Epithelial–mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma

Purpose

To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer.

Methods

We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan–Meier analysis and uni- and multivariate Cox regression analysis.

Results

Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan–Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS.

Conclusion

Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.

     

Antegrade Tibial Tunnel Technique for Posterior Cruciate Ligament Reconstruction

Posterior cruciate ligament (PCL) reconstruction remains a difficult procedure even in experienced hands0 because there is a lack of consensus regarding the most reliable and least technically challenging technique. The commonly used retrograde anteromedial tibial tunnel leads to excessive angulation at the posterior tibia and risks catastrophic neurovascular complications. We present a technique of drilling the transtibial PCL tunnel in an antegrade fashion through a posteromedial portal. This technique offers the advantage of an anterolateral route to reduce graft angulation, as well as drilling away from the important posterior neurovascular structures.     

Does photodynamic transurethral resection of bladder tumour improve the outcome of initial T1 high‐grade bladder cancer? A long‐term follow‐up of a randomized study

OBJECTIVE

To evaluate, in a long‐term follow‐up of T1 high‐grade bladder cancer treated in a prospective, randomized trial, whether fluorescence diagnosis (FD) increases recurrence‐free survival (RFS) or reduces progression to muscle‐invasive stages.

PATIENTS AND METHODS

In all, 191 patients with suspected superficial bladder cancer were treated with transurethral resection under white light (WL) or with FD; 46 presented with initial T1 high‐grade BC (WL, 25; FD, 21). There were no differences in multifocality of tumours, concomitant carcinoma in situ or tumour size in either group.

RESULTS

Patients were followed for a median of 7.3 (WL) and 7.5 (FD) years to evaluate RFS. In the WL group there were 11, and in the FD group three, recurrent tumours of the same stage and grade. The RFS at 4 and 8 years was 69% and 52% in the WL, and 91% and 80% in FD group, respectively. With FD, the RFS was significantly longer according to Kaplan‐Meier analysis (P = 0.025). In the WL group, three (12%), and in the FD group four (19%) patients progressed to muscle‐invasive stages (≥ T2).

CONCLUSION

In initial T1 high‐grade bladder cancer, FD is significantly better than conventional WL transurethral resection for RFS. However, the progression rate to muscle‐invasive disease was not reduced by FD. Thus the clinical course (progression) of T1 high‐grade bladder cancer remains unaffected by FD.     

Membrane proteinase 3 and Wegener's granulomatosis

Proteinase 3 (PR3) is found in neutrophil and monocyte lysosomal granules. Anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for PR3 are characteristic for patients with Wegener's granulomatosis. The interaction of ANCA with neutrophilic ANCA antigens is necessary for the development of ANCA-associated diseases. ANCA bind to membrane-expressed PR3 and induce full-blown activation in primed neutrophils. We discuss two different aspects of membrane PR3 (mPR3). The first aspect is the amount of PR3 and mechanisms controlling this issue. The second aspect is the presence of two neutrophil subsets that differ in the mPR3 expression phenotype.     

Functional analysis of <Emphasis Type="Italic">BMP4</Emphasis> mutations identified in pediatric CAKUT patients

Human congenital anomalies of the kidney and urinary tract (CAKUT) represent the major causes of chronic renal failure (CRF) in children. This set of disorders comprises renal agenesis, hypoplasia, dysplastic or double kidneys, and/or malformations of the ureter. It has recently been shown that mutations in several genes, among them BMP4, are associated with hereditary renal developmental diseases. In BMP4, we formerly identified three missense mutations (S91C, T116S, N150K) in five pediatric CAKUT patients. These BMP4 mutations were subsequently studied in a cellular expression system, and here we present functional data demonstrating a lower level of messenger RNA (mRNA) abundance in Bmp4 mutants that indicates a possible negative feedback of the mutants on their own mRNA expression and/or stability. Furthermore, we describe the formation of alternative protein complexes induced by the S91C-BMP4 mutation, which results in perinuclear endoplasmic reticulum (ER) accumulation and enhanced lysosomal degradation of Bmp4. This work further supports the role of mutations in BMP4 for abnormalities of human kidney development.     

Psychosocial rehabilitation and satisfaction with life in adults with childhood-onset of end-stage renal disease

Little information is available on vocational rehabilitation and satisfaction with the quality of life in adult patients with early onset of end-stage renal disease (ESRD). A sample of 39 patients (mean age =26.7±6, range, 18 to 43 years, n =13 on dialysis, n =26 transplanted successfully) were required to report data on their vocational qualification and employment, and their degree of general and health-related satisfaction with life was surveyed. Data on psychosocial rehabilitation were collected by a structured questionnaire, whereas satisfaction with the quality of life was assessed with the standardized Questionnaire on Satisfaction in Life (FLZ). Fifty-eight percent of the patients had left school with certificates equivalent to high school graduation, 87% had completed vocational training and 67% were in paid employment. Forty-nine percent lived on their own or with a partner and 72% fully or partly earned their own living. The mean general and health-related satisfaction with life is significantly reduced compared to the general population. The patients were least satisfied in the areas partnership/sexuality and family life/offspring in general, as well as physical condition and ability to relax within health-orientated satisfaction. Final mean body height was 167.6±11.9 (SDS –1.54±1.59) for male and 153.77±8.29 for female patients (SDS –1.58±1.54). Thirty-six percent reported to be dissatisfied with their present body height compared to 4% of age-matched healthy controls. Positive perception of quality of life was significantly correlated to satisfaction with adult height ( r =0.41, P =0.008). Vocational rehabilitation of adult patients with early onset of ESRD achieves lower values than among the general population, however, more favorable percentages than among young adult patients or patients with adult onset of ESRD. The patients self-evaluation of both their general and health-related quality of life proves to be clearly muted, which is a clear indication of the physical and psychological strain of living with a chronic disease.     

Excellent long-term results of the Müller acetabular reinforcement ring in primary total hip arthroplasty

Background and purpose — The original Müller acetabular reinforcement ring (ARR) shows favorable medium-term results for acetabular reconstruction in total hip arthroplasty, where it is used when the acetabular bone stock is deficient. However, there are no data regarding long-term survival of the device. We therefore investigated long-term survival and analyzed radiological modes of failure.

Patients and methods — Between 1984 and 2002, 321 consecutive primary arthroplasties using an ARR were performed in 291 patients. The mean follow-up time was 11 (0–25) years, and 24 hips were lost to follow-up. For survival analysis, we investigated 321 hips and the end of the follow-up was the date of revision, date of death, or the last patient contact date with implant still in situ. Radiological assessment was performed for 160 hips with a minimum of 10 years of follow-up and with radiographs of sufficient quality. It included evaluation of osteolysis, migration, and loosening.

Results — 12 ARR THAs were revised: 1 isolated ARR revision for aseptic loosening, 4 revisions of the ARR and the stem for aseptic loosening, 6 for infection, and 1 for recurrent dislocation. The cumulative revision rate for all components, for any reason, at 20 years was 15% (95% CI: 10–22), while for the ARR only it was 7% (95% CI: 4–12) for any reason and 3.4% (95% CI: 1–9) for aseptic loosening. 21 (13%) of 160 ARR THAs examined had radiological changes: 7 had osteolysis but were not loose, and 14 were radiologically loose but were not painful and not revised.

Interpretation — Our data suggest that the long-term survival of the ARR is excellent.     

Secondary effects of femoral instrumentation on pulmonary physiology in a standardised sheep model: what is the effect of lung contusion and reaming?

Intramedullary nailing is the treatment of choice for patients with femoral shaft fractures. However, there is an ongoing debate in multiple trauma patients with associated lung contusion when primary or secondary definitive stabilisation of the long bone fracture should be performed, as nailing is thought to play an important role in the pathogenesis of adult respiratory distress syndrome (ARDS). In a standardised sheep model, this study aimed to quantify the development of acute pulmonary endothelial changes, to assess the activation of polymorphonuclear leucocytes (PMNL) and to observe the effects on the coagulation system associated with the reamed nailing procedure. Furthermore, the effect of coexisting lung contusion in an experimental model was evaluated. The animals were randomly assigned to one of four different groups (6 animals/group). In control groups, only a sham operation (thoracotomy) was performed, whereas in study groups, lung contusion was induced prior to femoral stabilisation either by external fixation or reamed femoral nailing. Using bronchoalveolar lavage (BAL) pulmonary permeability changes were quantified and PMNL activation was assessed by chemiluminescence. Additionally PMNL diapedesis and interstitial lung oedema were determined by histological analysis. All animals were sacrificed 4 h after the start of the femoral instrumentation. Without an associated lung injury, instrumentation of the femoral canal with the reamed nailing technique induced a transient increase in pulmonary permeability. In the face of an induced lung contusion, reamed femoral nailing resulted in significant increases in PMNL activation, pulmonary permeability and interstitial lung oedema, compared with external fixation. Without pulmonary contusion, reaming of the femoral canal was associated with a transient increase in pulmonary permeability. This was exacerbated in the presence of lung contusion along with increased PMNL activation. External fixation did not provoke similar changes. The findings of this study support the view that reaming of the femoral canal should be avoided in polytrauma patients with severe chest trauma as it could act as an additional stimulus for adverse outcome. Temporary external fixation appears to be a safe method for fracture stabilisation until inflammatory and coagulatory disturbances after trauma have been normalized.     

Incidence of maxillary sinusitis and oro-antral fistulae in bisphosphonate-related osteonecrosis of the jaw

ObjectiveBisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side-effect of bisphosphonate therapy. In the majority of cases BRONJ occurs in the mandible. As a consequence a detailed investigation of BRONJ of the maxilla and in particular of involvement of the maxillary sinus has largely so far been neglected. The aim of this study was to analyse the frequency of maxillary sinusitis and oro-antral fistulae in BRONJ of the maxilla.Subjects and methodsA retrospective multicentre analysis was carried out in three Departments of Oral and Maxillofacial Surgery focussing on patients suffering from BRONJ in the maxilla. The role of involvement of the maxillary sinus, in particular sinusitis and oro-antral fistula, was analysed.ResultsOut of a total of 170 patients suffering from BRONJ 53 cases (31.2%) with involvement of the maxilla were identified. At least one sign of maxillary sinusitis was present in 43.6% (23/53) and an oro-antral fistula in the course of the disease was detected in 35.8% (19/53) of those patients. The mean length of time of bisphosphonate intake was 36.16 ± 16.32 months. Zoledronate was most frequently associated (60.4%) with symptoms, followed by the combination of Zoledronate/Ibandronate (13.2%), and Zoledronate/Pamidronate or Pamidronate alone (both 7.5%).ConclusionMaxillary sinusitis and oro-antral fistulae are associated with a BRONJ manifestation in the upper jaw in approximately 44%. The involvement of the maxillary sinus should be given special attention and three-dimensional imaging modalities might be necessary, not only to evaluate the extent of necrosis, but also to exclude involvement of the maxillary sinus.