Urinary bladder cancer in Wegener's granulomatosis: is it more than cyclophosphamide?
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Publications and source records attributed to D Jocham.
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Renal cell carcinoma is often regarded as an "immunogenic tumor". Organ-confined tumors are best treated by operative removal. Adjuvant strategies, however, may improve the outcome after operative therapy. Recently, a phase-III trial using an autologous renal tumor cell vaccine was able to demonstrate a reduction of the risk of progression in patients after radical nephrectomy for renal cell carcinoma larger than 2.5 cm. These results were achieved with minimal side effects. Patients with metastases have a poor prognosis. Thirty years ago autologous tumor cell vaccination resulted in remissions in a small number of patients. Almost all vaccination reports focus on patients with metastatic renal cell carcinoma. These reports differ considerably in their modes of preparation, stimulation, application route and intervals and other relevant parameters. More important, clinical response is limited in most studies. For metastatic renal cell carcinoma none of the various vaccination approaches are being currently investigated in phase-III trials. Ongoing efforts focus on development of more powerful vaccines. This review summarizes vaccination approaches for renal cell carcinomas published in the past 4 years.
We report the results from a nonrandomized comparison of open flank vs laparoscopic nephrectomy in patients with benign renal disease. Between 1993 and 2002, 549 nephrectomies for benign renal disease were performed at the Department of Urology of the Medical University of Lübeck and the Urological Department of the Martin Luther University in Halle/Wittenberg. There were 236 patients in the open flank nephrectomy group and 313 patients in the laparoscopic nephrectomy group. Clinical parameters were compared among both groups. Median operative time in the open flank nephrectomy group was 90 min (range: 30-240 min) and also 90 min in the laparoscopic nephrectomy group (range: 41-210 min). There were 54 complications (17.2%) in the laparoscopic nephrectomy group compared to 60 complications (25.4%) in the open flank nephrectomy group. Patients in the laparoscopy group demonstrated clear advantages in terms of analgesic use for pain control, hospital stay, and convalescence. Laparoscopic nephrectomy results in a significantly briefer postoperative course when compared to open flank nephrectomy. However, due to a limited number of patients, a laparoscopic nephrectomy is mainly reserved for laparoscopic centers. Nevertheless, the laparoscopic approach should be offered to the majority of patients with benign renal disease requiring nephrectomy.
PURPOSE: We compare the therapeutic efficacy and toxicity of intravesical bacillus Calmette-Guerin (BCG) with mitomycin C on recurrence of stages Ta and T1 bladder carcinoma. MATERIALS AND METHODS: Combined published and unpublished data from comparative studies on BCG versus mitomycin C for superficial bladder carcinoma considering possible confounding factors were analyzed. Odds ratio (OR) and its 95% CI were used as primary effect size estimate. Toxicity data were evaluated descriptively. RESULTS: In 11 eligible clinical trials 1,421 patients were treated with BCG and 1,328 were treated with mitomycin C. Within the overall median followup time of 26 months 38.6% of the patients in the BCG group and 46.4% of those in the mitomycin C group had tumor recurrence. In 7 of 11 studies BCG was significantly superior to mitomycin C, in 3 studies no significant difference was found, while in 1 study mitomycin C was significantly superior to BCG. An overall statistically significant superiority of BCG versus mitomycin C efficacy in reducing tumor recurrence was detected (OR 0.56, 95% CI 0.38 to 0.84, p = 0.005). In the subgroup treated with BCG maintenance all 6 individual studies showed a significant superiority of BCG over mitomycin C (OR 0.43, 95% CI 0.35 to 0.53, p <0.001). In 4 of the 5 studies with reported data on toxicity BCG associated cystitis was significantly more frequent than in the mitomycin C group (53.8% versus 39.2%). The combined cystitis OR was 1.81 (95% CI 1.48 to 2.23, p <0.001). The OR for cystitis in the BCG maintenance group did not significantly differ from that in the nonmaintenance therapy group. CONCLUSIONS: The results suggest superiority of BCG over mitomycin C for prevention of tumor recurrences in the combined data and particularly in the BCG maintenance treatment subgroup, irrespective of the actual (intermediate or high) tumor risk status. The toxicity with BCG is higher but does not differ between BCG maintenance and nonmaintenance groups.
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Prostate cancer, bladder cancer, renal cancer and testicular cancer are the most frequent malignancies in urology. Additional to parameters such as patient age, course of the disease, different forms of therapy and survival rates, quality of life is gaining more importance. This parameter is usually evaluated using general and disease-specific questionnaires. The SF-36 and the QLQ-C30 (EORTC) questionnaires are well established to determine quality of life in general. Disease-specific questionnaires for renal cancer and testicular cancer are currently under development. Bladder cancer can be evaluated by two EORTC modules investigating parameters such as voiding, bowel function and sexual function. The QLQ-BLS24 is made for patients with superficial bladder cancer and contains 24 questions. Also, side effects from intravesical therapy and repeated cystoscopies are determined. The QLQ-BLM30 is used for invasive bladder cancer. There are 30 questions to determine the impact of a urostoma (< >) or repeated catheterization. For prostate cancer many disease-specific questionnaires are available, however, only few are translated into German. One is the prostate cancer module QLQ-PR25 with 25 questions highlighting side effects (voiding, bowel function, sexual function) from prostatectomy, radiotherapy or antihormonal therapy. Despite problems when comparing different studies concerning quality of life in patients with localized prostate cancer one finds that radical prostatectomy is inferior in terms of continence, inferior or equal concerning sexual function and superior with respect to bowel function when compared with radiotherapy. It is noteworthy that there is no difference between prostatectomy and radiotherapy with respect to overall quality of life. Beside the development of disease-specific questionnaires, a future major issue is the standardized determination of the parameter quality of life to achieve a basis to compare the results of different studies.
Even M0 RCC is associated with tumour progression in approximately 30% of all patients after radical nephrectomy. Nevertheless, no effective adjuvant treatment after radical nephrectomy has been established. In a multicentre phase-III trial we investigated the impact of an adjuvant autologous tumour cell-lysate vaccination on the progression-free survival of patients with M0 RCC after radical nephrectomy. Between January 1997 and August 1998 a total of 558 patients with a renal tumour were enrolled at 55 different centres (study group) in Germany. Prior to radical nephrectomy all patients were centrally randomized (Quintiles Germany) to either receive an adjuvant autologous tumour cell-lysate vaccine (6 applications at 4-week intervals after radical nephrectomy) or to receive no adjuvant treatment (control group) after radical nephrectomy. All patients were evaluated following standardized diagnostic investigations at 6-month intervals. Following the inclusion criteria (RCC stages pT2-3bpN0-3M0, TNM-classification, UICC 1993), 365 patients were evaluable for the 3-year progression-free survival analysis. There were 240 patients with stage pT2pN0M0 (104 in the vaccine group and 136 patients in the control group) and 89 patients with stage pT3pN0M0 (46 in the vaccine group and 43 patients in the control group). The remaining 36 patients had positive lymph nodes. The trial was performed according to ICH-GCP guidelines. The 3-year progression-free survival rate for all tumour stages was 84.7% in the vaccine group and 80.9% in the control group. Patients with RCC stage pT3pN0-3M0 in the vaccine group demonstrated an advantage (74.4% in the vaccine group vs 65.9% in the control group). For RCC stage pT2pN0-3M0 the 3-year progression-free survival rate in the vaccine group was 89.7% compared to 85.7% in the control group. Follow-up of all patients enrolled in this trial is ongoing. This is the first randomized trial indicating a benefit from an adjuvant vaccination in patients with M0 RCC after radical nephrectomy. The advantage in terms of progression-free survival was more pronounced in patients with T3-tumours. However, it must be emphasized that the results of the final study report (2003) must be awaited before definite recommendations can be made.
This paper describes the use of urological laparoscopy in borderline patients, focussing on geriatric patients and those with renal failure. Laparoscopy must not only be feasible but also at least as effective concerning operative and postoperative parameters when compared to standard open surgery. For laparoscopic nephrectomy most of these factors have tested positive. However, only a few papers have been published concerning borderline patients. In some cases the pneumoperitoneum may not be suitable for borderline patients and open operative techniques are preferred. Apart from this, the current literature supports the effectiveness of laparoscopy even when certain risk factors are present. Especially borderline patients can benefit from the laparoscopic approach for nephrectomy. Although data are scarce concerning other laparoscopic procedures in borderline patients, the results of laparoscopic nephrectomy should probably apply to other laparoscopic procedures.
Vital aging is difficult to define; however, most people would agree that vital aging is something desirable. Voiding problems are frequent in the aging population. Obstruction of the lower urinary tract is often the cause of these problems with subsequent impact on the general quality of life. Etiologic and pathophysiologic investigations not only focus on the prostate itself but also on the interaction between prostate, bladder, and sphincter apparatus and the regulation of the voiding process. Correlation to other disorders as well as therapeutic aspects and issues of sexual function and quality of life are only some issues on the "to do" list in an aging population. A proper patient selection for therapy and a mobilization of the symptomatic patient will also be important targets in the future.
PURPOSE: Hematogenous spread of bacillus Calmette-Guerin (BCG) after intravesical instillation for bladder cancer is rare but it may result in systemic infection and hypersensitivity reaction. We investigated fluoroquinolones and steroids in an animal model to improve the therapeutic options in local and systemic BCG infection. Furthermore, the antitumor effectiveness of intravesical BCG with simultaneous application of fluoroquinolones and/or steroids was tested. MATERIALS AND METHODS: Oral antimicrobial therapy with and without steroids was started immediately after intraperitoneal injection using fluoroquinolones or trimethoprim-sulfamethoxazole. To evaluate the therapeutic options against a hyperergic reaction after repeat systemic BCG infection re-challenge was performed with intraperitoneal BCG 7 days after primary infection and oral therapy was given with fluoroquinolones or trimethoprim-sulfamethoxazole with and without steroids. The influence of continuous oral fluoroquinolone therapy on the antitumor effect of BCG was also tested in the MB 49 orthotopic murine bladder tumor model. RESULTS: After primary systemic infection fluoroquinolone therapy alone led to significantly prolonged survival in mice (log rank test p = 0.041), whereas trimethoprim-sulfamethoxazole was ineffective. There was no additional effect of steroid administration. Steroids alone led to premature death (log rank test p = 0.022). After secondary BCG infection only steroid treated animals had prolonged survival (log rank test p = 0.032), whereas antimicrobials alone had no effect. The therapeutic efficacy of BCG in the orthotopic bladder tumor model was not affected by continuous oral fluoroquinolones in terms of survival (log rank test p = 0.001) or bladder weight (Wilcoxon test p = 0.001) compared with untreated controls. CONCLUSIONS: In a mouse model fluoroquinolones had a beneficial effect for primary systemic BCG infections, whereas the hyperergic reaction after repeat BCG infection was susceptible only to steroids. Administering fluoroquinolones during an intravesical treatment course does not affect the antitumor efficacy of BCG.
PURPOSE: A presumed reason for the high recurrence rate of superficial bladder cancer after transurethral tumor resection is the reimplantation of tumor cells. Because tumor cell adhesion to the extracellular matrix is mediated by integrin molecules, we tested specific integrin receptor blocking oligopeptides to prevent this mechanism. MATERIALS AND METHODS: An in vitro cell adherence assay with various bladder cancer cell lines and extracellular matrices, including fibronectin, collagen type I, laminin and combinations, was used to analyze the inhibition of tumor cell adhesion by the matrix specific oligopeptides GRGDS, DGEA and EILDV. In therapeutic in vivo experiments the orthotopic murine bladder tumor model MB49 was used. The ability of oligopeptides to interfere with tumor cell adhesion and consecutive tumor outgrowth was evaluated and compared with that of nonspecific peptides, commercially available irrigation fluid and single dose epirubicin chemotherapy. RESULTS: In vitro fibronectin specific oligopeptides showed a concentration dependent inhibition of tumor cell adherence to fibronectin, whereas adhesion to laminin, collagen and combined matrices was not inhibited. In contrast, combinations of integrin receptor blocking oligopeptides were highly active. In vivo local tumor take was not affected by irrigation fluid, nonspecific peptides or monospecific oligopeptides alone, whereas the combination of the 3 oligopeptides effectively inhibited tumor outgrowth. CONCLUSIONS: Combining oligopeptides with various specificities significantly inhibited tumor cell adhesion and tumor outgrowth. Application of this principle in a clinical setting may be an effective method for reducing the recurrence rate of superficial bladder cancer.
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BACKGROUND: A lymphocele is a common finding after renal transplantation and occurs in up to 20% of patients. The majority of patients are asymptomatic. However, once a lymphocele has become symptomatic (e.g., through transplant dysfunction) this condition has to be treated. We report our 9-year experience with laparoscopic lymphocele fenestration and discuss the current management options for posttransplant lymphoceles. METHODS: Since 1993, 19 patients (11 males and 8 females; median age 56 years, range 22-68 years) of a total of 31 patients with a symptomatic posttransplant lymphocele have undergone laparoscopic fenestration of their lymphocele at a median of 66 days (range, 19-111 days) following successful renal transplantation in our department. As a first-line treatment, a percutaneous pigtail drainage catheter was inserted in all patients. In case of failure in resolving the fluid collection, the next step included sclerotherapy by instillation of tetracycline or ethanol into the lymphocele cavity in some cases. In patients with a persistent lymphocele, a laparoscopic lymphocele fenestration via a transabdominal approach was undertaken to achieve adequate drainage. RESULTS: Primary laparoscopic lymphocele fenestration was successful in all except two patients, who required a conversion. The median operating time was 36 min (range, 20-70 min). Following the procedure, renal transplant function remained stable or returned to individually normal levels in all patients. Median duration of hospital stay was 4 days (range, 1-13 days). At median follow-up of 27 months, all patients were alive with a functioning transplant. CONCLUSIONS: Laparoscopic lymphocele fenestration is reserved for patients in whom temporary drainage with or without sclerotherapy failed to resolve the fluid collection. In these cases the laparoscopic approach offers obvious technical and clinical advantages compared to open operative techniques.
Adjuvant intravesical bacillus Calmette-Guérin (BCG) therapy is a well-established and successful adjuvant immunotherapy in the treatment of superficial bladder cancer. Although the function of natural killer (NK) cells in other immunotherapeutic regimens (e.g., lymphokine-activated killer [LAK] cell or interleukin-2 [IL-2] therapy) has been established, the contribution of NK cells to effective BCG immunotherapy is not clear. We used a human in vitro system to analyze the role of NK cells in BCG-induced cellular cytotoxicity. After stimulation of mononuclear cells with BCG for 7 days, these BCG-activated killer (BAK) cells displayed substantial cytotoxicity against bladder tumor cells. Magnetic depletion experiments and fluorescence activated cell sorting revealed that NK cells were the major effector cell population. To address NK cell function in vivo, we studied a syngeneic orthotopic murine bladder cancer model and compared BCG immunotherapy in C57BL/6 wild-type mice, NK-deficient beige mice and mice treated with anti-NK1.1 monoclonal antibody. Four weekly instillations of viable BCG significantly prolonged survival in wild-type mice compared with control mice treated with solvent alone. In contrast, BCG therapy was completely ineffective in NK-deficient beige mice and in mice treated with anti-NK1.1 monoclonal antibody. These findings suggest a key role for NK cells during BCG immunotherapy.
Every year in Germany approximately 12,000 people are afflicted by superficial carcinoma of the urinary bladder. In addition, the number of recurrences is not inconsiderable. The goal of optimal therapy, therefore, is not only to cure the patients but also to lower the high rate of recurrence by appropriate prophylaxis. After transurethral resection, treatment options include various topical modalities of instillation therapy, e.g., chemotherapy or immunotherapy. The individual decision on which treatment modality is chosen should be based on the risk of relapse and the progression of the tumor. This depends on tumor stage, degree of differentiation, and the presence of recurrence. Some treatment options, such as instillation of bacillus Calmette-Guérin, have been validated by large randomized studies in the sense of evidence-based medicine.
Primary therapy of penile cancer (carcinoma in situ/T1 tumors) consists of circumcision, microsurgical excision, application of 5-fluorouracil cream, radiation, or laser treatment. In cases of larger T1 tumors or T2 and distal T3 tumors, partial penectomy with a 2-cm margin of clearance is mandatory. Secondary therapy includes inguinal lymphadenectomy 4-6 weeks after primary treatment and antibiotic prophylaxis. Independent prognostic factors for the presence of lymph node metastases are T stage and grading. Only patients with noninvasive G1 or G2 tumors and nonpalpable inguinal lymph nodes are candidates for surveillance with careful follow-up. Inguinal lymphadenectomy is performed in a radical or modified (Catalona) manner. Sentinel biopsy (Cabanas) may regain importance with the use of gamma probes. Complication rates of inguinal lymphadenectomy correlate to the extent of the procedure and must be weighed against the possibility of cure with lymphadenectomy. In cases of inguinal lymph node metastasis, removal of the iliac lymph nodes (one- or two-step procedure) is necessary.
PURPOSE: Mental and physical burden of physicians, especially surgeons, is high. The degree of burn-out was estimated among urologists in the German federal county of Schleswig-Holstein, with special emphasis on differences related to age, qualification and hospital versus private practice. MATERIALS AND METHODS: The Maslach Burnout Inventory was mailed to all urologists and urologists in training registered in the county of Schleswig-Holstein to determine the frequency and intensity of the 3 burn-out subscales of emotional exhaustion, depersonalization and low personal accomplishment, together with a questionnaire covering demographic data. RESULTS: Of 128 urologists 75 (58.6%) replied. Levels of burn-out in the subscales of emotional exhaustion and depersonalization were increased among hospital urologists, urologists in training and urologists younger than 45 years. Urologists in private practices, fully trained urological specialists and urologists older than 45 years showed a low degree of burn-out, corresponding to normal values, whereas young urologists in training and working in hospitals had the highest risk of burn-out. The personal accomplishment level was generally high in all groups. CONCLUSIONS: The constellation of being a urologist in private practice and older than 45 years appears to provide some protection against burn-out that might be due to a more personal relationship to the patients, lesser hierarchical situation and workload related income. In times of increasing pressure on the health care system, the personal situation of physicians in training should not be overlooked.