺血性损伤可使依赖于子宫收缩才能体验的子宫阴道性欲高潮受到影响,子宫肌瘤UAE术后引起性欲减低 [48] 。

4. 结论

总之,UAE作为妇产科疾病保守治疗的方法得到了临床广泛的推广及应用,取得了治疗效果,同时随着时间的延长,临床并发症及副作用也不断的出现,应当引起临床医生的注意,术前需充分选择合适的疾病人群,充分的病情告知,把握UAE临床应用的适应症,术中细心操作,术后严密观察病情变化,及时处理并发症。未来如何改进UAE,使之能安全应用和推广UAE成为临床研究的重点问题。

文章引用:
陈星, 赖筱琍, 朱含笑, 叶丽娅, 梅双双, 糜若然. UAE在妇产科疾病治疗中的新评价[J]. 临床医学进展, 2019, 9(3): 365-372. https://doi.org/10.12677/ACM.2019.93056

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