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Background: Sufficient quantities of quality air and controlled, unidirectional flow are important elements in providing a safe building environment for operating rooms., Methods: To make dynamic assessments of an operating room environment, a validated method of testing the multiple factors influencing the air quality in health care settings needed to be constructed. These include the following: temperature, humidity, particle load, number of microbial contaminants, pressurization, air velocity, and air distribution. The team developed the name environmental quality indicators (EQIs) to describe the overall air quality based on the actual measurements of these properties taken during the mock surgical procedures. These indicators were measured at 3 different hospitals during mock surgical procedures to simulate actual operating room conditions. EQIs included microbial assessments at the operating table and the back instrument table and real-time analysis of particle counts at 9 different defined locations in the operating suites. Air velocities were measured at the face of the supply diffusers, at the sterile field, at the back table, and at a return grille., Results: The testing protocol provided consistent and comparable measurements of air quality indicators between institutions. At 20 air changes per hour (ACH), and an average temperature of 66.3°F, the median of the microbial contaminants for the 3 operating room sites ranged from 3-22 colony forming units (CFU)/m 3 at the sterile field and 5-27 CFU/m 3 at the back table. At 20 ACH, the median levels of the 0.5-µm particles at the 3 sites were 85,079, 85,325, and 912,232 in particles per cubic meter, with a predictable increase in particle load in the non-high-efficiency particulate air-filtered operating room site. Using a comparison with cleanroom standards, the microbial and particle counts in all 3 operating rooms were equivalent to International Organization for Standardization classifications 7 and 8 during the mock surgical procedures., Conclusions: The EQI protocol was measurable and repeatable and therefore can be safely used to evaluate air quality within the health care environment to provide guidance for operational practices and regulatory requirements., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

In metastatic ovarian cancer, resistance to platinum chemotherapy is common. Although the orphan nuclear receptor TR3 (nur77/NR4A1) is implicated in mediating chemotherapy-induced apoptosis in cancer cells, its role in ovarian cancer has not been determined. In an ovarian cancer tissue microarray, TR3 protein expression was elevated in stage I tumors, but downregulated in a significant subset of metastatic tumors. Moreover, TR3 expression was significantly lower in platinum-resistant tumors in patients with metastatic disease, and low TR3 staining was associated with poorer overall and progression-free survival. We have identified a direct role for TR3 in cisplatin-induced apoptosis in ovarian cancer cells. Nucleus-to-cytoplasm translocation of TR3 was observed in cisplatin-sensitive (OVCAR8, OVCAR3, and A2780PAR) but not cisplatin-resistant (NCI/ADR-RES and A2780CP20) ovarian cancer cells. Immunofluorescent analyses showed clear overlap between TR3 and mitochondrial Hsp60 in cisplatin-treated cells, which was associated with cytochrome c release. Ovarian cancer cells with stable shRNA- or transient siRNA-mediated TR3 downregulation displayed substantial reduction in cisplatin effects on apoptotic markers and cell growth in vitro and in vivo. Mechanistic studies showed that the cisplatin-induced cytoplasmic TR3 translocation required for apoptosis induction was regulated by JNK activation and inhibition of Akt. Finally, cisplatin resistance was partially overcome by ectopic TR3 overexpression and by treatment with the JNK activator anisomycin and Akt pathway inhibitor, wortmannin. Our results suggest that disruption of TR3 activity, via downregulation or nuclear sequestration, likely contributes to platinum resistance in ovarian cancer. Moreover, we have described a treatment strategy aimed at overcoming platinum resistance by targeting TR3., (©2013 AACR.)

Insulin-like growth factor-II messenger RNA-binding protein 3 (IGF2BP3 or IMP3) is a biomarker whose expression has been found to be a negative prognostic factor in several neoplasms including ovarian clear cell carcinoma (CCC). In this study, we analyzed the frequency and clinicopathologic significance of IMP3 expression, as assessed by immunohistochemistry and as scored using a modified H-score system, in a cohort of 50 endometrial CCCs. Cases with scores of 0 to 100, 101 to 200, and 201 to 300 were classified as negative/mildly positive (n = 17), moderately positive (n = 20), and strongly positive (n = 13), respectively. A distinctive pattern of increased staining at the myoinvasive front (relative to the main tumor) was evident in 46% of the cases with evaluable foci of myometrial invasion. Moderate/strong IMP3 staining was associated with a tumor architectural pattern that has been reported to be of poor prognostic significance: at least 10% of the tumor composed of solid architecture or individual infiltrating tumor cells (P = .01). Increasing levels of IMP3 expression showed a trend toward decreasing relapse-free survival (RFS; median survival, 75.6, 81.3, and 48.4 months for the negative/mildly, moderately, and strongly positive groups, respectively [P = .09]). However, IMP3 expression was not significantly associated with reduced overall survival or RFS in a multivariate analytic model. The finding in a subset of our cases of increased IMP3 expression at the tumoral myoinvasive front is consistent with a role for IMP3 in invasiveness, as is the trend toward reduced RFS in cases expressing IMP3 at high levels. These preliminary findings suggest that IMP3 expression may be involved in the pathogenesis of CCC and is worthy of further exploration., (Copyright © 2013 Elsevier Inc. All rights reserved.)

TP53 mutation (and associated p53 protein overexpression) is probably a negative prognostic marker in endometrial cancers, but its relevance in the rarer histologic subtypes, including clear cell carcinomas, has not been delineated. Preclinical studies suggest functional interactions between p53 and the BAF250a protein, the product of a tumor suppressor gene ARID1A (adenine-thymine (AT)-rich interactive domain containing protein 1A) that is frequently mutated in ovarian clear cell carcinoma. In this study, we evaluated the significance of p53 and BAF250a expression, as assessed by immunohistochemistry, in a group of 50 endometrial clear cell carcinomas. Of 50 cases, 17 (34%) were p53+, and the remaining 33 cases had a p53 wild-type (p53-wt) immunophenotype. Of the 11 relapses/recurrences in the entire data set, 73% were in the p53+ group (P=0.008). On univariate analyses, the median overall survival for the p53-wt patients (83 months) was longer than the p53+ patients (63 months) (P=0.07), and the median progression-free survival for the p53-wt group (88 months) was significantly longer than the p53+ group (56 months) (P=0.01). On multivariate analyses, p53 expression was not associated with reduced overall or progression-free survival. In addition, p53 status was not significantly associated with pathologic stage or morphologic patterns. Of the 50 cases, 10 (20%) showed a complete loss of BAF250a expression. There was no significant correlation between p53 and BAF250a expression. The p53+/BAF250a-, p53+/BAF250a+, p53-wt/BAF250a+ and p53-wt/BAF250a- composite immunophenotypes were identified in 8%, 26%, 54% and 12% of cases, respectively, and neither loss of BAF250a expression nor composite p53/BAF250a expression patterns were associated with reduced overall or progression-free survival. In conclusion, a significant subset of CCC express p53, and these cases are apparently not definable by their morphologic features. P53 expression may be a negative prognostic factor in this histotype, and warrants additional studies. Loss of BAF250a expression has no prognostic significance in endometrial clear cell carcinomas.

Objective: The purpose of this article is to discuss and illustrate the use of contrast-enhanced transvaginal sonography for the early detection of ovarian cancer and suggest how this technique may best be used to distinguish benign from malignant ovarian masses., Conclusion: Microbubble-enhanced transvaginal sonography can enhance the evaluation of ovarian masses by early detection of tumor microvascularity.

Objective: The aim of this study was to evaluate diagnostic parameters to differentiate between benign versus malignant ovarian masses using contrast-enhanced transvaginal sonography (TVS)., Methods: Thirty-three consecutive patients with 36 morphologically abnormal ovarian masses (solid or cystic with papillary excrescences, focally thickened walls, or irregular solid areas) smaller than 10 cm received a microbubble contrast agent intravenously while undergoing pulse inversion harmonic TVS. The following parameters were assessed: presence of contrast enhancement, time to peak enhancement, peak contrast enhancement, half wash-out time, and area under the enhancement curve (AUC). Tumor histologic analysis was used to distinguish benign from malignant ovarian tumors., Results: Twenty-six benign masses and 10 malignancies were studied. Of all examined criteria, an AUC of greater than 787 seconds(-1) was the most accurate diagnostic criterion for ovarian cancer, with 100.0% sensitivity and 96.2% specificity. Additionally, peak contrast enhancement of greater than 17.2 dB (90.0% sensitivity and 98.3% specificity) and half wash-out time of greater than 41.0 seconds (100.0% sensitivity and 92.3% specificity) proved to be useful., Conclusions: Our data suggest that the AUC, peak enhancement, and half wash-out time had the greatest diagnostic accuracy for contrast-enhanced TVS in differentiation between benign and malignant ovarian masses.

Raman spectroscopy has the potential to differentiate among the various stages leading to high-grade cervical cancer such as normal, squamous metaplasia, and low-grade cancer. For Raman spectroscopy to successfully differentiate among the stages, an applicable statistical method must be developed. Algorithms like linear discriminant analysis (LDA) are incapable of differentiating among three or more types of tissues. We developed a novel statistical method combining the method of maximum representation and discrimination feature (MRDF) to extract diagnostic information with sparse multinomial logistic regression (SMLR) to classify spectra based on nonlinear features for multiclass analysis of Raman spectra. We found that high-grade spectra classified correctly 95% of the time; low-grade data classified correctly 74% of the time, improving sensitivity from 92 to 98% and specificity from 81 to 96% suggesting that MRDF with SMLR is a more appropriate technique for categorizing Raman spectra. SMLR also outputs a posterior probability to evaluate the algorithm's accuracy. This combined method holds promise to diagnose subtle changes leading to cervical cancer.

Objective: The purpose of this study was to determine the rate of unsatisfactory Papanicolaou tests between gynecology and nongynecology providers at a single institution., Study Design: Vanderbilt University Medical Center data were used to obtain a list of all liquid-based cervical Papanicolaou smears that were collected between September 2002 and October 2006. Unsatisfactory samples were identified as 2 groups (gynecology vs nongynecology) for statistical comparison., Results: There were 69,129 Papanicolaou smears that had been collected between September 2002 and October 2006; 47,165 smears were in the gynecology group, and 21,964 smears were in the nongynecology group. Of these, 1206 smears were designated to be "unsatisfactory." A nongynecology provider was more likely to have an unsatisfactory Papanicolaou test result, compared with a gynecology physician (3% [602/21,964] vs 1% [604/47,165]; P < .001). The odds of having an unsatisfactory Papanicolaou test result was 2 times higher with nongynecology, compared with gynecology, physicians (odds ratio, 2.17; 95% CI, 1.94-2.43)., Conclusion: Rates of liquid-based smears reported as unsatisfactory are higher among nongynecology providers. Competency-based learning programs might help to address this discrepancy.

Objective: This study was undertaken to determine whether the use of hormonal contraception affects the adequacy of colposcopic examination of the cervix., Study Design: A retrospective chart review of patients seen in the Vanderbilt University Medical Center Colposcopy Clinic from 2000-2002. Patient age, use of hormonal contraception, and adequacy of colposcopic examination were recorded for analysis., Results: Of all the colposcopic records reviewed, 526 of 1156 met inclusion criteria. Study patients ranged in age from 14 to 51 years. The prevalence of the visible squamocolumnar junction ranged from 75% to 91%. The multivariate logistic regression analysis showed that both age and use of hormonal contraception significantly influence adequacy of colposcopic examination (P < .001, P = .001, respectively)., Conclusion: The use of combination oral contraceptives is associated with an increased likelihood of adequate colposcopy.

Objective: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions., Accme Accreditation: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. The ASCCP designates this continuing medical education activity for 1 credit hour Category I of the Physician's Recognition Award of the American Medical Association. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements.

Objective: To determine the efficacy of using complementary techniques for detecting sentinel lymph nodes (SLNs) in vulvar carcinoma and to evaluate the utility of microstaging techniques., Study Design: Patients with invasive vulvar carcinoma underwent sentinel lymph node detection (SLND) using preoperative lymphoscintigraphy, intraoperative isosulfan blue dye injection and an intraoperative hand-held gamma-detecting probe. Eleven patients were included and a total of 16 groins evaluated. Sentinel nodes identified were excised, bisected and examined in surgical pathology using hematoxylin and eosin (H&E) staining. Pathologically negative SLNs were subjected to additional microstaging via serial sectioning and immunohistochemical staining for cytokeratin. Surgical management of the vulvar cancer and extent of inguinal-femoral lymphadenectomy were individualized based on clinicopathologic parameters, including depth of invasion, location of the tumor and patient performance status., Results: Lymphoscintigraphy, dye and gamma-detector methods led to the total detection of 16, 19 and 17 SLNs, respectively. In two cases the isosulfan blue dye assisted in the isolation of an additional sentinel node over that of the gamma probe. Each method individually identified SLNs in 10/11 patients (91%). A total of 19 sentinel nodes were isolated. One SLN (5%) was positive for metastatic disease using H&E staining. Of the 18 negative SLNs, 2 (11%) had micrometastases (< 0.2 mm) upon serial sectioning and immunohistochemical staining., Conclusion: Combined-modality mapping enhances detection of SLNs in vulvar carcinoma. Histologic microstaging improves the detection of micrometastases within SLNs.

To increase the sensitivity of the cervical Papanicolaou (Pap) smear, several automated devices now are commercially available. In the last 2 years, the U.S. Food and Drug Administration approved three of these devices, each of which operates differently from the others. The ThinPrep 2000 is a method whereby the traditional Pap smear is substituted by a liquid-based smear collection technique that allows the preparation of thin layers, which addresses the problems of obscuring blood, inflammation, and overlapping cells on traditional smears. The AutoPap 300 QC is a rescreening device that selects from a batch of negative smears the 10% most likely abnormal smears for manual rescreening. The PAPNET Testing System is a neural network-based semiautomated screening system used for adjunctive testing of negative Pap smears. The system selects and displays the most abnormal-looking cells for review by the cytotechnologist, thus improving the detection of missed abnormalities. The effectiveness of the introduction of these devices for cervical cancer detection is discussed.

Purpose of Investigation: To review our management experience with uterine mixed mullerian tumors (MMTs) in order to evaluate potential prognostic indicators, and assess the efficacy of various treatment modalities., Methods: A retrospective, clinicopathologic evaluation of 43 patients presenting for treatment of uterine MMTs between 1982 and 1992 was conducted. Diagnostic criteria for inclusion was the presence of both a malignant glandular or squamous epithelial component, and a homologous or heterologous stromal component., Results: Overall 2- and 5-year cancer related Kaplan-Meier survival estimates with 95% confidence intervals were 44 (.28, .59) and 26% [.12, .39], respectively. Survivals were 83 [.62, .99] and 58% [.31, .85] when disease was confined to the uterus, and 22 [.03, .41] and 7% [.01, .20] when disease extended beyond the uterus. Clinical staging was often inaccurate, with 29% of clinical stage I or II disease being upstaged at laparotomy. A significant survival advantage was found in patients with stage I or II disease treated with surgery plus pelvic irradiation (p = 0.001), as compared to those treated with surgery alone. The prognosis after disease recurrence was poor, irrespective of secondary therapy, with a median survival of 11 months., Conclusions: A therapeutic advantage may be gained from postoperative pelvic irradiation in the treatment of surgical stage I or II uterine MMT.

Objective: Our purpose was to assess the potentials and limitations of the early detection of ovarian cancer in protocols that involve transvaginal color Doppler ultrasonography., Study Design: Retrospective analysis was performed on the data from 206 referred patients who either had surgical or clinical follow-up of ovarian masses evaluated by transvaginal color Doppler ultrasonography. Most of the patients were referrals or had risk factors., Results: In this series of 206 patients, 26 ovarian cancers were detected, > 70% of which were stage I or II., Conclusion: Transvaginal color Doppler ultrasonography is capable of early detection of ovarian carcinoma. An improved detection rate may be realized with better identification of high-risk patients who should be studied with transvaginal color Doppler ultrasonography.

This study correlates the color Doppler sonography (CDS) findings in ovarian masses according to histomorphologic groups. Sixty-two surgically excised ovarian masses (31 benign and 31 malignant) in patients who underwent CDS were retrospectively reviewed. Lowest pulsatility index (PI) was used in benign and malignant unilocular cysts, septated cysts, predominantly cystic masses with solid components, predominantly solid masses with cystic areas and solid masses. The mean of the lowest PIs of benign lesions (1.7 +/- 0.7) were statistically significantly different (p < 0.05) from malignancies (0.7 +/- 0.3). The group of septated cysts (1.8 +/- 0.5 vs. 0.61 +/- 0.3) and predominantly cystic masses with solid areas (1.1 +/- 0.1 vs. 0.6 +/- 0.2) achieved statistical significance for benign vs. malignant masses. Predominantly solid masses with cystic areas (1.8 +/- 0.5 vs. 0.8 +/- 0.2) and solid masses (1.4 +/- 1.0 vs. 0.7 +/- 0.3) were not statistically significantly different. Because of a limited number of cases, statistically significant differences in the mean of the lowest PIs of benign vs. malignant unilocular cysts (2.1 +/- 0.5 vs. 1.9) could not be determined. When analyzed according to histomorphology, CDS findings were of predictive value in certain morphologies and not as much in others. This fact should be taken into account when evaluating an ovarian mass for malignancy with CDS.

Background: Although the Bethesda System provides concise, specific descriptions for classifying cervical cytology, its usefulness has been questioned in the United States and abroad. The author attempted to evaluate the impact of the Bethesda System on cervical screening and subsequent management decisions., Methods: A MedLine search provided statistical information for comparison of screening procedures and results before and since introduction of the Bethesda System. The effect of the Bethesda System was evaluated by specimen adequacy, inclusion of human papillomavirus changes in the squamous intraepithelial lesion (SIL) category, and effect on the number of abnormal Pap smears., Results: By 1992, 85% of cytology laboratories were using Bethesda system terminology. Diagnosis and treatment of patients with atypical squamous cells of undetermined significance (ASCUS) and low grade squamous intraepithelial lesions were reviewed. In women with ASCUS smears, follow-up studies showed that between 5% and 13% actually had high grade cervical lesions. For patients with a cytologic diagnosis of low grade SIL, one study found an 18.6% incidence of high grade lesions demonstrated by colposcopically directed cervical biopsy. An estimated 2% increase has occurred in the number of women with abnormal Pap smear results who require additional evaluation costing more than $1 billion., Conclusions: The Bethesda System has improved the quality of Pap smear diagnosis in the United States, but the number of women with abnormal Pap smear results has increased. Although this increase is partly due to the terminology of the Bethesda System, other factors play a role. Whether this has improved cancer prevention is unknown.

Transrectal sonography was used to provide intraoperative guidance for dilatation and curettage and placement of intrauterine tandem apparatus in 20 patients in whom the external cervical os could not be visualized adequately. Transrectal sonography was found to be useful in providing guidance for these procedures and at the same time helped avoid uterine perforation. This method also was used during cerclage placement in two patients who had undergone several conizations. Transperineal sonography was used in three patients whose area of abnormality was best approached transperineally. These cases included transvaginal biopsy of a metastatic trophoblastic tumor and one guided aspiration of a perirectal abscess after pelvic exenteration. The potential advantages and pitfalls in the intraoperative use of transrectal and transperineal sonography for guided intrauterine procedures are discussed and illustrated.

Transvaginal color Doppler sonography (TV-CDS) was performed on 64 women with adnexal masses at 3, 6 and 12 weeks after initial presentation. In 47 (72% of patients studied), the pelvic mass demonstrated a decrease in size and increase in pulsatility index (PI) after 12 weeks. Of the patients undergoing surgery in this group, one had a tubo-ovarian abscess, one diverticular abscess and one hydrosalpinx. In seven patients (10%), there was no change in size or PI. Three in this group had an endometrioma, whereas two had a peritoneal cyst. In five (7%), there was no change in size and an increase in PI. One of these patients had a mucinous cystadenoma. In three (5%), there was a decrease in size and PI. Two of these patients had a tubo-ovarian abscess. In two (3%) patients studied, the mass showed an increase in size and decrease in PI; both had corpora luteum cysts with acute hemorrhage. Seventy-two percent of masses with high impedance underwent regression, whereas only 21% of lesions with low impedance did. Only 20% of masses demonstrating low impedance or morphologically complex structure regressed. Sixty-five percent of lesions that regressed had a significant drop in PI, whereas all the lesions that showed no change in size or enlargement had either no change or decrease in PI. Probability of regression was the greatest in young women (less than 40 years of age) and in masses < 5 cm. Ninety-three percent of women with persistent masses that underwent progestational suppression demonstrated regression with decrease of PI and peak systolic velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: To evaluate the prognostic significance of ureteral obstruction in women with cervical cancer and the result of aggressive urinary diversion., Methods: The clinical history and X-rays of 52 women with Stage III and IV cervical cancer seen at Vanderbilt University between 1981 and 1991 were retrospectively reviewed., Results: Twenty-nine (55.8%) of these patients had unilateral [15] or bilateral [14] ureteral obstruction. There was no statistically significant difference in the survival of patients whether or not ureteral obstruction was present. Ten of fourteen women with bilateral ureteral obstruction and 4 of the 15 patients with unilateral obstruction underwent urinary diversion by percutaneous nephrostomy [9] or retrograde ureteral catheterization [5]. Complications were few. Although patients who underwent urinary diversion had somewhat better survival, it was not statistically significant., Conclusions: Some patients with ureteral obstruction due to advanced cervical cancer can be salvaged by prompt, aggressive urinary diversion, but large trials are needed to validate this approach.

Many malignancies appear to occur with increased frequency and aggressive patterns of spread in patients seropositive for human immunodeficiency virus (HIV). The relationship between HIV infection and cervical neoplasia suggests that these patients present with more advanced disease and demonstrate poor response to therapy. To date, there have been no reported cases of ovarian cancer with concomitant HIV infection. We describe a young, gravid woman with an advanced ovarian carcinoma diagnosed at the time of delivery. Following poor response to cytoreductive surgery and initial chemotherapy, she was found to be HIV-seropositive. She received multiple chemotherapeutic regimens and experienced significant complications associated with her treatment and HIV infection. She progressively deteriorated and died within 13 months of diagnosis. Based on these findings and experience with other HIV-associated malignancies, it is apparent that the conventional approach to therapy is inadequate to treat the advanced and more aggressive form of disease seen in women infected with HIV.

This study analyzed vessel location, maximum systolic velocity, impedance, and waveform shape in 25 benign and 25 malignant surgically excised and pathologically examined ovarian masses as depicted by transvaginal or transabdominal color Doppler sonography, or both. Those parameters that achieved statistical significance (P > 0.05) between the two types of masses included vessel location, impedance, and waveform shape. Malignant masses typically were characterized by centrally located vessels that had low impedance without a diastolic "notch" in the waveform. Maximum systolic velocities are statistically similar in benign and malignant lesions. Multiparameter analysis may improve the diagnostic specificity and sensitivity of this technique in distinguishing benign from malignant ovarian masses.

The use of transvaginal and transabdominal color Doppler sonography for the assessment of ovarian tumor vascularity was investigated in 62 cases of surgically excised and histologically examined ovarian masses. The modality was used to differentiate tumor neovascularity from normal arterioles (which contain smooth muscle in their media) on the basis of differences in the pulsatility observed in Doppler waveforms. Of the 25 malignant tumors in the series, 20 had low-impedance flow (pulsatility index of less than 1.0), and none had the diastolic notch seen in vessels in normal tissue. Three benign lesions, including two dermoid cysts and one tubo-ovarian abscess, also had low-impedance flow. The negative predictive value of color Doppler sonography was 98%, whereas the positive predictive value was 83%. Color Doppler sonography seems to be accurate for excluding malignancy, but some misdiagnosis may occur in cases of inflammatory and metabolically active benign masses.

From April 1989 to August 1990, 17 patients with Stage 3 or 4 epithelial ovarian cancer (EOC) were treated with intravenous carboplatin (160-400 mg/m2) for refractory or recurrent disease after first-line treatment with cisplatin-based combination chemotherapy. Of fifteen patients evaluable for activity, two complete responses and two partial responses were seen, for a response rate of 27%. The duration of response was 4.5, 5, 8, and 9.2 months, respectively, and responders survived longer than nonresponders. Of the nine evaluable patients receiving carboplatin as the first salvage treatment, four responses were seen. Dose selection for the first cycle of carboplatin was based on previous treatment, and adjustments were made on the basis of myelosuppression. In general, treatment was well tolerated--severe myelosuppression occurred after 6 of 73 cycles. This review confirms previous reports of anti-tumor activity of carboplatin in patients with refractory or recurrent advanced EOC who respond to first-line treatment with cisplatin. Further evaluation may help define the toxicity and efficacy of salvage treatment with carboplatin compared to cisplatin in patients who recur after a prolonged disease-free interval after first-line cisplatin-based therapy.

A postmenopausal patient presented with a pelvic mass and ascites. The CA-125 level was 329 U/ml, and transvaginal color Doppler sonography of the tumor vasculature suggested malignancy. At laparotomy, a luteinized thecoma and cytologically benign ascites were found. On rare occasions ovarian thecoma may be associated with ascites without hydrothorax. Preoperative evaluation of the patient with ascites and a pelvic mass may suggest malignancy, but histologic confirmation is necessary to exclude this rare association.

This report describes the results of transvaginal color Doppler sonography (TV-CDS) of 43 surgically proved ovarian masses. Waveform analyses of the signals arising from specific vessels (i.e., peripheral, central, septal) adjacent to and within these masses were correlated to those seen on macroscopic pathologic evaluation. The mean and standard deviation of the pulsatility indices (PI) of 32 benign lesions (1.8 +/- 0.8) were higher than 11 malignant ones (0.8 +/- 0.6) (P = 0.03). However, the range of benign (4.0 to 0.7) and malignant (1.5 to 0.4) lesions did overlap. Low PIs (less than 1.0) were found in five relatively benign lesions (one case each of dermoid cyst, cystadenoma containing a dermoid cyst, endometrioma, benign sclerosing stromal tumor, and thecoma), but also in all 11 malignant or borderline malignant lesions (nine cystadenocarcinomas, two germ cell tumors), causing an overlap between the PIs of some benign and malignant masses. With a 100% negative predictive value, our preliminary data suggest that TV-CDS can effectively exclude malignancy. However, with a positive predictive value of 73%, one in four malignant lesions diagnosed by TV-CDS will be benign.

The sonographic appearance of 67 ovaries in 34 postmenopausal women who underwent preoperative transvaginal sonography (TVS) was correlated to findings on pathologic examination. Both ovaries were detected by TVS in 60% of the women examined; in 85%, at least one ovary was detected. The size of the normal, sonographically visualized postmenopausal ovary was 2.2 +/- 0.7 cm in transverse, 1.2 +/- 0.3 cm in anteroposterior, and 1.1 +/- 0.6 cm in longitudinal axes, with an average volume of 2.6 +/- 2.0 cm3. The average size of ovaries that were not detected by TVS was 0.7 x 0.4 cm (range, 0.3 to 1.3 cm); most of these (five of six) were atrophic on pathologic exam. The difference between actual and sonographically measured size was negligible (TVS overestimated by 0.3 cm). Four simple cysts that ranged from 0.5 to 3.5 cm were found by TVS and confirmed pathologically, as were three benign serous cystadenomas that ranged from 2.5 to 3.5 cm, one 3 x 6-cm tubal carcinoma, and one 1 X 4-cm paratubal cyst. TVS missed a 6-cm dermoid, a 2.5-cm cystadenoma, a 0.8-cm Sertoli cell tumor, and a 0.5-cm fibrothecoma that were nonpalpable but that were found on pathologic examination. None of the missed lesions were palpable preoperatively. The positive predictive value was 94% for detection of an ovarian mass; the negative predictive value for exclusion of an ovarian lesion was 92%. It is concluded that TVS can accurately delineate the ovaries in most, but not all, postmenopausal women and that only rarely will pathologic lesions not be detected by TVS.

Excessive daytime sleepiness has various causes, and appropriate treatment varies accordingly. The diagnosis requires a history, physical examination, and polysomnographic study. A case report exemplifies the clinical approach.

To evaluate the contribution of hexamethylmelamine (HMM) to the treatment of advanced ovarian cancer with combination chemotherapy, we compared the results of treatment with HMM, cyclophosphamide, doxorubicin, and cisplatin (H-CAP regimen) to treatment results using cyclophosphamide, doxorubicin, and cisplatin (CAP regimen). The treatment regimens were identical in dosage and schedule with the exception of the addition of HMM to one regimen. Fifty-five patients treated with H-CAP at Vanderbilt University Hospital between August 1977 and March 1980 were compared with a subsequent group of 22 patients who received CAP between October 1984 and October 1987. Following six months of therapy, patients were restaged either with second-look laparotomy or with clinical restaging. Fifty-three of 55 patients (96%) had objective responses to H-CAP compared with 14 of 21 patients (67%) treated with CAP (p = 0.001). The pathologic complete response rate was also higher in the patients who received H-CAP (35% versus 19%). The median survival of patients receiving H-CAP is 47 months compared to 21 months for the CAP patients. When patients with limited residual disease (maximum tumor diameter less than or equal to 3 cm) were compared, the median survival also favored the H-CAP treatment (101 months versus 21 months, p = 0.002). The median time to progression was also greater in patients receiving H-CAP versus those receiving CAP (67 months versus 16 months, p = 0.045). Treatment-related toxicity did not differ substantially between the two regimens. Our findings suggest that the addition of HMM to CAP chemotherapy prolongs the median survival in patients with ovarian cancer and limited residual disease following cytoreductive surgery.

Transrectal sonography was used for intraoperative guidance in intrauterine tandem placement for intracavitary radiation therapy and in dilation and curettage procedures. The authors describe the method and three representative cases in which it was applied. It is concluded that the technique may prevent complications such as uterine perforation or bladder injury in tandem placement, and that it can facilitate dilation and curettage in complicated cases.

In an effort to augment public awareness of the benefits of screening mammography and to encourage the use of screening mammograms, the Tennessee Division of the American Cancer Society initiated the Breast Cancer Detection Awareness Program in March 1988. As a result of the initiative, 3,473 women telephoned for information, and 3,123 were found to be eligible for a screening mammogram. Of the 2,248 mammograms actually obtained, 1,764 (78%) were interpreted as normal, whereas 484 (22%) were classified as abnormal. Of the 484 women with abnormal mammograms, 277 (57%) were advised to have follow-up mammograms and 57 (12%) had excisional biopsy. The 55 biopsies reported showed benign changes in 83.6% and malignancy in 16.4%. Thus, nine malignancies were discovered from 2,248 screening mammograms (four malignancies per 1,000 mammograms). No malignancies were found in women between 35 and 39 years old.

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

We describe in physiological terms the increasing glomerular capillary wall (GCW) dysfunction of 20 patients with diabetic glomerulopathy and heavy proteinuria. The clearances of uncharged polysaccharide markers of graded size were used to probe the glomerular filter on three occasions over a 24-mo period. The findings were analyzed with a theoretical model of solute transport that depicts most of the GCW as an isoporous membrane and the minor portion as a nondiscriminatory shunt pathway. Initially, the mean glomerular ultrafiltration coefficient Kf is computed to have been 3-5 times lower and mean pore radius of the major membrane component (r0) 2 A smaller than normal control values. In contrast, the model computes the fraction of filtrate volume permeating the nondiscriminatory shunt pathway (omega 2) to have been sixfold elevated above control values and to have correlated strongly in individual patients with the fractional clearances of albumin (r = .72) and of IgG (r = .73). Sequential studies after 12 and 24 mo revealed an invariable decline in glomerular filtration rate (GFR). Fractional clearances of albumin and IgG increased with time in most patients but declined in a few instances (20-25%). Change in omega 2 tended to occur in parallel with fractional protein clearance, regardless of its direction. We conclude that in progressive diabetic glomerulopathy GFR declines because of a loss by glomerular capillaries of ultrafiltration capacity, proteinuria is largely a consequence of increasingly impaired barrier-size selectivity, and the foregoing injuries reflect damage to different parts of the GCW and may become dissociated from one another with the passage of time.