Article(id=1208516101143655394, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208516099369464789, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2022.01.0097, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1618848000000, receivedDateStr=2021-04-20, revisedDate=null, revisedDateStr=null, acceptedDate=1620662400000, acceptedDateStr=2021-05-11, onlineDate=1766062291656, onlineDateStr=2025-12-18, pubDate=1643299200000, pubDateStr=2022-01-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766062291656, onlineIssueDateStr=2025-12-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766062291656, creator=13701087609, updateTime=1766062291656, updator=13701087609, issue=Issue{id=1208516099369464789, tenantId=1146029695717560320, journalId=1189873630562394117, year='2022', volume='47', issue='1', pageStart='1', pageEnd='101', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766062291230, creator=13701087609, updateTime=1766062975431, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208518969208738485, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208516099369464789, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208518969208738486, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208516099369464789, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=97, endPage=101, ext={EN=ArticleExt(id=1208516101722469355, articleId=1208516101143655394, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Research progress in etiology, diagnosis and treatment of female urethral stricture, columnId=1190243275882729994, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Female urethral stricture is considered to be one of the important causes of female lower urinary tract symptoms, but it is relatively rare in clinical practice and lacks relevant diagnostic and therapeutic guidelines. In the past, urethral dilation was used as the first-line treatment option for this disease. However, due to its low success rate, high recurrence rate of stricture, and with the development of research on the structure of the female urethra, a variety of urethroplasty procedures have been applied. The success rate of urethroplasty is high, but it is not clear which procedure is more superior. This article reviews the research progress in the etiology, diagnosis and treatment of female urethral stricture to provide a reference for urologists to carry out a variety of treatment methods, and to promote the clinical application of related diagnosis and treatment.

, correspAuthors=Wei-Bing Shuang, authorNote=null, correspAuthorsNote=
*E-mail:
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女性尿道狭窄被认为是引起女性下尿路症状的重要原因之一,但其在临床较为罕见,缺乏相关诊断及治疗指南。既往尿道扩张术为该病的一线治疗方式,但成功率较低,狭窄复发率较高。随着对女性尿道结构研究的深入,多种尿道成形术相继应用于临床。尿道成形术成功率较高,但何种术式更为优越尚未明确。本文对女性尿道狭窄的病因、诊断及治疗研究进展进行综述,以期为泌尿外科医师开展多种治疗方式提供参考,并推进相关诊断及治疗方式在临床中的应用。

, correspAuthors=双卫兵, authorNote=null, correspAuthorsNote=
双卫兵,E-mail:
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颉红杰,硕士研究生,主要从事泌尿外科疾病的临床研究

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颉红杰,硕士研究生,主要从事泌尿外科疾病的临床研究

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颉红杰,硕士研究生,主要从事泌尿外科疾病的临床研究

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女性尿道狭窄的病因及诊疗研究进展
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颉红杰 1 , 双卫兵 2, *
解放军医学杂志 | 综述 2022,47(1): 97-101
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解放军医学杂志 | 综述 2022, 47(1): 97-101
女性尿道狭窄的病因及诊疗研究进展
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颉红杰1, 双卫兵2, *
作者信息
  • 1山西医科大学第一临床医学院,太原 030001
  • 2山西医科大学第一医院泌尿外科,太原 030001
  • 颉红杰,硕士研究生,主要从事泌尿外科疾病的临床研究

通讯作者:

双卫兵,E-mail:
Research progress in etiology, diagnosis and treatment of female urethral stricture
Hong-Jie Xie1, Wei-Bing Shuang2, *
Affiliations
  • 1The First Clinical Medical College of Shanxi Medical University, Taiyuan 030001, China
  • 2Department of Urology, the First Hospital of Shanxi Medical University, Taiyuan 030001, China
出版时间: 2022-01-28 doi: 10.11855/j.issn.0577-7402.2022.01.0097
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女性尿道狭窄被认为是引起女性下尿路症状的重要原因之一,但其在临床较为罕见,缺乏相关诊断及治疗指南。既往尿道扩张术为该病的一线治疗方式,但成功率较低,狭窄复发率较高。随着对女性尿道结构研究的深入,多种尿道成形术相继应用于临床。尿道成形术成功率较高,但何种术式更为优越尚未明确。本文对女性尿道狭窄的病因、诊断及治疗研究进展进行综述,以期为泌尿外科医师开展多种治疗方式提供参考,并推进相关诊断及治疗方式在临床中的应用。

女性尿道狭窄  /  病因  /  诊断  /  治疗

Female urethral stricture is considered to be one of the important causes of female lower urinary tract symptoms, but it is relatively rare in clinical practice and lacks relevant diagnostic and therapeutic guidelines. In the past, urethral dilation was used as the first-line treatment option for this disease. However, due to its low success rate, high recurrence rate of stricture, and with the development of research on the structure of the female urethra, a variety of urethroplasty procedures have been applied. The success rate of urethroplasty is high, but it is not clear which procedure is more superior. This article reviews the research progress in the etiology, diagnosis and treatment of female urethral stricture to provide a reference for urologists to carry out a variety of treatment methods, and to promote the clinical application of related diagnosis and treatment.

female urethral stricture  /  etiology  /  diagnosis  /  treatment
颉红杰, 双卫兵. 女性尿道狭窄的病因及诊疗研究进展. 解放军医学杂志, 2022 , 47 (1) : 97 -101 . DOI: 10.11855/j.issn.0577-7402.2022.01.0097
Hong-Jie Xie, Wei-Bing Shuang. Research progress in etiology, diagnosis and treatment of female urethral stricture[J]. Medical Journal of Chinese People’s Liberation Army, 2022 , 47 (1) : 97 -101 . DOI: 10.11855/j.issn.0577-7402.2022.01.0097
女性尿道狭窄(female urethral stricture,FUS)是一种临床罕见疾病,多项研究发现,在有下尿路症状的女性患者中,膀胱出口梗阻(bladder outlet obstruction,BOO)的发病率为2.7%~8.0%,而约有10%的梗阻性排尿患者存在解剖性尿道狭窄[1-3]。虽然FUS发病率较低,但由于患者无法有效排空膀胱,通常出现下尿路症状,如尿频、尿急、排尿踌躇、排尿无力、排尿后滴沥及夜尿增多,部分患者甚至出现尿失禁和反复的泌尿系感染[3-5],严重影响生活质量。目前,临床对于该疾病的研究多为小样本研究,缺乏相对统一的诊断及治疗原则。本文结合女性尿道结构的特点,对FUS的病因及现有治疗方式进行阐述,以拓展其临床治疗手段。
成年女性的尿道具有短、宽、直的特点,长3~5 cm,直径约0.6 cm;尿道肌层由内侧纵行肌层和外侧环形肌层构成,纵行肌层与逼尿肌相延续,在膀胱颈处发育较差;平滑肌向远端尿道显著变薄,以纤维环结束。尿道平滑肌的表面是尿道外括约肌,该肌延伸尿道全长且在尿道中1/3处最厚,以靠近耻骨侧较为显著,这种肌组织构型被描述为马蹄形/ω形。阴蒂组织支持尿道背侧,神经血管束通常沿着坐骨耻骨支走行,远离尿道[6]。因此,女性尿道的生理结构决定了其不易发生狭窄,但由于位置较深,邻近组织解剖结构较复杂,增加了手术治疗的难度。
流行病学研究发现,特发性因素、医源性因素(如膀胱镜、扩张尿道等经尿道操作及放疗)、创伤性因素(如产伤、骨盆骨折等)、反复的尿道感染、阴道萎缩及扁平苔藓等多种因素与FUS的发生发展相关[3,7]。此外,绝经、慢性移植物抗宿主病等也参与了FUS的形成[8-9]。新近研究发现,特发性因素仍为FUS最主要的病因,占比达51.3%,其次为医源性因素(32.8%)。值得注意的是,尿道扩张既可作为尿道狭窄的治疗方法之一,同时也会导致FUS[10-11]
由于FUS较为少见,临床表现无特异性,目前仍缺乏标准的定义及具体的诊断标准。因此,通常需要较为系统的检查以明确FUS的狭窄部位、长度及狭窄程度,并区分解剖狭窄与括约肌协同失调、排尿功能障碍或外部压迫相关的功能性或生理性梗阻。近期有学者提出,将FUS定义为在有下尿路症状的患者中,不能留置大于F14号尿管,并经影像学或内镜证实为尿道狭窄[12]
对于拟诊断为FUS的患者,妇科检查必不可少,可直接检出尿道狭窄和硬化性苔藓、盆腔器官脱垂或尿道周围异常的存在,着重评估可能用于尿道重建的局部组织质量[13],明确患者是否可行尿道成形术。
部分FUS患者常以排尿踌躇、排尿无力为主要表现,产生尿潴留、膀胱结石及肾积水等严重并发症,常需施行留置导尿或间歇性清洁导尿(intermittent clean catheterization,ICC)以缓解相关症状。ICC还可诊断绝对性狭窄,将FUS与膀胱、尿道功能性病变相鉴别。绝对性尿道狭窄患者一般不能留置大于F14号尿管,而膀胱尿道功能性改变则可留置大于F14号的尿管。因此,ICC可在为患者在缓解症状的同时提供诊断依据,但存在伴随感染及进一步加重狭窄的风险。目前推荐将女性尿道不能留置大于F14号尿管作为FUS的特异性诊断标准之一[12,14]
对于可疑尿路梗阻的患者,行尿流率测定可对FUS做出初步诊断,与逼尿肌括约肌协同等疾病相鉴别。在进行尿流率测定时,要求排尿量在150~500 ml,以降低人为因素或逼尿肌过度牵拉所产生的影响。健康男性最大尿流率(Qmax)>15 ml/s,而女性Qmax<12 ml/s时可考虑下尿路梗阻或逼尿肌收缩力减低。下尿路梗阻时,尿流率曲线表现为伴随排尿时间延长的低平曲线[15-16]。膀胱残余尿测定有助于了解膀胱功能、判断尿道梗阻程度。目前尿流率及膀胱残余尿测定除应用于尿道狭窄的初步诊断外,还可用于评估FUS患者的术后恢复情况。
对于可通过膀胱镜的患者可在直视下确诊尿道狭窄,观察狭窄部位、狭窄程度及长度[17]。但当狭窄段无法通过膀胱镜时,则无法提供狭窄近端的相关情况,此时需结合其他影像学检查。
逆行尿路造影是男性尿道狭窄的标准评价方式。部分研究结果显示,对于FUS,逆行尿路造影因不能持续填充尿道并显示狭窄而存在一定局限性[4]。排泄膀胱尿道造影(voiding cysto-urethrography,VCUG)通过耻骨上造瘘管或者小口径导管将造影剂注入膀胱,可评估下尿路功能,提供狭窄位置、长度、部位等信息,表现为狭窄近端出现扩张,并在狭窄部位突然变窄的“酒杯样”图像,并能明确可能存在的膀胱憩室及膀胱输尿管反流[18]。盆腔MRI在FUS中并非常规检查,如果怀疑尿道或局部组织异常、存在恶性肿瘤及尿道憩室可能时,可行盆腔MRI检查排除相关诊断并对制定手术方案提供指导。
FUS在明确诊断后需尽早治疗,以解除梗阻及相关症状,同时避免产生尿失禁、性功能障碍等多种并发症[19]。目前尿道扩张术、尿道内切开术、瓣膜和移植物尿道成形术,以及组织工程尿道内支架置入术等多种方式已应用于FUS的临床治疗,不同手术方式的结果差异显著,据报道成功率为14%~100%[12,20]
尿道扩张术可用于尿道外口、远端及中段尿道轻度狭窄的治疗[14],也可用于女性反复泌尿系感染、膀胱出口梗阻及吊带术后排尿困难等相关疾病的治疗[21]。扩张前需明确狭窄部位、狭窄长度及是否为再次扩张等尿道狭窄的基本状况,扩张后需观察患者症状缓解程度及是否复发。女性尿道扩张时使用Hegar尿道探子或宫颈扩张器等器械扩张尿道,迫使狭窄部位黏膜撕裂,尿液浸润狭窄部位,形成新的尿道口径,从而保持尿路通畅。尿道扩张术能够缓解大部分患者一定时间范围内的排尿困难症状,但需要注意以下问题:(1)尿道扩张成功率低、复发率高且复发率随着扩张次数的增多而逐渐增高,女性尿道扩张成功率低于50%,男性低于60%;对男性患者进行研究发现,当进行3次及以上的扩张时,尿道狭窄的复发率可达100%且复发间隔更短;(2)术后狭窄复发患者不宜再行尿道扩张术,因反复扩张导致的黏膜糜烂及周围出血可加重局部纤维化,降低后期尿道成形术的成功率[10-11,22-23];(3)尿道扩张术可产生出血、疼痛、假道形成及感染等并发症[21]。目前随着尿道重建手术的发展,尿道扩张术在FUS治疗中的地位逐渐下降,但部分学者提倡对尿道扩张2次后狭窄复发的患者再进行尿道重建,对于因局部黏膜不适合手术或拒绝手术的患者,姑息性的自我扩张是保持尿道直径的合理选择[6]
尿道外口与远端尿道狭窄可采用尿道口与尿道内切开术,能明显缓解患者的症状。尿道内切开术具有手术难度低、手术时间短等优点[24],但与尿道扩张术相比,其发生尿失禁、性功能障碍及尿道阴道瘘等并发症的风险显著增高。在男性尿道狭窄中,小于1.5 cm的孤立性尿道狭窄较为适用尿道内切开术,当狭窄段>1.5 cm时其成功率不足20%。研究发现,行尿道外口切开术的FUS患者感染及排尿梗阻等相关症状显著缓解[25-26]
FUS患者多选择尿道扩张术作为初始治疗方式,但常伴随较高的复发率,对于症状未缓解或复发的患者可选择尿道重建术。近年来描述的女性尿道重建术包括切除狭窄段的尿道端端吻合术与使用皮瓣、黏膜移植物的尿道成形术。多项研究发现,尿道重建术有效率可达80%以上,但因女性尿道相对较短,尿道括约肌分布于整个尿道,术后尿失禁、尿道阴道瘘及神经感觉功能障碍的风险相对较高。根据狭窄段的分布、局部组织基本状况、外科技术的掌握程度可选择相应的术式。
由于女性尿道较短,对狭窄患者行尿道端端吻合术具有一定的挑战性。尿道端端吻合术可用于尿道损伤较小及特定的尿道狭窄患者,如盆底吊带引起的尿道糜烂,女性中段尿道损伤后行一期尿道缝合,术后排尿体验有所改善,但存在发生压力性尿失禁及远端尿道断流的风险[27]。目前在女性尿道中段狭窄患者中行一期尿道端端吻合术的证据很少。对于骨盆骨折引起的尿道断裂也可行尿道端端吻合术,可在降低尿道瘢痕狭窄风险的同时建立正常的生理尿道[28]。此外,Rosenblum等[29]对于极远端尿道(距尿道口0.5~1 cm)狭窄采取一期切除和尿道口成形术,将狭窄近端黏膜间断缝合于健康的尿道组织以防止黏膜回缩,同时切除远端尿道,然后将健康的尿道黏膜向远端缝合至阴道黏膜,获得了良好的疗效。
尿道成形术多适用于尿道扩张术后复发的患者,其成功率高,能显著增高尿流率、减少残余尿量。依据移植物的不同,尿道成形术可分为局部带蒂皮瓣成形术和黏膜移植物成形术;根据手术入路的不同,尿道成形术可分为腹侧入路和背侧入路(腹侧为向后指向阴道的部分,背侧为靠近耻骨一侧)。Sarin等[12]的系统性研究发现,带蒂皮瓣、阴道/阴唇黏膜移植和口腔黏膜移植等不同形式的尿道成形术均显示出较好的成功率(86%~93%)。目前尚无证实移植物及手术入路优越性的大样本研究,FUS的尿道成形术式选择依据包括狭窄的位置和长度、局部或移植物组织的可用性以及临床医师对术式的熟练程度。
颊黏膜是尿道成形术的理想移植物,特别适用于局部瘢痕严重和绝经后局部皮瓣黏膜发生萎缩的狭窄患者。与皮瓣相比,颊黏膜来源相对充足、易获取、弹性较好,且具有与尿道黏膜相似的生物学特性,即无毛、良好的抗菌性能,以及适用于潮湿环境等,但因其自身缺少血管组织,生存能力较大程度上取决于局部组织环境[30-31]。Mukhtar等[15]对平均狭窄长度为2 cm的22例FUS患者行颊黏膜尿道成形术,术后随访6个月发现,95.5%的患者获得了较好的治疗效果,尿流率得到显著改善,残余尿量从100 ml降至15 ml,仅1例发生了轻度压力性尿失禁,通过非手术治疗后治愈。既往临床上多采用颊黏膜移植物,近年来舌黏膜移植物的应用逐渐增多,以避免颊黏膜移植潜在的腮腺导管和局部神经损伤风险。
生殖器黏膜较早应用于FUS患者,Osman等[6]随访25例生殖器黏膜移植患者发现,术后成功率为80%,最大尿流率及排尿后残余量得到显著改善。但生殖器黏膜移植具有较大的局限性:伴随绝经后雌激素的改变,阴道黏膜发生萎缩,不适用于FUS的治疗;对于尿道重建后的患者,可能会导致FUS复发。对于阴道自身存在病变或硬化性苔藓导致的FUS患者,不适合采用生殖器黏膜进行尿道重建[4,14]
阴道或阴唇带蒂皮瓣是一种介于阴道黏膜与尿道周围筋膜之间的先进皮瓣,自身血运良好,对局部组织的要求较低(相较黏膜移植物)。对中段或狭窄段<2 cm的FUS患者,可选用此类尿道成形方法。Hajebrahimi等[17]对14例尿道中、远端狭窄患者行皮瓣手术,术后最大尿流率为(15.82±3.27) ml/s,残余尿量下降至(27.35±18.76) ml。West等[20]对阴道皮瓣相关的5项研究进行分析,结果显示,共55例患者行腹侧或背侧入路带蒂皮瓣手术,总体成功率达91%。与阴道或阴唇黏膜移植物类似,放疗、雌激素水平的改变均会限制带蒂皮瓣的应用。
脱细胞真皮基质(acellular dermal matrix,ADM)是通过生物工程技术将异体或异种真皮组织去除具有免疫源性的细胞成分而得到的胶原聚集体。初始ADM经过生物、化学及物理方法改性处理,具有合适的孔隙、力学强度、结构稳定性及生物相容性,将ADM移植于创面修复时,可扮演真皮模板的角色,能够为细胞生长提供支架,促进细胞生长及血管化[32-33]。ADM移植能够避免病理性增生及瘢痕形成,减少狭窄复发,目前已应用于尿道成形术、输尿管手术及盆底悬吊等多种泌尿外科重建手术中,在生物医药材料领域具有良好的应用前景。
对既往尿道成形手术的系统研究发现,背侧入路尿道狭窄修复成功率为88%,而腹侧入路可达95%[12]。但这并不代表腹侧入路手术在临床上更受欢迎,对于何种入路更为可靠应基于局部解剖特点进行判断。女性尿道背侧具有更为丰富的尿道括约肌、局部神经及血管组织,采取背侧入路能够为移植物提供血管良好的移植床及机械支撑,避免憩室和瘘管形成,但对尿道括约肌和阴蒂的神经血管供应存在较高的风险。相较背侧入路,阴道前壁的腹侧入路结构简单,行腹侧入路手术能够避免压力性尿失禁和性功能损伤,但会增加尿道阴道瘘的发生风险,以及破坏可能的盆底吊带手术路径[3,34-35]
组织工程尿道支架置入技术是将具有活性的组织细胞与生物材料相结合,体外构建组织与器官,从而达到修复组织或器官的目的。组织工程尿道支架包括脂肪干细胞附着于聚乳酸-羟基乙酸共聚物支架、聚氨酯覆膜支架等。支架置入可为移植物来源不足或局部组织病变未能行尿道成形术的FUS患者提供治疗选择,具有恢复快、手术时间短及应用人群广的特点[14,36]。但目前的支架置入研究多集中于男性患者,且成功率不高。
传统的尿道支架置入术难以控制支架孔隙及微观结构,且影响细胞生长及物质交换,无法构建充足的滋养血管。目前提出以尿源干细胞或脂肪干细胞制备仿生尿道,该技术利用干细胞的多向分化能力,构建复合细胞膜片进行尿道重建。研究发现,该技术细胞浓度显著增加,细胞分布更为均匀,构建了细胞间的正常联系,同时可避免支架材料的免疫学干扰,有利于保持细胞活性,促进细胞生长[37-38]。石磊等[39]使用脂肪间充质干细胞双向诱导上皮/平滑肌细胞膜片修复兔2 cm尿道缺损,与无细胞小肠黏膜下脱细胞基质相比,实验组能够获得更好的尿道重建结果,可形成多层组织结构及血管样组织分布。因此,细胞膜片仿生尿道技术可为临床尿道修复提供新的思路。
女性尿道狭窄相对少见,相关研究多为小样本研究,缺乏可比性和可靠性,其诊断及治疗缺乏统一标准。近年来逐渐提出在有下尿路症状的患者中,以不能留置大于F14号尿管为诊断基础,并经影像学或内镜证实尿道狭窄作为FUS的定义及诊断标准。既往认为,尿道扩张术能够减轻FUS患者的狭窄程度,并改善患者的主观感受,但近年来研究表明,多次尿道扩张会加重FUS复发患者的狭窄程度,并影响后期的尿道重建手术。因此,以口腔黏膜移植为主的尿道成形术可作为首选方案治疗复发性狭窄及狭窄段较长的FUS患者,能够显著提高治愈率并减少并发症。目前,脱细胞真皮基质、生物支架置入及细胞膜片等组织工程技术的发展,为FUS患者特别是移植物较为局限等不适宜自体组织移植的患者提供了新的治疗方案,具有较好的应用前景。
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2022年第47卷第1期
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doi: 10.11855/j.issn.0577-7402.2022.01.0097
  • 接收时间:2021-04-20
  • 首发时间:2025-12-18
  • 出版时间:2022-01-28
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  • 收稿日期:2021-04-20
  • 录用日期:2021-05-11
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    1山西医科大学第一临床医学院,太原 030001
    2山西医科大学第一医院泌尿外科,太原 030001

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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