Barriers to Office Hysteroscopy in Fellowship Education and Practice.

STUDY OBJECTIVE: To identify the top 3 perceived barriers to performing office hysteroscopy (OH) by minimally invasive gynecologic surgery (MIGS) faculty and fellows and identify opportunities for education on this key topic that will be most effective in fellowship training and MIGS practice. DESIGN: Cross-sectional survey study targeted at all American Association of Gynecologic Laparoscopists-accredited Fellowship in Minimally Invasive Gynecologic Surgery fellows, program directors, and associate program directors in February to April 2022. The survey was designed by faculty who have extensive experience in OH procedures. In addition, a literature search was performed to aid with question design. SETTING, PATIENTS, AND INTERVENTIONS: This was a REDCap electronic survey administered through the Fellowship in Minimally Invasive Gynecologic Surgery listserv. No additional follow-up was performed after survey completion. The 15-minute survey was sent to 60 program directors, 92 assistant program directors, and 158 fellows, including the incoming class of 2024 and the 2022 fellowship graduates. MEASUREMENTS AND MAIN RESULTS: A total of 93 responses were received; 67% of respondents performed OH but 73% of those performed 5 procedures or less per month. Most participants controlled pain with nonsteroidal anti-inflammatory drugs +/- paracervical block. The most common perceived barrier to performing OH was concern over pain management. Other commonly cited concerns were equipment costs, sterilization costs, and office staff training; 37% to 44% of respondents also cited lack of departmental support and insufficient clinic time, respectively, as barriers, and 56% indicated they are interested in educational materials on OH. CONCLUSION: Our study suggests general interest in, but a low volume of, OH among MIGS fellows and faculty. The most common perceived barrier was concern regarding pain management. This has been well studied in the literature and likely presents an area for greater education to improve OH utilization. We also uncovered concerns regarding systemic barriers, such as equipment costs, departmental support, and clinic structure. This is an area for further research and advocacy efforts to address barriers to OH on a system level.

Best practices for repair of iatrogenic bladder injury.

Gynecologic surgery carries a known risk of injury to the urinary tract, especially in the presence of risk factors. Injury to the bladder, particularly a mechanical injury, is more common than injury to the ureter. Urinary tract injuries occur in 0.3% to 0.8% of all gynecologic procedures, and injuries to the bladder occur in 0.05% to 0.66% of such surgeries. The risk of bladder injury increases in hysterectomy procedures. Most research studies have cited occurrence of bladder injuries to be 1.0% to 1.8% in laparoscopically assisted vaginal hysterectomies and vaginal hysterectomies. Despite its frequency, there is limited research on best practices for bladder injury repair. The authors performed a literature search through the PubMed database using the terms "bladder anatomy," "bladder injury," "bladder repair," "cystotomy," "routine cystoscopy," and "vesicovaginal fistula." This review uses gynecologic and trauma literature and discusses prevention, recognition, types of iatrogenic bladder injuries, their clinical significance, current guidelines on bladder injury repair, and the expected follow-up care, and concludes by identifying areas for further research.

Prospective Study Investigating Change in Carboxyhemoglobin Blood Level During Operative Hysteroscopy.

STUDY OBJECTIVES: To evaluate whether the use of radiofrequency energy during resectoscopy leads to increases in patient blood levels of carboxyhemoglobin (COHb) and investigate procedural variables associated with these elevations. DESIGN: A prospective cross-sectional study of 40 subjects undergoing a hysteroscopic procedure using bipolar radiofrequency energy. SETTING, PATIENTS, AND INTERVENTIONS: The study was conducted at an ambulatory surgery center. Procedures for uterine leiomyoma, septa, products of conception, or a combination of these pathologies were included. We measured blood COHb levels before and immediately after the surgery. Abnormal postoperative COHb level was defined as an increase of plasma COHb ≥3.0%. All patients with abnormal postoperative levels were contacted and screened for carbon monoxide toxicity symptoms. Summary statistics included frequency for categorical variables and averages for continuous variables. p values were reported without modification. MEASUREMENTS AND MAIN RESULTS: A total of 17.5% of subjects met the criteria for abnormal postoperative COHb levels. None of these subjects reported symptoms of carbon monoxide toxicity. One subject with an elevated postoperative COHb level had intraoperative hemodynamic changes possibly related to COHb elevation. An abnormal postoperative COHb level was associated with a higher fluid deficit (p = .024) and greater myoma volume (p = .04). CONCLUSION: This study demonstrates that systemic absorption of carbon monoxide is a reproducible phenomenon in hysteroscopic resections using bipolar diathermy. Greater absorption is associated with a higher fluid deficit and greater myoma volume. Although none of the subjects with an abnormal increase screened positive for symptoms in the postoperative setting and only 1 experienced hemodynamic changes intraoperatively, our study looked at a healthy and young patient population. More research is needed on the safety of this COHb exposure in patients with medical comorbidities. Special consideration should be given to the possibility of carbon monoxide absorption and the uncertain long-term effects when planning extensive hysteroscopic resections.

Office Hysteroscopy: Setting up Your Practice for Success.

Office hysteroscopy is a highly effective procedure for the evaluation and treatment of intrauterine pathology. The "see and treat" approach allows for patient treatment with the fewest amount of patient visits. The development of smaller cameras and instruments, as well as the employment of a vaginoscopy technique, has led to greater tolerability of office hysteroscopy and significant success of the "see and treat" approach. Most office hysteroscopic procedures can be accomplished with minimal premedication. There are many choices for equipment types and sterilization methods for the office hysteroscopy practice. Reimbursement for office hysteroscopy has improved, but economic challenges remain.

Surgical Outcomes in Benign Gynecologic Surgery Patients during the COVID-19 Pandemic (SOCOVID study).

STUDY OBJECTIVE: To determine the incidence of perioperative coronavirus disease (COVID-19) in women undergoing benign gynecologic surgery and to evaluate perioperative complication rates in patients with active, previous, or no previous severe acute respiratory syndrome coronavirus 2 infection. DESIGN: A multicenter prospective cohort study. SETTING: Ten institutions in the United States. PATIENTS: Patients aged >18 years who underwent benign gynecologic surgery from July 1, 2020, to December 31, 2020, were included. All patients were followed up from the time of surgery to 10 weeks postoperatively. Those with intrauterine pregnancy or known gynecologic malignancy were excluded. INTERVENTIONS: Benign gynecologic surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of perioperative COVID-19 infections, which was stratified as (1) previous COVID-19 infection, (2) preoperative COVID-19 infection, and (3) postoperative COVID-19 infection. Secondary outcomes included adverse events and mortality after surgery and predictors for postoperative COVID-19 infection. If surgery was delayed because of the COVID-19 pandemic, the reason for postponement and any subsequent adverse event was recorded. Of 3423 patients included for final analysis, 189 (5.5%) postponed their gynecologic surgery during the pandemic. Forty-three patients (1.3% of total cases) had a history of COVID-19. The majority (182, 96.3%) had no sequelae attributed to surgical postponement. After hospital discharge to 10 weeks postoperatively, 39 patients (1.1%) became infected with severe acute respiratory syndrome coronavirus 2. The mean duration of time between hospital discharge and the follow-up positive COVID-19 test was 22.1 ± 12.3 days (range, 4-50 days). Eleven (31.4% of postoperative COVID-19 infections, 0.3% of total cases) of the newly diagnosed COVID-19 infections occurred within 14 days of hospital discharge. On multivariable logistic regression, living in the Southwest (adjusted odds ratio, 6.8) and single-unit increase in age-adjusted Charlson comorbidity index (adjusted odds ratio, 1.2) increased the odds of postoperative COVID-19 infection. Perioperative complications were not significantly higher in patients with a history of positive COVID-19 than those without a history of COVID-19, although the mean duration of time between previous COVID-19 diagnosis and surgery was 97 days (14 weeks). CONCLUSION: In this large multicenter prospective cohort study of benign gynecologic surgeries, only 1.1% of patients developed a postoperative COVID-19 infection, with 0.3% of infection in the immediate 14 days after surgery. The incidence of postoperative complications was not different in those with and without previous COVID-19 infections.

An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity.

Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. We previously described a chemical inhibitor of RAD51, called RI-1 (referred to as compound 1 in this report). The chloromaleimide group of this compound is thought to act as a Michael acceptor and react with the thiol group on C319 of RAD51, using a conjugate addition-elimination mechanism. In order to reduce the likelihood of off-target effects and to improve compound stability in biological systems, we developed an analogue of compound 1 that lacks maleimide-based reactivity but retains RAD51 inhibitory activity. This compound, 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione, named RI-2 (referred to as compound 7a in this report), appears to bind reversibly to the same site on the RAD51 protein as does compound 1. Like compound 1, compound 7a specifically inhibits HR repair in human cells.

p19Arf represses platelet-derived growth factor receptor ß by transcriptional and posttranscriptional mechanisms.

In addition to cancer surveillance, p19(Arf) plays an essential role in blocking signals stemming from platelet-derived growth factor receptor ß (Pdgfrß) during eye development, but the underlying mechanisms have not been clear. We now show that without Arf, pericyte hyperplasia in the eye results from enhanced Pdgfrß-dependent proliferation from embryonic day 13.5 (E13.5) of mouse development. Loss of Arf in the eye increases Pdgfrß expression. In cultured fibroblasts and pericyte-like cells, ectopic p19(Arf) represses and Arf knockdown enhances the expression of Pdgfrß mRNA and protein. Ectopic Arf also represses primary Pdgfrß transcripts and a plasmid driven by a minimal promoter, including one missing the CCAAT element required for high-level expression. p19(Arf) uses both p53-dependent and -independent mechanisms to control Pdgfrß. In vivo, without p53, Pdgfrß mRNA is elevated and eye development abnormalities resemble the Arf (-/-) phenotype. However, effects of p53 on Pdgfrß mRNA do not appear to be due to direct p53 or RNA polymerase II recruitment to the promoter. Although p19(Arf) controls Pdgfrß mRNA in a p53-dependent manner, it also blunts Pdgfrß protein expression by blocking new protein synthesis in the absence of p53. Thus, our findings demonstrate a novel capacity for p19(Arf) to control Pdgfrß expression by p53-dependent and -independent mechanisms involving RNA transcription and protein synthesis, respectively, to promote the vascular remodeling needed for normal vision.

RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells.

Homologous recombination serves multiple roles in DNA repair that are essential for maintaining genomic stability. We here describe RI-1, a small molecule that inhibits the central recombination protein RAD51. RI-1 specifically reduces gene conversion in human cells while stimulating single strand annealing. RI-1 binds covalently to the surface of RAD51 protein at cysteine 319 that likely destabilizes an interface used by RAD51 monomers to oligomerize into filaments on DNA. Correspondingly, the molecule inhibits the formation of subnuclear RAD51 foci in cells following DNA damage, while leaving replication protein A focus formation unaffected. Finally, it potentiates the lethal effects of a DNA cross-linking drug in human cells. Given that this inhibitory activity is seen in multiple human tumor cell lines, RI-1 holds promise as an oncologic drug. Furthermore, RI-1 represents a unique tool to dissect the network of reaction pathways that contribute to DNA repair in cells.