Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets

Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P < 0.0001), and lymph node metastases (P = 0.011). These associations were driven mainly by the subset without TMPRSS2:ERG fusion, in which high JUP expression was an independent predictor of poor prognosis (multivariate analyses, P = 0.0054) and early biochemical recurrence (P = 0.0003). High JUP expression was further linked to strong androgen receptor expression (P < 0.0001), high cell proliferation, and PTEN and FOXP1 deletion (P < 0.0001). In the ERG‐negative subset, high JUP expression was additionally linked to MAP3K7 (P = 0.0007) and CHD1 deletion (P = 0.0021). Contrasting the overall prognostic effect of JUP, low JUP expression indicated poor prognosis in the fraction of CHD1‐deleted patients (P = 0.039). In this subset, the association of high JUP and high cell proliferation was specifically absent. In conclusion, the controversial biological roles of JUP are reflected by antagonistic prognostic effects in distinct prostate cancer patient subsets.     

Guiding Breast-Conserving Surgery in Patients After Neoadjuvant Systemic Therapy for Breast Cancer: A Comparison of Radioactive Seed Localization with the ROLL Technique

Background

Radioguided occult lesion localization (ROLL) with technetium-99 m colloid (ROLL-^99mTc) is commonly used to perform breast-conserving surgery in patients with nonpalpable breast tumors. Radioactive seed localization is a relatively new technique that localizes the tumor with a radioactive iodine-125 (¹²⁵I) seed. The feasibility and outcome of these techniques after neoadjuvant systemic treatment has not been widely investigated.

Methods

All patients treated with neoadjuvant systemic treatment between 2007 and 2010 in the Netherlands Cancer Institute who underwent breast-conserving surgery with the ROLL-^99mTc technique (n = 83) or with ¹²⁵I seed localization (n = 71) were analyzed. The weight of the resected specimen, the margins, and the percentage of patients requiring a second surgical intervention as a result of positive margins were assessed.

Results

Patient and tumor characteristics and systemic treatment regimens were comparable between both groups. The median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7 vs. 8 %) did not differ significantly between patients treated with the ROLL-^99mTc technique and ¹²⁵I seed localization.

Conclusions

The ROLL-^99mTc technique and ¹²⁵I seed localization demonstrate comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Because ¹²⁵I seed localization does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling. Therefore, we prefer ¹²⁵I seed localization to perform breast-conserving surgery after neoadjuvant systemic treatment.     

13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence,Controversies, Consensus – Opinion of a German Team of Experts (Zurich 2013)

Zusammenfassung

Alle zwei Jahre findet in St. Gallen (Schweiz) die internationale Konsensuskonferenz zur Behandlung des primären Mammakarzinoms statt. Da sich das internationale Panel in St. Gallen aus Experten unterschiedlicher Länder zusammensetzt, spiegelt der Konsensus ein internationales Meinungsbild wider. Vor diesem Hintergrund erscheint es aus deutscher Sicht sinnvoll, die Abstimmungsergebnisse für den Therapiealltag in Deutschland zu konkretisieren. Eine deutsche Arbeitsgruppe mit acht Brustkrebsexperten, von denen zwei Mitglieder des internationalen St. Gallen-Panels sind, hat daher die Abstimmungsergebnisse der St. Gallen-Konsensuskonferenz (2013) für den Klinikalltag in Deutschland kommentiert. Inhaltliche Schwerpunkte der diesjährigen St. Gallen-Konferenz waren operative Fragestellungen der Brust und der Axilla, strahlentherapeutische und systemische Therapieoptionen sowie die klinische Relevanz der Tumorbiologie. Intensiv diskutiert wurde der klinische Einsatz von Multigen-Assays, inkl. ihrer Bedeutung für die individuelle Therapieentscheidung.     

Quantitative MRI and loss of free ambulation in Duchenne muscular dystrophy

The purpose of this ethics approved trial was to correlate quantitative MRI with functional abilities in both ambulant and non-ambulant Duchenne muscular dystrophy (DMD). Twenty patients with genetically confirmed DMD were recruited. Physical assessment was performed using the motor function measurement (MFM) scale. Axial 3T MRI scans of the thighs were acquired using T1-weighted in- and opposed-phase images (TR = 20 ms, TE₁ = 2.45 ms, TE₂ = 3.68 ms, flip angle = 15°) to calculate the relative fat fraction according to the two-point Dixon method in the knee extensors, flexors, and adductor muscles. The average MFM was 65.3 % and correlated negatively to age (r ² = 0.60). Overall mean fat fraction correlated positively to age (r ² = 0.51–0.64). An average of 5 % increase in mean fat fraction per year was calculated. Mean fat fraction of the quadriceps showed a high negative correlation (r ² = 0.93) to the D1 (standing position and transfers) component of the MFM. A cutoff for mean fat fraction of 50 % predicted loss of ambulation with a sensitivity of 100 % and a specificity of 91 %. Therefore, quantitative muscle MRI seems to be a promising endpoint for short clinical trials evaluating the effect of newer treatments on the time of loss of ambulation in DMD.     

Potential Curative Space in Relational Family Therapy

A human being is in essence a being of relationships, a being of dialogue, which is why everyone, consciously or unconsciously, unstoppably longs for a relationship with others. Every relationship in this sense contains a potential psychic space between I and you, where the most important psychic elements are created and are conducive to new curative experiences. In this article we demonstrate this creative dimension of the human experience in a psychotherapeutic setting, namely in relational family therapy, where the relationship with others and the therapist is considered as the most significant therapeutic phenomena on the basis of which change and transformation are possible.     

Development and Psychometric Properties of a Computer-Based Standardized Emotional Competence Inventory (MeKKi) for Preschoolers and School-Aged Children

Child Psychiatry & Human Development - A computer-based emotional competence inventory for preschoolers and school-aged children (MeKKi) was developed to assess five components of emotional...     

Oxidative Stress in Adults with Autism Spectrum Disorder: A Case Control Study

Journal of Autism and Developmental Disorders - Oxidative stress has been proposed as being important in the pathophysiology of autism spectrum disorders (ASD), and heightened levels of oxidative...