Testicular Microlithiasis: Patient Compliance in a Two-Year Follow-Up Program.

Introduction: We present a retrospective 2-year follow-up cohort of 103 men with testicular microlithiasis (TML) and discuss patient compliance and the value of surveillance. Methods: A retrospective analysis of patients examined with scrotal ultrasonography (US) in the period from 2008 through 2010 was performed. A total of 103 men with TML were diagnosed and offered US follow-up every 6 months for 2 years. They were retrospectively analyzed regarding demographics and follow-up details, including the development of any kind of malignancy until March 2015, using the Danish Electronic Pathology Registry. Results: The prevalence of TML was 10.3%. Of the 103 men with TML, 23 (22.3%) had TML in the left testicle, 38 (36.9%) in the right (p=0.002), and 42 (40.8%) had bilateral TML. Patient compliance was low with 11.7% participating in all US follow-up examinations. 5 men presented risk factors (testicular atrophy (N=1) and previous testicular cancer (N=4)), but no cases of testicular malignancy were found in the follow-up period. Conclusion: The low patient compliance conflicts with the ESUR Scrotal Imaging Subcommittee guidelines that recommend scrotal US follow-up annually for TML until the age of 55 years. The fact that no cancers were found during follow-up using the pathology registry calls the value of follow-up into question.

The relationship between ultra-short telomeres, aging of articular cartilage and the development of human hip osteoarthritis.

INTRODUCTION: Ultra-short telomeres caused by stress-induced telomere shortening are suggested to induce chondrocyte senescence in human osteoarthritic knees. Here we have further investigated the role of ultra-short telomeres in the development of osteoarthritis (OA) and in aging of articular cartilage in human hips. MATERIALS AND METHODS: Cartilage was obtained from four different distances of the central weight-bearing area in human femoral heads (14 OA and 9 non-OA). Samples were split into three: one for quantification of ultra-short single telomeres by Universal STELA and mean telomere length measurement by Q-PCR; one for histological grading of OA, and one for immunohistochemical staining. RESULTS: Load of ultra-short telomeres increased closer to the central weight-bearing area and correlated with cartilage degradation in both OA and non-OA samples. Mean telomere length decreased with decreasing distance to the central weight-bearing area, however, unexpectedly increased in the most central zone. This increase was associated with immunohistochemical findings of cells expressing markers characteristic of progenitor-like cells. CONCLUSION: These findings suggest a role of short telomeres in the development of OA and in aging of articular cartilage. Furthermore, progenitor-like cells with long telomeres may be recruited to the most damaged areas of the cartilage.

The prognostic importance of miR-21 in stage II colon cancer: a population-based study.

BACKGROUND: Despite several years of research and attempts to develop prognostic models a considerable fraction of stage II colon cancer patients will experience relapse within few years from their operation. The aim of the present study was to investigate the prognostic importance of miRNA-21 (miR-21), quantified by in situ hybridisation, in a unique, large population-based cohort. PATIENTS AND METHODS: The study included 764 patients diagnosed with stage II colon cancer in Denmark in the year 2003. One section from a representative paraffin-embedded tumour tissue specimen from each patient was processed for analysis of miR-21 and quantitatively assessed by image analysis. RESULTS: The miR-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumours. We found that patients expressing high levels of miR-21 had significantly inferior recurrence-free cancer-specific survival (RF-CSS): HR=1.26; 95% CI: 1.15-1.60; P<0.001. In Cox regression analysis, a high level of miR-21 retained its prognostic importance and was found to be significantly related to poor RF-CSS: HR=1.41; 95% CI: 1.19-1.67; P<0.001. CONCLUSION: The present study showed that increasing miR-21 expression levels were significantly correlated to decreasing RF-CSS. Further investigations of the clinical importance of miR-21 in the selection of high-risk stage II colon cancer patients are merited.

Comparative investigations of T cell receptor gamma gene rearrangements in frozen and formalin-fixed paraffin wax-embedded tissues by capillary electrophoresis.

AIM: To compare clonal T cell receptor gamma (TCRgamma) gene rearrangements in frozen and formalin-fixed paraffin wax-embedded (FFPE) tissue, using capillary electrophoresis for use in diagnostics, as T cell lymphomas may be difficult to diagnose by conventional methods. METHODS: The DNA for PCR was extracted from frozen and FFPE tissue, cell lines and blood. PCR primers Vgamma1-8, Vgamma9, Vgamma10 or Vgamma11 (5' end labelled) combined with a mixture of JgammaP1/JgammaP/JgammaP2/Jgamma2 (unlabelled) were used. Monoclonal cases were sequenced and clonality, reproducibility, sensitivity and specificity analyses were carried out. RESULTS: In all cases the molecular test was found to be in agreement with the histological diagnosis. Discrepancies were found between frozen and FFPE tissue in 18 of 56 (32%) tests. The method was highly reproducible. The sensitivity was found to be 0.5% for cell lines and 1% for patient specimens and the specificity 100%. The junctional region between the Vgamma and Jgamma segments was specific for each patient. CONCLUSIONS: Capillary electrophoresis of PCR products from frozen and FFPE tissue is suitable for detecting clonal TCRgamma gene rearrangements. It is important, however, to correlate the results with conventional morphological and immunohistochemical studies.

Intestinal microdialysis--applicability, reproducibility and local tissue response in a pig model.

BACKGROUND AND AIMS: Microdialysis has been applied to the intestinal wall for the purpose of monitoring local ischemia. The aim of this study was to investigate the applicability, reproducibility and local response to microdialysis in the intestinal wall. MATERIALS AND METHODS: In 12 pigs two microdialysis probes were inserted into the ileal wall, one in the peritoneal cavity and one in the psoas muscle. Relative recovery was measured for all probes by the no net flux method. Metabolic measurements of glucose, lactate and glycerol were performed over six hours. The ileal wall segments containing the probes were processed for histological examination. RESULTS: Large intra- and inter-group differences in the relative recovery were found between all locations. Absolute values of metabolites showed no significant changes during the study period. The lactate in blood was 25-30% of the intra-tissue values. A severe inflammatory reaction was seen in the ileal wall around all probes. CONCLUSION: Measurement of the relative recovery is essential for valid measurements of metabolites when using microdialysis. The inflammatory reaction around the probe in the intestinal wall is likely to affect metabolism and measurements hereof. Therefore intestinal wall microdialysis seems confined to experimental research, and future studies should consider the intra-peritoneal approach.

The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer.

The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low-risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter < or = 50 mm, and no histological evidence of invasion of skin or deep fascia (= T1N0M0 and T2N0M0). The median follow-up time was 104 months (range 5-143 months). Immunohistochemical analysis of OA-519 expression was performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity was estimated using a Ki-67 equivalent monoclonal antibody (MIB-1), which is applicable on formalin-fixed, paraffin-embedded tissue after microwave pretreatment. OA-519 was expressed in about one-third of the tumours and the percentage of proliferating cells (the MIB-1 index) ranged between 1 and 72 per cent (median 17 per cent). Using multivariate Cox analysis, both the MIB-1 index and OA-519 expression were of independent prognostic value (2p < or = 0.01), and the combined immunohistological approach may therefore be useful in selecting patients with node-negative breast cancer who might benefit from adjuvant therapy.