Sebastian L. Hofbauer

The preoperative prognostic nutritional index is an independent predictor of survival in patients with renal cell carcinoma

OBJECTIVE Accurate postoperative stratification of patients with renal cell carcinoma (RCC) in distinct prognostic groups is essential for tailoring follow-up, medical therapy, and inclusion in clinical trials. Increasing evidence suggests that Onodera׳s prognostic nutritional index (PNI) is a stage- and grade-independent predictor of poor outcomes in patients with cancer, but there are no data in RCC. MATERIALS AND METHODS We reviewed medical records of 1,344 patients with RCC who underwent radical or partial nephrectomy at the Medical University of Vienna and the University of California-Los Angeles between 1991 and 2012. Associations with cancer-specific survival were assessed with univariable and multivariable Cox proportional hazards models. Discrimination was measured with the C-index. RESULTS The median postoperative follow-up was 40 months. An increase of PNI by 1 unit was associated with a decrease in the risk of death from RCC by 7% (hazard ratio = 0.93, P<0.001). In multivariable analyses, the PNI was an independent prognostic factor (P<0.001). Adding the PNI improved the discrimination of a base model by 0.4%. CONCLUSIONS The PNI is an independent prognostic factor in patients with RCC. Its use increases the accuracy of established prognostic factors. PNI may be a meaningful adjunct for tailoring surveillance, medical therapy, and clinical trial design.

Preoperative serum cholesterol is an independent prognostic factor for patients with renal cell carcinoma (RCC)

To assess the prognostic role of preoperative serum cholesterol in patients with renal cell carcinoma (RCC), as increasing evidence suggests that alterations in the lipid profile are associated with the development, progression and prognosis of various cancers.

Small high-density lipoprotein is associated with monocyte subsets in stable coronary artery disease

Objective: High-density lipoprotein (HDL) particles are heterogeneous in structure and function and the role of HDL subfractions in atherogenesis is not well understood. It has been suggested that small HDL may be dysfunctional in patients with coronary artery disease (CAD). Monocytes are considered to play a key role in atherosclerotic diseases. Circulating monocytes can be divided into three subtypes according to their surface expression of CD14 and CD16. Our aim was to examine whether monocyte subsets are associated with HDL subfractions in patients with atherosclerosis. Methods: We included 90 patients with angiographically stable CAD. Monocyte subsets were defined as classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). HDL subfractions were measured by electrophoresis on polyacrylamide gel. Results: Serum levels of small HDL correlated with circulating pro-inflammatory NCM and showed an inverse relationship to circulating CM independently from other lipid parameters, risk factors, inflammatory parameters or statin treatment regime, respectively. IM were not associated with small HDL. In particular, patients with small HDL levels in the highest tertile showed dramatically increased levels of NCM (14.7 ± 7% vs. 10.7 ± 5% and 10.8 ± 5%; p = 0.006) and a decreased proportion of CM (79.3 ± 7% vs. 83.7 ± 6% and 83.9 ± 6%; p = 0.004) compared to patients in the two lower tertiles. In contrast, intermediate HDL, large HDL and total HDL were not associated with monocyte subset distribution. Conclusion: Small HDL levels are associated with pro-inflammatory NCM and inversely correlated with CM. This may suggest that small HDL could have dysfunctional anti-inflammatory properties in patients with established CAD.

Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma.

Background:Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC).Methods:Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months.Results:Median pretherapeutic serum GGT level was 25 U l−1. Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l−1 was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l−1), normal high (17.5 to <34.5 U l−1), elevated (34.5 to <181.5 U l−1), and highly elevated (⩾181.5 U l−1). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit.Conclusions:Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.

The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: A retrospective study

To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC.

Monocyte subset distribution in patients with stable atherosclerosis and elevated levels of lipoprotein(a)

Background Lipoprotein(a) (Lp(a)) is a proatherogenic plasma lipoprotein currently established as an independent risk factor for the development of atherosclerotic disease and as a predictor for acute thrombotic complications. In addition, Lp(a) is the major carrier of proinflammatory oxidized phospholipids (OxPL). Today, atherosclerosis is considered to be an inflammatory disease of the vessel wall in which monocytes and monocyte-derived macrophages are crucially involved. Circulating monocytes can be divided according to their surface expression pattern of CD14 and CD16 into at least 3 subsets with distinct inflammatory and atherogenic potential. Objective The aim of this study was to examine whether elevated levels of Lp(a) and OxPL on apolipoprotein B-100–containing lipoproteins (OxPL/apoB) are associated with changes in monocyte subset distribution. Methods We included 90 patients with stable coronary artery disease. Lp(a) and OxPL/apoB were measured, and monocyte subsets were identified as classical monocytes (CMs; CD14++CD16−), intermediate monocytes (IMs; CD14++CD16+), and nonclassical monocytes (NCMs; CD14+CD16++) by flow cytometry. Results In patients with elevated levels of Lp(a) (>50 mg/dL), monocyte subset distribution was skewed toward an increase in the proportion of IM (7.0 ± 3.8% vs 5.2 ± 3.0%; P = .026), whereas CM (82.6 ± 6.5% vs 82.0 ± 6.8%; P = .73) and NCM (10.5 ± 5.3 vs 12.8 ± 6.0; P = .10) were not significantly different. This association was independent of clinical risk factors, choice of statin treatment regime, and inflammatory markers. In addition, OxPL/apoB was higher in patients with elevated Lp(a) and correlated with IM but not CM and NCM. Conclusions In conclusion, we provide a potential link between elevated levels of Lp(a) and a proatherogenic distribution of monocyte subtypes in patients with stable atherosclerotic disease.

Association of small dense LDL serum levels and circulating monocyte subsets in stable coronary artery disease.

Objective Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels. Methods We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel. Results Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels. Conclusion The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.

Association of human telomerase reverse transcriptase gene polymorphisms, serum levels, and telomere length with renal cell carcinoma risk and pathology.

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase and plays a key role in telomere restitution and gene regulation. Evidence suggests that hTERT is linked with the risk and progression of several malignancies, but there are no comprehensive data in renal cell carcinoma (RCC). In this case–control study, we assessed seven polymorphic hTERT gene variants (MNS16A, rs2736100, rs2736098, rs7726159, rs2853677, rs13172201, and rs10069690), hTERT serum levels, and the telomere length of 663 individuals, including 243 with clear cell RCC and 420 age‐ and gender‐matched healthy controls. The SL and SS genotypes of MNS16A were associated with a decreased risk for RCC on the multivariable logistic regression analysis (SL‐OR 0.72, SS‐OR 0.37, P < 0.001). The GG genotype of rs2736098 was associated with a decreased risk for RCC compared with AA (OR 0.18, P < 0.001). Both telomere length and hTERT serum levels increased with every G allele in rs2736098 (P = 0.008). Pretherapeutic hTERT serum levels were higher in patients with advanced tumor stages (P = 0.037) and distant metastases (P = 0.006). Rs2736100, rs7726159, rs2853677, rs13172201, and rs10069690 were not linked with RCC risk, and none of the polymorphisms was associated with RCC pathology. In conclusion, the polymorphic number of tandem repeats in hTERT (MNS16A) and rs2736098 may be linked with the risk for RCC. Rs2736098 may have an important role in telomere length restitution and serum hTERT levels may represent a novel biomarker for RCC.

Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients

To compare outcomes of patients with lymph node (LN)‐positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin‐based combined adjuvant chemotherapy (AC) after radical cystectomy (RC).

Associations between presenting symptoms, clinicopathological parameters, and prognosis in a contemporary series of patients with renal cell carcinoma.

Purpose To evaluate the impact of presenting symptoms on survival in a contemporary series of patients with renal cell carcinoma (RCC). Materials and Methods We prospectively recorded data on the presenting symptoms, pathology, and RCC-specific survival of 633 consecutive RCC patients who underwent surgery between 2003 and 2012. Results Four hundred thirty-three RCCs (68%) were incidental, 111 (18%) were associated with local symptoms, and 89 (14%) were associated with systemic symptoms. Among those with incidental RCC, 317 patients (73%) were completely asymptomatic and 116 patients (27%) presented with symptoms not related to the tumor. During a median follow-up interval of 40 months (interquartile range: 39 to 69 months), 77 patients died from RCC. In univariate analyses, symptom classification was significantly associated with RCC-specific survival (p<0.001). Patients with incidental RCC and unrelated symptoms tended to have worse prognosis than did patients who were completely asymptomatic, although this difference was not statistically significant (p=0.057). The symptom classification was associated with advanced TNM stages (p<0.001) and grade (p<0.001). Conclusions This study confirms that presenting symptoms are associated with tumor characteristics and survival. The majority of RCCs are diagnosed incidentally in patients without any symptoms or with symptoms not related to RCC. Patients in the latter group tend to have a worse prognosis than do patients who are completely asymptomatic. With the increasing number of incidentally diagnosed RCCs, substratification of patients with incidental tumors may be prognostically relevant.