M. Signorelli

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

BACKGROUNDnThe present study is aimed to identify genetic pathways correlated with chemoresistance in epithelial ovarian cancer (EOC).nnnMETHODSnWe 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.nnnRESULTSnIn 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.nnnCONCLUSIONnSome genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms.

Myometrial invasion in endometrial cancer: diagnostic performance of diffusion-weighted MR imaging at 1.5-T

ObjectiveTo determine the diagnostic accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging in the preoperative assessment of myometrial invasion by endometrial cancer.Materials and methodsIn this prospective study, 47 patients with histologically confirmed endometrial cancer underwent preoperative MR imaging and total hysterectomy. The MR protocol included spin-echo multishot T2-weighted, dynamic T1-weighted and DW images acquired with b-values of 0 and 500xa0s/mm2. Myometrial tumour spread was classified as superficial (<50%) or deep (≥50% myometrial thickness). Postoperative histopathological findings served as a reference standard. Indices of diagnostic performance were assessed for each sequence.ResultsAt histopathological examination, superficial myometrial invasion was found in 34 patients and deep myometrial invasion in 13. In the assessment of tumour invasion, sensitivity, specificity, positive and negative predictive values of T2-weighted images were 92.3%, 76.5%, 60.0% and 96.3%, respectively. The corresponding values for dynamic images were 69.2%, 61.8%, 40.9% and 84.0%, and for DW images 84.6%, 70.6%, 52.4% and 92.3%. T2-weighted and DW imaging proved to be the most accurate techniques for tumour spread determination.ConclusionDW imaging proved to be accurate in assessing myometrial invasion, and it could replace dynamic imaging as an adjunct to routine T2-weighted imaging for preoperative evaluation of endometrial cancer.

A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study

BACKGROUNDnThe efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control.nnnPATIENTS AND METHODSnIn all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) + cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal [no residual tumor (complete response) or residual disease with < or = 3 mm stromal invasion (PR1)] or suboptimal response.nnnRESULTSnPatient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III-IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3-4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP.nnnCONCLUSIONnTP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.

The use of TachoSil for the prevention of postoperative complications after groin dissection in cases of gynecologic malignancy

To evaluate the effect of TachoSil in preventing postoperative complications after groin dissection performed for primary or recurrent gynecologic malignancy.

Modified radical hysterectomy versus extrafascial hysterectomy in the treatment of stage I endometrial cancer: results from the ILIADE randomized study

BackgroundFive percent to 20% of stage I endometrial cancer patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy develop vaginal and pelvic recurrences. Adjuvant radiotherapy can improve locoregional control but not survival. This randomized trial aimed to determine whether a modified radical (Piver–Rutledge class II) hysterectomy can improve survival and locoregional control compared to the standard extrafascial (Piver–Rutledge class I) hysterectomy.MethodsEligible patients (nxa0=xa0520) with stage I endometrial cancer were randomized to class I or class II hysterectomy. Primary endpoint was overall survival.ResultsThe median length of parametria and vagina removed were 15 and 5 vs. 20xa0mm and 15xa0mm for class I and class II hysterectomy, respectively (Pxa0>xa00.001). Operating time and blood loss were statistically significantly higher for class II hysterectomy. At a median follow-up of 70xa0months, 51 patients had died. Five-year disease-free and overall survival were similar between arms (87.7 and 88.9% in the class I arm and 89.7 and 92.2% in the class II arm, respectively). The unadjusted hazard ratios for recurrence was 0.91 (95% confidence interval, 0.55–1.51, Pxa0=xa00.72), and the hazard ratio for death was 0.77 (95% confidence interval, 0.44–1.33, Pxa0=xa00.35).ConclusionsClass II hysterectomy did not improve locoregional control and survival compared to class I hysterectomy, but when an adequate vaginal cuff transection is not feasible with class I hysterectomy, a modified radical hysterectomy allows to obtain an optimal vaginal and pelvic control of disease with a minimal increase in surgical morbidity.

Systematic lymphadenectomy in ovarian cancer at second-look surgery: A randomised clinical trial

Background:The role of systematic aortic and pelvic lymphadenectomy (SAPL) at second-look surgery in early stage or optimally debulked advanced ovarian cancer is unclear and never addressed by randomised studies.Methods:From January 1991 through May 2001, 308 patients with the International Federation of Gynaecology and Obstetrics stage IA–IV epithelial ovarian carcinoma were randomly assigned to undergo SAPL (n=158) or resection of bulky nodes only (n=150). Primary end point was overall survival (OS).Results:The median operating time, blood loss, percentage of patients requiring blood transfusions and hospital stay were higher in the SAPL than in the control arm (P<0.001). The median number of resected nodes and the percentage of women with nodal metastases were higher in the SAPL arm as well (44% vs 8%, P<0.001 and 24.2% vs 13.3%, P:0.02). After a median follow-up of 111 months, 171 events (i.e., recurrences or deaths) were observed, and 124 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for progression and death were not statistically different (hazard ratio (HR) for progression=1.18, 95% confidence interval (CI)=0.87–1.59; P=0.29; 5-year progression-free survival (PFS)=40.9% and 53.8%; HR for death=1.04, 95% CI=0.733–1.49; P=0.81; 5-year OS=63.5% and 67.4%, in the SAPL and in the control arm, respectively).Conclusion:SAPL in second-look surgery for advanced ovarian cancer did not improve PFS and OS.

Tunneled modified lotus petal flap for surgical reconstruction of severe introital stenosis after radical vulvectomy

INTRODUCTIONnWe presented the anatomical, functional and aesthetic results achieved with lotus petal flap in case of introital stenosis as a results of inadequate primary plastic reconstruction. We discussed the potential advantages of lotus petal flap compared to others vulvar reconstructive techniques.nnnPRESENTATION OF CASEnWe report a case of a 44-years old woman presenting a severe introital stenosis following radical surgery for vulvar cancer. She could not have a normal sexual activity life because the narrow scarred introitus resulting after primary closure of a large vulvar defect. The patient comes to our attention after three years from primary surgery. Once the scar was removed we performed a vulvoperineal reconstruction with bilateral tunneled lotus petal flaps.nnnDISCUSSIONnLotus petal flap is a safe, easy and quick technique, has a good functional and cosmetic results in this young woman, and represents an optimal alternative solution for plastic reconstruction in case of severe introital stenosis after primary closure of large vulvoperineal defect.nnnCONCLUSIONnTunneled lotus petal flaps represents a feasible, attractive and versatile surgical reconstructive technique that can be easily performed after surgical treatment of vulvoperineal neoplasms.

Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study

OBJECTIVESnTo evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction.nnnMETHODSnA multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period.nnnRESULTSnA total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction.nnnCONCLUSIONSnThis is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

P11.05: Subjective ultrasound assessment and the ADNEX model to differentiate between benign and malignant ovarian tumours

Methods: All the patients found in our Clinic database affected by ovarian/tubaric carcinoma, who carried a mutation on BRCA1 or BRCA2 genes, and whom the ultrasonographic images were available of, have been included in our study. Results: 26 patients have been recruited in our study. In 100% of the cases histological report revealed that the patients had a high grade (G3) istotype of carcinoma. Nineteen out of twenty-six lesions (73%) were solid and six out of twenty-six lesions (23%) were multilocular-solid. In one patient out of twenty-six (4%) we found a unilocular-solid lesion. The echotexture of the lesions was heterogeneous in twenty-three out of twenty-six patients (88%) and lesions appeared to have irregular margins in twenty-two out of twenty-six of the cases (85%); lesions appeared to be hypoechoic in twenty-five out of twenty-six cases (96%). Vascularisation of the lesions was discrete to high (colour-score 3-4) in twenty-five out of twenty-six patients (96%). Twenty-three out of twenty-six patients (88%) did not have ascites; only three out of twenty-six patients (12%) presented a huge ascites at the ultrasonographic study. Conclusions: In conclusion, in our study ovarian cancer appeared to be a solid or multilocular-solid lesion and, moreover, we found ascites in only three patients (12%), data which has been confirmed by the surgery, even though in 73% of the cases cancer was found at FIGO stage IIIC or IV.