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Bolla M.,Center Hospitalier University challon | Van Poppel H.,Universitair Ziekenhuis Gasthuisberg | Tombal B.,Cliniques Universitaires St Luc | Vekemans K.,Virga Jesse Ziekenhuis | And 14 more authors.
The Lancet | Year: 2012

Background We report the long-term results of a trial of immediate postoperative irradiation versus a wait-and-see policy in patients with prostate cancer extending beyond the prostate, to confi rm whether previously reported progression-free survival was sustained. Methods This randomised, phase 3, controlled trial recruited patients aged 75 years or younger with untreated cT0-3 prostate cancer (WHO performance status 0 or 1) from 37 institutions across Europe. Eligible patients were randomly assigned centrally (1:1) to postoperative irradiation (60 Gy of conventional irradiation to the surgical bed for 6 weeks) or to a wait-and-see policy until biochemical progression (increase in prostate-specifi c antigen >0.2 μg/L confi rmed twice at least 2 weeks apart). We analysed the primary endpoint, biochemical progression-free survival, by intention to treat (two-sided test for diff erence at α=0.05, adjusted for one interim analysis) and did exploratory analyses of heterogeneity of eff ect. This trial is registered with ClinicalTrials.gov, number NCT00002511. Findings 1005 patients were randomly assigned to a wait-and-see policy (n=503) or postoperative irradiation (n=502) and were followed up for a median of 10·6 years (range 2 months to 16·6 years). Postoperative irradiation signifi cantly improved biochemical progression-free survival compared with the wait-and-see policy (198 [39·4%] of 502 patients in postoperative irradiation group vs 311 [61·8%] of 503 patients in wait-and-see group had biochemical or clinical progression or died; HR 0·49 [95% CI 0·41-0·59]; p<0·0001). Late adverse eff ects (any type of any grade) were more frequent in the postoperative irradiation group than in the wait-and-see group (10 year cumulative incidence 70·8% [66·6-75·0] vs 59·7% [55·3-64·1]; p=0.001). Interpretation Results at median follow-up of 10·6 years show that conventional postoperative irradiation signifi cantly improves biochemical progression-free survival and local control compared with a wait-and-see policy, supporting results at 5 year follow-up; however, improvements in clinical progression-free survival were not maintained. Exploratory analyses suggest that postoperative irradiation might improve clinical progression-free survival in patients younger than 70 years and in those with positive surgical margins, but could have a detrimental eff ect in patients aged 70 years or older.


Smith M.R.,Massachusetts General Hospital | Saad F.,University of Montréal | Coleman R.,Weston Park Hospital | Shore N.,Carolina Urological Research Center | And 16 more authors.
The Lancet | Year: 2012

Background: Bone metastases are a major cause of morbidity and mortality in men with prostate cancer. Preclinical studies suggest that osteoclast inhibition might prevent bone metastases. We assessed denosumab, a fully human anti-RANKL monoclonal antibody, for prevention of bone metastasis or death in non-metastatic castration-resistant prostate cancer. Methods: In this phase 3, double-blind, randomised, placebo-controlled study, men with non-metastatic castration-resistant prostate cancer at high risk of bone metastasis (prostate-specific antigen [PSA] ≥8.0 μg/L or PSA doubling time ≤10.0 months, or both) were enrolled at 319 centres from 30 countries. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous denosumab 120 mg or subcutaneous placebo every 4 weeks. Randomisation was stratified by PSA eligibility criteria and previous or ongoing chemotherapy for prostate cancer. Patients, investigators, and all people involved in study conduct were masked to treatment allocation. The primary endpoint was bone-metastasis-free survival, a composite endpoint determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause. Efficacy analysis was by intention to treat. The masked treatment phase of the trial has been completed. This trial was registered at ClinicalTrials.gov, number NCT00286091. Findings: 1432 patients were randomly assigned to treatment groups (716 denosumab, 716 placebo). Denosumab significantly increased bone-metastasis-free survival by a median of 4.2 months compared with placebo (median 29.5 [95% CI 25.4-33.3] vs 25.2 [22.2-29.5] months; hazard ratio [HR] 0.85, 95% CI 0.73-0.98, p=0.028). Denosumab also significantly delayed time to first bone metastasis (33.2 [95% CI 29.5-38.0] vs 29.5 [22.4-33.1] months; HR 0.84, 95% CI 0.71-0.98, p=0.032). Overall survival did not differ between groups (denosumab, 43.9 [95% CI 40.1-not estimable] months vs placebo, 44.8 [40.1-not estimable] months; HR 1.01, 95% CI 0.85-1.20, p=0.91). Rates of adverse events and serious adverse events were similar in both groups, except for osteonecrosis of the jaw and hypocalcaemia. 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo. Hypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%) on placebo. Interpretation: This large randomised study shows that targeting of the bone microenvironment can delay bone metastasis in men with prostate cancer. Funding: Amgen Inc. © 2012 Elsevier Ltd.


Chevalier X.,University Paris Est Creteil | Jerosch J.,Klinik fur Orthopadie | Goupille P.,French Institute of Health and Medical Research | Van Dijk N.,AMC UVA | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Objectives: The primary objective was to compare a single, 6 ml, intra-articular injection of hylan G-F 20 with placebo in patients with symptomatic knee osteoarthritis. The safety of a repeat injection of hylan G-F 20 was also assessed. Methods: Patients with primary osteoarthritis knee pain were randomly assigned to arthrocentesis plus a 6 ml intra-articular injection of either hylan G-F 20 or placebo in a prospective, double-blind (one injector/one blinded observer) study. Results were evaluated at 4, 8, 12, 18 and 26 weeks post-injection. The primary outcome criterion was change from baseline over 26 weeks in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index A pain. Secondary outcome measures included WOMAC A1 and C, patient global assessment (PGA) and clinical observer global assessment (COGA) and Outcome Measures in Rheumatology, Osteoarthritis Research Society International responder rates. A 4-week, open, repeat treatment phase evaluated safety only. Results: A total of 253 patients (Kellgren-Lawrence grade II or III) was randomly assigned. Patients receiving hylan G-F 20 experienced statistically significantly greater improvements in WOMAC A pain scores (20.15, SE 0.076, p = 0.047), and several of the secondary outcome measures (WOMAC A1, PGA and COGA), than patients receiving placebo. There was no difference between the safety results of the two groups. No increased risk of local adverse events was observed in the open, repeat treatment phase. Conclusions: This placebo-controlled study demonstrated that, in patients with knee osteoarthritis, a single 6 ml intra-articular injection of hylan G-F 20 is safe and effective in providing statistically significant, clinically relevant pain relief over 26 weeks, with a modest difference versus placebo. Trial registration number: NCT00131352.


Volpe A.,University of Piemonte Orientale | Blute M.L.,Harvard University | Ficarra V.,University of Udine | Gill I.S.,University of Southern California | And 6 more authors.
European Urology | Year: 2015

Context: Partial nephrectomy (PN) is the current gold standard treatment for small localized renal tumors.; however, the impact of duration and type of intraoperative ischemia on renal function (RF) after PN is a subject of significant debate. Objective: To review the current evidence on the relationship of intraoperative ischemia and RF after PN. Evidence acquisition: A review of English-language publications on renal ischemia and RF after PN was performed from 2005 to 2014 using the Medline, Embase, and Web of Science databases. Ninety-one articles were selected with the consensus of all authors and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Evidence synthesis: The vast majority of reviewed studies were retrospective, nonrandomized observations. Based on the current literature, RF recovery after PN is strongly associated with preoperative RF and the amount of healthy kidney parenchyma preserved. Warm ischemia time (WIT) is modifiable and prolonged warm ischemia is significantly associated with adverse postoperative RF. Available data suggest a benefit of keeping WIT <25 min, although the level of evidence to support this threshold is limited. Cold ischemia safely facilitates longer durations of ischemia. Surgical techniques that minimize or avoid global ischemia may be associated with improved RF outcomes. Conclusions: Although RF recovery after PN is strongly associated with quality and quantity of preserved kidney, efforts should be made to limit prolonged WIT. Cold ischemia should be preferred when longer ischemia is expected, especially in presence of imperative indications for PN. Additional research with higher levels of evidence is needed to clarify the optimal use of renal ischemia during PN. Patient summary: In this review of the literature, we looked at predictors of renal function after surgical resection of renal tumors. There is a strong association between the quality and quantity of renal tissue that is preserved after surgery and long-term renal function. The time of interruption of renal blood flow during surgery is an important, modifiable predictor of postoperative renal function. © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Penninckx F.,Universitair Ziekenhuis Gasthuisberg | Kartheuser A.,Cliniques Universitaires Saint Luc | Van De Stadt J.,Erasme University Hospital | Pattyn P.,Ghent University | And 6 more authors.
British Journal of Surgery | Year: 2013

Background There are few reports on the oncological quality of resection and outcome after laparoscopic versus open total mesorectal excision (TME) for rectal cancer in everyday surgical practice. Methods Between January 2006 and October 2011, data for patients with mid or low rectal adenocarcinoma who underwent elective TME were recorded in the PROCARE database. A multivariable model and the propensity score as a co-variable in Cox or logistic regression models were used for adjustment of differences in patient mix and non-random assignment of surgical approach. Results Data for 2660 patients from 82 hospitals were recorded. Implementation of laparoscopic TME was highly variable. The oncological quality of resection was similar in the laparoscopic and the open group: incomplete mesorectal excision in 13·2 and 11·4 per cent respectively, circumferential resection margin positivity in 18·1 per cent, and a median of 11 lymph nodes examined per specimen in both groups. The hazard ratio for survival after laparoscopic versus open TME was 1·05 (95 per cent confidence interval 0·88 to 1·24) after correction for differences in patient mix, and 1·06 (0·89 to 1·25) after correction for the propensity score. The definitive colostomy rate was similar in the two groups: 31·0 per cent after open and 31·4 per cent after laparoscopic TME. Postoperative morbidity was lower and length of stay was shorter after laparoscopic TME compared with open TME. Survival was not negatively affected by converted laparoscopic resection, whereas postoperative morbidity, mortality and length of stay after converted laparoscopy were comparable with those after open TME. Conclusion Oncological outcome is comparable after laparoscopic and open TME in everyday surgical practice. Oncological safety confirmed © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.


Viaene L.,University Hospital Leuven | Meijers B.K.I.,University Hospital Leuven | Vanrenterghem Y.,University Hospital Leuven | Evenepoel P.,University Hospital Leuven | Evenepoel P.,Universitair Ziekenhuis Gasthuisberg
American Journal of Nephrology | Year: 2012

Introduction: Calcium and phosphorus are essential to many vital physiological processes. Little is known about the net and fractional intestinal absorption of calcium and phosphorus in patients with chronic kidney disease (CKD) and their clinical and hormonal determinants. Methods: Blood and 24-hour urine samples were collected in 20 healthy volunteers (HV) and 72 stable CKD stage 1-4 patients and analyzed for parameters of mineral metabolism including calcidiol, calcitriol, and parathyroid hormone (PTH). Dietary intake was assessed by dietary history. Results: The 24-hour urinary calcium excretion, as opposed to the phosphorus excretion, showed a stepwise decrease across CKD stages (median of 219, 84, 40, and 22 mg/day in HV and patients with CKD stages 1-2, 3 and 4, respectively). Younger age, high serum calcitriol, and high estimated GFR were associated with a high 24-hour urinary calcium excretion. High serum calcitriol levels and dietary phosphorus intake were associated with a high 24-hour urinary phosphorus excretion. The fractional intestinal calcium absorption, as estimated by the urinary-to-ingested calcium ratio, decreased across CKD stages. Conclusions: The 24-hour urinary excretion of calcium, as opposed to phosphorus, is markedly decreased in CKD, even in early-stage disease. This is partly explained by low calcitriol levels and older age. Assuming a neutral calcium balance at the time of urine collection, we infer that net intestinal calcium absorption may be severely impaired in CKD. © 2012 S. Karger AG, Basel.


Jaeken J.,Universitair Ziekenhuis Gasthuisberg
Journal of Inherited Metabolic Disease | Year: 2011

Congenital disorders of glycosylation (CDG) is a booming class of metabolic diseases. Its number has increased nearly fourfold (to 45) since 2003, the year of the Komrower lecture, entitled 'Congenital disorders of glycosylation CDG): It's all in it!'. This paper presents an overview of recently discovered CDG and CDG phenotypes, of a diagnostic approach, of (the lack of) treatment, of CDG genetics, of a novel CDG nomenclature and classification, and of some future directions in the CDG field. © 2011 SSIEM and Springer.


Besouw M.T.,Universitair Ziekenhuis Gasthuisberg
Nederlands tijdschrift voor geneeskunde | Year: 2011

Lipoblastoma and lipoblastomatosis are rare benign fatty tumours that mainly occur in children under the age of 3 years. Several body sites can be affected. The term 'lipoblastoma' is reserved for an encapsulated neoplasm; 'lipoblastomatosis' for tumours demonstrating infiltrative growth. Most of the clinical symptoms arise from a mass effect of the tumour on surrounding tissues. The tumours should be differentiated from lipoma, myxoid liposarcoma and hibernoma. A clear distinction can be made by cytogenetic analysis, since each of these tumours is known for its own typical genetic abnormalities. In lipoblastoma and lipoblastomatosis, these include a breakpoint in the 8q11-13 region or polysomy of chromosome 8, both leading to the activation of the oncogenic pleomorphic adenoma gene 1 (PLAG1) on 8q12. Treatment consists of surgical resection; there is no need for radiotherapy or chemotherapy. Clinical outcome depends on the completeness of the resection and damage that is done to the surrounding tissues during surgery.


Abdollah F.,Ford Motor Company | Briganti A.,Vita-Salute San Raffaele University | Montorsi F.,Vita-Salute San Raffaele University | Stenzl A.,University of Tübingen | And 4 more authors.
European Urology | Year: 2015

Context Prostate cancer (PCa) patients with isolated clinical lymph node (LN) relapse, limited to the regional and/or retroperitoneal LNs, may represent a distinct group of patients who have a more favorable outcome than men with progression to the bone or to other visceral organs. Some data indirectly denote a beneficial impact of pelvic LN dissection on survival in these patients. Objective To provide an overview of the currently available literature regarding salvage LN dissection (SLND) in PCa patients with clinical relapse limited to LNs after radical prostatectomy (RP). Evidence acquisition A systematic literature search was conducted using the Medline, Embase, and Web of Science databases to identify original articles, review articles, and editorials regarding SLND. Articles published between 2000 and 2012 were reviewed and selected with the consensus of all the authors. Evidence synthesis Contemporary imaging techniques, such as 11C-choline positron emission tomography and diffusion-weighted magnetic resonance imaging, appear to enhance the accuracy in identifying LN relapse in patients with biochemical recurrence (BCR) and after RP. In these individuals, SLND can be considered as a treatment option. The currently available data suggest that SLND can delay clinical progression and postpone hormonal therapy in almost one-third of the patients, although the majority will have BCR. An accurate and attentive preoperative patient selection may help improve these outcomes. The most frequent complication after SLND was lymphorrhea (15.3%), followed by fever (14.5%) and ileus (11.2%). It is noteworthy that all examined cohorts originated from retrospective single-institution series, with limited sample size and short follow-up. Consequently, the current findings cannot be generalized and warrant further investigation in future prospective trials. Conclusions The current data suggest that SLND represents an option in patients with disease relapse limited to the LNs after RP; however, more robust data derived from well-designed clinical trials are needed to validate the role of SLND in this selected patient population. Patient summary Salvage lymph node dissection (SLND) represents a treatment option in for patients with prostate cancer relapse limited to the lymph nodes; however, more robust data derived from well-designed clinical trials are needed to validate the role of SLND in this selected patient population. © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Brosens V.,Health Science University | Ghijselings I.,Health Science University | Lemiere J.,Universitair Ziekenhuis Gasthuisberg | Fieuws S.,Hasselt University | And 2 more authors.
European Journal of Orthodontics | Year: 2014

SUMMARYOBJECTIVES:As a continuation of a baseline study on oral health-related quality of life (OHRQoL) and the role of self-esteem (SE), the aim of this research is to investigate the changes in OHRQoL reports in children during orthodontic treatment and the influence of SE.SUBJECTS AND METHODS:This longitudinal study comprised 109 children (50 boys and 59 girls) aged 11-16 years, all receiving orthodontic treatment. Questionnaires were administered at baseline and at follow-up (1 year after start of orthodontic treatment). OHRQoL was assessed by the child perception questionnaire (CPQ). The Dutch adaptation of the Harter's Self-Perception Profile for Adolescents was used to assess SE and the Index of Orthodontic Treatment Need defined the need for treatment. The questionnaires also included questions related to motivation for treatment. Spearman correlations, Wilcoxon signed rank tests and Mann-Whitney U-tests were performed.RESULTS:A significant increase in total CPQ score was found during orthodontic treatment. This increase was also significant for the subdomains functional limitations, oral symptoms, and social well-being, whereas for the subdomain emotional well-being a non-significant decrease in CPQ score was found. Children with high SE at baseline showed significantly lower variability in OHRQoL measures at follow-up.CONCLUSIONS:OHRQoL deteriorates in children during orthodontic treatment. There is evidence that SE can be a protective factor in OHRQoL during orthodontic treatment. © The Author 2013.

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