Molecular diagnostic tools for the detection of nodal micrometastases in prostate cancer patients undergoing radical prostatectomy with extended pelvic lymph node dissection: a prospective study

Background: Routine pathological examination can miss micro-metastatic tumor foci in the lymph nodes (LN) of patients with prostate cancer (PCa) that undergo radical prostatectomy and pelvic lymph node dissection (PLND). The aim of the present prospective study was to evaluate the impact of micrometastases assessed by serial section (SS), immunohistochemistry (IHC), and Real-time Polymerase Chain Reaction (RT-PCR) in patients undergoing radical prostatectomy with extended PLND. Materials and methods: 32 consecutive patients who underwent radical prostatectomy with extended PLND (obturator, internal/external and distal 2cm common iliac lymph-nodes (LN)) for intermediate (clinical T1c-T2 and PSA:10-20 ng/mL and clinical Gleason Score = 7) or high (clinical stage T3 or PSA>20 or clinical Gleason Score = 8-10) PCa were enrolled. The nodes were processed by the one uropathologist, both according to the routine pathological examination (analysis of the central section for 4 mm nodes or every 2 mm for LN>4 mm), which served as comparative method, both according to SS, IHC with antibodies against PSA and broad-spectrum Cytokeratins (BSCK), and quantitative RT-PCR targeting PSA, PSMA (PS Membrane Antigen), and Glucuronidase-S-Beta (GUSB) mRNA, that are over-expressed in prostatic cancer cells. Results: A total of 628 LN were analyzed, with a mean number of LN removed of 19.6 (SD = 7.2). Applying the routine pathological examination, 10 (31.2%) patients and 23 (3.9%) LN resulted positive for nodal involvement, with mean positive LN of 2.2 (SD = 1.4). After applying the SS and the molecular method of analysis (IHC and RT-PCR), micrometastases were found in 7 LN (SS showed micrometastases in 3 of them, IHC in 6 of them and RT-PCR in 7 of them); a total of 3 (9.3%) node-negative patients showed micrometastases at routine pathological examination (in 2 patients with RT-PCR and in 1 with IHC). Conclusions: The significance of micrometastases in PCa and the potential therapeutic role of PLND is not yet clarified, but the molecular analysis of the LN can detect a significant percentage of patients who harbor micro-metastatic PCa missed at routine pathological examination, and can enhance the accuracy of lymphadenectomy as a staging method.     

Multiple brain networks support processing speed abilities of patients with multiple sclerosis

Objectives: Many people affected by multiple sclerosis (MS) experience cognitive impairment, especially decreases in information processing speed (PS). Neural disconnection is thought to represent the neural marker of this symptom, although the role played by alterations of specific functional brain networks still remains unclear. The aim is to investigate and compare patterns of association between PS-demanding cognitive performance and functional connectivity across two MS phenotypes.

Methods: Forty patients with relapsing-remitting MS (RRMS) and 25 with secondary progressive MS (SPMS) had neuropsychological and MRI assessments. Multiple regression models were used to investigate the relationship between performance on tests of visuomotor and verbal PS, and on the verbal fluency tests, and functional connectivity of four cognitive networks, i.e. left and right frontoparietal, salience and default-mode, and two control networks, i.e. visual and sensorimotor.

Results: Patients with SPMS were older and had longer disease history than patients with RRMS and presented with worse overall clinical conditions: higher disease severity, total lesion volume, and cognitive impairment rates. However, in both patient samples, cognitive performance across tests was negatively correlated with functional connectivity of the salience and default-mode networks, and positively with connectivity of the left frontoparietal network. Only the visuomotor PS scores of the RRMS group were also associated with connectivity of the sensorimotor network.

Conclusions: PS-demanding cognitive performance in patients with MS appears mainly associated with strength of functional connectivity of frontal networks involved in the evaluation and manipulation of information, as well as the default mode network. These results are in line with the hypothesis that multiple neural networks are needed to support normal cognitive performance across MS phenotypes. However, different PS measures showed partially different patterns of association with functional connectivity. Therefore, further investigations are needed to clarify the contribution of inter-network communication to specific cognitive deficits due to MS.     

The effects of atrial fibrillation on functional recovery in post-stroke patients

Purpose : This study evaluates the negative effects of atrial fibrillation (AF) on after stroke recovery and its relationship with age and other concomitant diseases. Method : One hundred and ninety-nine consecutive inpatients, after their first stroke, were enrolled and entered a rehabilitation program lasting 60 days. The mean interval since the stroke was 19 days. The disability, both at admission and at discharge, was assessed by Functional Independence Measure (FIM). Atrial fibrillation was diagnosed at admission on the basis of electrocardiographic recordings. Gender, age, blood pressure and blood sugar level were also taken into account. Results : Stroke patients suffering from AF, when compared to those lacking AF, have higher disability at admission as well as at discharge and had a lesser gain in functional recovery. No statistical difference of the AF occurrence was found between male and female patients. The negative correlation between age and functional gain was found only in AF patients. There was also a significant association between AF and hypertension, but not between AF and diabetes. At the beginning and at the end of the study, the median FIM scores of all the patients with AF were quite similar irrespective of manifesting hypertension, diabetes or neither of these two. Conclusions : The presence of AF has a negative prognostic value on post stroke outcome, particularly in the elderly patients. The pattern of recovery of stroke subjects having AF is not influenced by concomitant diseases like hypertension or diabetes.     

Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma

The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHLs) is associated with chromosomal translocations that deregulate the expression of various oncogenes. Recently, a novel mechanism of genetic lesion, termed aberrant hypermutation, has been identified in diffuse large B-cell lymphoma (DLBCL) of immunocompetent hosts. In these tumors, the somatic hypermutation (SHM) process that normally targets immunoglobulin V (IgV) genes in B cells appears to misfire and causes mutations in the 5' sequences of multiple proto-oncogenes, including PIM-1, PAX-5, RhoH/TTF, and c-MYC. To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these 4 genes in various histologic subtypes. Mutations in 1 gene or more were detected in 19 of 39 (48.7%) AIDS-NHL cases (10 of 18 AIDS-diffuse large B-cell lymphoma; 4 of 11 AIDS-Burkitt lymphoma; 4 of 6 AIDS-primary effusion lymphoma; 1 of 4 AIDS-primary central nervous system lymphoma), with 9 of 39 (23.1%) cases carrying mutations in 2 or more genes. Overall, PIM-1 was mutated in 5 of 39 (12.8%), PAX-5 in 8 of 39 (20.5%), RhoH/TTF in 9 of 39 (23.1%), and c-MYC in 7 of 27 (25.9%) AIDS-NHL cases. Mutations were represented mainly by single base pair substitutions (n = 63) with rare deletions/insertions (n = 5) and displayed features typical of the IgV-associated SHM process. In addition, a number of mutations in PIM-1 and c-MYC were found to affect coding exons, leading to amino acid substitutions with likely functional consequences. Analysis of intraclonal heterogeneity documented that the aberrant hypermutation activity may be ongoing in at least some cases. These data indicate that aberrant hypermutation is associated with various subtypes of AIDS-NHL and may represent a major contributor to their pathogenesis.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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Assessment of volume preservation performed before or after partial nephrectomy accurately predicts postoperative renal function: Results from a prospective multicenter study

Purpose

Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function.

Patency of the supraclinoid internal carotid artery branches after flow diversion treatment. A meta-analysis

Background and purpose

Placement of flow-diverters across the ostia of major ICA branches carries a risk of arterial occlusion. We determined the rate of occlusion of the supraclinoid ICA branches and the related symptoms, following coverage with flow-diverters.

Moderately Hypofractionated Helical IMRT,FDG–PET/CT-guided,for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs

Introduction

The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments.