Cadherins are a family of calcium-dependent cell-cell adhesion molecules involved in cell-cell aggregation and morphoregulatory cell function. Dysfunction of the cadherin pathway is involved in tumour invasiveness and disease progression for a variety of carcinomas. E-cadherin is a prognostic marker in prostatic cancer, based on the correlation of the grade of E-cadherin expression and tumour grade, stage, metastasis and survival, as well as recurrence after radical prostatectomy. P-cadherin was shown to be lost in all prostatic cancers, although this most likely reflects loss of the basal cell population rather than a transcriptional down-regulation, suggesting that loss of P-cadherin expression is an early event in the tumorigenesis of prostatic carcinomas. Catenins, particularly alpha-catenin, also play an important role in the dysfunction of the cell adhesion complex. Mechanisms of inactivation of the cadherin-catenin pathway include LOH, gene deletions and gene promoter hypermethylation. Therapeutic strategies have been investigated in tumour models, i.e. the use of demethylating agents for the hypermethylated promoter region of E-cadherin or gene transfer in PC-3 cells with homozygous deletion of the alpha-catenin gene. The complexity of neoplastic changes cannot be explained by alterations of cell adhesion molecules alone; but as demonstrated, cadherins and catenins play an important role in this process.
Introduction: Obesity may influence postoperative outcome after tumor surgery. We evaluated the impact of patients’ body mass index (BMI) on peri- and postoperative morbidity and outcome following radical cystectomy for bladder cancer. Patients and Methods: 390 consecutive patients who underwent radical cystectomy due to bladder cancer from January 1986 to December 2004 were reviewed. According to WHO criteria, patients were divided into normal weight (NW, 45.6%), overweight (OW, 44.4%) and obese (10.0%) subgroups. The BMI of patients was associated to the time of surgery, amount of intraoperative blood units, TNM stage, postoperative complication rate as well as overall survival. Results: The time of cystectomy increased with the degree of patients’ obesity (NW, 330 min; OW, 355 min; p = 0.007). Between NW and OW patients no significant differences were noted in respect to intraoperative blood transfusion rate (NW, 3.0; OW, 2.0; p = 0.47), postoperative TNM stage (pTis–pT2b: 42.6 vs. 48.6%; pT3a–4: 38.2 vs. 27.2%; pN+: 20.2 vs. 24.2%) and postoperative complications, except for postoperative bleeding, which was more common in OW patients (p = 0.02). Mean overall survival times showed no significant differences between NW and OW patients receiving ileal conduits (5-year survival rate: 34.0 vs. 41.1%; p = 0.140) or ileal neobladders (5-year survival rate: 65.1 vs. 70.8%; p = 0.127). Conclusions: Increased BMI poses a greater challenge for surgical interventions such as radical cystectomy in bladder cancer patients. However, in our series, intra- and postoperative morbidity was not significantly elevated in OW patients. Overall survival was not reduced in OW compared to NW patients. Therefore, elevated BMI is not an exclusion criterion for radical cystectomy in bladder cancer patients.
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