Börje Ljungberg

University of Groningen, Groningen, Province of Groningen, Netherlands

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Publications (105)427.94 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Objective. Treatment of renal cell carcinoma (RCC) with radical nephrectomy (RN) induces chronic kidney disease more frequently compared with nephron-sparing surgery (NSS), which may have an impact on overall survival. Thus, NSS is recommended for RCCs up to 7 cm (T1). The aim of this study was to determine the extent to which these recommendations are implemented in clinical practice. Material and methods. Data were extracted from the Swedish National Kidney Cancer Register, a population-based register covering 98% of all RCCs in Sweden. In total, 3158 patients (1892 men, 1266 women) were primarily diagnosed with cT1N0M0 and treated surgically during 2005-2011. The administered treatments were evaluated between different hospitals as well as between the 21 independent healthcare counties. Results. In all, 742 patients were treated with NSS, 2339 with RN and 77 with minimally invasive ablative treatments. For cT1a RCC, patients treated with NSS increased from 22% in 2005 to 53% in 2011, and for cT1b from 2% to 10%. Nephron-sparing treatments for cT1a RCC were performed in 62% in university hospitals, 34% in intermediate- and 11% in low-volume hospitals. There was significant (p < 0.001) variation (31-67%) between the university hospitals and also for patient care in the 21 different counties (16-78%). There was an increased relative survival after NSS for T1a patients compared with RN. The register design by itself indicates limitations using data gathered from all Swedish hospitals. Conclusions. NSS was underutilized in many hospitals and a patient's chance of being offered NSS varied according to their place of residence. Patients with cT1a RCC treated with NSS had a significantly better relative survival than those treated with RN.
    Scandinavian journal of urology. 03/2014;
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    ABSTRACT: Abstract Objective. Tumour characteristics, preoperative work-up and surgical treatment in patients diagnosed with renal cell carcinoma (RCC) between 2005 and 2010, and changes over time were studied in a national population-based cohort. Material and methods. The National Swedish Kidney Cancer Register (NSKCR) contains information on histopathology, Fuhrman grade and clinical stage at presentation, and on the preoperative work-up and surgical treatment of patients with RCC. Between 2005 and 2010, 5553 RCC patients were registered in the NSKCR, 99% of those registered in the National Cancer Registry. Results. During the study period the mean tumour size decreased from 70 to 64 mm (p = 0.024) and the frequency of metastatic RCC decreased from 22% to 15% (p < 0.001). The use of preoperative chest computed tomography increased from 59% to 84%. In total, 4229 (76%) patients were treated with curative intent, 3453 (82%) underwent radical nephrectomy, 606 (14%) partial nephrectomy (PN) and 170 (4%) cryotherapy or radiofrequency ablation. In tumours up to 4 cm, PN was performed in 33% of the surgically treated patients. PN irrespective of size increased from 8% to 20% and laparoscopic nephrectomy increased from 6% to 17% during the period. In patients with metastatic RCC, 55% underwent cytoreductive nephrectomy. Conclusions. The NSKCR explores population-based data on the clinical handling of patients with RCC. This study, between 2005 and 2010, shows significant decrease in tumour size and metastatic RCC at presentation, a more complete preoperative work-up, and significantly increased use of PN and laparoscopic nephrectomy in Sweden.
    Scandinavian journal of urology. 03/2014;
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    ABSTRACT: Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study of smoking and bladder cancer risk based on primary scan data from 3,002 cases and 4,411 controls from the NCI Bladder Cancer Genome- Wide Association Study (GWAS). Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P-values <5x10(-5) were evaluated further in an independent dataset of 2,422 bladder cancer cases and 5,751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial data set and in the combined data set, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers (combined OR=1.34, 95% CI=1.20-1.50, P-value=5.18x10(-7)); and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR=0.75, 95% CI=0.67-0.84, P-value=6.35x10(-7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, while the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.
    Carcinogenesis 03/2014; · 5.64 Impact Factor
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    ABSTRACT: Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2,422 bladder cancer cases and 5,751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6,911 cases and 11,814 controls of European descent. TaqMan genotyping of 13 promising SNPs with P< 1x10(-5) was pursued in a follow-up set of 801 cases and 1,307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P=4.53×10(-9)) and rs907611 on 11p15.5 (P=4.11×10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P=7.13×10(-7)) and rs4510656 on 6p22.3 (P=6.98×10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
    Human Molecular Genetics 10/2013; · 7.69 Impact Factor
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    ABSTRACT: Abstract Prostate cancer is the most common type of cancer among men worldwide. Mechanical properties of prostate tissue are promising for distinguishing prostate cancer from healthy prostate tissue. The aim was to investigate the indentation loading response of a resonance sensor for discriminating prostate cancer tissue from normal tissue. Indentation measurements were done on prostate tissue specimens ex vivo from 10 patients from radical prostatectomy. The measurement areas were analysed using standard histological methods. The stiffness parameter was linearly dependent on the loading force (average R(2 )= 0.90) and an increased loading force caused a greater stiffness contrast of prostate cancer vs normal tissue. The accuracy of the stiffness contrast was assessed by the ROC curve with the area under the curve being 0.941 for a loading force of 12.8 mN. The results are promising for the development of a resonance sensor instrument for detecting prostate cancer.
    Journal of Medical Engineering & Technology 08/2013;
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    ABSTRACT: Abstract Objective. The aim of this study was to evaluate enterocystometry, voiding pattern and urine leakage of four types of orthotopic bladder substitute. Material and methods. At eight urological departments, 78 consecutive men were studied: 66 with an ileal neobladder [30 Studer pouches (S), 24 Hautmann pouches (H) and 12 T-pouches (T)] and 12 with a right colonic [Goldwasser type (G)] neobladder. Enterocystometry, determination of residual urine, micturition protocol and 24 h pad weight test were performed 6 and 12 months postoperatively. Results. Colonic neobladders had higher pouch pressure at first desire, normal desire and strong desire than ileal neobladders (except at first and normal desire at 12 months) (p < 0.02) and contraction was present more often at both 6 and 12 months (p < 0.01 and p < 0.01). Compliance was good in all types of pouch. Intermittent self-catheterization was more common in H patients at 6 months (p = 0.033). All patients with colonic neobladders used pads during the day and night. In patients with ileal pouches 32% used pads during the day and 70% during the night at 12 months. Urine leakage was higher in patients with colonic bladders at 6 and 12 months during the day (mean/median of 98/31 ml and 82/16 ml versus 10/0 ml and 4/0 ml, p < 0.001). T-pouches had excellent day-time continence, but nocturnal leakage was high. Conclusions. The Hautmann pouch and the Studer pouch behaved similarly at enterocystometry and clinically, and continence was good in the majority of patients. The low number of patients with the other two types of pouch precludes definitive statements.
    Scandinavian journal of urology. 07/2013;
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    ABSTRACT: Tensin3 is a cytoskeletal regulatory protein that inhibits cell motility. Downregulation of the gene encoding Tensin3 (TNS3) in human renal cell carcinoma (RCC) may contribute to cancer cell metastatic behavior. We speculated that epigenetic mechanisms, e.g., gene promoter hypermethylation, might account for TNS3 downregulation. In this study, we identified and validated a TNS3 gene promoter containing a CpG island, and quantified the methylation level within this region in RCC. Using a luciferase reporter assay we demonstrated a functional minimal promoter activity for a 500-bp sequence within the TNS3 CpG island. Pyrosequencing enabled quantitative determination of DNA methylation of each CpG dinucleotide (a total of 43) in the TNS3 gene promoter. Across the entire analyzed CpG stretch, RCC DNA showed a higher methylation level than both non-tumor kidney DNA and normal control DNA. Out of all the CpGs analyzed, two CpG dinucleotides, specifically position 2 and 8, showed the most pronounced increases in methylation levels in tumor samples. Furthermore, CpG-specific higher methylation levels were correlated with lower TNS3 gene expression levels in RCC samples. In addition, pharmacological demethylation treatment of cultured kidney cells caused a 3-fold upregulation of Tensin3 expression. In conclusion, these results reveal a differential methylation pattern in the TNS3 promoter occurring in human RCC, suggesting an epigenetic mechanism for aberrant Tensin downregulation in human kidney cancer.
    Epigenetics: official journal of the DNA Methylation Society 05/2013; 8(7). · 4.58 Impact Factor
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    ABSTRACT: CONTEXT: Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3-T4N0M0. OBJECTIVE: To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND. EVIDENCE ACQUISITION: Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. EVIDENCE SYNTHESIS: A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes. CONCLUSIONS: There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3-T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.
    European Urology 04/2013; · 10.48 Impact Factor
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    ABSTRACT: Abstract Objective. This study evaluated the impact of hospital volume on local recurrence and distant metastasis in a population-based series of radical cystectomy patients in Sweden. Material and methods. All patients who underwent cystectomy for bladder cancer in 1997-2002 in Sweden and were reported to the National Bladder Cancer Registry were included. A high-volume hospital (HVH) was defined as one with ≥10 cystectomies/year and a low-volume hospital (LVH) as one with <10 cystectomies/year. Information on preoperative tumour, node, metastasis (TNM) classification, operative procedure, postoperative course and follow-up was obtained from medical records. Results. Of the 1126 patients, 827 (74%) were males. The mean age was 66 years and median follow-up 47 months. Of the 610 (54%) HVH patients, 68 (11%) were pT0, 123 (20%) < pT2, 177 (29%) pT2, 242 (40%) > pT2 and 69 (11%) were microscopic non-radical. Corresponding figures for the 516 (46%) LVH patients were 35 (7%), 68 (13%), 191 (37%), 222 (43%) and 96 (19%). Local recurrence was observed in 245 patients (22%): 113 (19%) at HVHs and 132 (26%) at LVHs. Distant metastasis was found in 363 (32%): 203 (33%) at HVHs and 160 (31%) at LVHs. Perioperative chemotherapy was given to 193 (17%). Multivariate Cox proportional hazards analysis showed that local recurrence was associated with LVHs and non-organ-confined disease, whereas distant metastasis was correlated with non-organ-confined disease and lymph-node metastases. Conclusions. In this retrospective analysis, local tumour recurrence after cystectomy was common, particularly in patients with non-organ-confined disease. Furthermore, local recurrence was more frequent at LVHs than HVHs, and overall survival was better at HVHs. These findings suggest that concentrating cystectomies in HVHs may improve outcomes such as local recurrence and overall survival.
    Scandinavian journal of urology. 04/2013;
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    ABSTRACT: Previous studies have shown that obesity and hypertension are associated with increased risk of renal cell carcinoma (RCC), but less is known about the association to other metabolic factors. In the Metabolic Syndrome and Cancer project (Me-Can) data on body mass index (BMI, kg/m2), blood pressure, and circulating levels of glucose, cholesterol, and triglycerides were collected from 560,388 men and women in cohorts from Norway, Austria, and Sweden. By use of Cox proportional hazard models, hazard ratios (HR) were calculated for separate and composite metabolic exposures. During a median follow-up of 10 years, 592 men and 263 women were diagnosed with RCC. Among men, we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 1.51, 95% CI 1.13-2.03), systolic blood pressure, (HR = 3.40, 95% CI 1.91-6.06), diastolic blood pressure, (HR = 3.33, 95% CI 1.85-5.99), glucose, (HR = 3.75, 95% CI 1.46-9.68), triglycerides, (HR = 1.79, 95% CI 1.00-3.21) and a composite score of these metabolic factors, (HR = 2.68, 95% CI 1.75-4.11). Among women we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 2.21, 95% CI 1.32-3.70) and the composite score, (HR = 2.29, 95% CI 1.12-4.68). High levels of the composite score were also associated with risk of death from RCC among both men and women. No multiplicative statistical or biological interactions between metabolic factors on risk of RCC were found. High levels of BMI, blood pressure, glucose and triglycerides among men and high BMI among women were associated with increased risk of RCC.
    PLoS ONE 01/2013; 8(2):e57475. · 3.73 Impact Factor
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    ABSTRACT: Over the last decade, telomere length (TL) has gained attention as a potential biomarker in cancer disease. We previously reported that long blood TL was associated with a poorer outcome in patients with breast cancer and renal cell carcinoma. Based on these findings, we hypothesized that certain immunological components may have an impact on TL dynamics in cancer patients. One aim of the present study was to investigate a possible association between serum cytokines and TL of peripheral blood cells, tumors and corresponding kidney cortex, in patients with clear cell renal cell carcinoma. For this purpose, a multiplex cytokine assay was used. Correlation analysis revealed significant positive correlations between tumor TL and peripheral levels of three cytokines (IL-7, IL-8 and IL-10). In a parallel patient group with various kidney tumors, TL was investigated in whole blood and in immune cell subsets in relation to peripheral levels of regulatory T cells (Tregs). A significant positive association was found between whole blood TL and Treg levels. However, the strongest correlation was found between Tregs and TL of the T lymphocyte fraction. Thus, patients with higher Treg levels displayed longer T cell telomeres, which might reflect a suppressed immune system with fewer cell divisions and hence less telomere shortening. These results are in line with our earlier observation that long blood TL is an unfavorable prognostic factor for cancer-specific survival. In summary, we here show that immunological components are associated with TL in patients with renal cell carcinoma, providing further insight into the field of telomere biology in cancer.
    PLoS ONE 01/2013; 8(2):e55543. · 3.73 Impact Factor
  • Börje Ljungberg
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    ABSTRACT: Despite contemporary innovations in systemic therapy and surgical treatment, renal cell carcinoma (RCC) remains the most lethal urologic malignancy. Still, around 20 % of patients with RCC present with metastases at diagnosis, and 40-50 % of those with localized advanced disease will ultimately progress to metastatic disease. Although the new, targeted therapy paradigms have changed the treatment of patients with advanced RCC and offer prolonged survival, cure is extremely uncommon in the absence of surgical resections. In this paper, the current role of metastasectomy is reviewed. Searches were carried out in the PubMed database and the Cochrane Library of Controlled Clinical Trials. While there is no randomized study available, recent large observational studies have better defined the prognosis of patients with metastatic RCC with or without metastasectomy. In multivariate analysis, independent predictive factors included male gender, disease-free interval > 1 year, single metastatic site and complete metastasectomy. Other reports from selected patient materials show 29-31 % 5-year overall survival rates. In patients with recurrent disease after resection of a lung metastasis, 60 % were able to undergo a subsequent resection, compared with 25 % with recurrent bone metastasis. Also, metastasectomy after initial systemic therapy gave partial or complete response in a majority of patients. In these patients, the median survival was 4.7 years and 21 % remained free of disease at last follow-up. Patients with metastatic renal cell carcinoma should be considered for multimodal therapy, including surgery of metastatic lesions. A proportion of patients will achieve long-term survival with aggressive surgical resection.
    Current Urology Reports 12/2012;
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    ABSTRACT: Published associations between dietary carotenoids and vitamin C and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. We investigated the association between plasma carotenoids and vitamin C and risk of urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 856 patients with newly diagnosed UCC were matched with 856 cohort members by sex, age at baseline, study center, date and time of blood collection, and fasting status. Plasma carotenoids (α- and β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin) were measured by using reverse-phase HPLC, and plasma vitamin C was measured by using a colorimetric assay. Incidence rate ratios (IRRs) were estimated by using conditional logistic regression with adjustment for smoking status, duration, and intensity. UCC risk decreased with higher concentrations of the sum of plasma carotenoids (IRR for the highest compared with the lowest quartile: 0.64; 95% CI: 0.44, 0.93; P-trend = 0.04). Plasma β-carotene was inversely associated with aggressive UCC (IRR: 0.51; 95% CI: 0.30, 0.88; P-trend = 0.02). Plasma lutein was inversely associated with risk of nonaggressive UCC (IRR: 0.56; 95% CI: 0.32, 0.98; P-trend = 0.05). No association was observed between plasma vitamin C and risk of UCC. Although residual confounding by smoking or other factors cannot be excluded, higher concentrations of plasma carotenoids may reduce risk of UCC, in particular aggressive UCC. Plasma lutein may reduce risk of nonaggressive UCC.
    American Journal of Clinical Nutrition 09/2012; 96(4):902-10. · 6.50 Impact Factor
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    ABSTRACT: BACKGROUND: Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: After 8.9years of follow-up, 947UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. RESULTS: Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95%confidence interval (CI) 0.78-1.00 and HR 0.87; 95%CI 0.77-0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95%CI 0.77-0.98). CONCLUSION: Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded.
    European journal of cancer (Oxford, England: 1990) 08/2012; · 4.12 Impact Factor
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    ABSTRACT: CONTEXT: For the treatment of localised renal cell carcinoma (RCC), uncertainties remain over the perioperative and quality-of-life (QoL) outcomes for the many different surgical techniques and approaches of nephrectomy. Controversy also remains on whether newer minimally invasive nephron-sparing interventions offer better QoL and perioperative outcomes, and whether adrenalectomy and lymphadenectomy should be performed simultaneously with nephrectomy. These non-oncological outcomes are important because they may have a considerable impact on localised RCC treatment decision making. OBJECTIVE: To review systematically all the relevant published literature comparing perioperative and QoL outcomes of surgical management of localised RCC (T1-2N0M0). EVIDENCE ACQUISITION: Relevant databases including Medline, Embase, and the Cochrane Library were searched up to January 2012. Randomised controlled trials (RCTs) or quasi-randomised controlled trials, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The outcome measures were QoL, analgesic requirement, length of hospital stay, time to normal activity level, surgical morbidity and complications, ischaemia time, renal function, blood loss, length of operation, need for blood transfusion, and perioperative mortality. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. EVIDENCE SYNTHESIS: A total of 4580 abstracts and 380 full-text articles were assessed, and 29 studies met the inclusion criteria (7 RCTs and 22 NRSs). There were high risks of bias and low-quality evidence for studies meeting the inclusion criteria. There is good evidence indicating that partial nephrectomy results in better preservation of renal function and better QoL outcomes than radical nephrectomy regardless of technique or approach. Regarding radical nephrectomy, the laparoscopic approach has better perioperative outcomes than the open approach, and there is no evidence of a difference between the transperitoneal and retroperitoneal approaches. Alternatives to standard laparoscopic radical nephrectomy (LRN) such as hand-assisted, robot-assisted, or single-port techniques appear to have similar perioperative outcomes. There is no good evidence to suggest that minimally invasive procedures such as cryotherapy or radiofrequency ablation have superior perioperative or QoL outcomes to nephrectomy. Regarding concomitant lymphadenectomy during nephrectomy, there were low event rates for complications, and no definitive difference was observed. There was no evidence to base statements about concomitant ipsilateral adrenalectomy during nephrectomy. CONCLUSIONS: Partial nephrectomy results in significantly better preservation of renal function over radical nephrectomy. For tumours where partial nephrectomy is not technically feasible, there is no evidence that alternative procedures or techniques are better than LRN in terms of perioperative or QoL outcomes. In making treatment decisions, perioperative and QoL outcomes should be considered in conjunction with oncological outcomes. Overall, there was a paucity of data regarding QoL outcomes, and when reported, both QoL and perioperative outcomes were inconsistently defined, measured, or reported. The current evidence base has major limitations due to studies of low methodological quality marked by high risks of bias.
    European Urology 07/2012; · 10.48 Impact Factor
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    European Urology. 07/2012; 62(1):193.
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    ABSTRACT: Objective. To evaluate the relationship between osteopontin (OPN) in serum and plasma and parathyroid hormone-related protein (PTHrP) in serum, plasma and tumour tissue, and to assess the prognostic impact of OPN and PTHrP in human renal cell carcinoma (RCC). Material and methods. The study included 269 patients with RCC. In 189 patients, immunohistochemical (IHC) PTHrP tumour tissue expression was evaluated, and OPN and PTHrP in serum were assessed. In 80 patients, plasma OPN and PTHrP were analysed. Tumour type, TNM stage, nuclear grade and RCC-specific survival were also registered. In a sub-group, IHC expression of CD 31 was assessed. The prognostic information of the factors was analysed using uni- and multivariate analyses. Results. The median OPN level was 2.3 times higher in plasma than in serum. Serum OPN was significantly higher in patients with papillary RCC compared to clear cell RCC and chromophobe RCC. Both serum and plasma OPN levels were positively correlated to TNM stage and nuclear grade. Multivariate analysis showed that serum and plasma OPN levels were independent prognostic factors for RCC-specific survival, along with TNM stage. Immunohistochemical expression of PTHrP associated to TNM stage but not to nuclear grade or serum OPN. Furthermore, IHC expression of PTHrP was positively correlated to serum PTHrP but inversely to tumour CD31 expression. Plasma PTHrP was increased in 20% of the patients and related to TNM stage but not to nuclear grade. Plasma OPN was significantly higher in patients with increased PTHrP levels, compared to those with normal levels. Conclusion. Plasma OPN levels differed between RCC types, and in clear cell RCC, both serum and plasma OPN levels were independent predictors of survival. We found no evidence for prognostic value related to circulating levels or the IHC expression of PTHrP.
    Acta oncologica (Stockholm, Sweden) 06/2012; · 2.27 Impact Factor
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    ABSTRACT: Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.
    International Journal of Cancer 05/2012; · 6.20 Impact Factor
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    ABSTRACT: Previous studies have revealed altered expression of epidermal growth factor receptor (EGFR)-family members and their endogenous inhibitor leucine-rich and immunoglobulin-like domains 1 (LRIG1) in renal cell carcinoma (RCC). In this study, we analyzed the gene expression levels of EGFR-family members and LRIG1, and their possible associations with clinical parameters in various types of RCC. Gene expression levels of EGFR-family members and LRIG1 were analyzed in 104 RCC samples, including 81 clear cell RCC (ccRCC), 15 papillary RCC (pRCC), and 7 chromophobe RCC (chRCC) by quantitative real-time RT-PCR. Associations between gene expression levels and clinical data, including tumor grade, stage, and patient survival were statistically assessed. Compared to kidney cortex, EGFR was up-regulated in ccRCC and pRCC, LRIG1 and ERBB2 were down-regulated in ccRCC, and ERBB4 was strongly down-regulated in all RCC types. ERBB3 expression did not differ between RCC types or between RCC and the kidney cortex. The expression of the analyzed genes did not correlate with patient outcome. This study revealed that the previously described up-regulation of EGFR and down-regulation of ERBB4 occurred in all analyzed RCC types, whereas down-regulation of ERBB2 and LRIG1 was only present in ccRCC. These observations illustrate the need to evaluate the different RCC types individually when analyzing molecules of interest and potential biological markers.
    BMC Research Notes 05/2012; 5:216.
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    ABSTRACT: Renal cell carcinoma (RCC) accounts for 2-3% of adult malignancies. There remain uncertainties over the oncological outcomes for the surgical management of localised RCC. Systematically review relevant literature comparing oncological outcomes of surgical management of localised RCC (T1-2N0M0). Relevant databases including Medline, Embase, and the Cochrane Library were searched up to October 2010, and an updated scoping search was performed up to January 2012. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The main outcomes were overall survival, cancer-specific survival, recurrence, and metastases. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A total of 4580 abstracts and 389 full-text articles were assessed. Thirty-four studies met the inclusion criteria (6 RCTs and 28 NRSs). Meta-analyses were planned but were deemed inappropriate due to data heterogeneity. There were high risks of bias and low-quality evidence across the evidence base. Open radical nephrectomy and open partial nephrectomy showed similar cancer-specific and overall survival, but when both open and laparoscopic approaches are considered together, the evidence showed improved survival for partial nephrectomy for tumours ≤4cm. The overall evidence suggests either equivalent or better survival with partial nephrectomy. Laparoscopic radical nephrectomy offered equivalent survival to open radical nephrectomy, and all laparoscopic approaches achieved equivalent survival. Open and laparoscopic partial nephrectomy achieved equivalent survival. The issue of ipsilateral adrenalectomy or complete lymph node dissection with radical nephrectomy or partial nephrectomy remains unresolved. The evidence base suggests localised RCCs are best managed by nephron-sparing surgery where technically feasible. However, the current evidence base has significant limitations due to studies of low methodological quality marked by high risks of bias.
    European Urology 02/2012; 61(5):972-93. · 10.48 Impact Factor

Publication Stats

1k Citations
427.94 Total Impact Points


  • 2013
    • University of Groningen
      • Department of Critical Care
      Groningen, Province of Groningen, Netherlands
    • Linköping University
      Linköping, Östergötland, Sweden
  • 1997–2013
    • Umeå University
      • • Department of Medical Biosciences
      • • Department of Surgical and Perioperative Sciences
      • • Department of Applied Physics and Electronics
      • • Department of Radiation Sciences
      Umeå, Vaesterbotten, Sweden
  • 2012
    • University of Aberdeen
      • Academic Urology Unit
      Aberdeen, SCT, United Kingdom
  • 2010–2012
    • National Institute for Public Health and the Environment (RIVM)
      • Centre for Nutrition and Health
      Utrecht, Utrecht, Netherlands
    • Charité Universitätsmedizin Berlin
      • Department of Urology
      Berlin, Land Berlin, Germany
  • 2009–2012
    • University of Oxford
      • Nuffield Department of Clinical Medicine
      Oxford, ENG, United Kingdom
    • Universität Heidelberg
      • Department of Molecular Oncology
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2011
    • Uppsala University Hospital
      • Department of Urology
      Uppsala, Uppsala, Sweden
  • 2007
    • Institutul Clinic Fundeni
      Bucureşti, Bucureşti, Romania
  • 2006
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany