Interval to biochemical recurrence following radical prostatectomy does not affect survival in men with low-risk prostate cancer

Objectives

To evaluate the temporal relationship between interval to biochemical recurrence (BCR) following radical prostatectomy (RP) and prostate cancer-specific mortality (PCSM).

Patients and methods

The study comprised of 2,116 men from the Victorian Radical Prostatectomy Register, a whole-of-population database of all RPs performed between 1995 and 2000 in Victoria, Australia. Follow-up prostate-specific antigen and death data were obtained via record linkage to pathology laboratories and the Victorian Registry of Births, Deaths and Marriages. Poisson regression models with PCSM as the outcome were fit to the data. Models included age at surgery, Gleason score and tumour stage as covariates.

Results

Median post-surgery and post-BCR follow-up was 10.3 and 7.5 years, respectively. 695 men (33 %) experienced BCR during follow-up, of which 82 % occurred within 5 years of RP; 66 men died from prostate cancer. Men with combined high Gleason sum (≥4 + 3) and extra-prostatic (≥pT3a) disease had substantially increased mortality rate with early BCR, while those experiencing BCR after a longer interval had significantly lower mortality. Men with combined low Gleason sum (≤3 + 4) and organ-confined disease (≤pT2c) risk disease were not at any substantial risk of death in this time frame regardless of timing of BCR following RP.

Conclusions

This study evaluates the temporal relationship between BCR and PCSM using a whole-of-population cohort of men treated with RP. Men with low-risk features of prostate cancer at time of RP have low mortality even if they experience early BCR. This subgroup may be counselled regarding their favourable long-term prognosis.     

An In Vivo Comparison of the Orientation of the Transverse Acetabular Ligament and the Acetabulum

Aligning the acetabular component with the Transverse Acetabular Ligament (TAL) to ensure optimal anteversion has been reported to reduce dislocation rates. However, to our knowledge in vivo measurement of the TAL angle has not yet been reported in a large cohort of normal hips. CT scans of 218 normal hips were analyzed. The TAL and four acetabular rim anteversion angles were measured (superiorly to inferiorly) relative to the anterior pelvic plane. The mean TAL anteversion angle was 20.5° ± 7.0°, and the acetabular rim angles from superior to inferior were 11.0° ± 12.9°, 19.9° ± 8.8°, 20.9° ± 6.2° and 25.1° ± 6.2° respectively. Both the TAL and the acetabular rim were significantly more anteverted in females than in males. The TAL anteversion angle was comparable to the predominant orientation (central rim section) of the native acetabulum while the superior acetabulum was comparatively retroverted and the inferior was relatively more anteverted.     

Intracellular distribution of differentially phosphorylated dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A)

The gene encoding dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) is located within the Down syndrome (DS) critical region of chromosome 21. DYRK1A interacts with a plethora of substrates in the cytosol, cytoskeleton, and nucleus. Its overexpression is a contributing factor to the developmental alterations and age‐associated pathology observed in DS. We hypothesized that the intracellular distribution of DYRK1A and cell‐compartment‐specific functions are associated with DYRK1A posttranslational modifications. Fractionation showed that, in both human and mouse brain, almost 80% of DYRK1A was associated with the cytoskeleton, and the remaining DYRK1A was present in the cytosolic and nuclear fractions. Coimmunoprecipitation revealed that DYRK1A in the brain cytoskeleton fraction forms complexes with filamentous actin, neurofilaments, and tubulin. Two‐dimensional gel analysis of the fractions revealed DYRK1A with distinct isoelectric points: 5.5–6.5 in the nucleus, 7.2–8.2 in the cytoskeleton, and 8.7 in the cytosol. Phosphate‐affinity gel electrophoresis demonstrated several bands of DYRK1A with different mobility shifts for nuclear, cytoskeletal, and cytosolic DYRK1A, indicating modification by phosphorylation. Mass spectrometry analysis disclosed one phosphorylated site in the cytosolic DYRK1A and multiple phosphorylated residues in the cytoskeletal DYRK1A, including two not previously described. This study supports the hypothesis that intracellular distribution and compartment‐specific functions of DYRK1A may depend on its phosphorylation pattern. © 2013 Wiley Periodicals, Inc.     

The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells

Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.     

A Longitudinal Investigation of Changes to Social Resources Associated With Psychological Distress Among Kurdish Torture Survivors Living in Northern Iraq

Social resources can buffer against psychological distress following potentially traumatic events. Psychological distress can also lead to social resource deterioration. This longitudinal study evaluated whether baseline psychological distress symptoms and changes in these symptoms were associated with changes in social resources 5 months later among 96 adult male (52.6%) and female treatment‐seeking torture survivors residing in Kurdistan, Iraq. Adapted versions of the Hopkins Symptom Checklist‐25, Harvard Trauma Questionnaire, and a traumatic grief measure were used. Locally derived scales measured perceived social support, social integration, and frequency of social contact. Multinomial logistic regression models assessed the association between symptoms and loss or gain in social resources. We hypothesized that higher mental health symptoms would relate to decreased social resources. Higher baseline depression (adjusted conditional odds ratio [ACOR] = 1.14), posttraumatic stress disorder (PTSD; ACOR = 1.09), and traumatic grief symptoms (ACOR = 1.14) increased the odds of loss of social integration. For some, higher traumatic grief symptoms were associated with increased social integration (ACOR = 1.17). Increased anxiety (ACOR = 1.23) and PTSD symptoms (ACOR = 1.07) was associated with declines in social contact; decreased depression (ACOR = 1.06) and PTSD symptoms (ACOR = 1.04) were related to gaining social contact. This study highlights the complex relationship between mental health symptoms and losses and gains in social resources among torture survivors.