Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Implementing Enhanced Recovery After Surgery for hysterectomy in a hospital network with audit and feedback: A stepped-wedge cluster randomised trial.

OBJECTIVE: To evaluate the effectiveness of implementing the Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing elective hysterectomy in a network of regional hospitals, supported by an intensive audit-and-feedback (A&F) approach. DESIGN: A multi-centre, stepped-wedge cluster randomised trial (ClinicalTrials.gov NCT04063072). SETTING: Gynaecological units in the Piemonte region, Italy. POPULATION: Patients undergoing elective hysterectomy, either for cancer or for benign conditions. METHODS: Twenty-three units (clusters), stratified by surgical volume, were randomised into four sequences. At baseline (first 3 months), standard care was continued in all units. Subsequently, the four sequences implemented the ERAS protocol successively every 3 months, after specific training. By the end of the study, each unit had a period in which standard care was maintained (control) and a period in which the protocol, supported by feedback, was applied (experimental). MAIN OUTCOME MEASURES: Length of hospital stay (LOS), without outliers (>98th percentile). RESULTS: Between September 2019 and May 2021, 2086 patients were included in the main analysis with an intention-to-treat approach: 1104 (53%) in the control period and 982 (47%) in the ERAS period. Compliance with the ERAS protocol increased from 60% in the control period to 76% in the experimental period, with an adjusted absolute difference of +13.3% (95% CI 11.6% to 15.0%). LOS, moving from 3.5 to 3.2 days, did not show a significant reduction (-0.12 days; 95% CI -0.30 to 0.07 days). No difference was observed in the occurrence of complications. CONCLUSIONS: Implementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance, but without meaningful effects on LOS and complications. This study confirms the effectiveness of A&F in promoting important innovations in an entire hospital network and suggests the need of a higher compliance with the ERAS protocol to obtain valuable improvements in clinical outcomes.

Factor structure of post-operative quality of recovery questionnaire (QoR-15): An Italian adaptation and validation.

Background: The Quality of Recovery questionnaire (QoR-15) is an English instrument for measuring quality of recovery in surgical patients, not yet translated and validated in Italian when the Enhanced Recovery After Surgery (ERAS) Piemonte studies were planned. Objective: To produce the Italian version of the QoR-15 questionnaire, to evaluate its factorial structure and to assess the invariance between two types of surgery. Methods: The Italian version (QoR-15I) was obtained translating and adapting the original version to the Italian context. The validation was performed suppling the QoR-15I to 3,784 patients enrolled in two parallel stepped wedge cluster randomised trials (ERAS Colon-rectum Piemonte; ERAS Gyneco Piemonte). The factor structure and its invariance between types of surgery was tested using confirmatory bifactor model and multi-group analysis. Comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR) fit indices and their changes between nested models were used to assess the factor structure and the invariance. Results: The bifactor model showed good fit (RMSEA = 0.049, CFI =0.957, SRMR = 0.036) and provided a general recovery factor and two specific factors for physical and mental recovery. Eighty-four percent of the common variance is attributable to the general factor, and thus the QoR-15I is sufficiently 'one-dimensional' with an adequate reliability (ωh = 0.70). The ωs values for the physical and mental recovery factors were 0.01 and 0.13, respectively. Multigroup analysis supported configural (RMSEA = 0.053, CFI = 0.950, SRMR = 0.035) and metric invariance (ΔRMSEA = -0.004; ΔCFI = -0.002; ΔSRMR = 0.014), whereas the intercept constraint was removed from item 15 to obtain partial scalar invariance (ΔRMSEA = 0.002; ΔCFI = 0.007; ΔSRMR = 0.004). Construct validity was supported by a negative association of QoR-15I scores with all variables related to worse patient condition and more complex surgery. Conclusion: Our results support the use of the QoR-15I as a valid, reliable, and clinically feasible tool for measuring the quality of recovery after surgery. The results of the confirmatory factor analyses suggest that a unique recovery score can be calculated and support measurement invariance of the QOR-15I across the two type of surgery, suggesting that the questionnaire has the same meaning and the same measurement parameters in colorectal and gynaecologic patients.

Laparoscopic stripping of endometriomas negatively affects ovarian follicular reserve even if performed by experienced surgeons.

In order to estimate the impact of laparoscopic stripping of endometriomas on the ovarian follicular reserve, 43 normo-ovulatory women were studied by endocrine (anti-Müllerian hormone (AMH), FSH, LH, inhibin B, oestradiol) and ultrasonographic (antral follicle count (AFC)) methods before surgery, and 3 and 9 months after surgery. The operation was performed by experienced laparoscopists, particularly aware of the need to avoid damaging the healthy part of the ovary. Serum AMH concentrations significantly decreased after the operation (1.4±0.2 ng/ml after 3 months and 1.3±0.3 ng/ml after 9 months versus 3.0±0.4 ng/ml before surgery; P<0.0001), whereas basal FSH, LH, oestradiol and inhibin B concentrations remained unchanged. The volume of the operated ovary significantly diminished after surgery (P<0.0001), whereas the AFC was not significantly altered. Overall, the data show that laparoscopic stripping of endometriomas reduces ovarian reserve. The significant decrease of AMH after surgery confirms that part of the healthy ovarian pericapsular tissue, containing primordial and preantral follicles, is removed or damaged despite all the surgical efforts to be atraumatic. This must be carefully considered when laparoscopic cystectomy surgery is scheduled for patients with no relevant symptoms besides infertility or with already small ovarian reserve.

Laparoscopy and body mass index: feasibility and outcome in obese patients treated for gynecologic diseases.

STUDY OBJECTIVE: To compare feasibility and surgical outcome of laparoscopic gynecologic surgery between obese, overweight, normal-weight, and underweight women. DESIGN: Retrospective case control study (Canadian Task Force classification II-3). SETTING: Surgery Unit of Minimally Invasive Gynaecology. PATIENTS: A total of 503 women who underwent laparoscopic procedures for both benign disease and malignancies. INTERVENTIONS: Four main categories of gynecologic disease were identified: uterine fibroids, benign adnexal masses, endometriosis, and endometrial cancer (stage I). For each category patients were divided into 4 groups: underweight (BMI <18.5 kg/m(2)), normal-weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI ≥30 kg/m(2)). MEASUREMENTS AND MAIN RESULTS: Selected outcomes were duration of surgery, rate of laparotomy conversion, intraoperative and postoperative complications, and duration of hospital stay. No statistical difference regarding demographic data, surgical and medical history, and intraoperative findings was present between groups. No laparotomy conversion occurred. Regarding duration of surgery, we found no statistical difference among the BMI groups with regard to benign diseases, whereas pelvic lymphadenectomy in obese patients with endometrial cancer had a statistically significant longer duration than in the control group (122 +/- 47 min vs 65 +/- 21 min, p <.001). The postoperative complication rate was 0.01%: 3 cases of blood transfusion and 1 case of hemoperitoneum among myomectomies; 1 ureteral fistula in surgery for pelvic endometriosis; and 1 case of postoperative lymphocele in endometrial cancer group. No statistically significant difference was found in duration of hospital stay among the BMI groups in any of the categories of disease. For each category we conducted an analysis to identify any possible risk factors other than BMI in the surgical outcomes. CONCLUSION: Laparoscopic approach in the various applications of gynecologic surgery does not appear to be significantly influenced by BMI in terms of surgical outcomes, laparotomy conversion rate, intraoperative and postoperative complications rate, and duration of hospital stay. The technical difficulties can be solved if skilled surgeons and anesthetists are available.

Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis.

BACKGROUND: this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis. METHODS: Eighty cases of histologically confirmed endometriosis affecting the ureter, 10 of which with bladder involvement were prospectively studied. In detail, patients were 13 women with ureteral stenosis (7 with hydronephrosis), 32 with circular lesions totally encasing the ureter, and 35 with endometriotic foci on the ureteral wall, but not completely encasing it. They were submitted to laparoscopic ureterolysis with or without partial cystectomy, ureteroneocistostomy. The rate of surgical complications, the recurrence rate, the patients' satisfaction rate was assessed during 22 months (median) follow-up. RESULTS: Laparoscopic ureterolysis was employed for all patients and set free the ureter from the disease in 95% of cases, whereas ureteroneocystostomy was necessary for 4 patients showing severe stenosis with hydronephrosis, among which 2 had intrinsic endometriosis of the ureteral muscularis. Three post-surgery ureteral fistulae occurred in cases with ureteral involvement longer than 4 cm: two cases were successfully treated placing double J catheter, the third needed ureteroneocistostomy. During follow-up, ureteral endometriosis recurred in 2 patients who consequently underwent ureteroneocystostomy. Most patients expressed high satisfaction rate throughout the whole follow-up period. CONCLUSION: laparoscopic ureterolysis is effective and well tolerated in most cases of ureteral endometriosis. Ureteroneocystostomy is a better strategy for patients with extended (more than 4 cm) ureteral involvement or with severe stenosis with or without hydronephrosis.