Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

OBJECTIVES: Nodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition. Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. METHODS: Clinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. RESULTS: Fifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case. Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT. Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. CONCLUSIONS: In this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

Ultrasonographic diagnosis of adnexal masses: interobserver agreement in the interpretation of videos, using IOTA terminology.

OBJECTIVES: Aim of this study is to estimate interobserver agreement in classifying adnexal tumors using IOTA terms, simple rules and subjective assessment. In addition, we related observers' accuracy with their experience in gynecological ultrasonography and the year of IOTA certification. METHODS: Eleven observers with three different levels of experience evaluated videoclips of 70 adnexal masses, defining tumor type according to IOTA terms and definitions, classifying the mass using IOTA Simple rules and Subjective assessment as well as providing Color Score evaluation. Sensitivity, specificity and area under the ROC curve were calculated and the year of IOTA certification was related with operators' accuracy through Pearson correlation coefficient. Interobserver agreement was estimated calculating percentage of agreement, Fleiss kappa and Cohen's kappa. RESULTS: We found a positive correlation between the year of IOTA certification and operators' accuracy (Pearson coefficient 0.694), especially among the observers with the least experience, the residents (p = 0.003). For tumor type classification, identification of papillary projections and classification of tumors using subjective assessment, agreement among all observers was moderate (Fleiss kappa 0.455, 0.552, and 0.476, respectively) and increased with the years of experience. Agreement in the application of Simple Rules was moderate in all examiners with IOTA certification, with Fleiss kappa in the range of (0.403, 0.498). For Color Score assignment interobserver agreement among all observers was fair (Cohen's kappa 0.380). CONCLUSIONS: Even among expert examiners, the results of adnexal lesion assessment can be inconsistent. Experience impacts on accuracy and agreement in subjective assessment, while the application of Simple Rules can mitigate the role of experience in interobserver agreement. The knowledge of IOTA models among residents seams to improve their diagnostic accuracy, showing the benefits of IOTA terminology for in training sonographers.

Straining to void at preoperative urodynamic study as a risk factor for prolapse recurrence after surgery.

OBJECTIVES: Straining to void is the need to make a muscular effort in order to initiate, maintain or improve the urinary stream, through an increase in abdominal pressure. This pattern of bladder emptying is frequently observed in women with pelvic organ prolapse causing urinary obstruction, to overcome the increased resistance to urine flow. However, frequent increases in abdominal pressure are a risk factor for developing pelvic organ prolapse, and might play a role in its recurrence after surgery. The aim of this study was to investigate the role of straining identified at urodynamic study in prolapse recurrence after surgical repair. STUDY DESIGN: This was a retrospective study on women submitted to prolapse repair by vaginal hysterectomy with modified McCall culdoplasty and anterior colporraphy. All patients underwent a preoperative urodynamic evaluation including a pressure-flow study performed after prolapse reduction by means of a vaginal pessary; straining was defined by a simultaneous and similar increase in intravesical and abdominal pressures of at least 10 cmH2O over the baseline during bladder emptying, corresponding to intermittent peaks of urine flow. Patients were divided into two groups according to the presence or absence of straining, and they were compared for surgical results at 12 months and for the rate of anterior or central recurrence over time. RESULTS: Women with straining (n = 16), compared to women with normal voiding (n = 43), showed a higher risk of anterior recurrence over time at Kaplan-Meier curves, for both stage II (p = 0.02) and stage III prolapse (p = 0.02). No difference was seen for central recurrence during the follow up period. POP-Q staging at 12 months was similar for the two groups, except for the location of the Aa point which was significantly better for women without straining (-1.6 ± 0.1 cm vs -0.8 ± 0.3 cm, p = 0.03). CONCLUSIONS: Straining to void identified in preoperative urodynamic study seems to increase the risk of anterior recurrence after surgical repair of pelvic organ prolapse.

Clinical, Sonographic, and Hysteroscopic Features of Endometrial Carcinoma Diagnosed after Hysterectomy in Patients with a Preoperative Diagnosis of Atypical Hyperplasia: A Single-Center Retrospective Study.

BACKGROUND: atypical endometrial hyperplasia (AEH) is a precancerous condition implying a high risk of concurrent endometrial cancer (EC), which might be occult and only diagnosed at postoperative histopathological examination after hysterectomy. Our study aimed to investigate potential differences in preoperative clinical, sonographic, and hysteroscopic characteristics in patients with AEH and postoperative diagnosis of EC. METHODS: a retrospective single-center study was carried out on a case series of 80 women with AEH undergoing diagnostic workup, including ultrasonography and hysteroscopy, with subsequent hysterectomy. Women with AEH confirmed at the histopathological examination were compared with patients with a postoperative diagnosis of EC. RESULTS: in our population, EC was diagnosed in 53 women, whereas the preoperative diagnosis of AEH was confirmed in 27 cases. At ultrasonography, women with occult EC showed greater endometrial thickness (20.3 mm vs. 10.3 mm, p 0.001) and size of the endocavitary lesion (maximum diameter 25.2 mm vs. 10.6 mm, p 0.001), and a higher prevalence of irregular endometrial-myometrial junction (40.5% vs. 6.7%, p 0.022) and endouterine vascularization at color Doppler (64.2% vs. 34.6%, p 0.017). At hysteroscopy, patients with occult EC showed a higher prevalence of necrosis (44.2% vs. 4.2%, p 0.001) and atypical vessels (70.6% vs. 33.3%, p 0.003), whereas true AEH mainly presented as a protruding intracavitary lesion (77.8% vs. 50.9%, p 0.029). In EC, subjective assessment by the operator was more frequently indicative of cancer (80.0% vs. 12.5%). No difference was found for clinical variables. CONCLUSIONS: occult EC in AEH may exhibit some differences in ultrasonographic and hysteroscopic patterns of presentation compared with real AEH, which could prompt a more significant suspect for the possible presence of concurrent EC at preoperative diagnostic workup.

End-to-end versus side-to-end anastomosis after bowel resection for deep infiltrating endometriosis: A retrospective study.

OBJECTIVE: Deep infiltrating endometriosis(DIE) of the bowel may require segmental bowel resection. The subsequent reconstruction can be performed through an end-to-end(E-E) or a side-to-end (S-E)anastomosis, the latter being used in low resection due to the reduced risk of anastomotic leakage. This study aims at comparing those two anastomosis techniques in women submitted to bowel resection for DIE, in terms of post-operative morbidity and functional outcomes. METHODS: This was a single-center retrospective study on women undergoing laparoscopic rectal resection for deep infiltrating endometriosis with subsequent E-E or S-E anastomosis performed according to the level of rectal resection. The two groups were compared for postoperative complication rates and functional outcomes by means of validated questionnaires. RESULTS: The study population included 30 patients undergoing a S-E anastomosis (group A), and 49 cases undergoing an E-E anastomosis (group B). No differences were found between the two groups in terms of length of hospital stay, anastomotic leakages, protective ileostomies and short-term complications. At follow up no differences were found between the two groups in terms of bowel function and pain symptoms. CONCLUSIONS: A S-E anastomosis in case of low rectal resections for DIE presents similar complication rates and functional outcomes compared with an E-E anastomosis.

Fixation of uterosacral ligaments to anterior vaginal wall during modified McCall culdoplasty after vaginal hysterectomy.

OBJECTIVES: McCall culdoplasty is a commonly performed procedure for pelvic organ prolapse surgical repair; despite its good efficacy, however, anterior prolapse recurrence frequently occurs. The aim of our study was to verify whether fixation of utero-sacral ligaments (USLs) to anterior vaginal wall during a modified McCall culdoplasty (MMC) could reduce the rate of anterior recurrence of prolapse. STUDY DESIGN: This was a retrospective study on women submitted to MMC after vaginal hysterectomy and anterior colporraphy for prolapse repair. Patients undergoing concurrent anterior fixation of USLs (AF) were compared to cases treated with MMC alone, evaluating potential differences in anatomic result of prolapse repair at 12 months, rate of anterior recurrence over time, operative data and post-operative morbidity. RESULTS: Women undergoing MMC with AF (n = 45), compared with patients treated with MMC alone (n = 77), showed better results in terms of anatomic support in the anterior compartment at 12 months, assessed by means of POP-Q system parameters Aa (-1.8 cm vs -1.2 cm, p 0.0025) and Ba (-2.0 cm vs -1.3 cm, p 0.00015), and a lower rate of anterior recurrence (11.1% vs 29.9%, p 0.025); the other parameters of prolapse anatomic staging did not differ significantly, nor did operative data or post-operative morbidity. Follow up confirmed a longer disease-free survival over time for women treated with MMC with AF (p 0.028) CONCLUSIONS: Fixation of USLs to anterior vaginal wall at time of post-hysterectomy MMC appears to improve anatomic outcomes of the procedure reducing the risk of anterior prolapse, without implying a reduced safety, nor a greater surgical complexity.

Could a 2D/3D US based model be helpful in the assessment of myometrial invasion at time of intraoperative frozen section? A pilot study.

BACKGROUND: The assessment of myometrial invasion is a pivotal step in the preoperative staging of endometrial cancer. Intraoperative frozen section (FS) represents a reliable tool in directing surgeon's choices. Preoperative transvaginal ultrasound (US) showed high accuracy in evaluating myometrial invasion. This study aimed to understand if the application of a standardized ultrasonographic protocol for the pre-operative evaluation of myometrial invasion can help pathologists in improving the accuracy of FS. Furthermore, the agreement between US and FS in the assessment of myometrial invasion was assessed. METHODS: Sixty-six patients who underwent surgery for endometrial cancer were analyzed. Preoperative 2D/3D ultrasound was performed in all the patients. Myometrial invasion was estimated by subjective assessment and objective measurement techniques. Data from US were reported to pathologists through a prefilled form with depth and site of the maximum myometrial invasion. Diagnostic performance of US and FS were compared having the definitive histological examination as the gold standard. RESULTS: Influenced by the information given by our 3D US-model, FS showed a 90% sensitivity and a 93% specificity, with a 93% PPV and an 89% NPV. The agreement with histology was strong (K=0.824). Myometrial invasion was missed at the level of the isthmus by FS just in one case. Subjective assessment was confirmed as the most reliable ultrasonographic technique in assessing myometrial invasion, with 90% sensitivity, 78% specificity, 80% PPV and 89% NPV. The agreement with histology was substantial (K=0.68). CONCLUSIONS: The application of a preoperative 2D/3D US assessment would seem to help pathologists in detecting myometrial invasion in difficult areas of the uterus such as the isthmus, reducing downstaging and overtreatment.

Estradiol/nomegestrol acetate as a first-line and rescue therapy for the treatment of ovarian and deep infiltrating endometriosis.

PURPOSE: Estradiol valerate/nomegestrol acetate (E2V/NOMAC) is a new combined oral contraceptive with a good tolerability profile and low drop-out rates, which was shown to improve menstrual-related symptoms. This study aims to evaluate its effectiveness in the control of symptoms and progression of disease in women with ovarian endomestriomas and deep infiltrating endometriosis (DIE). METHODS: This was a retrospective cohort study on 39 women with pelvic endometriosis treated with E2V/NOMAC. We assessed for each patient, at the beginning of treatment and after 6 months, the painful symptoms, through a global VAS (Visual Analogue Scale) index and the size of the greatest ovarian and/or deep infiltrating endometriotic lesions. RESULTS: After 6 months of treatment, a significant reduction was observed for the global VAS score for pain symptoms and for the mean size of ovarian endometriomas, whereas DIE lesions did not present significant changes in mean size. CONCLUSIONS: E2/NOMAC was effective in reducing pain symptoms associated with pelvic endometriosis and the size of ovarian endometriomas, whereas DIE lesions remained stable. This therapy could provide good results in the control of symptoms and disease progression in women with pelvic endometriosis.

Fractional CO2 vaginal laser for the genitourinary syndrome of menopause in breast cancer survivors.

Adjuvant chemotherapy and endocrine therapy can induce early iatrogenic menopause or worsen pre-existing menopausal symptoms in breast cancer survivors (BCS). The second most frequent menopausal symptom after hot flushes is the genitourinary syndrome (GSM). Since hormone replacement therapy is contraindicated in BCS, vaginal laser might represent a new nonhormonal option for GSM. This study aims at evaluating the effectiveness of the fractional CO2 vaginal laser for GSM in BCS compared with healthy women. This is a retrospective study on 135 postmenopausal women (45 BCS and 90 healthy women) who underwent fractional CO2 laser for GSM. Objective (VHI and VVHI) and subjective outcomes (VAS for dyspareunia and vaginal dryness and a pain questionnaire) were evaluated at baseline visit and at every follow-up visit. Subjective and objective parameters improved significantly in both groups after laser therapy. The improvement was progressive and long-lasting up to 12 months after the end of the treatment. No severe adverse events were observed during the treatment. Fractional CO2 vaginal laser induces a significant and long-lasting improvement on GSM symptoms in BCS. However, this improvement is slower than in healthy women undergoing the same treatment. Laser therapy turns out to be safe and well-tolerated.

Sonographic features of endometriosis infiltrating the lateral parametrium.

OBJECTIVE: Lateral parametrium endometriosis (LPE) can be associated with infiltration of ureters and hypogastric plexus, causing severe painful symptoms and functional impairment, and requiring complex and extensive surgery. The aim of this study was to evaluate the presentation of LPE lesions at transvaginal ultrasound, identifying sonographic features for disease recognition and mapping. METHODS: This was a retrospective case-series of women with sonographic suspect of LPE confirmed at surgical exploration. We carried out a descriptive analysis of the ultrasound patterns of presentation and compared the features of the lesions according to their location cranially or caudally to the uterine artery. RESULTS: Our population included 23 women, with a total of 26 parametrial lesions: all of them were hypoechoic, with absence of vascularization. Lesions lying above the uterine artery presented more frequently as ill-defined nodules (78.6 %, p < 0.01) and were associated with ipsilateral reduced or absent ovarian mobility (92.9 %, p < 0.01); the ones located below the uterine artery appeared more frequently as fan-shaped lesions with retraction of the surrounding tissues (83.3 %). Ureteral involvement was observed at surgery in 43.5 % of cases. In all patients, deep infiltrating endometriosis of the posterior compartment was observed: the utero-sacral ligaments were the most common location affected concurrently. CONCLUSIONS: LPE may present at transvaginal sonography as hypoechoic, not vascularized lesions, most frequently with a nodular or with a fan-shaped appearance, respectively cranially or caudally to the uterine artery. Reduced ovarian sliding and ureteral involvement are commonly associated.

Potential effectiveness of Ospemifene on Detrusor Overactivity in patients with vaginal atrophy.

OBJECTIVES: To report the effects on the urinary function of ospemifene prescribed for vulvovaginal atrophy (VVA) in patients with overactive bladder (OAB) symptoms refractory to the first line of pharmacologic treatment with antimuscarinic or ß3-agonists drugs. We also try to identify any predictors of response to the ospemifene treatment. STUDY DESIGN: Twenty-five patients with OAB confirmed by detrusor overactivity at urodynamics, refractory to first-line therapy for OAB, were enrolled for the study. All of them received ospemifene 60 mg for 12 weeks because of concomitant VVA. We performed a clinical examination, a 3-day voiding diary, ultrasound examination of bladder wall thickness (BWT), and evaluation by Visual Analogic Scale (VAS) of vaginal dryness at baseline and at 12 weeks. We evaluated urinary symptoms and their impact on the quality of life with UDI-6 SF and OAB-Q (Qol, sf) questionnaires. RESULTS: After 12 weeks of treatment, we observed a significant reduction in the daily (24 h) numbers of episodes of micturition, of nocturia, of urgency and of incontinence. We also found a significant reduction in BWT and vaginal dryness, together with an improvement of OAB-Q and UDI6 SF scores. Among patients who subjectively benefited from the treatment, we found a baseline lower prevalence of constipation and a higher degree of vaginal dryness. CONCLUSIONS: Ospemifene might be a useful option for postmenopausal women with VVA and OAB symptoms, refractory to the first line of treatment with ß3-agonists or antimuscarinic drugs, before considering invasive options.

Concomitant stress urinary incontinence and pelvic organ prolapse surgery: Opportunity or overtreatment?

OBJECTIVES: The association between pelvic organ prolapse (POP) and stress urinary incontinence (SUI) is very common. When POP surgery is indicated and the patient has concomitant SUI, there are two treatment strategies: the one-step strategy (concomitant correction of POP and SUI) and the two-step strategy (correction of POP with subsequent evaluation of SUI). Guidelines from the International Continence Society and International Consultation on Incontinence recommend that a urodynamic assessment (UA) should be performed before surgery as this can reveal the presence of urodynamic SUI, but the role of UA is the subject of debate as it does not seem to improve treatment decisions. The aim of this study was to identify the presence of pre-operative urodynamic parameters that were predictive of POSUI, and to identify patients who could benefit from concomitant correction of SUI during POP surgery STUDY DESIGN: A retrospective evaluation was undertaken of 155 patients with at least second-degree POP who underwent POP surgery after UA between 2009 and 2016 in an Italian gynaecology and obstetrics department. Of these, 61 patients were clinically incontinent before surgery and 94 patients were clinically continent. After UA, patients were stratified using a maximum urethral closure pressure (MUCP) cut-off of 50 cmH2O; the risk of POSUI was calculated using this value. RESULTS: POP surgery alone resolved SUI in 60 % of the 61 clinically incontinent patients; only 30 % of these patients had urodynamic SUI and >50 % did not have POSUI. Thirty-six percent of the 94 continent patients had occult SUI on UA and 16 % developed de-novo POSUI. Seventy-five percent of all patients with occult SUI did not develop de-novo SUI. MUCP was lower in patients with POSUI than in patients without POSUI (p=0.013). The probability of POSUI was higher in patients with MUCP ≤50 cmH2O. The number needed to treat (NNT) to prevent one case of POSUI in these patients was 2, compared with an NNT of 4 in the continent group. Eight percent of patients underwent further surgery for SUI. CONCLUSIONS: Clinically incontinent patients with MUCP ≤50 cmH2O will gain the greatest benefit from concomitant POP and SUI surgery. However, concomitant surgery has more severe adverse events. Given that 62.3 % of patients resolved SUI after POP surgery alone, it is important not to overtreat these women. Clinical pre-operative SUI is the best indicator of POSUI and was found to increase the risk of POSUI (odds ratio 3.2, 95 % confidence interval 1.5-6.8; p=0.003). Despite the small sample size, the two-step strategy appears to result in lower use of mid-urethral slings and a clear reduction in complications. It is important not to focus on the diagnosis of urodynamic SUI in continent patients but to evaluate MUCP carefully.

Predictors of response after a second attempt of pharmacological labor induction: a retrospective study.

PURPOSE: The aim of our study was to assess the outcomes of a prolonged induction carried out with a second sequential cycle of pharmacological stimulation after unsatisfactory response to a first attempt, and to highlight variables correlated with higher response rates. METHODS: A retrospective study was carried out on 157 women who underwent a two-step labor induction by vaginal prostaglandins followed by a second cycle of prostaglandins or intravenous oxytocin. Outcomes assessed were mode of delivery and maternal and neonatal morbidity. Main variables of pregnancy and delivery were collected to identify factors predicting the mode of delivery. RESULTS: Among 157 patients, 63 (40.1%) achieved a vaginal delivery, whereas 94 (59.9%) underwent Cesarean section, 9 women (5.7%) had postpartum hemorrhage; in 2 cases (1.3%), an Apgar score < 7 at 5 min from birth was reported. Higher risk of Cesarean section was observed with advanced maternal age (OR 1.13 for additional year, CI 1.04-1.22) and nulliparity (OR 8.84, CI 2.69-29.06), whereas the response rates were better in carriers of group B streptococcus colonization (OR 0.38, CI 0.17-0.84) and in women with favorable cervical status after the first stimulation (OR 0.81 for additional point of Bishop score, CI 0.70-0.94). CONCLUSION: Labor induction with two cycles of pharmacological stimulation is a procedure with fairly good success rates and a low risk of maternal and neonatal complications. Factors predicting its success encompass younger age, parity, a positive recto-vaginal swab for group B streptococcus and a favorable cervix following the first cycle of stimulation.

Transvaginal high uterosacral ligament suspension: An alternative to McCall culdoplasty in the treatment of pelvic organ prolapse.

OBJECTIVES: Defects in female pelvic organ support are highly prevalent. Uterosacral ligament suspension at the time of primary prolapse repair (McCall culdoplasty) is a well-established surgical option to prevent prolapse recurrences. Recently Shull's high uterosacral ligament suspension technique has gained increasing popularity among Uro-Gynaecologists. A study carried out in 2017 by Spelzini et al. compared these two techniques, showing proper safety and efficacy in the treatment of prolapse, with no statistically significant differences as to operative time, complication rate, anatomical, functional and subjective outcomes [1]. Our study aims at comparing the effectiveness, complication rate, recurrence rate, quality of life and functional result of the two techniques. STUDY DESIGN: This is a retrospective study carried out on 224 patients who underwent vaginal cuff suspension for pelvic organ prolapse. Cases were extracted from hospital medical records of all women managed with surgical prolapse repair at our Gynaecology and Obstetrics department between January 2013 and February 2017. Shull suspension (group A) or McCall culdoplasty (group B) were performed according to surgeon's familiarity with the two suspension techniques. RESULTS: A total of 224 patients (69 in group A and 155 in group B) underwent surgical cuff suspension. Median operating time was 88 min for both techniques and ureteral injuries were very rare in both group A and B (1 and 0 respectively). In the evaluation of postoperative questionnaires, no statistically significant differences were found, except for "Urinary Impact Questionnaire" (UIQ), which showed significantly less urinary subjective symptoms in group A. Median follow up was 13 months in group A and 15 months in group B. Post-operative Pop-Q items analysis revealed only a higher Aa point in group A at 12 months follow up visit. Objective vaginal cuff recurrence was observed in 1 patient (1,4%) in group A and 4 patients in group B (2,6%) with no statistically significant difference between the two groups. CONCLUSIONS: Both uterosacral ligament suspension procedures are safe and highly effective. There were no statistically significant differences concerning surgical data, complication rates, and the majority of anatomical, functional and subjective outcomes between Shull suspension and McCall culdoplasty.