论文题名(中文): | 人口腔黏膜与包皮生物特性的研究及其在前尿道狭窄外科治疗中的应用 |
姓名: | |
论文语种: | chi |
学位: | 博士 |
学位类型: | 专业学位 |
学校: | 北京协和医学院 |
院系: | |
专业: | |
指导教师姓名: | |
论文完成日期: | 2025-05-01 |
论文题名(外文): | Comparative Study of Tissue Property of Buccal Mucosa and Penile Skin and Their Applications in Surgical Management of Anterior Urethral Stricture |
关键词(中文): | |
关键词(外文): | Anterial urethral stricture Urethral reconstruction Complications Buccal Mucosa Penile Skin Flap Biomechanical Properties |
论文文摘(中文): |
目的 目前临床实践中组织移植物的选择往往更多依赖于术者对患者临床特征作出 的经验性判断,缺乏统一且客观的决策依据。本研究以前尿道狭窄修复中组织移 植物的选择为切入点,旨在评估口腔黏膜和包皮的组织结构、生物力学特性、透水性及渗透压耐受性差异,从而为临床前尿道狭窄修复术中的移植物选择提供依据。 目前包皮瓣和分期口腔黏膜移植在前尿道狭窄外科治疗的效果缺乏全面的研究。本研究通过回顾在本中心接受前尿道狭窄手术的成年男性患者的临床资料,分析包皮瓣与分期口腔黏膜移植两种术式的手术效果,并比较二者既往尿道下裂 手术史相关的结果、短期及长期随访相关的并发症、患者满意度及成功率和狭窄 复发的相关危险因素进行分析。 方法 本研究收集的 53 例口腔黏膜和 59 例包皮样本来源于我院接受阴茎及尿道手术的患者。通过苏木精-伊红染色评估组织学特征,CD31 和 D2-40 免疫荧光染色分析血管和淋巴管的分布特征。通过机械拉伸试验评估弹性模量、抗拉强度和拉 伸应变等生物力学性能。通过氘水(D2O)扩散试验评估组织的透水性及低渗、 等渗及高渗条件下的渗透压耐受性。 回顾分析 2000 年 4 月至 2023 年 8 月间,于我院接受手术治疗的 145 例前尿 道狭窄的成年男性患者。主要分析包皮瓣尿道成形术和分期口腔黏膜尿道成形术 的手术结果。纳入的患者数据包括:性别、年龄、身高、体重、联系方式、临床 症状、症状持续时间、既往操作的类型及次数、狭窄部位、数量和病因、手术时 间、随访时长、手术方式以及组织移植物大小。将 100 个月视为区分短期和长期 随访的时间节点,对患者短期和长期手术成功率进行分析。采用 Clavien-Dindo 分类,评估术后三个月,即手术早期的并发症;使用患者报告结局量表(PROM)评估手术成功率;满意度评分评估患者满意度;采用 Logistic 回归模型,评估手术失败的风险因素。 结果苏木精-伊红染色显示,口腔黏膜的上皮显著厚于包皮分别为 628.8 ± 213.3 µm 和 148.2 ± 62.1 µm(p < 0.05)。免疫荧光分析显示,口腔黏膜固有层上部具 有密集的 CD31 阳性血管和 D2-40 阳性淋巴结构网络,而包皮在浅筋膜层分布了密集的粗大血管。机械拉伸试验表明口腔黏膜的弹性模量 10.0 ± 3.93 MPa 和抗拉 强度 4.63 ± 1.92 MPa 显著高于包皮弹性模量:4.99 ± 2.62 MPa;抗拉强度:3.36 ± 1.99 MPa(p < 0.05)。然而,包皮的拉伸应变 2.23 ± 1.78 显著高于口腔黏膜 0.96 ± 0.58(p < 0.05),表明其具有更优越的柔韧性。水分渗透性测试显示,口腔黏 膜的氘水累计扩散量在所有时间点均显著高于包皮(p < 0.05)。在低渗环境下, 包皮的上皮厚度变化比例显著高于口腔黏膜,而在等渗(p > 0.05)和高渗(p > 0.05)条件下,二者的上皮厚度变化比例无显著差异。 本研究共纳入接受包皮瓣或分期口腔黏膜尿道成形术治疗的男性前尿道狭窄 患者 74 例,分别为 22 例和 52 例。包皮瓣组患者平均狭窄长度为 2.2 ± 1.1 cm, 随访时间 10.2 ± 6.5 年,手术成功率为 72.7%;分期口腔黏膜组患者平均狭窄长度 为 4.1 ± 1.5 cm,随访时间 9.5 ± 4.7 年,成功率为 73.1%。两组术后总体满意度均 为 4.1 ± 1.4,早期并发症发生率分别为 27.3%和 50.0%,远期并发症发生率分别为 18.2%和 17.3%。Clavien 分级主要集中于 I 至Ⅲ级,未见Ⅳ级或 V 级并发症。在 既往接受尿道下裂修复术的患者中,不同手术次数及术式选择对最终手术成功率 无显著影响(p > 0.05)。随访分析显示,两种术式的手术成功率均随时间延长 而下降,分期口腔黏膜组下降更为显著(p < 0.05),但两组的无狭窄生存率比 较无统计学差异(log-rank 检验,χ² = 1.6,p > 0.05)。患者满意度与远期并发 症在短期与长期随访中均无显著差异(p > 0.05)。Logistic 回归模型提示,狭窄 复发风险与狭窄症状持续时间(p < 0.05)及既往尿道成形术史(p < 0.05)显著 相关,而是否使用组织移植(p > 0.05)及移植类型(p > 0.05)与复发无显著关 联。 结论 口腔黏膜上皮厚、力学强度高、水分渗透性好,血管与淋巴分布丰富。较包 皮在抵御张力、维持屏障功能和促进愈合方面更具优势,更适合作为尿道修复移 植物。 包皮瓣与分期口腔黏膜尿道成形术手术成功率相近,既往尿道下裂手术次数 不会影响手术结果。分期口腔黏膜尿道成形术长期随访手术成功率较短期随访显 著降低。狭窄复发主要与症状持续时间和既往手术史相关。 |
论文文摘(外文): |
Objective: In current clinical practice, the selection of graft materials largely relies on the surgeon’ s judgment based on the patient’s clinical characteristics, lacking a unified and objective decision-making basis. This study focuses on graft selection in anterior urethral stricture repair, aiming to evaluate the differences between buccal mucosa and penile skin in terms of tissue structure, biomechanical properties, permeability, and osmotic tolerance, thereby providing evidence to guide graft selection in clinical anterior urethral reconstruction. At present, comprehensive studies on the efficacy of penile skin flaps and staged buccal mucosa grafts in the surgical treatment of anterior urethral stricture are lacking. This study retrospectively analyzes the clinical data of adult male patients who underwent anterior urethral stricture surgery at our center, comparing the surgical outcomes of penile skin flap and staged buccal mucosa graft urethroplasty. The analysis includes the impact of prior hypospadias repair, complications in short- and long-term follow-up, patient satisfaction, surgical success rates, and risk factors associated with stricture recurrence. Methods: Human Buccal mucosa (n = 53) and penile skin flap (n = 59) samples were obtained from patients undergoing penile and urethral reconstructive surgery. Histological features were examined using H&E staining, and blood and lymph vessel patterns were analyzed through immunofluorescence staining for CD31 and D2-40. Biomechanical properties, including elastic modulus, tensile strength, and tensile strain, were assessed through mechanical testing. Water permeability was evaluated using deuterium oxide diffusion assays, and osmotic stress responses were tested under hypo-, iso-, and hypertonic conditions. Statistical analyses were performed to identify significant differences between buccal mucosa and penile skin flaps. A retrospective study was conducted on 145 male patients diagnosed with anterior urethral stricture, who underwent penile skin flap urethroplasty and multistage buccal mucosa grafting between April 2000 and August 2023. We defined 100 months as the cut-off time point to distinguish short-term and long-term follow-up. Early surgical complications were scored using the Clavien-Dindo classification at 3 months. Patient-Reported Outcome Measure (PROM) was applied to evaluate surgical success. Risk factors for wound complications were evaluated using univariable and multivariable analysis. Results: H&E staining revealed that the buccal mucosa epithelium was significantly thicker (628.8 ± 213.3 µm) than that of the penile skin flap (148.2 ± 62.1 µm; p < 0.05). Immunofluorescence analysis showed a dense network of CD31-positive blood vessels and D2-40-positive lymphatic structures in the upper lamina propria of the buccal mucosa, whereas the penile skin flap exhibited densely distributed thick blood vessels in the superficial fascial layer. Mechanical testing demonstrated that the buccal mucosa had significantly higher elastic modulus (10.0 ± 3.93) MPa and tensile strength (4.63 ± 1.92) MPa compared to the penile skin flap (elastic modulus: 4.99 ± 2.62 MPa; tensile strength: 3.36 ± 1.99 MPa; p < 0.05). However, the penile skin flap exhibited greater tensile strain (2.23 ± 1.78) than the buccal mucosa (0.96 ± 0.58; p < 0.05), indicating superior flexibility. Water permeability testing revealed that the cumulative diffusion of deuterium oxide (D2O) through the buccal mucosa was significantly higher at all time points compared to the penile skin flap (p < 0.05). In the Hypo group, the ratio of variation in epithelial thickness was significantly higher in the penile skin flap compared to the buccal mucosa. No statistical differences in the ratio of epithelial thickness variation were observed under Iso (p > 0.05) and Hyper (p > 0.05) conditions. The primary limitation of this study is the relatively small sample size. Additionally, the in vitro model lacks the ability to fully replicate the urethral microenvironment, where multiple interacting factors influence graft survival. A total of 74 male patients with anterior urethral stricture treated with either penile skin flap or staged buccal mucosa urethroplasty were included in this study, with 22 and 52 cases in each group, respectively. In the penile skin flap group, the mean stricture length was 2.2 ± 1.1 cm, with a follow-up duration of 10.2 ± 6.5 years and a surgical success rate of 72.7%. In the staged buccal mucosa group, the mean stricture length was 4.1 ± 1.5 cm, follow-up was 9.5 ± 4.7 years, and the success rate was 73.1%. Both groups reported a mean postoperative satisfaction score of 4.1 ± 1.4. The early complication rates were 27.3% and 50.0%, and the late complication rates were 18.2% and 17.3%, respectively. Clavien classification of complications ranged from grade I to III, with no grade IV or V complications observed. Among patients with a history of hypospadias repair, neither the number of previous surgeries nor the choice of urethroplasty technique (penile flap vs staged buccal mucosa graft) had a significant effect on the surgical success rate (p > 0.05). Follow-up analysis showed a declining trend in success rates over time for both techniques, more pronounced in the staged buccal mucosa group (p < 0.05), while no significant difference was observed in stricture-free survival between the two groups (log-rank test, χ² = 1.6, p > 0.05). Patient satisfaction and the incidence of long-term complications showed no significant differences between short- and long-term follow-up groups (p > 0.05). Logistic regression analysis indicated that stricture recurrence was significantly associated with symptom duration (p < 0.05) and prior urethroplasty history (p < 0.05), while the use of grafts (p > 0.05) and graft type (p > 0.05) were not significantly related to recurrence. Conclusion: Buccal mucosa exhibits a thicker epithelium, greater mechanical strength, superior water permeability, and richer vascular and lymphatic networks. Compared to penile skin, it offers greater advantages in withstanding tension, maintaining barrier function, and promoting healing, making it a more suitable graft material for urethral reconstruction. The surgical success rates of penile skin flap and staged buccal mucosa urethroplasty are comparable. The number of prior hypospadias repair does not affect surgical outcomes. However, the long-term success rate of staged buccal mucosa grafting significantly declines over time. Stricture recurrence is significantly associated with symptom duration and prior surgical |
开放日期: | 2025-06-17 |