G. Zannoni

Reproductive effects of dietary soy in female Wistar rats

This study was designed to assess the effects of administration of dietary soy on reproductive function and fertility of female Wistar rats. Four groups, each of 20 females, were used. Control animals were fed a standard cereal-based diet for rats. Treated animals were fed a standard diet supplemented with 0.7%, 1.2% or 2.4% of a soy extract. Treatment started at weaning and continued until day 7 post-partum (day of sacrifice). Growth depression was seen in the 2.4% soy group. Vaginal opening occurred earlier in females receiving soy supplemented feed when compared with controls. Analysis of vaginal smears revealed that all animals were cycling, although an increase in the mean duration of each cycle was seen in the 2.4% soy group. Uterine effects were observed in high-dose females and included increases in weight, oedema, endothelial hyperplasia and leucocytic infiltration. Vaginal modifications (i.e. inflammation, hyperkeratosis and dyskeratosis) and alterations in the distribution of follicular size in the ovaries were also observed among treated animals. These data suggest that long-term exposure to high doses of phytoestrogens can produce significant agonistic actions in several oestrogen-dependent tissues and parameters, even though in this model no clear influence on reproductive processes was observed.

Localized cervical cancer (stage <IIB): accuracy of MR imaging in planning less extensive surgery

PurposeThis study was undertaken to determine the accuracy of magnetic resonance (MR) imaging in the preoperative staging of patients with clinically localised cervical cancer eligible for less extensive surgery.Materials and methodsFifty-three patients with biopsy-proven carcinoma of the uterine cervix and eligible for conservative surgery prospectively underwent MR imaging. Images were assessed for tumour site and size, infiltration of the cervical stroma, infiltration of vaginal fornices and relationship between the tumour and the internal os of the endocervical canal and the presence and dimensions of pelvic and lumboaortic lymph nodes (cutoff values 1 cm and 0.5 cm minimum axial diameter). MR imaging data were compared with the histopathological findings.ResultsThe endocervix was the site of origin of 25% (13/53) of the cervical tumours and the exocervix the site of origin of 75% (40/53). In the assessment of cervical stroma infiltration, there was agreement between MR imaging and histopathology in 75% of cases. MR imaging had 67% sensitivity, 92% specificity and 91% diagnostic accuracy in assessing infiltration of the vaginal fornices. In the evaluation of the infiltration of the internal os, MR imaging had 86% sensitivity, 93% specificity and 92% accuracy. In the assessment of the lymph nodes, when using a cutoff value of 1 cm, MR imaging had a sensitivity, specificity and diagnostic accuracy of 28%, 100% and 89%, respectively. With a cutoff value of 0.5 cm, MR imaging had a sensitivity, specificity and diagnostic accuracy of 33%, 92% and 83%, respectively.ConclusionsMR imaging had a high level of accuracy in the preoperative assessment of the extent of cervical tumour in patients eligible for conservative surgery. Accuracy is lower in the evaluation of the pelvic and lumboaortic lymph nodes.RiassuntoObiettivoValutare l’accuratezza della RM nella stadiazione pre-operatoria delle neoplasie localizzate della cervice uterina, candidate ad una chirurgia meno aggressiva.Materiali e metodiSono state sottoposte ad esame RM 53 pazienti con carcinoma della cervice uterina confermato istologicamente, candidate a chirurgia conservativa. L’analisi delle immagini ha compreso: localizzazione e dimensioni del tumore, infiltrazione dell’anello stromale, infiltrazione dei fornici vaginali ed estensione oltre l’orifizio uterino interno, presenza e dimensioni di linfonodi pelvici o lombo-aortici (valore soglia 1 cm e 0,5 cm di diametro assiale minimo). I risultati sono stati confrontati con quelli istopatologici.RisultatiNella valutazione dell’infiltrazione dello stroma cervicale vi è stata una concordanza RM/istopatologia in 40/53 (75%) casi. Nella valutazione dell’infiltrazione dei fornici vaginali la RM ha riportato una sensibilità del 67%,una specificità del 92% ed un’accuratezza diagnostica del 91%; nella valutazione dell’estensione oltre l’orifizio uterino interno dell’ 86%, 93% e 92%, rispettivamente. Nella valutazione dei linfonodi la RM ha riportato una sensibilità, specificità ed accuratezza diagnostica del 28%, 100% e 89%, usando come valore soglia 1 cm; e del 33%, 92% e 83%, con un valore soglia di 0,5 cm.ConclusioniLa RM ha dimostrato un’elevata accuratezza nella valutazione pre-operatoria dell’estensione (T) tumorale in pazienti candidate ad intervento chirurgico conservativo. L’accuratezza è minore nella valutazione dei linfonodi pelvici e lombo-aortici.

Identification of high-grade serous ovarian cancer miRNA species associated with survival and drug response in patients receiving neoadjuvant chemotherapy: a retrospective longitudinal analysis using matched tumor biopsies

BACKGROUND Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum (Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen. PATIENTS AND METHODS One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC-IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis. RESULTS Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression-free survival (P < 0.05); miR-199a-3p, miR-199a-5p and miR-181a-5p associated with residual tumor volume and Pt-free interval (P < 0.05). Immuno-histochemical staining confirmed an enrichment of P-Smad2, a marker of transforming growth factor-β activation, in tumors from patients with shorter PFS and OS, and with high levels of expression of miR-181a-5p (P < 0.05). Kaplan-Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P < 0.001). CONCLUSIONS This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.

Total Laparoscopic Hysterectomy in Early-Stage Endometrial Cancer Using an Intrauterine Manipulator: Is It a Bias for Frozen Section Analysis? Case-Control Study

STUDY OBJECTIVE To evaluate whether the systematic use of an intrauterine manipulator influences the accuracy of frozen section analysis in early-stage endometrial cancer. DESIGN Case-control study (Canadian Task Force classification II-1). PATIENTS Three hundred fourteen consecutive women with early-stage endometrial cancer. INTERVENTIONS Between January 2004 and December 2009, 314 women with early-stage endometrial cancer underwent staging at laparoscopy (case group) or laparotomy (control group). All women in the case group underwent total laparoscopic hysterectomy using an intrauterine manipulator. MEASUREMENTS AND MAIN RESULTS The positive predictive value of frozen section analysis for myometrial infiltration, histotype, and grade of differentiation was 97.2%, 100%, and 97.2%, respectively. The correct diagnosis rate was of 85.7%. The accuracy of frozen section analysis, rate of correct diagnosis, and rate of tumor vascular invasion did not seem to be significantly modified by systematic use of an intrauterine manipulator for total laparoscopic hysterectomy compared with total abdominal hysterectomy in early-stage endometrial cancer staging. CONCLUSIONS Frozen section analysis of early-stage endometrial cancer is highly accurate, and systematic use of an intrauterine manipulator does not represent a bias for correct evaluation of the specimen.

Dietary soy modulation of biochemical parameters in DMBA-induced mammary tumors.

The aim of this study was to extend our previous observations on the soy modulation of biochemical parameters in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors, by simultaneously investigating the expression of estrogen receptor-alpha (ERalpha), estrogen receptor-beta (ERbeta), progesterone receptor (PR), apoptosis, neu, and markers of cell proliferation, such as proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The percentage of ERalpha positive tumors was 65.8% in masses from control animals, and significantly dropped to 36.8% in tumors from soy treated rats (P=0.010). The percentage of ERbeta positive tumors was 70.3% in masses from control animals vs. 50.0% in tumors from soy exposed animals (P=0.066). Moreover, the percentage of cases which were both ERalpha and ERbeta positive was significantly lower (17.6%) in soy treated than in control animals (51.3%) (P=0.006). The percentage of PR positive tumors was 34.2% in control animals vs. 2.6% in tumors from soy treated rats (P=0.0006). There were no statistically significant differences in the percentage of tumors positively stained for neu, apoptosis, or PCNA, in control vs. soy treated rats. However, when analyzing the reciprocal correlation among the different biochemical parameters we showed that, in treated animals, the majority of ERalpha positive tumors (91.7%) were also PCNA positive (P=0.036). The median percentage of PCNA positivity was significantly higher in ERalpha positive than in ERalpha negative tumors (25 vs. 5%) (P=0.0031). Moreover, an association was found between PCNA and neu status since all neu positive tumors were also PCNA positive (P=0.011).

Imaging in gynecological disease (9): clinical and ultrasound characteristics of tubal cancer

To describe clinical history and ultrasound findings in patients with tubal carcinoma.

Imaging in gynecological disease (11): clinical and ultrasound features of mucinous ovarian tumors

To describe the clinical and ultrasound findings in patients with mucinous ovarian tumors.

Benign cystic peritoneal mesothelioma incorrectly diagnosed as an ovarian borderline mucinous tumor of intestinal type at transvaginal preoperative ultrasound evaluation

A 42-year-old sexually inactive woman presented to our emergency department with worsening abdominal pain and high fever of 1 day’s duration. During the previous month, she had had occasional mild lower abdominal pain, but without other symptoms. Her past medical history was unremarkable except for a myomectomy 10 years previously. Physical examination revealed diffuse abdominal tenderness with rebound. Laboratory data were notable for a leukocyte count of 42 880 per mm3 with a left shift. Pelvic sonography showed a large unilocular cystic structure in the upper pelvis measuring 9.0 × 8.0 × 6.5 cm that demonstrated internal debris and a hyperechoic thick wall (Figure 1a). Contrast-enhanced computed tomography revealed a large cystic mass with a thick wall, which was posterior to and superior to the uterus (Figures 2a and c). Bilateral ovarian cysts were also noted (Figure 2b). Even in the absence of risk factors for ascending genital-tract infection, tubo-ovarian abscess was still the primary consideration based on the laboratory results and imaging findings. Antibiotic therapy was started immediately, but the patient’s symptoms persisted. The following day an exploratory laparotomy revealed purulent material in the peritoneal cavity and a thick-walled pelvic mass containing purulent material. The mass was found to originate from the posterior wall of the uterus. Myomectomy could not be performed because the mass had severe adhesions. Instead, a tumor incision, marsupialization and drainage were performed. Microscopically, the mass consisted of fibrous tissue and smooth muscle cells, along with granulation tissue and chronic inflammation. No evidence of malignancy was noted. The patient had an uneventful recovery and was discharged within a week after surgery. Pelvic ultrasound 4 months after surgery showed that the size of the mass had decreased to 3 cm (Figure 1b). She remained well at the 12-month follow-up visit. Pyomyoma, or a suppurative leiomyoma, is a rare and potentially fatal complication of uterine leiomyoma. Only 21 cases have been reported since 19451–10. Most cases occur during pregnancy or after menopause, and are caused by ascending genitaltract infection. To our knowledge, this is the first case of pyomyoma described in a healthy premenopausal female and unrelated to any focus of infection. Figure 1 (a) Preoperative ultrasound image showing a large unilocular cystic structure in the upper pelvis that demonstrated internal debris and a hyperechoic thick wall. (b) Pelvic ultrasound image 4 months after surgery showed that the size of the subserosal fibroid had decreased to 3 cm. M, tumor mass; U, uterus.

Imaging in gynecological disease (12): clinical and ultrasound features of invasive and non‐invasive malignant serous ovarian tumors

To describe clinical and ultrasound features of different subclasses of malignant serous ovarian tumors according to the World Health Organization 2014 classification.

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to predict partial response in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery

Chemoradiation‐based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC), but ultrasound variables used to predict partial response to neoadjuvant treatment are not well defined. Our goal was to analyze prospectively the potential role of transvaginal ultrasound in early prediction of partial pathological response, assessed in terms of residual disease at histology, in a large, single‐institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery.