The Fragility of Statistically Significant Results in Gynaecologic Surgery: A Systematic Review.

OBJECTIVE: To use the fragility index (FI) to evaluate the robustness of gynaecologic surgery trials that report statistically significant results. The FI defines the minimum number of patients who must have an alternative outcome to alter statistical significance. DATA SOURCES: We searched MEDLINE, Web of Science, Embase, and ClinicalTrials.gov from 2011 to 2021 to identify gynaecologic surgery randomized controlled trials (RCTs). STUDY SELECTION: A total of 4775 trials were screened for eligibility. All included studies evaluated benign gynaecologic surgery interventions or peri-operative medical interventions. Only 2-arm RCTs with statistically significant dichotomous primary outcomes were included. Ninety-three trials were ultimately included for analysis. DATA EXTRACTION AND SYNTHESIS: Data from the included studies, including sample size, loss to follow-up, and number of events, were recorded. The FI of each study was calculated using a predefined technique. The overall FI and FIs by subgroup (clinical subspecialty, country of origin, and statistical test used) are reported as medians alongside their interquartile ranges (IQRs). The Kruskal-Wallis test was applied to find possible statistically significant relationships between FI and the nominal subgroups. Among this cohort, the median FI was 3 (IQR 1-7). The FI was 0 in 13 trials (14%), and in 39 trials (42%), the number of patients lost to follow-up was greater than the FI. The median FI within clinical subspecialty groups (general gynaecology, anaesthesia, urogynaecology, and fertility) did not differ (P = 0.122). CONCLUSION: Statistically significant results of RCTs in gynaecologic surgery are fragile, suggesting that clinicians should interpret results with caution. This is particularly true when the number of patients lost to follow-up is greater than the FI. The FI serves as a quality metric that can be used to evaluate robustness of results when applying the outcomes of RCTs to clinical practice or guideline development.

Asymptomatic Atypical Hyperplasia and Endometriosis Following Treatment with Tamoxifen: A Case Report and Review of the Literature.

BACKGROUND: Tamoxifen may cause proliferative effects in the endometrium. Patients on tamoxifen have an increased risk for endometriosis, but are not routinely screened for this. CASE: A 49-year-old postmenopausal patient presented for a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy several years after initiating tamoxifen for breast cancer. She had no clinical history to suggest endometriosis, but was found to have extensive pelvic endometriosis intraoperatively with polypoid hyperplasia found on the pathology of the uterine and the ovarian tissue. CONCLUSION: This is the first case reported of an asymptomatic patient on tamoxifen with a new diagnosis of endometriosis along with atypical hyperplasia in the ectopic tissue. The potential for pre-malignant/malignant transformation may alter the treatment course if identified following tamoxifen exposure.

Does Ulipristal Acetate Affect Surgical Experience at Laparoscopic Myomectomy?

STUDY OBJECTIVE: To compare surgical experience of laparoscopic/robotic myomectomy in premenopausal patients pretreated with ulipristal acetate (UPA) with women not hormonally pretreated. DESIGN: A retrospective, multicenter cohort study of laparoscopic/robotic myomectomy procedure videos (Canadian Task Force Classification III). SETTING: Multiple university-affiliated tertiary care hospitals. PATIENTS: Fifty-five premenopausal women who underwent laparoscopic/robotic myomectomy for intramural myomas and were either pretreated with 3 months of UPA or had no hormonal pretreatment. INTERVENTIONS: Laparoscopic/robotic myomectomy surgical videos were independently reviewed by 2 gynecologists blinded to whether or not patients received pretreatment with UPA. Each procedure was scored using a novel 22-point surgical global rating tool containing 6 subscales: depth of myometrial incision, ease of myoma-myometrium cleavage plane identification, ease of myoma detachment, blood loss during myoma detachment, myometrial blood loss after myoma detachment, and myoma consistency. MEASUREMENTS AND MAIN RESULTS: Participating surgeons submitted 55 videos of laparoscopic/robotic myomectomy procedures recorded over a 3-year period (2012-2015). Fifty met the inclusion criteria (25 UPA-treated patients and 25 patients without hormonal pretreatment). Patients treated with UPA were more likely to be older than patients with no medical pretreatment (mean age = 33.5 vs 38.3 years, p = .002). There were no statistically significant differences regarding other baseline characteristics such as the largest diameter of myoma removed, the number of myomas removed, or the estimated blood loss. There was no difference in the physician assessors' mean global rating score for patients with UPA pretreatment versus no pretreatment (12.4 vs 13.4, p = .23). Within the 6 subscales, no differences were observed between the 2 groups. Each video was graded independently by 2 assessors, and there was high inter-rater agreement for the total score and each subscale. CONCLUSION: There was no difference in surgical experience for myomectomies of patients pretreated with UPA versus those without medical pretreatment.

Options to Evaluate Ureter Patency at Cystoscopy in a World Without Indigo Carmine.

Intraoperative cystoscopy has been studied as a means to identify ureteral injuries at the time of gynecologic surgery. The majority of published studies investigating intraoperative cystoscopy have used indigo carmine to dye the urine to allow visualization of ureteral jets; unfortunately, however, this dye is currently not available in North America. The unavailability of indigo carmine may be a permanent reality that forces gynecologists to examine alternatives for the evaluation of ureteral integrity. Various alternative methods have been suggested, ranging from cystoscopy without dye to other commercially available products that dye the urine. Alternatives to cystoscopy for assessing ureteral integrity exist as well. This review provides an evidence-based review of the various methods available for evaluating ureteral patency, with specific information on dosing, adverse effects, and contraindications. This review will equip practicing gynecologists to choose an alternative method for assessing ureteral integrity that is tailored to their specific needs.

Evaluating the effect of distractions in the operating room on clinical decision-making and patient safety.

BACKGROUND: Answering telephone calls and pagers is common distraction in the operating room. We sought to evaluate the impact of distractions on patient care by (1) assessing the accuracy and safety of responses to clinical questions posed to a surgeon while operating and (2) determining whether pager distractions affect simulation-based surgical performance. METHODS: We conducted a randomized crossover study of obstetrics and gynecology residents. After studying a patient sign-out list, subjects performed a virtual salpingectomy. They were randomized to a distraction phase followed by quiet phase or vice versa. In the distraction phase, a pager beeped and subjects were asked questions based on the sign-out list. Accuracy of responses and the number of unsafe responses were recorded. In the quiet phase, trainees performed the task uninterrupted. Measures of surgical performance were successful task completion, time to task completion and operative blood loss. RESULTS: The mean score for correct responses to clinical questions during the distracted phase was 80 % (SD ±14 %). Nineteen residents (63 %) made at least 1 unsafe clinical decision while operating on the simulator (range 0-3). Subjects were more likely to successfully complete the surgical task in the allotted time under the quiet compared to distraction condition (OR 11.3, p = 0.03). There was no difference between the conditions in paired analysis for mean time (seconds) to task completion [426 (SD 133) vs. 440 (SD 186), p = 0.61] and mean operative blood loss (mL) [73.14 (SD 106) vs. 112.70 (SD 358), p = 0.47]. CONCLUSIONS: Distractions in the operating room may have a profound impact on patient safety on the wards. While multitasking in a simulated setting, the majority of residents made at least one unsafe clinical decision. Pager distractions also hindered surgical residents' ability to complete a simulated laparoscopic task in the allotted time without affecting other variables of surgical performance.

Antigen presentation by exosomes released from peptide-pulsed dendritic cells is not suppressed by the presence of active CTL.

Despite the potency of dendritic cells (DCs) as a vaccine carrier, they are short-lived and sensitive to CTL-mediated elimination. Thus, it is believed that the longevity of Ag presentation by peptide-pulsed DC is limited in vivo. Surprisingly, however, we found that although the majority of injected DCs disappeared from the draining lymph nodes within 7 days, Ag presentation persisted for at least 14 days following DC immunization. This prolonged Ag presentation was not mediated by the remaining injected DCs or through Ag transfer to endogenous APCs. We provide evidence that exosomes released by DCs might be responsible for the persistence of Ag presentation. Functional exosomes could be recovered from the draining lymph nodes of C57BL/6 mice following DC vaccination and, in contrast to DCs, T cell stimulation by exosomes in vivo was not affected by the presence of CTL. Our findings demonstrate that Ag presentation following delivery of DC vaccines persists for longer than expected and indicate that the exosome may play a previously unrecognized role in Ag presentation following DC vaccination. Furthermore, our study reinforces the application of exosomes as a vaccination platform and suggests that exosome-based vaccines may be advantageous for booster immunizations due to their resistance to CTL.