Diagnostic Utility of Culdocentesis in Patients with a Suspicious Adnexal Mass

描述(申请人提供)：卵巢上皮癌(EOC)是最致命的妇科恶性肿瘤。在美国，近1000万女性面临着患EoC的高风险，每年新增诊断病例超过2.1万例。超过60%的确诊患者患有晚期卵巢癌，五年生存率不到30%，而局部疾病的五年生存率超过90%。第一阶段的EOC很难在非特异性症状中被发现，这些症状会推迟检查，直到发现盆腔肿块。一旦发现附件肿块，目前的诊断工具包括对肿瘤进行超声分级，并分析血清肿瘤标志物、癌症抗原125[CA-125]和人类附睾蛋白4[HE4]的水平。据报道，HE4是检测I期卵巢癌最敏感的生物标志物，而血清CA-125水平升高(e 35U/mL)本身并不足以确定诊断的敏感性和特异性。据我们所知，HE4可在尿液中检测到，但尚未在腹腔液中检测到，尽管多年来导管穿刺术在妇科领域一直是一种有用的技术，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进行卵巢切除术，因为良性疾病可能导致不必要的并发症。具体目的：确定肿瘤标志物(CA-125和HE4)水平和腹膜冲洗液细胞学检查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记物可能会增加对卵巢皮质以外癌细胞存在的敏感性，这可能会导致更早发现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外科分期包括收集腹膜冲洗液。我们的创新技术不同于标准的球囊穿刺术，它将生理盐水注入死胡同，然后重新抽出进行收集(即腹膜冲洗)。腹膜活检的细胞学将与肿瘤标志物CA-125和HE4的水平一起进行分析。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上皮性卵巢癌。决定接受良性疾病的卵巢切除术可能会导致不适合手术的患者出现不必要的并发症。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，以避免延迟对潜在的恶性肿瘤进行手术干预。建议的努力至少将有助于回答以临床为基础的非手术导管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，从而提高卵巢癌患者的存活率。

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.