Management of Bladder Pain Syndrome (BPS): A Practical Guide.

Bladder pain syndrome (BPS) is a prevalent and pervasive disease. The physical and psychological sequelae can be very burdensome for the patient, and the condition represents a real challenge for the clinician as well. With no simple pathognomonic test, finding harmony in navigating patient care can be demanding. Diagnosis and management rely upon a multidisciplinary and holistic approach. Treatment options include conservative measures and pharmacotherapies as well as bladder instillation therapies. Ultimately, surgery may be offered but only in cases of refractory disease. This article offers a pragmatic guide for clinicians managing this challenging disease.

Rules and regulations for a pregnant endourologist: the European perspective.

INTRODUCTION: Working in surgery while pregnant is challenging. Navigating this period safely is of paramount importance. Anecdotal observation suggests that there exists great variation among European nations in regard to maternity leave and radiation safety. The aim of this article was to gain insight into policy patterns and variations across Europe regarding these issues. METHODS: A series of core question items was distributed to representatives across 12 nations Austria, Belgium, Germany, Greece, Iceland, Italy, Netherlands, Norway, Poland, Republic of Ireland, Spain and the United Kingdom). RESULTS: The total number of weeks with full pay ranged from as little as 4 weeks in Belgium to 32 and Iceland. All countries included in this study give the option of additional weeks beyond the initial period, however at reduced pay. Some offer unpaid leave beyond this. Only 5/12 countries had a specific policy on when the pregnant surgeon should come off the on-call rota. Only Austria, Italy and Poland stipulate a requirement for the pregnant clinician to be replaced or be completely exempt in cases involving radiation. Only Germany, Iceland, Norway and Poland highlight the need to limit radiation dose in the first trimester. Beyond this, Germany alone provides written guidance for reduction in gown weight and along with Poland, display arguably the most forward-thinking approach to resting. CONCLUSION: There is a marked range in maternal leave policies across Europe. There also exists a lack of universal guidance on radiation safety for the pregnant urologist. There is urgent need for this void to be addressed.

Current Status of Intravesical Therapies for Bladder Pain Syndrome (BPS): A Narrative Review of Emerging Evidence.

Bladder pain syndrome (BPS) is a complex condition, which can have debilitating sequelae for patients. Many elements of BPS remain poorly understood including pathophysiology, diagnosis and treatment. Navigating patient care can therefore be challenging for the clinician. Management mandates a multidisciplinary and symptom-based approach. Intravesical treatments such as instillation therapies remain a cornerstone of most treatment algorithms and there are a range of agents that can be selected. This review offers an up-to-date evaluation of the evidence for these intravesical treatments.

The levels of IL-6 and soluble IL-33R are increased in the renal vein during surgery for clear cell renal cell carcinoma.

PURPOSE: The main aim was to map serum levels of IL-1/IL-6 family cytokines and relevant receptors from serum samples taken across treatment in patients with Renal Cell Carcinoma (RCC). Additionally, we explored the possible interactions between these measurements, immunohistochemistry and intratumoral blood flow. METHODS: We included 40 patients undergoing open surgery for renal tumors. Blood samples were collected before, during (taken simultaneously from a peripheral site and the renal vein (RV) before clamping) and after surgery. Samples were analyzed for IL-6, IL-27, IL-31, OSM, TNF-α, serum (s)-gp130, s-IL-6Rα, s-IL-33R, IL-1Rα and VEGF. All 35 RCC tumors were histologically subtyped as clear cell (CCRCC), papillary or chromophobe. Immunohistochemistry for the CCRCC group included expression of IL-6/IL-6R. Intratumoral blood flow was determined by calculating intratumoral contrast enhancement on preoperative computerized tomography (CT) imaging. RESULTS: In the CCRCC patients, the intraoperative RV concentration of IL-6 was significantly higher than in both the preoperative and postoperative samples (p = 0.005 and p = 0.032, respectively). Furthermore, the intraoperative ratio showed significantly higher levels of IL-6 in the RV than in the simultaneously drawn peripheral sample. Immunohistochemistry showed general expression of IL-6 (23/24) in both tumor cells and the vasculature (20/23). Moreover, s-IL-6R was expressed in tumor cells in 23/24 studied patients. Increased blood flow in the CCRCC tumors predicted increased IL-6 levels in the RV (p < 0.001). The other cytokines and receptors showed an overall stability across the measurements. However, the intraoperative ratios of IL-33R and gp130 showed significantly higher levels in the RV. CONCLUSION: Serum levels of IL-6 increased during surgery. Intraoperative IL-6 and s-IL-33R values were higher in the RV compared to the periphery, suggesting secretion from the tumor or tumor microenvironment itself. Supportive of this is an almost general expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature in the tumor microenvironment. Other studied cytokines/receptors were remarkably stable across all measurements.

Serum levels of the IL-6 family of cytokines predict prognosis in renal cell carcinoma (RCC).

PURPOSE: An improved understanding of RCC immunology should shed further light on RCC tumor biology. Our objective was to study to what extent serum levels of the IL-6 family of cytokines at diagnosis were relevant to survival. METHODS: A total of 118 consecutively patients with RCC, in which the tumor was surgically removed at Haukeland University Hospital during the period from 2007 to 2010, were included. The patients were followed-up for 10 years. The morning before surgery blood was sampled and serum frozen, with levels of IL-6, IL-27, IL-31, OSM, CNTF, IL-6Rα and gp130 determined. RESULTS: Among patients with the highest quartile of IL-6 (> 8 pg/ml) (n = 29), six of nine who had metastasis at diagnosis had such high IL-6 values. Among presumed radically treated patients, a high IL-6 and IL-27 strongly predicted recurrence. In particular, the predictions among patients with large (diameter > 7 cm) tumors were excellent regarding both IL-6 and IL-27 values. High gp130 serum levels predicted an overall survival (OS) among RCC patients with large tumors. Patients with a high IL-6 exhibited a strong expression of IL-6 in endothelial- and vascular smooth muscle cells. Moreover, the level of intra-tumoral CD3-positive cells predicted survival. CONCLUSIONS: IL-6 and IL-27 seem to play a role in RCC biology. IL-6 enables the pinpointing of metastatic condition at diagnosis, as well as together with IL-27, the predicting of survival and recurrence. Endothelial cells and vascular smooth muscle cells are both suggested as important sources of IL-6.

The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile.

High serum levels of the acute phase protein C-reactive protein (CRP) are associated with an adverse prognosis in renal cancer. The acute phase reaction is cytokine-driven and includes a wide range of inflammatory mediators. This overall profile of the response depends on the inducing event and can also differ between patients. We investigated an extended acute phase cytokine profile for 97 renal cancer patients. Initial studies showed that the serum CRP levels had an expected prognostic association together with tumor size, stage, nuclear grading, and Leibovich score. Interleukin (IL)6 family cytokines, IL1 subfamily mediators, and tumor necrosis factor (TNF)α can all be drivers of the acute phase response. Initial studies suggested that serum IL33Rα (the soluble IL33 receptor α chain) levels were also associated with prognosis, although the impact of IL33Rα is dependent on the overall cytokine profile, including seven IL6 family members (IL6, IL6Rα, gp130, IL27, IL31, CNTF, and OSM), two IL1 subfamily members (IL1RA and IL33Rα), and TNFα. We identified a patient subset characterized by particularly high levels of IL6, IL33Rα, and TNFα alongside an adverse prognosis. Thus, the acute phase cytokine reaction differs between renal cancer patients, and differences in the acute phase cytokine profile are associated with prognosis.

A prospective risk-stratified follow-up programme for radically treated renal cell carcinoma patients: evaluation after eight years of clinical use.

PURPOSE: In mid-2007, we introduced a new risk-stratified follow-up programme (FUP) for surgically treated localized renal cell carcinoma. After inclusion, the patients have been followed prospectively. In this study, we present the results in regard to stratification, completeness of the FUP and recurrences. METHODS: The FUP consists of three risk groups: low risk (LR), intermediate risk (IR) and high risk (HR), based on the risk stratification model introduced by Leibovich et al. (Cancer 97(7):1663-1671, 2003). In all risk groups, the patients are scheduled for ten follow-up visits (FUV) over 5 years, but seven, five and three FUVs, respectively, are outsourced to the patient's general practitioner (GP). Chest X-ray and abdomen CT are the imaging modalities used in the FUP. RESULTS: Of 312 included patients, 195 (62.5 %) had a complete FUP. However, in 86 patients the scheduled FUP had to be reduced, leaving 86.3 % of the remaining patients with a complete FUP. By including GPs, the number of FUVs at the hospital was reduced by ~60 %. The 5-year probability for freedom of recurrence is 0.98, 0.84 and 0.52 for the LR, IR and HR groups, respectively. Of 31 recurrences, 20 patients (65 %) were diagnosed within the FUP. Eleven patients (35 %) were diagnosed due to symptoms, and five of these had recurrences in locations not covered by standard imaging. Patients diagnosed within the FUP showed a better prognosis for survival and could in greater part receive tumour-directed treatment. CONCLUSIONS: After 8 years of clinical use, the outcome measures of the FUP seem to be within acceptable ranges.

Preoperative high levels of serum vascular endothelial growth factor are a prognostic marker for poor outcome after surgical treatment of renal cell carcinoma.

OBJECTIVE: The aim of this study was to determine whether concentrations of vascular endothelial growth factor (VEGF) in blood taken preoperatively can predict subtype, survival and recurrence in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: The patient group consisted of 124 patients with an RCC that was surgically removed with nephrectomy or nephron-sparing surgery at Haukeland University Hospital from 2007 to 2010. All subtypes and stages were included. Preoperative blood samples were taken on the day of surgery, and the samples were prepared and frozen at -80 °C. The level of VEGF in serum was analysed using Luminex® immunobead technology. The patients were followed until death or to 31 October 2014 (>4.5 years). RESULTS: Patients with higher levels of VEGF were more likely to have clear cell RCC [odds ratio (OR) 2.43, p = 0.046], as were older patients (OR 1.04, p = 0.024). In a multivariate analysis, high VEGF, stage and nuclear grade all had a significant predictive value for cancer-specific survival (OR 4.56, p = 0.017; OR 11.54, p < 0.001; and OR 7.85, p = 0.015, respectively). VEGF, stage and nuclear grade predicted recurrence in patients presumed to have been radically treated (OR 4.37, p = 0.03; OR 5.02, p = 0.011; and OR 6.57, p = 0.008, respectively). CONCLUSIONS: Tumour stage and a high level of serum VEGF were predictors for an increased risk of recurrence and cancer-specific death. Furthermore, the study showed that serum VEGF may be used to determine the subtype of RCC preoperatively.

Contemporary external validation of the Leibovich model for prediction of progression after radical surgery for clear cell renal cell carcinoma.

OBJECTIVE: The aim of this study was to externally validate in an up-to-date setting the predictive ability of the model for recurrence after radical treatment of clear cell renal cell carcinoma (CCRCC) published by Leibovich in 2003. MATERIALS AND METHODS: The study included a total of 386 consecutive patients with CCRCC between January 1997 and May 2013, treated with partial or radical nephrectomy. All patients were scored with points between 0 and 11, and further subdivided into low-, intermediate- and high-risk groups according to the original paper. Well-recognized statistical methods for the evaluation of Cox's proportional hazard-based prognostic models were applied. To validate the discriminative ability, Harrell's concordance (c) index and hazard ratios (HRs) between risk groups were used, and calibration was graphically explored. RESULTS: The 10 year recurrence-free survival rates for the low-, intermediate- and high-risk groups were 87.3%, 63.8% and 19.8%, respectively Harrell's c index was 0.864. The HRs across risk groups for the intermediate- and high-risk groups were 5.29 and 21.56, respectively, with the low-risk group as a reference category. A gross comparison of the survival estimates between the patients showed an overall similarity. However, differences within the intermediate- and high-risk groups were seen in the first year of follow-up. CONCLUSIONS: The Leibovich model seems to discriminate well between risk groups, but for the intermediate- and high-risk groups the calibration is not optimal. This study validates the model in a present-day Nordic patient population. The model can be used as a risk stratification tool for follow-up after radical treatment of CCRCC.

Incidentally detected renal cell carcinomas are highly associated with comorbidity and mortality unrelated to renal cell carcinoma.

OBJECTIVE: The aim of this study was to investigate the underlying reasons for symptomatic (SRCC) and incidental diagnosis of renal cell carcinoma (IRCC), and possible differences in cancer-specific (CSS) and overall survival (OS) with regard to reasons for detection. MATERIAL AND METHODS: Between 1997 and 2010, 413 patients underwent surgery for renal cell carcinoma (RCC). SRCCs were divided into groups with general and classical symptoms. IRCCs were divided into "true" IRCCs, found owing to investigation of another definitive medical condition, and "unrelated" IRCCs, found owing to investigation for signs and symptoms presumed to be unrelated to RCC. Gender- and age-adjusted estimated overall survival (EOS) rates based on national mortality data were calculated for both the total material and the subgroups. RESULTS: IRCC tumours were smaller, and of lower stage and grade than SRCCs, which was also reflected in the lower CSS in this group. Most IRCCs were found during investigations related to another definitive condition. There was a significantly higher level of comorbidity in the IRCC group, and the "true" IRCC group had the highest rates. The two IRCC subgroups had similar CSS and tumour characteristics. In the SRCC group, however, those with general symptoms had worse tumour characteristics and lower rates of CSS compared to those with classical symptoms. The true IRCC group had significantly inferior OS compared to the unrelated IRCCs (p = 0,040). Only the unrelated IRCC patients had an OS similar to the EOS; for all other subgroups the OS was inferior to the EOS. CONCLUSIONS: Most IRCCs were found during investigations for other medical conditions, and the OS rate in this group of patients was lower than expected.

Obesity is associated with an improved cancer-specific survival, but an increased rate of postoperative complications after surgery for renal cell carcinoma.

OBJECTIVE: This study aimed to assess the impact of preoperative body mass index (BMI) on postoperative complications, cancer-specific survival (CSS) and overall survival (OS) in patients operated for renal cell carcinoma (RCC). MATERIAL AND METHODS: The study included 397 patients with BMI values, who underwent surgery for RCC between 1 January 1997 and 31 December 2010. Obese patients (BMI > 30 kg/m(2)) were compared to non-obese patients (BMI < 30 kg/m(2)) in regard to CSS and OS. A Cox proportional hazard model was used for the multivariate survival analyses. The mean age of the patients was 62.1 years. There were 259 males (65%) and 325 patients (82%) were non-obese. Mean BMI was 26 kg/m(2). RESULTS: In the total material, CSS was 94.7% for obese patients and 74.8% for non-obese patients (p = 0.06). The obese group had significantly better CSS in univariate analysis for presumed radically treated disease (pT1-3N0M0). Obesity was a significant protective prognostic factor in multivariate analysis. An accelerating protective effect for CSS was found with increasing levels of BMI. In regard to OS, no difference was found between the two groups. Obese patients had a significantly lower age, and a higher rate of diabetes mellitus, hypertension and incidental detection. Obese patients had a significantly higher total incidence of postoperative complications, but not surgery-related complications. CONCLUSIONS: In this material, increasing BMI was associated with improved CSS for presumed radically treated patients. However, obese patients had a higher total rate of postoperative complications.

Simultaneous bilateral spontaneous pneumothorax in metastatic testicular cancer.

Simultaneous bilateral spontaneous pneumothorax (SBSP) is a very rare condition, mainly detected in patients with underlying pulmonary disease. This study reports a case of SBSP following chemotherapy for metastatic testicular cancer.