Failure Phenotyping: Functional Anatomy-Based Prediction of Pelvic Organ Prolapse Recurrence

失败表型：基于功能解剖学的盆腔器官脱垂复发预测

• 批准号: 9910416
• 负责人: CAROLYN W SWENSON
• 金额: $ 7.8万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9910416
• 关键词: Address; Anatomy; Apical; Area; Back; Biological Markers; Clinical; Clinical Data; Data; Data Analyses; Defect; Failure; Funding; Future; Genital system; Goals; Gold; High Prevalence; High Risk Woman; Knowledge; Lead; Logistic Regressions; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Operative Surgical Procedures; Outcome; Patients; Pelvic Floor Disorders; Pelvic Floor Muscle; Pelvis; Phenotype; Postoperative Period; Prospective Studies; Ptosis; Recurrence; Repeat Surgery; Research; Resources; Rest; Risk Factors; Sample Size; Scanning; Site; Stress; Structure; Support System; Surgeon; Surgical Management; Surgical Models; Techniques; Testing; Thromboplastin; Tissues; United States National Institutes of Health; Vagina; Woman; Work; base; clinical examination; cost; evidence base; high risk; indexing; levator ani muscle; novel; novel therapeutics; operation; pelvic organ prolapse; predictive modeling; repaired; success; surgery outcome

Abstract Over 200,000 women undergo surgery for pelvic organ prolapse each year. One of the biggest current challenges is recurrent prolapse following surgery. At seven years, the failure rate for the “gold standard” operation performed by expert surgeons in the NIH Pelvic Floor Disorders Network is 25%. While improvements in surgical management have led to better long-term outcomes for Level I (apical) support, emerging data indicate that Level III (genital hiatus) support is not addressed by Level I surgery and may be the most significant predictor of prolapse recurrence. Current progress is blocked by our lack of understanding regarding the specific anatomical defects that lead to recurrent prolapse, as well as our inability to identify women prior to surgery who are at high risk for recurrence. From a prior NIH-funded study, our research group has preoperative MRIs on 133 women who underwent surgery for prolapse, and for a subset of these we have limited clinical data about prolapse recurrence. Preliminary analyses of these data suggest that a novel preoperative MRI measure of the genital hiatus (∆gh), which is the change in genital hiatus from rest to strain, may be associated with postoperative recurrence; however, our current sample size is too small to be able to conduct multivariable logistic regression. We seek funding to bring these women back for clinical exams to identify anatomical preoperative biomarkers responsible for prolapse recurrence and, for a subset, acquire postoperative MRI to identify structural failure sites. Pilot data from this study can then be used to power a larger, definitive study. AIM 1: Identify preoperative factors associated with recurrence: We hypothesize that the ability to maintain a closed genital hiatus (gh) will be a predictor of surgical success. Specifically, we propose a new variable to assess levator status, ∆gh, which is the change in genital hiatus size from rest to strain. We expect women with a smaller preoperative ∆gh to have a higher prevalence of recurrence. We will test the hypothesis that preoperative ∆gh is a stronger predictor of surgical failure than existing measurements associated with levator ani muscles. AIM 2: Postoperative failure phenotyping: Acquire and compare postoperative Stress MRI for 10 women with recurrence versus 10 women with long-term success following prolapse surgery. a) We will identify structural failure sites on postoperative MRIs for women with anatomical recurrence following prolapse surgery. b) We will test the null hypothesis that there is no difference in Level III support measures between women with prolapse recurrence and those with long-term success.

摘要 每年有20多万妇女接受盆腔器官脱垂手术。一个最大的 目前的挑战是手术后复发性脱垂。七年后， 由国家卫生研究院骨盆底疾病专家外科医生进行的“黄金标准”手术 网络占25%。虽然手术管理的改善导致了更好的长期 I级（心尖）支持的结局，新数据表明III级（生殖器裂孔） I级手术不能解决支持问题，可能是最重要的预测因素， 脱垂复发。目前的进展受到阻碍，原因是我们对 导致复发性脱垂的特定解剖缺陷，以及我们无法识别 手术前复发风险高的女性。 从先前NIH资助的研究中，我们的研究小组对133名妇女进行了术前MRI检查， 接受了脱垂手术，对于其中的一个子集，我们的临床数据有限， 脱垂复发。对这些数据的初步分析表明，一种新型的术前MRI 生殖裂孔的测量值（RIGGH），即生殖裂孔从静止到应变的变化， 可能与术后复发有关;然而，我们目前的样本量太小 能够进行多变量逻辑回归。我们寻求资金让这些妇女 返回进行临床检查，以确定导致脱垂的解剖学术前生物标志物 复发，并且对于一个子集，获取术后MRI以识别结构失效部位。试点 这项研究的数据可以用来支持一项更大的确定性研究。 目的1：确定与复发相关的术前因素：我们假设， 保持闭合的生殖器裂孔（GH）将是手术成功的预测因素。我们特别 提出了一个新的变量来评估提肌状态，即生殖裂孔大小的变化 从休息到紧张。我们预计术前子宫颈较短的女性， 复发率。我们将检验术前高血糖比术前低血糖更强的假设。 与现有的肛提肌相关测量相比， 目的2：术后失败表型：获取并比较10例患者的术后应力MRI 复发的女性与脱垂手术后长期成功的10名女性。 a）我们将在术后MRI上识别解剖结构不全的女性的结构性失效部位。 脱垂手术后复发。 B）我们将检验零假设，即III级支持措施没有差异 脱垂复发的女性和长期成功的女性之间的差异。