Ultrasonographic Visualization of the Ovaries to Detect Ovarian Cancer According to Age, Menopausal Status and Body Type.

Because the effects of age, menopausal status, weight and body mass index (BMI) on ovarian detectability by transvaginal ultrasound (TVS) have not been established, we determined their contributions to TVS visualization of the ovaries. A total of 29,877 women that had both ovaries visualized on their first exam were followed over 202,639 prospective TVS exams. All images were reviewed by a physician. While visualization of both ovaries decreased with age, one or both ovaries could be visualized in two of every three women over 80 years of age. Around 93% of pre-menopausal women and ~69% of post-menopausal women had both ovaries visualized. Both ovaries were visualized in ~72% of women weighing over 300 lbs. and in ~70% of women with a BMI over 40. Conclusions: Age had the greatest influence on the visualization of the ovaries. The ovaries can be visualized well past the menopause. Body habitus was not limiting to TVS ovarian imaging, and TVS should be considered capable of imaging one or both ovaries in two of every three women over 80 years of age. Thus, older and obese patients remain good candidates for TVS exams.

Significance of Pelvic Fluid Observed during Ovarian Cancer Screening with Transvaginal Sonogram.

The primary objective was to examine the role of pelvic fluid observed during transvaginal ultrasonography (TVS) in identifying ovarian malignancy. A single-institution, observational study was conducted within the University of Kentucky Ovarian Cancer Screening trial from January 1987 to September 2019. We analyzed true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) groups for the presence of pelvic fluid during screening encounters. Measured outcomes were the presence and duration of fluid over successive screening encounters. Of the 48,925 women surveyed, 2001 (4.1%) had pelvic fluid present during a TVS exam. The odds ratio (OR) of detecting fluid in the comparison group (TN screen; OR = 1) significantly differed from that of the FP cases (benign pathology; OR: 13.4; 95% confidence interval (CI): 9.1-19.8), the TP cases with a low malignant potential (LMP; OR: 28; 95% CI: 26.5-29.5), TP ovarian cancer cases (OR: 50.4; 95% CI: 27.2-93.2), and FN ovarian cancer cases (OR: 59.3; 95% CI: 19.7-178.1). The mean duration that pelvic fluid was present for women with TN screens was 2.2 ± 0.05 encounters, lasting 38.7 ± 1.3 months. In an asymptomatic screening population, free fluid identified in TVS exams was more associated with ovarian malignancy than in the control group or benign ovarian tumors. While pelvic free fluid may not solely discriminate malignancy from non-malignancy, it appears to be clinically relevant and warrants thoughtful consideration.

Disease-Specific Survival of Type I and Type II Epithelial Ovarian Cancers-Stage Challenges Categorical Assignments of Indolence & Aggressiveness.

Epithelial ovarian cancers (EOC) consist of several sub-types based on histology, clinical, molecular and epidemiological features that are termed "histo-types", which can be categorized into less aggressive Type I and more aggressive Type II malignancies. This investigation evaluated the disease-specific survival (DSS) of women with Type I and II EOC using histo-type, grade, and stage. A total of 200,658 EOC cases were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data. Kaplan-Meier survival analyses, one-factor ANOVA and Chi-square analyses were performed on 10-year DSS survivals. DSS strongly supported a 2-tiered classification (grade 1 vs. grade 2 & 3) for serous EOC. DSS of early stage serous EOC for grade 2 was significantly different from grade 3 indicating that a 2-tier classification for serous EOC applied only to late stage. DSS of Type I EOC was much better than Type II. However, DSS was 46-58% lower with late stage Type I than with early stage Type I indicating that Type I ovarian cancers should not be considered indolent. Early stage Type II EOC had much better DSS than late stage Type II stressing that stage has a large role in survival of both Type I and II EOC.

Uterine Corpus Malignancies in Appalachia Kentucky: Incidence, Survival, and Related Health Disparities.

OBJECTIVES: Uterine cancer is the nation's most common gynecologic malignancy, but it is understudied in the geographically and socioeconomically diverse state of Kentucky (KY). Our aim was to assess the frequency, distribution, and survival of uterine corpus malignancies in KY, and specifically the differences between Appalachia (AP) and non-Appalachia (NAP) KY. METHODS: This population-based cohort study used Surveillance, Epidemiology, and End Results data and the Kentucky Cancer Registry to study uterine corpus malignancy between January 1, 2000 and December 31, 2014. The analysis looked at the incidence between diagnoses in AP and NAP. The evaluation criteria included tumor histology (type I, type II, sarcoma, and mixed uterine malignancy), age, race, smoking status, stage at diagnosis, insurance status, and county of residence at diagnosis. RESULTS: The overall age-adjusted incidence rate and survival are similar for US and KY populations; however, histologic types and distribution differ. Compared with the United States, the incidence of corpus cancers in KY is higher for type I (P = 0.03), but lower for type II (P = 0.003), sarcoma (P = 0.006), and mixed (P < 0.001). AP KY has a higher incidence of type I (P < 0.0001) and mixed malignancy (P = 0.04), younger age at diagnosis (P < 0.0001), larger non-Hispanic white population (P < 0.0001), fewer smokers (P = 0.002), and more uninsured and Medicaid recipients (P < 0.0001) compared with NAP KY. The hazard ratio for death is similar in AP and NAP KY (0.896; 95% confidence interval 0.795-1.009). CONCLUSIONS: Type I and mixed uterine corpus cancers have a higher age-adjusted incidence and a younger age at diagnosis in AP compared with NAP KY.

Clinical Factors Associated with Longer Hospital Stay Following Ovarian Cancer Surgery.

Background: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy and is treated with a combination of cytoreductive surgery and platinum-based chemotherapy. Extended length of stay (LOS) after surgery can affect patient morbidity, overall costs, and hospital resource utilization. The primary objective of this study was to identify factors contributing to prolonged LOS for women undergoing surgery for ovarian cancer. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify women from 2012-2016 who underwent hysterectomy for ovarian, fallopian tube and peritoneal cancer. The primary outcome was LOS >50th percentile. Preoperative and intraoperative variables were examined to determine which were associated with prolonged LOS. Results: From 2012-2016, 1771 women underwent elective abdominal surgery for OC and were entered in the ACS-NSQIP database. The mean and median LOS was 4.6 and 4.0 days (IQR 0-38), respectively. On multivariate analysis, factors associated with prolonged LOS included: American Society of Anesthesiologists (ASA) Classification III (aOR 1.71, 95% CI 1.38-2.13) or IV (aOR 1.88, 95% CI 1.44-2.46), presence of ascites (aOR 1.88, 95% CI 1.44-2.46), older age (aOR 1.23, 95% CI 1.13-1.35), platelet count >400,000/mm3 (aOR 1.74, 95% CI 1.29-2.35), preoperative blood transfusion (aOR 11.00, 95% CI 1.28-94.77), disseminated cancer (aOR 1.28, 95% CI 1.03-1.60), increased length of operation (121-180 min, aOR 1.47, 95% CI 1.13-1.91; >180 min, aOR 2.78, 95% CI 2.13-3.64), and postoperative blood transfusion within 72 h of incision (aOR 2.04, 95% CI 1.59-2.62) (p < 0.05 for all). Conclusions: Longer length of hospital stay following surgery for OC is associated with many patient, disease, and treatment-related factors. The extent of surgery, as evidenced by perioperative blood transfusion and length of surgical procedure, is a factor that can potentially be modified to shorten LOS, improve patient outcomes, and reduce hospital costs.

Survival of Women With Type I and II Epithelial Ovarian Cancer Detected by Ultrasound Screening.

OBJECTIVE: To estimate the effect of ultrasound screening on stage at detection and long-term disease-specific survival of at-risk women with epithelial ovarian cancer. METHODS: Eligibility included all asymptomatic women 50 years of age or older and women 25 years of age or older with a documented family history of ovarian cancer. From 1987 to 2017, 46,101 women received annual ultrasound screening in a prospective cohort trial. Women with a persisting abnormal screen underwent tumor morphology indexing, serum biomarker analysis, and surgery. RESULTS: Seventy-one invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential were detected. No women with a low malignant potential tumor experienced recurrent disease. Stage distribution for screen-detected invasive epithelial ovarian cancers was stage I-30 (42%), stage II-15 (21%), stage III-26 (37%), and stage IV-0 (0%). Follow-up varied from 9.2 months to 27 years (mean 7.9 years). Disease-specific survival at 5, 10, and 20 years for women with invasive epithelial ovarian cancer detected by screening was 86±4%, 68±7%, and 65±7%, respectively, vs 45±2%, 31±2%, and 19±3%, respectively, for unscreened women with clinically detected ovarian cancer from the same geographic area who were treated at the same institution by the same treatment protocols (P<.001). Twenty-seven percent of screen-detected malignancies were type I and 73% were type II. The disease-specific survival of women with type I and type II screen-detected tumors was significantly higher than that of women with clinically detected type I and type II tumors and was related directly to earlier stage at detection. CONCLUSION: Annual ultrasound screening of at-risk asymptomatic women was associated with lower stage at detection and increased 5-, 10-, and 20-year disease-specific survival of women with both type I and type II epithelial ovarian cancer. CLINICAL TRIAL REGISTRATION: OnCore Clinical Trials Management System, NCI-2013-01954.

Population-Based Analysis of Patient Age and Other Disparities in the Treatment of Ovarian Cancer in Central Appalachia and Kentucky.

OBJECTIVES: Adherence to National Comprehensive Cancer Network (NCCN) guidelines for ovarian cancer treatment improves patient outcomes. The aim of this study was to assess disparities associated with ovarian cancer treatment in the state of Kentucky and central Appalachia. METHODS: Data on patients diagnosed as having ovarian cancer from 2007 through 2011 were extracted from administrative claims-linked Kentucky Cancer Registry data. NCCN compliance was defined by stage, grade, surgical procedure, and chemotherapy. Selection criteria were reviewed carefully to ensure data quality and accuracy. Descriptive analysis, logistic regression, and Cox regression analyses were performed to examine factors associated with guidelines compliance and survival. RESULTS: Most women were aged 65 years or older (62.5%) and had high-grade (65.9%) and advanced-stage (61.0%) ovarian cancer. Two-thirds of cases (65.9%) received NCCN-recommended treatment for ovarian cancer. The hazard ratio of death for women who did not receive NCCN-compliant care was 62% higher compared with the women who did receive NCCN-compliant treatment. Results from the logistic regression showed that NCCN-compliant treatment was more likely for women aged 65 to 74 years compared with women aged 20 to 49 years, late-stage compared with early-stage cancers, receipt of care at tertiary care hospitals, and privately insured compared with Medicaid or Medicare. CONCLUSIONS: When the treatment of ovarian cancer did not follow NCCN recommendations, patients had a significantly higher risk of death. Women were less likely to receive NCCN-compliant care if they were younger (20-49 years), had early-stage disease, did not have private insurance, or had care provided at a nontertiary care hospital.

Symptoms Relevant to Surveillance for Ovarian Cancer.

To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and >9500 women completed it more than one four times for >43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073%) for identifying ovarian cancer based on symptoms alone would predict one malignancy for 1368 cases taken to surgery due to reported symptoms. Confidence on the first questionnaire (83.3%) decreased to 74% when more than five questionnaires were completed. Age-related decreases in confidence were significant (p < 0.0001). Women reporting at least one symptom expressed more confidence (41,984/52,379 = 80.2%) than women reporting no symptoms (11,882/18,355 = 64.7%), p < 0.0001. Confidence was unrelated to history of hormone replacement therapy or abnormal ultrasound findings (p = 0.30 and 0.89). The frequency of symptoms relevant to ovarian cancer was much higher than the occurrence of ovarian cancer. Approximately 80.1% of women expressed confidence in what they reported.

Complications from Surgeries Related to Ovarian Cancer Screening.

The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients who underwent surgery for a positive screen in the Kentucky Ovarian Cancer Screening Program from 1988-2014. Data were abstracted from operative reports, discharge summaries, and office notes for 406 patients. Another 142 patients with incomplete records were interviewed by phone. Complete information was available for 548 patients. Complications were graded using the Clavien-Dindo (C-D) Classification of Surgical Complications and considered minor if assigned Grade I (any deviation from normal course, minor medications) or Grade II (other pharmacological treatment, blood transfusion). C-D Grade III complications (those requiring surgical, endoscopic, or radiologic intervention) and C-D Grade IV complications (those which are life threatening) were considered "major". Statistical analysis was performed using SAS 9.4 software. Complications were documented in 54/548 (10%) subjects. For women with malignancy, 17/90 (19%) had complications compared to 37/458 (8%) with benign pathology (p < 0.003). For non-cancer surgery, obesity was associated with increased complications (p = 0.0028). Fifty patients had minor complications classified as C-D Grade II or less. Three of 4 patients with Grade IV complications had malignancy (p < 0.0004). In the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial, 212 women had surgery for ovarian malignancy, and 95 had at least one complication (45%). Of the 1080 women with non-cancer surgery, 163 had at least one complication (15%). Compared to the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial, the Kentucky Ovarian Cancer Screening Program had significantly fewer complications from both cancer and non-cancer surgery (p < 0.0001 and p = 0.002, respectively). Complications resulting from surgery performed as a result of the Kentucky Ovarian Cancer Screening Program were infrequent and significantly fewer than reported in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Complications were mostly minor (93%) and were more common in cancer versus non-cancer surgery.

Probability of fallopian tube and ovarian detection with transvaginal ultrasonography in normal women.

OBJECTIVE: Some ovarian malignancies may originate in the fallopian tube. The feasibility of ultrasonographically visualizing the fallopian tube is presented. METHODS: In total, 549 normal women participated in the fallopian tube visualization trial, while ovarian visualization was studied in 43,521. Chi-square analysis, t-tests and multivariate analysis determined significance and interactions. RESULTS: Ovaries were observed in 82.7% while fallopian tubes were detected in 77.2% of women and 85.2% of the time when an ovary was detected. Age, BMI or parity was not significantly different when one or both fallopian tubes were visualized. Elevated BMI had slightly greater influence than age in limiting visualization of the fallopian tubes in multivariate analysis. CONCLUSION: Fallopian tubes can often be identified sonographically. Ovarian visualization provides the strongest indicator favoring fallopian tube detection. Thus, ultrasonographic examinations for adnexal cancer could include evaluation of fallopian tubes even in women >60 years and in women with BMI ≥25.

Serial ultrasonographic evaluation of ovarian abnormalities with a morphology index.

OBJECTIVE: Transvaginal ultrasonography with tumor morphology index (MI) has been used to predict the risk of ovarian malignancy. Our objective was to analyze changes in serial MI scores for malignant and non-malignant ovarian tumors in a large and asymptomatic population. METHODS: Eligible subjects participated in the University of Kentucky Ovarian Cancer Screening Program and had abnormalities that included cysts, cysts with septations, complex cysts with solid areas, and solid masses. Analysis included: MI, change in MI (delta MI), delta MI per scan and per month, number and duration of scans. RESULTS: From 1987 to 2012, 38,983 women received 218,445 scans. Of the 7104 eligible subjects, 6758 tumors were observed without surgery and 472 were surgically removed. Eighty-six percent (5811) of observed tumors were resolved. There were 74 malignant and 272 non-malignant tumors. Eighty-five percent of malignancies had MI ≥5 at decision for surgery. The risk of malignancy based on MI was: MI=5 (3%), MI=6 (3.7%), MI=7 (12.6%), MI=8 (26.7%), MI=9 (27.8%), MI=10 (33.3%). The mean delta MI per month decreased for tumors that resolved (delta MI -1.0, p<0.001) or persisted without surgery (delta MI -0.7, p<0.001). For abnormalities surgically removed, the mean delta MI per month increased significantly more for malignancies than for benign tumors (delta MI +1.6 vs. +0.3, p<0.001). CONCLUSIONS: The mean MI for malignant ovarian tumors increases over time, while non-malignant tumors have a decreasing or stable MI. Serial MI analysis can improve the prediction of ovarian malignancy by reducing false-positive results, thereby decreasing the number of operations performed for benign abnormalities.

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.

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.

Small cell carcinoma of the ovary of hypercalcemic type: a case report.

The authors report a case of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), in a mother and daughter and discuss the possibility of a heritable risk. Both mother and daughter were treated at the same institution for SCCOHT. A 23-year-old woman presented with hypercalcemia 4 months after giving birth to her daughter. She was diagnosed as having SCCOHT. Despite surgery, chemotherapy, and radiation, she died of the disease 11 months after diagnosis. Eleven years later, her daughter presented with a histologically and immunophenotypically identical SCCOHT tumor. She received postoperative chemotherapy and radiation but, eventually, relapsed and died of the disease at 27 months after the initial diagnosis. Small cell carcinoma of the ovary, hypercalcemic type, is an uncommon and aggressive malignancy that occurs in young women, which is associated with a solid ovarian tumor and hypercalcemia. Despite aggressive multimodality treatment, most patients die within 2 years of diagnosis. Genetic counseling, sonographic ovarian surveillance and serum calcium monitoring at early age, and even prophylactic oophorectomy should be considered for surviving at-risk family members.

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.

Cervical cancer survival for patients referred to a tertiary care center in Kentucky.

OBJECTIVES: To identify prognostic factors influencing cervical cancer survival for patients referred to a tertiary care center in Kentucky. METHODS: A cohort study was performed to assess predictive survival factors of cervical cancer patients referred to the University of Kentucky from January 2001 to May 2010. Eligibility criteria included those at least 18 years-old, cervical cancer history, and no prior malignancy. Descriptive statistics were compiled and univariable and multivariable Cox proportional hazard analysis were performed. RESULTS: 381 patients met entry criteria. 95% were Caucasian (N=347) and 66% (N=243) lived in Appalachian Kentucky. The following covariates showed no evidence of a statistical association with survival: race, body mass index, residence, insurance status, months between last normal cervical cytology and diagnosis, histology, tumor grade, and location of primary radiation treatment. After controlling for identified significant variables, stage of disease was a significant predictor of overall survival, with estimated relative hazards comparing stages II, III, and IV to stage I of 3.09 (95% CI: 1.30, 7.33), 18.11 (95% CI: 7.44, 44.06), and 53.03(95% CI: 18.16, 154.87), respectively. The presence of more than two comorbid risk factors and unemployment was also correlated with overall survival [HR 4.25 (95% CI: 1.00, 18.13); HR 2.64 (95% CI 1.29, 5.42), respectively]. CONCLUSIONS: Residence and location of treatment center are not an important factor in cervical cancer survival when a tertiary cancer center can oversee and coordinate care; however, comorbid risk factors influence survival and further exploration of disease comorbidity related to cervical cancer survival is warranted.

Risk for residual adenocarcinoma in situ or cervical adenocarcinoma in women undergoing loop electrosurgical excision procedure/conization for adenocarcinoma in situ.

OBJECTIVE: To evaluate the risk for residual adenocarcinoma in situ (AIS) or cervical adenocarcinoma in women undergoing loop electrosurgical excision procedure (LEEP)/conization as the initial management for AIS. STUDY DESIGN: A retrospective chart study was conducted from 1990 to 2005. Patients with AIS were identified from a pathology database. RESULTS: Forty-three patients were identified with AIS of the cervix who were initially treated with LEEP/conization. Twelve cases of invasive adenocarcinoma (28%) were identified on LEEP/conization. Margin status was available for 41 patients. Twenty (49%) patients had a positive margin, and 21 (51%) patients had a negative margin. Nineteen women with positive margins underwent definitive surgical therapy; 68% had residual AIS. Eleven women with negative margins underwent hysterectomy; 45% had residual AIS. Women with positive and negative margins were compared and found to differ significantly in regard to diagnosis of adenocarcinoma on LEEP/conization. CONCLUSION: Women status post-LEEP/conization for AIS have a high risk of residual AIS, even with negative conization margins. If definitive hysterectomy is deferred, close follow-up is mandatory.

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.

Performance of the American College of Obstetricians and Gynecologists' ovarian tumor referral guidelines with a multivariate index assay.

OBJECTIVE: The American College of Obstetricians and Gynecologists (the College) published referral guidelines for women with a pelvic mass that incorporate CA 125. A new multivariate index assay assesses the malignant risk of ovarian tumors before surgery. Our objective was to estimate the performance of the College guidelines with this new multivariate index assay. METHODS: This prospective, multi-institutional trial included 27 primary care and specialty sites throughout the United States. The College guidelines were evaluated in women scheduled for surgery for an ovarian mass. Clinical criteria and blood for biomarkers were collected before surgery. A standard CA 125-II assay was used and the value applied to the multivariate index assay algorithm and the CA 125 analysis. Study results were correlated with surgical pathology. RESULTS: Of the 590 women enrolled with ovarian mass on pelvic imaging, 516 were evaluable. There were 161 malignancies (45 premenopausal and 116 postmenopausal). The College referral criteria had a modest sensitivity in detecting malignancy. Replacing CA 125 with the multivariate index assay increased the sensitivity (77-94%) and negative predictive value (87-93%) while decreasing specificity (68-35%) and positive predictive value (52-40%). Similar trends were noted for premenopausal women and early-stage disease. CONCLUSION: Replacing CA 125 with the multivariate index assay improves the sensitivity and negative predictive value of the College referral guidelines while decreasing specificity and positive predictive value. The high sensitivity is maintained in premenopausal women and early-stage disease.