Diagnostic Utility of Culdocentesis in Patients with a Suspicious Adnexal Mass

描述（申请人提供）：上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤。在美国，近1000万女性处于EOC的高风险中，每年有超过21,000例新诊断。超过60%的确诊患者为晚期EOC， 5年生存率低于30%，而局部疾病的5年生存率超过90%。I期EOC在非特异性症状中很难发现，这些症状会延迟检查，直到发现盆腔肿块。一旦发现附件肿块，目前的诊断手段包括超声对肿瘤分级，分析血清肿瘤标志物、癌抗原125 （Cancer Antigen 125, CA-125）和人附睾蛋白4 （Human epididymis protein 4, HE4）水平。据报道，HE4是检测I期EOC最敏感的生物标志物，而单独升高的血清CA-125水平（约35 U/mL）缺乏足够的敏感性和特异性来确定诊断。据我们所知，HE4可在尿液中测量，但尚未在腹膜液中测量，尽管培养刺针术多年来一直是妇科领域的一项有用技术，并且可以在门诊环境中进行。需要一种微创、可靠的诊断工具，以避免因良性疾病而行卵巢切除术，避免不必要的发病率。特异性目的：确定肿瘤标志物（CA-125和HE4）水平和通过死胡同获得的腹膜冲洗细胞学与上皮性卵巢癌的诊断是否相关。我们假设，从腹膜液中联合测量这些标记物可能会增加对卵巢皮层以外癌细胞存在的敏感性，从而可能导致早期发现EOC。研究设计：前瞻性研究将招募并同意60名妇女的方便抽样，计划对可疑的附件肿块进行手术分期。子宫内膜癌和卵巢癌的手术分期包括收集腹膜冲洗液。我们的创新技术不同于标准的培养刺针术，将生理盐水注入囊腔死角，然后重新吸气收集（即腹膜冲洗）。将分析腹膜下陷的细胞学以及肿瘤标志物、CA-125和HE4的水平。相关性：我们的研究目标是开发一种简单的非手术诊断工具，可以在手术分期之前可靠地识别EOC。由于良性疾病而决定进行卵巢切除术可能会导致不适合手术的患者不必要的发病率。研究结果可能会改变目前的临床模式：对潜在的良性肿瘤进行手术治疗，以避免延迟对潜在恶性肿瘤的手术干预。所提出的努力至少将有助于回答基于临床的非手术培养刺针在盆腔肿块分类和卵巢癌诊断中的潜在效用。一种微创、可靠的诊断工具将改善早期发现，从而提高EOC患者的生存率。

DESCRIPTION (provided by applicant): Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Nearly 10 million women in the US are at high risk for EOC with greater than 21,000 new annual diagnoses. Over 60% of diagnosed patients have advanced stage EOC, with a five-year survival rate less than 30%, compared to over 90% five-year survival for localized disease. Stage I EOC is difficult to detect amid non-specific symptoms that delay workup until a pelvic mass is found. Once an adnexal mass is found, the current diagnostic armamentarium includes sonographic grading of the tumor and analyzing serum levels of tumor markers, Cancer Antigen 125 [CA-125] and Human epididymis protein 4 [HE4]. HE4 is reported to be the most sensitive biomarker for detecting stage I EOC, while elevated serum levels of CA-125 (e 35 U/mL) alone lack adequate sensitivity and specificity for a definitive diagnosis. HE4, measurable in urine, to our knowledge, has not been measured in peritoneal fluid, although culdocentesis has been a useful technique in the field of gynecology for many years and can be performed in an outpatient setting. A minimally invasive, reliable diagnostic tool is needed for poor surgical candidates to avoid an oophorectomy for benign disease that could result in unnecessary morbidity. Specific Aim: To determine if levels of tumor markers (CA-125 and HE4) and cytology from peritoneal washings obtained via the cul-de-sac correlate with a diagnosis of epithelial ovarian cancer. We hypothesize that measuring these markers in combination from peritoneal fluid may increase the sensitivity to the presence of cancer cells beyond the ovarian cortex which may result in earlier detection of EOC. Study design: The prospective study will recruit and consent a convenience sampling of 60 women scheduled for surgical staging of a suspicious adnexal mass. Surgical staging of endometrial and ovarian carcinomas includes the collection of peritoneal washings. Our innovative technique differs from standard culdocentesis by infusing saline into the cul-de-sac and re-aspirating for collection (i.e. peritoneal washings). Cytology of peritoneal aspirations will be analyzed along with levels of tumor markers, CA-125 and HE4. Relevance: Our research goal is to develop a simple, non-surgical diagnostic tool that could reliably identify EOC prior to surgical staging. Th decision to undergo an oophorectomy for benign disease may result in unnecessary morbidity in patients who are poor surgical candidates. Study results could change the current clinical paradigm: operative management of a potentially benign tumor to avoid delayed surgical intervention of a potential malignancy. The proposed efforts will, at the very least, help answer the potential utility of clinic- based, non-surgical culdocentesis in pelvic mass triaging and ovarian cancer diagnosis. A minimally invasive, reliable diagnostic tool would improve early detection and, therefore, patient survival rates for EOC.