[The 1-cm lower calyx calculus: SWT, URS or Mini-PCNL? Guidelines vs. reality.] / Der 1 cm UKG-Stein: ESWL, URS oder Mini-PCNL? Leitlinien versus Realität.

Urinary stones of the upper urinary tract can be considered a widespread public health concern due to their high incidence and prevalence and their health policy-related and financial implications. A significant proportion of newly diagnosed kidney stones are lower-pole stones, i.e., stones affecting the lower calyx group of the renal pelvicalyceal system. These are often diagnosed by chance, i.e., as incidental findings during ultrasound or CT scans performed for other reasons, or as "secondary stones" detected during the diagnostic work-up of symptomatic urinary stones in other locations. Residual disintegrates after extracorporeal shock-wave lithotripsy (ESWL) or endoscopic stone therapy constitute a further, quantitatively significant group. These incidentally discovered lower-pole stones are often characterised by their small size and lack of symptoms. It stands to reason that some of these small, asymptomatic lower-pole stones do not always remain small and asymptomatic, and that treatment tends to become more complex with increasing size. There has been an astonishing lack of published studies with a high level of evidence over the last 20 years to provide a conclusive and reproducible answer to the question posed in this review. Small, asymptomatic stones can be monitored. Symptomatic and rapidly growing stones should be treated. There is a lack of valid risk factors allowing an identification of subgroups that should be treated prophylactically at the asymptomatic stage. In active therapy, a 10-to-20-year-old principle still holds true today: a high stone-free rate in one therapy session is offset by an increased complication rate, with increasing miniaturisation in endourology (retrograde and percutaneous) and increasingly effective laser disintegration shifting this basic principle more and more in favour of flexible URS and (mini, micro) PCNL. The range of indications for ESWL is undoubtedly becoming smaller, and this also applies to lower-pole stones. The results of an ongoing prospective randomised study comparing the different treatment modalities, albeit with recruitment difficulties, are still pending.

[CpG-ODN instillation boosts ICAM-1 expression in an orthotopic murine UCC model: immunohistochemical evaluation of the local response to immunostimulatory DNA]. / ICAM-1-Induktion durch CpG-ODN im murinen, orthotopen UCC-Modell ­ Immunhistochemische Analyse der lokalen Immunantwort auf immunstimulatorische DNA-Sequenzen.

BACKGROUND: Immunostimulatory CpG oligodeoxynucleotides (CpG-ODN) have been verified as an effective antineoplastic agent for intravesical application in a murine orthotopic C57-BL6 /MB-49 urothelial cell carcinoma (UCC). To date, many details in the mode of action have remained unclear. Preceding studies pointed towards a Th1-weighted response. The aim of this work was to identify the local lymphocyte subsets in murine tumour-bearing bladders and to examine effects on the expression of Intercellular Adhesion Molecule 1 (ICAM-1) after treatment with CpG-ODN. MATERIAL AND METHODS: Different instillation schedules were applied in an established orthotopic C57-BL6 /MB49 UCC model. After 13 days, fresh frozen sections of the harvested bladders were immunohistochemically examined for the infiltration density of lymphocytes expressing CD 3, CD4, CD8 and CD19. In a second series of the same animal model, healthy and tumour-bearing bladders were exposed to CpG-ODN or PBS and later stained for the expression of ICAM-1. RESULTS: CpG-ODN instillation led to augmented T-cell infiltration (represented by CD3). Further T-cell subdifferentiation between T-helper cells (CD4) and cytotoxic T cells (CD 8a) did not show a perceptible variety between groups. The B-cell population (CD19) was found to decrease over the course of treatment. In the second series, treatment provoked a strong expression of ICAM-1 by infiltrating leukocytes, endothelial cells and particularly by the cancer cells themselves. DISCUSSION: The previously observed augmented lymphocyte density was classified as T-cell infiltration. The decline of the B-cell concentration over the course of treatment suggests a Th2 suppression in favour of a Th-1 polarisation. These findings support the assumption that a cell-mediated immune response is the mode of action underlying the antineoplastic CpG-ODN capacities. The marked upregulation of ICAM-1 expression, especially on tumour cells, suggests a crucial role of this membrane protein for the initiation and maintenance of anticancer immune response. CONCLUSION: CpG-ODN might be a prospective alternative to established instillation therapies. With a view to the current BCG shortage and the well-known toxicities, an amplification of the topic therapy armamentarium could be achievable. The now described capability of ICAM-1 induction on carcinoma cells and, by association, the reversal of escape strategies to cancer immunity may also make the agent interesting as an adjuvant for modern checkpoint inhibition.

Efficacy and safety of the Accordion stone-trapping device: in vitro results from an artificial ureterolithotripsy model.

One of the challenges of intracorporeal ureterolithotripsy is undesired stone migration. Stone-trapping devices have been designed to prevent this quite common phenomenon. These devices have to be effective in terms of ureteral obstruction and safe in terms of resistance to the action of commonly used lithotriptors. This work was conducted to evaluate the efficacy and safety of the recently approved Accordion stone-trapping device in vitro. In a rigid, submerged ureteral model with two different diameters (8 and 10 mm), artificial stones were positioned in direct contact with the engaged Accordion device. A defined number of pneumatic pulses of the LithoClast master at different performance levels was applied and the migration distance of the stone was measured after each single pulse. As a control, the same series was repeated without the stone-trapping device. Secondly, the Accordion device was exposed to a previously defined number of pneumatic or Ho:YAG-laser pulses, in direct contact with the lithotripsy probe, up to a total activation time of 2 min. At different time points, the device was controlled for damage and functionality. The mean stone migration distance without the Accordion device was between 39.2 and 52.8 mm and between 37.8 and 75.4 mm in the 8 and 10 mm tubes, respectively. In comparison, the stone or fragment travelling distance with the device was in the 0-2 mm range. This difference was highly significant. Both pneumatic and laser lithotriptor did not affect the functionality of the Accordion device. The Ho:YAG laser causes small perforations of the film without affecting the devices' stability. The Accordion device appears to be highly efficient and safe in vitro. Clinical trials will have to assess its value in endourological practice. Randomised comparative trials comparing different stone-trapping devices are needed.

Urinary collecting system invasion in renal cell carcinoma: incidence and long-term prognosis.

OBJECTIVES: Current data on the prognostic impact of urinary collecting system (UCS) invasion by renal cell carcinoma (RCC) are highly conflicting. The aim of the present study was to assess incidence and long-term prognosis of RCC patients with and without UCS involvement. METHODS: We evaluated 780 patients who had undergone renal surgery between 1990 and 2005. The mean follow-up was 5.44 years. RESULTS: Sixty-seven patients (8.6%) demonstrated UCS invasion. These patients had a significant increase in the likelihood of cancer-related death (hazard ratio [HR] 1.9, 95% confidence interval: 1.4-2.7; P = 0.001). Their median 5-year tumor-specific survival rate was 61%, as opposed to 79% for patients without UCS invasion (P = 0.001). UCS invasion was significantly associated with tumor stage, grade, clinical symptoms, lymph node and visceral metastasis at diagnosis, but not with age, gender, histologic subtype or body mass index. However, by means of multivariate analysis, UCS invasion was disqualified as an individual prognostic marker for RCC. CONCLUSION: We do not advocate the inclusion of UCS invasion into upcoming Tumor-Nodes-Metastasis staging systems. In contrast, future research should focus on the prognostic role of novel molecular tumor markers and/or specific immunological characteristics of RCC patients.

Comparison of a 20-min pad test with the 1-hour pad test of the international continence society to evaluate post-prostatectomy incontinence.

OBJECTIVES: Urinary incontinence is a hygienic and socially distressing problem for affected people and causes high healthcare costs. Objective standardized noninvasive quantification of urinary incontinence is highly important and, in addition, enables control of therapeutic efficacy. The aim of this prospective study was to evaluate the feasibility, accuracy and reproducibility of a standardized 20-min pad test to measure urinary incontinence after radical prostatectomy in comparison to the 1-hour pad-weighing test recommended by the International Continence Society (ICS). METHODS: We applied a standardized questionnaire, the ICS 1-hour pad test and a simplified 20-min pad test to evaluate subjective and objective post-prostatectomy urinary incontinence in 56 men. RESULTS: The technical feasibility of the 20-min pad test was excellent; the results correlated significantly with both the self-assessment via questionnaire (r = 0.63; p < 0.001) and the 1-hour pad test (ICS; r = 0.66; p < 0.001). Moreover, it was highly reliable (r = 0.74; p < 0.0005) with excellent patient acceptance. CONCLUSIONS: The 20-min pad test qualified as a reliable, cost-effective and noninvasive tool which can easily be applied in urologic or physiotherapeutic practice to assess post-prostatectomy urinary incontinence and to evaluate the success of therapeutic approaches.

In vitro and in vivo effects of CpG-Oligodeoxynucleotides (CpG-ODN) on murine transitional cell carcinoma and on the native murine urinary bladder wall.

BACKGROUND: Intravesical BCG instillation is established and efficient in the prophylaxis of recurrent transitional cell carcinoma. A Th-1 biased immune response is postulated. Recent work has proven the efficacy of synthetic CpG-Oligodeoxynucleotides (ODN) as inducers and adjuvants for a strong Th1-response and there is evidence for a direct and/or adjuvant anti-neoplastic effect. The purpose of this study was to examine the local effects of CpG-ODN on the murine bladder wall after intravesical instillation and the effects on cytokine expression in an orthotopic murine bladder cancer model. MATERIALS AND METHODS: Histopathology, immunohistochemistry and fluorescence microscopy were performed after different instillation schedules of stimulatory, non-stimulatory biotinylized and FITC-labelled CpG-ODN into the murine bladder. MB-49 murine bladder cancer cells were tested for TLR-9 expression to exclude a potential direct responsiveness to CpG-ODN. Furthermore induction of apoptosis was tested by annexin V staining and FACS analysis of CpG-ODN stimulated tumor cells. In an orthotopic C57/Bl6 murine bladder cancer model, the expressions of IL-12, IFNgamma, IL-10 and TGF-beta were evaluated after repeated CpG-ODN treatment. RESULTS: Single and repeated instillation of CpG-ODN induced subepithelial and urothelial lymphocytic infiltrations with consecutive apoptoses. PBS and non-stimulative ODN induced no visible reaction. Bladder submucosa stained positive for biotin. Controls showed no endogenic biotin staining. FITC-labelled ODN adhered to the bladder mucosa and penetration of the mucosal barrier was not detected. MB-49 TCC cells did not express TLR-9 and CpG-ODN did not induce apoptosis in these cells. Repeated intravesical instillations of CpG-ODN in orthotopic murine tumor bearing urinary bladders resulted in significant up-regulation of both Th-1 and Th-2 cytokines. CONCLUSION: CpG-ODNs have promising anti-neoplastic potential. They exert a pronounced immunological response both in the native murine urinary bladder and in murine TCC. The mechanisms of action appear to be mediated immunologically, There was no direct effect of CpG-ODN on the tumor cells in this model.

Overweight is associated with improved cancer-specific survival in patients with organ-confined renal cell carcinoma.

OBJECTIVES: Overweight/obesity is known to increase the risk of developing renal cell carcinoma (RCC). However, data on the prognostic impact of overweight in RCC is still conflicting. We assessed whether different body mass index (BMI) levels at the time of surgery had an effect on the long-term prognosis of RCC patients. METHODS: We evaluated 771 patients, with complete information about their BMI, who had undergone renal surgery for RCC between 1990 and 2005 at the authors' institution; the mean follow-up was 5.48 years. RESULTS: Underweight, normal weight, pre-obesity, and obesity were diagnosed in 4 (0.5%), 239 (31%), 356 (46.2%), and 172 (22.3%) RCC patients, respectively. Overweight (BMI >25) was significantly associated with younger age (P = 0.004) and positive nodal status (P = 0.04) but not with tumor stage, grade, visceral metastasis, gender, histological subtype, or tumor-related symptoms. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 80% as opposed to 72% for patients with a BMI below 25 (P = 0.003). Interestingly, subgroup analysis revealed that the positive association between overweight and survival was even more pronounced in organ-confined (P < 0.001) RCC, but no correlation was observed in advanced disease (P = 0.23). CONCLUSION: We were able to identify overweight as an independent prognostic marker of improved tumor-specific survival in patients with organ-confined RCC. Basic research is required to resolve the dilemma of why, if a higher BMI predisposes to RCC, it concurrently prolongs survival after patients have undergone (partial) nephrectomy.

Clinical significance of a prostate-specific antigen flare phenomenon in patients with hormone-refractory prostate cancer receiving docetaxel.

Docetaxel has shown promise for the treatment of hormone-refractory prostate cancer and has become the standard of care. The flare phenomenon is a known entity in androgen-deprivation therapy of advanced prostate cancer and it has also been described in palliative chemotherapy of hormone-refractory prostate cancer. The aim of this study was to evaluate the clinical impact of a prostate-specific antigen flare phenomenon in docetaxel-treated hormone-refractory prostate cancer patients. From December 2002 to August 2005, we treated 44 patients with hormone-refractory prostate cancer applying docetaxel-based regimens. Prostate-specific antigen levels were determined before therapy and weekly thereafter. Patients were divided into three groups: response (group 1), progression (group 2) and flare (group 3). Flare was defined as initially rising prostate-specific antigen under therapy, dropping thereafter to values below baseline. The groups were compared for overall survival by Kaplan-Meier analysis. We observed a prostate-specific antigen flare phenomenon in eight (18%) of 44 evaluable patients; 24 (54.5%) patients were primary responders and 12 (27.3%) experienced progressive disease. In group 3, prostate-specific antigen levels rose to 107-180% from baseline and then dropped to 21-68%. Kaplan-Meier analysis showed significantly better overall median survival for groups 1 (18 months, P=0.0005) and 3 (19 months, P=0.006) than for group 2 (7 months). Survival in groups 1 and 3 was comparable. Grade 3 and 4 toxicity was below 5% and equally distributed between the 3 groups. In our limited patient cohort, prostate-specific antigen flare phenomenon does not seem to be a clinically relevant issue in terms of overall survival. Thus, an initial rise of prostate-specific antigen under docetaxel therapy in hormone-refractory prostate cancer does not indicate therapeutic failure and should not lead to early withdrawal from therapy in the absence of clinical signs of progression.