Frailty predicts outcome of partial nephrectomy and guides treatment decision towards active surveillance and tumor ablation.

PURPOSE: To examine frailty and comorbidity as predictors of outcome of nephron sparing surgery (NSS) and as decision tools for identifying candidates for active surveillance (AS) or tumor ablation (TA). METHODS: Frailty and comorbidity were assessed using the modified frailty index of the Canadian Study of Health and Aging (11-CSHA) and the age-adjusted Charlson-Comorbidity Index (aaCCI) as well as albumin and the radiological skeletal-muscle-index (SMI) in a cohort of n = 447 patients with localized renal masses. Renal tumor anatomy was classified according to the RENAL nephrometry system. Regression analyses were performed to assess predictors of surgical outcome of patients undergoing NSS as well as to identify possible influencing factors of patients undergoing alternative therapies (AS/TA). RESULTS: Overall 409 patient underwent NSS while 38 received AS or TA. Patients undergoing TA/AS were more likely to be frail or comorbid compared to patients undergoing NSS (aaCCI: p < 0.001, 11-CSHA: p < 0.001). Gender and tumor complexity did not vary between patients of different treatment approach. 11-CSHA and aaCCI were identified as independent predictors of major postoperative complications (11-CSHA ≥ 0.27: OR = 3.6, p = 0.001) and hospital re-admission (aaCCI ≥ 6: OR = 4.93, p = 0.003) in the NSS cohort. No impact was found for albumin levels and SMI. An aaCCI > 6 and/or 11-CSHA ≥ 0.27 (OR = 9.19, p < 0.001), a solitary kidney (OR = 5.43, p = 0.005) and hypoalbuminemia (OR = 4.6, p = 0.009), but not tumor complexity, were decisive factors to undergo AS or TA rather than NSS. CONCLUSION: In patients with localized renal masses, frailty and comorbidity indices can be useful to predict surgical outcome and support decision-making towards AS or TA.

Prospective geriatric assessment for perioperative risk stratification in partial nephrectomy.

PURPOSE: Comorbidities and frailty are determinants of surgical outcome. The aim of the study was to examine various measures of frailty and comorbidities in predicting postoperative outcome of partial nephrectomy (PN). METHODS: We prospectively analyzed the frailty and comorbidity status of 150 patients undergoing PN between 2015 and 2018. Primary endpoint was the occurrence of major postoperative complications (MPC) and secondary endpoints were the failure of Trifecta achievement and the need for hospital readmissions. For the transfer into clinical practice the most significant frailty parameters were summarized in a multi-dimensional test. RESULTS: Median age was 67 (33-93) years, 64.7% of the patients were male. Univariable regression analysis showed, that patients with increased frailty indices (Hopkins frailty score ≥2 (OR = 3.74, p = 0.005), Groningen frailty index ≥4 (OR = 2.85, p = 0.036)) are at higher risk to develop MPC. Furthermore, poor physical performance, such as a low handgrip strength or a Full-Tandem-Stand (FTS) < 10 s were associated with MPC (OR = 4.76, p = 0.014; OR = 4.48, p = 0.018) and Trifecta failure (OR = 3.60, p = 0.037, OR = 5.50, p = 0.010). Six measures were combined to the geriatric assessment in partial nephrectomy score (GAPN). A GAPN-score ≥3 proved to be a significant predictor for MPC (OR = 4.30, p = 0.029) and for Trifecta failure (OR = 0.20, p = 0.011) in multivariable regression analysis. CONCLUSION: The frailty status and comorbidities are important determinants of the postoperative course after PN. These parameters should be assessed preoperatively and included in the treatment planning, especially in light of available alternative therapies. In this context, the GAPN-score may be a suitable tool.

Influence of symptomatic pseudoaneurysms on postoperative renal function after partial nephrectomy: results of a matched pair analysis.

PURPOSE: A symptomatic pseudoaneurysm (SPA) is a rare but severe complication after partial nephrectomy (PN). Selective trans-arterial embolization (TAE) is the treatment of choice with high success rates. However, the influence of this intervention on postsurgical renal function has not been studied. METHODS: Between 2005 and 2016 we performed 1047 PNs at our institution. Postsurgical SPA occurred in 40 patients (3.8%). Patients with and without SPA were matched in a 1:2 ratio concerning tumor complexity (RENAL) and pre-operative renal function (CKD stage). Any CKD upstage and a relevant CKD progression (CKD ≥ III) were defined as endpoints. Furthermore, the influence of the amount of contrast agent applied during TAE was assessed. RESULTS: All patients with SPA were treated successfully with TAE. No significant difference could be detected concerning clinical, functional and surgical aspects. Median follow-up time accounted for 12.5 (6.75-27.5) months. Kaplan-Meier analyses detected an increased rate of any CKD upstage (p = 0.066) and relevant CKD progression (p = 0.01) in patients with SPA. Multivariate analysis identified post-operative SPA to be an independent predictor for a relevant CKD progression (HR 4.15, p = 0.01). The amount of contrast agents used did not have an impact on the development of a relevant CKD progression (p = 0.72). CONCLUSION: Patients treated with TAE after PN show an additional risk for an impairment of renal function over time. Hence, those patients should explicitly be informed about possible consequences and closely monitored by nephrologists.

[Ablative therapy of small renal masses]. / Ablative Therapien kleiner Nierentumoren.

Renal cell cancer is nowadays predominantly diagnosed in early stages due to the widespread use of sectional imaging for unrelated symptoms. Small renal masses (<4 cm) feature a largely indolent biology with a very low risk for metastasis or even a benign biology in up to 30% of the cases. Consequently, there is a need for less invasive therapeutic alternatives to nephron-sparing surgery. Meanwhile, there is a broad portfolio of local ablation techniques to treat small renal tumors. These include the extensively studied radiofrequency ablation and cryoablation techniques as well as newer modalities like microwave ablation and irreversible electroporation as more experimental techniques. Tumor ablation can be performed percutaneously under image guidance or laparoscopically. In particular, the percutaneous approach is a less invasive alternative to nephron-sparing surgery with lower risk for complications. Comparative studies and meta-analyses report a higher risk for local recurrence after renal tumor ablation compared to surgery. However, long-term oncological results after treatment of small renal masses are promising and do not seem to differ from partial nephrectomy. The possibility for salvage therapy in case of recurrence also accounts for this finding. Especially old patients with an increased risk of surgical and anesthesiological complications as well as patients with recurrent and multiple hereditary renal cell carcinomas may benefit from tumor ablation. Tumor biopsy prior to intervention is associated with very low morbidity rates and is oncologically safe. It can help to assess the biology of the renal mass and prevent therapy of benign lesions.

Prognostic significance of Fuhrman grade and age for cancer-specific and overall survival in patients with papillary renal cell carcinoma: results of an international multi-institutional study on 2189 patients.

PURPOSE: Because the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series. METHODS: We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (<50 years, 50-75 years, >75 years) on cancer-specific mortality (CSM). RESULTS: CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p < 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p < 0.001) in comparison to FG 1. CSM was significantly worse in patients aged >75 (HR 2.85, 95% CI 2.06-3.95; p < 0.001) compared to <50 years. CONCLUSIONS: FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.

[Renal cell carcinoma in older and geriatric patients]. / Nierenzellkarzinom des alten und geriatrischen Patienten.

BACKGROUND: Renal cell carcinoma (RCC) is a disease of older humans. Due to increased detection of tumours by ultrasound and computed tomography, the number of incidentally diagnosed RCCs has increased. These tumours are usually smaller and of lower stage. Furthermore, there is an increase of older people in the population. OBJECTIVES: Characteristics of tumour biology, prognosis, diagnostics and therapy of localized, advanced and metastatic RCC in old and geriatric patients are provided. METHODS: Systematic literature review, analysis and discussion of original research articles and expert opinions. RESULTS: The surgical treatment of RCC in old and geriatric patients requires attention to increased morbidity and mortality. Active surveillance or ablations are alternatives to surgical treatment in localized RCC. Systemic therapy in metastatic tumours exhibit analogous efficacy with slightly worse toxicity. CONCLUSIONS: RCC in old and geriatric patients requires an adaptation of classic therapeutic strategies. Management should be adjusted individually to age and comorbidities. Efficacy, risk and toxicity of all therapeutic options should be considered. A multidisciplinary approach is important for diagnosis, assessment and therapy. Recommendations should be discussed with patients and their relatives according to the individual needs, and treatment decisions should be based on patient preferences wherever possible.

Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.

BACKGROUND: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. METHODS: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. RESULTS: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. CONCLUSION: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

Applicability of robot-assisted laparoscopic radical prostatectomy in renal allograft recipients.

PURPOSE: To evaluate the general applicability of robotic-assisted laparoscopic radical prostatectomy (RALP) in renal transplant recipients and potential surgical modifications due to the position of the transplanted kidney in the iliac fossa, as RALP has proven to be an effective and safe treatment option for prostate cancer (PCa) removal. PROCEDURES: A 71-year-old patient who had undergone renal transplantation was diagnosed with biopsy-proven localized Gleason 7a PCa. The prostate-specific antigen value was 12.4 ng/mL. RALP was performed by a transperitoneal approach using six ports. By partial mobilization of the bladder, the working space for the radical prostatectomy was created, while leaving the renal transplant and ureter untouched. Lymph node dissection was performed only on the contralateral side of the transplanted kidney. RESULTS: The procedure concluded after 220 minutes and the estimated blood loss was 300 mL. The perioperative clinical course was uneventful. The kidney function remained normal with a creatinine value of 1.2 mg/dL. A complete extirpation of the prostate with negative surgical margins was achieved. After catheter removal, the patient was completely continent. CONCLUSIONS: RALP in renal transplant recipients is feasible and can be achieved with favorable oncological and functional outcome. No modifications to the standard RALP technique are required in these patients, except from a partial dissection of the bladder from the abdominal wall and a one-sided lymph node dissection.

[Tumours of the Kidney: CT vs. MRI. Nearly equal alternatives with minor differences]. / Raumforderungen der Niere: CT vs. MRT. Zwei fast gleichwertige Alternativen mit feinen Unterschieden.

Because of progress in imaging, the incidence of renal tumours, especially small lesions, has been rising over the last years. Therefore, imaging must be done to decide how to proceed further. But which is the most effective modality: computed tomography (CT) or magnetic resonance imaging (MRI)? From the technical point of view, the two alternatives appear to be nearly equal. Multidetector CT remains the reference standard for staging and lesion characterisation, whereas MRI is the method of choice for determining caval extension of a tumour thrombus and infiltration of the renal vein. If an accurate diagnosis cannot be specified, the remaining modality should be used complementarily.

Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney.

The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms alpha and beta were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific.

Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis.

Cancer cells are typically characterized by apoptosis deficiency. In order to investigate a possible role for the anti-apoptotic livin gene in renal cell cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC-derived cell lines. In addition, we studied the contribution of livin to the apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene expression was detected in a significant portion of RCC tumor tissue specimens (13/14, 92.9%) and tumor-derived cell lines (12/15, 80.0%). Moreover, targeted inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic stimuli, such as UV irradiation or the chemotherapeutic drugs etoposide, 5-fluorouracil, and vinblastine. These effects were specific for livin expressing tumor cells. We conclude that livin can contribute significantly to the apoptosis resistance of RCC cells. Targeted inhibition of livin could represent a novel therapeutic strategy to increase the sensitivity of renal cancers towards pro-apoptotic agents.

[Palliative and supportive therapy in cases of renal cell carcinoma]. / Palliative und supportive Therapie des Nierenzellkarzinoms.

At the time of diagnosis, 25-30% of all patients with renal cell carcinoma already present with metastatic disease. Furthermore, 20-30% of patients with renal cell carcinoma will have progressive disease despite radical nephrectomy with complete tumor resection. In this review, we discuss the current therapeutic options for patients with metastatic renal cell carcinoma: These include palliative radical nephrectomy, surgery of metastasis, tumor embolisation and medical treatment options (e.g. immunotherapy, chemotherapy and targeted therapy), as well as supportive pain treatment.

Neurogenic bladder dysfunction in patients with neoplastic spinal cord compression: adaptation of the bladder management strategy to the underlying disease.

OBJECTIVES: To study the outcome of different bladder management strategies in patients with neoplastic spinal cord compression. METHODS: 22 patients with neoplastic spinal cord compression underwent urodynamic examination. According to the urodynamic data and the underlying disease different bladder management strategies were recommended. In patients with curatively treated disease a full bladder rehabilitation program was arranged. In patients with metastatic malignant disease, voluntary voiding was continued if possible or a suprapubic catheter was placed. RESULTS: Eight patients were treated with curative intention. Of those, 2 patients were able to void during urodynamics continued normal voluntary voiding. Six patients were taught intermittent catheterisation, with three additionally received oral anticholinergic treatment because of UMN lesion. At follow-up, all patients had successfully finished bladder rehabilitation program and at follow up, all patients were continuing their previously recommended bladder rehabilitation program. Fourteen patients had malignant disease and were treated palliatively. In 2 patients with UMN lesion, voluntary control of micturition was maintained and both continued voluntary voiding. In 12 patients a suprapubic catheter was inserted. At follow-up, 9 out of 14 had died (mean 8 month after primary visit), the remaining 5 continued treatment with suprapubic catheters. CONCLUSION: Underlying disease and life expectancy should be considered for the selection of bladder management in patients with neoplastic spinal cord compression. In patients with curatively treated disease, a full bladder rehabilitation program is recommended while in patients with malignant disease and palliative care, a suprapubic catheter might be the treatment of choice.

[Vesicovaginal fistulas]. / Vesikovaginale Fisteln. Diagnostik und Therapie.

Vesicovaginal fistulas are often the result of obstetric trauma in third world countries or gynaecologic surgery in developed countries. The incidence of obstetric trauma is approximately 3-4/1000 births in West Africa. The incidence of fistulas as a result of surgery has remained relatively unchanged for years; 75% occur during gynaecologic procedures. The main clinical symptom of a vesicovaginal fistula is urine loss. Different surgical techniques with similar repair results are available: transvaginal approach, transvesical approach and transperitoneal approach. Irrespective of the approach used, requirements for successful repair include adequate surgical exposure, wide mobilization of the bladder and vagina, excision of the fistula tract, tension-free closure of the bladder and vagina, and placement of an interposition flap, i.e. Martius flap, omentum, peritoneum, when indicated. Using these surgical techniques, around 85% of women can be cured from their vesicovaginal fistula with a single operation.

The genetically-engineered secretory B27/Q10 chimeric molecule inhibits HLA-B27 restricted alloreactive T-lymphocytes.

OBJECTIVES: Intracellularly persisting bacterial infections and high association with HLA-B27 are the hallmarks of reactive arthritis. Soluble HLA-B27 molecules are induced by bacterial infection; however their biological role in arthritis is unknown. It was the aim of this study to generate soluble HLA-B27 molecule and to analyze its effect on cytotoxic HLA-B27 alloreactive CD8+ T-lymphocytes in order to better understand potential functional links between persistent infection and HLA-B27 association. METHODS: Using PCR Exons 1 through 4 of HLA-B*2705 were fused to Exon 5 of the soluble murine MHC class I variant Q10 and stably transfected into Hela-cells. Transfectants were analyzed using specific PCR, RT-PCR and intracellular and extracellular staining with anti-HLA-B27 monoclonal antibody ME1. Secretion of B27Q10 in the supernatant was examined by isoelectric focusing (IEF). The effect of B27Q10 on T-cells was analyzed using either HLA-B27- or HLA-A2-restricted alloreactive T-cells in a standard 51Cr-release assay. RESULTS: PCR and RT-PCR demonstrated the DNA and mRNA of B27Q10 in the transfectants. By intracellular and extracellular staining with ME1 B27Q10-molecule was detected intracellularly but was not expressed in the cell membrane. Using IEF soluble B27Q10-molecules were found in supernatants of transfectants in a concentration of up to 1.342 microg/ml. Soluble B27QJO-molecule inhibited specifically the cytotoxicity of HLA-B27-restricted alloreactive T-cells by about 30%. CONCLUSION: The secretory non-membrane-expressed molecule B27Q10 inhibits HLA-B27 specific T-cells. The inhibition of cytotoxic T-cells by bacteria induced soluble HLA-B27 may thus enable bacterial persistence.