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Background The Silk Vista Baby (SVB) flow diverter (FDS) is the only FDS deliverable via a 0.017 inch microcatheter and is specifically designed for the distal vasculature. We sought to evaluate the safety and efficacy of the SVB. Materials and Methods We performed a retrospective review to identify SVB cases at 4 tertiary neurosurgical centres within the U.K. Clinical, procedural, angiographic and follow-up data were collected. Results We identified 60 patients (35 female, 58%) of average age 54 ± 10.5 (range 30–72) with 61 aneurysms, 50 (81.9%) located in the anterior circulation. The majority of the aneurysms treated were unruptured (46, 75.4%) and saccular (46, 75.4%). Dome size was 6.2 ± 6.2 mm (range 1–36mm) and parent vessel diameter was 2.3 ± 0.4 mm (range 1.2-3.3 mm). An average number of 1.07 devices were implanted. Coils or other devices were implanted in 14 aneurysms (23.3%). At last angiographic follow-up (n = 55), 7.5 ± 4.2 months post-procedure, 32 aneurysms (57.1%) were graded as RRC I, 7 (12.5%) RRC II, and 17 RRC III (30.4%). Clinical complications, excluding death, were seen in 4 patients (6.8%) including 1 delayed aneurysm rupture and 3 symptomatic ischaemic events. Only one patient had permanent morbidity (mRS 1). 3 patients died during follow-up (5.1%); 2 deaths were related to the aneurysms (3.4%) – one ruptured dissecting MCA aneurysm, and one giant partially thrombosed posterior circulation aneurysm. 93% of patients were mRS ≤ 2 at last follow-up. Conclusion The SVB has high rates of technical success and an acceptable safety profile. Distal aneurysms may occlude slower due to relative oversizing of the devices.

Hypoxia-induced miR-210 is a crucial component of the tissue response to ischemia, stimulating angiogenesis and improving tissue regeneration. Previous analysis of miR-210 impact on the transcriptome in a mouse model of hindlimb ischemia showed that miR-210 regulated not only vascular regeneration functions, but also inflammation. To investigate this event, doxycycline-inducible miR-210 transgenic mice (Tg-210) and anti-miR-210 LNA-oligonucleotides were used. It was found that global miR-210 expression decreased inflammatory cells density and macrophages accumulation in the ischemic tissue. To dissect the underpinning cell mechanisms, Tg-210 mice were used in bone marrow (BM) transplantation experiments and chimeric mice underwent hindlimb ischemia. MiR-210 overexpression in the ischemic tissue was sufficient to increase capillary density and tissue repair, and to reduce inflammation in the presence of Wt-BM infiltrating cells. Conversely, when Tg-210-BM cells migrated in a Wt ischemic tissue, dysfunctional angiogenesis, inflammation, and impaired tissue repair, accompanied by fibrosis were observed. The fibrotic regions were positive for α-SMA, Vimentin, and Collagen V fibrotic markers and for phospho-Smad3, highlighting the activation of TGF-β1 pathway. Identification of Tg-210 cells by in situ hybridization showed that BM-derived cells contributed directly to fibrotic areas, where macrophages co-expressing fibrotic markers were observed. Cell cultures of Tg-210 BM-derived macrophages exhibited a pro-fibrotic phenotype and were enriched with myofibroblast-like cells, which expressed canonical fibrosis markers. Interestingly, inhibitors of TGF-β type-1-receptor completely abrogated this pro-fibrotic phenotype. In conclusion, a context-dependent regulation by miR-210 of the inflammatory response was identified. miR-210 expression in infiltrating macrophages is associated to improved angiogenesis and tissue repair when the ischemic recipient tissue also expresses high levels of miR-210. Conversely, when infiltrating an ischemic tissue with mismatched miR-210 levels, macrophages expressing high miR-210 levels display a pro-fibrotic phenotype, leading to impaired tissue repair, fibrosis, and dysfunctional angiogenesis. ispartof: CELL DEATH & DISEASE vol:12 issue:5 ispartof: location:England status: published

ObjectiveNon-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm.DesignIn a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS.ResultsCompared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%.ConclusionZonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.

About 75% of urothelial bladder cancers are non-muscle invasive (NMIBC), and limited to mucosa (Ta or CIS) or sub-mucosa (T1). An increase of androgen expression and androgen receptors has a positive effect on oncogenic expression. We aimed to evaluate whether 5-alpha reductase inhibitors (5-ARI) have a role in NMIBC.We retrospectively evaluated the clinical and pathological data of 423 patients with NMIBC who underwent transurethral bladder resection. We considered the number of resections, number of total recurrences, time of recurrences, and histopathology details. The population was classified into two groups: treated and untreated with 5-ARIs. The enrolled patients were in treatment with 5ARIs for symptomatic prostatic hyperplasia for at least 12 months. Mean follow-up time was 30.43 months.Patients treated with 5-ARIs had a lower rate of recurrence (14%) than the untreated group (37%). There was a significant difference in the mean number of recurrences between the untreated and the treated group (P=0.006). Furthermore, the treated group showed a significantly greater number of low than high grade tumors, compared to the untreated group (P≤0.05). There was a significant decrease in the number of muscle invasive tumors in treated patients (P=0.032). The recurrence-free survival rate of patients treated with 5-ARIs was significantly higher (P=0.0001).Long-term treatment with 5-ARIs might reduce the risk of bladder tumor recurrence, extension of lesions and increase the recurrence-free survival rate. A long-term, randomized prospective study could definitively assess the possible role of these drugs.

Aim of the current study is to describe our technique of hydrodissection (HD) of the retroprostatic space (RPS) performed between the Denonvillier's fascia (DF) and prostatic capsule (PC) and to evaluate its impact on the outcomes of nerve-sparing robot-assisted radical prostatectomy (nsRALP) during the learning-curve period.This randomized study enrolled 25 consecutive male patients with indication of nsRALP. The HD and the subsequent dissection of the seminal vesicles (SVs) and RPS was performed by a resident in learning curve for RALP; the residual portion of RALP was performed by an expert. The perioperative, oncologic and functional outcomes of 2 groups of patients (Group A: nsRALP after HD of the RPS and Group B: standard nsRALP without HD) were compared. Two analyses were performed, considering a per-protocol (PP) population regarding only randomized patients with correct HD and an Intention-To-Treat (ITT) population regarding all randomized patients.In 4/14 (29%) of patients of Group A the injected fluid was not intraoperatively identified in the expected plane. The groups were statistically homogeneous in relation to the baseline variables. A statistically significant difference was observed between the SVs/RPS dissection time and the SVs-related estimated blood loss in both analyses. A significantly higher rate of dry patients was observed in group A at 1 month after nsRALP. A statistically significant correlation was observed between the effective time of dissection of the SVs and the postoperative IIEF-5 drop.The transrectal ultrasound-guided transperineal HD seems useful for the preliminary development of the RPS during the learning curve period of nsRALP. It seems associated with less time and blood loss for the dissection of the SVs and RPS. Studies on larger cohorts are needed to draw more robust conclusions.

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut–brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut–brain interaction.

Hypoxia-induced miR-210 is a crucial component of the tissue response to ischemia, stimulating angiogenesis and improving tissue regeneration. Previous analysis of miR-210 impact on the transcriptome in a mouse model of hindlimb ischemia showed that miR-210 regulated not only vascular regeneration functions, but also inflammation. To investigate this event, doxycycline-inducible miR-210 transgenic mice (Tg-210) and anti-miR-210 LNA-oligonucleotides were used. It was found that global miR-210 expression decreased inflammatory cells density and macrophages accumulation in the ischemic tissue. To dissect the underpinning cell mechanisms, Tg-210 mice were used in bone marrow (BM) transplantation experiments and chimeric mice underwent hindlimb ischemia. MiR-210 overexpression in the ischemic tissue was sufficient to increase capillary density and tissue repair, and to reduce inflammation in the presence of Wt-BM infiltrating cells. Conversely, when Tg-210-BM cells migrated in a Wt ischemic tissue, dysfunctional angiogenesis, inflammation, and impaired tissue repair, accompanied by fibrosis were observed. The fibrotic regions were positive for α-SMA, Vimentin, and Collagen V fibrotic markers and for phospho-Smad3, highlighting the activation of TGF-β1 pathway. Identification of Tg-210 cells by in situ hybridization showed that BM-derived cells contributed directly to fibrotic areas, where macrophages co-expressing fibrotic markers were observed. Cell cultures of Tg-210 BM-derived macrophages exhibited a pro-fibrotic phenotype and were enriched with myofibroblast-like cells, which expressed canonical fibrosis markers. Interestingly, inhibitors of TGF-β type-1-receptor completely abrogated this pro-fibrotic phenotype. In conclusion, a context-dependent regulation by miR-210 of the inflammatory response was identified. miR-210 expression in infiltrating macrophages is associated to improved angiogenesis and tissue repair when the ischemic recipient tissue also expresses high levels of miR-210. Conversely, when infiltrating an ischemic tissue with mismatched miR-210 levels, macrophages expressing high miR-210 levels display a pro-fibrotic phenotype, leading to impaired tissue repair, fibrosis, and dysfunctional angiogenesis.

Critical limb ischemia is the most serious form of peripheral artery disease, characterized by severe functional consequences, difficult clinical management and reduced life expectancy. The goal of this study was to investigate the miR-210 role in the neo-angiogenic response after acute limb ischemia. Complementary approaches were used in a mouse model of hindlimb ischemia: miR-210 loss-of-function was obtained by administration of LNA-oligonucleotides anti-miR-210, for miR-210 gain-of-function, a doxycycline-inducible miR-210 transgenic mouse was used. We tested miR-210 ability to stimulate vascular regeneration following ischemia. We found that miR-210 was necessary and sufficient to stimulate blood perfusion recovery, as well as arteriolar and capillary density increase, in the ischemic muscle. To clarify the molecular events underpinning miR-210 pro-angiogenic action, the transcriptomic changes in ischemic muscles upon miR-210 blocking were analyzed. We found that miR-210 impacted the transcriptome significantly, regulating pathways and functions linked to vascular regeneration. In agreement with a pro-angiogenic role, miR-210 also improved cardiac function and left ventricular remodeling after myocardial infarction. Moreover, miR-210 blocking decreased capillary density in a Matrigel plug assay, indicating that miR-210 is necessary for angiogenesis independently of ischemia. Collectively, these data indicate that miR-210 plays a pivotal role in promoting vascular regeneration.

The aim of this study was to compare the perioperative and functional results between laparoscopic and robot-assisted simple prostatectomy (LSP and RASP) and Holmium laser enucleation of prostate (HoLEP) in prostate volumes ≥120 mL. The primary endpoint was to investigate and compare minimally invasive techniques in the management of large prostate gland volume, and the secondary endpoint was to evaluate the frequency and type of postoperative complications according to Clavien Dindo Classification.This multicenter study was conducted on male patients with LUTS associated with BPO candidates for surgical treatment. The surgery approach choice in relation to the prostatic volume ≥120 mL was HoLEP or minimally-invasive simple prostatectomy (LSP or RASP). All patients were prospectively randomized into three groups, according to a simple computed randomization: HoLEP, LSP and RASP groups. During the follow-up, all patients underwent postoperative control at 1, 3, 6, 12 and 24 months from the surgical procedure.One hundred ten male patients were randomized in three homogeneous groups: 36 in LSP, 32 in RASP and 42 in HoLEP group. During the follow-up (mean 26.15 months), despite the significant improvement compared to baseline results, no significant differences were shown, between the groups in terms of functional and perioperative outcomes. The only statistically significant data was reported for catheterization time, that resulted longer in the LSP group than RASP and HoLEP groups (P=0.002). Furthermore, MISP resulted in longer hospitalization, and lower rate of patients with new-onset irritative symptoms.This prospective randomized study is the first to compare extraperitoneal LSP, RASP and HoLEP in the treatment of LUTS secondary to benign prostatic hyperplasia for prostate volumes ≥120 mL. Our findings confirm the safety and efficacy of MISP, demonstrating its equivalence in functional outcomes and perioperative morbidity in comparison to HoLEP.

AIMS Shear wave elastosonography (SWE) is a non-invasive ultrasound imaging modality used to assess the mechanical properties of tissues such as rigidity and elasticity. In this prospective study, we investigated the effect of laparoscopic varicocelectomy on the elasticity, degree of fibrosis and function of the testes through SWE and we evaluated the correlation with semen parameters and histology findings. METHODS Male patients with monolateral left varicocele and progressive alteration of the semen quality were enrolled prospectively. Patients were evaluated before varicocelectomy, 3 and 6 months after surgery with semen analysis, ecocolordoppler US and SWE. In all patients, a left testicular biopsy was performed at the time of varicocelectomy and it was repeated after 6 months in 55% of patients in order to investigate the histological findings and to correlate with SWE results. RESULTS The study was conducted on 82 patients. SWE showed a statistically significant difference between left and right testicles. Three months after surgery the mean left testicular volume increased, mean left SWE features decreased, and sperm count increased (P values

BackgroundWhile anatomic features associated with the risk of posterior communicating artery (PcoA) occlusion after embolization of aneurysms of the PcoA segment of the internal carotid artery (ICA) are well known, the link between perforator origin and perforator infarction has only been reported following neurosurgical clipping. The aim of this study was to determine the origin of anterior thalamic perforators and correlate it with risk of perforator infarction after embolization of PcoA segment aneurysms.MethodsOne-hundred-and-ninety consecutive patients treated for PcoA segment aneurysms between 2017 and 2019 were included. PcoA and anterior thalamic perforator origin anatomy was assessed with computed tomography (CT) angiography, digital subtracted angiography, and high-resolution three-dimensional rotational cone-beam CT angiography (CBCT-A) by two independent interventional neuroradiologists. The presence of perforator infarction after embolization was ascertained from the patient’s notes and follow-up imaging.ResultsCBCT-A was superior in demonstrating the origin of perforators (PConclusionsOur study suggests that anterior thalamic perforators may arise from aneurysm wall when there is no PcoA. Anatomic association between PcoA agenesis and perforator arising from ICA could underlie such findings, and careful consideration is essential before aneurysm repair to anticipate the risk of thalamic infarction in such cases.

Post-prostatectomy urinary incontinence is an adverse event leading to significant distress. Our aim was to evaluate immediate urinary continence (UC) recovery in a single-surgeon prospective randomized comparative study between the traditional robot-assisted laparoscopic radical prostatectomy (TR-RALP) and the Retzius-sparing RALP (RS-RALP), for the treatment of the clinically localized prostate cancer (PCa). 102 consecutive PCa patients were prospectively randomized to TR-RALP (57) or RS-RALP (45). Postoperative continence was defined as patient-reported absence of leakage or use of 0 pads/day. The immediate continence rate and 95% confidence interval (CI 95%) were calculated for each treatment. Univariable and multivariate logistic regressions were used to assess predictors of immediate continence following RALP. Continence rates from 1 to 6 months were calculated by Kaplan–Meier curves; log-rank test was used for the curve comparison. Two analyses were performed, considering a per-protocol (PP) population regarding all randomized patients that received nerve-sparing RALP and an Intention-To-Treat (ITT) population regarding all randomized patients that received RALP. In the PP analysis, the rates of immediate continence were 12/40 (30%) (CI 95% 17–47%) for the TR-RALP and 20/39 (51.3%) (CI 95% 35–68%) for the RS-RALP (p = 0.05). In the ITT analysis, the corresponding rates were 12/57 (21%) (CI 95% 11–34%) for the TR-RALP and 23/45 (51%) (CI 95% 36–66%) for the RS-RALP (p = 0.001). Median time to continence was 21 days for the TR-RALP and 1 day for RS-RALP, respectively (p = 0.02). The relative Kaplan–Meier curves regarding continence resulted statistically different when compared with the log rank test (p = 0.02). In the multivariate analysis, lower age and the Retzius-sparing approach were significantly associated to earlier continence recovery. The Retzius-sparing approach significantly reduces time to continence following RALP. Further studies are required to confirm the reproducibility of our results and investigate the role of the RS-RALP as an additional “protective” factor for postoperative continence in the elderly population.

Background: Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula. Methods: Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth-associated protein 43, GAP43+fibers). Key Results: No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells. Conclusions and Inferences: Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.

Circular RNAs (circRNAs) constitute a recently re-discovered class of non-coding RNAs functioning as sponges for miRNAs and proteins, affecting RNA splicing and regulating transcription. CircRNAs are generated by &ldquo, back-splicing&rdquo, which is the linking covalently of 3&prime, and 5&prime, ends of exons. Thus, circRNA levels might be deregulated in conditions associated with altered RNA-splicing. Significantly, growing evidence indicates their role in human diseases. Specifically, myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by expanded CTG repeats in the DMPK gene which results in abnormal mRNA-splicing. In this investigation, circRNAs expressed in DM1 skeletal muscles were identified by analyzing RNA-sequencing data-sets followed by qPCR validation. In muscle biopsies, out of nine tested, four transcripts showed an increased circular fraction: CDYL, HIPK3, RTN4_03, and ZNF609. Their circular fraction values correlated with skeletal muscle strength and with splicing biomarkers of disease severity, and displayed higher values in more severely affected patients. Moreover, Receiver-Operating-Characteristics curves of these four circRNAs discriminated DM1 patients from controls. The identified circRNAs were also detectable in peripheral-blood-mononuclear-cells (PBMCs) and the plasma of DM1 patients, but they were not regulated significantly. Finally, increased circular fractions of RTN4_03 and ZNF609 were also observed in differentiated myogenic cell lines derived from DM1 patients. In conclusion, this pilot study identified circRNA dysregulation in DM1 patients.

Aims Antisense long noncoding RNAs (ncRNAs) are transcripts emerging from the opposite strand of a coding-RNA region and their role in heart failure (HF) is largely unknown. Additionally, HF and Alzheimer's disease (AD) share several non-genetic effectors and risk factors. We investigated the regulation of the β-secretase-1 (BACE1) gene and of its antisense transcript BACE1-AS in ischaemic HF. Methods and results BACE1 and BACE1-AS expression was measured in left ventricle biopsies from 18 patients affected by non-end stage ischaemic HF and 17 matched controls. The levels of both transcripts were increased in HF patients. Likewise, both transcripts increased also in a mouse model of ischaemic HF, and their expression was directly correlated. BACE1-AS was expressed by all cardiac cell types and BACE1-AS up- or down-modulation in cultured cardiomyocytes and endothelial cells induced a concordant regulation of the cognate BACE1 transcript. Interestingly, BACE1 increase also induced the intracellular accumulation of its product β-amyloid. In keeping with these findings, higher BACE1 protein and β-amyloid peptide levels were also observed in HF. Moreover, increased β-amyloid 1-40 was also found in the plasma of HF patients. Transcriptomic changes of BACE1-AS overexpressing and β-amyloid 1-40 treated cells were largely overlapping and indicated changes of relevant biological process such as 'cell cycle and proliferation', 'apoptosis', and 'DNA repair' as well as 'TGFβ-, TNFα-, p38-, EGFR-signalling', suggesting a potential maladaptive role of the BACE1-AS/BACE1/β-amyloid axis. Accordingly, the administration of β-amyloid peptides decreased the cell viability in endothelial cells and in both human IPS-derived and mouse cardiomyocytes. Moreover, both β-amyloid treatment and BACE1-AS overexpression increased endothelial cell apoptosis, and this effect was prevented by BACE1 silencing. Conclusion Given the neurotoxic role of β-amyloid in AD, dysregulation of the BACE1/BACE1-AS/β-amyloid axis might be relevant in HF pathogenesis, further implicating ncRNAs in the complex scenario of proteotoxicity in cardiac dysfunction.

Objectives The aim of our study is to evaluate the role of preoperative quality of life (QL) as a possible risk factor for post robotic assisted radical prostatectomy (RARP) urinary incontinence. The secondary aim is to evaluate the possible effect of preoperative QL on post RARP lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). Methods and materials Between 2012 and 2017, all patients undergoing RARP for prostate cancer were enrolled. Patient's demographic, clinical, and histological characteristics were recorded. ED, LUTS, urinary incontinence, and QL were evaluated at baseline and postoperatively at 3, 6, and 12 months. Incontinence was evaluated with the International Consultation on Incontinence Questionnaire – Urinary Incontinence Short Form questionnaire and QL with the EORTC QLQ-C30 global health score (QLQ-GHS). Multivariate logistic regression analysis was used to evaluate the risk of postoperative incontinence, moderate/severe incontinence, LUTS, and moderate/severe ED. Results Overall 4,603 patients were enrolled. Incontinence rates at 3, 6, and 12 months were respectively 17%, 10%, and 8%. On multivariate analysis, QL was an independent predictor of early incontinence (QLQ-GHS:0.71, CI:0.59–0.86; P= 0.001), severe incontinence (QLQ-GHS:0.65, CI:0.49–0.97; P= 0.006), and LUTS (QLQ-GHS:0.48, CI:0.41–0.57; P= 0.001). Single center design may be considered a limitation. Conclusions In our study a comprehensive evaluation of preoperative patient's QL, assessed by the EORTC QLQ-C30 questionnaire, can predict the early and long-term moderate/severe incontinence risk in RARP treated patients. Further studies should confirm our results.

Introduction: The aim of this study was to report our experience in the management of hematospermia observed in 16 patients suffering from xanthogranulomatous prostatitis. Methods: Recurrent episodes of hematospermia were the onset symptom in all patients, and in 25% of patients it was combined with fever. All patients reported PSA value elevation and the digital rectal examination (DRE) revealed an increase of the gland size and of its consistency in all cases. In all patients, the hematospermia was treated with the oral administration of two tablets of pollen extract in a single (1 g) dose daily for 30 days. Results: Sixteen patients were observed between 2008 and 2016, referring hematospermia, progressive lower urinary tract symptoms (LUTS), and serum PSA level increase. To exclude the prostate cancer presence all patients were submitted to transperineal TRUS guided biopsy. In all the patients complete resolution of hematospermia was achieved treatment with pollen extract. All patients were subsequently treated for LUTS (alpha-adrenergic blockers), but none reported any significant improvement of symptoms. Basing on these pieces of evidence, after 90 days of alpha-blockers therapy, all patients underwent bipolar TURP. Histological examination of resected prostatic tissue revealed in all patients the diagnosis of xanthogranulomatous prostatitis. Conclusions: Patients with xanthogranulomatous prostatitis especially experience irritative symptoms, sometimes combined with fever or hematospermia. Hematospermia as the onset symptom has not been reported so far. The administration of the pollen extract for 30 days was associated with a complete resolution of hematospermia.

Therapies based on circulating proangiogenic cells (PACs) have shown promise in ischemic disease models but require further optimization to reach the bedside. Ischemia-associated hypoxia robustly increases microRNA-210 (miR-210) expression in several cell types, including endothelial cells (ECs). In ECs, miR-210 represses EphrinA3 (EFNA3), inducing proangiogenic responses. This study provides new mechanistic evidences for a role of miR-210 in PACs. PACs were obtained from either adult peripheral blood or cord blood. miR-210 expression was modulated with either an inhibitory complementary oligonucleotide (anti-miR-210) or a miRNA mimic (pre-miR-210). Scramble and absence of transfection served as controls. As expected, hypoxia increased miR-210 in PACs. In vivo, migration toward and adhesion to the ischemic endothelium facilitate the proangiogenic actions of transplanted PACs. In vitro, PAC migration toward SDF-1α/CXCL12 was impaired by anti-miR-210 and enhanced by pre-miR-210. Moreover, pre-miR-210 increased PAC adhesion to ECs and supported angiogenic responses in co-cultured ECs. These responses were not associated with changes in extracellular miR-210 and were abrogated by lentivirus-mediated EFNA3 overexpression. Finally, ex-vivo pre-miR-210 transfection predisposed PACs to induce post-ischemic therapeutic neovascularization and blood flow recovery in an immunodeficient mouse limb ischemia model. In conclusion, miR-210 modulates PAC functions and improves their therapeutic potential in limb ischemia.

The aim of the study was to evaluate the long-term outcomes of pelvic floor muscle (PFM) rehabilitation in males with lifelong premature ejaculation (PE), using intravaginal ejaculatory latency time (IELT) and the self-report Premature Ejaculation Diagnostic Tool (PEDT) as primary outcomes. A total of 154 participants were retrospectively reviewed in this study, with 122 completing the training protocol. At baseline, all participants had an IELT ≤60 s and PEDT score >11. Participants completed a 12-week program of PFM rehabilitation, including physio-kinesiotherapy treatment, electrostimulation, and biofeedback, with three sessions per week, with 20 min for each component completed at each session. The effectiveness of intervention was evaluated by comparing the change in the geometric mean of IELT and PEDT values, from baseline, at 3, 6, and 12 months during the intervention, and at 24 and 36 months postintervention, using a paired sample 2-tailed t-test, including the associated 95% confidence intervals. Of the 122 participants who completed PFM rehabilitation, 111 gained control of their ejaculation reflex, with a mean IELT of 161.6 s and PEDT score of 2.3 at the 12-week endpoint of the intervention, representing an increase from baseline of 40.4 s and 17.0 scores, respectively, for IELT and PEDT (P < 0.0001). Of the 95 participants who completed the 36-month follow-up, 64% and 56% maintained satisfactory ejaculation control at 24 and 36 months postintervention, respectively.

Purpose To evaluate the differences between the old and the new Gleason score classification systems in upgrading and downgrading rates. Materials and methods Between 2012 and 2015, we identified 9703 patients treated with retropubic radical prostatectomy (RP) in four tertiary centers. Biopsy specimens as well as radical prostatectomy specimens were graded according to both 2005 Gleason and 2014 ISUP five-tier Gleason grading system (five-tier GG system). Upgrading and downgrading rates on radical prostatectomy were first recorded for both classifications and then compared. The accuracy of the biopsy for each histological classification was determined by using the kappa coefficient of agreement and by assessing sensitivity, specificity, positive and negative predictive value. Results The five-tier GG system presented a lower clinically significant upgrading rate (1895/9703: 19,5% vs 2332/9703:24.0%; p = .001) and a similar clinically significant downgrading rate (756/9703: 7,7% vs 779/9703: 8%; p = .267) when compared to the 2005 ISUP classification. When evaluating their accuracy, the new five-tier GG system presented a better specificity (91% vs 83%) and a better negative predictive value (78% vs 60%). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens were poor and good respectively for the five-tier GG system and for the 2005 Gleason score (k = 0.360 ± 0.007 vs k = 0.426 ± 0.007). Conclusions The new Epstein classification significantly reduces upgrading events. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications, particularly in prostate cancer management.

Treatment of patients with prostate cancer has evolved considerably in the last decade, especially in terms of minimization of the negative impacts on erectile function and continence to ensure good quality of life for treated patients. New surgical devices, such as dissectors and hemostatic scalpels, allow precise definition of the surgical field with finer dissection of the anatomic structures, with subsequent reductions in operative times and better oncologic and functional outcomes. Although monopolar scissors (MS) are still widely used, radiofrequency (RF) and ultrasound (US) scalpels have been introduced recently in laparoscopic radical prostatectomy (LRP). Despite the widespread use of these scalpels, however, few studies have compared these devices in terms of oncologic and functional outcomes after radical prostatectomy. The present study aimed to prospectively assess the impact of MS, RF, and US scalpels on margin status at apex, and recovery of urinary continence and erectile function in patients undergoing extraperitoneal LRP.A total of 150 men were prospectively enrolled between September 2009 and April 2013 and postoperatively evaluated for continence and clinical factors.There were no differences in terms of operative times (P=0.9433), blood loss (P=0.9681), apical margin positivity (P=0.3965) or postoperative hospital stay (P=0.9257) among the groups. Moreover, no differences in the functional outcome scores, as evaluated by the International Consultation on Incontinence self-administered Questionnaire, at 1, 3, and 6 months postsurgery were observed.Our study represents the first evaluation of continence recovery in LRP with respect to different devices used for prostatic apex dissection. We found that the oncologic, functional, and operative outcomes were similar between these different devices during LRP, with no scalpel demonstrating superiority in continence recovery.

Monopolar transurethral resection of the prostate (TURP) is the gold standard surgical treatment for bothersome moderate to severe lower urinary tract symptoms (LUTS) secondary to benign prostate obstruction. The aim of the study is to compare monopolar versus bipolar TURP focusing on operative and functional outcomes, and evaluating complications with a long-term follow-up. From January 2007 to July 2014, a total of 497 patients were randomized and prospectively scheduled to undergo bipolar (251) or monopolar (246) TURP. International prostate symptom score (IPSS), IPSS-Quality of life (QoL), post-void residual and maximum flow rate were assessed preoperatively and postoperatively at 3, 12, 24 and 36 months. Operative time, length of catheterization and hospitalization were all recorded. Complications were classified and reported. All patients completed the 36-month follow-up visit. Perioperative results showed no statistical significance between the two groups in terms of catheterization days, post-void residual, IPSS, IPSS-QoL score. The hospitalization length was found statistically significant in favor of the bipolar group. The 3-, 12-, 24- and 36-month follow-up showed significant and equal improvements in LUTS related to BPO in the two treatment groups. Regarding TURP complications, significant differences were observed in relation to urethral strictures, blood transfusion and TUR syndrome in favor of the bipolar group. Monopolar and bipolar TURP are safe and effective techniques for BPH management. Bipolar TURP in our prospective study reported the same efficacy of monopolar prostate resection, with a significant reduction of related complications.

Background Long noncoding RNAs (lncRNAs) are non-protein coding transcripts regulating a variety of physiological and pathological functions. However, their implication in heart failure is still largely unknown. The aim of this study is to identify and characterize lncRNAs deregulated in patients affected by ischemic heart failure. Methods LncRNAs were profiled and validated in left ventricle biopsies of 18 patients affected by non end-stage dilated ischemic cardiomyopathy and 17 matched controls. Further validations were performed in left ventricle samples derived from explanted hearts of end-stage heart failure patients and in a mouse model of cardiac hypertrophy, obtained by transverse aortic constriction. Peripheral blood mononuclear cells of heart failure patients were also analyzed. LncRNA distribution in the heart was assessed by in situ hybridization. Function of the deregulated lncRNA was explored analyzing the expression of the neighbor mRNAs and by gene ontology analysis of the correlating coding transcripts. Results Fourteen lncRNAs were significantly modulated in non end-stage heart failure patients, identifying a heart failure lncRNA signature. Nine of these lncRNAs (CDKN2B-AS1/ANRIL, EGOT, H19, HOTAIR, LOC285194/TUSC7, RMRP, RNY5, SOX2-OT and SRA1) were also confirmed in end-stage failing hearts. Intriguingly, among the conserved lncRNAs, h19, rmrp and hotair were also induced in a mouse model of heart hypertrophy. CDKN2B-AS1/ANRIL, HOTAIR and LOC285194/TUSC7 showed similar modulation in peripheral blood mononuclear cells and heart tissue, suggesting a potential role as disease biomarkers. Interestingly, RMRP displayed a ubiquitous nuclear distribution, while H19 RNA was more abundant in blood vessels and was both cytoplasmic and nuclear. Gene ontology analysis of the mRNAs displaying a significant correlation in expression with heart failure lncRNAs identified numerous pathways and functions involved in heart failure progression. Conclusions These data strongly suggest lncRNA implication in the molecular mechanisms underpinning HF. Electronic supplementary material The online version of this article (doi:10.1186/s12967-016-0926-5) contains supplementary material, which is available to authorized users.

SummaryIntroduction Benign prostatic hyperplasia (BPH) resulting in lower urinary tract symptoms (LUTS) is a widespread disease that strongly interferes with the quality of life (QoL) of elderly males. It represents a real clinical and socio-economic problem may be due to the lack of a diagnostic, therapeutic and care pathway (DTCP) tool for LUTS/BPH that considers elderly people population in its whole complexity. The aim of this study was to evaluate the clinical effectiveness of the proposed DTCP LUTS/BPH tool. Methods This prospective study was conducted on 278 patients over 75 years old with non-neurogenic LUTS recruited from February to July 2014 by 10 general practitioners (GP) and two assisted sanitary residences (ASR). Only five GPs and one ASR were provided with the complete DTCP LUTS/BPH tool to create two different groups of patients: group A (138 patients) was treated without the aid of the DTCP; group B (140 patients) was treated according to the DTCP. Results At 1 year of follow-up, the patients of Group B compared with Group A achieved a greater and significant mean reduction in the questionnaires score (International Prostate Symptom Score, Quick prostate test and QoL) linked to a higher increase in the flowmetry parameters (Qmax) and a lower postvoid residual. Furthermore, in Group B compared to Group A, a greater improvement of hydronephrosis, creatinine values and erectile dysfunction (ED) were obtained at 1 year of follow-up. Conclusion The encouraging results obtained from this study are significant and support the use of this diagnostic, therapeutic and care tool (DTCP) as the ideal pathway management for elderly men with LUTS associated to BPH and ED. Further studies with greater number of elderly subjects and long-term follow-up are needed to confirm DTCP utility in the clinical management of LUTS/BPH and ED.

Background/Aims: To evaluate whether sustained response to α-interferon improves clinical outcome in patients with chronic hepatitis C. Methods: A cohort of 410 consecutive patients (65% with chronic hepatitis, 35% with cirrhosis) were treated with α-interferon in two trials (mean follow-up 62.1 months, range 7–109 months). All were serum HCV RNA positive before therapy and received first 10 then 5 million units of α-2b or α-n1 interferon three times weekly for 6 to 12 months. Sustained response was defined as normal aminotransferases 12 months after stopping interferon. Results: Sixty-two patients (15.1%: 54 with chronic hepatitis, eight with cirrhosis) were sustained responders. At the end of follow-up, 56 out of 62 sustained responders (90.3%) were serum HCV RNA negative. No biochemical relapse after 12 months was seen in sustained responders, regardless of initial histology, HCV genotype or persistence of HCV RNA. Although three died of non-hepatic causes, no liver-related events were observed among sustained responders. Complications of liver disease occurred in 34 relapser/non-responders: nine hepatocellular carcinomas, 21 ascites and four portal hypertensive bleedings. Eleven relapsers/nonresponders died: eight of hepatic and three of non-hepatic causes. Event-free survival was significantly longer in sustained responders than in all the remaining patients. In a regression analysis, sustained response to interferon, low age and absence of cirrhosis were independent predictors of event-free survival. Conclusion: Hepatitis C virus is probably eradicated and progression of liver disease is prevented in most patients who remain HCV RNA negative with normal transaminases for more than 1 year after stopping treatment.

Purpose Bladder dysfunction, secondary to diabetes, is mainly characterized by poor bladder emptying and overflow incontinence. However, there is evidence in literature that storage symptoms, as those suggestive for overactive bladder (OAB), may also affect people with diabetes. The aim of this study was to evaluate the prevalence of overactive bladder, the complaint of urinary urgency with/ without urge incontinence, usually with frequency and nocturia, in people with diabetes compared to healthy subjects (control group). Methods Symptoms were assessed through the overactive bladder questionnaire (OAB-q), an investigative tool, specifically developed for OAB diagnosis. Results OAB-q scores resulted higher in diabetic people than those of the control group. Age and disease duration resulted in measurements that showed a statistical correlation with the OAB-q scores. Conclusions OAB symptoms are more prevalent in diabetic people than in non-diabetic people. This prompts further research to determine whether the onset of OAB symptoms can be considered as an indicator of diabetic neuropathy.

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.

To evaluate the accuracy of contrast material-enhanced multi-detector row computed tomographic (CT) colonography for preoperative staging of colorectal cancer.Forty-one patients with colorectal carcinoma underwent preoperative contrast-enhanced multi-detector row CT colonography. Images were obtained in the arterial (start delay of 35 seconds) and portal venous (start delay of 70 seconds) phases. The arterial phase was focused on the suspected region of neoplasm, whereas the venous phase included the whole abdomen and pelvis. Two radiologists independently evaluated the depth of tumor invasion into the colorectal wall (T) and regional lymph node involvement (N) on transverse CT images alone and in combination with multiplanar reformations (MPRs). Disagreements were resolved by means of consensus. CT findings were compared with pathologic results, which served as the reference standard. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were assessed. Differences in accuracy for T and N staging were assessed by using the McNemar test.In T staging, overall accuracy was 73% when transverse images were evaluated alone and 83% when they were evaluated in combination with MPRs. This difference was not significant. N staging was associated with an overall accuracy of 59% with transverse images alone and 80% with combined transverse and MPR images (P.01).Contrast-enhanced multi-detector row CT colonography is an accurate technique for preoperative local staging of colorectal tumors.

To evaluate the role of MR Cholangiopan-creatography (MRCP) as a first imaging modality in patients with suspected biliary tree pathology and indications to endoscopic retrograde cholangiopancreatography (ERCP).Eighty-eight patients, with clinical signs of biliary tree pathology underwent MRCP, performed with a 1.5 T unit and a phased-array coil. Surgery, intraoperative cholangiography, percutaneous transhepatic cholangiography (PTC) or ERCP were regarded as the gold standard in patients with obstruction; the remaining patients underwent follow-up MRCP examinations at 6-9 months. The MR examination was performed with baseline T1w 2D FLASH and T2w TSE sequences, followed by the MRCP study (single-slab breath-hold RARE and multislice breath-hold HASTE sequences). The MR images were independently evaluated by two radiologists.MRCP showed normal findings in 20 patients; 68 patients had biliary duct dilatation. In 11 out of 68 patients MRCP did not identify any obstruction (9/11 were true negative cases). A diagnosis of benign obstruction was expressed in 36/59 patients (4 chronic pancreatitis, 29 choledocolithiasis, 4 inflammatory obstruction, 2 primary sclerosing cholangitis), with 1 false positive and 5 false negatives (sensitivity, specificity and diagnostic accuracy of 86%, 95% and 90%, respectively). MRCP identified 23 neoplastic stenoses (20/23 were true positives): the sensitivity, specificity and diagnostic accuracy values were 100%, 87% and 95%, respectively. MRCP correctly identified the level of obstruction in 100% of cases.MRCP may be considered as a first-step imaging method in patients with clinical signs of biliary disease. The workload of ERCP in the diagnostic stage could therefore be reduced and its use be reserved for therapeutic indications.

The aim of this study was to assess the long-term outcome in hepatitis B virus (HBV)-infected patients according to HBV, hepatitis C virus (HCV), and hepatitis D virus (HDV) replication, focusing on survival, liver failure, and hepatocellular carcinoma (HCC). A cohort of 302 hepatitis B surface antigen (HBsAg)-positive subjects (mean age, 34 +/- 15.3 years; male/female 214/88; 39 subjects under 14 years) with biopsy-proven chronic hepatitis (86 with cirrhosis) was prospectively assessed, with a median follow-up of 94 +/- 37.6 months. One hundred nine patients received interferon alfa (IFN). At baseline, 86 subjects (28.5%) were hepatitis B e antigen (HBeAg)-positive (wild-type HBV), 80 (26.5%) were HBeAg-negative, HBV-DNA-positive, 76 (25.2%) had HDV infection, 43 (14.2%) had dual HBV/HCV infection, and 17 (5.6%) were negative for HBV-DNA, anti-HCV, and anti-HDV. During follow-up, decompensation of disease occurred in 46 subjects: 8 developed HCC, 36 developed ascites, and 2 developed jaundice. Five patients underwent transplantation. Thirty-five subjects died: 33 of hepatic and 2 of nonhepatic causes. Overall mortality was 5.2-fold that of the general population (95% CI: 3.6-7.3; 35 deaths observed, 6.7 expected; P.0001). By Cox regression analysis, survival was independently predicted by young age, absence of cirrhosis at baseline, and sustained normalization of aminotransferases during follow-up. Survival without decompensation was independently predicted by the same factors and by IFN treatment. Chronic hepatitis B infection increases mortality in comparison with the general population in our area regardless of specific virological profiles at presentation. Presence of cirrhosis and persistent necroinflammation markedly increase the risk of death.

In chronic hepatitis C the rate of relapse after an end-of-treatment response to interferon may exceed 50%. The usefulness of retreatment of relapsers with interferon in obtaining a complete sustained response and the role of clinical, virological and immunological features in determining long-term efficacy of retreatment are unclear. We aimed to assess the efficacy of interferon retreatment in obtaining a complete sustained response, to evaluate whether increasing the dose may enhance responsiveness, and to identify possible predictors of sustained response. We enrolled 42 patients with biopsy-proven chronic hepatitis C without cirrhosis who had previously responded to a six-month course of Interferon-alpha2b (total dose: group A, 22 patients, 234 MU; group B, 20 patients, 468 MU) and then relapsed. All, except one, were HCV-RNA negative at the end of first cycle of interferon; most (31/42, 74%) were infected by HCV 1b. Subjects were randomly allocated to receive another cycle of interferon either at the original dose (group A1: 234 MU, 11 patients; group B1 468 MU, 10 patient) or twice the original dose (group A2: 468 MU, 11 patients; group B2: 936 MU, 10 patients). At the end of the second cycle of interferon, 24 subjects (57%) had normal ALT and were HCV-RNA negative, and 16 (39%) had normal ALT, but were HCV-RNA positive. A complete sustained response was obtained in eight patients (19%), at a similar rate in all treatment groups. Complete sustained responders were different from the other patients in terms of age (35.9 +/- 10.4 vs 44.1 +/- 8.8, P = 0.027), rate of infection with non-1b HCV (6/8 vs 5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428 median copies/ml, P = 0.037) and serum levels of 90K/MAC-2 BP (5.76 +/- 3.01 vs 10.25 +/- 5.16 units/ml, P = 0.02), an N-glycoprotein implicated in cellular defense functions. Multivariate logistic analysis validated age and HCV genotype as independent predictors of CSR. Among noncirrhotic relapsers who received a total interferon doseor = 234 MU in the first cycle, retreatment usually induced end-of-treatment response. A complete sustained response was obtained in only one of every five subjects. Increasing the dose of interferon above that of the first cycle did not enhance the rate of sustained response. In conclusion we might assert that young subjects infected by non-1b HCV and with low levels of HCV-RNA and of 90K/MAC-2 BP are the best candidates for retreatment.

BACKGROUND & AIMS: Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C. METHODS: A cohort of 384 European cirrhotic patients was enrolled at seven tertiary referral hospitals and followed up for a mean period of 5 years. Inclusion criteria were biopsy-proven cirrhosis, abnormal serum aminotransferase levels, absence of complications of cirrhosis, and exclusion of hepatitis A and B viruses and of metabolic, toxic, or autoimmune liver diseases. RESULTS: Antibodies against hepatitis C virus were positive in 98% of 361 patients tested. The 5-year risk of hepatocellular carcinoma was 7% and that of decompensation was 18%. Death occurred in 51 patients (13%), with 70% dying of liver disease. Survival probability was 91% and 79% at 5 and 10 years, respectively. Two hundred five patients (53%) were treated with interferon alfa. After adjustment for clinical and serological differences at baseline between patients treated or not treated with interferon, the 5-year estimated survival probability was 96% and 95% for treated and untreated patients, respectively. CONCLUSIONS: In this cohort of patients, life expectancy is relatively long, in agreement with the morbidity data showing a slowly progressive disease. (Gastroenterology 1997 Feb;112(2):463-72)

In chronic hepatitis C virus (HCV) infection, the rate of sustained response to interferon is low. We evaluated, in patients responding to a 26-week course of interferon, the effect of high-dose maintenance therapy in preventing relapse. Three hundred and ten patients with chronic HCV infection (38.3% with cirrhosis, 80.6% with HCV type 1) received interferon alfa-2b for 26 weeks (10 MU tiw for 8 weeks, then 5 MU tiw for 18 weeks). One hundred and twenty-four subjects (40%) normalized aminotransferases, and were allocated randomly either to continue on 5 MU tiw for a further 26 weeks (prolonged therapy group: 60 patients) or to stop interferon (brief therapy group: 64 patients). Fifty-two weeks after stopping interferon the overall sustained biochemical response rate was 13.2% (41/310). The number of patients with normal aminotransferases was comparable between the prolonged and brief therapy groups (30% vs. 35.9%, P = n.s.), and the rate of HCV-RNA clearance was similar (48.8% vs. 42.4%, P = n.s.). The timing of posttreatment relapse was not influenced by the duration of therapy. Fifty-nine patients (19%) did not complete therapy due to adverse effects. Multivariate analysis identified four features predicting sustained biochemical response in subjects normalizing aminotransferases under therapy: negative HCV-RNA at end of therapy, normal aminotransferases at 4 weeks of therapy, high baseline aminotransferases, and high baseline platelets. Infection with HCV type 1 was not a significant predictor of response, due to its high prevalence in our population (80.6%). It is concluded that in patients with chronic hepatitis C mostly infected by HCV type 1, a prolonged high-dose interferon course (900 MU over 52 weeks) did not increase the rate of sustained biochemical response and of HCV-RNA clearance in comparison to a brief course (510 MU over 26 weeks).

Background This study aimed to evaluate the behavior of non-muscle-invasive bladder cancer (NMIBC) in patients submitted to transurethral bladder resection (TURB) comparing subjects in chronic therapy with aspirin, statins, or both drugs to untreated ones. Methods This retrospective study was conducted on 574 patients diagnosed with NMIBC who underwent TURB between March 2008 and April 2013. The study population was divided into two main groups: treated (aspirin and/or statins) and untreated. The treated group was further divided into three therapeutic subgroups: Group A (100 mg of aspirin, daily for at least two years); Group B (20 mg or more of statins, daily for at least two years); and Group C (100 mg of aspirin and 20 mg of statins together). The mean follow-up of patients was 45.06 months. Results No significant differences were observed among the different groups at baseline. On multivariate analysis, statin treatment, smokers and high stage disease (T1) achieved the level of independent risk factor for the occurrence of a recurrence. When patients were stratified according to the different treatment; patients treated with statins (Group B) presented an higher rate of failure (56/91 patients; 61.5%) when compared to Group A (42/98 patients; 42.9%), Group C (56/98; 57.1%) and (133/287 patients; 46.3%). This difference corresponds to a significant difference in recurrence failure free survival (p = 0.01). Conclusions Our results suggest that long-term treatment with aspirin in patients with NMIBC might play a role on reducing the risk of tumor recurrence. In contrast, in our investigation data from statins and combination treatment groups showed increased recurrence rates. A long-term randomized prospective study could definitively assess the possible role of this widely used drugs in NMIBC.

The mouse Htf9-a gene encodes a small hydrophilic protein, named Ran-binding protein 1 (RanBP-1), for its interaction with the Ras-related Ran protein; RanBP-1 binds the biologically active form of Ran. Ran has been implicated in a variety of nuclear events including DNA replication, RNA export and protein import, and monitoring completion of DNA synthesis before the onset of mitosis; it biological activity is thought to be regulated in S phase. We have investigated whether expression of the Htf9-a/RanBP-1 gene is linked to cell proliferation. Expression of the Htf9-a/RanBP-1 transcript appeared to be dependent on the proliferating state of the cells and peaked in S phase. We have identified a promoter region required for Htf9-a cell cycle-dependent expression and for responsiveness to cell cycle regulators. An E2F-binding site was identified within the cell cycle-regulated promoter region. Expression of the E1A oncoprotein prevented Htf9-a down-regulation in quiescent cells; in addition, both pRb and its relative p107 inhibited transcription from the Htf9-a promoter. These results link the control of Htf9-a/RanBP-1 expression to the cell cycle progression.

Background Metastatic penile carcinoma derived from cholangiocarcinoma (CCA) has not been previously reported in the literature. Common metastatic sites for CCA include the regional lymph nodes and adjacent organs. CCAs are not highly vascularised tumours, making hematogenous metastases uncommon. Hematogenous CCA metastases commonly occur at distant organs such as the lungs, adrenal glands, and bones. Median survival for patients with metastatic disease is generally less than 1 year. Case presentation A 74-year-old Caucasian man consulted us after having undergone penile ultrasonography for pain and increased thickness at the base of the penis after self-examination. The patient presented with a history of hepatitis C-related cirrhosis and intrahepatic CCA, diagnosed 3 years previously. A biopsy of the corpora cavernosa on both sides revealed a carcinoma harbouring the same histological and immunophenotypical features as the primary hepatic lesion. Conclusions To date, there is no case of penile or urogenital system metastasis from CCA described in the literature. Therefore, this article represents the first case report of penile metastasis from CCA.

The incidence of multiple primary malignant neoplasms increases with age, reflecting an increase in overall cancer risk in older patients. Cases of two or more concurrent primary cancers are still rare, although its incidence is increasing. Here, we report the case of a 57-year-old man who was referred to our institution with synchronous squamous cell carcinoma of the skin on the forehead, infiltrating ductal carcinoma of the breast, and transitional cell carcinoma of the urinary bladder. To the best of our knowledge, this is the first reported case in literature of this combination of primary neoplasms.