生物可降解尿道支架种植尿道移行上皮细胞的研究

我们应用人工合成的生物可降解性单纯型尿道内支架修复战伤性尿道狭窄,证实该材料及方法是可行的[1].本实验旨在将自体的尿道上皮细胞体外培养后,种植于单纯尿道内支架上,制备成附有自体尿道上皮细胞的复合型尿道内支架,为修复尿道损伤提供较实用有效的治疗方法.     

尿道、阴茎

生物可降解性尿道内支架修复战伤性尿道狭窄的研究;输尿管镜下尿道会师术治疗尿道球部损伤;经尿道超脉冲等离子治疗尿道狭窄（附48例报告）;输尿管镜尿道置管术与开放性尿道吻合术治疗球部尿道损伤的比较；超声检查在男性创伤性尿道狭窄诊断中的价值     

尿道细胞外基质修复尿道缺损的研究

目的 寻求一种较理想的尿道修复材料。方法 20只家兔尿道制成尿道细胞外基质(ECM)；另40只随机分3组：尿道ECM移植组(实验组)，对照组Ⅰ及对照组Ⅱ。实验组切除尿道1．O～1．5cm后用尿道ECM修复并于术后10d、3周、6周及24周行组织再生情况观察；另于术后10周、24周各取4只行膀胱尿道造影；24周时实验组及对照组Ⅰ各取4只行尿流动力学检测；24周实验组取4只行尿道镜检查。结果 缺损修复术后10d，基质中见单层上皮细胞且有血管长入ECM；3周时尿道ECM管腔已完全被上皮细胞覆盖；6周时可见平滑肌细胞再生，炎性细胞消失；24周后其组织结构与正常组织相比差异无统计学意义。膀胱尿道造影无尿液外渗，无梗阻及结石形成。尿流动力学检测结果实验组与对照组Ⅰ差异无统计学意义；尿道镜检查证实尿道黏膜完整光滑，尿道内径及其形态正常。结论 尿道细胞外基质是一种理想的尿道修复材料。     

尿道支架双套管在尿道下裂Ⅱ期尿道成形术中的应用

目的:探讨自制尿道支架双套管在尿道下裂Ⅱ期成形术中的应用价值。方法:2016年9~12月在22例尿道下裂Ⅱ期尿道成形术中使用自制尿道支架双套管(使用6~8cm F10胃管作为前尿道支架管,于前尿道支架管中另插F6胃管作为导尿管)作为新成形尿道的支架管,观察术后并发症及疗效。术后2周拔除导尿管,术后3周拔除前尿道支架管,拔除前尿道支架管1周后行尿道探子尿道检查、尿常规等,所有患儿术后随访3~6个月。结果:22例患儿手术均获成功,导尿管(内支架管)平均放置时间10d;前尿道支架管(外支架管)的平均放置时间为4周,在带管期间,无患儿出现支架管脱出和排尿困难等现象,无尿瘘、感染及尿道狭窄等常见的手术并发症。1例患儿在术后3个月随访中出现尿道狭窄,该患儿在麻醉后行尿道镜检查发现为尿道板吻合处狭窄,行尿道扩张后再次置入F12外支架管,术后2周拔除后痊愈。其余患儿在随访时间内未见尿瘘、感染及尿道狭窄等常见的术后并发症。结论:自制的尿道支架双套管能够有效降低尿道下裂Ⅱ期尿道成形术后相关并发症如泌尿系感染、尿道狭窄、尿瘘等的发生,具有制作方法简单、护理方便、患儿易接受、可行性强等优点,适合临床推广应用。     

冻干无细胞膀胱黏膜下基质修复兔尿道缺损

目的　探讨冻干无细胞膀胱黏膜下基质修复尿道缺损的效果。方法　应用反复冻融-酶法及冷冻干燥技术制备冻干无细胞人体膀胱黏膜下基质。 18只新西兰白兔建立尿道中段部分缺损模型 ,尿道缺损面积约 1 0cm× 0 5cm。其中 14只兔作为实验组 ,以冻干无细胞膀胱黏膜下基质修补尿道缺损 ,术后 1、2、3、4、8、12、2 4周分别取 2只行逆行性尿道造影 ,观察尿道情况 ,并采取尿道组织进行大体、组织学及超微结构观察 ;4只兔作为对照组 ,未采用任何材料修补尿道缺损 ,直接缝合尿道海绵体包膜、皮下组织及阴茎皮肤 ,术后 2、4周分别取 2只行逆行性尿道造影 ,采取尿道组织进行大体观察。结果　实验组 14只兔均未发现明显的尿道狭窄。冻干无细胞膀胱黏膜下基质组织相容性良好 ,移植后无细胞膀胱黏膜下基质内有细胞长入 ,新生血管形成 ,术后 2周无细胞膀胱黏膜下基质移植区完全上皮化。随着移植时间的延长 ,移植区胶原纤维排列由紊乱趋于规则。结论　冻干无细胞膀胱黏膜下基质能够诱导尿道黏膜细胞迁徙、生长和上皮化 ,初步认为可以作为尿道缺损修复材料。     

尿道细胞外基质在兔尿道重建中的应用

目的 评价尿道细胞外基质作为一种生物材料重建尿道的效果. 方法 切取新西兰兔的尿道制备尿道细胞外基质.手术切除实验组1～1.5 cm的尿道片段后用细胞外基质修复缺损,采用ELISA法检测术前、术后12、24及48 h血清TNFα的水平,评估术后兔的免疫反应状态.术后10d和3、6、24周取修复段尿道,行组织学观察并做尿道造影、尿道镜及尿流动力学检查. 结果 术后实验组血清TNFα水平较对照组略有升高,但无统计学意义(P>0.05).术后10 d,上皮细胞开始从边缘向细胞外基质移行并出现新生小血管;3周上皮细胞覆盖细胞外基质的整个管腔;6周出现排列不规则的平滑肌纤维;24周平滑肌数量明显增多,成束状排列.尿道造影、尿道镜及尿流动力学检测检查显示,尿道基质管壁光滑,排尿通畅. 结论 尿道细胞外基质是一种安全有效的尿道重建材料.     

脱细胞基质载体和表皮细胞结合构建尿道的实验研究

目的探索组织工程修复技术在尿道构建中的应用前景。方法采用同种异体家兔膀胱,经显微外科分离和脱细胞液处理,制成无细胞的生物支架,12只雄兔随机分为成实验和对照2组,剥离实验对象尿道黏膜2cm;实验组切取小块兔包皮组织,消化收集分离出的表皮细胞,经过增殖、传代培养,植入生物支架中,培养2周,并加入Brdu标记物,将其卷成管状,植入实验组人工尿道缺损区域;对照组单纯采用无细胞植入的生物支架修复尿道;术前和术后1、2、6个月每组各处死2只家兔/批,分别行尿道造影、大体外形、修复段尿道黏膜的HE染色、免疫组化和荧光标记。结果术后动物伤口愈合正常,排尿通畅,无尿瘘发生。修复尿道大体形态和尿道造影显示带细胞修复的尿道形态完整,清晰宽敞,无狭窄发生;术后1个月,HE和免疫组化显示,修复段尿道黏膜层次单一,缺乏复层和乳头结构。术后2个月基本恢复正常尿道结构,复层上皮结构形成,角蛋白染色阳性。术后6个月黏膜复层上皮结构更为丰富,角蛋白染色阳性;Brdu标记在术后1个月清晰显示植入上皮细胞层存在,术后2个月植入的原始上皮细胞显影稀少。术后6个月尿道黏膜结构中未见显影;而单纯生物支架修复组的实验对象则出现排尿变细,任何观察时段,均出...     

简易外固定尿道支架管在前尿道狭窄术后的应用(附16例报告)

目的探讨简易外固定尿道支架管在治疗前尿道狭窄术后的应用效果。方法 2015年6月~2018年10月对16例前尿道狭窄行尿道扩张术后,将弹性束缚带固定在冠状沟凹陷处,尿道支架管置入前尿道后留置支架管,再将支架管与束缚带相固定,留置支架管2~4周后移除。结果 16例均可耐受并保持支架管固定在位2周以上。无尿路感染、附睾炎等发生,无支架管脱出或脱入等。14例支架管拔除后随访3个月监测最大尿流率均 15 ml/s; 2例留置2周拔管后再次出现排尿尿线变细,再次尿道扩张并留置2周后达到临床治愈。16例术后最大尿流率15. 6~23. 0 ml/s,(18. 4±1. 8) ml/s,明显高于术前尿流率(7. 2±3. 1) ml/s(t=-13. 186,P=0. 000)。结论前尿道狭窄行尿道扩张、狭窄内切开术后使用简易外固定尿道支架管舒适性好,并发症少,可考虑作为替代留置导尿管的方法。     

异种膀胱无细胞基质替代尿道的研究

目的探讨异种膀胱无细胞基质(ACM)管状替代尿道的可行性。方法19只成年雄性新西兰白兔分成3组：A组3只，为假手术对照组；B组10只，切除一段1．0cm尿道；C组6只，切除一段3．5～4．0cm尿道，之后应用已经事先制备好的异种膀胱ACM制成相当长度的管状替代被切除的尿道。术后1、2、4、8、16周动态观察替代尿道的尿道上皮、平滑肌和血管的再生情况。结果所有实验动物在术后7d拔除尿管后都恢复了自主排尿，没有排斥、尿瘘、感染等并发症发生。组织学检查显示实验组术后2周尿道上皮再生良好，4周完全覆盖尿道内腔，术后8周平滑肌见于近吻合口处，平滑肌生长缓慢，观察期内未能覆盖全长尿道。尿道造影未见明显尿道狭窄和憩室。结论异种膀胱ACM是一种良好的尿道修复和替代的材料。     

犬尿道狭窄动物模型的建立

目的制作犬尿道狭窄动物模型。方法健康雄性成年犬15只，10g／L戊巴比妥钠（30mg／kg）静脉麻醉后，切开阴茎腹侧包皮，逆行尿道造影，随机抽取3只犬设为对照组，同步观察，余12只犬为试验组，以好克公司F10小儿电切镜直视下行前尿道电切术。术后第15和30天时分别麻醉动物，做尿道镜及尿道造影检查，评价模型制作效果。结果1只（8．3％）犬死于术后尿道感染，3只（25％）犬术后当天发生尿潴留，术后第15天，4只（36．3％）犬在尿道损伤部位发生瘢痕性狭窄，术后30d，存活的11只（91．7％）犬全部出现尿道狭窄，对照组犬尿道正常。结论采用小儿电切镜制造犬前尿道损伤能成功制作出尿道狭窄动物模型，为瘢痕性尿道狭窄的发生机理和分子生物学研究提供实验对象。     

Biodegradable urethral stents seeded with autologous urethral epithelial cells in the treatment of post‐traumatic urethral stricture: a feasibility study in a rabbit model

OBJECTIVE

To evaluate the adhesion and growth of rabbit urethral epithelial cells (UECs) on a biodegradable unbraided mesh urethral stent, and to assess the feasibility and effect of the cell‐seeded urethral stent for treating post‐traumatic urethral stricture (PTUS) in a rabbit model.

MATERIALS AND METHODS

Rabbit UECs were collected by biopsy from adult rabbit urethra and seeded onto the outer layer of a mesh biodegradable urethral stent. The growth of UECs in cell‐scaffolds was assessed by scanning electron microscopy, immunohistochemical and fluorescence staining. In all, 32 male New Zealand rabbits were used, with either PTUS or uninjured, as a control group. Cell‐seeded stents were implanted into the rabbits strictured urethra. The histological and immunohistochemical findings were assessed after death at 1, 2, 8, 12 and 24 weeks, respectively. The reconstruction and function were evaluated by urethroscopy and retrograde urethrography.

RESULTS

The cultured UECs adhered to the stent and grew well. Immunohistochemistry showed that the cells were stained positively for cytokeratin. At 4 weeks, vs 2 weeks, the thickness of the papillary projections of the epithelium decreased and inflammatory cell infiltration diminished. At 24 weeks the injured urethra was completely covered by integrated regeneration of three to five layers of urothelium. There was no evidence of voiding difficulty, stricture recurrence or other complications.

CONCLUSIONS

The unbraided mesh biodegradable urethral stent with autologous UECs seemed to be feasible for treating PTUS in the rabbit urethra, and provides a hopeful avenue for clinical application allowing reconstruction of PTUS.     

小肠黏膜下层修复尿道的实验研究

目的探讨小肠黏膜下层(small intestinal submucosa,SIS)在尿道修复重建中的应用价值.方法 24只日本雄性大耳白兔,随机分为A、B、C及D组(n=6).A、B组切除前尿道2.0 cm,A组,用管状SIS修复尿道缺损;B组将其断端与周围组织直接缝合作为对照.C、D组仅切除2.0 cm尿道前壁,保留一半尿道壁为底板,C组用片状SIS修复尿道缺损;D组将其残端与周围组织直接缝合作为对照.均于修复后6、12周行组织学观察;12周行尿道膀胱造影及尿动力学检查.结果术后6周,A、C组修复的尿道有单层上皮细胞覆盖,基层组织中可见SIS的微小碎片包裹,出现不规则紊乱的平滑肌细胞生长,A组较C组的炎性反应重,有白细胞及淋巴细胞浸润,C组出现新生血管.术后12周,C组的上皮组织及基层下组织与D组无明显差别,平滑肌排列规则,血管数目进一步增多,炎性反应消失,未见SIS组织;A组中仍可见少数SIS的微小碎片;B组1只、D组2只尿道自行修复,余可见尿道闭塞,大量结缔组织生长,炎性细胞浸润,无正常上皮结构.术后12周尿道膀胱造影,A、C组可见尿道完整、光滑,无尿液外渗、尿道憩室等形成;尿动力学检查示A、C组的膀胱容量、最大尿道压分别与术前比较,差异无统计学意义(P＞0.05),而B、D组不能置入测压管检测.结论 SIS可作为兔尿道修复重建的良好支架材料,片状SIS修复优于管状SIS修复.     

应用异体脱细胞尿道基质修复尿道缺损

目的探讨应用同种脱细胞尿道基质修复尿道缺损的可行性。方法将14只雄性新西兰兔分为两组，切除实验组长约1.0～1．5cm的尿道，用相应长度脱细胞尿道基质修复；对照组行假手术。术后行尿道造影并取尿道标本作病理检查。结果12只实验兔的脱细胞基质移植物没有移位。除2例狭窄、2例尿瘘外，其余满意效果。病理检测示，术后3周尿道管腔上皮化，6个月基质中平滑肌及血管再生明显。结论同种脱细胞尿道基质材料可以修复兔尿道部分缺损。     

An experimental model of bulbar urethral stricture in rabbits using endoscopic radiofrequency coagulation

OBJECTIVES: To develop an experimental model of endoscopic urethral stricture mimicking the human clinical situation. METHODS: Twenty-four New Zealand male rabbits were included. Eighteen animals (study group) underwent videourethroscopy with a pediatric resectoscope, and a 3 to 5-mm-long circumferential electrocoagulation of the bulbar urethra was performed, without postoperative urinary diversion. Six animals underwent the same procedure without application of electrocautery (control group). Each animal was assessed for urethral stricture on day 15 and day 30 by videourethroscopy and voiding cystogram. Among the study group, 8 animals were killed on day 15 and 10 on day 30 for histologic evaluation. All the control animals were killed on day 30 for histologic examination. RESULTS: Nine animals (50%) in the study group developed a significant bulbar stricture (reducing the lumen by more than 50%) at day 15. Histologic examination confirmed the presence of hyalin fibrosis mutilating the urethral wall. No spontaneous improvement of the stricture was observed on day 30. None of the controls developed urethral stricture, and histologic examination showed a normal urethra in each case. CONCLUSIONS: Endoscopic electrocoagulation of the urethral wall provides a reproducible model of stricture in the rabbit.     

Gray scale and color Doppler sonography with extended field of view technique for the diagnostic evaluation of anterior urethral strictures

PURPOSE: We compared the clinical relevance of radio urethrography with that of sonourethrography for evaluating male urethral strictures. MATERIALS AND METHODS: From 2002 to 2004, 93 men were referred to our institution for urethral strictures. Patients were evaluated by conventional voiding cystourethrography, retrograde urethrography, and gray scale and color Doppler sonourethrography. For sonourethrography the extended field of view technique was used to obtain 1 image of the whole anterior urethra. In all cases the urethra was evaluated cystoscopically or at open surgery. Radio urethrography and sonourethrography findings were compared with cystoscopy or surgery findings. RESULTS: All strictures were evaluated and treated cystoscopically with visual internal urethrotomy (34%) or at open operation (66%), which allowed comparison of the ability of each study to predict operative stricture length. Sonourethrography correctly identified the stricture and its site in all cases, whereas radio urethrography yielded 2 false-negative results. There was a significant difference between stricture length measured by radio urethrography compared to that measured by sonourethrography (correlation coefficient 0.72 vs 0.92, p<0.005). Mean+/-SD stricture length measured by radio urethrography was 1.5+/-1.3 cm and by sonourethrography it was 2.1+/-0.9 cm. Comparison of radio urethrography and sonourethrography stricture length with operative lengths demonstrated a good correlation in the penile urethra (correlation coefficient 0.91 vs 0.98), whereas a poor correlation was found in the bulbar urethra (correlation coefficient 0.65 vs 0.92). CONCLUSIONS: Gray scale and color Doppler sonourethrography using the extended field of view technique with a Siemens Sonoline Elegra is a promising tool for defining male urethral strictures. It seems to be superior to radio urethrography for treatment planning.     

非编织状聚乙醇酸膜片重建兔尿道的实验研究

目的探讨非编织状聚乙醇酸膜片重建兔全层尿道的效果。方法制备1cm×1cm的非编织状PGA膜片。建立新西兰大白兔尿道腹侧1cm全层尿道缺损动物模型,将PGA膜片植入尿道缺损区域,修补尿道缺损。术后1、2、3个月进行尿道造影、大体观察和组织学观察评价尿道重建情况。结果PGA膜片修复新西兰兔全层尿道缺损,9只动物除1只术后1个月发生尿瘘外．其余动物均排尿通畅。组织学检查发现尿道黏膜再生良好,但尿道海绵体区域主要以纤维瘢痕增生为主,未见明显尿道海绵体再生。结论PGA膜片能够修复新西兰大白兔1cm尿道黏膜的缺损,但缺乏尿道海绵体再生。     

Staged pendulous-prostatic anastomotic urethroplasty followed by reconstruction of the anterior urethra: an effective treatment for long-segment bulbar and membranous urethral stricture

OBJECTIVES: To describe a novel surgical technique for male long-segment urethral stricture after pelvic trauma using the intact and pedicled pendulous urethra to replace the bulbar and membranous urethra, followed by reconstruction of the anterior urethra. METHODS: Two patients with long-segment post-traumatic bulbar and membranous urethral strictures with short left pendulous urethras who had undergone several failed previous surgeries were treated with staged pendulous-prostatic anastomotic urethroplasty followed by reconstruction of the anterior urethra. This procedure was divided into three stages. First-stage surgery was mobilization of the anterior urethra down to the coronary sulcus and then rerouted to the prostatic urethra followed by pendulous-prostatic anastomotic urethroplasty with transposition of the penis to the perineum. Second-stage surgery was transecting the anterior urethra at the revascularised coronary sulcus 6 mo later, followed by straightening of the penis and urethroperineostomy. Third-stage surgery was reconstruction of the anterior urethra 6 mo later. RESULTS: Postoperatively, the two patients reported satisfactory voiding. For patient 1, retrograde urethrography showed that the urethra was patent, and that the mean maximal flow rate (MFR) was 18.4 ml/s with no postvoiding residual urine after the third-stage surgery and at 3-yr follow-up. For patient 2, a 22F urethral catheter could pass smoothly through the urethra, and the MFR was 19.5 ml/s with no postvoiding residual urine at 2-yr follow-up. CONCLUSIONS: This procedure was an effective surgical option for men with complex long-segment post-traumatic bulbar and membranous urethral strictures, especially for those who had undergone failed previous surgical treatments.     

Sonographic staging of anterior urethral strictures

PURPOSE: Although radiographic retrograde urethrography has traditionally been the gold standard for imaging the anterior urethra, sonourethrography has proved to be precise and effective for evaluating urethral strictures. We review the evolution of sonourethrography and demonstrate its practical contemporary applications. MATERIALS AND METHODS: We performed literature reviews on MEDLINE and chart reviews of our patient records from 1988 to 1998. RESULTS: Sonourethrography measures stricture length in the bulbar urethra more accurately than conventional retrograde urethrography. Spongiofibrosis is manifested sonographically by a lack of urethral distensibility during retrograde instillation of saline solution. Posterior shadowing is noted in severe posttraumatic cases. Sonographic staging before treatment of complex or reoperative anterior strictures elucidates complicating features, such as calculi, urethral hair, false passage and stent encrustation. CONCLUSIONS: Sonographic staging of anterior urethral strictures offers clinically important information that may be useful in guiding reconstructive therapy.     

螺旋CT尿道三维重建诊断后尿道狭窄或闭锁

目的 探讨螺旋CT尿道三维重建技术在后尿道狭窄或闭锁诊断中的应用价值.方法 对30例创伤性后尿道狭窄或闭锁患者术前行螺旋CT薄层扫描和尿道三维重建、X线尿道造影,观察狭窄或闭锁部位、长度以及尿道周围组织解剖结构的改变,并与开放性手术中发现的结果进行对比研究.结果 X线尿道造影检测狭窄或闭锁段长度为1.0～7.0 cm,平均4.0 cm,狭窄或闭锁长度相关系数为0.92,定位准确率为70%(21/30);螺旋CT尿道三维重建检测狭窄或闭锁段长度为1.2～7.6 cm,平均4.3 cm,狭窄或闭锁长度相关系数为0.96,定位准确率为93%(28/30);术中发现后尿道狭窄或闭锁长度为1.5～7.5 cm,平均4.2 cm.5例合并尿道直肠瘘者螺旋CT尿道三维重建可以清楚显示瘘管位置、长度及大小;X线尿道造影则无法清楚显示.结论 螺旋CT尿道三维重建对了解伤后尿道的解剖结构改变、测量尿道狭窄或闭锁部位和长度、指导手术方式选择有较高价值,尤其对合并尿道直肠瘘者有重要的诊断意义.