The impact of bladder removal and urinary diversion for patients' everyday life is largely unknown. The aims of this study were to compare subjective morbidity of ileal neobladder to the urethra versus ileal conduit urinary diversion and to elucidate its influence on quality of life. A total of 102 patients who underwent cystectomy due to a bladder malignancy were included in the study. In 69 patients (67.6%) an orthotopic neobladder and in 33 patients (32.4%) an ileal conduit was performed as urinary diversion. The compliance was 99% and mean follow-up was 37 months. All patients completed two retrospective quality of life questionnaires, namely the QLQ-C30 and a questionnaire developed at our institution to ask for urinary diversion specific items. The questioning and assessment was performed by non-urologists. The results obtained from the validated (QLQ-C30) and our own specially compiled questionnaire clearly demonstrate that patients with an orthotopic neobladder are more able to adapt to the new situation than patients with an ileal conduit. In addition, neobladder to the urethra improves the quality of life because it improves self-confidence, causes better rehabilitation as well as the restoration of leisure, professional, travelling, and social activities, and reduced risk of inadvertent loss of urine. For example, 92.8% of neobladder patients did not feel handicapped at all, and 87% did not feel sick or ill, in contrast to 51.5% and 66.7% of ileal conduit patients, respectively. Of the neobladder patients, 74.6% felt absolutely safe with the urinary diversion in contrast to 33.3% in the ileal conduit group. Only 1.5% of neobladder patients had wet clothes caused by urine leakage during the day, versus 48.5% of ileal conduit patients. Moreover, 97% of our neobladder patients would recommend the same urinary diversion to a friend suffering from the same disease, but only 36% of ileal conduit patients would do so. These results demonstrate that the quality of life is preserved to a higher degree after orthotopic neobladder than after ileal conduit urinary diversion.

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There is increasing evidence that chemokines and chemokine receptors are causally involved in tumorigenesis by facilitating tumor proliferation and metastasis. Little is known about the possible function of chemokine receptors in the development and progression of renal cell carcinoma (RCC). We, therefore, analyzed the expression of chemokine receptors in tumor specimens and adjacent healthy kidney tissues [normal kidney cell (NKC)] from 10 RCC patients.We also characterized the permanent RCC cell line A-498. CCR6, CXCR2, and CXCR3 were consistently expressed by both malignant cells and NKCs. A-498 displayed additional expression of CXCR4. Importantly, the expression of CCR3 was almost absent on NKCs but clearly enhanced in a substantial proportion of RCC specimens. The primary CCR3 ligand, eotaxin-1/CCL11, induced intracellular Ca 2+ mobilization, receptor internalization, and proliferation in A-498 cells confirming signaling competence of RCC-associated CCR3. In addition, we screened tumor tissue sections of 219 patients and found that 28% (62 of 219) expressed the CCR3 receptor. The presence of CCR3 in tumor samples seemed to correlate with the grade of malignancy. Previous work has established that eotaxin-1expression is induced by tumor necrosis factor-a, a cytokine known to be present in RCC tissue. Our data, therefore, supports a scenario in which eotaxin-1 as part of tumor-associated inflammation promotes progression and dissemination of CCR3-positive RCC.Cancers of the kidney account for 2% to 3% of all malignancies and have a peak incidence in the fifth and sixth decades of life. Renal cell carcinoma (RCC) is the most common malignant renal tumor with an incidence of 4 to 5 in 100 people. At diagnosis, 20% to 30% of the patients have metastatic disease and even a higher percentage of patients develop metachronous metastases after nephrectomy. When in metastatic progression, systemic therapies of RCC are largely ineffective in impacting disease response or patient survival. Therefore, defining the factors involved in disease progression and metastasis constitutes a necessary approach in the development of effective therapies.Multiple factors are known to contribute to the development and progression of neoplasias in general. Among them, chemokines are increasingly being recognized as key players (for reviews, see refs. 1, 2). Chemokines constitute a family of small (8-10 kDa) secreted proteins that act in paracrine or autocrine fashion. Most chemokines are expressed in response to stimuli [e.g., tumor necrosis factor-a (TNF-a) or IFN-g], but constitutive expression might also occur in a tissue-specific manner. Chemokines exert their activity via interaction with a large family of seven-transmembrane-spanning G protein -coupled receptors (3). There are f20 chemokine receptors described thus far and many of the receptors exhibit widespread binding properties. Thus, several chemokines can signal through the same receptor.Originally, chemokines were discovered as chemoattractants and activators of ...

In this phase I/II study, we evaluated the feasibility, safety and efficacy of allogeneic dendritic cells (DCs) with or without cyclophosphamide in the treatment of patients with metastatic renal cell carcinoma (RCC). Immunomagnetic beads were used to isolate CD14(+) monocytes from healthy donor leukapheresis products, and CD83(+) antigen-pulsed monocyte-derived DCs (moDCs) loaded with tumor lysate and keyhole limpet hemocyanin (KLH) were generated. Twelve patients were treated with allogeneic moDCs alone, while ten patients also received cyclophosphamide on days 4 and 3 prior to vaccination. Of the 22 patients enrolled, 20 received full treatment consisting of at least three vaccinations at monthly intervals. Two mixed responses with substantial tumor regression were observed. In 3 patients, disease stabilization occurred, in 13 patients disease progressed and 4 patients were lost to follow-up. Overall, immune responses against KLH and tumor lysate were weak or absent; however, the strongest increases in antigen-independent and KLH-specific responses were observed in the 2 patients with mixed responses. In addition, 1 of them showed a substantial increase in oncofetal antigen (OFA)-specific IFN-gamma production. Importantly, the 2 mixed responders and 1 patient with stable disease belonged to the cyclophosphamide group. Median overall survival in the cyclophosphamide group was 23.2 and 20.3 months in the group that received allogeneic moDCs alone. Allogeneic immunotherapy with moDCs is feasible and well tolerated. However, the immunogenicity of allogeneic moDCs is clearly less pronounced than that of autologous moDC immunotherapy. Cyclophosphamide may have the capacity to augment DC-induced antitumor immunity.