Rodolfo Milani

Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer.

BACKGROUND Stage Ib and IIa cervical carcinoma can be cured by radical surgery or radiotherapy. These two procedures are equally effective, but differ in associated morbidity and type of complications. In this prospective randomised trial of radiotherapy versus surgery, our aim was to assess the 5-year survival and the rate and pattern of complications and recurrences associated with each treatment. METHODS Between September, 1986, and December, 1991, 469 women with newly diagnosed stage Ib and IIa cervical carcinoma were referred to our institute. 343 eligible patients were randomised: 172 to surgery and 171 to radical radiotherapy. Adjuvant radiotherapy was delivered after surgery for women with surgical stage pT2b or greater, less than 3 mm of safe cervical stroma, cut-through, or positive nodes. The primary outcome measures were 5-year survival and the rate of complications. The analysis of survival and recurrence was by intention to treat and analysis of complications was by treatment delivered. FINDINGS 170 patients in the surgery group and 167 in the radiotherapy group were included in the intention-to-treat analysis; scheduled treatment was delivered to 169 and 158 women, respectively, 62 of 114 women with cervical diameters of 4 cm or smaller and 46 of 55 with diameters larger than 4 cm received adjuvant therapy. After a median follow-up of 87 (range 57-120) months, 5-year overall and disease-free survival were identical in the surgery and radiotherapy groups (83% and 74%, respectively, for both groups), 86 women developed recurrent disease: 42 (25%) in the surgery group and 44 (26%) in the radiotherapy group. Significant factors for survival in univariate and multivariate analyses were: cervical diameter, positive lymphangiography, and adeno-carcinomatous histotype. 48 (28%) surgery-group patients had severe morbidity compared with 19 (12%) radiotherapy-group patients (p = 0.0004). INTERPRETATION There is no treatment of choice for early-stage cervical carcinoma in terms of overall or disease-free survival. The combination of surgery and radiotherapy has the worst morbidity, especially urological complications. The optimum therapy for each patient should take account of clinical factors such as menopausal status, age, medical illness, histological type, and cervical diameter to yield the best cure with minimum complications.

Functional and anatomical outcome of anterior and posterior vaginal prolapse repair with prolene mesh

Objective  To evaluate the effects of prolene mesh on urinary, bowel and sexual function in prolapse surgery.

Class II versus Class III Radical Hysterectomy in Stage IB–IIA Cervical Cancer: A Prospective Randomized Study

OBJECTIVE The objective of this study was to determine the role of the extent of the radicality in the treatment of stage IB-IIA cervical carcinoma with respect to survival, pattern of relapse, and morbidity. METHODS Two-hundred forty-three patients with cervical carcinoma (FIGO stages IB and IIa) were enrolled in a prospective randomized study comparing two types of radical hysterectomy (Piver-Rutledge-Smith class II and class III) between April 1987 and December 1993, and 238 are evaluable. Disease-free survival, overall survival, pattern of recurrences, and morbidity were the endpoints of this study. RESULTS Mean operative time was significantly (P = 0. 05) shorter in the group of patients undergoing class II hysterectomy (135 min vs 180 min), whereas mean blood loss (530 ml vs 580 ml) and number of patients requiring transfusions (35% vs 43%) were similar in the two arms of treatment. Complications unrelated to the extent of the surgical dissection and mean postoperative stay were similar in the two arms of treatment. Late morbidity was significantly lower in patients in the class II arm (especially urologic morbidity, 13% vs 28%). Postoperative radiotherapy was administered to 64 patients (54%) in class II and to 65 patients (55%) in the class III arm. Recurrence rate (24% class II vs 26% class III) and number of patients dead of disease (18% class II vs 20% class III) were not significantly different in the two groups of treatment. Overall 5-year survival was 81 and 77% and disease-free survival was 75 and 73%, respectively. Multivariate analysis confirms that survival does not depend on the type of operation. CONCLUSIONS Class II and class III radical hysterectomies are equally effective in surgical treatment of cervical carcinoma, but the former is associated with a lesser degree of late complications.

Randomised comparison of Burch colposuspension versus anterior colporrhaphy in women with stress urinary incontinence and anterior vaginal wall prolapse

Objective To compare the Burch colposuspension and the anterior colporrhaphy in women with both stress urinary incontinence and advanced anterior vaginal wall prolapse (cystocele).

Effect of different gonadotrophin priming on IVM of oocytes from women with normal ovaries: a prospective randomized study

This study was designed to determine if the efficiency of in-vitro maturation (IVM) in women with normal ovaries can be improved by gonadotrophin administration. 400 women were randomly allocated in four groups: group A, non-primed cycles; group B, human chorionic gonadotrophin (HCG)-primed cycles; group C, FSH-primed cycles; and group D, FSH- plus HCG-primed cycles. There were significant differences in the IVM rate among the groups. In groups where HCG was used, the overall maturation rate was higher (57.9% in group B and 77.4% in group D; 48.4% in group A and 50.8% in group C) and the percentage of total available metaphase II-stage oocytes was higher (60.4% in group B and 82.1% in group D; 48.4% in group A and 50.8% in group C). The overall clinical pregnancy rate per transfer (CPR) was 18.3% and the implantation rate (IR) was 10.6%. There was a difference in CPR among the groups: group D (29.9%) versus group A (15.3%), P = 0.023; group D versus group B (7.6%), P < 0.0001; group D versus group C (17.3%), P = 0.046. The results of this study are clearly in favour of FSH plus HCG priming. FSH priming and HCG priming alone showed no significant effects on clinical outcome.

Sacrospinous ligament fixation and modified McCall culdoplasty during vaginal hysterectomy for advanced uterovaginal prolapse

OBJECTIVE Our purpose was to compare anatomic and functional results of 2 procedures performed at vaginal hysterectomy for vaginal vault suspension in patients with advanced uterovaginal prolapse. STUDY DESIGN A retrospective case-control study was designed comparing 62 patients who underwent sacrospinous ligament fixation and 62 members of a matched control group who underwent modified McCall culdoplasty during vaginal hysterectomy and reconstructive pelvic surgery. The 62 pairs were matched for grade of uterine prolapse, age, parity, dystocia, menopause, body mass index, previous prolapse surgery, heavy work, constipation, and chronic cough. RESULTS Operative time and blood loss were significantly greater (P < .001) in the group with sacrospinous suspension. With a follow-up from 4 to 9 years, 17 (27%) patients receiving sacrospinous suspension had prolapse recurrence at any vaginal site compared with 9 (15%) patients receiving modified McCall culdoplasty (P = .14). Recurrent vault prolapse was recorded in 5 (8%) and 3 (5%) subjects, respectively (P = .72). Thirteen (21%) and 4 (6%) patients, respectively, had recurrent cystocele (matched odds ratio 4.1, 95% confidence interval 1.3 to 14.2, P = .04). No significative difference was observed in postoperative sexual function. CONCLUSION Sacrospinous ligament fixation is not recommended as a prophylactic measure at vaginal hysterectomy in patients with uterovaginal prolapse.

Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer

BACKGROUND The present study is aimed to identify genetic pathways correlated with chemoresistance in epithelial ovarian cancer (EOC). METHODS We compared the molecular profiles of 23 tumour biopsies of stage III-IV (training set) at primary surgery, before chemotherapy, to the profile from the same patients at second surgery, after several lines of platinum (Pt)-based chemotherapy when the tumours were resistant. In the hypothesis that identified markers were related to Pt-resistance and to prognosis, we validated this signature in 52 EOC taken at primary surgery (validation set) selected to be either very sensitive to the first line therapy, i.e. not relapsing before one year from the end of therapy, or resistant, i.e. relapsing within 6 months from the end of therapy. RESULTS In the training set, we identified a resistance signature indicative of the activation of epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)-beta pathway. We then validated this signature in 52 EOC taken at primary surgery (validation set). Some genes involved in EMT, such as BMP and activin membrane-bound inhibitor (BAMBI), and mir-141 resulted in association with overall or progression free survival. CONCLUSION Some genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms.

Conservative management of early-stage epithelial ovarian cancer: results of a large retrospective series

BACKGROUND To assess the long-term oncological outcome and the fertility of young women with early-stage epithelial ovarian cancer (ES/EOC) treated with fertility-sparing surgery (FSS). PATIENTS AND METHODS All patients treated with FSS for ES/EOC in two Italian centers were considered for this analysis. Univariate and multivariate analyses were used to test demographic characteristics and clinical features for the association with overall survival (OS), recurrence-free survival (RFS) and fertility. RESULTS From 1982 to 2010, 240 patients with malignant ES/EOC were treated with FSS in two tertiary centers in Italy. At a median follow-up of 9 years, 27 patients had relapsed (11%) and 11 (5%) had died of progressive disease. Multivariate analysis found only grade 3 negatively affected the prognosis of patients [hazard ratio (HR) for recurrence: 4.2, 95% confidence interval (CI): 1.5-11.7, P=0.0067; HR for death: 7.6, 95% CI: 2.0-29.3, P=0.0032]. Grade 3 was also significantly associated with extra-ovarian relapse (P=0.006). Of the 105 patients (45%) who tried to become pregnant, 84 (80%) were successful. CONCLUSIONS Conservative treatment can be proposed to all young patients when tumor is limited to the ovaries, as ovarian recurrences can always be managed successfully. Patients with G3 tumors are more likely to have distant recurrences and should be closely monitored.

Identification of risk factors for genital prolapse recurrence.

To assess the relationship between prolapse recurrence and some risk factors in a group of women submitted to reconstructive pelvic surgery.

The Burch colposuspension for women with and without detrusor overactivity

Objective To compare the results of the Burch colposuspension in women with stress urinary incontinence and detrusor overactivity with those obtained in women with stress incontinence and stable bladders. Additionally, to analyse the value of two detrusor instability indexes and of standard cystometric parameters in predicting the surgical outcome.