Pregnancy-associated Breast Cancer.

Breast cancer is one of the most common malignancies affecting pregnancy. Pregnancy-associated breast cancer refers to breast cancer that is diagnosed during pregnancy or within the first postpartum year. The incidence is increasing as more women delay childbearing. Breast cancer can be safely diagnosed, staged, and treated during pregnancy while protecting the fetus and mother with excellent outcomes for both. Avoiding diagnostic delays is vital to prognosis. This article provides an overview of the diagnosis, staging, management, and prognosis of pregnancy-associated breast cancer. Relevant current literature is reviewed.

Abundance and Frequency of the Asiatic Oak Weevil (Coleoptera: Curculionidae) and Defoliation on American, Chinese, and Hybrid Chestnut (Castanea).

The Asiatic oak weevil, Cyrtepistomus castaneus Roelofs (Coleoptera: Curculionidae), is a nonnative defoliator of trees in the Fagaceae family in the United States but has not been studied on Castanea species in the southern Appalachian Mountains. Planted trees of Castanea dentata (Marsh.) Borkh. (Fagales: Fagaceae), Castanea mollissima Blume (Fagales: Fagaceae), and four hybrid breeding generations were evaluated in 2012 for insect defoliation and C. castaneus abundance and frequency. Defoliation was visually assessed throughout the growing season at two sites in the southern Appalachian Mountains (western North Carolina and eastern Tennessee). C. castaneus abundance and frequency were monitored on trees using beat sheets and emergence was recorded from ground traps. Asiatic oak weevils were more abundant and more frequently collected on American chestnut (Ca. dentata) and its most closely related BC3F3 hybrid generation than on the Asian species Ca. mollissima. In most months, C. castaneus colonization of hybrid generations was not significantly different than colonization of parental species. Frequency data for C. castaneus suggested that adults were distributed relatively evenly throughout the study sites rather than in dense clusters. Emergence of C. castaneus was significantly higher under a canopy dominated by Quercus species than under non-Quercus species or open sky. C. castaneus emergence began in May and peaked in late June and early July. These results may be useful for resource managers trying to restore blight-resistant chestnut to the Southern Appalachians while minimizing herbivory by insect pests.

Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer.

OBJECTIVE: We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix. METHODS: Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m(2) day 1, topotecan 0.75 mg/m(2) days 1, 2 and 3 and bevacizumab 15 mg/kgday 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy. RESULTS: Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities. CONCLUSION: The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity.

Subthreshold opioid use disorder prevention (STOP) trial: a cluster randomized clinical trial: study design and methods.

BACKGROUND: Preventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD. METHODS: The STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180 days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups using an intent-to-treat population. DISCUSSION: Given a growing interest in interventions for the management of patients with risky opioid use, and the need for primary care-based interventions, this study potentially offers a blueprint for a feasible and effective approach to improving outcomes in this population. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT04218201, January 6, 2020.

Wound complications after gynecologic cancer surgery.

OBJECTIVE: To explore clinical correlates of wound complications in high-risk women undergoing abdominal gynecologic surgery in a tertiary referral center. METHODS: Retrospective analysis of patient demographics, pre-operative and intra-operative information, and outcomes was performed in a cohort of patients who underwent abdominal surgery for suspected gynecologic malignancy between 1/2005 and 6/2008. The primary outcome was wound complication within 6 weeks of surgery. Univariate and multivariate logistic regression analyses were employed. A nomogram predicting post-operative wound complications was created and validated by receiver operating characteristic (ROC) curve analysis and 10-fold cross-validation. RESULTS: Median age of 373 women analyzed was 57years (range 25-88), median body mass index (BMI) 32.3kg/m(2) (range 14.0-70.7). A total of 150 patients (40%) had prior abdominal surgery; 40 (11%) had a pre-operative serum albumin <3.5g/dl; and 78 (21%) had pulmonary disease. Wound complications occurred in 125 patients (34%). In multivariate analysis wound complications were correlated with BMI of 30-39.9kg/m(2) (OR=5.62, 95% CI 2.08-15.19, p<0.0001) and BMI≥40kg/m(2) (OR=10.27, 95% CI 3.66-28.88, p<0.0001), prior abdominal surgery (OR 3.28, 95%CI1.89-5.70, p<0.0001), serum albumin≤3.5g/dl (OR 4.24, 95%CI 1.87-9.61, p=0.0005), pulmonary disease (OR 2.22, 95%CI 1.09-4.51, p=0.03), lysis of adhesions (OR 3.57, 95%CI 1.04-12.26, p=0.04), and length of surgery (OR 2.42, 95%CI 1.35-4.35, p=0.003). Risk for wound complication was lower with pelvic drain placement (OR 0.26, 95%CI 0.11-0.64, p=0.003). CONCLUSIONS: Wound complications are common in gynecologic oncology. Further studies should explore whether risk factor modification decreases complications.

Clinical and pathologic features of vulvar intraepithelial neoplasia in premenopausal and postmenopausal women.

OBJECTIVE: To explore the clinical and pathologic differences between vulvar intraepithelial neoplasia (VIN) in premenopausal and postmenopausal women cared for in a tertiary referral center. METHODS: Between January 1997 and June 2008, 145 women received care at our institution for VIN and VIN-associated squamous cell carcinoma (SCC). All patients' demographic characteristics and recurrence histories were recorded throughout the study period and were retrieved retrospectively. Menopausal status was self-reported at the time of initial diagnosis. χ, odds ratio, and logistic regression analyses were used. RESULTS: The median age was 50 years (range = 19-91 y) with 77% (111/145) of patients white, 20% (29/145) African American, and 3% (5/145) other ethnicity. Sixty percent of patients diagnosed with VIN were current smokers, 18% (26/145) were immunocompromised (positive for human immunodeficiency virus/transplant/steroids), and 30% (44/145) had concomitant or previous lower genital tract dysplasia. Vulvar intraepithelial neoplasia or VIN-related cancer recurred in 57 (39%) of 145 patients; of these, 40 (71%) had recurrence of VIN and 18 (29%) had recurrence of cancer. Fifty-one percent (74/145) of patients were menopausal at initial VIN diagnosis. Among women with VIN, the odds of initially presenting with a VIN-related SCC was 3.2 times greater in postmenopausal than in premenopausal women (confidence interval = 1.5-7.1, p < .01), and postmenopausal women were more likely to present with stage II to IV SCC (p = .021). Recurrence risk of SCC, but not VIN, was associated with menopause status (p < .05). CONCLUSIONS: Among women with VIN, the risk of SCC is higher in postmenopausal than in premenopausal women both initially and at recurrence. Excisional therapies to identify occult invasion are especially important for postmenopausal women with VIN.

Chemoradiation in locally advanced cervical carcinoma: an analysis of cisplatin dosing and other clinical prognostic factors.

OBJECTIVES: The aim of this study was to evaluate the effect of number of chemotherapy cycles and other clinical and pathologic factors on progression-free (PFS) and overall survival (OS) in patients with newly diagnosed cervical cancer. METHODS: We identified 118 patients with locally advanced cervical cancer (stages IB2-IVA) treated with combination weekly cisplatin (40 mg/m(2)) and radiation therapy (RT) between 2003 and 2007. Kaplan-Meier and Cox proportional hazard models were utilized to evaluate PFS and OS for associations with number of chemotherapy cycles and other factors. RESULTS: The majority of patients had stage IB2 or II disease (70%), squamous histology (91%), and size <6 cm (65%). Median RT duration was 50 days and 95% received brachytherapy. Thirty percent of patients completed <6 cycles of chemotherapy, and estimated PFS and OS were 63% and 75%, respectively. In multivariate analyses, the number of chemotherapy cycles was independently predictive of PFS and OS. Patients who received <6 cycles of cisplatin had a worse PFS (HR 2.65; 95% CI 1.35-5.17; p=0.0045) and OS (HR 4.47; 95% CI 1.83-10.9; p=0.001). Advanced stage, longer time to RT completion, and absence of brachytherapy were also associated with decreased OS and PFS (p<0.05). Similar results were found when analysis was conducted using a breakpoint of at least five but not less than five chemotherapy cycles. Higher grade was associated with decreased PFS (p=0.03) but not OS. Age, race, BMI, tumor size, smoking, histology, and IMRT were not statistically significant for OS or PFS. CONCLUSIONS: Aggressive supportive care to minimize missed chemotherapy treatments may improve survival after chemoradiation.

"Surgical Apgar Score" predicts postoperative complications after cytoreduction for advanced ovarian cancer.

OBJECTIVE: A 10-point "Surgical Apgar Score" (SAS) for predicting postoperative complications after general and vascular operations has recently been developed and validated. We sought to estimate the ability of this metric to predict major postoperative complications in women undergoing ovarian cancer cytoreductive procedures. METHODS: All eligible patients with stage III and IV epithelial ovarian, fallopian tube and primary peritoneal cancer undergoing surgical cytoreduction at our institution between 1999 and 2005 were included. Medical records were reviewed and demographic data, clinicopathologic characteristics, comorbidities and intra and postoperative complications were analyzed. The surgical score was calculated from intraoperative blood loss, lowest mean arterial pressure and lowest heart rate as previously described. Descriptive statistics, univariable and multivariable analyses were used as appropriate. Occurrence of major postoperative complications represented the primary outcome. RESULTS: A total of 232 cases were analyzed. Mean age was 62 years. Most patients were Caucasian (92%) and diagnosed with stage III disease (83%). Mean duration of surgical procedure was 171 (70-350) minutes. Median SAS was 6 points (range 1-9). On multivariable analyses, occurrence of major postoperative complications was associated with multiple comorbidities (OR 2.2; 95% CI:1.5-3.1; p<0.0001), stage IV disease (OR 2.5; 95% CI:1.1-5.7; p=0.03), ASA class (OR 2.4; 95% CI:1.2-4.7; p=0.01) and SAS

Using a health information technology survey to explore the availability of addiction treatment data in the electronic health records: A National Drug Abuse Treatment Clinical Trials Network study.

BACKGROUND: Healthcare data from electronic health records (EHRs) and related health information technology (IT) tools are critical data sources for pragmatic clinical trials and observational studies aimed at producing real-world evidence. To unlock the full potential of such data to advance science, the data must be complete and in structured formats to facilitate research use. METHODS: A Health IT survey was conducted within the National Drug Abuse Treatment Clinical Trials Network (CTN) to explore information related to data completeness and presence of unstructured data (e.g., clinical notes, free text) for conducting the EHR-based research for substance use disorders (SUDs). The analysis was based on 36 participants from 36 facilities located in 14 states and affiliated with the CTN. RESULTS: The mean age of the participants (n = 34) was 48.0 years (SD = 9.8). Of the participants enrolled, 50.0% were female and 82.4% were white. Participants' facilities were from four census-defined regions (South 35.3%, Northeast 29.4%, West 20.6%, Midwest 11.8%, Missing 2.9%) and represented diverse settings. The EHR was used by all surveyed facilities including 17 different kinds of EHR platforms or vendors, and 17.6% (n = 6) of surveyed facilities also used a separate EHR for behavioral health care (e.g., SUD care). Paper records were also used by 76.5% of surveyed facilities for clinical care (e.g., for health risk appraisal questionnaires, substance use screening or assessment, check-in screening, substance use specific intervention/treatment or referral, or labs/testing). The prevalence of using a patient portal, practice management system, and mHealth for patient care was 76.5%, 50.0%, and 29.4%, respectively. CONCLUSION: While results are descriptive in nature, they reveal the heterogeneity in the existing EHRs and frequent use of paper records to document patient care tasks, especially for SUD care. The use of a separate EHR for behavioral healthcare also suggests the challenge of obtaining complete EHR data to support research for SUDs. Much EHR development, integration, and standardization needs to be done especially in regard to SUD treatment to facilitate research across disparate healthcare systems.

The role of PET/CT in the management of patients with cervical cancer: practice patterns of the members of the Society of Gynecologic Oncologists.

OBJECTIVES: Recent data has highlighted the role of PET/CT in the pretreatment evaluation and follow-up of patients with cervical cancer. The objective of our study was to assess the acceptance of PET/CT into the management of patients with cervical cancer. We also explored potential barriers to the use of these imaging modalities in patients with cervical cancer. METHODS: A 14-item electronic questionnaire was initially sent to all working addresses of members of the SGO (n=1048). An opt-out option was offered. For members who did not respond within 3 weeks, a second electronic invitation was sent. A third request was finally sent to further improve response rates. Data were collected and analyzed using a commercially available on-line survey database. RESULTS: A total of 305 responses were collected for an overall 30% response rate. PET/CT appears to be widely available (99%) and accessible (75%) in most practices. Although 83% of members order routine CT imaging for all newly diagnosed cervical cancer cases, only 28% routinely order a PET/CT. Conversely, 64% would order a PET/CT for newly diagnosed patients with advanced disease or those at high risk for distant metastatic disease. Most members (82%) do not routinely use PET/CT to assess response to treatment. Twenty percent of members believe that no useful prognostic information can be obtained from routine use of molecular imaging in patients with cervical cancer. The most common barriers for use of PET/CT cited by members were perceived lack of third-party payer coverage and lack of scientific evidence. CONCLUSIONS: Despite clear scientific data supporting the use of PET/CT in patients with cervical cancer and apparent widespread availability, this imaging modality remains highly underutilized in clinical practice. Clarifying insurance coverage early in the evaluation process and replicating studies that have shown effectiveness of PET/CT in multiple roles may improve adoption of this potentially useful imaging modality.

The value of perioperative imaging in patients with uterine sarcomas.

OBJECTIVE: To explore the yield and impact of perioperative imaging on management among patients undergoing surgical resection and treatment of uterine sarcomas. METHODS: A retrospective chart review was done for women with histologically confirmed uterine sarcomas treated at Barnes Jewish Hospital/Washington University from 2001 to 2007. Descriptive statistics, Cox multivariate models, and Kaplan-Meier plots were used to evaluate associations and survival. RESULTS: A total of 92 patients were identified and 55 (60%) were diagnosed with stage III-IV disease. Perioperative imaging was obtained in 84 (91%) cases, including chest X-ray in 66 (72%), computerized tomography (CT) of the abdomen and pelvis in 59 (64%), chest CT in 33 (36%), positron emission tomography (PET) in 8 (9%), and CT of the head, pelvic magnetic resonance imaging (MRI), or bone scan in a total of 2 (2.2%). Imaging identified abnormalities concerning for metastases in 30 (32%) studies. Thirty-four recurrences have been documented, and 21 (62%) of these treatment failures were extrapelvic. Multivariate analysis of this series noted that tomographic evidence of extrauterine disease predicted recurrence (p=0.028) and incomplete surgical resection (p=0.003, HR 6.0 95% CI 1.9-19.9) predicted disease-free survival. Imaging contributed to change in surgical and post-surgical treatment decisions in 8 (9%) patients. CONCLUSION: Pretreatment imaging studies change management in a minority of patients with newly diagnosed uterine sarcomas.

Clinical Workflow and Substance Use Screening, Brief Intervention, and Referral to Treatment Data in the Electronic Health Records: A National Drug Abuse Treatment Clinical Trials Network Study.

INTRODUCTION: The use of electronic health records (EHR) data in research to inform recruitment and outcomes is considered a critical element for pragmatic studies. However, there is a lack of research on the availability of substance use disorder (SUD) treatment data in the EHR to inform research. METHODS: This study recruited providers who used an EHR for patient care and whose facilities were affiliated with the National Institute on Drug Abuse's National Drug Abuse Treatment Clinical Trials Network (NIDA CTN). Data about providers' use of an EHR and other methods to support and document clinical tasks for Substance use screening, Brief Intervention, and Referral to Treatment (SBIRT) were collected. RESULTS: Participants (n = 26) were from facilities across the country (South 46.2%, West 23.1%, Midwest 19.2 percent, Northeast 11.5 percent), representing 26 different health systems/facilities at various settings: primary care (30.8 percent), ambulatory other/specialty (26.9 percent), mixed setting (11.5 percent), hospital outpatient (11.5 percent), emergency department (7.7 percent), inpatient (3.8 percent), and other (7.7 percent). Validated tools were rarely used for substance use screen and SUD assessment. Structured and unstructured EHR fields were commonly used to document SBIRT. The following tasks had high proportions of using unstructured EHR fields: substance use screen, treatment exploration, brief intervention, referral, and follow-up. CONCLUSION: This study is the first of its kind to investigate the documentation of SBIRT in the EHR outside of unique settings (e.g., Veterans Health Administration). While results are descriptive, they emphasize the importance of developing EHR features to collect structured data for SBIRT to improve health care quality evaluation and SUD research.

Clustering of Lynch syndrome malignancies with no evidence for a role of DNA mismatch repair.

OBJECTIVES: We ascertained a large kindred with an excess of Lynch syndrome-associated cancers. Our objective was to determine if a defect in one of the DNA mismatch repair (DMMR) genes was the probable cause of cancer susceptibility as microsatellite instability (MSI) and immunohistochemical (IHC) analysis of the probands' tumors did not provide a clear indication. METHODS: A detailed history and review of medical records was undertaken to construct a four-generation pedigree. Blood samples were obtained for analysis of germline DNA. Polymorphic repeats from the MLH1, MSH2, MSH6, and PMS2 loci were genotyped and the co-segregation of markers and disease was assessed. DMMR gene expression for all available tumors was evaluated by IHC. Combined bisulfite restriction analysis (COBRA) of MLH1 was utilized to test for germline epimutation. RESULTS: Four gynecologic carcinomas, 3 colon carcinomas, and 13 cases of adenomatous polyps were identified. The family met Amsterdam II criteria. The mean age of cancer diagnosis in the kindred was 63 years (range 44-82 years). DNA marker analyses excluded linkage to MLH1, MSH2, MSH6, and PMS2. Furthermore, MSI and IHC analysis of tumors did not suggest a role for DMMR. Methylation of the MLH1 promoter was identified in the peripheral blood leukocytes (PBLs) of a family member with an early onset colon cancer. CONCLUSIONS: We identified a large family with multiple Lynch malignancies and no evidence for an inherited defect in DMMR. This family represents an important but poorly understood form of autosomal dominant inherited cancer susceptibility. Aberrant MLH1 promoter methylation in normal tissues may be a marker for cancer susceptibility in families such as this.

Safety and efficacy of intralesional triamcinolone administration for treatment of mast cell tumors in dogs: 23 cases (2005-2011).

OBJECTIVE To evaluate the safety and efficacy of intralesional triamcinolone administration, as a sole or adjuvant treatment, in dogs with mast cell tumors. DESIGN Retrospective case series ANIMALS 23 dogs with mast cell tumors. PROCEDURES Medical records of dogs treated for a confirmed diagnosis of a mast cell tumor between 2005 and 2011 were reviewed. Patients with a confirmed diagnosis and measurable disease (tumor longest dimension ≥ 0.5 cm) that had received ≥ 1 intralesional treatment with triamcinolone, regardless of prior, concurrent, or adjuvant treatments, were eligible for inclusion. Data collected included patient characteristics, results of cytologic and histologic testing and tumor staging, triamcinolone dosage, treatment response, and adverse events. RESULTS 23 dogs with 24 tumors were included. Tumors were treated by means of intralesional triamcinolone administration alone (n = 5), intralesional triamcinolone administration with concurrent oral administration of glucocorticoids (6), and intralesional triamcinolone administration with concurrent cytotoxic chemotherapy, with or without oral administration of corticosteroids and radiation therapy (13). Of 5 dogs treated with intralesional triamcinolone administration alone, 1 achieved a complete response, 3 achieved a partial response, and 1 maintained stable disease. The response rate for all 24 tumors (23 dogs) was 67% (16/24), including 4 with a complete response and 12 with a partial response. The median time to progression was 63 days (range, 6 to 447 days). Three dogs experienced adverse events (local hemorrhage [n = 1]; suspected gastrointestinal ulceration [2]). CONCLUSIONS AND CLINICAL RELEVANCE Intralesional triamcinolone administration may be well tolerated and effective for treatment of nonresectable mast cell tumors in dogs.

Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma.

Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS) and individual collagen fiber characteristics (width, length and straightness) in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor-stromal interactions in breast cancer.

Cervical intraepithelial neoplasia in adolescent women: incidence and treatment outcomes.

OBJECTIVE: We sought to estimate the incidence of cervical intraepithelial neoplasia (CIN) and treatment outcomes in adolescents with abnormal cytology. METHODS: Adolescent women (ages 14-21 years) referred to colposcopy clinic for abnormal cytology from 1992 to 2004 were identified by computerized database. Only adolescents with biopsy-proven CIN were evaluated. Demographic and risk factor data were obtained from medical records. Referral cytology, histology on biopsy and loop electrosurgical excisional procedure (LEEP), and follow-up cytology were analyzed and compared. Statistical analysis was performed by chi(2) or Fisher exact test, Student t tests, and logistic regression. RESULTS: Of 1,678 adolescents, 517 had biopsy-proven CIN and follow-up. Seventy-seven patients were referred with atypical squamous cells of undetermined significance (ASCUS) cytology; 174 patients were referred with low-grade squamous intraepithelial lesions (LSIL), 258 with high-grade squamous intraepithelial lesions (HSIL) and eight with atypical glandular cells (AGC). The rate of CIN 2/3 in patients with ASCUS, LSIL, and HSIL was 35% (95% confidence interval 24-46%), 36% (29-43%), and 50% (44-56%), respectively. A total of 192 patients with biopsy-proven CIN 2/3 underwent a LEEP. No patients were diagnosed with cervical carcinoma. Fifty-five percent (95% confidence interval 48-62%) of patients had abnormal cytology on follow-up, suggesting recurrence or reinfection. CONCLUSION: Adolescents with abnormal cytology have a high incidence of CIN2/3 and high rates of abnormal cytology after LEEP. Cervical intraepithelial neoplasia 2/3 is common in adolescents with abnormal cytology, yet no cases of cancer were identified. Importantly, LEEP fails to meet its therapeutic goals given a high incidence of abnormal follow-up cytology and may represent overly aggressive therapy because the majority of human papillomavirus infections are transient with high regression rates. LEVEL OF EVIDENCE: III.

A prospective blinded evaluation of the accuracy of frozen section for the surgical management of endometrial cancer.

OBJECTIVE: To prospectively evaluate in a blinded fashion the accuracy of frozen section in endometrial cancer. METHODS: 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. RESULTS: 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%). CONCLUSION: 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. LEVEL OF EVIDENCE: II-2.

Misoprostol for labor induction in women with term premature rupture of membranes: a meta-analysis.

OBJECTIVE: To systematically review published data evaluating the comparative use of misoprostol with placebo/expectant management or oxytocin for labor induction in women with term (> or = 36 weeks of gestation) premature rupture of membranes. DATA SOURCES: PubMed (1966-2005), Ovid (1966-2005), CINAHL, The Cochrane Library, ACP Journal Club, OCLC, abstracts from scientific forums, and bibliographies of published articles were searched using the following keywords: premature rupture of membranes, misoprostol, labor induction, and cervical ripening. Primary authors were contacted directly if the data sought were unavailable or only published in abstract form. METHODS OF STUDY SELECTION: Only randomized controlled trials evaluating the efficacy and safety of misoprostol in comparison with placebo or expectant management (n = 6) and oxytocin (n = 9) published in either article or abstract form were analyzed and included in the meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Studies were reviewed independently by all authors. Meta-analysis was performed, and the relative risks (RRs) were calculated and pooled for each study outcome. Misoprostol, compared with placebo, significantly increased vaginal delivery less than 12 hours (RR 2.71, 95% confidence interval [CI] 1.87-3.92, P < .001). Misoprostol was similar to oxytocin with respect to vaginal delivery less than 24 hours (RR 1.07, 95% CI 0.88-1.31, P = .50) and less than 12 hours (RR 0.98, 95% CI 0.71-1.35, P = .90). Misoprostol was not associated with an increased risk of tachysystole, hypertonus, or hyperstimulation syndrome when compared with oxytocin and had similar risks for adverse neonatal and maternal outcomes. CONCLUSION: Misoprostol is an effective and safe agent for induction of labor in women with term premature rupture of membranes. When compared with oxytocin, the risk of contraction abnormalities and the rate of maternal and neonatal complications were similar among the 2 groups.

Subcutaneous tissue reapproximation, alone or in combination with drain, in obese women undergoing cesarean delivery.

OBJECTIVE: To compare the efficacy of subcutaneous suture reapproximation alone with suture plus subcutaneous drain for the prevention of wound complications in obese women undergoing cesarean delivery. METHODS: We conducted a multicenter randomized trial of women undergoing cesarean delivery. Consenting women with 4 cm or more of subcutaneous thickness were randomized to either subcutaneous suture closure alone (n = 149) or suture plus drain (n = 131). The drain was attached to bulb suction and removed at 72 hours or earlier if output was less than 30 mL/24 h. The primary study outcome was a composite wound morbidity rate (defined by any of the following: subcutaneous tissue dehiscence, seroma, hematoma, abscess, or fascial dehiscence). RESULTS: From April 2001 to July 2004, a total of 280 women were enrolled. Ninety-five percent of women (268/280) had a follow-up wound assessment. Both groups were similar with respect to age, race, parity, weight, cesarean indication, diabetes, steroid/antibiotic use, chorioamnionitis, and subcutaneous thickness. The composite wound morbidity rate was 17.4% (25/144) in the suture group and 22.7% (28/124) in the suture plus drain group (relative risk 1.3, 95% confidence interval 0.8-2.1). Individual wound complication rates, including subcutaneous dehiscence (15.3% versus 21.8%), seroma (9.0% versus 10.6%), hematoma (2.2% versus 2.4%), abscess (0.7% versus 3.3%), fascial dehiscence (1.4% versus 1.7%), and hospital readmission for wound complications (3.5% versus 6.6%), were similar (P > .05) between women treated with suture alone and those treated with suture plus drain, respectively. CONCLUSION: The additional use of a subcutaneous drain along with a standard subcutaneous suture reapproximation technique is not effective for the prevention of wound complications in obese women undergoing cesarean delivery.

The retinoblastoma tumor suppressor regulates a xenobiotic detoxification pathway.

The retinoblastoma tumor suppressor (pRb) regulates cell cycle entry, progression and exit by controlling the activity of the E2F-family of transcription factors. During cell cycle exit pRb acts as a transcriptional repressor by associating with E2F proteins and thereby inhibiting their ability to stimulate the expression of genes required for S phase. Indeed, many tumors harbor mutations in the RB gene and the pRb-E2F pathway is compromised in nearly all types of cancers. In this report we show that both pRb and its interacting partners, the transcriptional factors E2F1-2-3, act as positive modulators of detoxification pathways important for metabolizing and clearing xenobiotics--such as toxins and drugs--from the body. Using a combination of conventional molecular biology techniques and microarray analysis of specific cell populations, we have analyzed the detoxification pathway in murine samples in the presence or absence of pRb and/or E2F1-2-3. In this report, we show that both pRb and E2F1-2-3 act as positive modulators of detoxification pathways in mice, challenging the conventional view of E2F1-2-3 as transcriptional repressors negatively regulated by pRb. These results suggest that mutations altering the pRb-E2F axis may have consequences beyond loss of cell cycle control by altering the ability of tissues to remove toxins and to properly metabolize anticancer drugs, and might help to understand the formation and progression rates of different types of cancer, as well as to better design appropriate therapies based on the particular genetic composition of the tumors.