Prediction of Clinically Significant Prostate Cancer Using Multiparametric MRI, Biparametric MRI, and Clinical Parameters.

Introduction: Multiparametric MRI (mpMRI) is gold standard for the primary diagnostic work-up of clinically significant prostate cancer (csPCa). The aim of this study was to assess the benefit of the perfusion sequence and the non-inferiority of an MRI without contrast administration (bpMRI) compared to mpMRI while taking clinical parameters into account.

Methods: In this retrospective, non-interventional study we examined MRI data from 355 biopsy-naïve patients, performed on a 3T MRI system, evaluated by a board-certified radiologist with over 10 years of experience with subsequent mpMRI-TRUS fusion biopsy.

Comparative genomic profiling of glandular bladder tumours.

Primary glandular bladder tumours (bladder adenocarcinoma [BAC], urachal adenocarcinoma [UAC], urothelial carcinoma with glandular differentiation [UCg]) are rare malignancies with histological resemblance to colorectal adenocarcinoma (CORAD) in the majority of this subgroup. Definite case numbers are very low, molecular data are limited and the pathogenesis remains poorly understood. Therefore, this study was designed to complement current knowledge by in depth analysis of BAC (n = 12), UAC (n = 13), UCg (n = 11) and non-invasive glandular lesions (n = 19).

Meta-Analysis of Genome-Wide Association Studies and Network Analysis-Based Integration with Gene Expression Data Identify New Suggestive Loci and Unravel a Wnt-Centric Network Associated with Dupuytren's Disease.

Dupuytren´s disease, a fibromatosis of the connective tissue in the palm, is a common complex disease with a strong genetic component. Up to date nine genetic loci have been found to be associated with the disease. Six of these loci contain genes that code for Wnt signalling proteins.

Differential diagnosis of bladder versus colorectal adenocarcinoma: keratin 7 and GATA3 positivity in nuclear ß-catenin-negative glandular tumours defines adenocarcinoma of the bladder.

Aims: This study evaluates immunohistochemical markers for the differential diagnosis of primary bladder adenocarcinoma (BAC) from secondarily involving colorectal adenocarcinoma (CAC). Additional staining of putative precursor lesions (cystitis cystica et glandularis (CC) and intestinal metaplasia (IM)) supports insights into metaplastic cell development and aberrant differentiation in tumours.

Methods: Tissue microarray sections of formalin-fixed, paraffin-embedded tissues from clinically verified 11 BAC, 11 CAC, 18 invasive urothelial carcinomas (UCs), 22 normal urothelium samples, 25 CC and 15 IM were stained for keratin 7, 5/6, 5/14 and 20, ß-catenin, e-cadherin, cadherin 17, cdx2, uroplakin II and III, CD10, androgen receptor (AR), S100P, MUC2, MUC5AC and GATA3 expression.

Comparison of structural genetics of non-schistosoma-associated squamous cell carcinoma of the urinary bladder.

Little is known about genetic changes in squamous differentiation of non-schistosomiasis-associated bladder cancer. Therefore, we investigated pure squamous cell carcinomas (SqCC), squamous parts of mixed urothelial carcinomas with squamous differentiation (MIX) and mere urothelial cancers (UC) for structural genetic differences. Tissue microarray slides (n = 29 SqCC, n = 35 MIX and n = 23 UC) were analyzed by ZytoLight SPEC p16/CEN3/7/17 Quadruple Color Probe fluorescence-in-situ-hybridization (FISH) and DNA was investigated by comparative genomic hybridization (CGH) (n = 35 SqCCs, n = 40 MIX and n = 36 UC).

Mutations Causing Complex Disease May under Certain Circumstances Be Protective in an Epidemiological Sense.

Guided by the practice of classical epidemiology, research into the genetic basis of complex disease has usually taken for granted the dictum that causative mutations are invariably over-represented among clinically affected as compared to unaffected individuals. However, we show that this supposition is not true and that a mutation contributing to the etiology of a complex disease can, under certain circumstances, be depleted among patients. Populations with defined disease prevalence were repeatedly simulated under a Wright-Fisher model, assuming various types of population history and genotype-phenotype relationship.

Shannon's equivocation for forensic Y-STR marker selection.

Short tandem repeat (STR) markers are widely and continuously used in forensic applications. However, past research has demonstrated substantial allelic association between STR markers on both autosomes and the X chromosome, leading to partially redundant information that these markers can provide. Here, we quantify the allelic association between Y-chromosomal STR markers that are part of established forensic panels, separately for three different continental groups.

Comparison of two exploratory dietary patterns in association with the metabolic syndrome in a Northern German population.

Diet is related to many chronic disease conditions such as the metabolic syndrome (MetS). We set out to compare behaviour-related with disease-related patterns and their association with the MetS in a German cross-sectional study. A total of 905 participants of a Northern German cohort (aged 25-82 years) completed a FFQ, underwent anthropometric assessments and provided a blood sample.

Postdiagnosis body mass index and risk of mortality in colorectal cancer survivors: a prospective study and meta-analysis.

Purpose: Aim of this study was to investigate the association between postdiagnosis body mass index (BMI) and all-cause mortality in colorectal cancer (CRC) survivors in a prospective study and meta-analysis.

Methods: We conducted a prospective cohort study on 2,143 CRC survivors in Germany. Participants were recruited to the study on average 4 years after diagnosis, and postdiagnosis BMI was assessed at recruitment using a self-administered questionnaire.

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed.

Dietary patterns associated with magnetic resonance imaging-determined liver fat content in a general population study.

Background: The association between diet and fatty liver disease (FLD) has predominantly been analyzed for single nutrients or foods, and findings have been inconsistent.

Objective: We aimed to compare associations of hypothesis-driven and exploratory dietary pattern scores with liver fat content.

Design: Liver fat was measured by using magnetic resonance imaging as liver signal intensity (LSI) in a population-based, cross-sectional study that included 354 individuals.

Diagnosing fatty liver disease: a comparative evaluation of metabolic markers, phenotypes, genotypes and established biomarkers.

Background: To date, liver biopsy is the only means of reliable diagnosis for fatty liver disease (FLD). Owing to the inevitable biopsy-associated health risks, however, the development of valid noninvasive diagnostic tools for FLD is well warranted.

Aim: We evaluated a particular metabolic profile with regard to its ability to diagnose FLD and compared its performance to that of established phenotypes, conventional biomarkers and disease-associated genotypes.

Genome-wide investigation of gene-environment interactions in colorectal cancer.

Colorectal cancer (CRC), one of the most frequent neoplasias worldwide, has both genetic and environmental causes. As yet, however, gene-environment (G × E) interactions in CRC have been studied mostly for a small number of candidate genes only. Therefore, we investigated the possible interaction, in CRC etiology, between single-nucleotide polymorphisms (SNPs) on the one hand, and overweight, smoking and alcohol consumption on the other, at a genome-wide level.

Prognostic value of perinodal lymphovascular invasion following radical cystectomy for lymph node-positive urothelial carcinoma.

Background: Metastasis of urothelial carcinoma of the bladder (UCB) into regional lymph nodes (LNs) is a key prognosticator for cancer-specific survival (CSS) after radical cystectomy (RC). Perinodal lymphovascular invasion (pnLVI) has not yet been defined.

Objective: To assess the prognostic value of histopathologic prognostic factors, especially pnLVI, on survival.

Dual energy CT in patients with polycystic kidney disease.

Objectives: To evaluate the diagnostic efficacy of dual source-dual energy CT (DECT) in the detection of neoplasia in patients with polycystic kidney disease (PKD).

Methods: A total of 21 patients with PKD underwent DECT on a dual source system, using kVp settings of Sn140/100 or 140/80. Colour-coded iodine maps and virtual unenhanced images were used to determine enhancement within cysts and to differentiate haemorrhagic from simple cysts.

Outcome of laser-assisted laparoscopic partial nephrectomy without ischaemia for peripheral renal tumours.

Objectives: Evaluation of clamp-off laser-assisted laparoscopic partial nephrectomy technique (LLPN) compared to the clamp-off laparoscopic (LPN) and open (OPN) techniques.

Patients And Methods: Between September 2008 and July 2011, 36 patients suffering from small peripheral renal tumours (RT) underwent LLPN (n = 12), LPN (n = 12) and OPN (n = 12) in a prospective single-centre study. RT were excised with laser, Sonosurg or monopolar scissors during LLPN, LPN and OPN, respectively.

Transcript signature predicts tissue NK cell content and defines renal cell carcinoma subgroups independent of TNM staging.

Clear cell renal cell carcinoma (ccRCC) is an aggressive and difficult to manage cancer. Immunotherapy has the potential to induce long-lasting regression in a small group of patients. However, severe side effects limit broad application which highlights the need for a marker to distinguish responder from nonresponder.

Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations.

Tissue dendritic cells (DCs) may influence the progression of renal cell carcinoma (RCC) by regulating the functional capacity of antitumor effector cells. DCs and their interaction with T cells were analyzed in human RCC and control kidney tissues. The frequency of CD209(+) DCs in RCCs was found to be associated with an unfavorable T(H)1 cell balance in the tissue and advanced tumor stages.

APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans.

The allele ε4 of apolipoprotein E (APOE), which is a key regulator of lipid metabolism, represents a risk factor for cardiovascular diseases and Alzheimer's disease. Despite its adverse effects, the allele is common and shows a nonrandom global distribution that is thought to be the result of evolutionary adaptation. One hypothesis proposes that the APOE ε4 allele protects against vitamin D deficiency.

Different immunohistochemical and ultrastructural phenotypes of squamous differentiation in bladder cancer.

Besides worse prognosis of bladder cancer with squamous differentiation (pure squamous cell carcinoma (SCC) or mixed urothelial carcinoma (UC/SCC)), high-grade non-keratinising squamous differentiation is difficult to identify in haematoxylin-eosin stainings. This study aims to validate routine immunohistochemical markers for squamous differentiation in a larger cohort of patients. Tissue microarrays of 89 pure SCCs and mixed UC/SCCs, 66 urothelial carcinomas (UC), precursor lesions and normal urothelium were stained for cytokeratin (CK) 5/6, CK 5/14, CK 7, CK 20 and uroplakin III.

DNA hypermethylation in papillary renal cell carcinoma.

Objective: To investigate the pattern of DNA CpG island hypermethylation in papillary renal cell carcinoma (pRCC).

Material And Methods: DNA from pRCC (n= 32) and adjacent normal tissue (n= 15) was isolated. A quantitative methylation-specific PCR was performed to analyse the methylation pattern at APC (actin beta), CDH1 (E-cadherin), GSTP1 (glutathione S-transferase pi 1), RASSF1A (Ras association domain family member 1A) and TIMP3 (TIMP metallopeptidase inhibitor 3); a sequence of ACTB without CpG was used to normalize for DNA input and to calculate the relative amount of methylated DNA (normalized index of methylation, NIM).

Detection of inguinal lymph node involvement in penile squamous cell carcinoma by 18F-fluorodeoxyglucose PET/CT: a prospective single-center study.

Background: The extent of lymph node involvement is the most relevant prognostic factor in patients with penile cancer.

Objective: To prospectively analyze the diagnostic accuracy of 18F-FDG-PET/CT-scan in the assessment of inguinal lymph node involvement in patients with invasive penile carcinoma.

Patients And Methods: Thirty-five patients with invasive penile carcinoma were staged prospectively by 18F-FDG-PET/CT-scan, and blindly evaluated by 2 nuclear medicine physicians.

Complete remission achieved with angiogenic therapy in metastatic renal cell carcinoma including surgical intervention.

Background: Former systemic therapy for metastatic renal cell cancer (mRCC) based on immunomodulation could achieve complete remissions (CR) in only some patients. Angiogenic therapy with sunitinib, sorafenib, and temsirolimus changed the paradigm of treating mRCC based on a doubled progression-free survival (PFS) and 10% to 30% of patients achieving partial remission (PR). Unfortunately, CR is rarely seen.

Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis?

In patients with mastocytosis, gastrointestinal symptoms are a frequent phenomenon. However, there are only limited data about the quantity and distribution pattern of mast cells in the gastrointestinal mucosa. We stained gastroduodenal biopsy specimens from 27 patients with mastocytosis and 48 control subjects for mast cell tryptase, CD117, and CD25.