Photodynamic diagnosis for superficial bladder cancer: do all risk-groups profit equally from oncological and economic long-term results?

OBJECTIVE: Photodynamic diagnosis (PDD) of superficial bladder cancer decreases recurrence rates. We present oncological results of a randomized, prospective study, comparing transurethral resection (TUR) performed under conventional white light (WL) with PDD. The follow-up period is the longest reported to date. As costs might be reimbursed by prolonged recurrence-free survival in certain patients cost analysis in regard to risk-groups was performed. MATERIAL AND METHODS: Using chi-square test and log-rank test we compared recurrence rates of 103 patients after WL-TUR and of 88 patients after PDD-TUR. Cost analysis was performed according to risk-groups of recurrence. RESULTS: Mean follow-up was 99 months. Recurrence rate was 57% in WL vs. 28% in PDD (p < 0.001). Costs incurred by subsequent TUR averaged euro 2310 per WL patient vs. euro 713 per PDD patient. Savings per patient by PDD amounted to euro 1597. PDD costs were reimbursed in low, intermediate and high risk patients, respectively. CONCLUSIONS: PDD-TUR is significantly superior to conventional WL-TUR in terms of recurrence rate. While economic benefit is most prominent in intermediate risk patients, PDD related costs are reimbursed in all risk-groups.

Bladder sparing approach for initial T1G3 bladder cancer: Do multifocality, size of tumor or concomitant carcinoma in situ matter? A long-term analysis of 132 patients.

OBJECTIVES: In T1 bladder cancer (BC) multifocality, size of tumor (> or =3 cm) and concomitant carcinoma in situ (CIS) are used to stratify patients' risk. We compared the long-term results in patients with initial T1G3 bc treated with transurethral resection of the bladder (TURB), bacille Calmette-Guérin (BCG) instillations and repeat resection with special regard to these clinical risk factors. The aim was to determine if they influence the outcome in the bladder sparing approach for initial T1G3 bc. METHODS: One hundred and thirty-two consecutive patients with initial T1G3 and no prior history of BC were identified. All patients completed six weekly adjuvant BCG instillations followed by control TURB. Follow-up consisted of cystoscopy with bladder wash cytology every 3 months for 2 years and every 6 months thereafter. RESULTS: Forty-two percent of patients had residual disease, 65% developed recurrence of any stage and 41% had progression to muscle-invasive disease. Cancer-specific survival was 89% and 78% at 5 and 10 years, respectively. Only CIS was significantly correlated with all end points on multivariate analysis. While the presence of one or two risk factors was not related to recurrence, progression or cancer-related death, the presence of all three risk factors predicted the latter. CONCLUSIONS: While no guideline has been established for the decision between cystectomy and bladder sparing, concomitant CIS and the presence of all three risk factors together seem to predict an adverse oncological outcome in the bladder sparing approach.

Clinically relevant reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acid-induced fluorescence diagnosis: 8-year results of prospective randomized study.

OBJECTIVES: Several studies have shown that 5-aminolevulinic acid (5-ALA)-induced fluorescence cystoscopy improves the detection of superficial bladder cancer. The results have suggested a reduced rate of recurrent tumors with the use of 5-ALA fluorescence before bladder tumor resection. We performed a prospective, randomized trial to investigate whether the long-term tumor recurrence and residual tumor rates can be decreased using 5-ALA fluorescence diagnosis (FD). METHODS: A total of 301 patients with suspected superficial bladder carcinoma were randomized to transurethral resection (TUR) using conventional white light (WL) or FD. TUR was repeated to evaluate the residual tumor rate. In addition, patients were followed up for a median of 83 (WL) and 86 (FD) months to evaluate recurrence-free survival (RFS). RESULTS: Of the 301 patients, 191 were available for the efficacy analysis. The residual tumor rate was 25.2% in the WL arm versus 4.5% in the FD arm (P <0.0001). The RFS rate after 2, 4, 6, and 8 years was 73%, 64%, 54%, and 45% in the WL group and 88%, 84%, 79%, and 71% in the FD group, respectively, revealing a statistically significant difference in favor of fluorescent TUR (P = 0.0003). CONCLUSIONS: 5-ALA-induced FD is significantly superior statistically to conventional WL TUR with respect to the residual tumor rate and RFS. This advantage of decreased bladder tumor recurrence risk was maintained with high statistical significance for at least 8 years. The differences in RFS imply that FD offers a clinically relevant procedure to reduce the incidence of tumor recurrence.

Photodynamic diagnostics and noninvasive bladder cancer: is it cost-effective in long-term application? A Germany-based cost analysis.

OBJECTIVES: Noninvasive urothelial carcinoma of the bladder (UCB) causes an enormous economic burden to public health systems due to its life-long character and frequent recurrences. While white light (WL) cystoscopy is considered to be the gold standard for transurethral resection of the bladder, photodynamic diagnostic (PDD) has been shown to improve final outcome. Escalating healthcare costs warrant increased effectiveness in treating noninvasive UCB. No data based on assessment of costs have been published to date. METHODS: A series of 301 patients with noninvasive UCB were randomized prospectively to standard WL or PDD transurethral resections of the bladder. Intravesical adjuvant therapy was administered as reflected in the appropriate guidelines. Expenditures of subsequent procedures and PDD-associated costs were assessed. RESULTS: Median follow-up was 7.1 yr. Disease recurrence was found in 42% and 18% of WL and PDD patients, respectively (p=0.0003). In the WL group 2.0 and in the PDD group 0.8 transurethral resections of the bladder were noted per patient. In the WL group 1.0 and in the PDD group 0.3 recurring UCB occurred per patient, resulting in costs of 1750 euro per WL patient versus 420 euro per PDD patient in the follow-up period, respectively. Because a single expenditure of 135 euro was assessed for PDD, overall costs were significantly lower (by 1195 euro) in PDD patients. As the median follow-up was 7.1 yr, costs saved by PDD per patient per year were 168 euro. CONCLUSION: Our data suggest that PDD significantly cut costs related to recurring UCB. Further studies are needed from an economic point of view.

Vacuum-assisted closure versus conventional wound care in the treatment of wound failures following inguinal lymphadenectomy for penile cancer: a retrospective study.

OBJECTIVES: Impaired wound healing is a frequent event in inguinal surgery and very common after lymphadenectomy for penile cancer. Although vacuum therapy has been reported to expedite the healing of complex wound failures, vacuum-assisted closure (VAC) has been reported to be contraindicated in malignancy. In the present study we evaluated the use of VAC in the treatment of complex wound failures following inguinal lymphadenectomy for penile cancer in comparison to conventional wound care (CWC) implying debridement and saline-soaked gauze. METHODS: We retrospectively identified six inguinal wounds following inguinal lymphadenectomy for penile cancer and subsequent use of VAC from 2003 to 2006 at our institution. Data on surgical interventions, complications, length of time required for closure, and outcome were compared to 10 inguinal defects treated with CWC between 2000 and 2003. RESULTS: Wound volume was comparable for both groups. Wound breakdown occurred at a median of 7.4 d after inguinal lymphadenectomy and was treated by CWC for a mean of 69.8 d. In the VAC group, the median duration until complete closure was 38.9 d. Thus, VAC was shown to result in complete wound healing in less time (p<0.001). No local recurrence in the VAC group was noted despite positive lymph nodes. CONCLUSIONS: VAC therapy is effective in complex inguinal wound failures following lymphadenectomy for penile cancer and appears to be superior to CWC. VAC seems to offer adequate safety concerning local recurrence.

Chlamydia pneumoniae in an ex vivo human artery culture model.

The role of the obligate intracellular pathogen Chlamydia pneumoniae in the development of atherosclerosis could not be completely clarified. Reasons are the highly discrepant results obtained in the hitherto existing studies and the lack of an experimental system allowing the direct examination of chlamydial effects in the human vasculature. We established a human ex vivo organ culture model for the characterization of vascular chlamydial infection. Ninety sections of renal arteries, obtained from nephrectomies, were inoculated with Chlamydia pneumoniae. Using a monoclonal FITC-conjugated antibody, chlamydial LPS was broadly detected in inoculated arteries during the entire observation period of 35 days. However, recultivation of viable organisms from the artery vessel wall was impossible, indicating that productive infection in human arteries did not occur even under optimized conditions. This was substantiated by low recovery rates of Chlamydia pneumoniae, low amounts of detectable chlamydial 16S rRNA and ultramorphological presence of polymorph multilamellar bodies in experimentally infected smooth muscle cells originating from aortas, coronary and renal arteries. We could demonstrate that the complex environment of a human artery did not support the growth of Chlamydia pneumoniae although the presence of chlamydial LPS in the artery vessel wall following experimental infection was a common event. The presence of chlamydial LPS in the absence of viable organisms within the artery vessel wall may explain the failure of antibiotic treatment strategies for atherosclerosis.

Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic acid induced fluorescence diagnosis in patients with superficial bladder tumors.

PURPOSES: Fluorescence diagnosis induced by 5-aminolevulinic acid enables more thorough transurethral resection of superficial bladder carcinoma compared with conventional white light. We performed a prospective, single institution, randomized trial to investigate whether the residual tumor rate and long-term tumor recurrence can be decreased by fluorescence diagnosis. MATERIALS AND METHODS: A total of 301 patients underwent transurethral resection of bladder tumors with white light or fluorescence diagnosis. Transurethral resection was repeated 5 to 6 weeks later to evaluate the residual tumor rate. To determine recurrence-free survival patient followup was performed every 3 months by white light cystoscopy and urine cytology. Recurrence-free survival was analyzed via Kaplan-Meier methods and multivariable Cox regression analysis. RESULTS: A total of 191 patients with superficial bladder carcinoma were available for efficacy analysis. The residual tumor rate was 25.2% in the white light arm versus 4.5% in the fluorescence diagnosis arm (p <0.0001). Median followup in the white light arm in 103 cases was 21.2 months (range 4 to 40) compared with 20.5 (range 3 to 40) in the 88 in the fluorescence diagnosis arm. Recurrence-free survival in the fluorescence diagnosis group was 89.6% after 12 and 24 months compared with 73.8% and 65.9%, respectively, in the white light group (p = 0.004). This superiority proved to be independent of risk group. The adjusted hazard ratio of fluorescence diagnosis versus white light transurethral resection was 0.33 (95% confidence interval 0.16 to 0.67). CONCLUSIONS: Fluorescence diagnosis is significantly superior to conventional white light transurethral resection with respect to the residual tumor rate and recurrence-free survival. The differences in recurrence-free survival imply that fluorescence diagnosis is a clinically relevant procedure for decreasing the number of tumor recurrences.