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Despite mounting evidence that large intramural leiomyomas decrease fecundity during in vitro fertilization cycles, few studies have demonstrated a mechanism for this impact. We hypothesize that large intramural leiomyomas (IM) decrease the expression of endometrial implantation factors during the window of implantation. We prospectively recruited sub-fertile patients with IM 3 cm or greater in size planning myomectomy and performed endometrial biopsies the day of planned myomectomy (n = 9). Preoperative screening demonstrated no intercavitary lesions. Control endometrial samples were obtained from young, normally menstruating women free of uterine leiomyomas (n = 8). Endometrial samples were obtained in the mid-secretory phase (average cycle day for control patients and intramural leiomyoma patients were 24.5 and 21.3, respectively). Expression of implantation markers HOXA10, leukemia inhibitory factor (LIF), ER-α, and PR was compared using quantitative immunohistochemistry. Standard descriptive statistics were used to compare H-scores between the cohorts. Patients with intramural leiomyomas were found to have decreased LIF compared to controls (p value

The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3.Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue.Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort.pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy.

To investigate whether tumor cells could be detected in the vagina of women with serous ovarian cancer through TP53 analysis of DNA samples collected by placement of a vaginal tampon.Women undergoing surgery for a pelvic mass were identified in the gynecologic oncology clinic. They placed a vaginal tampon before surgery, which was removed in the operating room. Cells were isolated and DNA was extracted from both the cells trapped within the tampon and the primary tumor. In patients with serous carcinoma, the DNA was interrogated for the presence of TP53 mutations using a method capable of detecting rare mutant alleles in a mixture of mutant and wild-type DNA.Thirty-three patients were enrolled. Eight patients with advanced serous ovarian cancer were included for analysis. Three had a prior tubal ligation. TP53 mutations were identified in all eight tumor samples. Analysis of the DNA from the tampons revealed mutations in three of the five patients with intact tubes (sensitivity 60%) and in none of the three patients with tubal ligation. In all three participants with mutation detected in the tampon specimen, the tumor and the vaginal DNA harbored the exact same TP53 mutation. The fraction of DNA derived from exfoliated tumor cells ranged from 0.01% to 0.07%.In this pilot study, DNA derived from tumor was detected in the vaginas of 60% of patients with ovarian cancer with intact fallopian tubes. With further development, this approach may hold promise for the early detection of this deadly disease.

OBJECTIVE. Carcinosarcomas are rare and aggressive ovarian malignancies. Treatment recommendations, which include surgical cytoreduction followed by platinum based chemotherapy, have been based on small amounts of retrospective data or extrapolated from experience with high-grade epithelial ovarian adenocarcinoma. Our objective was to determine the effects of radical primary cytoreduction on progression-free survival (PFS) and overall survival (OS). METHODS. Following IRB approval, records of women with ovarian carcinosarcomas diagnosed between 2000 and 2012 at our institution were reviewed. Demographics, tumor characteristics, treatments, PFS, and OS were collected. Patients were divided into three groups based on the amount of residual disease: N1 cm of disease, ≤1 cm of disease, or no visible disease. Chi-square and student’s t-test were used to compare variables among groups. Kaplan–Meier survival curves were generated and compared with the log-rank test. RESULTS. 51 patients with ovarian carcinosarcoma were identified and all underwent primary cytoreductive surgery. Following surgical cytoreduction, 18 patients (35%) had no visible disease, 20 (39%) had ≤1 cm of disease, and 13 (25%) had >1 cm of residual disease. Median PFS varied significantly among groups: 29 vs. 21 vs. 2 months (p = 0.036) as did median OS: 57 vs. 32 vs. 11 months (p = 0.015). When patients with stage 3 disease were analyzed separately, median OS still varied significantly among groups: 57 versus 31 versus 3 months (p = 0.009). CONCLUSION. Degree of surgical cytoreduction appears to correlate with PFS and OS. Radical surgery resulting in no visible disease is recommended for the upfront surgical treatment of ovarian carcinosarcoma.

Advanced cases of epithelial ovarian, primary peritoneal, and primary tubal malignancies have a relatively poor prognosis and collectively remain the most deadly of all gynecologic malignancies. Although traditionally thought of as one disease process, ongoing research suggests that there is not 1 single site or cell type from which these cancers arise. A majority of the serous tumors appear to originate from dysplastic lesions in the distal fallopian tube. Therefore, what we have traditionally considered “ovarian” cancer may in fact be tubal in origin. In this article, we will review epithelial ovarian cancer classification and genetics, theories regarding cells of origin with a focus on tubal intraepithelial carcinoma, and implications for prevention and screening.

Malignant transformation in a mature cystic teratoma (MCT) is rare, with a reported incidence of approximately 1% to 3%. To our knowledge, no case has been reported previously with the invasion of malignant tumor of MCT into the adjacent small intestine. We report a case of squamous cell carcinoma arising within a MCT and invading into the adjacent small bowel. The patient is a 73-yr-old African American woman who noted the presence of a relatively asymptomatic abdominal mass over the past 40 yr. The mass had become more symptomatic over the past several months, with right-sided abdominal pain and constipation. She underwent an exploratory laparatomy, which demonstrated a cystic abdominal mass measuring 24 cm in diameter and weighing 8 kg. The mass contained necrotic debris, a cloudy fluid, hair, and cartilage. It was adherent to the small intestine in an area associated with focal thickening of the cystic wall of the mass. Histologically, the mass demonstrated a MCT within which arose a well-differentiated squamous cell carcinoma. At the point of attachment to the small intestine, histologic sections demonstrated a transmural invasion of the squamous cell carcinoma into the attached segment of the small intestine through the muscularis propria and the submucosa reaching the mucosal surface. Thirteen regional lymph nodes were isolated near the portion of the small intestine involved with the tumor; however, none of them exhibited metastatic carcinoma.

• HVO focuses on the education, surgical training and development of research skills of surgical oncology residents.

This study aimed at evaluating the expression of tyrosine kinase receptors c-kit, (platelet-derived growth factor receptor-alpha (PDGFR-alpha), and PDGFR-beta in ovarian granulosa cell tumors (GCTs).Primary ovarian GCT specimens were obtained for immunohistochemical staining.The expressions of c-kit, PDGFR-alpha, and PDGFR-beta were analyzed and scored by a semiquantitative (SQ) method. Normal ovarian tissue from the same patients' specimens served as internal controls.A total of 21 specimens were available for evaluation. C-kit was expressed in only 2 samples, whereas both PDGFR-alpha and PDGFR-beta stained positive in 100% of tumors. PDGFR targets demonstrated strong positive expression in intensity and amount of tissue stained. Normal ovarian tissue demonstrated complete absence of staining for all 3 antibodies evaluated.The data demonstrated significant expression of PDGFR targets of imatinib mesylate in GCTs, whereas normal ovarian tissues had a complete absence of staining.This expression profile provides the rationale to investigate the role of imatinib mesylate in PDGFR-positive GCTs.

In this report, we present the case of a 32-year-old woman with Wegener's granulomatosis of the uterine cervix, review the literature, and discuss the differential diagnosis.

Describe the effect of 50 mcg vaginal 17-β-estradiol (E2) cream on vaginal maturation, serum estrogen levels, atrophic symptoms, and biomarkers of oxidative stress and tissue remodeling in postmenopausal women without prolapse.Seventeen women, 65 years or older, applied intravaginal E2 cream nightly for eight weeks, then twice weekly for eight weeks. Vaginal biopsies, serial blood draws, and atrophic symptoms were obtained at baseline, eight, and sixteen weeks. Changes in atrophic symptoms, vaginal maturation indices (VMI), and serum E2 were measured. Immunohistochemical staining characterized levels of transforming growth factor-beta (TGF-β), nuclear factor kappa B (NFKB), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and thrombospondin (TSP).Serum E2 levels (pg/ml) were unchanged from baseline (mean (SD)) 7.7 (3.3) to eight 9.7 (5.7) and sixteen 8.7 (5.8) (p=0.24) weeks. VMI (mean (SD)) improved from baseline 34.2 (18.3) to eight 56.7 (13.1) and sixteen 54.5 (11.3) (p0.001) weeks with no difference between eight and sixteen weeks. Vaginal dryness (p=0.03) and itching (p=0.02) improved. Tissue biomarker levels did not change (TGF-β p=0.35, NFKB p=0.74, eNOS p=0.80, iNOS p=0.24, TSP p=0.80).Vaginal E2 improved atrophic symptoms and VMI without elevating serum E2. Tissue remodeling biomarkers did not change.

To prospectively evaluate in a blinded fashion the accuracy of frozen section in endometrial cancer.Sixty patients with endometrial cancer or complex atypical hyperplasia were consecutively enrolled. Intraoperatively, a frozen section was obtained, processed, and stored for interpretation by blinded pathologists. Final pathologic diagnosis was conducted in the usual fashion with the pathologists blinded to frozen results. Histologic grade and myometrial invasion on frozen section was correlated with final pathology.Median age was 61 years (range, 39-82 years). Fifty-seven percent of patients were white, and mean body mass index was 40 mg/kg2. Depth of invasion on frozen correlated with final pathology in 67% (95% confidence interval [CI] 55-79%). Twenty-eight percent (95% CI 17-39%) of patients were upstaged from frozen to final. Patients with no invasion on frozen were upstaged in 46% (95% CI 28-64%). Histologic grade on frozen correlated with final pathology in 58% (95% CI 46-70%); 38% (95% CI 26-50%) of patients were upgraded by final grade. Patients with frozen grade 1 histology or less were upgraded in 61% (95% CI 45-77%). Clinically relevant upstaging occurred in 11 patients (18%) (95% CI 8-28%).Frozen section for histologic grade and depth of myometrial invasion in endometrial cancer correlates poorly with final pathology. Because a large number of patients are potentially understaged with the use of frozen section with a subsequent risk of over and under treatment, we recommend consideration of comprehensive surgical staging for all patients with endometrial cancer.II-2.

A 23-year-old female underwent a cesarean section for breech presentation at term. Her postpartum course was complicated by multiple admissions for pelvic pain presumed to be endometritis. Her symptoms were temporarily alleviated with intravenous antibiotics during each hospitalization. Imaging to evaluate persistent abdominal pain revealed a large cystic right lower quadrant mass adjacent to the ovary. Findings at diagnostic laparoscopy included a 15-cm × 4-cm appendix with pathology confirming myxoglobulosis. This case describes the only reported case of myxoglobulosis of the appendix presenting as a rare cause of pelvic pain in a postpartum patient. (J GYNECOL SURG 20:127)

Background: Despite its favorable prognosis, endometrial stromal sarcoma (ESS) commonly recurs in the abdomen and pelvis. Rarely, it recurs in the cardiovascular system. A case of isolated cardiac ESS recurrence without concurrent vascular or abdominal disease is presented in this report. Case: A 53-year-old woman with previously diagnosed and treated ESS presented to her physician with tachycardia and fatigue. Transthoracic echocardiogram revealed an intra-atrial pedunculated mass without caval involvement. Results: Surgical resection was performed successfully with alleviation of the patient'sher symptoms. Pathology confirmed isolated intracardiac recurrent ESS. Conclusions: This is the first documented case of intracardiac recurrence of ESS without concurrent abdominal or intracaval disease. This isolated recurrence supports a hematogenous mechanism of spread for ESS rather than intracavitary diffusion. Aggressive surgical management continues to be an option for treatment. (J GYNECOL SURG 28:140)

Objective. The Wnt/β-catenin pathway is known to regulate cellular proliferation and plays a role in chemoresistance. Niclosamide, an FDA approved salicyclamide derivative used for the treatment of tapeworm infections, targets the Wnt/β-catenin pathway. Therefore, the objective of this study was to investigate niclosamide as a potential therapeutic agent for ovarian cancer. Methods. Tumor cells isolated from 34 patients' ascites with primary ovarian cancer were treated with niclosamide (0.1 to 5 μM) ± carboplatin (5 to 150 μM). Cell viability was assessed using the ATP-lite assay. LRP6, Axin 2, Cyclin D1, survivin and cytosolic free β-catenin levels were determined using Western blot analysis. Tumorspheres were treated, and Wnt transcriptional activity was measured by the TOPflash reporter assay. ALDH and CD133 were analyzed by Flow cytometry and IHC. ALDH1A1 and LRP6 were analyzed by IHC in solid tumor and in ascites before and after treatment with niclosamide. Results. Combination treatment produced increased cytotoxicity compared to single agent treatment in 32/34 patient samples. Western blot analysis showed a decrease in Wnt/β-catenin pathway proteins and the expression of target genes. A significant reduction of Wnt/β-catenin signaling was confirmed by TOPflash assay. There was increased staining of ALDH1A1 and LRP6 in ascites compared to solid tumor which decreased after treatment. Conclusion. This study demonstrates that niclosamide is a potent Wnt/β-catenin inhibitor. Targeting the Wnt/β-catenin pathway led to decreased cellular proliferation and increased cell death. These findings warrant further research of this drug and other niclosamide analogs as a treatment option for ovarian cancer.

Nonpuerperal uterine inversion is an extremely rare gynecologic event. The vast majority of nonpuerperal inversions occur in association with a uterine tumor, of which approximately 20% are malignant. The case of a 74-year-old patient with suspected primary cervical sarcoma is presented. At the time of surgery, nonpuerperal uterine inversion was identified. High-grade endometrial stromal sarcoma was confirmed on pathologic examination. The etiologic factors that constitute the differential diagnosis are discussed, as well as strategies for managing this unusual entity.

Background. Clear cell adenocarcinoma (CCA) of the vagina is traditionally treated with radical surgical resection with tailored postoperative radiation when indicated. Due to a bimodal distribution, women of reproductive age are frequently affected and could benefit from radical trachelectomy to preserve fertility. Case. A 22 year old female was diagnosed with clinical stage I vaginal clear cell adenocarcinoma in the left fornix abutting the cervix. The patient desired future fertility; therefore, she underwent radical abdominal trachelectomy and upper vaginectomy. Twenty-eight months after initial surgery, she has no evidence of recurrence with regular menstrual cycles. Conclusion. For patients with CCA of the upper vagina, where removal of the cervix is necessary, a radical trachelectomy with upper vaginectomy should be considered to conserve fertility.

Background. Although mature cystic teratoma is the most common tumor of the ovary, squamous cell carcinoma arising from a mature teratoma is a rare event. Prognosis depends on clinical stage, grade, and recently described mode of tumor infiltration. Case. This case involves a 52-year-old woman with stage II squamous cell carcinoma arising in a mature cystic teratoma of the left ovary. Final pathology demonstrated poorly differentiated squamous cell carcinoma with gamma mode of tumor infiltration. The patient completed adjuvant chemotherapy and subsequently died of progressive disease. Conclusion. Squamous cell carcinoma arising from a benign cystic teratoma is a rare event. Studies have shown stage, grade, and mode of infiltration to be predictors of recurrence and prognosis. This case supports the growing evidence linking the mode of tumor infiltration with overall prognosis of survival.

Background Positron emission tomography (PET) is commonly used to detect occult or recurrent malignancy, including tumors of the female genital tract. Recently, there have been reports of PET scans used in patients with Gestational Trophoblastic Disease (GTD). Case A 22-year-old female presented with vaginal bleeding and elevated β-hCG 7 months after a spontaneous vaginal delivery of a healthy infant. She had a history of molar pregnancy and persistent GTD requiring multi-agent chemotherapy. Metastatic evaluation with computed tomography and magnetic resonance imaging showed no evidence of GTD. A positron emission tomography/computed tomography (PET/CT) scan revealed a focus of metabolic activity in the left pelvis. The patient underwent an exploratory laparotomy that revealed metastatic choriocarcinoma in the left broad ligament. Conclusion PET/CT may be useful in the evaluation of occult choriocarcinoma when conventional imaging fails to identify metastatic disease.

To determine the radiographic characteristics of ovarian granulosa cell tumors (GCTs) and to evaluate the use of CA125 levels35 in combination with imaging as an algorithm for preoperative diagnosis.A retrospective analysis of women from two academic medical centers who were diagnosed with ovarian GCT between January 1998 and August 2012 was conducted. Clinical data included tumor appearance on pre-operative imaging and CA125 levels. Ovarian cysts were defined as complex if imaging exhibited multicystic areas, hemorrhagic, solid, or cystic and solid components. A CA125 level35 was abnormal.One hundred and fifteen women were diagnosed with GCTs, of whom 63 underwent pre-operative imaging. Median age at surgery was 46 years (12-87). Forty women had preoperative ultrasounds, 43 had CT scans and 20 underwent both modalities. GCTs were almost exclusively classified as complex cysts in 62 (98%) cases. The most common morphology was solid and cystic (n=44 (70%)). Forty-four (70%) patients had tumors10 cm. Forty-two patients had a pre-operative CA125 performed. Eighteen (43%) patients had complex masses and CA12535. Twenty-three (55%) had CA12535 with a complex mass, and one (2%) had a unilocular cyst with a CA12535.In this study, there was a near equal distribution of patients with complex masses and CA125 levelsor35. If established strategies to predict malignancy are applied to GCTs, we will frequently fail to make the diagnosis pre-operatively. Additional research is necessary to generate an appropriate algorithm to guide pre-operative referral to a gynecologic oncologist.

BACKGROUND: Uterine leiomyosarcoma is an aggressive tumor that has a propensity for distant metastasis. Distant sites of spread include the lung, liver, brain, and bone. CASE: A woman in her 5th decade was diagnosed with stage IV leiomyosarcoma of the uterus. Distant metastasis in the chest was confirmed by thoracotomy at the time of her original diagnosis. She subsequently experienced multiple episodes of metastasis including metastatic disease to her thyroid. She survived 71 months after diagnosis of stage IV disease. CONCLUSION: Our case represents the first reported experience with uterine leiomyosarcoma metastatic to the thyroid. Additionally the case is notable because the patient experienced multiple episodes of asymptomatic stable disease after repetitive chemotherapeutic regimens.

To evaluate patterns of failure and overall survival for patients with surgical stage I uterine carcinosarcoma managed conservatively without adjuvant therapy. A computerized database identified 27 patients whose conditions have been diagnosed with surgical stage I uterine carcinosarcoma from 1993 to 2002. Charts were abstracted for patient demographics, tumor characteristics, recurrence, and survival. Of 27 patients, 23(85%) did not receive adjuvant therapy after undergoing total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy. Five patients were stage IA, 14 were stage IB, and 4 were stage IC. Fourteen patients had either poorly differentiated endometrioid carcinoma alone or in combination with papillary serous carcinoma (61%) as their epithelial tumor component. The median nodal count was 9 (range, 3-21). Eleven patients are alive without evidence of disease with a median follow-up of 63 months (range, 12-164 months). Eleven patients had recurrence with a median time to recurrence of 13 months (range, 6-39 months), and all are dead of disease. Univariate analysis demonstrated that poorly differentiated epithelial or papillary serous histologic diagnosis was the only predictor variable associated with recurrence and, consequently, death (P = 0.04). Approximately 50% of patients with surgical stage I carcinosarcoma who are observed without adjuvant therapy will experience a recurrence. Because most patients will recur distantly, systemic chemotherapy should be considered for patients with early stage uterine carcinosarcoma.

Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (HE) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed HE alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using HE diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for HE/p16/Ki-67 combined were comparable to that of HE alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, HE/p16/Ki-67 combined, and HE alone.Interobserver agreement for diagnosis of AIN was fair when based solely on HE preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with HE, Ki-67, and HE/p16/Ki-67 combined.

Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is the most common hereditary cancer syndrome in the United States and Europe. More than 50% of women diagnosed with Lynch syndrome will present with a gynecologic malignancy as their sentinel cancer; the majority of these cancers will be endometrial cancer.1 HNPCC is caused by a germline mutation in the DNA mismatch repair mechanism that works to ensure the fidelity of the genome during cell division.2 The most common mutations are MLH1, MSH2, MSH6, and PMS2; defects in these genes result in microsatellite instability.3 Per the Modified Bethesda criteria recommendations, patients less than age 50 diagnosed with colorectal cancer should undergo testing to determine whether they have a genetic mutation associated with Lynch syndrome (see the Box). Although approximately 11% of patients under the age of 50 diagnosed with endometrial cancer will have a mutation consistent with Lynch syndrome,4 no recommendations for genetic testing exist specific to endometrial cancer.5 Modified Bethesda Criteria Tumors from individuals should be tested for microsatellite instability in the following situations: Colorectal cancer diagnosed in a patient who is less than 50 years of age. Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumors,* regardless of patient age. Colorectal cancer with the microsatellite instability-H–like histology diagnosed in a patient who is less than 60 years of age. Colorectal cancer diagnosed in a patient with one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed before the age of 50. Colorectal cancer diagnosed in a patient with two or more first- or second-degree relatives with HNPCC-related tumors, regardless of age. *HNPCC-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, and brain tumors; sebaceous gland adenomas and keratoacanthomas in Muir-Torre syndrome; and carcinoma of the small bowel. The purpose of this study was to estimate the frequency of mismatch repair deficiencies detected by immunohistochemistry and microsatellite instability testing in women less than age 50 with endometrial cancer. Additionally, we sought to evaluate whether obesity affected the frequency of mismatch repair deficiencies.

The purpose of this study was to explore whether endometrial microbial colonization and plasma cell endometritis are risk factors for adverse pregnancy outcomes, and whether these outcomes are influenced by interactions between interconceptional antibiotics and the micro-flora.Subgroup analyses of data from a double-blind, randomized, placebo-controlled trial of a course of metronidazole plus azithromycin given every 4 months to women with a prior preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histology were obtained at randomization and repeated 2 weeks after the first treatment. Fifty-nine on antibiotics versus 65 on placebo had pregnancy outcomes. Prevalence of adverse pregnancy outcomes (pregnancy loss or preterm birth37 weeks) was stratified by treatment group and endometrial characteristics. Subgroups were assessed and screened for potential interaction (P values for significance set a priori at.01), prior to formal statistical testing for interaction (P values.05).The prevalence of adverse pregnancy outcome was 62.7% in the presence of endometrial microbial colonization at baseline (any microbe) and 50% in the absence of colonization (RR = 1.25; 99% CI 0.42-3.7). Prevalence of adverse pregnancy outcomes was 61.9% with plasma cell endometritis, and 70.8% without; RR = 0.87 (0.50-1.5). There was a nonsignificant reduction in adverse pregnancy outcome in the absence of Gardnerella vaginalis or gram-negative rods with RR (95% CI) = 0.60 (0.3-1.2) and 0.66 (0.4-1.2), respectively. In the presence of these microbes, antibiotics appeared to increase adverse outcomes: RR = 1.5 (1.1-2.0) and 1.5 (1.1-2.1), respectively. This reversal of impact represents a crossover interaction.Neither baseline endometrial microbial colonization nor plasma cell endometritis were risk factors for adverse pregnancy outcome. However, colonization with specific microbes interacted with antibiotics to increase adverse outcomes.

OBJECTIVE A pilot study to determine genomic microarray differences in patients with normal cervical tissue and cervical intraepithelial neoplasia (CIN) 3. MATERIALS AND METHODS After institutional review board approval, patients referred to the University of Alabama at Birmingham Colposcopy Clinic for a loop electrosurgical excisional procedure were identified. Tissue biopsies of both normal tissue and CIN 3 from fresh loop electrosurgical excisional procedure specimens were obtained and sent to pathology for histological confirmation. Procurement of these 2 types of tissue from the same patient controls for different types of human papillomavirus infection, smoking and nutritional status, age, immunocompetency, and other microenvironment factors (i.e., the patient serves as their own control). Standard RNA extraction techniques (Qiagen, Inc., Valencia, CA) were used to prepare the tissue specimens for microarray analysis with the Affymetrix GeneChip U133A expression array (Affymetrix, Inc., Santa Clara, CA). Paired samples were eligible for microarray analysis only when both normal tissue and CIN 3 were confirmed by pathology. The data were then subsequently subjected to a log-like transformation and analyzed with a t test. For this study, p

The purpose of this study was to evaluate the impact of an interconception antibiotic regimen on endometrial microbial flora and histologic type.This was a secondary analysis of a double-blind randomized placebo-controlled trial of prophylactic metronidazole plus azithromycin that was given to 241 women (antibiotics, 118 women; placebo, 123 women) with a previous preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histologic types were obtained at randomization and 2 weeks after treatment. The prevalence of either the new acquisition or the resolution of individual microbes, categories of microbes, and plasma cell endometritis were compared by chi-square or Fishers' exact tests.Overall, antibiotics were associated with lower acquisition and higher resolution of microbes. Of women without Gardnerella at baseline, 14% of the women who received antibiotics vs 34% of the women who received placebo had positive endometrial culture for the organism after treatment (P.05); of those women with G. vaginalis at baseline, 57% of the women who received antibiotics vs 33% of the women who received placebo (P.05) had a negative follow-up culture. Other gram-negative rods, especially aerobes in general, manifested similar patterns. The impact on anaerobes and plasma cell endometritis was not definitive, but there was a trend toward the increased resolution of the former (77% vs 55%) and reduced acquisition of the latter (28% vs 50%).The antibiotic regimen prevented the acquisition and promoted the resolution, but not the eradication, of gram-negative rods such as G. vaginalis and the aerobic subcategory.

Background Inflammatory pseudotumor is a rare benign cause of lymphadenopathy previously reported in several anatomic locations that can simulate malignant neoplasm. Case A postmenopausal woman presented with abdominal pain, generalized malaise, leukocytosis, and intermittent fevers up to 102 degrees F. A 5-day course of antibiotics was given with persistence of symptoms. Computed tomography of the abdomen and pelvis demonstrated an ill-defined, retroperitoneal soft-tissue density, and lymphadenopathy. She underwent an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and unilateral pelvic and paraaortic lymphadenotomy. Histologic examination revealed inflammatory pseudotumor of the lymph nodes, with immunohistochemical studies demonstrating actin-positive myofibroblastic cells. Four months after surgery, the patient remains asymptomatic without evidence of disease. Conclusion Inflammatory pseudotumor of the pelvic lymph nodes is a rare entity and should be included in the differential diagnosis of patients with persistent fever and lymphadenopathy.

Background. Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD) that is generally resistant to conventional chemotherapeutic treatment. Patients with localized disease are usually managed with hysterectomy. Case. A 29-year-old female presented with vaginal bleeding and an elevated serum human chorionic gonadotropin (HCG). After initial observation, the patient experienced continued vaginal bleeding and a persistently elevated HCG. Therefore, she underwent a dilation and curettage and final pathology revealed PSTT. Since the patient desired future fertility, the patient received combination chemotherapy with etoposide, methotrexate, actinomycin-D followed by etoposide and cisplatin (EMA-EP). The patient had a complete response to chemotherapy and subsequently delivered a term infant 2 years after completion of therapy. Conclusion. PSTT is thought to be a chemoresistant disease and the preferred method of treatment is hysterectomy or local uterine resection. However, combination chemotherapy is a reasonable option in a properly counseled patient who strongly desires future fertility.

Background. Basosquamous cell carcinoma (BSC) of the vulva is a rare entity with interesting prognostic and therapeutic implications. Currently, there is no definitive treatment due to its low incidence. Case. A case of recurrent BSC of the vulva treated with unilateral radical vulvectomy and unilateral lymph node dissection is reported. Conclusion. BSC is a rare disorder of the vulva. The metastatic potential of this tumor is not fully understood, but likely is intermediate between squamous cell carcinoma and basal cell carcinoma. Local recurrence is common and close follow-up is warranted.

Objective This study was undertaken to determine whether asymptomatic bacterial vaginosis (BV) is associated with an increased risk of endometrial microbial colonization or plasma cell endometritis in nonpregnant women. Study design In this observational cohort study conducted between August 1995 and August 2001, microbial cultures (n = 769) and histopathology (n = 482) were performed on endometrial specimens obtained from women with a recent preterm or term delivery (83 ± 16 days). Endometritis was defined as the presence of plasma cells. BV was defined using Amsel and Nugent criteria. Results The study population was 71% black, 29% white, 69% single, and 31% had 12 years or more of education. Endometrial cultures were positive for at least 1 microorganism in 83% (n = 637/769) of the women and plasma cell endometritis was present in 39% (n = 190/482). BV was present in 26% (n = 191/722) by Amsel and 38% (n = 289/769) by Nugent criteria. Women with Nugent-BV (RR [relative risk] = 1.12, 95% CI 1.05-1.19) but not Amsel-BV (RR = 1.06, 95% CI 1.00-1.13) were significantly more likely to have a positive endometrial culture. A consistent and significant association was observed between BV (by Amsel or Nugent criteria) and an increased frequency of endometrial colonization with BV-associated microorganisms grouped and defined in various ways (RR ranged from 1.96-4.22). No association between BV and plasma cell endometritis was observed. Conclusion Asymptomatic BV is associated with a modest increased likelihood of endometrial microbial colonization and colonization by BV-associated bacteria but is not associated with plasma cell endometritis in nonpregnant women.

Background. Although uterine anomalies are uncommon, gynecologists must be aware of the anatomical challenges that may be encountered from these anomalies. Cervical cancer in the context of a mullerian lateral fusion defect is rare. Case. A case of a unilateral IB1 squamous cell carcinoma of the cervix in the setting of a complete uterovaginal septum and cervix duplex is described. Conclusion. Uterine anomalies compound diagnostic difficulty of routine pathology. Thorough examination and evaluation are crucial for timely diagnosis and treatment. Genital tract duplication, although rare, should always be considered.

Objective This study was undertaken to determine whether endometrial microbial colonization or plasma cell endometritis is increased after spontaneous versus indicated preterm delivery or a spontaneous term delivery. Study design Postpartum, endometrial specimens were obtained after a spontaneous (mean 83, ± 17.6 days) or indicated (mean 83, ± 16.7 days) preterm delivery before 34 weeks' gestation and after a spontaneous term delivery (mean 82, ± 15.7 days; P =.980). Cultures for aerobic and anaerobic bacteria, Trichomonas vaginalis , and genital mycoplasmas were performed. Histologic endometritis was defined as the presence of plasma cells. Results The study population (n=820) was 71% black, 29% white, 69% unmarried, and 31% had less than 12 years of education. Endometrial cultures were positive for at least 1 microorganism in 82% of the women. No significant difference in positive endometrial cultures were observed among women after a spontaneous versus an indicated preterm delivery (85% vs 79%, P =.102), or a spontaneous preterm versus a spontaneous term delivery (85% vs 81%, P =.123). Plasma cell endometritis was present in 39% of 506 specimens sufficient for histologic examination and was also similar in the three groups ( P =.160). Conclusion Microbial colonization of the endometrium and plasma cell endometritis are similar 3 months after spontaneous or indicated preterm or term births. Therefore, chronic infection and inflammation of the endometrium (documented at 3 months postpartum) do not appear to be risk factors for subsequent delivery in women with a prior spontaneous delivery less than 34 weeks' gestation.

Background . Metastatic cancer to the vulva is a rare diagnosis and is estimated to account for 5–8% of all vulvar cancers. Case . A 57-year-old postmenopausal woman was referred for the evaluation of a new vulvar mass. CT scan of the pelvis demonstrated a 4 × 6 cm lobular mass of the left labia. An outpatient excisional biopsy revealed a poorly differentiated large cell carcinoma with prominent necrosis and focal perineural invasion consistent with a bronchogenic carcinoma. A subsequent PET scan of the chest revealed a large primary lung carcinoma confirmed by CT-guided biopsy that was identical to the vulvar tumor. Conclusion . This case represents the only literature described primary lung carcinoma presenting as a vulvar metastasis.

Objective. The objective of this study was to determine whether clinicopathologic findings or the immunohistochemical presence of molecular markers are predictive of clinical outcome in patients with small cell carcinoma of the cervix (SCCC). Methods. A retrospective review of cases of carcinoma of the cervix was conducted to identify SCCC. From 1978 to 1999, 16 patients were identified at our institution with the diagnosis of SCCC. Microscopic sections of paraffin-embedded tissue specimens were evaluated for confirmation of diagnosis. Specimens were immunohistochemically stained with antibodies to three neuroendocrine markers: neuron-specific enolase, chromagranin (CGR), and synaptophysin. Specimens were also stained for protein expression of p53, erbB2, proliferating cell nuclear antigen, and c- myc. The relationship between molecular markers and clinical outcome was determined. Results. All 16 cases met the histologic criteria for SCCC. Fourteen of 16 tumors (88%) stained positive for neuroendocrine differentiation. Eleven of 16 patients (69%) died from disease with a median survival of 19 months; there were 3 long-term survivors (greater than 5 years). CGR was positive in 8 (50%) specimens and was found to be highly predictive of death ( P = 0.001). Complete loss of p53 protein was seen in 8 patients, 7 of whom died with a median survival of 20 months. Conclusion. Immunohistochemistry can be helpful in confirming difficult cases of SCCC. Further studies are necessary to define molecular markers that may be predictive of outcome in patients with SCCC.

A large number of very early spontaneous preterm births are ascribed to bacterial infection of the upper genital tract or chorioamnionitis, without symptoms in either instance. Many believe that ascending infection by bacteria initially present in the cervix and vagina leads to microbial colonization of the chorioamnion and amniotic fluid. This study was an attempt to determine whether antibiotic treatment during the interpregnancy interval in women having a previous preterm birth before 34 weeks gestational age might lower the risk of spontaneous preterm birth in a subsequent pregnancy. A total of 241 women with a history of spontaneous birth before 34 weeks gestational age were randomized, in a double-masked trial, to receive either 2 1-g doses of azithromycin orally 4 days apart plus 750 mg daily of sustained-release metronidazole for 1 week or identical-appearing placebos. The regimen was repeated at 4-month intervals until a subsequent pregnancy began, as was the case for 124 women, 59 of whom received antibiotics. The antibiotic-treated and control women were similar in most respects, but the actively treated women were significantly more compliant in keeping study appointments and taking their assigned medications. Approximately 80% of women in both groups received a course of treatment within 6 months before the subsequent conception. Positive endometrial cultures at the time of randomization were comparably frequent in the antibiotic and placebo groups: 86% and 91%, respectively. Median numbers of individual microbial species isolated from the endometrium also did not differ significantly. Plasma cell endometritis was found in 31% of the antibiotic group and 47% of placebo recipients. Repeat endometrial cultures taken 2 weeks later showed a lower number of individual bacterial species in 49% of women given antibiotics and 31% of the control group. There was no apparent difference in the resolution of endometritis. The risk of a subsequent preterm birth did not differ significantly between the 2 groups, and the same was the case for miscarriage before 15 weeks gestation. Although not statistically significant, average gestational age at delivery was 2.4 weeks shorter in the antibiotic group, and average birth weight was 418 g lower than in the placebo group.

Objectives The objectives of this study are to determine the utility of re-excision after a primary diagnosis of vulvar carcinoma by assessing the frequency of residual carcinoma found upon re-excision and to quantitate the wound breakdown and carcinoma recurrence rates. Methods We reviewed 1122 cases of VIN or vulvar carcinoma. Women who underwent re-excisional procedures, as part of their initial surgical treatment were identified. Associations between the margin status of the original excisional sample and histology of re-excision, as well as association between the depth of invasion upon initial excision and histology of re-excision were analyzed with Chi-square tests. Results We identified 84 evaluable patients, 72 with stage I disease, 4 with stage II, and 7 with stage III disease. Upon the initial excisional procedure, 33 patients (39%) had carcinoma-positive margins, 27 patients had VIN-positive margins (32%) and 24 patients (28%) had negative margins (>1mm). Upon re-excision, 1/24 (4%) patients with negative margins, 2/27 (7%) patients with VIN-positive margins, and 11/33 (33%) patients with carcinoma-positive margins were found to have carcinoma in the re-excision specimens ( p χ 2 =31). Deeper tumor invasion of the initial excisional specimen (1–12mm) was associated with a higher chance of finding carcinoma upon re-excision (range 18–42%, depending on depth of invasion) ( p =0.015, χ 2 =19). Nineteen patients (23%) had vulvar wound breakdown post re-excision. Twelve patients (15%) experienced recurrences. Conclusions The yield of micro- or invasive carcinoma at re-excision is low, with a high wound breakdown rate. Re-excision should be considered for patients with margins positive for carcinoma, especially for women with deep invasion, while women with VIN or close but clear margins may be followed.