Christopher P. DeSimone

Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors

OBJECTIVE: To compare the effectiveness of physician assessment with a new multivariate index assay in identifying high-risk ovarian tumors. METHODS: The multivariate index assay was evaluated in women scheduled for surgery for an ovarian tumor in a prospective, multi-institutional trial involving 27 primary- care and specialty sites throughout the United States. Preoperative serum was collected, and results for the multivariate index assay, physician assessment, and CA 125 were correlated with surgical pathology. Physician assessment was documented by each physician before surgery. CA 125 cutoffs were chosen in accordance with the referral guidelines of the American College of Obstetricians and Gynecologists. RESULTS: The study enrolled 590 women, with 524 evaluable for the multivariate index assay and CA 125, and 516 for physician assessment. Fifty-three percent were enrolled by nongynecologic oncologists. There were 161 malignancies and 363 benign ovarian tumors. Physician assessment plus the multivariate index assay correctly identified malignancies missed by physician assessment in 70% of nongynecologic oncologists, and 95% of gynecologic oncologists. The multivariate index assay also detected 76% of malignancies missed by CA 125. Physician assessment plus the multivariate index assay identified 86% of malignancies missed by CA 125, including all advanced cancers. The performance of the multivariate index assay was consistent in early- and late-stage cancers. CONCLUSION: The multivariate index assay demonstrated higher sensitivity and lower specificity compared with physician assessment and CA 125 in detecting ovarian malignancies. LEVEL OF EVIDENCE: III

Malignant struma ovarii: a case report and analysis of cases reported in the literature with focus on survival and i131 therapy

BACKGROUND Malignant struma ovarii is a rare type of germ cell tumor that is most often diagnosed postoperatively. The natural history and optimal treatment regimen for the disease are essentially unknown due to the small numbers of published cases. CASE A 32-year-old woman presented with pelvic pain and an ovarian mass that was ultimately treated by total abdominal hysterectomy/bilateral salpingo-oophorectomy. Postoperatively, she was diagnosed with a malignant struma ovarii. The patient was subsequently treated with thyroidectomy and I(131) ablation and is currently disease free. A Medline literature search was performed and clinical data from 23 additional cases were compiled. CONCLUSION In this review of 24 cases, 16 patients were followed conservatively postoperatively while 8 received varied additional therapy (4 with I(131)). There were 8 recurrences and all occurred in the conservatively managed patients. I(131) for recurrent disease provided an initial complete response in 7 women. Treatment with thyroidectomy and I(131) should be considered in the first line of management for malignant struma ovarii.

Ten-year relative survival for epithelial ovarian cancer.

OBJECTIVE: Most patients with epithelial ovarian cancer who are alive at 5 years have active disease. Thus, 10-year survival rather than 5-year survival may be a more appropriate endpoint. Relative survival adjusts for the general survival of the United States population for that race, sex, age, and date at which the diagnosis was coded. Our objective was to estimate relative survival in epithelial ovarian cancer over the course of 10 years. METHODS: Using the Surveillance, Epidemiology and End Results 1995–2007 database, epithelial ovarian cancer cases were identified. Using the actuarial life table method, relative survival over the course of 10 years was calculated, stratified by stage, classification of residence, surgery as the first course of treatment, race, and age. RESULTS: There were 40,692 patients who met inclusion criteria. The overall relative survival was 65%, 44%, and 36% at 2, 5, and 10 years, respectively. The slope of decline in relative survival was reduced for years 5–10 as compared with years 1–5 after diagnosis. Relative survival at 5 years was 89%, 70%, 36%, and 17%, and at 10 years relative survival was 84%, 59%, 23%, and 8% for stages I, II III, and IV, respectively. At all stages, patients with nonsurgical primary treatment and those with advanced age had reduced relative survival. CONCLUSIONS: The 10-year relative survival for stage III is higher than expected. This information provides the physician and the patient with more accurate prognostic information. LEVEL OF EVIDENCE: III

Violence against Women Raises Risk of Cervical Cancer

BACKGROUND An emerging literature suggests that violence against women (VAW), particularly sexual violence, may increase the risk of acquiring a sexually transmitted infection (STI) and, therefore, may be associated with cervical cancer development. The purpose of this cross-sectional analysis was to determine if women who had experienced violence had higher prevalence rates of invasive cervical cancer. METHODS Women aged 18-88 who joined the Kentucky Womens Health Registry (2006-2007) and completed a questionnaire were included in the sample. Multivariate logistic regression analyses were used to adjust odds ratio (OR) for confounders (e.g., age, education, current marital status, lifetime illegal drug use, and pack-years of cigarette smoking). RESULTS Of 4732 participants with no missing data on violence, cervical cancer, or demographic factors, 103 (2.1%) reported ever having cervical cancer. Adjusting for demographic factors, smoking, and illegal drug use, experiencing VAW was associated with an increased prevalence of invasive cervical cancer (adjusted OR [aOR] = 2.6, 95% CI = 1.7-3.9). This association remained significant when looking at three specific types of VAW: intimate partner violence (IPV) (aOR = 2.7, 95% CI = 1.8-4.0), adult exposure to forced sex (aOR = 2.6, 95% CI = 1.6-4.3), and child exposure to sexual abuse (aOR = 2.4, 95% CI = 1.4-4.0). CONCLUSIONS Rates of cervical cancer were highest for those experiencing all three types of VAW relative to those never experiencing VAW. Because VAW is common and has gynecological health effects, asking about VAW in healthcare settings and using this information to provide tailored healthcare may improve womens health outcomes.

Long-term Survival of Women With Epithelial Ovarian Cancer Detected by Ultrasonographic Screening

OBJECTIVE: To estimate the effect of ultrasonographic screening on stage at detection and long-term disease-specific survival of women with epithelial ovarian cancer. METHODS: Eligibility included all asymptomatic women aged 50 years and older and women aged 25 years and older with a documented family history of ovarian cancer. From 1987 to 2011, 37,293 women received annual ultrasonographic screening. Women with abnormal screens underwent tumor morphology indexing, serum biomarker analysis, and surgery. RESULTS: Forty-seven invasive epithelial ovarian cancers and 15 epithelial ovarian tumors of low malignant potential were detected. No women with low malignant potential tumors experienced recurrent disease. Stage distribution for invasive epithelial cancers was: stage I, 22 (47%); stage II, 11 (23%); stage III, 14 (30%), and stage IV, 0 (0%). Follow-up varied from 2 months to 20.1 years (mean, 5.8 years). The 5-year survival rate for invasive epithelial ovarian cancers detected by screening was: stage I, 95%±4.8%; stage II, 77.1%±14.5%; and stage III, 76.2%±12.1%. The 5-year survival rate for all women with invasive epithelial ovarian cancer detected by screening as well as interval cancers was 74.8%±6.6% compared with 53.7%±2.3% for unscreened women with ovarian cancer from the same institution treated by the same surgical and chemotherapeutic protocols (P<.001). CONCLUSION: Annual ultrasonographic screening of asymptomatic women achieved increased detection of early-stage ovarian cancer cases and an increase in 5-year disease-specific survival rate for women with ovarian cancer. LEVEL OF EVIDENCE: II

Ultrasound Screening for the Early Detection of Ovarian Cancer

Ovarian cancer screening in the general population has been performed using ultrasound examination of the female pelvis and serum tumor marker determinations. Ultrasound examinations, particularly transvaginal sonography (TVS), have been advocated as potentially useful modalities. Investigators from the University of Kentucky (Lexington, KY) and Hirosaki University (Hirosaki, Japan) have recently published results from ultrasound-based ovarian cancer screening studies. The Kentucky trial screened 14,469 women using TVS on an annual basis. One hundred eighty women underwent surgery, and 17 ovarian cancers were detected, 11 of which were invasive epithelial lesions. The Hirosaki trial reported the results of an ultrasound-based screening study among 51,550 women who were first-time participants. Three hundred twenty-four women underwent surgery, and 22 ovarian cancers were detected. In each of these trials, the positive predictive value of gray-scale sonography was low. Morphologic tumor indexing and Doppler examinations have both been proposed as potential second-line studies, which could increase the positive predictive value of gray-scale ultrasound. A review of these techniques is presented. At present, ovarian cancer screening in the general population using ultrasound examinations is an experimental technique. Further studies are needed to determine whether second-line testing can improve the positive predictive value of gray-scale sonography such that asymptomatic women do not undergo unnecessary surgery for benign masses.

Predicting risk of malignancy in adnexal masses.

OBJECTIVE: To estimate the accuracy of preoperative ultrasonography, serum CA 125, and patient demographics as a means of predicting risk of malignancy in women with a ultrasonographically confirmed adnexal mass. METHODS: Tumor morphology derived from ultrasonographic images, tumor size, tumor bilaterality, serum CA 125, and patient demographics were evaluated preoperatively in 395 patients undergoing surgery from 2001 to 2008. Tumor morphology was classified as complex, solid, or cystic. Preoperative findings were compared with tumor histologic findings at the time of surgery. Multivariable classification and regression tree analysis were used to identify a group of patients at high risk of ovarian malignancy. RESULTS: One hundred eighteen patients had ovarian cancer, 13 patients had ovarian tumors of borderline malignancy, and 264 had benign ovarian tumors. Multivariable classification and regression tree analysis defined women at high risk of ovarian malignancy as those with an adnexal mass having complex or solid morphology and a serum CA 125 value greater than 35 units/mL. This definition had a positive predictive value of 84.7% and a negative predictive value of 92.4% and correctly identified 77.3% of patients with stage I and stage II ovarian cancer and 98.6% of patients with stage III and stage IV ovarian cancer. CONCLUSION: Patients with solid or complex ovarian tumors and an elevated serum CA 125 level (greater than 35 units/mL) are at high risk of ovarian malignancy. LEVEL OF EVIDENCE: II

Rate of pathology from atypical glandular cell Pap tests classified by the Bethesda 2001 nomenclature.

OBJECTIVE: To estimate the risk of significant pathology from atypical glandular cell (AGC) Pap tests classified by the 2001 Bethesda system and to assess potential differences in AGC management practices between physician specialties. METHODS: A chart study was conducted to assess outcomes from AGC Pap tests diagnosed during 2001–2005. RESULTS: One hundred thirty-one AGC Pap tests were identified from 84,748 Pap tests. The incidence of AGC was 0.15%. Thirty-nine AGC Pap tests (30%) were excluded from analysis, leaving 92 AGC Pap tests from 82 patients available for review. Thirty-one of 82 women (38%) had significant pathology. Seventeen women (21%) had preinvasive disease: cervical intraepithelial neoplasia 2 or 3, adenocarcinoma in situ and endometrial hyperplasia, whereas 14 women (17%) had invasive adenocarcinomas of the endometrium, cervix, ovary, and rectum. Women who were aged 40 years or younger differed significantly from women aged older than 40 years with regard to final pathology (P = .002). Specifically, they were more likely to have preinvasive disease and less likely to have invasive carcinoma. Recommended management for AGC includes colposcopy with or without biopsy, endocervical curettage, and endometrial biopsy. Sixty-three of 82 (77%) women were managed by recommended guidelines, and there was a statistically significant difference in physician adherence when comparing gynecologists to primary care physicians (87% compared with 50%, P < .001). CONCLUSION: Atypical glandular cell cytology confers a risk (38%) of either preinvasive disease or carcinoma, with the risk of carcinoma increasing significantly for women aged older than 40. Adherence to recommended AGC management guidelines is crucial to identify underlying malignancies. LEVEL OF EVIDENCE: II-2

Frequency and Disposition of Ovarian Abnormalities Followed With Serial Transvaginal Ultrasonography

OBJECTIVE: To examine the prevalence, incidence, persistence, and resolution of ovarian abnormalities using serial transvaginal ultrasonography. METHODS: A group of 39,337 women in the University of Kentucky Ovarian Cancer Screening Program were monitored with 221,576 baseline and interval transvaginal ultrasonography. RESULTS: The transvaginal ultrasonogram was normal for first and all subsequent visits for 31,834 participants (80.9%), whereas 6,807 women (17.3%) had transvaginal ultrasonograms interpreted as abnormal and were monitored over 21,588 ultrasonograms. Ovarian cysts were more common in premenopausal (prevalence 34.9%, incidence 15.3%) than in postmenopausal women (prevalence 17.0%, incidence 8.2%). For the group with abnormalities, the initial transvaginal ultrasonogram was abnormal in 46.7% of the cases, of which 63.2% resolved to normal on subsequent ultrasonograms. Of 35,314 cases classified as normal on the first examination, 9.9% were abnormal on subsequent annual examinations. The abnormal findings were classified as follows: unilocular cysts (11.5%), cysts with septations (9.8%), cysts with solid areas (7.1%), and solid masses (1.8%). Many transvaginal ultrasonographic abnormalities were followed to resolution. Surgery was performed on 557 participants for 85 ovarian malignancies and 472 nonmalignancies. Over the duration of the study, the positive predictive value (PPV) increased from 8.1% to 24.7%. CONCLUSION: Serial ultrasonography has shown that many ovarian abnormalities resolve, even if the initial appearance is complex, solid, or bilateral. Thus, it is advantageous to avoid a single transvaginal ultrasonographic abnormality as the sole trigger for surgery and to take a measured serial approach to reduce false-positive results and increase the PPV. LEVEL OF EVIDENCE: II

Risk of malignancy in sonographically confirmed septated cystic ovarian tumors

OBJECTIVE To determine the risk of malignancy in septated cystic ovarian tumors. MATERIALS 1319 (4.4%) of 29,829 women were identified by transvaginal sonography (TVS) as having a complex cystic ovarian tumor with septations without solid areas or papillary projections and were placed on long-term ultrasound surveillance for ovarian malignancy. RESULTS These 1319 patients had a total of 2870 septated cystic ovarian tumors. 2288 tumors (79.7%) had a septal width <2 mm and 582 (20.3%) had a septal width >or=2 mm. 2286 tumors (79.6%) were <5 cm in diameter and 584 (20.4%) were>or=5 cm in diameter. 1114 septated cystic tumors (38.8%) resolved spontaneously (mean duration to resolution-12 months) and 1756 (61.2%) tumors persisted. 128 patients underwent surgical tumor removal within 3 months of ultrasound. Most common histopathology was: serous cystadenoma (75), mucinous cystadenoma (13), and endometrioma (10). One patient had an ovarian tumor of borderline malignancy (Stage IB). There were no cases of ovarian cancer. Patients were followed from 4 to 252 months (mean-77 months). One patient developed papillary morphology in the contralateral ovary 3.2 years after detection of a septated ovarian cyst and had epithelial ovarian cancer in that ovary and in the omentum (Stage IIIC disease). The remaining patients are all free of ovarian neoplasia after a total of 7642 follow-up years. CONCLUSIONS Septated cystic ovarian tumors without solid areas or papillary projections have a low risk of malignancy and can be followed sonographically without surgery.