Loss of AQP3 protein expression is associated with worse progression-free and cancer-specific survival in patients with muscle-invasive bladder cancer

Purpose Urothelial carcinoma has recently been shown to express several aquaporins (AQP), with AQP3 being of particular interest as its expression is reduced or lost in tumours of higher grade and stage. Loss of AQP3 expression was associated with worse progression-free survival (PFS) in patients with pT1 bladder cancer. The objective of this study was to investigate the prognostic value of AQP3 expression in patients with muscle-invasive bladder carcinoma (MIBC). Methods Retrospective single-centre analysis of the oncological outcome of patients following radical cystectomy (Cx) due to MIBC. Immunohistochemistry was used to assess AQP3 protein expression in 100 Cx specimens. Expression levels of AQP3 were related to clinicopathological variables. The impact of biomarker expression on progression-free, cancer-specific and overall survival was determined by multivariate Cox regression analysis (MVA). Results High expression of AQP3 by the tumour was associated with a statistically significantly improved PFS (75 vs. 19 %, p = 0.043) and CSS (75 vs. 18 %, p = 0.030) and, alongside lymph node involvement, was an independent predictor of PFS (HR 2.871, CI 1.066–7.733, p = 0.037), CSS (HR 3.325, CI 1.204–8.774, p = 0.019) and OS (HR 2.001, CI 1.014–3.947) in MVA. Conclusions Although the results of the study would be strengthened by a larger, more appropriately powered, prospective, multi-institutional study, our findings strongly suggest that AQP3 expression status may represent an independent predictor of PFS and CSS in MIBC and may help select patients in need for (neo-)adjuvant chemotherapy

Mirror-Mark Tests Performed on Jackdaws Reveal Potential Methodological Problems in the Use of Stickers in Avian Mark-Test Studies

Some animals are capable of recognizing themselves in a mirror, which is considered to be demonstrated by passing the mark test. Mirror self-recognition capacity has been found in just a few mammals having very large brains and only in one bird, the magpie (Pica pica). The results obtained in magpies have enormous biological and cognitive implications because the fact that magpies were able to pass the mark test meant that this species is at the same cognitive level with great apes, that mirror self-recognition has evolved independently in the magpie and great apes (which diverged 300 million years ago), and that the neocortex (which is not present in the bird's brains) is not a prerequisite for mirror self-recognition as previously believed. Here, we have replicated the experimental design used on magpies to determine whether jackdaws (Corvus monedula) are also capable of mirror self-recognition by passing the mark test. We found that our nine jackdaws showed a very high interest towards the mirror and exhibited self-contingent behavior as soon as mirrors were introduced. However, jackdaws were not able to pass the mark test: both sticker-directed actions and sticker removal were performed with a similar frequency in both the cardboard (control) and the mirror conditions. We conclude that our jackdaws' behaviour raises non-trivial questions about the methodology used in the avian mark test. Our study suggests that the use of self-adhesive stickers on sensitive throat feathers may open the way to artefactual results because birds might perceive the stickers tactilely.JMPS was funded by Ministerio de Educación and Consejería de Innovación, C 420 iencia y Empresa under International Excellence Campus Program (CEI Granada) and TPC was funded by Ministerio de Educación y Ciencia by a postdoctoral contract from the project CGL2011-25634

The long-term results of meniscus transplantation for articular cartilage defects in the knee joint

Purpose: The purpose of this study was to examine the long-term clinical results of meniscus transplantation for articular cartilage defects in the knee joint. Type of study: Case series. Method: From October 1990 to June 1995, 8 cases underwent allogenic or autogenic meniscus transplantations for articular cartilage defects, and 7 cases were available for follow-up evaluations. The age at surgery ranged from 14 to 42 years old (average 22.5). In one case, a transplantation of tissue-engineered cartilage was performed due to pain 5 years after surgery. The other 6 cases were followed up for 8 to 13 years (average 10.1). The size of the cartilage defect ranged from 1.0 cm2 to 6.3 cm2 (average 2.8cm2). Patients were evaluated with the Lysholm score and MR images. We also performed arthroscopic examinations in 3 cases at the final evaluation. Results: The Lysholm scores ranged from 76 points to 100 points. In MR images, the congruities between the grafted lesions and normal cartilage were evaluated as smooth surfaces in 4, slightly irregular surface in 1, irregular surface in 1, and one had disappeared. In arthroscopic findings at 11 years after surgery, the grafted meniscus could not be found in one knee that had severe osteoarthritis changes, and in the other knee the lesion of the transplanted meniscus resembled a flap tear. In another case, the grafted meniscus and the surrounding cartilage displayed irregular surfaces during transplantation of tissue-engineered cartilage. In histological findings, at 11 years after surgery a small lesion in the grafted area was not hyaline cartilage but fibrocartilage. Conclusions: This study leads us to the conclusion that meniscus transplantation for articular cartilage damage is not compared to ACI although two cases showed good clinical results for a short term but the tissue was remained fibrocartilage tissues for long term.. Level of Evidence: Level 4, case series

Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

<p>Abstract</p> <p>Background</p> <p>Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC.</p> <p>Method</p> <p>AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test.</p> <p>Results</p> <p>59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025).</p> <p>Conclusions</p> <p>Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.</p