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.

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.

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.

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.

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.

Background: Pelvic lymph node dissection during standard radical cystectomy (stdRC) for muscle invasive bladder cancer is performed as separate templates. In the modernized en bloc radical cystectomy (mEbRC), the bladder is removed together with all its associated lymphatic tissue as one specimen. Our aim was to evaluate the oncological and surgical outcomes of mEbRC with a propensity-matched national cohort of stdRC cases. Methods: 935 patients (mEbRC: 214 and stdRC: 721) were eligible for analysis, and 1:2 propensity score matching was performed regressing mEbRC treatment on the variables age, gender, neoadjuvant chemotherapy, Charlson Comorbidity Index, lymph node metastases at final pathology, carcinoma in situ, and pT-stage. The primary outcome was recurrence-free survival (RFS). Secondary endpoints were overall survival (OS) and cancer-specific survival (CSS), survival for female patients. and perioperative measures. Results: There were no significant differences between the groups regarding complications, 30-day readmission rates, and 30- and 90-day mortality rates. In the propensity score matched groups, the 5-year RFS was 83% in the mEbRC group vs. 67% in the stdRC group (p < 0.001), the CSS was 89% and 78% (p ≤ 0.001), and OS 81% vs. 68% (p < 0.001) in the same groups, respectively. The results were confirmed by Cox regression analyses with hazard ratios ranging from 0.41 to 0.50 and p-values ≤ 0.001, favoring mEbRC. The 5-year OS for female patients was 86% for mEbRC and 60% for stdRC (p = 0.022). Conclusions: Performing mEbRC over stdRC might yield significantly better oncological outcomes, with equal survival rates for both genders.