Christina E. Dancz

Inducible Control of Virulence Gene Expression in Listeria monocytogenes: Temporal Requirement of Listeriolysin O during Intracellular Infection

We have constructed a lac repressor/operator-based system to tightly regulate expression of bacterial genes during intracellular infection by Listeria monocytogenes. An L. monocytogenes strain was constructed in which expression of listeriolysin O was placed under the inducible control of an isopropyl-beta-D-thiogalactopyranoside (IPTG)-dependent promoter. Listeriolysin O (LLO) is a pore-forming cytolysin that mediates lysis of L. monocytogenes-containing phagosomes. Using hemolytic-activity assays and Western blot analysis, we demonstrated dose-dependent IPTG induction of LLO during growth in broth culture. Moreover, intracellular growth of the inducible-LLO (iLLO) strain in the macrophage-like cell line J774 was strictly dependent upon IPTG. We have further shown that iLLO bacteria trapped within primary phagocytic vacuoles can be induced to escape into the cytosol following addition of IPTG to the cell culture medium, thus yielding the ability to control bacterial escape from the phagosome and the initiation of intracellular growth. Using the iLLO strain in plaque-forming assays, we demonstrated an additional requirement for LLO in facilitating cell-to-cell spread in L2 fibroblasts, a nonprofessional phagocytic cell line. Furthermore, the efficiency of cell-to-cell spread of iLLO bacteria in L2 cells was IPTG dose dependent. The potential use of this system for determining the temporal requirements of additional virulence determinants of intracellular pathogenesis is discussed.

Assessment of intraoperative judgment during gynecologic surgery using the Script Concordance Test

OBJECTIVE We sought to develop a valid, reliable assessment of intraoperative judgment by residents during gynecologic surgery based on Script Concordance Theory. STUDY DESIGN This was a multicenter prospective study involving 5 obstetrics and gynecology residency programs. Surgeons from each site generated case scenarios based on common gynecologic procedures. Construct validity was evaluated by correlating scores to training level, in-service examinations, and surgical skill and experience using a Global Rating Scale of Operative Performance and case volumes. RESULTS A final test that included 42 case scenarios was administered to 75 residents. Internal consistency (Cronbach alpha = 0.73) and test-retest reliability (Lin correlation coefficient = 0.76) were good. There were significant differences between test scores and training levels (P = .002) and test scores correlated with in-service examination scores (r = 0.38; P = .001). There was no association between test scores and total number of cases or technical skills. CONCLUSION The Script Concordance Test appears to be a reliable, valid assessment tool for intraoperative decision-making during gynecologic surgery.

Colorectal and anal symptoms in women with urinary incontinence and pelvic organ prolapse

Introduction and hypothesisOur aim was to determine the prevalence of colorectal and anal (CRA) symptoms in women with urinary incontinence and pelvic organ prolapse (UI/POP) in a predominantly Latina population.MethodsWe reviewed charts of women seen in the urogynecology clinic for UI/POP for those who completed the colorectal anal distress inventory-8 (CRADI-8) on their first visit. A detailed history was taken independent of the questionnaire.ResultsTwo hundred sixty-five women completed the questionnaire; 94% were Latina; 89% completed the questionnaire in Spanish. Of the women, 88% indicated at least one CRA symptom: 60% reported needing to strain hard to have a bowel movement; 59% reported sensation of incomplete bowel emptying; 21% indicated incontinence of solid or liquid stool, and an additional 30% of women reported flatal incontinence only, for a total anal incontinence rate of 58%.ConclusionCRA symptoms are highly prevalent among women with UI/POP who completed the CRADI-8 in a predominantly Latina patient population.

Massive cystic degeneration of a pedunculated leiomyoma

A 51-year-old woman presented with a large abdominopelvic mass suspicious on preoperative imaging for ovarian malignancy. At laparotomy, a large cystic mass was found originating from the uterus and adherent to the proximal ileum. Pathologic evaluation confirmed the diagnosis of cystic leiomyoma.

Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia

OBJECTIVE Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. METHODS A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. RESULTS The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. CONCLUSIONS Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients.

Comparison of 2 simulation models for teaching obstetric anal sphincter repair.

Objective The purpose of this study was to compare the utility of 2 surgical models for obstetric anal sphincter repair for improving resident knowledge, confidence level, and repair technique. Study Design Third- and fourth-year obstetrics and gynecology residents at LAC + USC Medical Center performed simulated anal sphincter repair on both sponge and beef tongue surgical models. Resident knowledge, confidence, technical skill, and preference were assessed after each model was performed. Results Both models significantly improved resident confidence (sponge, P = 0.017; tongue, P = 0.016) and knowledge (60% correct before intervention vs. 92% correct after intervention, P < 0.001). There was no difference detected between the 2 models. All participants preferred the tongue model to the sponge model. When performing both models, performing the tongue model after the sponge model resulted in a further increase in confidence (P = 0.008) Conclusions Both models are excellent tools to aid in resident teaching of obstetric anal sphincter repair and significantly increase residents’ knowledge and confidence.

Outcomes of Treatment for Endometrial Hyperplasia in Women Younger Than Age 35 Years

INTRODUCTION: The objective of this study was to describe treatment outcomes in young women with endometrial hyperplasia. METHODS: A retrospective cohort study of women younger than 35 years with a biopsy diagnosis of endometrial hyperplasia was performed. Demographics, treatment, and histopathology were compared. The institutional review board at the University of Southern California approved this protocol. RESULTS: Two hundred twenty-three patients were identified: 70 atypical and 153 nonatypical endometrial hyperplasia. Mean age was 29.9±4.1 years, and mean body mass index was 40.1±10.5 kg/m2. There was no difference between groups in age, body mass index, gravidity, or parity. Women with atypical endometrial hyperplasia were more likely to have diabetes (25.7% compared with 13.7%, P=.037) and to have a thicker endometrium on ultrasound examination (15.2 mm compared with 12.1 mm, P=.03). Forty-six (20.6%) women had one biopsy and were lost to follow-up. For women managed nonsurgically, the median number of biopsies was four (range one to 22) and the mean follow-up was 24.1±23.3 months. The most common treatment was systemic progestin therapy (75.6%). Among women treated for nonatypical endometrial hyperplasia, the most recent biopsy was benign in 64 of 102 (62.7%), nonatypical in 24.5%, atypical in 11.8%, and cancer in 1.0%. Among women treated for atypical endometrial hyperplasia, the most recent biopsy was benign in 30 of 56 (53.6%), nonatypical in 19.6%, atypical in 17.9%, and cancer in 8.9%. CONCLUSIONS: After 2 years of treatment, nonatypical endometrial hyperplasia rarely progresses to cancer, but 11.8% progress to atypical endometrial hyperplasia. Atypical endometrial hyperplasia progresses to cancer in 8.9% of patients despite treatment. A high lost-to-follow-up rate highlights the need for aggressive counseling and outreach in this high-risk population.