Diagnostic Utility of Culdocentesis in Patients with a Suspicious Adnexal Mass

描述（由申请人提供）：上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤。在美国，近1000万女性面临EOC的高风险，每年新诊断超过21，000例。超过60%的确诊患者患有晚期EOC，五年生存率低于30%，而局部疾病的五年生存率超过90%。一旦发现附件包块，目前的诊断方法包括超声对肿瘤进行分级，并分析血清肿瘤标志物、癌抗原125 [CA-125]和人附睾蛋白4 [HE 4]的水平。据报道，HE 4是用于检测I期EOC的最敏感的生物标志物，而单独升高的CA-125血清水平（e 35 U/mL）缺乏用于明确诊断的足够的灵敏度和特异性。据我们所知，尽管后穹窿穿刺术多年来一直是妇科领域的一种有用技术，并且可以在门诊环境中进行，但在尿液中可测量的HE 4尚未在腹膜液中测量。一个微创的，可靠的诊断工具是需要穷人的手术候选人，以避免卵巢切除术的良性疾病，可能会导致不必要的发病率。具体目标：确定肿瘤标志物（CA-125和HE 4）水平和经子宫陷凹获得的腹腔冲洗液细胞学检查结果是否与上皮性卵巢癌的诊断相关。我们推测，从腹腔液中联合检测这些标志物可能会增加对卵巢皮质以外癌细胞存在的敏感性，这可能会导致早期检测EOC。研究设计：这项前瞻性研究将招募并同意对60名计划对可疑附件肿块进行手术分期的妇女进行方便抽样。子宫内膜癌和卵巢癌的手术分期包括收集腹腔冲洗液。我们的创新技术与标准后穹窿穿刺术不同，将生理盐水注入后穹窿并重新抽吸收集（即腹膜冲洗液）。将沿着分析腹膜穿刺液的细胞学以及肿瘤标志物CA-125和HE 4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。良性疾病患者行卵巢切除术可能会导致不必要的并发症，而这些患者并不适合手术。研究结果可能会改变目前的临床模式：手术治疗潜在的良性肿瘤，以避免延迟手术干预的潜在恶性肿瘤。这些努力至少将有助于回答基于临床的非手术后穹窿穿刺术在盆腔肿块分类和卵巢癌诊断中的潜在效用。一种微创、可靠的诊断工具将提高早期发现率，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.