Physician attitudes and knowledge on prophylactic salpingectomy in perimenopausal patients.

PURPOSE: Eighty percent of the approximately 500,000 hysterectomies performed annually in the US are for benign indications. There is lack of consensus regarding concurrent removal of fallopian tubes and/or ovaries. Ovarian cancer risk reduction is the principal benefit but the adverse consequences of ovarian removal can include vasomotor disturbance, vaginal dryness, cardiovascular disease, osteoporosis, and cognitive decline. Emerging evidence on the role of fallopian tubes in ovarian carcinogenesis and the consequences of oophorectomy have led the American College of Obstetricians-Gynecologists (ACOG) to recommend bilateral salpingectomy with ovarian conservation during benign hysterectomy for women at population risk for ovarian cancer. METHODS: Five hundred members of the ACOG Collaborative Ambulatory Research Network (CARN) were randomly selected to participate in this survey study. RESULTS: 165 completed the survey (35.3% response rate). Most respondents reported that a family history of breast, ovarian or colon cancer and patient age influence their decision to offer salpingectomy more than 75% of the time. Factors that a majority of respondents reported discussing during counseling included possible ovarian cancer risk reduction, surgical menopause, severity of symptoms, and the effects on bone and cardiovascular health. The respondents mean score for the knowledge-based questions was only 1.7 (±0.92) out of 4 points. CONCLUSION: Several factors may affect decision making for prophylactic salpingectomy at the time of hysterectomy however paramount among these is cancer risk reduction. Most physicians found it difficult to discuss and implement a change in care for patients with preconceived notions of ovarian preservation or removal.

Washington State Surgeon Perspectives on Quality Measures in the Surgical Care of Stress Urinary Incontinence in Women.

INTRODUCTION: No consensus exists on outcomes that define high quality care in female stress urinary incontinence management. A working group of surgeons from diverse health care settings in Washington State who treat stress urinary incontinence was convened through a state level quality collaborative. Preliminary questions were developed and focus groups conducted to obtain surgeon input and perspectives on stress urinary incontinence surgery quality measures to guide future research. METHODS: Washington State surgeons who perform sling surgery were recruited via email. Focus groups were convened via teleconference using preliminary questions as discussion points. Participants were surgeons from a variety of locations and practice types. Focus groups were led by a trained moderator, recorded and transcribed verbatim, and qualitatively analyzed using inductive content analysis. RESULTS: Eight urologists and 6 gynecologists from 5 academic, 4 private practice and 5 hospital based settings participated in 3 focus groups. The 4 emergent concepts derived, were a perceived need to individualize rather than standardize the management approach to recurrent and persistent stress urinary incontinence, a need to establish and validate shared decision making tools for synthetic mesh procedures, a need to define risk factors and treatment strategies for unique populations, including those with mixed urinary incontinence, younger patients and those with concomitant prolapse, and an enthusiasm to identify practical and clinically meaningful quality measures. CONCLUSIONS: Focus groups with clinical experts on quality of stress urinary incontinence care identified several priority topics for future study. Further work is needed to refine research prioritization on this important area of women's health.

Mechanisms of Endogenous HIV-1 Reactivation by Endocervical Epithelial Cells.

Pharmacological HIV-1 reactivation to reverse latent infection has been extensively studied. However, HIV-1 reactivation also occurs naturally, as evidenced by occasional low-level viremia ("viral blips") during antiretroviral treatment (ART). Clarifying where blips originate from and how they happen could provide clues to stimulate latency reversal more effectively and safely or to prevent viral rebound following ART cessation. We studied HIV-1 reactivation in the female genital tract, a dynamic anatomical target for HIV-1 infection throughout all disease stages. We found that primary endocervical epithelial cells from several women reactivated HIV-1 from latently infected T cells. The endocervical cells' HIV-1 reactivation capacity further increased upon Toll-like receptor 3 stimulation with poly(I·C) double-stranded RNA or infection with herpes simplex virus 2 (HSV-2). Notably, acyclovir did not eliminate HSV-2-induced HIV-1 reactivation. While endocervical epithelial cells secreted large amounts of several cytokines and chemokines, especially tumor necrosis factor alpha (TNF-α), CCL3, CCL4, and CCL20, their HIV-1 reactivation capacity was almost completely blocked by TNF-α neutralization alone. Thus, immunosurveillance activities by columnar epithelial cells in the endocervix can cause endogenous HIV-1 reactivation, which may contribute to viral blips during ART or rebound following ART interruption.IMPORTANCE A reason that there is no universal cure for HIV-1 is that the virus can hide in the genome of infected cells in the form of latent proviral DNA. This hidden provirus is protected from antiviral drugs until it eventually reactivates to produce new virions. It is not well understood where in the body or how this reactivation occurs. We studied HIV-1 reactivation in the female genital tract, which is often the portal of HIV-1 entry and which remains a site of infection throughout the disease. We found that the columnar epithelial cells lining the endocervix, the lower part of the uterus, are particularly effective in reactivating HIV-1 from infected T cells. This activity was enhanced by certain microbial stimuli, including herpes simplex virus 2, and blocked by antibodies against the inflammatory cytokine TNF-α. Avoiding HIV-1 reactivation could be important for maintaining a functional HIV-1 cure when antiviral therapy is stopped.

Stress Urinary Incontinence Surgery in Washington State Before and After Introduction of the Mesh Midurethral Sling.

OBJECTIVES: Mesh midurethral slings (MUSs) are safe, effective treatments for female stress urinary incontinence (SUI), but many companies have ceased production because of controversies surrounding transvaginal mesh. To determine if introduction of MUS has increased the complication rate associated with SUI surgery, we compared women undergoing SUI surgery in the MUS era to those who had surgery prior its introduction. METHODS: This was a retrospective cohort study of a statewide hospital discharge database. Stress urinary incontinence surgeries from 1987 to 1996 and 2007 to 2013 were identified using International Classification of Diseases, Ninth Revision codes. RESULTS: A total of 30,723 SUI surgeries were performed during the study periods. After 2006, slings accounted for 91.8% of SUI surgeries. Patients were older (54.5 vs 53.0 years, P < 0.001) and sicker (22.6% vs 9.7% had ≥1 comorbid condition, P < 0.0001). Blood transfusion was more common in the MUS era (1.2% vs 0.4%, P < 0.001) however, other complications were either similar between groups or less common in the MUS era including 30-day readmission (2.5% vs 2.4%, P = 0.543), reoperation for urinary retention (0.1% vs 0.2%, P < 0.0375), and wound infection (0.1% vs 0.5%, P < 0.001), despite more concomitant prolapse surgeries (69.0 vs 26.9%, P < 0.001) and hysterectomies (53.0 vs 35.4%, P < 0.001) in the MUS era. Hospital stays were shorter after 2006 (1.0 vs 3.0 days, P < 0.001), and fewer women required reoperation for SUI within 2 years (0.5% vs 1.8%, P < 0.001). CONCLUSIONS: Following introduction of MUS, women who underwent SUI surgery were slightly older with more medical comorbidities yet did not appear to experience increased surgical complications. Fewer women underwent reoperation for recurrent SUI, and hospital stays were shorter, suggesting an improvement in care. This study supports the continued availability and use of MUSs.

Cryopreservation of human mucosal tissues.

BACKGROUND: Cryopreservation of leukocytes isolated from the cervicovaginal and colorectal mucosa is useful for the study of cellular immunity (see Hughes SM et al. PLOS ONE 2016). However, some questions about mucosal biology and sexually transmitted infections are better addressed with intact mucosal tissue, for which there is no standard cryopreservation protocol. METHODS AND FINDINGS: To find an optimal preservation protocol for mucosal tissues, we tested slow cooling (1°C/min) with 10% dimethylsulfoxide (designated "cryopreservation") and fast cooling (plunge in liquid nitrogen) with 20% dimethylsulfoxide and 20% ethylene glycol ("vitrification"). We compared fresh and preserved human cervicovaginal and colorectal tissues in a range of assays, including metabolic activity, human immunodeficiency virus infection, cell phenotype, tissue structure by hematoxylin-and-eosin staining, cell number and viability, production of cytokines, and microbicide drug concentrations. Metabolic activity, HIV infectability, and tissue structure were similar in cryopreserved and vitrified vaginal tissues. However, vitrification led to poor cell recovery from the colorectal mucosa, with 90% fewer cells recovered after isolation from vitrified colorectal tissues than from cryopreserved. HIV infection rates were similar for fresh and cryopreserved ectocervical tissues, whereas cryopreserved colorectal tissues were less easily infected than fresh tissues (hazard ratio 0.7 [95% confidence interval 0.4, 1.2]). Finally, we compared isolation of cells before and after cryopreservation. Cell recoveries were higher when cells were isolated after freezing and thawing (71% [59-84%]) than before (50% [38-62%]). Cellular function was similar to fresh tissue in both cases. Microbicide drug concentrations were lower in cryopreserved explants compared to fresh ones. CONCLUSIONS: Cryopreservation of intact cervicovaginal and colorectal tissues with dimethylsulfoxide works well in a range of assays, while the utility of vitrification is more limited. Cell yields are higher from cryopreserved intact tissue pieces than from thawed cryopreserved single cell suspensions isolated before freezing, but T cell functions are similar.

Attitudes and Beliefs Regarding the Utility of Robotically Assisted Gynecologic Surgery Among Practicing Gynecologists.

While use of robotic-assisted surgery has increased rapidly, little is known about the attitudes and beliefs of practicing gynecologists regarding the utility of the technology. We surveyed a large sample of gynecologists to examine their attitudes and beliefs about the benefits, utility, and factors driving use of robotic-assisted gynecologic surgery. A 51-item survey was mailed to 600 fellows or junior fellows of the American College of Obstetricians and Gynecologists. The survey included questions on use of robotic surgery, decision-making, and beliefs regarding the technology. Responses were stratified based on whether the respondent used robotic surgery or not. A total of 310 responses were received including 27.8% who used robotic surgery in their practices. Hysterectomy was the most commonly performed procedure. Opinions about the use and effectiveness of robotic procedures varied based on whether an individual was a robot user. Eighty-two percentage of robot users and 21% of nonrobot users believed robotic surgery provided benefits over laparoscopic (p < .0001). Among both groups, the ability to increase access to minimally invasive surgery and marketing were believed to be the greatest drivers of use of robotic surgery. Attitudes and beliefs about the effectiveness of robotic gynecologic surgery are highly variable among clinicians.

A study of the osmotic characteristics, water permeability, and cryoprotectant permeability of human vaginal immune cells.

Cryopreservation of specimens taken from the genital tract of women is important for studying mucosal immunity during HIV prevention trials. However, it is unclear whether the current, empirically developed cryopreservation procedures for peripheral blood cells are also ideal for genital specimens. The optimal cryopreservation protocol depends on the cryobiological features of the cells. Thus, we obtained tissue specimens from vaginal repair surgeries, isolated and flow cytometry-purified immune cells, and determined fundamental cryobiological characteristics of vaginal CD3(+) T cells and CD14(+) macrophages using a microfluidic device. The osmotically inactive volumes of the two cell types (Vb) were determined relative to the initial cell volume (V0) by exposing the cells to hypotonic and hypertonic saline solutions, evaluating the equilibrium volume, and applying the Boyle van't Hoff relationship. The cell membrane permeability to water (Lp) and to four different cryoprotective agent (CPA) solutions (Ps) at room temperature were also measured. Results indicated Vb values of 0.516 V0 and 0.457 V0 for mucosal T cells and macrophages, respectively. Lp values at room temperature were 0.196 and 0.295 µm/min/atm for T cells and macrophages, respectively. Both cell types had high Ps values for the three CPAs, dimethyl sulfoxide (DMSO), propylene glycol (PG) and ethylene glycol (EG) (minimum of 0.418 × 10(-3) cm/min), but transport of the fourth CPA, glycerol, occurred 50-150 times more slowly. Thus, DMSO, PG, and EG are better options than glycerol in avoiding severe cell volume excursion and osmotic injury during CPA addition and removal for cryopreservation of human vaginal immune cells.

Determination of the Membrane Permeability to Water of Human Vaginal Mucosal Immune Cells at Subzero Temperatures Using Differential Scanning Calorimetry.

To study mucosal immunity and conduct HIV vaccine trials, it is important to be able to cryopreserve mucosal specimens and recover them in functional viable form. Obtaining a good recovery depends, in part, on cooling the cells at the appropriate rate, which is determined by the rate of water transport across the cell membrane during the cooling process. In this study, the cell membrane permeabilities to water at subzero temperatures of human vaginal mucosal T cells and macrophages were measured using the differential scanning calorimetry method proposed by Devireddy et al. in 1998. Thermal histograms were measured before and after cell lysis using a Slow-Fast-Fast-Slow cooling program. The difference between the thermal histograms of the live intact cells and the dead lysed cells was used to calculate the temperature-dependent cell membrane permeability at subzero temperatures, which was assumed to follow the Arrhenius relationship, [Formula: see text], where Lpg is the permeability to water at the reference temperature (273.15 K). The results showed that Lpg = 0.0209 ± 0.0108 µm/atm/min and Ea = 41.5 ± 11.4 kcal/mol for T cells and Lpg = 0.0198 ± 0.0102 µm/atm/min and Ea = 38.2 ± 10.4 kcal/mol for macrophages, respectively, in the range 0°C to -40°C (mean ± standard deviation). Theoretical simulations predicted that the optimal cooling rate for both T cells and macrophages was about -3°C/min, which was proven by preliminary immune cell cryopreservation experiments.

Optimizing viable leukocyte sampling from the female genital tract for clinical trials: an international multi-site study.

BACKGROUND: Functional analysis of mononuclear leukocytes in the female genital mucosa is essential for understanding the immunologic effects of HIV vaccines and microbicides at the site of HIV exposure. However, the best female genital tract sampling technique is unclear. METHODS AND FINDINGS: We enrolled women from four sites in Africa and the US to compare three genital leukocyte sampling methods: cervicovaginal lavages (CVL), endocervical cytobrushes, and ectocervical biopsies. Absolute yields of mononuclear leukocyte subpopulations were determined by flow cytometric bead-based cell counting. Of the non-invasive sampling types, two combined sequential cytobrushes yielded significantly more viable mononuclear leukocytes than a CVL (p<0.0001). In a subsequent comparison, two cytobrushes yielded as many leukocytes (∼ 10,000) as one biopsy, with macrophages/monocytes being more prominent in cytobrushes and T lymphocytes in biopsies. Sample yields were consistent between sites. In a subgroup analysis, we observed significant reproducibility between replicate same-day biopsies (r = 0.89, p = 0.0123). Visible red blood cells in cytobrushes increased leukocyte yields more than three-fold (p = 0.0078), but did not change their subpopulation profile, indicating that these leukocytes were still largely derived from the mucosa and not peripheral blood. We also confirmed that many CD4(+) T cells in the female genital tract express the α4ß7 integrin, an HIV envelope-binding mucosal homing receptor. CONCLUSIONS: CVL sampling recovered the lowest number of viable mononuclear leukocytes. Two cervical cytobrushes yielded comparable total numbers of viable leukocytes to one biopsy, but cytobrushes and biopsies were biased toward macrophages and T lymphocytes, respectively. Our study also established the feasibility of obtaining consistent flow cytometric analyses of isolated genital cells from four study sites in the US and Africa. These data represent an important step towards implementing mucosal cell sampling in international clinical trials of HIV prevention.

Reoperation after sacral neuromodulation therapy: a single-institution experience.

OBJECTIVES: Sacral neuromodulation has become an accepted treatment for various types of lower urinary tract dysfunction. However, despite technologic advances in device implantation and a trial stimulation period, sacral neuromodulation still has a significant reoperation rate. We report our single-institution experience of reoperation rates. METHODS: We performed a retrospective review of our patients who had undergone the implantation of the InterStim device from April 1999 to December 2011 for lower urinary tract dysfunction. RESULTS: A total of 155 InterStim devices were implanted by 2 surgeons. Of the 142 patients with complete follow-up, 55 (38.2%) patients required reoperation, for either revision or explantation of the device. Revisions were performed in 30 (21.1%) patients, most commonly for mechanical failure of device, battery end-of-service, and pain, either at the site of the implanted pulse generator or with stimulation. Of the 30 patients who underwent revision, 14 had successful results, 6 had persistent symptoms, and 10 progressed to eventual explantation.The overall explantation rate was 24.6% (35 of 142 patients), and the average time to removal was 44 months. Most of the explantations were performed for poor symptom control and failure to maintain response (74.3%).Reoperation was not associated with age, sex, obesity, diabetes, chronic pain, use of the tined lead, or type of lower urinary tract dysfunction. CONCLUSIONS: Sacral neuromodulation has a substantial revision and explantation rate, without any clear predictors for these complications. Patients should be counseled to these complications before surgery.

Training the next generation of minimally invasive surgeons.

A paradigm shift is occurring in the educational approach to surgical procedures. A variety of pressures are forcing the initial education of surgeons of all disciplines out of the operating department and into simulation. Fortunately, increasing evidence suggests that surgeons can learn many fundamental skills and specific procedures with simulators. Evidence also supports the expectation that surgeons trained in simulation laboratories initially perform better in the operating department than those who are not. Minimally invasive procedures lend themselves to simulation particularly well. Currently, many different models are available for training and improvement in skills are seen with both low- and high-fidelity models. Developing an effective curriculum principally requires a commitment to the concept, and the time and space, for residents to learn and practice. Although many questions remain about how to optimally apply and evaluate the educational tools being developed, it appears certain that surgical simulation, in some form, is the educational paradigm of the present and future.

Incidence of recurrent pelvic organ prolapse 10 years following primary surgical management: a retrospective cohort study.

We conducted this study to estimate the rate of, and identify risk factors for, recurrent pelvic organ prolapse (POP) following primary surgical repair. The study consisted of a retrospective cohort study of 142 women who underwent primary surgical management of POP in 1993 and were followed up to 10 years. Prolapse severity was graded using an established classification system of clinical descriptors. Hazard ratios (HR) for recurrent POP were determined using Cox regression. 36 recurrent cases were identified (recurrence rate: 3.7 per 100 woman-years). A cystocele was the most frequent element of primary (87%) and recurrent (72%) prolapse. No predictors of the likelihood of recurrence were identified, though recurrence was somewhat more common among women with a history of two or fewer vaginal deliveries vs three or more (HR = 1.6; 95% confidence interval = 0.81-3.3). Recurrent POP following surgical management is common. Our ability to predict recurrence is limited.

Reoperation for urinary incontinence.

OBJECTIVE(S): The objective of the study was to describe the rate and associated factors of reoperation for urinary incontinence. STUDY DESIGN: A cohort study using Washington state hospitalization records from 1987 to 2005 of inpatient urinary incontinence surgeries. The cumulative reoperation rate was estimated for the entire cohort and by procedure. Cox regression was used to estimate the hazard of reoperation. RESULTS: A total of 41,705 women underwent either a sling or retropubic colposuspension (Burch); 1895 underwent reoperation for urinary incontinence (8.6%; 95% confidence interval, 7.8-9.5%), a rate of 5.5 per 1000 woman-years. Women undergoing Burch had a lower reoperation rate than those undergoing slings (4.2 vs 6.7 per 1000 woman-years; P < .001). Concomitant hysterectomy was associated with a lower reoperation rate for Burch and sling repairs (5.4-2.9 and 7.7-4.2 per 1000 woman-years). CONCLUSION(S): Reoperation for urinary incontinence occurs commonly in the general population. The variable reoperation rate observed should be further investigated, given current trends toward increased Sling use.

A curriculum for Burch colposuspension and diagnostic cystoscopy evaluated by an objective structured assessment of technical skills.

OBJECTIVE: The purpose of this study was to develop an effective curriculum for teaching colposuspension and diagnostic cystoscopy. STUDY DESIGN: Fifty-five residents underwent an Objective Structured Assessment of Technical Skills that was composed of a task-specific checklist and validated global assessment. Thirty of the residents had been exposed to a training curriculum, and 25 residents served as untrained control subjects. RESULTS: For the colposuspension and cystoscopy checklists, the reliability coefficient was 0.85 and 0.72, and the interrater reliability was 0.92 and 0.68, respectively. Although residents who were provided the curriculum performed better on both task-specific checklists, the differences did not reach statistical significance. Senior residents performed consistently better than junior residents for both tasks. When a comparison was made of the junior residents separately to account for previous experience, trained residents performed significantly better on the cystoscopy checklist (P = .029). CONCLUSION: This curriculum is an effective way to teach diagnostic cystoscopy to junior residents. The checklist for this Objective Structured Assessment of Technical Skills has good reliability and construct validity.

Complications from transvaginal pubovaginal slings using bone anchor fixation.

OBJECTIVES: To evaluate the history and management of complications from transvaginally placed pubovaginal slings using bone anchor fixation. METHODS: During a 3-year period, 10 patients were referred to us for complications related to transvaginally placed pubovaginal slings using bone anchor fixation. RESULTS: The patient age ranged from 42 to 73 years. All women had a vaginally introduced bone anchor sling for stress urinary incontinence. The presenting symptoms after surgery included fever, pain, and difficulty ambulating in 1; pain and/or vaginal dyspareunia with discharge in 5; pain or dyspareunia alone in 2; and vaginal discharge alone in 2 patients. Two patients ultimately developed bone lesions on radiologic studies consistent with osteomyelitis. Six patients developed sinus drainage tracts associated with granulation tissue from at least one bone anchor that was unresponsive to outpatient management. One of the patients with pain alone had a permanent suture extending into the bladder neck. Nine patients underwent surgery, of whom five had resolution of their presenting complaint. Four of these patients were continent at last follow-up. CONCLUSIONS: Transvaginally placed pubovaginal slings using bone anchors can be associated with serious complications that may be intractable to common therapies. This knowledge may enable practitioners who use this technique to better counsel their patients regarding these significant complications.

Posterior vaginal wall defects and their relation to measures of pelvic floor neuromuscular function and posterior compartment symptoms.

OBJECTIVE: The purpose of this study was to describe the pelvic floor neuromuscular function and posterior compartment symptoms in patients with posterior vaginal wall prolapse. STUDY DESIGN: Two hundred twenty-seven women who were referred to a urogynecology and urology clinic were enrolled prospectively. Each patient completed a health history questionnaire and standardized physical examination that specifically graded uterovaginal prolapse according to the pelvic organ prolapse quantification system. RESULTS: Sixty-nine women had a pelvic organ prolapse quantification system point (most dependent portion of the posterior vaginal wall during straining as measured from the hymeneal ring) of < or =-1. Older age, a history of hysterectomy, a genital hiatus of >3 cm (48% vs 24%; P =.002), and perineal descent of > or =2 cm (14% vs 5%; P =.042) were significantly more common in women with posterior vaginal prolapse. When women with posterior prolapse and symptomatic complaints were compared with asymptomatic women with prolapse, a perineal descent of > or =2 cm (21% vs 0%; P =.004) was significantly more common in the symptomatic group. CONCLUSION: Pelvic floor neuromuscular function should be related to posterior vaginal prolapse and symptoms; however, only perineal descent appears associated strongly with both symptoms and prolapse in this population.