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Verona, Italy

Amato E.,University of Verona | Molin M.D.,Sol Goldman Pancreatic Research Center | Molin M.D.,University of Verona | Mafficini A.,University of Verona | And 16 more authors.
Journal of Pathology | Year: 2014

Intraductal neoplasms are important precursors to invasive pancreatic cancer and provide an opportunity to detect and treat pancreatic neoplasia before an invasive carcinoma develops. The diagnostic evaluation of these lesions is challenging, as diagnostic imaging and cytological sampling do not provide accurate information on lesion classification, the grade of dysplasia or the presence of invasion. Moreover, the molecular driver gene mutations of these precursor lesions have yet to be fully characterized. Fifty-two intraductal papillary neoplasms, including 48 intraductal papillary mucinous neoplasms (IPMNs) and four intraductal tubulopapillary neoplasms (ITPNs), were subjected to the mutation assessment in 51 cancer-associated genes, using ion torrent semiconductor-based next-generation sequencing. P16 and Smad4 immunohistochemistry was performed on 34 IPMNs and 17 IPMN-associated carcinomas. At least one somatic mutation was observed in 46/48 (96%) IPMNs; 29 (60%) had multiple gene alterations. GNAS and/or KRAS mutations were found in 44/48 (92%) of IPMNs. GNAS was mutated in 38/48 (79%) IPMNs, KRAS in 24/48 (50%) and these mutations coexisted in 18/48 (37.5%) of IPMNs. RNF43 was the third most commonly mutated gene and was always associated with GNAS and/or KRAS mutations, as were virtually all the low-frequency mutations found in other genes. Mutations in TP53 and BRAF genes (10% and 6%) were only observed in high-grade IPMNs. P16 was lost in 7/34 IPMNs and 9/17 IPMN-associated carcinomas; Smad4 was lost in 1/34 IPMNs and 5/17 IPMN-associated carcinomas. In contrast to IPMNs, only one of four ITPNs had detectable driver gene (GNAS and NRAS) mutations. Deep sequencing DNA from seven cyst fluid aspirates identified 10 of the 13 mutations detected in their associated IPMN. Using next-generation sequencing to detect cyst fluid mutations has the potential to improve the diagnostic and prognostic stratification of pancreatic cystic neoplasms. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Palminteri E.,Center for Reconstructive Urethral and Genitalia Surgery | Gacci M.,University of Florence | Berdondini E.,Center for Reconstructive Urethral and Genitalia Surgery | Poluzzi M.,Ospedale Sacro Cuore | And 2 more authors.
European Urology | Year: 2010

Background: Urethral stent placement for recurrent anterior urethral strictures may cause restenosis and complications. Objective: To describe our experience with patients who had restenoses and complications following urethral stent placement for the treatment of recurrent anterior urethral strictures. Design, setting, and participants: We evaluated retrospectively the records of 13 men with anterior urethral stricture who experienced restenosis and complications after stent insertion. We recorded stent position, prestent and poststent urethral procedures, restenosis location, stent-related complications, and management of stent failures. Surgical procedure: The stent was removed en bloc with the whole strictured urethral segment or wire by wire after a ventral or a double-ventral plus dorsal-sagittal urethrotomy and stent section. Measurements: Successful outcome was defined as standard voiding, without need of any postoperative procedure, and full recovery from complications. Results and limitations: Four patients did not undergo surgery and the stent was left in situ. Of these patients, two required permanent suprapubic cystostomy. Nine patients underwent challenging surgical stent removal and salvage urethrostomy: After the first stage, three patients are waiting for further reconstructive steps, five elected the urethrostomy as a permanent diversion, and one completed the staged reconstruction using a buccal mucosa graft at the second stage. After surgery, seven of the nine patients (77.8%) were free of strictures and stent-related complications, while a restenosis occurred in two of the nine (22.2%) cases. Conclusions: The management of urethral stent failure represents a therapeutic challenge. The stent risks converting a simple stenosis into a complex stenosis requiring a staged urethroplasty, a definitive urethrostomy, or a permanent suprapubic diversion. © 2009 European Association of Urology.

van Zeeburg E.J.T.,The Rotterdam Ophthalmic Institute | Cereda M.G.,The Rotterdam Eye Hospital | van der Schoot J.,The Rotterdam Ophthalmic Institute | Pertile G.,Ospedale Sacro Cuore | And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2011

PURPOSE. To study early flow and revascularization in a free, autologous, retinal pigment epithelium (RPE)-choroid graft. METHODS. This prospective cohort study used spectral domain- optical coherence tomography (SD-OCT) after RPE-choroid graft surgery in 12 patients. This SD-OCT was combined with fluorescein angiography (FA) and indocyanine green angiography (ICGA) in 5 patients. RESULTS. SD-OCT revealed that vessel diameter, number of vessels, and graft thickness increased in 10 of 12 patients, starting between 3 and 10 days after surgery. A subsequent decrease in thickness was found in all 10 patients, beginning as early as 8 days after surgery. Initially, the graft vessels were optically clearer than the underlying choroidal recipient vessels. Between 8 and 30 days after surgery, the optically clear vessels became gray, similar to the recipient choroid. FA and ICGA revealed perfusion in 4 of 5 patients between postoperative days 6 and 15. Between postoperative days 12 and 60, the entire choroidal structure of the graft was visible on ICGA. CONCLUSIONS. These data suggest that enlargement of vessel diameter, increase in the number of choroidal vessels, and graft thickening visualized by SD-OCT correspond with the ingrowth of afferent vessels, as demonstrated by ICGA. The subsequent establishment of efferent vessels results in flow, imaged as a change in color of the graft's vessels from optically clear to gray, graft thinning on SD-OCT, and complete revascularization on ICGA. SD-OCT, a noninvasive examination, can be used to demonstrate early graft perfusion in patients (trialregister. nl/trialreg/admin/rctview.asp number, NTR1768). © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Giannelli S.G.,San Raffaele Scientific Institute | Demontis G.C.,University of Pisa | Pertile G.,Ospedale Sacro Cuore | Rama P.,San Raffaele Scientific Institute | And 2 more authors.
Stem Cells | Year: 2011

There is growing evidence that Müller glia cells (MGCs) might act as regenerative elements in injured retinas of fishes and amniotes. However, their differentiation potential in humans is yet unknown. We isolated Müller glia from adult human retinas and propagated them in vitro revealing for the first time their ability to differentiate into rod photoreceptors. These results were also confirmed with mice retinas. Here, we describe conditions by which human MGCs adopt a rod photoreceptor commitment with a surprising efficiency as high as 54%. Functional characterization of Müller glia-derived photoreceptors by patch-clamp recordings revealed that their electrical properties are comparable to those of adult rods. Interestingly, our procedure allowed efficient derivation of MGC cultures starting from both injured and degenerating and postmortem human retinas. Human transplanted Müller glia-derived photoreceptors integrate and survive within immunodeficient mouse retinas. These data provide evidence that Müller glia retains an unpredicted plasticity and multipotent potential into adulthood, and it is therefore a promising source of novel therapeutic applications in retinal repair. © AlphaMed Press.

Schwartzman M.L.,New York Medical College | Iserovich P.,SUNY Optometry | Gotlinger K.,New York Medical College | Bellner L.,New York Medical College | And 8 more authors.
Diabetes | Year: 2010

OBJECTIVE - This study was aimed at obtaining a profile of lipids and proteins with a paracrine function in normal and diabetic vitreous and exploring whether the profile correlates with retinal pathology. RESEARCH DESIGN AND METHODS - Vitreous was recovered from 47 individuals undergoing vitreoretinal surgery: 16 had nonproliferative diabetic retinopathy (NPDR), 15 had proliferative diabetic retinopathy, 7 had retinal detachments, and 9 had epiretinal membranes. Protein and lipid autacoid profiles were determined by protein arrays and mass spectrometry-based lipidomics. RESULTS - Vitreous lipids included lipoxygenase (LO)- and cytochrome P450 epoxygenase (CYP)-derived eicosanoids. The most prominent LO-derived eicosanoid was 5-hydroxyeicosate traenoic acid (HETE), which demonstrated a diabetes-specific increase (P = 0.027) with the highest increase in NPDR vitreous. Vitreous also contained CYP-derived epoxyeicosatrienoic acids; their levels were higher in nondiabetic than diabetic vitreous (P < 0.05). Among inflammatory, angiogenic, and angiostatic cytokines and chemokines, only vascular endothelial growth factor (VEGF) showed a significant diabetes-specific profile (P < 0.05), although a similar trend was noted for tumor necrosis factor (TNF)-α. Soluble VEGF receptors R1 and R2 were detected in all samples with lowest VEGF-R2 levels (P < 0.05) and higher ratio of VEGF to its receptors in NPDR and PDR vitreous. CONCLUSIONS - This study is the first to demonstrate diabetes-specific changes in vitreous lipid autacoids including arachidonate and docosahexanoate-derived metabolites indicating an increase in inflammatory versus anti-inflammatory lipid mediators that correlated with increased levels of inflammatory and angiogenic proteins, further supporting the notion that inflammation plays a role the pathogenesis of this disease. © 2010 by the American Diabetes Association.

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