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Objective: To estimate the efficacy of a fluid-based, thin-layer preparation (TP) compared with the conventional Pap (CP) test to detect biopsy confirmed precancerous cervical lesions.Materials and Methods: A total of 10,226 evaluable patients at 10 separate clinical sites were screened for cervical abnormalities using the TP (ThinPrep pap test; Cytyc Corporation, Boxborough, MA). Results were compared with an historical control cohort of 20,918 patients from a similar patient population and with a similar patient profile who had received CP screening.Results: The TP significantly increased the detection rate of high-grade squamous intraepithelial lesion and more severe (HSIL+) cytologic results as compared with the CP smear. Overall, the TP method yielded a 59.7% increase in the detection of HSIL+ compared with the CP smear. Overall, the TP method yielded a 59.7% increase in the detection of HSIL+ compared with the conventional method (3.9% vs. 2.4%; p < .001). There was also a significant increase in the detection of low-grade squamous intraepithelial lesions with TP (p < .01). The rates of cancer, atypical squamous cells of undetermined significance, and atypical glandular cells of undetermined significance were similar for the TP and CP groups.Conclusions: The overall cytologic detection of HSIL and low-grade squamous intraepithelial lesions with the TP method was significantly increased compared with a control group screened with the CP method. Histologic confirmation showed increased detection, not an increased false-positive cytologic interpretation. [ABSTRACT FROM AUTHOR]

Background  Trauma in pregnancy can lead to life-threatening hemorrhage. Conventional treatments of hemorrhage include medical and surgical management. However, if these measures fail uterine compression is an option to control bleeding. We present a case where this management was employed. Case  A patient presented at 36 weeks of gestation with multiple injuries after a motor vehicle collision and experienced disseminated intravascular coagulation (DIC). The use of a Bakri balloon in combination with external compression with Coban, a sterile self-adherent bandage, after delivery temporized her bleeding and allowed her to become stable for further management. Conclusion  When other measures fail and a hysterectomy is considered unsafe, the combination of internal and external uterine compression is an option.

Objectives: The purpose of this study is to describe the clinical history leading up to and the outcomes after vaginal mesh removal surgery at an academic hospital., Methods: A retrospective case series of patients who underwent vaginal mesh removal from 2008 to 2015 was conducted. Demographics, clinical history, physical examination, pre- and postoperative symptoms, and number and type of reoperations were abstracted., Results: Between February 2008 and November 2015, 83 patients underwent vaginal mesh removal surgery at our hospital. The median time interval from initial mesh placement to removal was 58 months (range, 0.4-154 months). The most common preoperative symptoms were vaginal pain (n = 52, 62%), dyspareunia (n = 46, 55%), and pelvic pain (n = 42, 50%). Intraoperative complications were infrequent (n = 3, 4%). Of patients presenting for follow-up within 4 to 6 weeks postoperatively, the most common symptoms were urinary incontinence (n = 15, 28%), vaginal pain (n = 7, 13%), buttock pain (n = 5, 9%), and urinary tract infection (n = 5, 9%). There were no identifiable risk factors to predict which patients would have persistent postoperative symptoms or who would require more than 1 mesh removal surgery. After vaginal mesh removal, 29 patients (35%) required 1 or more reoperations, with 3 being the highest number of reoperations per patient. The total number of reoperations was 43, with a total of 63 individual procedures performed. Forty-four percent (n = 28) of the procedures were graft removals, 40% (n = 25) were pelvic organ prolapse surgeries (only native tissue repairs), and 16% (n = 10) were stress incontinence surgeries. More than 1 procedure was performed in 49% (n = 21) of the reoperations., Conclusions: Vaginal mesh removal surgery is safe; however, some patients require more than 1 procedure, and the risk factors for reoperations are unclear.

Objective: The aim of this study was to assess the role of intraoperative frozen section (FS) in guiding decision making for surgical staging of endometrioid endometrial cancer (EC)., Methods: Medical records were collected retrospectively on 112 patients with endometrioid EC, who underwent total hysterectomy and bilateral salpingo-oophorectomy at the University of Arizona Medical Center from January 1, 2010, to December 31, 2014. Only patients with endometrioid adenocarcinoma, grade 1, less than 50% myometrial invasion, and tumor size less than 2 cm determined by intraoperative FS omitted lymphadenectomy; otherwise, surgical staging was performed with lymph node dissection. The FS results were compared with the permanent paraffin sections (PSs) to assess the diagnostic accuracy., Results: The concordance rate of different variables between FS and PS in EC was 100%, 89.3% (100/112), 97.3% (109/112), and 95.5% (107/112), respectively, with respecting to histological subtype, grade, myometrial invasion, and tumor size. Diagnostic accurate rate of combined risk factors deciding surgical staging at the time of FS was 95.5% (107/112), and the discordance rate of all risk factors considered between FS and PS was 4.5%, resulting 3 cases (2.7%) undertreated and 2 cases (1.8%) overtreated., Conclusions: Despite nonideal FS evaluation, intraoperative FS diagnosis for EC is highly reliable by providing guidance for the intraoperative decisions of surgical staging at our institution, and such guidelines may be referenced by the institutions with sufficient gynecologic pathology expertise.

With early detection, 5-year survival rates for ovarian cancer exceed 90%, yet no effective early screening method exists. Emerging consensus suggests over 50% of the most lethal form of the disease originates in the fallopian tube. Twenty-eight women undergoing oophorectomy or debulking surgery provided informed consent for the use of surgical discard tissue samples for multispectral fluorescence imaging. Using multiple ultraviolet and visible excitation wavelengths and emissions bands, 12 fluorescence and 6 reflectance images of 47 ovarian and 31 fallopian tube tissue samples were recorded. After imaging, each sample was fixed, sectioned, and stained for pathological evaluation. Univariate logistic regression showed cancerous tissue samples had significantly lower intensity than noncancerous tissue for 17 image types. The predictive power of multiple image types was evaluated using multivariate logistic regression (MLR) and quadratic discriminant analysis (QDA). Two MLR models each using two image types had receiver operating characteristic curves with area under the curve exceeding 0.9. QDA determined 56 image type combinations with perfect resubstituting using as few as five image types. Adaption of the system for future in vivo fallopian tube and ovary endoscopic imaging is possible, which may enable sensitive detection of ovarian cancer with no exogenous contrast agents.

Objective: The aim of this study is to evaluate the performance of a confocal fluorescence microlaparoscope for in vivo detection of ovarian cancer., Methods/materials: Seventy-one patients scheduled for open or laparoscopic oophorectomy were consented for the imaging study. High-resolution confocal microlaparoscopic images of the epithelial surface of the ovary were acquired in vivo or ex vivo after tissue staining using acridine orange. Standard histologic evaluation of extracted tissue samples was performed and used as the gold standard of disease diagnosis. Trained human observers from different specialties viewed the microlaparoscopic images, rating each image on a 6-point scale ranging from "definitely not cancer" to "definitely cancer." Receiver operating characteristic curves were generated using these scores and the gold standard histopathologic diagnosis. Area under the receiver operating characteristic curve (AUC) was calculated as a performance metric., Results: Forty-five of the consented patients were used in the final evaluation study. From these 45 patients, 63 tissue locations or samples were identified and imaged with the confocal microlaparoscope. Twenty of the samples were high-grade cancers, and the remaining 43 samples were normal or noncancerous. Twenty-three of the samples were imaged in vivo, and the remaining 40 samples were imaged ex vivo. The average AUC score and standard error (SE) for detection of cancer in all images were 0.88 and 0.02, respectively. An independent-samples t test was conducted to compare AUC scores for in vivo and ex vivo conditions. No statistically significant difference in the AUC score for in vivo (AUC, 0.850; SE, 0.049) and ex vivo (AUC, 0.888; SE, 0.027) conditions was observed, t(6) = 1.318, P = 0.2355., Conclusions: Area under the receiver operating characteristic curve scores indicate that high-resolution in vivo images obtained by the confocal laparoscope can distinguish between normal and malignant ovarian surface epithelium. In addition, in vivo performance is similar to that which can be obtained from ex vivo tissue.

Recent evidence suggests that ovarian cancer can originate in the fallopian tube. Unlike many other cancers, poor access to the ovary and fallopian tubes has limited the ability to study the progression of this deadly disease and to diagnosis it during the early stage when it is most amenable to therapy. A rigid confocal microlaparoscope system designed to image the epithelial surface of the ovary in vivo was previously reported. A new confocal microlaparoscope with an articulating distal tip has been developed to enable in vivo access to human fallopian tubes. The new microlaparoscope is compatible with 5-mm trocars and includes a 2.2-mm-diameter articulating distal tip consisting of a bare fiber bundle and an automated dye delivery system for fluorescence confocal imaging. This small articulating device should enable the confocal microlaparoscope to image early stage ovarian cancer arising inside the fallopian tube. Ex vivo images of animal tissue and human fallopian tube using the new articulating device are presented along with in vivo imaging results using the rigid confocal microlaparoscope system.

Background: Serous tubal intraepithelial carcinoma (STIC) and the p53 signature in tubal mucosa have been supported to be precursor lesions in high-grade serous carcinoma (HGSC) of the fallopian tube, ovary, and peritoneum. It remains critical to find biomarkers for precursor lesions in order to detect HGSCs efficiently. IMP3 is an oncoprotein that has been explored in human malignancies. No studies have specifically addressed the expression of IMP3 in precursor or early lesions of HGSC. The main purposes of this study are to evaluate if IMP3 plays any role in the process of pelvic serous carcinogenesis by examining its expression in HGSC precursor lesions, to examine the relationship between IMP3 and p53 in those precursor lesions, and to check if IMP3 can be used as a biomarker for early diagnosis., Methods: Immunohistochemistry for IMP3 and p53 was performed and evaluated in 48 HGSCs with STIC, 62 HGSCs without STIC, and 60 benign cases as negative controls. Sections of fallopian tubes with or without STIC , as well as cancers within the ovaries, were studied. IMP3 signature was defined as strong IMP3 cytoplasmic staining in 10 or more consecutive benign-looking tubal epithelial cells. The relationship between IMP3 and p53 overexpression was examined., Results: In the 48 HGSC patients with STIC, IMP3 was positive in 46% of STIC lesions and had a similar positive rate in the invasive components of HGSC. IMP3 was also expressed in normal appearing tubal epithelia (IMP3 signature) in 15 (31%) of 48 HGSC cases with STIC and 10 (16%) of 62 cases without STIC. In contrast, no single IMP3 signature was found in the benign control group. Concordant expression of IMP3 and p53 signatures in the STIC group was found in up to one-third of the cases. There were also five (10%) STIC cases with positive IMP3 and negative p53., Conclusions: We conclude that IMP3 may be involved in the process and progression of pelvic HGSC and may serve as a complimentary biomarker in diagnosing STIC.

Ovarian cancer is the most deadly gynecologic cancer, a fact which is attributable to poor early detection and survival once the disease has reached advanced stages. Intraoperative laparoscopic volume holographic imaging has the potential to provide simultaneous visualization of surface and subsurface structures in ovarian tissues for improved assessment of developing ovarian cancer. In this ex vivo ovarian tissue study, we assembled a benchtop volume holographic imaging system (VHIS) to characterize the microarchitecture of 78 normal and 40 abnormal tissue specimens derived from ovarian, fallopian tube, uterine, and peritoneal tissues, collected from 26 patients aged 22 to 73 undergoing bilateral salpingo-oophorectomy, hysterectomy with bilateral salpingo-oophorectomy, or abdominal cytoreductive surgery. All tissues were successfully imaged with the VHIS in both reflectance- and fluorescence-modes revealing morphological features which can be used to distinguish between normal, benign abnormalities, and cancerous tissues. We present the development and successful application of VHIS for imaging human ovarian tissue. Comparison of VHIS images with corresponding histopathology allowed for qualitatively distinguishing microstructural features unique to the studied tissue type and disease state. These results motivate the development of a laparoscopic VHIS for evaluating the surface and subsurface morphological alterations in ovarian cancer pathogenesis.

Purpose: This phase I trial evaluated intraperitoneal (i.p.) pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer., Experimental Design: Dose escalation of day 1 i.p. pemetrexed accrued three patients to each of five dose levels (60-1,000 mg/m(2)), along with day 2 i.p. cisplatin (75 mg/m(2)) and day 8 i.p. paclitaxel (60 mg/m(2)). The goals were to determine maximum tolerated dose (MTD), 18-month progression-free survival (PFS), and pharmacokinetics of i.p. pemetrexed., Results: Cycles, given every 21 days, had an 80% 6-cycle completion rate. There was minimal grade III toxicity in the first 4 dose levels and remarkably an almost complete absence of peripheral neuropathy and alopecia. At the highest dose level, two of three patients experienced ≥ grade III and dose-limiting toxicity (DLT; hematologic, infection, gastrointestinal). There was a pharmacokinetic advantage for i.p. pemetrexed with an intraperitoneal:plasma area under the concentration-time curve ratio of 13-fold. Neither analysis of pharmacokinetic nor homocysteine levels explains the unexpected severity of toxicity in those two patients. On the basis of plasma C(24h) levels, the 42 cycles at ≥ 500 mg/m(2) i.p. pemetrexed without DLT, the MTD appears to be 500 mg/m(2). Median PFS is 30.1 months; 18-month PFS is 78.6% (median follow-up 22.4 months)., Conclusions: This i.p.-only regimen in front-line ovarian cancer is feasible with PFS in line with recent literature. We suggest phase II trials of this regimen in this population with i.p. pemetrexed at 500 mg/m(2). The favorable toxicity profile at doses <1,000 mg/m(2), which needs to be confirmed, appears to compare well with standard combination i.v./i.p. platinum/taxane chemotherapy in this disease., (©2012 AACR.)

With no sufficient screening test for ovarian cancer, a method to evaluate the ovarian disease state quickly and nondestructively is needed. The authors have applied a wide-field spectral imager to freshly resected ovaries of 30 human patients in a study believed to be the first of its magnitude. Endogenous fluorescence was excited with 365-nm light and imaged in eight emission bands collectively covering the 400- to 640-nm range. Linear discriminant analysis was used to classify all image pixels and generate diagnostic maps of the ovaries. Training the classifier with previously collected single-point autofluorescence measurements of a spectroscopic probe enabled this novel classification. The process by which probe-collected spectra were transformed for comparison with imager spectra is described. Sensitivity of 100% and specificity of 51% were obtained in classifying normal and cancerous ovaries using autofluorescence data alone. Specificity increased to 69% when autofluorescence data were divided by green reflectance data to correct for spatial variation in tissue absorption properties. Benign neoplasm ovaries were also found to classify as nonmalignant using the same algorithm. Although applied ex vivo, the method described here appears useful for quick assessment of cancer presence in the human ovary., (© 2012 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Purpose: This phase II trial evaluated bevacizumab plus erlotinib in platinum-resistant ovarian cancer; exploratory biomarker analyses, including that of tumor vascular endothelial growth factor A (VEGF-A), were also done., Experimental Design: Forty heavily pretreated patients received erlotinib (150 mg/d orally) and bevacizumab (10 mg/kg i.v.) every 2 weeks until disease progression. Primary end points were objective response rate and response duration; secondary end points included progression-free survival (PFS), toxicity, and correlations between angiogenic protein levels, toxicity, and efficacy., Results: Grade 3 toxicities included skin rash (n = 6), diarrhea (n = 5), fatigue (n = 4), and hypertension (n = 3). Grade 4 toxicities were myocardial infarction (n = 1) and nasal septal perforation (n = 1). Only one grade 3 fistula and one grade 2 bowel perforation were observed. Nine (23.1%) of 39 evaluable patients had a response (median duration, 36.1+ weeks; one complete response), and 10 (25.6%) patients achieved stable disease, for a disease control rate of 49%. Median PFS was 4 months, and 6-month PFS was 30.8%. Biomarker analyses identified an association between tumor cell VEGF-A expression and progression (P = 0.03); for every 100-unit increase in the VEGF-A score, there was a 3.7-fold increase in the odds of progression (95% confidence interval, 1.1-16.6)., Conclusions: Bevacizumab plus erlotinib in heavily pretreated ovarian cancer patients was clinically active and well tolerated. Erlotinib did not seem to contribute to efficacy. Our study raises the intriguing possibility that high levels of tumor cell VEGF-A, capable of both autocrine and paracrine interactions, are associated with resistance to bevacizumab, emphasizing the complexity of the tumor microenvironment., (©2010 AACR.)

Early detection of ovarian cancer could greatly increase the likelihood of successful treatment. However, present detection techniques are not very effective, and symptoms are more commonly seen in later stage disease. Amino acids, structural proteins, and enzymatic cofactors have endogenous optical properties influenced by precancerous changes and tumor growth. We present the technical details of an optical spectroscopy system used to quantify these properties. A fiber optic probe excites the surface epithelium (origin of 90% of cases) over 270 to 580 nm and collects fluorescence and reflectance at 300 to 800 nm with four or greater orders of magnitude instrument to background suppression. Up to four sites per ovary are investigated on patients giving consent to oophorectomy and the system's in vivo optical evaluation. Data acquisition is completed within 20 s per site. We illustrate design, selection, and development of the components used in the system. Concerns relating to clinical use, performance, calibration, and quality control are addressed. In the future, spectroscopic data will be compared with histological biopsies from the corresponding tissue sites. If proven effective, this technique can be useful in screening women at high risk of developing ovarian cancer to determine whether oophorectomy is necessary.

Objective: The objective of the study was to develop a clinical confocal microlaparoscope for imaging ovary epithelium in vivo with the long-term objective of diagnosing cancer in vivo., Study Design: A confocal microlaparoscope was developed and used to image the ovaries of 21 patients in vivo using fluorescein sodium and acridine orange as the fluorescent contrast agents., Results: The device was tested in vivo and demonstrated to be safe and function as designed. Real-time cellular visualization of ovary epithelium was demonstrated., Conclusion: The confocal microlaparoscope represents a new type of in vivo imaging device. With its ability to image cellular details in real time, it has the potential to aid in the early diagnosis of cancer. Initially the device may be used to locate unusual regions for guided biopsies. In the long term, the device may be able to supplant traditional biopsies and allow the surgeon to identify early-stage ovarian cancer., (2010 Mosby, Inc.)

Objectives: Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10-20 microm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo., Methods: A custom LOCT device was fabricated specifically for laparoscopic imaging of the ovaries in patients undergoing oophorectomy. OCT images were compared with histopathology to identify preliminary architectural imaging features of normal and pathologic ovarian tissue., Results: Thirty ovaries in 17 primarily peri- or post-menopausal women were successfully imaged with LOCT: 16 normal, 5 endometriosis, 3 serous cystadenoma, and 4 adenocarcinoma. Preliminary imaging features developed for each category reveal qualitative differences in the homogeneous character of normal post-menopausal ovary, the ability to image small subsurface inclusion cysts, and distinguishable features for endometriosis, cystadenoma, and adenocarcinoma., Conclusions: We present the development and successful implementation of the first laparoscopic OCT probe. Comparison of OCT images and corresponding histopathology allowed for the description of preliminary microstructural features for normal ovary, endometriosis, and benign and malignant surface epithelial neoplasms. These results support the potential of OCT both as a diagnostic tool and an imaging modality for further evaluation of ovarian cancer pathogenesis.

Successful treatment of cancer is highly dependent on the stage at which it is diagnosed. Early diagnosis, when the disease is still localized at its origin, results in very high cure rates-even for cancers that typically have poor prognosis. Biopsies are often used for diagnosis of disease. However, because biopsies are destructive, only a limited number can be taken. This leads to reduced sensitivity for detection due to sampling error. A real-time fluorescence confocal microlaparoscope has been developed that provides instant in vivo cellular images, comparable to those provided by histology, through a nondestructive procedure. The device includes an integrated contrast agent delivery mechanism and a computerized depth scan system. The instrument uses a fiber bundle to relay the image plane of a slit-scan confocal microlaparoscope into tissue. It has a 3-mum lateral resolution and a 25-mum axial resolution. Initial in vivo clinical testing using the device to image human ovaries has been done in 21 patients. Results indicate that the device can successfully image organs in vivo without complications. Results with excised tissue demonstrate that the instrument can resolve sufficient cellular detail to visualize the cellular changes associated with the onset of cancer.

Extra mammary Paget disease (EMPD) is a neoplastic disease of apocrine gland bearing skin. Surgical excision is the standard of care for EMPD; however, it is accompanied by recurrence in more than 60% of the patients. Recently, imiquimod cream has been reported to induce complete responses in primary or recurrent EMPD. We report on 2 women with vulva EMPD who achieved biopsy-confirmed resolution of their disease after topical application of imiquimod 5% cream.

Study Objective: In this study we investigated whether teaching advanced laparoscopic procedures like laparoscopic-assisted surgical staging (LASS) for endometrial cancer negatively affects the learning curve of the attending surgeon., Design: Retrospective study (Canadian Task Force classification II-3.), Setting: Department of Obstetrics and Gynecology, University of Arizona, Tucson., Patients: One hundred twenty-four patients undergoing LASS for endometrial cancer at our institution from 1992 through 2004 were included for analysis., Interventions: Cases were classified into 3 groups. Group A comprised the initial learning phase where 2 attending gynecologic oncologists used other faculty as assistants (first 30 cases). Groups B and C comprised procedures after the learning phase involving attendings (n = 27, group B) or obstetrics and gynecology residents (n = 67, group C) as trainees. Groups were compared with respect to general outcome parameters and disease-free survival., Measurements and Main Results: Patients within all groups were comparable with respect to age and height or body mass index. In the subgroup analysis, a decrease in blood loss and length of stay occurred mainly during the group B series. Pelvic lymph node yield reached oncologic standards during the initial learning curve (median 12-13) and remained stable during both teaching phases. Intraoperative and postoperative complications occurred in 2.4% and 13.7% of cases, respectively. Ninety percent of intraoperative and 64% of postoperative complications occurred within the first half of the series and were not correlated with type of assistance. Survival data were obtainable in 65% of cases with a median follow-up of 3.6 years. Disease free-survival was 92.5% in stage I disease and without significant difference among the groups., Conclusion: After gaining proficiency in the procedure, more or less surgically experienced trainees can be actively included without hampering the progress of the attending's learning curve.

VIN 3 is most likely a cancer precursor and is induced by infection with high-risk types of HPV. VIN 3 lesions may be asymptomatic or present with itching and/or burning or the appearance of a vulval lesion (often raised and hyperpig-mented), which may be unifocal or multifocal. All vulval lesions should be biopsied to confirm the diagnosis. Treatment options include laser vaporization, excision or cautery. Long term follow up is essential., (© 2006 International Federation of Gynecology and Obstetrics.)

The clinical manifestation of infection with HPV is determined by multi-ple factors which include the type of HPV, the type of skin infected, the status of host immunity and smoking. The incubation period for HPV is 3 weeks to 8 months. While there is no specific anti-HPV therapy, local topical therapy, excision, cautery and laser vaporization have all been used with a range of success rates., (© 2006 International Federation of Gynecology and Obstetrics.)

Objective: In this analysis, we summarize our experiences with the laparoscopic parametrectomy/upper vaginectomy (LPUV) as a treatment option for patients with an unexpected finding of cervical cancer after simple hysterectomy as well as for patients with cancer of the vaginal cuff., Methods: From 1995-2004, 6 of our patients underwent LPUV including 5 patients with stage Ib(1) cervical cancer and one patient with Ia(1) cervical cancer. Prior procedures were TVH (n = 3), TAH (n = 2) or LAVH (n = 1). Charts were reviewed and follow-up data were collected., Results: Mean age was 40.5 (38-49) years and Quetelet index was 31.5 (25-40) kg/m(2). Average time from hysterectomy to LPUV was 54 (30-84) days. Retrospective FIGO staging revealed stage Ib(1) (n = 5) and stage Ia(1) (n = 1) cervical cancer. Mean duration of surgery was 207 (151-265) min, average blood loss 300 (100-500) mL. One patient had an intraoperative bladder injury and one patient a bowel injury. Histopathological evaluation found residual adenocarcinoma in situ in one patient and no malignancy in all other specimen. All pelvic (average 22 (10-36) nodes, n = 6) and paraaortic nodes (9 nodes, n = 1) were negative for malignancy. One patient had postoperative hematocrit drop and required blood transfusion, mean hematocrit difference pre- vs. postoperative was 6.4 (0.2-10.9) %. There were no further postoperative complications during the average hospital stay of 3.5 (2-5) days. No patient required adjuvant therapy after the operation. There were no recurrences or late complications in an average of 21.5 (3-50) months of follow-up., Conclusion: LPUV is an alternative to open parametrectomy or radiation therapy in patients with unexpected cervical cancer after simple hysterectomy or cancer of the vaginal stump. Bladder injuries must be considered to be a specific complication of this otherwise safe procedure.

Objective: To derive an objective, numeric measure for the progression of intraepithelial and invasive squamous cell cervical lesions., Study Design: Thin-layer cervical cytology preparations from colposcopically confirmed normal cervix, low grade squamous intraepithelial lesions, high grade squamous intraepithelial lesions and carcinoma were identified from a cross-sectional study. Fifty-nine cases representing 4 diagnostic categories were selected, and 2,375 nuclei from epithelial cells representative of the diagnostic category were randomly selected for imaging and measurement from these cases. Additionally, 1,378 visually normal appearing intermediate cells from low and high grade squamous intraepithelial lesions, as well as from carcinoma cases, were identified for analysis. The nuclei were quantitatively characterized, and discriminant analyses were performed to derive a progression curve from normal cytology to carcinoma., Results: The lesion signatures show a clear increase in nuclear abnormality with increasing progression. A progression curve was derived based on mean discriminant function scores for each diagnostic category and on the mean nuclear abnormality values for the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei., Conclusion: A numeric assessment of lesion progression for cervical precancerous and cancerous lesions based on karyometric measurements is possible and may provide an objective, precise characterization of each lesion as well as a basis for improved performance in automated cytology-based cervical cancer screening.

Objective: To improve the survival of women with stage IV epithelial ovarian cancer the Southwest Oncology Group conducted a phase II trial examining two novel treatment strategies: (a) modification of the chemotherapy regimen (carboplatin/paclitaxel) based on evidence of response during treatment and (b) "maintenance therapy," with the monthly administration of single agent paclitaxel (maximum 2 years)., Methods: Individuals with histologically documented stage IV ovarian, fallopian tube, or peritoneal cancers initially received a maximum of 3 courses of single agent carboplatin (AUC 6), with the decision to administer a subsequent course based on specific response criteria (i.e., declines in serum CA-125 or shrinkage of measurable mass lesions). This was followed by single agent paclitaxel (150 mg/m(2)), delivered every 2 weeks for a maximum of 6 courses, again based on evidence of continued response to the treatment program. Finally, in the absence of disease progression or unacceptable toxicity, patients received single agent paclitaxel (175 mg/m2) for a maximum of 24 monthly courses. The primary study end point was 2-year overall survival, which was to be compared to the survival of a previously published historical control population [stage IV ovarian cancer patients treated with a "standard" cisplatin/paclitaxel regimen (GOG 111; McGuire WP, N Eng E J Med 1996; 334:1)]. This analysis was employed to determine if this novel strategy was worthy of further clinical investigation in a controlled clinical trial., Results: There were 53 patients entered this multicenter study, of whom 50 were evaluable for toxicity and 51 for survival. There were 2 treatment-related deaths. Grades 2 and 3 neutrotoxicity were observed in 18 and 4% of patients, respectively. There were no major treatment-related protocol violations. The overall 2-year survival was 48% (95% CI, 34-62%), compared to 60% for the historical control group., Conclusions: While this trial demonstrated the feasibility of delivering a treatment regimen requiring frequent alternations in therapy based on predetermined changes in objective parameters of response, further exploration of this specific management approach does not appear warranted in stage IV ovarian cancer, based on the survival outcome compared to a reasonably similar historical control population. As this trial demonstrates, the prospective determination of clinical end points in a phase II study (e.g., 2-year survival) that will lead to continued evaluation of a particular investigative strategy in a large-scale randomized trial can be an effective method to reduce the bias and uncertainty often associated with this complex decision process.

Background: Urinary calculi formation is an infrequent but challenging late complication of continent urostomy. Percutaneous endoscopic management of two patients with symptomatic pouch urolithiasis is described., Cases: A 48-year-old woman with a history of cervical squamous cell carcinoma (SCC) treated with primary chemoradiotherapy presented with recurrent pain and urinary tract infections (pouchitis). She had undergone continent urostomy 4 years previously for management of a vesicovaginal fistula. A 59-year-old woman following exenteration with continent diversion for recurrent cervix SCC had a 6-month history of refractory pouchitis. In both women, multiple pouch urinary calculi were identified. Their continent reservoirs were, in part, created using titanium staplers. Percutaneous CO(2) endoscopy afforded identification and removal of their stones and staples without complication., Conclusion: Successful treatment of continent urostomy urolithiasis is accomplished by percutaneous endoscopy.

Objective: To determine the potential for both Pap testing and the Chlamydia direct fluorescence assay (DFA) from a single sample using the fluid-based ThinPrep Pap Test method (Cytyc Corporation, Boxborough, Massachusetts)., Study Design: Conventional DFA was compared to ThinPrep DFA in a direct-to-vial, double-blinded, multicenter protocol. Cervical scrapings were collected for the ThinPrep Pap Test, and then a second swab was used to collect an endocervical sample for a conventional DFA test. The DFA slide prepared from the ThinPrep Test and the conventional DFA sample prepared from the endocervical swab were evaluated independently. Discrepant cases were adjudicated by testing residual specimens using a Chlamydia direct DNA method., Results: Combining 636 adequate cases (94% of the total collected), 582 (91.5%) were negative on both slides, 43 (6.8%) positive by both and 11 (1.7%) discrepant. The prevalence of Chlamydia was 7.9% based on the conventional DFA method (range, 4.3-10.9%). McNemar's two-tailed test indicated the results not to be statistically different (P > .05). Adjudication favored ThinPrep 45% of the time and conventional 55%. Specimen adequacy favored ThinPrep with high statistical significance (McNemar's test, P > .01)., Conclusion: A second slide prepared from the same vial of cells as that used for the ThinPrep Pap Test can be used for Chlamydia testing by DFA. Fluid-based collection could allow multiple tests from a single sample.

Introduction: Extrarenal Wilms' tumors are rare, with only 55 well-documented cases in the literature and only 4 confined to the uterus. A fifth case along with review of the current literature is presented., Case: A 13-year-old girl presented with a 2-month history of irregular vaginal spotting. A 6.5 x 4.5 x 2.5-cm polypoid mass meeting criteria for an extrarenal Wilms tumor was removed from the superior aspect of the cervix, but recurred 8 months later on the posterior lip. The patient underwent a Schauta procedure, lymph node dissection, and bilateral oophoropexy. The surgery was followed by typical renal Wilms' tumor chemotherapy. The patient is without evidence of disease 5 years after surgery., Discussion: This case uniquely suggests that limited excision of the original tumor has inherent risks for relapse. Oophoropexy appears to be reasonable when fertility preservation is desired and reconfirms that treatment mimicking renal nephroblastomas offers good long-term survival., (Copyright 2000 Academic Press.)

Objective: To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of cisplatin and carboplatin against fresh cervical cancers from untreated patients., Methods: Specimens were obtained prior to irradiation or radical surgery from 20 patients with locally invasive cervical carcinoma. Cytotoxicity was measured after single cell suspensions were grown in agar using colony counts and incorporation of [3H]thymidine. Nedaplatin and cisplatin were tested at 1 and 10 micrograms/ml dose levels while carboplatin was tested at 10 and 100 micrograms/ml dose levels continuously. When single hour exposures were used, drug doses were increased by 10-fold., Results: The median drug concentrations associated with a 50% inhibition of growth (IC50) for nedaplatin, cisplatin, and carboplatin were 0.435, 0.73, and 18.6 micrograms/ml, respectively. At 10 micrograms/ml for both cisplatin and nedaplatin and 100 micrograms/ml for carboplatin, cisplatin was the most active drug with 70% of tumors sensitive (

Paired blood (collected after an overnight fast) and cervical tissue (cancerous, precancerous, and noncancerous) samples were obtained from 87 patients (age, 21-86 years) who had a hysterectomy or biopsy due to cervical cancer, precancer (cervical intraepithelial neoplasia I, II, and III), or noncancerous diseases. The samples were analyzed using high-performance liquid chromatography for 10 micronutrients (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, cis-beta-carotene, alpha-tocopherol, gamma-tocopherol, and retinol). The results indicated that: (a) among the three patient groups, the mean plasma concentrations of all micronutrients except gamma-tocopherol were lowest in the cancer patients; however, the mean tissue concentrations of the two tocopherols and certain carotenoids were highest in the cancerous tissue; and (b) among the 10 micronutrients, only the concentrations of beta-carotene and cis-beta-carotene were lower in both the plasma and tissue of cancer and precancer patients than in those of noncancer controls. These results suggest that: (a) not all of the micronutrient concentrations in plasma reflect the micronutrient concentrations in cervical tissue; thus, in some cases, it may be necessary to measure the tissue micronutrient concentrations to define the role of the micronutrients in cervical carcinogenesis; and (b) maintaining an adequate plasma and tissue concentration of beta-carotene may be necessary for the prevention of cervical cancer and precancer.

Objective: Our purpose was to evaluate the risk factors and prognosis in patients with stage IA squamous cell carcinoma of the cervix and 3 to 5 mm of invasion., Study Design: From 1981 to 1984 the Gynecologic Oncology Group conducted a prospective clinicopathologic study of patients with stage I carcinoma of the cervix. A selective study group that was previously defined and reported included patients with squamous cell carcinoma of the cervix who were treated with radical hysterectomy and pelvic lymphadenectomy and who had disease confined to the uterus, with or without microscopically positive lymph nodes., Results: One hundred eighty-eight patients had invasion of 3, 4, or 5 mm as determined by central pathology review. Patients who satisfied the 3 to 5 mm invasion definition of the current stage IA2 classification of the International Federation of Gynecology and Obstetrics (1995) are the subject of this report., Conclusions: Patients with stage IA2 carcinoma of the cervix who have 3 to 5 mm of invasion present on conization with no invasion in the hysterectomy specimen are at very low risk for lymph node metastases, recurrences, or death caused by cancer.

There is a critical need to find additional effective therapies in the management of ovarian cancer. A previously reported Gynecologic Oncology Group trial demonstrated that tamoxifen is an active drug when used in the salvage setting in this malignancy. Unfortunately, this original report did not specifically examine the utility of tamoxifen in patients with clinically defined platinum-refractory disease. In this reanalysis of the results of treatment of 102 evaluable patients entered into this multi-institutional trial, an objective response rate of 13% (95% confidence interval, 6.4-22.6%) was observed in patients with cisplatin-refractory ovarian cancer. The median response duration in this patient population was 4.4 months (range 1.2-9.2 months). Although the response rate is modest, this well-tolerated hormonal agent is a reasonable therapeutic option in selected patients with ovarian cancer when salvage therapy is to be considered. A possible role for this hormonal agent in other clinical settings in ovarian cancer will need to be defined through the conduct of carefully designed randomized clinical trials.

Purpose: Our goal was to evaluate laparoscopic pelvic lymph node dissection, para-aortic lymph node sampling, and laparoscopic radical vaginal hysterectomy (Schauta) in the treatment of early stage cervical cancer., Materials and Methods: In a retrospective study of 37 patients treated in the period between October 1993 and February 1996, we evaluated operative time, blood loss, length of hospital stay, lymph node count, and morbidity. Radical abdominal hysterectomy was compared with laparoscopic pelvic lymph node dissection and para-aortic lymph node sampling. Improvement over time was analyzed., Results: Mean operative time was 225 minutes, blood loss was 525 mL, and the average hospital stay was 3 days. This information was compared with a radical abdominal hysterectomy and pelvic and para-aortic lymph node dissection, where the operative time was 210 minutes, blood loss was 1500 mL, and the hospital stay was 9.7 days. Blood transfusion was required in 11% of patients compared with a range of 35%-95% reported in the literature for radical abdominal hysterectomy. The mean pelvic lymph node count was 35; the mean para-aortic lymph node count was 11. Two patients had cystotomies repaired at surgery without lengthening hospital stay or subsequent complication. Two patients had ureteral vaginal fistulae treated by a ureteral stent, which was removed 6 weeks later without further operative procedures or urinary damage. When the data were correlated with the length of experience using the analysis of variance test and linear regression, operative time, blood loss, and hospital costs significantly improved over time. Patient charges averaged $14,868.00 and estimated hospital costs averaged $6449.00., Conclusion: Laparoscopic pelvic lymph node dissection and para-aortic lymph node sampling can be performed with adequate lymph node counts and lower morbidity. Laparoscopic Schauta allows shorter hospital stay than radical abdominal hysterectomy, with significantly less blood loss and markedly fewer blood transfusions. Morbidity is higher early in the surgeon's experience but decreases over time.

The use of laparoscopy in the management of gynecologic malignancies has significantly increased over the last 5 years. The safety and adequacy of pelvic and para-aortic lymphadenectomy has been established by several investigators. Patients with early carcinoma of the cervix are now undergoing Schauta (radical vaginal) hysterectomy after laparoscopic lymphadenectomy. Patients with carcinoma of the endometrium are treated by laparoscopically assisted vaginal hysterectomy in conjunction with laparoscopic pelvic and para-aortic lymphadenectomy. Staging and second-look procedures are now being performed laparoscopically in patients with carcinoma of the ovary. The Gynecologic Oncology Group is currently investigating the role of laparoscopic surgery for patients with carcinoma of the cervix, endometrium, and ovary in four Phase II trials. A randomized Phase III trial comparing laparoscopy to laparotomy for patients with carcinoma of the endometrium will begin soon.

The feasibility of laparoscopic staging in patients with ovarian cancer was undertaken prospectively to determine the ability to adequately evaluate both the intraperitoneal cavity and the retroperitoneal lymph nodes. Two groups of ovarian cancer patients were evaluated: those with optimally debulked advanced disease undergoing second-look procedures and those with presumed stage I disease undergoing surgical staging. Twenty-four of the 44 laparoscopic second-look procedures (56%) were positive for persistent disease. Five of these patients had microscopic disease only, in the omentum, washings, pelvic peritoneum, and in para-aortic lymph nodes (2 patients). In the group of 14 patients undergoing staging for presumed early ovarian carcinoma, metastatic disease was discovered in 8 (57%) patients. Two patients had peritoneal washings positive for adenocarcinoma; 3 had pelvic disease, 1 confined to a fallopian tube and 2 to the pelvic peritoneum; and 3 patients had para-aortic lymph nodes positive for metastatic adenocarcinoma. There were no serious complications in this category. The average hospital stay was 1.6 days. Laparoscopic staging appears to be an accurate staging technique, and further investigation into the validity of this approach is warranted.