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Purpose of Investigation: The study was performed to evaluate four years of experience (2012-2015) in high risk-human papillomavirus (hr-HPV) testing in the cervical cancer screening in Latina (Italy). Materials and Methods: The hr-HPV as primary test is performed only on women aged 35-64, followed by a Pap test as triage, while women aged 25-34 are invited to perform only a Pap test. Results: Women resulted positive to hr-HPV test and positive to Pap test were 5.6% and 4.1%, respectively. Among women aged 25-34, the hr-HPV test was used as triage for women with atypical squamous cells of undetermined significance (ASCUS) and 69.9% resulted positive to the test. The positive predictive value (PPV) for high cervical intraepithelial lesions (HSIL) was higher in women aged 35-64 (9.9% vs. 6.9%), while the detection rate (DR) for HSIL was higher in young women (2.4‰ vs. 1.2‰). The authors found that 52.5% of women with hr-HPV+/Pap test resulted with hr-HPV+ at one-year recall and the DR for HSIL lesions of this population was very low (0.27‰). Discussion: The present data confirms that the application of hr-HPV test showed elevated performance in cervical cancer screening and that the application of hr-HPV test in managing ASCUS leads to a decreased use of inappropriate colposcopies. Finally, it may be useful to extend the period of follow-up for women hr-HPV+/Pap test to reduce unnecessary colposcopies. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the effect and performance of the new algorithm in cervical cancer screening program in two years' experience of Latina (Italy). Materials and Methods: The female population was divided into two groups, the first group was referred to PAP test and the second one to hr-HPV test according to national guidelines. Results: In two years the participation mean rate increased among women aged 35-64 compared to women aged 25-34. The primary PAP test positive rate and hr-HPV test positive rate were 4.0% and 5.2%, respectively. The PAP test positive rate among hr-HPV+ women decreased from 2012 to 2013. Women with hr-HPV+/PAP+ were referred immediately to colposcopy and this rate was 1.2%. The predictive positive value for CIN2+ to colposcopy was 10.9% in 2012 and 9.1% in 2013, while the detection rate for CIN2+ was 1.6% in 2012 and 1.4% in 2013. Conclusion: The stratification of the female population leads to a decreased inappropriate therapeutic path while the combination of hr-HPV test with PAP test in woman aged 35-64 lets obtain high levels specificity and sensitivity results. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs are emerging as new molecular players involved in many biological processes, such as proliferation, apoptosis, cell cycle, migration, and differentiation. Their aberrant expression has been reported in variety of diseases. The aim of this study is the identification and functional characterization of clinically relevant lncRNAs responsible for the inhibition of miR-145-5p, a key tumor suppressor in thymic epithelial tumors (TETs). Starting from gene expression analysis by microarray in a cohort of fresh frozen thymic tumors and normal tissues, we identified LINC00174 as upregulated in TET. Interestingly, LINC00174 expression is positively correlated with a 5-genes signature in TETs. Survival analyses, performed on the TCGA dataset, showed that LINC00174 and its associated 5-genes signature are prognostic in TETs. Specifically, we show that LINC00174 favors the expression of SYBU, FEM1B, and SCD5 genes by sponging miR-145-5p, a well-known tumor suppressor microRNA downregulated in a variety of tumors, included TETs. Functionally, LINC00174 impacts on cell migration and lipid metabolism. Specifically, SCD5, one of the LINC00174-associated genes, is implicated in the control of lipid metabolism and promotes thymic cancer cells migration. Our study highlights that LINC00174 and its associated gene signature are relevant prognostic indicators in TETs. Of note, we here show that a key controller of lipid metabolism, SCD5, augments the migration ability of TET cells, creating a link between lipids and motility, and highlighting these pathways as relevant targets for the development of novel therapeutic approaches for TET.

Purpose: Degenerative disc disease (DDD) is a common condition causing low-back pain, disability and, eventually, neurological symptoms. This investigation aimed to investigate intervertebral disc DDD-related changes, evaluating histomorphology and cytokines secretion, and their clinical-radiological correlations., Methods: This is a monocentric prospective observational study. A cohort of patients who underwent microdiscectomy for DDD, from June 2018 to January 2019, were enrolled. Discs samples were examined for histomorphology, chondrons count, immunohistochemistry for Hif-1α, Nf200 and Egr-1. Demographical and clinical data were also collected., Results: Twenty patients were finally included. MRI evaluation showed a Modic I alteration in nine patients and a Modic II in 11. The disability grade was low-moderate (ODI score was ≤ 40%) in eight patients and high (ODI score > 40%) in 12. The Modic I was associated with a low-moderate disability in two (22%) patients and to a high disability in seven (88%) (p < 0.01). In Modic I group and in ODI > 40% groups, there were a significative higher mean disability grade 48.4 (± 8.3)%, number of chondrons per section, cells per chondron, Nf200+ nerve fibers and Hif-1α expression, compared with Modic II and ODI ≤ 40% groups, respectively. There were no differences in terms of Egr-1 expression., Conclusions: The discs with Modic I MRI signal could represent potential targets for medical treatments, whereas Modic II seems to be a more likely point of no return in a degenerative process. Therefore, further investigations are to better investigate inflammatory pathways and degenerative mechanisms in DDD.

Background: MicroRNAs (miRNAs) are emerging as promising molecules in the diagnosis, prognosis and treatment of urological tumours. Recently, our group performed two independent studies highlighting that miR-210-3p may be a useful biomarker not only for diagnosis but also for post-surgery clear cell Renal Cell Carcinoma (ccRCC) management., Objective: The aim of this study is to further explore the effectiveness of miRNA as non-invasive biomarker for clinical outcomes and ccRCC response to the treatment., Methods: We analyzed miR-210-3p levels in neoplastic and healthy tissue and in urine specimens collected at surgery and during follow-up of 21 ccRCC patients by RTqPCR., Results: Firstly, we confirmed that the expression of miR-210-3p was upregulated in tumor tissues and in urine samples of analyzed cohort. Of note is that miR-210-3p expression was significantly reduced in urine samples from disease-free patients during follow-up (from 3 to 12 months) compared to the baseline levels observed at the time of surgery. In a small subgroup of patients presenting metastatic progression (such as bone, intestinal or lung metastasis), the urine levels of miR-210-3p correlated with responsiveness to the therapy., Conclusions: This pilot study highlights the relevance of secreted miR-210-3p as powerful non-invasive prognostic and predictive biomarker for the evaluation of clinical outcomes and treatment response during ccRCC follow up.

Barriers to following dietary recommendations have been described; however, they remain poorly understood. The purpose of this qualitative study was to explore perceived barriers to adherence to dietary recommendations in a diverse hemodialysis patient population. Participants were eligible to participate in a semi-structured qualitative telephone interview prior to randomization for an ongoing clinical trial to evaluate the efficacy of an intervention designed to reduce dietary sodium intake. Interviews were digitally recorded, transcribed verbatim and coded using an iterative qualitative process. In total, 30 (37% females, 53% Caucasians) participants, 63.2 ± 13.3 years, were interviewed. Time, convenience, and financial constraints hindered dietary adherence. Dietary counseling efforts were rated positively but require individualization. Ability to follow recommended guidelines was challenging. Suggestions for addressing barriers include technology-based interventions that allow patients to improve food choices and real-time decision-making, and permit tailoring to individual barriers and preferences.

Objective: Because unplanned pregnancies could cause maternal-fetal complications for women with diabetes, family planning vigilance (FPV) is imperative. The aims of this article are to operationalize and describe FPV and examine the associations among FPV behaviors and diabetes self-care management (DSM) and health outcomes of women with type 1 diabetes (T1D)., Research Design and Methods: Retrospective data were used from a follow-up study of adult women with T1D who participated as adolescents in a preconception counseling (PC) intervention trial and matched comparison women with T1D who did not receive the adolescent PC intervention. Participants completed online questionnaires regarding family planning behaviors, DSM, and clinical and reproductive health outcomes., Results: Participants (N = 102) were, on average, 23.7 years old (range 18-38) and 98.0% were white, 82.2% had some college, 25.8% were married, and 11.8% had biological children. Of those sexually active (n = 80, 78.4%), 50% were contraceptive vigilant and 11% were FPV (i.e., being contraceptive vigilant, receiving PC, and initiating discussions with health care professionals). Among FPV behaviors, only receiving PC and initiating discussion with health care professionals were correlated (r = 0.29, P = 0.010). Compared with nonvigilant women, contraceptive vigilant and FPV women used more effective contraceptive methods (P = 0.025) and experienced less diabetic ketoacidosis (P = 0.040) and hospitalizations (P = 0.064), whereas FPV women were aware of PC (P = 0.046) and younger when they received PC (P < 0.001). FPV components were associated with DSM and health outcomes (P < 0.05)., Conclusions: Women with diabetes should be FPV, but few were. FPV women were more likely to have PC earlier and better health outcomes, supporting early PC intervention., (© 2016 by the American Diabetes Association.)

With cervical cancer screening the choice of 1-year as a period of follow-up in positive high-risk HPV women without cytological lesions is still under discussion. We evaluated the management of these women and the role of HPV genotyping test. We did a cervical cancer screening study of women aged 35-64 with primary high-risk HPV test. Women positive for high-risk HPV with negative cytology were followed-up after 1 year. In this study we selected women with high-risk HPV+/PapTest- resulted high-risk HPV+ at recall and performed the PapTest and HPV genotyping test. The detection rate of squamous high grade (CIN2+) relative to the total screened cohort was 2.1‰, and it was 0.2‰ at the 1-year recall. The colposcopy performed in women referred at the 1-year recall accounted for 48.8% of the total (baseline + 1-year recall), and 84.3% of these women had no cytological lesions. The most frequent hr-HPV genotype detected was HPV16 and 66.7% of co-infections were due to HPV16 and HPV18. 54.5% of women presented a persistent infection at 1-year recall with the same HPV subtype, 50% of persistent infections was due to HPV16 and 16.7% of these were determined to be CIN2+ histological lesions. Our data show that it may be useful to extend the period of follow-up for women hr-HPV+/PapTest- so as to reduce the number of unnecessary colposcopies due to the transitory infections and that the genotyping test could help to identify the persistent infections in which HPV16 is involved.

Background: Granular cell tumors (GCTs) were firstly described by Weber in 1854 and 70 years later by Abrikossoff and classified as benign tumors. Originally considered muscle tumors, they have been identified as neural lesions, due to their close association with nerve and to their immunohystochemical characteristics. GCTs are uncommon tumors and they may arise in any part of the body; they have been mainly observed in tongue, chest wall and upper extremities; less frequent sites are larynx, gastrointestinal tract, breast, pituitary stalk and the female anogenital region. Here we report a case of GCT showing an uncommon localization such as the upper third of the right rectus muscle of the abdominal wall., Case Presentation: A 45 year-old woman of Caucasian origin presented to the surgeon with a 6-month history of light pain in the upper third of the abdominal wall. Radiological exams (Ultrasonography, Computed Tomography and Contrast magnetic resonance imaging) showed a localized in the right rectus abdominis muscle. After excision, histological and immunohystochemical analysis, with the support of electron microscopy, allowed making diagnosis of granular cell tumor., Discussion: After fist description by Abrikosoff in 1926 of GCT like mesenchymal tumor of unknown origin, in recent years immunohystochemical techniques definitely demonstrated the histogenetic derivation of GCT from Schwann cells. Granular cell tumors are rare, small, slow-growing, solitary and painless subcutaneous nodules which behave in a benign fashion, but can have a tendency to recur; in rare cases they can metastasize, when they became malignant; there are some clinical and histological criteria to suspect the malignance of this tumor., Conclusion: It is important that clinicians, radiologists and pathologists are aware of the clinical presentation and histopathology of GCT for appropriate management, counselling and follow-up. In our case we had a complete radiological, morphological and immunohystochemical characterization of the lesion and a definitive diagnosis of benignity confirmed by electron microscopy.

Infection with high-risk human papillomavirus (hr-HPV) 16, 18, and 45 causes 94% of cervical carcinoma. In the present screening center the authors perform the hr-HPV test followed by Pap test to women aged 35-64 years if they result hr-HPV+. The authors' aimed to provide data regarding the genotyping test and eventually to propose this test as alternative to triage cytology. They used a genotyping test to identify HPV 16, 18, and 45 in 22 women with histological diagnosis of CIN2+, 22 women with histological diagnosis of CIN1 and 22 women hr-HPV+/Pap-. The group of CIN2+ showed the higher positivity to the test and the higher positivity to HPV 16 than other groups. Analyzing the clinical performance of the genotyping test the authors observed that the specificity was 64%. From these data they concluded that the identification of HPV 16 is predictive for high-grade lesions but this test could not be used alternatively to triage cytology.

Background: Sonoelastography is a novel and promising imaging tool, which has been applied to breast, thyroid, and prostate tissues. The aim of this study was to evaluate focal lesions of the testes with diameters of <10 mm using sonoelastography, B-mode sonography (US), and colour Doppler ultrasonography (CDU)., Methods: Thirty patients who were referred to our outpatient clinics for varicocoeles, scrotal pain, scrotal enlargements, epididymitis, palpable testicular nodules, or infertility, were prospectively enrolled into this study. Ultrasound evaluations had revealed that 27 subjects had focal testicular lesions with diameters of <10 mm and 3 subjects had 10-mm spherical non-homogeneous testicular nodules. All lesions were evaluated using semiquantitative sonoelastography, and the patients underwent orchifunicolectomies. The testicular lesions were examined histopathologically. The vascularization of the lesions and the surrounding testicular parenchyma was evaluated by analysing the immunohistochemical distribution of the cluster of differentiation 31 and by calculating the vascular indices (VI). Potential associations between the strain ratios (stiffness of the lesions) and the VI were tested., Results: Analyses of the strain fields obtained using semiquantitative sonoelastography yielded different values for the masses and the surrounding tissues, which led to significant increases in the strain ratios. Sonoelastography upheld all of the diagnoses that were suspected when the patients were physically examined, when the serum markers were analysed, and after the patients had undergone US and CDU. Histopathological examinations confirmed the neoplastic characteristics of these masses. A significant inverse correlation was determined between the sonoelastographic strain ratio and the VI (Pearson correlation coefficient, r, = - 0.93; P < 0.001)., Conclusion: Our investigation shows that semiquantitative sonoelastography may provide additional objective information to support the algorithm used to diagnose testicular lesions. This might be of crucial diagnostic importance for lesions with diameters of <10 mm, particularly if they are not palpable, are negative for serum tumour markers, and if the findings from ultrasonography and CDU are equivocal. The findings from semiquantitative sonoelastography might indicate the need for surgical exploration. Further investigations with larger numbers of patients are required to corroborate these data and to support the use of semiquantitative sonoelastography in the evaluation of testicular lesions.

Background: Schwannomas are tumours arising from Schwann cells, which sheath the peripheral nerves. Here, we report a rare case of left intrascrotal, extratesticular schwannoma. Although rare, scrotal localisation of schwannomas has been reported in male children, adult men, and elderly men. They are usually asymptomatic and are characterised by slow growth. Patients generally present with an intrascrotal mass that is not associated with pain or other clinical signs, and such cases are self-reported by most patients. Imaging modalities (such as ultrasonography, computed tomography, and magnetic resonance imaging) can be used to determine tumour size, exact localisation, and extension. However, the imaging findings of schwannoma are non-specific. Therefore, only complete surgical excision can result in diagnosis, based on histological and immunohistochemical analyses. If the tumour is not entirely removed, recurrences may develop, and, although malignant change is rare, this may occur, especially in patients with a long history of an untreated lesion. Thus, follow up examinations with clinical and imaging studies are recommended for scrotal schwannomas., Case Presentation: A 52-year-old man presented with a 3-year history of asymptomatic scrotal swelling. Physical examination revealed a palpable, painless, soft mass in the left hemiscrotum. After surgical removal of the mass, its histological features indicated schwannoma., Conclusions: Schwannoma should be considered in cases of masses that are intrascrotal but extratesticular. Ultrasonography provides the best method of confirming the paratesticular localisation of the tumour, before surgical removal allows histopathological investigation and definitive diagnosis. Surgery is the standard therapeutic approach. To prevent recurrence, particular care should be taken to ensure complete excision. This case report includes a review of the literature on scrotal schwannomas.

Background/aims: Gastrointestinal stromal tumors (GISTs) strongly express a receptor tyrosine kinase (RTK, c-KIT-CD117) harboring a KIT mutation that causes constitutive receptor activation leading to the development and growth of tumors; 35% of GISTs without KIT mutations have platelet-derived growth factor receptor alpha (PDGFRA) mutations, and the type of mutation plays an important role in the response to treatment. This study aimed to establish the frequency of stop codon mutations in the RTKs, KIT, and PDGFRA, in GISTs and correlate this molecular alteration with protein expression and treatment responsiveness., Methods: Seventy-nine GISTs were analyzed for both KIT and PDGFRA mutations. Immunohistochemical expression was studied in tissue microarray blocks., Results: We found three rare KIT mutations in exon 11 that induced a stop codon, two at position 563 and one at position 589, which have never been described before. All three tumors were CD117-, DOG1-, and CD34-positive. Two patients with a KIT stop codon mutation did not respond to imatinib therapy and died shortly after treatment., Conclusions: The association between stop codon mutations in KIT and patient survival, if confirmed in a larger population, may be useful in choosing effective therapies.