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Persistent infection with high-risk Human papillomavirus (hr-HPV 16, 18, 31, 33, and 45) is the main risk factor for developing malignant genital lesions. Screening methods and follow-up schedules for cervical cancer are well known. A golden standard to screen and monitor men does not exist yet, because HPV-related, life threatening malignancies in men are rare. The importance of male HPV screening lies mainly in HPV vaccination. Young females are the target group for HPV, but men are considered to be the reservoir for HPV and to have a role in the perpetuation of the infection in the general population. We looked at the usefulness of urine as a tool for HPV screening. Pubmed was searched with the words ''HPV'', ''Urine,'' and ''HPV-DNA''. The chance of finding HPV-DNA in urine is higher in men with lesions in the urethra than outside the urethra, and in women with abnormal cervical cytology. In general, the results of testing urine for HPV-DNA are better for women than for men, probably because of the anatomical position of the urethra to the vagina, vulva, and cervix. In both genders, urine HPV prevalence is higher in HIVpos patients and in high-risk populations. Urine, to screen asymptomatic low-risk-profile (wo)men seems less useful because their urine samples are often inadequate. If urine proves to be the best medium to screen, a low-risk population remains controversial. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF)-A inhibitors exhibit unseen high responses and toxicity in recurrent epithelial ovarian cancer suggesting an important role for the VEGF/VEGFR pathway. We studied the correlation of VEGF signalling and AKT/mTOR signalling. Using a tissue microarray of clinical samples (N=86), tumour cell immunohistochemical staining of AKT/mTOR downstream targets, pS6 and p4E-BP1, together with tumour cell staining of VEGF-A and pVEGFR2 were semi-quantified. A correlation was found between the marker for VEGFR2 activation (pVEGFR2) and a downstream target of AKT/mTOR signalling (pS6) (R=0.29; P=0.002). Additional gene expression analysis in an independent cDNA microarray dataset (N=24) showed a negative correlation (R=-0.73, P<0.0001) between the RPS6 and the VEGFR2 gene, which is consistent as the gene expression and phosphorylation of S6 is inversely regulated. An activated tumour cell VEGFR2/AKT/mTOR pathway was associated with increased incidence of ascites (chi(2), P=0.002) and reduced overall survival of cisplatin-taxane-based patients with serous histology (N=32, log-rank test, P=0.04). These data propose that VEGF-A signalling acts on tumour cells as a stimulator of the AKT/mTOR pathway. Although VEGF-A inhibitors are classified as anti-angiogenic drugs, these data suggest that the working mechanism has an important additional modality of targeting the tumour cells directly. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the preoperative findings of abdominal/pelvic CT and MRI with the preoperative clinical International Federation of Obstetrics and Gynecology (FIGO) staging and postoperative pathology report in patients with primary cancer of the cervix. Thirty-six patients with surgical–pathological proven primary cancer of the cervix were retrospectively studied for preoperative staging by clinical examination, CT, and MR imaging. Studied parameters for preoperative staging were the presence of tumor, tumor extension into the parametrial tissue, pelvic wall, adjacent organs, and lymph nodes. The CT was performed in 32 patients and MRI (T1- and T2-weighted images) in 29 patients. The CT and MR staging were based on the FIGO staging system. Results were compared with histological findings. The group is consisted of stage 0 (in situ):1, Ia:1, Ib:8, IIa:2, IIb:12, IIIa:4, IVa:6, and IVb:2 patients. The overall accuracy of staging for clinical examination, CT, and MRI was 47, 53, and 86%, respectively. The MRI incorrectly staged 2 patients and did not visualize only two tumors; one was an in situ (stage-0) and one stage-Ia (microscopic) disease. The MRI is more accurate than CT and they are both superior to clinical examination in evaluating the locoregional extension and preoperative staging of primary cancer of the cervix. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 74-year-old woman who was referred to an orthopedic surgeon for a fibula metastasis. The examination reveals an isolated metastatic bone lesion in the right fibula of a primary squamous carcinoma of the vagina. The patient was given a palliative therapy including bone resection and radiotherapy of the metastatic lesion.

Cervical cancer can and should be a historical disease. The reality, however, is that every year more than half a million women are diagnosed with cervical cancer and a quarter of a million die of this disease. The causal factor for cervical cancer is a persistent HPV infection and therefore a vaccine was developed: prophylactic HPV vaccination will reduce cervical cancer by 70%. Screening based on cytology will miss more than 40% of the abnormalities. The introduction of vaccination should lead to the reintroduction of cervical cancer screening based on HPV detection. Primary HPV screening followed by cytology will detect almost all abnormalities. Not all HPV tests, however, are the same! Clinicians are generally not aware that there is a huge difference among HPV tests. If a low grade lesion progresses to a high grade or invasive cancer, their HPV is likely to integrate. During integration L1 expression can be lost, but E6/E7 expression will always remain present. If the viral HPV is completely integrated then a L1 test looking for only L1 expression will miss this (pre)cancer, while the E6/E7 test will not miss it. HPV tests used in cervical cancer screening should be based on the early (E) and the late (L) genes in order not to miss the abnormality. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 29-year-old woman who was diagnosed of having a desmoplastic small round cell tumor in the ovary. It states that the patient has used contraceptive pills for 14 years due to irregular menstrual cycles and has interrupted the assumption of the pill due to a desire for pregnancy. It adds that a laparoscopic right ovariectomy and an anatomical pathology have confirmed a right ovarian mass of 132 grams (g) in weight and an 8.5 centimeter (cm) in size.

Highlights • VALHUDES is a protocol for validation of HPV tests applied on vaginal self-samples and urine specimen. • VALHUDES will generate the first clinical data regarding the accuracy of HPV tests on vaginal & urine samples. • VALHUDES will generate comparative data sets for different combinations of HPV test and self-sample devices. • VALHUDES will contribute in defining validation criteria for HPV tests on self-samples. Abstract Back ground Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations. Objectives The VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples. Study design Five hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies. Results A first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTi m e High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene). Conclusion Given empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self-sample device combinations that can be translated to a primary screening setting. [ABSTRACT FROM AUTHOR]

Although the aetiology of urinary incontinence can be multifactorial, in some cases weight loss could be considered as a part of the therapeutic approach for urinary incontinence in people who are overweight. The objective of this study was to review and meta-analyse the effect of non-surgical weight loss interventions on urinary incontinence in overweight women. Web of Science, PubMed, Pedro, SPORTDiscus and Cochrane were systematically searched for clinical trials that met the a priori set criteria. Data of women who participated in non-surgical weight loss interventions (diet, exercise, medication or a combination) were included in the meta-analysis. After removing duplicates, 62 articles remained for screening on title, abstract and full text. Six articles (totalling 2,352 subjects in the intervention groups) were included for meta-analysis. The mean change in urinary incontinence (reported as frequency or quantity, depending on the study) after a non-surgical weight loss intervention, expressed as standardized effect size and corrected for small sample sizes ( Hedges' g), was −0.30 (95% CI = −0.47 to −0.12). This systematic review and meta-analysis shows evidence that a non-surgical weight loss intervention has the potential to improve urinary incontinence and should be considered part of standard practice in the management of urinary incontinence in overweight women. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Levonorgestrel (LNG), delivered locally into the uterine cavity has a profound effect on the endometrium. The aim of the study was to use a LNG intrauterine system to treat non-atypical and atypical endometrial hyperplasia in women and to evaluate the long-term cure (remission) rate. Methods: Each of the 20 women in the study, of whom eight were diagnosed with atypical hyperplasia, received a LNG–IUS, releasing 20μgLNG/day. The study is a non-comparative study with long-term follow-up (range 14–90 months). Results: All women developed a normal endometrium, except one asymptomatic woman with atypical hyperplasia who still had focal residual non-atypical hyperplasia at 3 years follow-up in the presence of a thin (<4mm) endometrium. Conclusion: Continuous intrauterine delivery of LNG appears to be a promising alternative to hysterectomy for the treatment of endometrial hyperplasia and could enhance the success rate when compared with other routes of progestagen administration as well as intrauterine progesterone delivery. The significant reduction of the PR expression observed during treatment with the LNG–IUS appears to be a marker for the strong antiproliferative effect of the hormone at a cellular level resulting in an inhibition of estrogen bioactivity and endometrial suppression. [Copyright &y& Elsevier]

Objective: To investigate endometrial histology and thickness of the endometrium after long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. Design: A 5-year non-comparative prospective clinical trial. Subjects: Out of 182 symptomatic postmenopausal women using estrogen substitution therapy (EST) combined with a novel T-shaped LNG-releasing intrauterine system (Femilis Slim LNG-IUS), to prevent endometrial proliferation and bleeding, only those women (n=102) who used two consecutive LNG-IUSs, were isolated with the aim to study the long-term effects on the endometrium. The mean age of the women was 57 years (range 47-71). The majority of women received percutaneous 17beta estradiol, 1.5mg daily, or an equivalent dose by patch or orally, on a continuous basis. Main Outcome Measures: Endometrial histology and ultrasonographic evidence of endometrial suppression, after a period of approximately 5 years of use. The mean duration of use of the regimen was 70 months (range 25-98). Results: The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. On transvaginal ultrasound, this corresponds with a thin endometrium (< or = 5 mm). Conclusion: The results of this 5-year study in 102 postmenopausal women using EST demonstrates that the LNG-IUS effectively opposes the estrogenic effect on the endometrium resulting in strong suppression during the entire period of EST. Due to its high efficacy and absence of systemic effects on organ tissues (e.g., breasts), target delivery in the uterine cavity could be a preferred route to administer a progestagen in women using EST. [ABSTRACT FROM AUTHOR]

PURPOSE: The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865. EXPERIMENTAL DESIGN: Retrospectively collected paraffin blocks from 169 patients with stages IIb-IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC). RESULTS: Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36-0.94, p=0.025) in addition to FIGO stage (HR 1.54, CI 1.08-2.21, p=or<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors. CONCLUSION: P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865. Experimental design: Retrospectively collected paraffin blocks from 169 patients with stages IIb–IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC). Results: Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36–0.94, p =0.025) in addition to FIGO stage (HR 1.54, CI 1.08–2.21, p =<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors. Conclusion: P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1cm. [Copyright &y& Elsevier]

The enhancing area surrounding breast carcinoma on MR mammography is correlated with findings from pathological examination. We studied 194 patients with breast cancer who underwent preoperative MR mammography. Of all malignant lesions presenting with an enhancing surrounding area on MR mammography, morphologic features including long spicules, a ductal pattern, diffuse enhancement or nodules were evaluated and compared with histopathological examination. A double breast coil was used; we performed a 3D FLASH sequence with contiguous coronal slices of 2 mm, before and after injection of 0.2 mmol/kg GD-DTPA, and subtraction images were obtained. In total, 297 malignant lesions were detected at MR mammography and 101 of them had one or more types of enhancing surrounding area. In 49 of the 53 cancers with long spicules and in 49 of the 55 cancers with surrounding ductal pattern of enhancement, pathological examination showed in situ and/or invasive carcinoma. Multiple nodules adjacent to the carcinoma were seen in 20 patients and corresponded with six cases of invasive and ten cases of ductal in situ carcinoma. A diffuse enhancing area next to a mass was seen in ten patients and consisted of carcinoma in all cases: seven in situ and three invasive carcinomas. Enhancing areas including long spicules, a ductal pattern, noduli, or diffuse enhancement surrounding a carcinoma corresponded with in situ or invasive extension of the carcinoma in 92.5, 89, 80 and 100% of cases, respectively. [ABSTRACT FROM AUTHOR]

To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC. [ABSTRACT FROM AUTHOR]