Long-term Cancer-specific Outcomes of TaG1 Urothelial Carcinoma of the Bladder

Background

Few studies have investigated the natural history of TaG1 urothelial carcinoma of the bladder (UCB).

Objective

To assess the long-term outcomes of patients with TaG1 UCB and the impact of immediate postoperative instillation of chemotherapy (IPIC).

Design, setting, and participants

A retrospective analysis of 1447 patients with TaG1 UCB treated between 1996 and 2007 at eight centers. Median follow-up was 67.2 mo (interquartile range: 67.9). Patients were stratified into three European Association of Urology (EAU) guidelines risk categories; high-risk patients (n = 11) were excluded.

Intervention

Transurethral resection of the bladder with or without IPIC.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression models addressed factors associated with disease recurrence, disease progression, death of disease, and any-cause death.

Results and limitations

Of the 1436 patients, 601 (41.9%) and 835 (58.1%) were assigned to low- and intermediate-risk categories, respectively. The actuarial estimate of 5-yr recurrence-free survival was 56% (standard error: ±1). Advancing age (p = 0.04), tumor >3 cm (p = 0.001), multiple tumors (p < 0.001), and recurrent tumors (p < 0.001) were independently associated with increased risk of disease recurrence, whereas IPIC was associated with decreased risk (p = 0.001). The actuarial estimate of 5-yr progression-free survival was 95% ± 1. Advancing age (p < 0.001) and multiple tumors (p = 0.01) were independent risk factors for disease progression. Five-year cancer-specific survival was 98% ± 1. Advancing age (p = 0.001) and previous recurrence (p = 0.04) were associated with increased risk, whereas female gender (p = 0.02) was associated with decreased risk of cancer-specific mortality. Compared with low-risk patients, intermediate-risk patients were at significantly higher risk of disease recurrence, disease progression, and cancer-specific mortality (all p < 0.01). Limitations include the retrospective design of the study and the lack of a central pathology review.

Conclusions

TaG1 UCB patients experience heterogeneous risks of disease recurrence. We validated the EAU guidelines risk stratification in TaG1 UCB patients. IPIC was associated with a reduced risk of disease recurrence in patients with low- and intermediate-risk TaG1 UCB.     

Perforation during TUR of bladder tumours influences the natural history of superficial bladder cancer

Objectives

Bladder perforation is the second most common complication during transurethral resection of bladder tumours. It is unknown whether perforation affects the natural history of the tumour through cell seeding. The aim of this study was to study the impact of perforation on the oncologic outcomes of bladder carcinoma.

Materials and methods

Between 2003 and 2007, 926 consecutive patients underwent transurethral resection of bladder tumours at our institution; 327 cases were staged ≥pT2 and were treated immediately with cystectomy and/or multimodal therapy and therefore excluded from the study. An additional 34 cases without urothelial carcinoma were excluded. Of the remaining 565 patients with non-muscle invasive bladder cancer, 457 (80.8 %) were male and 108 (19.2 %) were female with a mean age of 69.5 years in men and 67.3 years in women. Thirty-seven patients (6.5 %) experienced bladder perforation at the time of tumour resection. This group of patients (Group 1) was compared to the remaining 528 patients (Group 2) who did not experience a bladder perforation.

Results

Patients with bladder wall perforation experienced a shorter disease-free survival in both univariate (p = 0.003) and multivariate analyses (p = 0.006). In addition, subsequent recurrences revealed stage progression of recurrent disease (p = 0.05) and trended to a higher number of cystectomies in the perforated group of patients (p = 0.06). Nevertheless, perforation did not appear to influence overall survival (p = 0.127) or cancer-specific survival (p = 0.141).

Conclusion

The results indicate that bladder perforation during resection of superficial bladder tumours is burdened by a shortened disease-free survival and T-stage progression.     

Do surgical patellar interventions restore patellar kinematics in fixed-bearing,cruciate-retaining total knee arthroplasty? : An in vitro study

Despite different surgical patellar interventions, the decision how to treat the patella during TKA remains controversial. The purpose of this study was to quantify the effect of different reconstructive patellar interventions on patellar kinematics during TKA using optical computer navigation. We implanted ten navigated TKAs in full body specimens. During passive motion, the effect of different surgical patellar interventions on patellar kinematics was analysed. A contrarily tilt behaviour was observed in the TKA group without patellar intervention compared to the natural knee. Lateral release led to similar tilt values (P < 0.05). All surgical interventions led to a 3 to 5 mm medial shift of the patella (P < 0.05). None of the analysed surgical patellar interventions could restore natural patellar kinematics after TKA.     

MALDI imaging–based identification of prognostically relevant signals in bladder cancer using large-scale tissue microarrays

ObjectiveAlthough most patients with urinary bladder cancer present with noninvasive and low-malignant stages of the disease, about 20% eventually develop life-threatening metastatic tumors. This study was designed to evaluate the potential of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify molecular markers predicting the clinical course of bladder cancer.Materials and methodsWe employed MALDI-MSI to a bladder cancer tissue microarray including paraffin-embedded tissue samples from 697 patients with clinical follow-up data to search for prognostically relevant associations.ResultsAnalysis of our MALDI imaging data revealed 40 signals in the mass spectra (m/z signals) associated with epithelial structures. The presence of numerous m/z signals was statistically related to one or several phenotypical findings including tumor aggressiveness (stage, grade, or nodal status; 30 signals), solid (5 signals) or papillary (3 signals) growth patterns, and increased (6 signals) or decreased (12 signals) cell proliferation, as determined by Ki-67 immunohistochemistry. Two signals were linked with tumor recurrence in noninvasive (pTa category) tumors, of which one was also related to progression from pTa-category to pT1-category disease. The absence of one m/z signal was linked with decreased survival in the subset of 102 muscle-invasive cancers.ConclusionOur data demonstrate the suitability of combining MSI and large-scale tissue microarrays to simultaneously identify and validate clinically useful molecular markers in urinary bladder cancer.     

Tunable Pseudo-Piezoelectric Effect in Doped Calcium Titanate for Bone Tissue Engineering

CaTiO₃ is a promising candidate as a pseudo-piezoelectric scaffold material for bone implantation. In this study, pure and magnesium/iron doped CaTiO₃ are synthesized by sol-gel method and spark plasma sintering. Energy dispersive X-ray mapping confirm the homogenous distribution of doping elements in sintered samples. High-energy X-ray diffraction investigations reveal that doping of nanostructured CaTiO₃ increased the strain and defects in the structure of CaTiO₃ compared to the pure one. This led to a stronger pseudo-piezoelectric effect in the doped samples. The charge produced in magnesium doped CaTiO₃ due to the direct piezoelectric effect is (2.9 ± 0.1) pC which was larger than the one produced in pure CaTiO₃ (2.1 ± 0.3) pC, whereas the maximum charge was generated by iron doped CaTiO₃ with (3.6 ± 0.2) pC. Therefore, the pseudo-piezoelectric behavior can be tuned by doping. This tuning of pseudo-piezoelectric response provides the possibility to systematically study the bone response using different piezoelectric strengths and possibly adjust for bone tissue engineering.     

Gene replacement by homologous recombination in the multicellular green alga Volvox carteri

With only two different cell types, the haploid green alga Volvox represents the simplest multicellular model system. To facilitate genetic investigations in this organism, the occurrence of homologous recombination events was investigated with the intent of developing methods for gene replacement and gene disruption. First, homologous recombination between two plasmids was demonstrated by using overlapping nonfunctional fragments of a recombinant arylsulfatase gene (tubulin promoter/arylsulfatase gene). After bombardment of Volvox reproductive cells with DNA-coated gold microprojectiles, transformants expressing arylsulfatase constitutively were recovered, indicating the presence of the machinery for homologous recombination in Volvox. Second, a well characterized loss-of-function mutation in the nuclear nitrate reductase gene (nitA) with a single G → A nucleotide exchange in a 5′-splice site was chosen as a target for gene replacement. Gene replacement by homologous recombination was observed with a reasonably high frequency only if the replacement vector containing parts of the functional nitrate reductase gene contained only a few nucleotide exchanges. The ratio of homologous to random integration events ranged between 1:10 and 1:50, i.e., homologous recombination occurs frequently enough in Volvox to apply the powerful tool of gene disruption for functional studies of novel genes.     

Factors influencing heart rate variability in patients with severe aortic valve disease

Background and hypothesis: Heart rate variability (HRV) is an accepted tool for the assessment of cardiovascular autonomic tone. There are no sufficient data concerning its application to patients with severe aortic valve disease (AVD) requiring cardiac surgery. Methods: It was the aim of this study to examine HRV and its physiologic correlates in patients with severe aortic valve disease requiring cardiac surgery. The correlates of time domain indices of HRV obtained from 24-h Holter electrocardiographic recordings were analyzed in 36 consecutive patients (23 men and 13 women, mean age 62 ± 11 years) with AVD prior to cardiac surgery (aortic stenosis: 17 patients, aortic valve regurgitation: 3 patients, combined aortic valve disease: 16 patients). Results: Low values of HRV were found in the entire study group: SDNN 96.8 ± 30.9 ms, SDNNI 39.3 ± 14.4 ms, SDANN 86 ± 28.9 ms, and RMSSD 30 ± 18.1 ms. In a univariate analysis, there was no significant correlation between the time domain measures of HRV and age, gender, medication, left ventricular ejection fraction, peak aortic pressure gradient, fraction of aortic valve regurgitation, and left ventricular mass assessed by echocardiography. Patients in advanced functional classes of heart failure [New York Heart Association (NYHA) III or IV] had significantly lower values for SDNN (83.8 ± 33.6 vs. 107.3 ± 24.7 ms; p<0.05) and SDANN (72.7 ± 29.4 vs. 96.6 ± 24.3 ms; p<0.05) than patients in NYHA class I or II. Reassessment of HRV 1 week after aortic valve replacement was performed in 17 patients and showed a significant further decrease of SDNN (102.4 ± 29.7 vs. 61.5 ± 23.5 ms; p<0.001), SDNNI (40.7 ± 13.6 vs. 23.4 ± 12.4 ms; p<0.001) and SDANN (91.8 ±29.2 vs. 54.2 ± 22.8 ms;p<0.001). Conclusion: Patients with AVD requiring cardiac surgery reveal reduced time domain indices of HRV. This observation is pronounced in patients with a progressed clinical class of heart failure, whereas hemodynamic and echocardiographic parameters seem to have no significant influence on HRV parameters in this population. In addition, there is evidence of a further reduction of HRV time domain indices 1 week after uncomplicated aortic valve replacement.