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.

Factors associated with adherence to BRCA1/2 mutation testing after oncogenetic counseling in long-surviving patients with a previous diagnosis of breast or ovarian cancer.

BRCA1/2 mutations account for 5 to 10% of breast and 15% of ovarian cancers. Various guidelines on BRCA1/2 genetic counseling and testing have been issued, and the criteria have evolved over the years. Oncogenetic counseling aims to inform patients about the possibility and implications of undergoing predictive testing and risk management programs. We analyzed a cohort of 50 subjects with a previous personal history of breast or ovarian cancer who had not been tested for BRCA1/2 mutations at the time of diagnosis but were found eligible according to the most recent guidelines. All patients were offered pre-test oncogenetic counseling and BRCA1/2 genetic testing. The mean time from cancer diagnosis to genetic counseling was over 10 years. We analyzed socio-demographic and psychological parameters associated with the decision to undergo BRCA1/2 genetic testing or the reasons behind the withdrawal. Thirty-nine patients underwent BRCA1/2 genetic testing. Patients who accept the genetic test communicate more easily with family members than those who refuse. Factors associated with test refusal are having a long-term partner and having a negative perception of life. There is a trend, although not statistically significant, toward younger age at cancer diagnosis, more likely to participate in cancer screening programs (71.8% vs. 45.5%), and more likely to have daughters (63.3% vs. 37.5%) in the group that accepted the test. The offer of BRCA testing was well accepted by our study population, despite the many years since the cancer diagnosis. With the perspective of further broadening the access criteria to genetic testing, it is important to understand how to best approach pre-test counseling in long-surviving patients with a previous diagnosis of cancer.

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.

Retrospective study of histopathological and prognostic characteristics of primary fallopian tube carcinomas: twenty-year experience (SOCRATE).

OBJECTIVE: Primary fallopian tube carcinoma represents a rare entity, accounting for about 0.75%-1.2% of all gynecological malignancies. The rationale of our study is to describe the prognosis of primary fallopian tube carcinoma. METHODS: We retrospectively identified patients with FIGO stage I-IV, all histology types and grading primary fallopian tube carcinoma treated in three major oncological centers between January 2000 and March 2020. Exclusion criteria were bulky tubo-ovarian carcinomas, isolated serous tubal intraepithelial carcinoma or neoadjuvant chemotherapy. RESULTS: A total of 61 patients were included. The vast majority of primary fallopian tube carcinomas were serous (96.7%) and poorly differentiated (96.7%) and arose from the fimbriated end of the tube (88.5%). Larger tumor size correlated with higher probability of correct preoperative differential diagnosis of primary fallopian tube carcinoma (p=0.003). Up to 82.4% of patients with small tumors (≤15 mm) presented with high FIGO stage (≥IIA). The most common site of metastasis was pelvic peritoneum (18.8%) and among 59% of patients who underwent lymphadenectomy smaller tumors had higher rate of nodal metastasis (42.9%≤10 mm vs 27.3%>50 mm). After 46.0 months of mean follow-up there were 27 recurrences (48.2%). The most common site of relapse was diffuse peritoneal spread (18.5%). The 5-year disease-free survival was 45.2% and 5-year overall survival was 75.5%. Of note, 42.9% of patients with stage IVB survived >36 months. CONCLUSION: Primary fallopian tube carcinoma is a biologically distinct tumor from primary epithelial ovarian carcinoma and it is mostly located in the fimbriated end of the tube. In addition, it is characterized by a high rate of retroperitoneal dissemination even at apparently an early stage and its size does not correlate with FIGO stage at presentation.

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.

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.

Metastatic Bilateral Strumal Carcinoid: A Case Report and Review of the Literature.

Primary ovarian carcinoids are very rare tumors that belong to the germ cell family of ovarian malignancies. They account for less than 1% of all carcinoid tumors and for less than 0.1% of all ovarian neoplasms. Recurrences are even rarer, with only few cases reported in the literature. Strumal carcinoid has recently been recognized as an extremely rare distinct entity. We report on a patient with bilateral mature cystic teratoma with millimetric foci of ovarian strumal carcinoid who developed lymph node para aortic metastasis after 30 years from primary diagnosis. Our case is thus far the second report of a metastatic strumal carcinoid and the first one in which strumal carcinoid occurred bilaterally and was also metastatic.

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.

Treatment of climacteric symptoms in survivors of gynaecological cancer.

Different treatments (surgery, radiotherapy, chemotherapy) for gynaecological cancers may cause ovarian failure or increase menopausal symptoms. There is a widespread reluctance among physicians to prescribe hormone replacement therapy (HRT) to the survivors of gynaecological cancer. This review analyses the use of HRT and of alternative therapies in such women. Squamous cervical cancer is not estrogen dependent and thus HRT is not contraindicated. While a cautious approach to hormone-dependent cancer is warranted, for women treated for non-hormone-related tumours alternative treatments for menopausal symptoms should be given due consideration, as any reluctance to prescribe HRT for them has neither a biological nor a clinical basis. In studies of HRT for survivors of endometrial and ovarian cancer, for instance, no evidence of increased risk was found, although no definitive conclusions can yet be formulated. The positive effect of HRT on quality of life seems to outweigh the unfounded suspicion of an increased risk of recurrence of non-hormone-related tumours. Effective non-hormonal alternatives for vasomotor symptoms are selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitors.