DCLK1, a Putative Stem Cell Marker in Human Cholangiocarcinoma.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a very aggressive cancer showing the presence of high cancer stem cells (CSCs). Doublecortin-like kinase1 (DCLK1) has been demonstrated as a CSC marker in different gastroenterological solid tumors. Our aim was to evaluate in vitro the expression and the biological function of DCLK1 in intrahepatic CCA (iCCA) and perihilar CCA (pCCA). APPROACH AND RESULTS: Specimens surgically resected of human CCA were enzymatically digested, submitted to immunosorting for specific CSC markers (LGR5 [leucine-rich repeat-containing G protein-coupled receptor], CD [clusters of differentiation] 90, EpCAM [epithelial cell adhesion molecule], CD133, and CD13), and primary cell cultures were prepared. DCLK1 expression was analyzed in CCA cell cultures by real-time quantitative PCR, western blot, and immunofluorescence. Functional studies have been performed by evaluating the effects of selective DCLK1 inhibitor (LRRK2-IN-1) on cell proliferation (MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, cell population doubling time), apoptosis, and colony formation capacity. DCLK1 was investigated in situ by immunohistochemistry and real-time quantitative PCR. DCLK1 serum concentration was analyzed by enzyme-linked immunosorbent assay. We describe DCLK1 in CCA with an increased gene and protein DCLK1 expression in pCCALGR5+ and in iCCACD133+ cells compared with unsorted cells. LRRK2-IN-1 showed an anti-proliferative effect in a dose-dependent manner. LRRK2-IN-1 markedly impaired cell proliferation, induced apoptosis, and decreased colony formation capacity and colony size in both iCCA and pCCA compared with the untreated cells. In situ analysis confirmed that DCLK1 is present only in tumors, and not in healthy tissue. Interestingly, DCLK1 was detected in the human serum samples of patients with iCCA (high), pCCA (high), HCC (low), and cirrhosis (low), but it was almost undetectable in healthy controls. CONCLUSIONS: DCLK1 characterizes a specific CSC subpopulation of iCCACD133+ and pCCALGR5+ , and its inhibition exerts anti-neoplastic effects in primary CCA cell cultures. Human DCLK1 serum might represent a serum biomarker for the early CCA diagnosis.

Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer.

BACKGROUND: To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer. METHODS: This is a retrospective, a multi-institutional study evaluating 90-day surgery-related outcomes of patients undergoing treatment for early-stage cervical cancer before (period I: 01/01/2016-06/01/2018) and after (period II: 01/01/2019-06/01/2021) the publication of the results of the LACC trial. RESULTS: Charts of 1295 patients were evaluated: 581 (44.9%) and 714 (55.1%) before and after the publication of the LACC trial, respectively. After the publication of the LACC trial, the number of patients treated with minimally invasive radical hysterectomy decreased from 64.9% to 30.4% (p < 0.001). Overall, 90-day complications occurred in 110 (18.9%) and 119 (16.6%) patients in the period I and period II, respectively (p = 0.795). Similarly, the number of severe (grade 3 or worse) complications did not differ between the two periods (38 (6.5%) vs. 37 (5.1%); p = 0.297). Overall and severe 90-day complications were consistent between periods even evaluating stage IA (p = 0.471), IB1 (p = 0.929), and IB2 (p = 0.074), separately. CONCLUSIONS: The present investigation highlighted that in referral centers the shift from minimally invasive to open radical hysterectomy does not influence 90-day surgery-related morbidity.

Clear cell carcinoma of the endometrium.

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.

Correlation between preoperative imaging biomarkers and histological prognostic factors in endometrial cancer: A prospective study.

PURPOSE: We compared transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration, cervical involvement, and for measuring tumor volume in endometrial cancer patients. We also correlated tumor volume to worse histological prognostic factors. METHODS: We recruited women with a histological diagnosis of endometrial cancer between March 2019 and March 2021. Inclusion criteria were: age ≥ 18 years, written informed consent, biopsy-proven endometrial cancer, absence of previous neoadjuvant chemo- or radiotherapy treatment, patient suitable for primary surgery. Exclusion criteria were: advanced disease stage and other coexisting malignant tumors. TVUS and MRI were used, in the absence of any contraindication. We compared the preoperative imaging results with final histopathology. RESULTS: The accuracy of TVUS and MRI in evaluating myometrial infiltration, cervical invasion and tumor volume were comparable. A tumor volume ≥2 ml showed a positive correlation with worse histological prognostic factors, such as high tumor grade, diffuse lymphvascular space involvement (LVSI) and deep myometrial invasion (p < 0.05). CONCLUSION: TVUS should be used as first-line imaging modality, being more available, cost-effective, and more acceptable by patients. A careful local staging of endometrial cancer patients before surgery is fundamental in order to improve tailored treatment and minimize costs.

Sentinel node mapping vs. sentinel node mapping plus back-up lymphadenectomy in high-risk endometrial cancer patients: Results from a multi-institutional study.

OBJECTIVE: Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). METHODS: This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. RESULTS: Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p = 0.416, log-rank test) and overall survival (p = 0.940, log-rank test) than patients undergoing SLN alone. CONCLUSIONS: Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed.

Pregnant women's knowledge and behaviour to prevent cytomegalovirus infection: an observational study.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can negatively affect pregnancy outcomes, but may be prevented by simple precautions. Literature suggests that gynaecologists do not always adequately inform about preventive behaviour and most pregnant women have a low-level knowledge regarding cCMV infection. The aim of this study is to evaluate knowledge and risk behaviours related to cCMV infection in an unselected group of pregnant women. METHODS: An institutional based cross-sectional study was conducted in three Maternal and Fetal Divisions in Rome between November and February 2019 on 296 pregnant women, their knowledge on cCMV was measured using six cytomegalovirus (CMV) related questions. RESULTS: Out of the 296 respondents, 59.1% had heard, read or seen information about cCMV infection. Regarding the way of transmission, 96/296 (32.4%) correctly recognize children as a potential source of the infection but only 25/296 (8.44%) knew all prevention practices, 28/296 (9.5%) of women reported that they have never performed cCMV test during pregnancy. CONCLUSIONS: The results of this survey show that knowledge on cCMV infection among pregnant women is poor. This highlights the need to improve counselling on all preventive practices for cCMV infection during perinatal care consultation.

Hypoplasia of the Corpus Callosum: A Single Center Experience and a Concise Literature Review.

AimCorpus callosum hypoplasia is described as a fully formed corpus callosum with reduced thickness. Our purpose is to evaluate the current knowledge about this anomaly including it's effect on the neurodevelopmental outcome and to report our single center experience. Methods: PubMed, Medline and reference lists were searched using combinations of these terms: "Hypoplasia of corpus callosum and prenatal diagnosis" and "neurodevelopmental outcome". Results: Eleven studies were included, with a final population of 48 patients (45 cases from literature plus 3 of our own cases). Hypoplasia of the corpus callosum was detected by ultrasound scan alone in 77% of cases: magnetic resonance confirmed the ultrasound suspicion in the remaining 23% of cases. Isolated form was detected in 31% cases. Adverse fetal outcomes occurred in 62% of cases, while 38% of cases were born alive. The neurodevelopmental outcome was found to be normal in 33% of cases. Conclusion: Antenatal detection of corpus callosum hypoplasia remains challenging. Counseling is difficult because neurodevelopmental outcomes are variable.

Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study.

BACKGROUND: This randomized phase II study tested the hypothesis that schedule dependent chemo-immunotherapy with oregovomab improves progression free survival (PFS) and overall survival (OS) in optimally resected, Stage III/IV ovarian cancer. METHODS: Patients from both academic centers and private practice in the US and Italy with Stage III/IV optimally cytoreduced ovarian cancer were randomized to standard six cycle IV carboplatin-paclitaxel chemotherapy (CP) versus CP plus four immunizations with oregovomab (CPO). A translational assessment of a cellular immune response was the primary endpoint; PFS and OS were measured as secondary endpoints. FINDINGS: 97 patients at thirteen centers were accrued to the protocol, 47 to CPO and 50 to CP. Technical issues led to inconsistent performance of the primary CA125 ELISPOT leading to unevaluable results. At a median follow up of 42 months, PFS and OS outcomes revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4-18.6) for CP (p = 0.0027, HR 0.46, CI 0.28-0.7). For OS, the median for CPO has not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16-0.74). The oregovomab treatment resulted in no change in toxicity profile from CP. INTERPRETATION: The previously identified potential clinical benefit of IV CP when administered with oregovomab was further refined in this randomized phase II study. Increases of PFS and OS of statistically and clinically significant magnitude were evident in this study of a front line chemo-immunotherapy treatment of ovarian cancer.

Is ovarian response associated with adverse perinatal outcomes in GnRH antagonist IVF/ICSI cycles?

RESEARCH QUESTION: Is there an association between ovarian response and perinatal outcomes? DESIGN: A retrospective, single-centre cohort study including all women undergoing their first ovarian stimulation cycle in a gonadotrophin releasing hormone antagonist protocol, with a fresh embryo transfer that resulted in a singleton live birth from January 2009 to December 2015. Patients were categorized into four groups according to the number of oocytes retrieved: one to three (category 1), four to nine (category 2), 10-15 (category 3), or over 15 oocytes (category 4). RESULTS: The overall number of patients analysed was 964. No relevant statistical difference was found among neonatal outcomes across the four ovarian response categories. Neonatal weight (in grams) was comparable between all groups (3222 ± 607 versus 3254 ± 537 versus 3235 ± 575 versus 3200 ± 622; P = 0.85, in categories 1, 2, 3 and 4, respectively). No statistically significant differences were found among the ovarian response categories for birth weight z-scores (taking into account neonatal sex and delivery term). The incidence of pre-term birth and low birth weight was comparable across the different ovarian response groups (P = 0.127 and P = 0.19, respectively). Finally, the occurrence of adverse obstetric outcomes did not differ among the ovarian response categories. Multivariate regression analysis revealed that the number of oocytes was not associated with neonatal birth weight. CONCLUSIONS: No association was found between ovarian response and adverse perinatal outcomes in antagonist IVF and intracytoplasmic sperm injection cycles. Future, larger scale and prospectively designed investigations are needed to validate these results.

Severe hemoperitoneum due to endometriosis in a non-pregnant woman under dienogest therapy: a case report.

Endometriosis is a chronic, estrogen-dependent, inflammatory disease that mainly affects women of reproductive age and is defined by the presence of endometrial glands and stroma at ectopic sites. Spontaneous hemoperitoneum due to bleeding of pelvic endometriotic foci represents a very rare and severe complication of endometriosis, although most cases described in literature regard pregnant women. We hereby present a case of a severe hemoperitoneum in a non-pregnant, 42 years old woman, under dienogest therapy for deep endometriosis. This life-threatening condition was promptly managed by performing an exploratory laparoscopy where the source of bleeding was found and hemostasis successfully achieved.Bleeding from pelvic endometriotic foci ought to be considered in the differential diagnosis of gynecological causes of acute abdomen and hemoperitoneum, even under medical therapy.

Prognostic role of chemotherapy-induced neutropenia in first-line treatment of advanced ovarian cancer. A pooled analysis of MITO2 and MITO7 trials.

BACKGROUND: Chemotherapy-induced neutropenia (CIN) has been associated with improved prognosis in several cancer conditions. Contrasting data have been produced in ovarian cancer.

Assessing HPV vaccination perceptions with online social media in Italy.

OBJECTIVE: Because of the widespread availability of the internet and social media, people often collect and disseminate news online making it important to understand the underlying mechanisms to steer promotional strategies in healthcare. The aim of this study is to analyze perceptions regarding the human papillomavirus (HPV) vaccine in Italy. METHODS: From August 2015 to July 2016, articles, news, posts, and tweets were collected from social networks, posts on forums, blogs, and pictures about HPV. Using other keywords and specific semantic rules, we selected conversations presenting the negative or positive perceptions of HPV. We divided them into subgroups depending on the website, publication date, authors, main theme, and transmission modality. RESULTS: Most conversations occurred on social networks. Of all the conversations regarding HPV, more than 50% were about vaccination. With regard to conversations exclusively on the HPV vaccine, 47%, 32%, and 21% were positive, negative and neutral, respectively. Only 9% of the conversations mentioned the vaccine trade name and, in these conversations, perception was almost always negative. We observed many peaks in positive conversation trends compared with negative trends. The peaks were related to the web dissemination of particular news regarding HPV vaccination. CONCLUSIONS: In this study we have shown how mass media influences the diffusion of both negative and positive perceptions about HPV vaccines and suggest better ways to inform people about the importance of HPV vaccination.

'Primary gingival and later primary vulval carcinomas arising in lichen planus: report of a case and clinical suggestions for diagnosis of a neglected disease'.

Lichen planus (LP) is a chronic immune-mediated dermatosis mainly affecting skin, oral, and genital mucosa. The heterogeneous clinical presentation, spectrum of symptoms depending on subtype and overlap with other vulval and cutaneous disorders can lead to challenging in diagnosis. We report an unusual case of vulval SCC arising within a patient with initial oral mucosal lichen planus who later developed lichen planus of the vulva. Discussion of this case is important as it typifies the difficulties in diagnosis of vulvo-vaginal disorders and potential complications. Evidence is available that lichen planus may be potentially precancerous condition and is associated with SCC development. This case may confirm an inherent oncologic potential of the disease. All efforts must be made by specialists involved in the management of this disease to obtain an early diagnosis, ensure proper treatment and adequate follow up. This highlights the need to perform vulval examination in patients with symptoms or with a history muco-cutaneous LP and if necessary consider referral to specialist center for biopsy and management.

Texture analysis versus conventional MRI prognostic factors in predicting tumor response to neoadjuvant chemotherapy in patients with locally advanced cancer of the uterine cervix.

INTRODUCTION: To determine the performance of texture analysis and conventional MRI parameters in predicting tumoral response to neoadjuvant chemotherapy and to assess whether a relationship exists between texture tissue heterogeneity and histological type of uterine cervix cancer. METHOD AND MATERIALS: Twenty-eight patients with local advanced cervical cancer (FIGO IB2-IIIB), underwent MRI before chemotherapy. Texture analysis parameters were quantified on T2-weighted sequences, as well as the maximum diameter expressed in mm. ADC values were obtained on the ADC map. Statistical analysis included unpaired t test and ROC curve. RESULTS: No statistical correlation was found between conventional parameters and response to NACT. Mean and skewness showed a strong correlation with the histological type: Adenocarcinomas presented higher mean and skewness values (69.8 ± 10.5 and 0.55 ± 0.19) in comparison with squamous cell carcinomas. Using a cutoff value ≥ 29 for mean it was possible to differentiate the two histological types with a sensitivity of 100% and a specificity of 81%. Kurtosis showed a positive correlation with tumor response to NACT resulting higher in responders (v.m. 5.7 ± 1.1) in comparison with non-responders (2.3 ± 0.5). The optimal Kurtosis cutoff value for the identification of non-responders tumors was ≤ 3.7 with a sensitivity of 92% and a specificity of 75%. CONCLUSION: Texture analysis applied to T2-weighted images of uterine cervical cancer exceeded the role of conventional prognostic factors in predicting tumoral response; moreover, they showed a potential role to differentiate histological tumor types.

Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials.

BACKGROUND: Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations. METHODS: We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic. FINDINGS: Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0-9·6; EORTC, 9·2 years [IQR 7·3-10·4]; CHORUS, 5·9 years [IQR 4·3-7·4]). Median age was 63 years (IQR 56-71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8-13·0). 55 (5%) women had FIGO stage II-IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1-51·3] and 26·9 months [12·7-50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86-1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7-53·7) and 23·6 months (10·5-46·9), respectively (HR 1·20, 95% CI 1·06-1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1-47·6] and 21·2 months [10·0-36·4], respectively; HR 0·76, 95% CI 0·58-1·00; p=0·048; median progression-free survival 10·6 months [7·9-15·0] and 9·7 months [5·2-13·2], respectively; HR 0·77, 95% CI 0·59-1·00; p=0·049). INTERPRETATION: Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC-IV tubo-ovarian cancer, particularly in patients with a high tumour burden at presentation or poor performance status. FUNDING: National Cancer Institute and Vlaamse Liga tegen kanker (Flemish League against Cancer).

Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: a promising solution against HPV-infection.

BACKGROUND: Over recent years, a growing interest has developed in microbiota and in the concept of maintaining a special balance between Lactobacillus and other bacteria species in order to promote women's well-being. The aim of our study was to confirm that vaginal Lactobacilli long-lasting implementation in women with HPV-infections and concomitant bacterial vaginosis or vaginitis might be able to help in solving the viral infection, by re-establishing the original eubiosis. METHODS: A total of 117 women affected by bacterial vaginosis or vaginitis with concomitant HPV-infections were enrolled at Department of Gynecological Obstetrics and Urological Sciences, La Sapienza University, Rome, Italy between February 2015 and March 2016. Women were randomized in two groups, standard treatment (metronidazole 500 mg twice a day for 7 days or fluconazole 150 mg orally once a day for 2 consecutive days) plus short-term (3 months) vaginal Lactobacillus implementation (group 1, short probiotics treatment protocol group, n = 60) versus the same standard treatment plus long-lasting (6 months) vaginal Lactobacillus rhamnosus BMX 54 administration (group 2, treatment group, n = 57). RESULTS: After a median follow up of 14 months (range 9-30 months) the chance to solve HPV-related cytological anomalies was twice higher in probiotic long-term users (group 2) versus short probiotics implementation group (group 1) (79.4% vs 37.5%, p = 0.041). Moreover, a total HPV-clearance was shown in 11.6% of short schedule probiotics implementation patients compared to a percentage of 31.2% in vaginal Lactobacilli long term users (p = 0.044), assessed as negative HPV-DNA test documented at the end of the study period. CONCLUSIONS: The consistent percentage of clearance of PAP-smear abnormalities and HPV-clearance obtained in long-term treatment group has been interestingly high and encouraging. Obviously, larger and randomized studies are warranted to confirm these encouraging results, but we believe that eubiosis re-establishment is the key to tackle effectively even HPV-infection. TRIAL REGISTRATION: Retrospectively registered on PRS NCT03372395 (12/12/2017).

Assessment of Quality of Life and Urinary and Sexual Function After Radical Hysterectomy in Long-Term Cervical Cancer Survivors.

AIMS: The aim of this study was to evaluate long-term quality of life and urinary and sexual function in long-term cervical cancer survivors previously treated with radical hysterectomy (RH) type C2/type III. METHODS: All patients who presented at Campus Bio-Medico of Rome for RH type C2/type III for cervical cancer were considered eligible for this retrospective study protocol. We included exclusively patients with complete response to primary treatment with at least 36 months of follow up. Included subjects were interviewed with the European Organization for Research and Treatment of Cancer QLQ-CX24 Questionnaire, European Organization for Research and Treatment of Cancer QLQ-C30, and an Incontinence Impact Questionnaire 7. RESULTS: From January 2004 to June 2014, 251 patients affected by locally advanced cervical cancer were treated at Campus Bio-Medico of Rome treated with type C2/type III RH. At time point of March 2017, 90 patients were included with a mean age of 55.6 ± 8.5 years. The questionnaires were administered after a median follow-up of 49 months after the end of therapy. The symptoms of fatigue, nausea and vomiting, appetite loss, pain, insomnia, and dyspnea, as well as a negative financial impact, were reported as not frequent and rarely disabling. On the contrary, patients frequently reported gastrointestinal complaints. Diarrhea was present in 6% of patients and was referred as mild; constipation was present in 75% of women and was reported as mild in 30% of cases, moderate in 30%, and severe in 15%. Concerning sexual activity, data indicated a good level of sexual enjoyment with a slight worsening of sexual activity. Incontinence was reported in 28% of cases and appeared to be mild and rarely disabling (all mean values <2). CONCLUSIONS: Waiting for ongoing randomized controlled trials, this study confirmed that RH may be considered as a useful treatment plan, according to its negligible long-term impact on quality of life, urinary dysfunction, and sexual function.

Genetic Versus Epigenetic BRCA1 Silencing Pathways: Clinical Effects in Primary Ovarian Cancer Patients: A Study of the Tumor Bank Ovarian Cancer Consortium.

OBJECTIVES: The aim of the present study was to assess in a large cohort of primary epithelial ovarian cancer patients the incidence and the clinical effect of BRCA1 genetic and epigenetic silencing mechanisms. METHODS: A total of 188 primary epithelial ovarian cancer patients, treated between 2000 and 2011 at the Charité University Hospital of Berlin, were included. The patients' tumor and blood samples were obtained from the Tumor Bank Ovarian Cancer Network (www.toc-network.de). Direct sequencing of BRCA1 exon 11 was performed to detect germline mutations, whereas tumor samples were assessed for BRCA1 promoter hypermethylation by bisulphite-converted methylation-specific polymerase chain reaction. Basing on their BRCA1 status, patients were compared regarding clinicopathological variables and survival. RESULTS: Twenty-one patients (11.2%) showed hypermethylation in BRCA1 promoter (HMB), and 18 patients (9.6%) presented germline mutations in BRCA1 exon 11 (GMB). Patients with HMB showed a significantly younger age at diagnosis compared with BRCA1 wild type (BWT) patients (54 vs 61 years, P = 0.045), and both GMB and HMB patients were more likely to have high-grade serous ovarian cancer (76.2% and 77.8% vs 52.7%, P = 0.043 and P = 0.043). Positive family history of breast or ovarian cancer (OC) was more frequently reported among GMB patients with respect to BWT patients (44.4% vs 13.5%, P = 0.003); GMB, HMB, and BWT patients did not show significant differences in terms of tumor dissemination pattern, surgical outcomes, platinum response or survival; neither mutational nor hypermethylation BRCA1 status was found to be an independent prognostic factor for OC patients. CONCLUSIONS: Hypermethylation in BRCA1 is associated with earlier occurrence of OC. In addition, the coexistence of both GBM and HMB is an infrequent event, occurring in 0.5% of OC cases. Silencing of BRCA1 through mutation and hypermethylation confers to distinct clinical characteristics of OC patients but similar clinical outcome with respect to BWT patients.

Sonohysterosalpingography: Comparison of foam and saline solution.

PURPOSE: To compare sonohysterosalpingography (sono-HSG) with foam instillation (HyFoSy) versus saline solution (HyCoSy) in the evaluation of tubal patency. METHODS: We prospectively enrolled 37 infertile women, scheduled for laparoscopy. The women were randomized into two groups: HyFoSy (group I) and HyCoSy (group II). The patients of both groups underwent laparoscopy with dye test. We assessed the diagnostic performance (sensitivity, specificity, and overall accuracy) of HyFoSy and HyCoSy, compared with laparoscopy and dye test, in the assessment of tubal patency. RESULTS: Sono-HSG findings in tubal patency assessment obtained in the HyFoSy group were concordant with laparoscopic results in 94.4% of cases, with a sensitivity of 87.5% and a specificity of 100%, whereas in the HyCoSy group, concordance occurred in only 57.8% of examinations, with a sensitivity of 50% and a specificity of 66.6%. CONCLUSIONS: HyFoSy allows a more accurate diagnosis of tubal patency compared with HyCoSy. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:67-71, 2017.