Katarzyna Bochenska

A chemical compound that stimulates the human homologous recombination protein RAD51

RAD51 and other members of the RecA family of strand exchange proteins assemble on ssDNA to form presynaptic filaments, which carry out the central steps of homologous recombination. A microplate-based assay was developed for high-throughput measurement of hRAD51 filament formation on ssDNA. With this method, a 10,000 compound library was screened, leading to the identification of a small molecule (RS-1) that enhances hRAD51 binding in a wide range of biochemical conditions. Salt titration experiments showed that RS-1 can enhance filament stability. Ultrastructural analysis of filaments formed on ssDNA showed that RS-1 can increase both protein–DNA complex lengths and the pitch of helical filament turns. RS-1 stimulated hRAD51-mediated homologous strand assimilation (D-loop) activity by at least 5- to 11-fold, depending on the condition. This D-loop stimulation occurred even in the presence of Ca2+ or adenylyl-imidodiphosphate, indicating that the mechanism of stimulation was distinct from that conferred by Ca2+ and/or inhibition of ATPase. No D-loop activity was observed in the absence of a nucleotide triphosphate cofactor, indicating that the compound does not substitute for this requirement. These results indicate that RS-1 enhances the homologous recombination activity of hRAD51 by promoting the formation of active presynaptic filaments. Cell survival assays in normal neonatal human dermal fibroblasts demonstrated that RS-1 promotes a dose-dependent resistance to the cross-linking chemotherapeutic drug cisplatin. Given that RAD51-dependent recombination is a major determinant of cisplatin resistance, RS-1 seems to function in vivo to stimulate homologous recombination repair proficiency. RS-1 has many potential applications in both research and medical settings.

Fecal Incontinence: Epidemiology, Impact, and Treatment.

Fecal incontinence (FI) is a chronic and debilitating condition that carries a significant health, economic, and social burden. FI has a considerable psychosocial and financial impact on patients and their families. A variety of treatment modalities are available for FI including behavioral and dietary modifications, pharmacotherapy, pelvic floor physical therapy, bulking agents, anal sphincteroplasty, sacral nerve stimulation, artificial sphincters, magnetic sphincters, posterior anal sling, and colostomy.

Changing Referral Patterns to Urogynecology

Objective The study aims to identify sources of and changes in referral patterns for pelvic floor disorders. Methods All new patient visits to urogynecology at our institution between January 2010 and December 2015 were identified. Patient demographics, referral source, insurance type, and visit diagnoses using ICD-9 codes were abstracted. ICD-9 codes were grouped into 18 urogynecologic diagnoses. Data were analyzed using SPSS (Version 20; Chicago, IL). Results Five thousand seven hundred ninety-nine new patient visits were included in the analysis. The mean age was 54 ± 17 years and 59% were Caucasian. Forty-four percent were referred by obstetrician/gynecologists (OB/GYNs), 32% by primary care providers (PCPs), 14% by self-referral, and 9% by other specialties. New patient visits increased overall by 280% over 6 years; self- and PCP referrals increased by 480% and 320%, respectively. In comparison, OB/GYN referrals increased by only 229%. Patients diagnosed with prolapse and stress incontinence were more likely to be referred by an OB/GYN (P < 0.001), whereas PCPs were more likely to refer for urinary tract infections (P < 0.005) and urgency urinary incontinence (P < 0.001) than OB/GYNs. Conclusions Demand for pelvic floor specialists is growing quickly, with PCP and self-referrals outpacing referrals from obstetrician-gynecologists to tertiary care urogynecology practices.

Set-Up for Robotic Sacrocolpopexy

Patient selection and positioning, precise operative entry, operating room and equipment considerations, and a cohesive surgical team are pivotal to successful robotic sacrocolpopexy. Patients must provide informed consent and be medically able to tolerate pneumoperitoneum and steep Trendelenburg. Because steep Trendelenburg is critical to procedure completion, a variety of positioning mechanisms exist to secure the patient appropriately on the operating table. Abdominal port placement and docking is an essential component of performing a robotic sacrocolpopexy and varies depending on which robotic platform is used. Additionally, prior to commencing the surgical procedure, a survey should be performed to ensure that all necessary equipment and operating room staff are present and available.

Instructional Video and Medical Student Surgical Knot-Tying Proficiency: Randomized Controlled Trial

Background Many senior medical students lack simple surgical and procedural skills such as knot tying. Objective The aim of this study was to determine whether viewing a Web-based expert knot-tying training video, in addition to the standard third-year medical student curriculum, will result in more proficient surgical knot tying. Methods At the start of their obstetrics and gynecology clerkship, 45 students were videotaped tying surgical knots for 2 minutes using a board model. Two blinded female pelvic medicine and reconstructive surgery physicians evaluated proficiency with a standard checklist (score range 0-16) and anchored scoring scale (range 0-20); higher numbers represent better skill. Students were then randomized to either (1) expert video (n=26) or (2) nonvideo (n=24) groups. The video group was provided unlimited access to an expert knot-tying instructional video. At the completion of the clerkship, students were again videotaped and evaluated. Results At initial evaluation, preclerkship cumulative scores (range 0-36) on the standard checklist and anchored scale were not significantly different between the nonvideo and video groups (mean 20.3, SD 7.1 vs mean 20.2, SD 9.2, P=.90, respectively). Postclerkship scores improved in both the nonvideo and video groups (mean 28.4, SD 5.4, P<.001 and mean 28.7, SD 6.5, P=.004, respectively). Increased knot board practice was significantly correlated with higher postclerkship scores on the knot-tying task, but only in the video group (r=.47, P<.05). Conclusions The addition of a Web-based expert instructional video to a standard curriculum, coupled with knot board practice, appears to have a positive impact on medical student knot-tying proficiency.

Anal penetrative intercourse as a risk factor for fecal incontinence

Objective The aim of the study is to investigate the relationship between anal penetrative intercourse (API) and pelvic floor symptoms, specifically, anal incontinence (AI). Methods This was an institutional review board–approved, cross-sectional, e-mail survey of women enrolled in the Illinois Womens Health Registry. Participants were anonymously queried about their sexual practices and the effects of these on bowel and bladder symptoms. Urinary symptoms were assessed using the urogenital distress inventory-6 and bowel symptoms with the fecal incontinence severity index (FISI). Results One thousand three women (mean age of 46 ± 15 years) completed the survey. Eighty percent were white, 56% were married, and 99% reported ever being sexually active. Thirty-two percent had API at least once, and 12% considered it “part of their sexual practice.” Sixty percent of the cohort reported a bothersome urinary symptom on the urogenital distress inventory-6, 70% reported AI on the FISI, and 15% reported fecal incontinence. Of women who engaged in API, 18% reported it changed their stool consistency, and 10% reported it caused AI. Having engaged in API within the last month was correlated with higher FISI scores (P = 0.05) and with fecal incontinence on the FISI (28.3% vs 14.4%; P = 0.01; odds ratio, 2.48). In addition, API was more commonly practiced among women who reported that vaginal intercourse caused dyspareunia (17% vs 12%, P = 0.05) or changes in bladder symptoms such as urgency or dysuria (44% vs 30%, P < 0.001). Conclusions Self-reported AI and FI (as measured by the FISI scores) are higher in women who have had API, and frequency of API may be important in determining the risk of bowel symptoms.

74: Fibroids and urinary symptoms study (FUSS)

(+/346.8). One hundred sixty-two patients (95.8%) were discharged to home within one day or less. Final pathological diagnosis was benign in 99.4% of the cases. Uterine leiomyoma was the most common final pathology diagnosis. Occult malignancy was identified in one patient. There were no conversions to an open approach, no instances of containment bag tear or gross spillage during the manual tissue extraction process, and no complications related to the tissue extraction technique. CONCLUSION: Contained extracorporeal manual tissue extraction through an extended umbilical incision is a safe and feasible technique in women undergoing laparoscopic hysterectomy and laparoscopic myomectomy.

Estrogen and Pelvic Organ Prolapse

Pelvic organ prolapse (POP) is a multifactorial disease with a complex and largely unknown etiology and pathophysiology. Hypoestrogenemia may be one of the risk factors associated with POP. Recent studies suggest a potential role of estrogen and its receptors in the pathogenesis of POP. Here, we summarize current research regarding the relationship between estrogen and POP to establish a theoretical foundation for using estrogen in POP treatment. Estrogen plays an important role in collagen and elastin metabolism of connective tissues through down-regulating matrix metalloproteinases and increasing cystatin C expression. However, previous studies have shown contradictory data regarding estrogen receptor expression in patients with POP compared to non-POP controls. At this time, there is no conclusive evidence suggesting a causal role of estrogen in POP. Further welldesigned studies are necessary to illuminate both the molecular mechanisms of estrogen function and the role of estrogen in POP.

Utility of Postoperative Voiding Cystourethrogram After Lower Urinary Tract Repair.

Objective To characterize indications, timing, and results of voiding cystourethrogram (VCUG) studies after repair of the lower urinary tract and to determine how these results impact clinical management. Methods Women who underwent a VCUG between January 2006 and December 2012 were identified from a radiology billing database. After excluding women with abdominopelvic malignancies, demographic, clinical, index procedure and lower urinary tract repair characteristics, and VCUG results were analyzed. The impact of abnormal VCUG results on clinical management was assessed. Results Data were analyzed from 245 VCUG studies performed a median of 10 days (interquartile range, 8–12 days) after lower urinary tract repair. When classified by procedure type, VCUGs were performed a median of 9 days (7–13 days) after cystotomy repair, 11 days (10–12 days) after vesicovaginal fistula closure and 10 days (7–11 days) after diverticulectomy. Abnormal findings were noted in 7 of 245 (2.9%) VCUGs and included contrast extravasation (5/7) and urinary retention (2/7). In all cases, the abnormal VCUG prompted a change in clinical management with extended use of an indwelling catheter or intermittent self-catheterization in 1 case of urinary retention. Conclusions Voiding cystourethrograms are a useful clinical tool in guiding the duration of Foley catheter use after lower urinary tract repair. Depending on clinical practice, VCUGs may reduce catheter-associated morbidity by facilitating earlier catheter removal and, in the minority of cases, may identify patients with incomplete postoperative healing.