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. 2019 Dec 18;51(6):1052–1055. [Article in Chinese] doi: 10.19723/j.issn.1671-167X.2019.06.013

原发性女性膀胱出口梗阻的手术疗效随访及其发病机制

Outcome of surgical management and pathogenesis of female primary bladder neck obstruction

Xiao-peng ZHANG 1, Wei-yu ZHANG 1, Fei HUO 2, Hao HU 1, Qi WANG 1, Ke-xin XU 1,△
PMCID: PMC7433601  PMID: 31848503

Abstract

Objective

To investigate the effect of transurethral resection of bladder neck on primary female bladder neck obstruction and to analyze the expression of three kinds of sex hormone receptor (SR) in female bladder neck tissues diagnosed as primary bladder neck obstruction by the immunochemistry and statistics.

Methods

The clinical data of 40 female patients, admitted into Peking University People’s Hospital for difficulty of voiding during Oct.2008 and Dec.2013 and eventually diagnosed as bladder outlet obstruction (BOO) by urodynamics, were retrospectively reviewed. BOO was defined as a maximum flow rate (Qmax) less than 12 mL/s together with a detrusor pressure at maximum flow rate (Pdet Qmax) more than 25 cmH2O in urodynamic study in the absence of neurological disorders. Diagnosis was confirmed by the cystoscopy. Preoperative and postoperative AUASS scores were recorded and analyzed for observation of curative effects and complications. The immunochemical expression of SR of primary female bladder neck obstruction (PBNO) tissues and normal control was examined and applied to statistical analysis.

Results

There were significant changes postoperatively in voiding scores, storage scores and total scores (P<0.001). Postoperatively, 1 patient newly presented with overactive bladder (OAB), 4 patients newly presented with hematuria, and 1 patient underwent cystostomy. The symptoms of urinary retention with overflow incontinence in 2 patients disappeared after the surgery, and 3 patients complicated with OAB complained without urgency. In addition, pre-hydronephrosis improved postoperatively in six patients. The subjective satisfactory rate to the surgery of TURBN was 77.5% (31/40). Sex hormone receptor, including androgen receptor (AR), estrogen receptor (ER), progesterone receptor (PR), expressed in both bladder neck tissues of normal control and PBNO patients. In PBNO group, the expression of PR was significantly lower than that of control group (P<0.05), while the other 2 SRs expressed with no significantly statistical difference. PBNO patients were divided into 2 groups, according to their symptoms scores, and the expression of SRs showed no significant differences among the mild, moderate and severe groups (P>0.05).

Conclusion

The transurethral bladder neck resection is valid in treating with female PBNO patients, with rarely occurrence of complications. PR expressed less in the female bladder neck tissues, and is possibly correlated with the occurrence of female PBNO.

Keywords: Bladder neck obstruction, Transurethral resection of bladder neck, Sex hormone receptor, Immunohistochemistry

在下尿路症状女性患者中,膀胱出口梗阻的发生率约为2.7%~8.0%[1,2,3]。与男性不同的是,女性排尿通常是通过松弛盆底组织完成,在整个排尿过程中,逼尿肌的压力并没有明显升高,因此膀胱出口梗阻在女性中的发病率相对男性较低。此外,女性典型下尿路症状(如尿流缓慢、尿等待、排后滴沥)的发生率较男性低。女性患者通常表现出储尿期的症状,如尿频、尿急及急迫性尿失禁等[4,5]。通过对患者的临床症状进行分析,并完善尿动力学检查、膀胱镜检,在排除神经源性疾病的前提下,尿动力学检查提示最大尿流率时逼尿肌压大于25 cmH2O(1 cmH2O=0.098 kPa), 同时最大尿流率小于12 mL/s,考虑为膀胱出口梗阻。通过膀胱镜检查发现膀胱颈后唇抬高,膀胱内口缩窄,最终确诊为女性膀胱出口梗阻。原发性女性膀胱出口梗阻的治疗包括非手术和手术治疗,非手术治疗包括药物治疗、留置尿管等,手术治疗包括尿道扩张、膀胱颈切开等[6,7]。既往的研究已经证实了药物、尿道扩张对部分女性膀胱出口梗阻有效。对于药物反应性较差,尿道扩张效果不佳的患者,以及不愿意接受间歇清洁导尿的患者,经尿道膀胱颈切开术(transurethral resection of bladder neck, TURBN)是一个较好的治疗选择。目前国内外学者关于TURBN的长期手术疗效随访并不多见。女性原发性膀胱出口梗阻(primary bladder neck obstruction, PBNO)发病机制尚未明确阐明。近年来,许多学者认为性激素水平可能调节女性尿道周围腺体增生,产生与男性良性前列腺增生同样的症状[8,9]。本研究通过对患者进行临床随访,旨在了解经尿道膀胱颈切开术对女性膀胱出口梗阻的长期手术疗效,为临床应用及适应证选择提供依据。同时通过分析女性膀胱颈组织中性激素受体(sex hormone receptor, SR)的表达,探究PBNO可能的发生机制。

1. 资料与方法

1.1. 研究对象

选择2008年10月至2013年12月因排尿困难入北京大学人民医院住院治疗,而最终诊断为原发性膀胱出口梗阻的女性患者共40例。

纳入标准:(1)由于排尿困难初次住院;(2)尿动力学检查最大尿流率Qmax<12 mL/s, 最大尿流率时逼尿肌压PdetQmax>25 cmH2O;(3)尿道膀胱镜检查发现有膀胱颈后唇抬高,膀胱内口缩窄。

排除标准:(1)神经源性病变导致的下尿路症状者;(2)逼尿肌括约肌协同失调者;(3)尿失禁术后膀胱出口梗阻、盆腔脏器脱垂、尿道狭窄、尿道肿瘤者;(4)既往因膀胱出口梗阻行TURBN者;(5)入院后未行治疗或资料不完整者。

1.2. 组织标本

得到女性膀胱颈标本共54例,其中女性原发性膀胱出口梗阻标本47例(7例患者因需要取了两份标本),根据Blaiva-Groutz列线图进一步分为13例中重度梗阻和34例轻度梗阻;对照组标本7例,为膀胱颈活检取得的正常膀胱颈组织或根治性膀胱切除术取得的切缘阴性的膀胱颈组织。

1.3. 手术

TURBN采用Olympus标准电切镜(功率100 W), 用针状电极于5、7点处切开后尿道,长度为尿道的1/3,深达浆膜层(肌肉外层), 注意避免伤及括约肌。用环状电极将5、7点之间的隆起组织也一并切除,使后尿道与膀胱三角区平齐。术后留置尿管48~72 h。

1.4. 免疫组织化学检查

抗体购于Abcam公司,按说明书使用,实验方法见参考文献[10]。

1.5. 相关评估

进行临床伴随症状评估,包括膀胱过度活动症(overactive bladder, OAB)[11]、压力性尿失禁[12]、膀胱逼尿肌肌力下降[13]等。所有患者术前均采用Laborie尿动力学检查设备进行尿动力学检查,所有患者术前均进行膀胱镜检查。

应用AUAss评分,分别评价术前、术后患者的储尿期症状评分,排尿期症状评分以及生活质量评分。明确术后评分变化,以及患者对手术的主观满意程度。

受体阳性判断及半定量测定: 光镜下观察平滑肌细胞,按照强度将染色分为0(无染色)、1(弱染色)、2(中度染色)、3(强染色);按照阳性染色区域所占面积分为1(0%~25%)、2(25%~50%)、3(51%~75%)分、4(>75%)分。分值=染色强度×阳性所占面积;分值≥4,判断为阳性;分值<4,判断为阴性。

1.6. 统计学分析

应用SPSS 16.0统计学软件,在单因素分析中记数资料以例数和百分比表示,组间的比较应用卡方检验;计量资料经正态性检验,符合正态分布的应用t检验。P<0.05认为差异具有统计学意义。

2. 结果

随访时间(35.70±16.50)个月,平均年龄(59.72±13.94)岁,平均体重指数 (24.16±4.24) kg/cm2,术前平均肌酐水平(59.10±3.54) μmol/L。

术前有9位患者存在膀胱过度活动症状,有3位患者存在压力性尿失禁症状,有6位患者存在膀胱逼尿肌肌力下降,有7位患者存在肾积水,有6位患者术前留置尿管,有1位患者术前留置膀胱造瘘。

术前与术后相关评分的比较见表1,8例术后出现了压力性尿失禁,1例术后出现了膀胱过度活动症,4例术后出现短期血尿,1例术后仍留置膀胱造瘘管。2例术前有充溢性尿失禁的患者术后症状消失,3例术前伴有膀胱过度活动症的患者术后症状改善,6例术前伴有肾积水的患者术后肾积水减少或消失。40例患者中有31例对手术效果满意,满意率为77.5%。

1.

患者术前术后评分比较

AUAss comparison before and after TURBN

Items Before operation After operation P
AUAss, American Urological Association symptom score; Qol, quality of life.
AUAss storage phase 13.38±4.68 7.48±4.69 <0.001
AUAss urinating phase 11.85±3.92 5.95±3.40 <0.001
AUAss total score 25.22±7.47 13.42±4.99 <0.001
QoL 5.22±0.95 2.17±1.62 <0.001
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免疫组织化学染色发现ER、PR、AR在正常膀胱颈和PBNO患者组织中均有表达(图1),PBNO膀胱颈组织中,PR的阳性率低于正常对照组,差异有统计学意义(P<0.05)。按症状程度分组后,中重度的PBNO患者3种性激素受体的阳性率与轻度患者差异无统计学意义(P>0.05)。

1.

1

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免疫组织化学染色结果(×400)

3. 讨论

女性膀胱出口梗阻患病率较男性低,原发性女膀胱出口梗阻多是通过尿动力学检查与膀胱镜检进行诊断,治疗方法包括药物、尿道扩张、间歇清洁导尿、经尿道膀胱颈切开术等。对于女性原发性膀胱出口梗阻,TURBN是主要的手术方法。

在进行TURBN时,需要着重关注两个问题。第一个关键点是对横纹肌的精确识别,损伤横纹肌将有可能导致尿失禁。通过膀胱镜检可以看到横纹肌位于女性尿道二分之一处。为避免尿失禁的发生,最大切割长度应不超过近端尿道的1/3。第二个关键点是切除的深度。与男性不同,女性的膀胱颈相对较薄,临近阴道前壁,切除时动作应尽量轻柔,避免切除过深。本组病例,术后并未出现阴道前壁穿孔,出现尿失禁的病例多数在半年内恢复。因此切除过深可能导致压力性失禁,但是切除不足又会影响手术效果[14]。本组病例由同一位主任医师执刀手术,排除了操作手法不同引起的差异。

关于经尿道膀胱颈切开的具体术式还在讨论之中。12点方向切开,这样可以避免阴道壁的穿孔,但术后并发症的发生和手术获益尚不明确。Jin等[15]报道了3、6、9、12点钟方向的切开术式,5年内的主观和客改善程度都很明显,患者均不需要再次入院行手术治疗。Zhang等[16]报道了5、7点钟方向的切开方式,其中有3例患者术后出现了膀胱阴道瘘,这3例患者经过膀胱阴道瘘的修补术后没有再出现梗阻的症状。本研究采取的术式是5、7点钟方向切开膀胱颈。

本研究所有患者均进行了经尿道膀胱颈切开,术中切除环状纤维至膀胱颈外部的脂肪层,术后最常见的并发症是压力性尿失禁和血尿,其中有1例出现血尿的患者再次入院行电凝止血治疗。客观上,术后肾积水及其他合并症的情况较术前好转。主观上来讲,患者术后储尿期症状、排尿期症状评分和总评分均有了明显改善[17]。此外,本研究的患者对术式的主观满意程度也较高(77.5%)。

研究证实,雌激素受体多分布在鳞状上皮中,而孕激素受体表达在上皮下,大多是在未接受激素替代治疗的围绝经期女性中,这说明女性的下尿路是雌激素受体及孕激素受体的重要靶器官,也为激素替代治疗提供了依据[18,19]。本研究中,原发性女性膀胱出口梗阻患者雌激素受体的阳性率为42.5%(20/47),孕激素受体的阳性率为29.8%(14/47);在正常对照组中,雌激素受体的阳性率为71.4%(5/7),孕激素受体的阳性率为71.4% (5/7);原发性女性膀胱出口梗阻患者的孕激素受体的阳性率明显降低。

有研究提示[20],孕激素可以通过松弛括约肌起到扩充膀胱容量、提高膀胱顺应性的作用。动物实验可证实孕激素通过与孕激素受体结合,在cGMP/NO 通路中,激活BKCa 和KATP 通道,起到松弛膀胱颈部平滑肌的作用。而本研究结果提示原发性女性膀胱颈患者组与正常对照组相比,孕激素的阳性率较正常对照组低,推测孕激素与孕激素受体结合就会减少,孕激素的松弛膀胱颈部平滑肌的作用就会变弱,导致女性膀胱颈的持续收缩,继而出现梗阻症状。

综上所述,女性经尿道膀胱颈切开能有效治疗女性原发性膀胱出口梗阻,并发症相对较少。孕激素受体可能与女性PBNO 的发生相关。

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