Edward R. Kost

The accuracy of colposcopic grading for detection of high-grade cervical intraepithelial neoplasia

Objective. To relate aspects of online colposcopic image assessment to the diagnosis of grades 2 and 3 cervical intraepithelial neoplasia (CIN 2+). Methods: To simulate colposcopic assessment, we obtained digitized cervical images at enrollment after acetic acid application from 919 women referred for equivocal or minor cytologic abnormalities into the ASCUS-LSIL Triage Study. For each, 2 randomly assigned evaluators from a pool of 20 colposcopists assessed images using a standardized tool online. We calculated the accuracy of these assessments for predicting histologic CIN 2+ over the 2 years of study. For validation, a subset of online results was compared with same-day enrollment colposcopic assessments. Results. Identifying any acetowhite lesion in images yielded high sensitivity: 93% of women with CIN 2+ had at least 1 acetowhite lesion. However, 74% of women without CIN 2+ also had acetowhitening, regardless of human papillomavirus status. The sensitivity for CIN 2+ of an online colpophotographic assessment of high-grade disease was 39%. The sensitivity for CIN 2+ of a high-grade diagnosis by Reid Index scoring was 30%, and individual Reid Index component scores had similar levels of sensitivity and specificity. The performance of online assessment was not meaningfully different from that of same-day enrollment colposcopy, suggesting that these approaches have similar utility. Conclusions. Finding acetowhite lesions identifies women with CIN 2+, but using subtler colposcopic characteristics to grade lesions is insensitive. All acetowhite lesions should be assessed with biopsy to maximize sensitivity of colposcopic diagnosis with good specificity.

Cervical adenocarcinoma in situ: a systematic review of therapeutic options and predictors of persistent or recurrent disease.

The incidence of cervical adenocarcinoma in situ is increasing in frequency, and our limited knowledge about this lesion presents the physician with a therapeutic dilemma. Treatment for this lesion has included conservative therapy, large loop excision or cold-knife cone biopsy, or definitive therapy consisting of hysterectomy. But, rates of residual adenocarcinoma in situ after cone biopsy with negative margins vary from 0% to 40%, and residual disease rates as high as 80% have been noted when the margins are positive. Despite these recent data on follow-up after conservative therapy such as cone biopsy, it seems that this method is safe and gaining acceptance by many physicians and patients. However, the short follow-up duration and small number of patients limit the conclusions of many studies. The relative infrequency of this diagnosis has precluded extensive clinical experience with the natural history of this lesion. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives After completion of this article, the reader will be able to summarize the current data on the treatment of adenocarcinoma in situ of the cervix, to outline potential treatment options for the patient with adenocarcinoma in situ of the cervix, and to list the factors associated with disease recurrence.

Asian-Pacific Islander race independently predicts poor outcome in patients with endometrial cancer☆

OBJECTIVE The Department of Defense health care system provides access to care without respect to age, race, or socioeconomic status. We sought to determine the effect of race as a predictor of survival in patients with endometrial cancer treated in the Department of Defense medical system. METHODS Information on patients with endometrial carcinoma was extracted from the Department of Defense centralized tumor registry for the period 1988 to 1995. Data included age at diagnosis, military status, race, tumor histology, grade, FIGO surgical stage, adjuvant therapies, and disease-free survival. The chi(2) test was used for analysis of prognostic factors and adjuvant treatments between racial groups. Actuarial survival curves were calculated by using the method of Kaplan and Meier and compared by the log-rank test. Variables found to be significant on univariate analysis (P < 0.05) were entered into a multivariate Cox regression analysis. RESULTS Of 1811 patients meeting criteria for the study, racial distribution was 90% Caucasian, 4.4% African-American, and 5.5% Asian-Pacific Islander. African-Americans had more advanced stages of disease compared to Caucasians (P < 0.001). Both African-Americans and Asian-Pacific Islanders had higher grade tumors and less favorable histologic types than Caucasians (P < 0.05). The extent of adjuvant therapies was similar for racial groups. African-Americans and Asian-Pacific Islanders had significantly worse 5-year disease-free survivals than Caucasians (P = 0.007). Additional poor prognostic factors included age >60 years, grade, unfavorable histology, and stage. On multivariate analysis age >60 years, stage, and Asian-Pacific Islander race remained significant prognostic factors. CONCLUSION African-Americans and Asian-Pacific Islanders had worse survivals than Caucasians. After controlling for imbalances in clinicopathologic factors, Asian-Pacific Islander race was found to be a newly identified poor prognostic factor.

Coccidioidomycosis mimicking ovarian cancer.

BACKGROUND: Dissemination of coccidioidomycosis to the abdominal cavity is rare. No previous case of peritoneal coccidioidomycosis has presented as an adnexal mass. CASE: We report a case of peritoneal coccidioidomycosis mimicking ovarian carcinoma. The patient presented with a complex ovarian mass, ascites, omental caking, and an elevated CA 125. The ultimate diagnosis was not made until frozen section histopathology was performed at staging laparotomy. CONCLUSION: Peritoneal coccidioidomycosis can present with the clinical, radiographic, and serologic features of ovarian cancer. Although essential for diagnosis and staging, radiographic studies and tumor markers have limited specificity. Coccidioidomycosis now joins other benign conditions that comprise the differential diagnosis of patients who present with what seems to be advanced ovarian carcinoma. Infectious diseases consultation is recommended for the management of peritoneal coccidioidomycosis.

Cancer among first-degree relatives of probands with invasive and borderline ovarian cancer.

Objective The familial clustering of ovarian, breast, endometrial, colon, and prostate cancer was compared in firstdegree relatives of probands with invasive and borderline ovarian cancer to determine coaggregation. Methods Probands (n = 392), who had been patients in the Division of Gynecologic Oncology at Washington University, were ascertained consecutively. Family history on 2192 first-degree relatives was collected by personal interviews of the probands and other family members. Estimates of prevalence of cancers in first-degree relatives of the two proband groups were compared. Survival analysis was used to examine the age-at-onset distribution of each cancer in relatives of invasive probands versus relatives of borderline probands. Results Among the relatives were 24 cases of ovarian cancer, 46 cases of breast cancer, 13 cases of endometrial cancer, and 25 and 28 cases of colon and prostate cancer, respectively. There were no significant differences in the prevalence of any of these cancers in relatives of the invasive and borderline probands. Cumulative lifetime risk estimates did not differ between the relatives of the two groups for any cancers. Age-at-onset of ovarian cancer did not differ between probands with positive family histories of the five cancers and those with negative histories. The inability to reject the null hypothesis of no differences in the first-degree relatives of our two study groups might be from insufficient power to detect small differences, given our sample size. Conclusion These results suggest that relatives of patients with invasive and borderline ovarian cancer might share similar cancer risks and age-at-onset distributions.

Comparative assessment of hypercoagulability in women with and without gynecologic malignancies using the thromboelastograph coagulation analyzer

The hypercoagulability status of women with and without gynecologic malignancies was compared using the thromboelastograph coagulation analyzer. Blood specimens from 25 women with newly diagnosed gynecologic malignancies and from 21 age-matched controls were analyzed. Hypercoagulability is defined by a short R value (min), a short K value (min), an elevated maximum amplitude (MA) value (mm), and a broad α-angle (°). A two-tailed, two-sample t-test was used for statistical analysis. When compared with specimens from age-matched controls, specimens from women with gynecologic malignancies demonstrated values consistent with hypercoagulability. The specific parameters are presented as a mean (± SD). Patients with gynecologic malignancies were found to have a short R value (7.1 ± 2.1 vs. 11.8 ± 1.8 min; P < 0.001), a short K value (3.1 ± 0.9 vs. 4.6 ± 0.9 min; P < 0.001), a prolonged MA value (64.7 ± 5.4 vs. 58.8 ± 6.1 mm; P = 0.001), and a greater α-angle (70.6 ± 5.3 vs. 61.6 ± 4.9°; P < 0.001). Detection of hypercoagulability as measured by thromboelastography is statistically more common among women with gynecologic malignancies compared with age-matched controls. Future studies may address the use of thromboelastography to identify patients at risk for gynecologic malignancies.

The role of tumor necrosis factor receptors in tumor necrosis factor-α - mediated cytolysis of ovarian cancer cell lines

Abstract OBJECTIVE: Our purpose was to define the expression of tumor necrosis factor receptors on ovarian cancer cells and determine what role these receptors play in tumor necrosis factor-α - mediated cytolysis. STUDY DESIGN: Cell surface expression of tumor necrosis factor-α receptors was determined on ovarian cancer cell lines Caov-3, SK-OV-3, NIH : OVCAR-3, and A2780 by a tumor necrosis factor-α binding assay that used iodine 125 - labeled tumor necrosis factor-α. Monoclonal antibodies specific for the 55 to 60 kd (TR60) and 75 to 80 kd (TR80) tumor necrosis factor receptors were used to determine the relative density of each receptor type. To elucidate which receptor(s) was responsible for mediating the signal for cytolysis, 24-hour MTT cytolytic assays that used tumor necrosis factor-α and emetine were performed in the presence or absence of receptor-specific monoclonal antibodies. RESULTS: The four ovarian cell lines expressed a similar number of surface receptors, 4500 to 7000 per cell, had similar dissociation constants, 0.3 to 0.6 nmol/L, and expressed predominately the TR60 receptor subtype. Receptor function studies showed that the presence of the monoclonal antibody to the TR60 receptor completely inhibited tumor necrosis factor-α - mediated cytolysis, whereas the monoclonal antibody to the TR80 receptor only partially blocked cytolysis. CONCLUSIONS: Ovarian cancer cell lines express both tumor necrosis factor receptors, with the TR60 receptor being the dominant subtype. Tumor necrosis factor-α - mediated cytolysis appears to be dependent on the presence of a functional TR60 receptor. The TR80 receptor does not appear requisite for cytolysis; however, a complementary role cannot be excluded. Manipulation of tumor necrosis factor receptor subtypes on ovarian cancer cells may enhance the cytotoxic effects, thus improving the therapeutic efficacy of tumor necrosis factor-α. (AM J OBSTET GYNECOL 1996;174:145-53.)

Vulvar cancer in human immunodeficiency virus-seropositive premenopausal women: A case series and review of the literature

This review describes three cases of human immunodeficiency virus-infected women who were diagnosed with vulvar cancer before age 40 years. A retrospective chart review was performed for three patients who were younger than 40 years of age and who had histologically confirmed invasive squamous cell carcinoma of the vulva diagnosed between 1999 and 2002. Demographic, clinical, and laboratory data were recorded. Three human immunodeficiency virus-seropositive women were diagnosed with invasive squamous cell carcinoma of the vulva, stages IA, IB1, and III. All cases were characterized by extensive surrounding vulvar, vaginal, and cervical intraepithelial neoplasia. CD4 cell counts were 250, 330, and 900 cells/uL. Two patients experienced previous acquired immune deficiency syndrome-defining illnesses: toxoplasmosis and cervical cancer. Vulvar cancer in young human immunodeficiency virus-seropositive women may be associated with other human papillomavirus-related diseases and immunosuppression, as evidenced by low CD4 counts and the presence of antecedent acquired immune deficiency syndrome-defining illnesses.

Epithelioid trophoblastic tumor masquerading as invasive squamous cell carcinoma of the cervix after an ectopic pregnancy

☆ The view(s) expressed herein are those of the au official policy or position of Brooke Army Medical C Department, the U.S. Army Office of the Surgeon Genera Department of Defense or the U.S. Government. ☆☆ Poster presentation at the Armed Forces District and Gynecology, Honolulu, Hawaii, November 2009. ⁎ Corresponding author. Department of OB/GYN, 3851 Houston, TX 78234, USA. Fax: +1 210 916 5557. E-mail addresses: charles.leath@amedd.army.mil, Tr (C.A. Leath).

Hysteroscopy in the evaluation and treatment of mucinous adenocarcinoma

BACKGROUND Hysteroscopy to evaluate abnormal uterine bleeding is gaining popularity. The standard methods of evaluation, endocervical curettage, and endometrial biopsy frequently diagnose adenocarcinoma without determining location. Because the treatments of endometrial and endocervical cancers are different, knowing the neoplastic origin is desirable. CASES Two postmenopausal women were referred for abnormal uterine bleeding. Endometrial biopsies were consistent with mucinous adenocarcinoma without distinction between cervical and endometrial sites. Endocervical curettages were inconclusive. Both patients underwent hysteroscopy at the time of exploratory laparotomy, which revealed the location of the adenocarcinomas, one in the endocervix and one in the uterine fundus. CONCLUSION The location of adenocarcinoma may be further clarified by the use of intraoperative hysteroscopy, which can aid in determining surgical treatment.