Falke J.,Radboud University Nijmegen |
Lammers R.J.M.,Radboud University Nijmegen |
Arentsen H.C.,Radboud University Nijmegen |
Ravic M.,Pharma Integra Ltd |
And 4 more authors.
Journal of Urology | Year: 2013
Purpose: Imiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. Materials and Methods: We conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with 6 weekly instillations of TMX-101, starting 2 weeks after transurethral resection of bladder tumor. Patients were evaluated weekly, and pharmacokinetic and pharmacodynamic parameters were measured. Results: A total of 16 patients were included in the study with 4 per dose group. Two patients dropped out after instillation 2 in dose groups 1 and 2. Overall, 88 instillations were administered without serious adverse events. There were 118 adverse events, of which 84 were related to the study drug. All adverse events were mild or moderate and number or severity was not correlated with dose group. Of the related adverse events 70% were confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose group 3 (0.2%, 100 mg). Maximum plasma concentration in dose group 4 (0.4%, 200 mg) was 71.7 ng/ml. This is below plasma concentrations of 123 and 128 ng/ml without significant side effects measured in healthy volunteers after subcutaneous (30 mg) or oral intake (100 mg) of imiquimod, respectively. Conclusions: Intravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake. © 2013 American Urological Association Education and Research, Inc.
Moorman A.M.,Hospital Group Twente |
Vink R.,Pathology East Netherlands |
Heijmans H.J.,Hospital Group Twente |
Van Der Palen J.,University of Twente |
And 2 more authors.
European Journal of Surgical Oncology | Year: 2012
Background: Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with a good and poor outcome. Recent studies on tumour-stroma, found it to play an important role in tumour growth and progression. Objective: To evaluate the prognostic value of the tumour-stroma ratio (TSR) in triple-negative breast cancer. Methods: One hundred twenty four consecutive triple-negative breast cancer patients treated in our hospital were selected and evaluated. For each patient the Haematoxylin-Eosin (H&E) stained histological sections were evaluated for percentage of stroma. Patients with less than 50% stroma were classified as stroma-low and patients with ≥50% stroma were classified as stroma-high. Results: Of 124 triple-negative breast cancer patients, 40% had a stroma-high and 60% had a stroma-low tumour. TSR was assessed by two investigators (kappa 0.74). The 5-years relapse-free period (RFP) and overall survival (OS) were 85% and 89% in the stroma-low and 45% and 65% in the stroma-high group. In a multivariate cox-regression analysis, stroma amount remained an independent prognostic variable for RFP (HR 2.39; 95% CI 1.07-5.29; p = 0.033) and OS (HR 3.00; 95% CI 1.08-8.32; 0.034). Conclusion: TSR is a strong independent prognostic variable in triple-negative breast cancer. It is simple to determine, reproducible and can be easily incorporated into routine histological examination. This parameter can help optimize risk stratification and might lead to future targeted therapies. © 2011 Elsevier Ltd. All rights reserved.
Fortington L.V.,University of Groningen |
Geertzen J.H.B.,University of Groningen |
Van Netten J.J.,Hospital Group Twente |
Postema K.,University of Groningen |
And 2 more authors.
European Journal of Vascular and Endovascular Surgery | Year: 2013
Objective: To determine mortality rates after a first lower limb amputation and explore the rates for different subpopulations. Methods Retrospective cohort study of all people who underwent a first amputation at or proximal to transtibial level, in an area of 1.7 million people. Analysis with Kaplan-Meier curves and Log Rank tests for univariate associations of psycho-social and health variables. Logistic regression for odds of death at 30-days, 1-year and 5-years. Results 299 people were included. Median time to death was 20.3 months (95%CI: 13.1; 27.5). 30-day mortality = 22%; odds of death 2.3 times higher in people with history of cerebrovascular disease (95%CI: 1.2; 4.7, P = 0.016). 1 year mortality = 44%; odds of death 3.5 times higher for people with renal disease (95%CI: 1.8; 7.0, P < 0.001). 5-years mortality = 77%; odds of death 5.4 times higher for people with renal disease (95%CI: 1.8; 16.0,P = 0.003). Variation in mortality rates was most apparent in different age groups; people 75-84 years having better short term outcomes than those younger and older. Conclusions Mortality rates demonstrated the frailty of this population, with almost one quarter of people dying within 30-days, and almost half at 1 year. People with cerebrovascular had higher odds of death at 30 days, and those with renal disease and 1 and 5 years, respectively. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Kramp K.H.,Medical Center Leeuwarden |
van Det M.J.,Hospital Group Twente |
Hoff C.,Medical Center Leeuwarden |
Veeger N.J.G.M.,University of Groningen |
And 4 more authors.
Medical Education | Year: 2016
Context: Current methods of assessing candidates for medical specialties that involve laparoscopic skills suffer from a lack of instruments to assess the ability to work in a minimally invasive surgery environment. Objectives: A meta-analysis was conducted to investigate whether aptitude assessment can be used to predict variability in the acquisition and performance of laparoscopic skills. Methods: PubMed, PsycINFO and Google Scholar were searched to November 2014 for published and unpublished studies reporting the measurement of a form of aptitude for laparoscopic skills. The quality of studies was assessed with QUADAS-2. Summary correlations were calculated using a random-effects model. Results: Thirty-four studies were found to be eligible for inclusion; six of these studies used an operating room performance measurement. Laparoscopic skills correlated significantly with visual-spatial ability (r = 0.32, 95% confidence interval [CI] 0.25-0.39; p < 0.001), perceptual ability (r = 0.31, 95% CI 0.22-0.39; p < 0.001), psychomotor ability (r = 0.26, 95% CI 0.10-0.40; p = 0.003) and simulator-based assessment of aptitude (r = 0.64, 95% CI 0.52-0.73; p < 0.001). Three-dimensional dynamic visual-spatial ability showed a significantly higher correlation than intrinsic static visual-spatial ability (p = 0.024). Conclusions: In general, aptitude assessments are associated with laparoscopic skill level. Simulator-based assessment of aptitude appears to have the potential to represent a job sample and to enable the assessment of all forms of aptitude for laparoscopic surgery at once. A laparoscopy aptitude test can be a valuable additional tool in the assessment of candidates for medical specialties that require laparoscopic skills. © 2016 John Wiley & Sons Ltd.
Waaijman R.,University of Amsterdam |
Keukenkamp R.,University of Amsterdam |
De Haart M.,University of Amsterdam |
Polomski W.P.,Spaarne Hospital |
And 3 more authors.
Diabetes Care | Year: 2013
OBJECTIVE - Prescription custom-made footwear can only be effective in preventing diabetic foot ulcers if worn by the patient. Particularly, the high prevalence of recurrent foot ulcers focuses the attention on adherence, for which objective data are nonexisting. We objectively assessed adherence in patients with high risk of ulcer recurrence and evaluated what determines adherence. RESEARCH DESIGN AND METHODS - In 107 patients with diabetes, neuropathy, a recently healed plantar foot ulcer, and custom-made footwear, footwear use was measured during 7 consecutive days using a shoe-worn, temperature-based monitor. Daily step count was measured simultaneously using an ankle-worn activity monitor. Patients logged time away from home. Adherence was calculated as the percentage of steps that prescription footwear was worn. Determinants of adherence were evaluated in multivariate linear regression analysis. RESULTS - Mean ± SD adherence was 71 ± 25%. Adherence at home was 61 ± 32%, over 3,959 ± 2,594 steps, and away from home 87 ± 26%, over 2,604 ± 2,507 steps. In 35 patients with low adherence (< 60%), adherence at home was 28 ± 24%. Lower BMI, more severe foot deformity, and more appealing footwear were significantly associated with higher adherence. CONCLUSIONS - The results show that adherence to wearing custom-made footwear is insufficient, particularly at home where patients exhibit their largest walking activity. This low adherence is a major threat for reulceration. These objective findings provide directions for improvement in adherence, which could include prescribing specific off-loading footwear for indoors, and they set a reference for future comparative research on footwear adherence in diabetes. © 2013 by the American Diabetes Association.
Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): A randomised, single-blind, multicentre, non-inferiority trial
Von Birgelen C.,Thoraxcentrum Twente |
Von Birgelen C.,University of Twente |
Sen H.,Thoraxcentrum Twente |
Lam M.K.,Thoraxcentrum Twente |
And 17 more authors.
The Lancet | Year: 2014
Background: Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial. Methods: In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov, number NCT01331707. Findings: Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned study treatment (six [1%] in the zotarolimus-eluting stent group vs five [1%] in the everolimus-eluting stent group; p=0·22). 12-month follow-up results were available for 1810 patients (one patient in the zotarolimus-eluting stent group withdrew consent). The primary endpoint was met by 55 (6%) of 905 patients in the zotarolimus-eluting stent group and 47 (5%) of 905 in the everolimus-eluting stent group. The zotarolimus-eluting stent was non-inferior to the everolimus-eluting stent (absolute risk diff erence 0·88%, 95% CI-1·24% to 3·01%; upper limit of one-sided 95% CI 2·69%; non-inferiority p=0·006). We noted no significant between-group diff erences in individual components of the primary endpoint. Definite stent thrombosis occurred in three (0·3%) patients in the zotarolimus-eluting stent group and six (0·7%) patients in the everolimus-eluting stent group (p=0·34). Longitudinal stent deformation was seen only in the everolimus-eluting stent group (nine [1·0%] of 905 vs 0 of 906, p=0·002; nine of 1591 [0·6%] everolimus-eluting stents implanted became deformed), but was not associated with any adverse events. Interpretation: Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions. Funding: Boston Scientific, Medtronic.
Bus S.A.,University of Amsterdam |
Bus S.A.,Hospital Group Twente |
Waaijman R.,University of Amsterdam |
Arts M.,University of Amsterdam |
And 4 more authors.
Diabetes Care | Year: 2013
Objective-Custom-made footwear is the treatment of choice to prevent foot ulcer recurrence in diabetes. This footwear primarily aims to offload plantar regions at high ulcer risk. However, ulcer recurrence rates are high. We assessed the effect of offloading-improved custommade footwear and the role of footwear adherence on plantar foot ulcer recurrence. Research design and methods-We randomly assigned 171 neuropathic diabetic patients with a recently healed plantar foot ulcer to custom-made footwear with improved and subsequently preserved offloading (~20% peak pressure relief by modifying the footwear) or to usual care (i.e., nonimproved custom-made footwear). Primary outcome was plantar foot ulcer recurrence in 18 months. Secondary outcome was ulcer recurrence in patients with an objectively measured adherence of ≥80% of steps taken. Results-On the basis of intention-to-treat, 33 of 85 patients (38.8%) with improved footwear and 38 of 86 patients (44.2%) with usual care had a recurrent ulcer (relative risk -11%, odds ratio 0.80 [95% CI 0.44-1.47], P = 0.48). Ulcer-free survival curves were not significantly different between groups (P = 0.40). In the 79 patients (46% of total group) with high adherence, 9 of 35 (25.7%) with improved footwear and 21 of 44 (47.8%) with usual care had a recurrent ulcer (relative risk 246%, odds ratio 0.38 [0.15-0.99], P = 0.045). Conclusions-Offloading-improved custom-made footwear does not significantly reduce the incidence of plantar foot ulcer recurrence in diabetes compared with custom-made footwear that does not undergo such improvement, unless it is worn as recommended. © 2013 by the American Diabetes Association.
van Netten J.J.,Hospital Group Twente |
Bril A.,Hospital Group Twente |
van Baal J.G.,Hospital Group Twente
Journal of Foot and Ankle Research | Year: 2013
Background: Flexor tenotomy is a minimally invasive surgical alternative for the treatment of neuropathic diabetic foot ulcers on the distal end of the toe. The influence of infection on healing and time to heal after flexor tenotomy is unknown. Flexor tenotomy can also be used as a prophylactic treatment. The effectiveness as a prophylactic treatment has not been described before.Methods: A retrospective study was performed with the inclusion of all consecutive flexor tenotomies from one hospital between January 2005 and December 2011.Results: From 38 ulcers, 35 healed (92%), with a mean time to heal of 22 ± 26 days. The longest duration for healing was found for infected ulcers that were penetrating to bone (35 days; p = .042). Cases of prophylactic flexor tenotomies (n=9) did not result in any ulcer or other complications during follow-up.Conclusions: The results of this study suggest that flexor tenotomy may be beneficial for neuropathic diabetic foot ulcers on the distal end of the toe, with a high healing percentage and a short mean time to heal. Infected ulcers that penetrated to bone took a significantly longer time to heal. Prospective research, to confirm the results of this retrospective study, should be performed. © 2013 van Netten et al.; licensee BioMed Central Ltd.
Rakic S.,Hospital Group Twente |
Leblanc K.A.,Group of Baton Rouge
American Journal of Roentgenology | Year: 2013
OBJECTIVE. This article analyzes radiopaque properties of meshes currently used in hernia surgery. A search was conducted using PubMed and a combination of the terms "hernia repair," "mesh," "laparoscopy," "CT," "MRI," "radiopaque," and "high-resolution techniques." CONCLUSION. The visibility of meshes varies from not visible at all (e.g., Ultrapro), to hardly discernible (Prolene), to readily seen (Composix), and finally to the always visible (Dualmesh). Radiopaque properties of meshes have been insufficiently recognized by both the manufacturers and clinicians.
Moorman A.M.,Hospital Group Twente |
Bourez R.L.J.H.,Hospital Group Twente |
Heijmans H.J.,Hospital Group Twente |
Kouwenhoven E.A.,Hospital Group Twente
Annals of Surgical Oncology | Year: 2014
Background. The sentinel lymph node biopsy (SLNB) procedure is the method of choice for the identification and monitoring of regional lymph node metastases in patients with breast cancer. In the case of a positive sentinel lymph node (SLN), additional lymph node dissection is still warranted for regional control, although 40-65 % have no additional axillary disease. Recent studies show that after breast-conserving surgery, SLNB, and adjuvant systemic therapy, there is no significant difference between recurrence-free period and overall survival if there are ≤2 positive axillary nodes. The purpose of this study was preoperative identification of patients with limited axillary disease (≤2 macrometastases) by using ultrasonography. Methods. Data from 1,103 consecutive primary breast cancer patients with tumors smaller than 50 mm, no palpable adenopathy, and a maximum of 2 SLNs with macrometastases were collected. The variable of interest was US of the axilla. Results. Of the 1,103 patients included, 1,060 remained after exclusion criteria. Of these, 102 (9.6 %) had more than 2 positive axillary nodes on ALND. Selected by unsuspected US, the chance of having >2 positive lymph nodes (LNs) is substantially lower (4.2 %). This is significant on univariate and multivariate analysis. After excluding the patients with extracapsular extension of the SLN, the chance of having >2 positive LNs is only 2.6 %. For pT1-2, this is 2.2 %. Conclusions. The risk of more than 2 positive axillary nodes is relatively small in patients with cT1-2 breast cancer. US of the axilla helps in further identifying patients with a minimal risk of additional axillary disease, putting ALND up for discussion. © 2014 Society of Surgical Oncology.