Publications by authors named "Wim C J Hop"

211 Publications

A single blinded randomized controlled trial comparing semi-mechanical with hand-sewn cervical anastomosis after esophagectomy for cancer (SHARE-study).

J Surg Oncol 2020 Dec 28;122(8):1616-1623. Epub 2020 Sep 28.

Department of Surgery, Erasmus MC-Erasmus University Medical Centre, Rotterdam, The Netherlands.

Objective: The aim was to compare leak rate between hand-sewn end-to-end anastomosis (ETE) and semi-mechanical anastomosis (SMA) after esophagectomy with gastric tube reconstruction.

Background Data: The optimal surgical technique for creation of an anastomosis in the neck after esophagectomy is unclear.

Methods: Patients with esophageal cancer undergoing esophagectomy with gastric tube reconstruction and cervical anastomosis were eligible for participation after written informed consent. Patients were randomized in 1:1 ratio. Primary endpoint was anastomotic leak rate defined as external drainage of saliva from the site of the anastomosis or intra-thoracic manifestation of leak. Secondary endpoints included anastomotic stricture rate at one year follow up, number of endoscopic dilatations, dysphagia-score, hospital stay, morbidity, and mortality. Patients were blinded for intervention.

Results: Between August 2011 and July 2014, 174 patients with esophageal cancer underwent esophagectomy. Ninety-three patients were randomized to ETE (n = 44) or SMA (n = 49). Anastomotic leak occurred in 9 of 44 patients (20%) in the ETE group and 12 of 49 patients (24%) in the SMA group (absolute difference 4%, 95% CI -13% to +21%; p = .804). There was no significant difference in dysphagia at 1 year postoperatively (ETE 25% vs. SMA 20%; p = .628), in stricture rate (ETE 25% vs. 19% in SMA, p = .46), nor in median hospital stay (17 days in the ETE group, 13 days in the SMA group), morbidity (82% vs. 73%, p = .460) or mortality (0% vs. 4%, p = .175) between the groups.
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http://dx.doi.org/10.1002/jso.26209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821322PMC
December 2020

Watchful Waiting Versus Surgery of Mildly Symptomatic or Asymptomatic Inguinal Hernia in Men Aged 50 Years and Older: A Randomized Controlled Trial.

Ann Surg 2018 Jan;267(1):42-49

Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.

Objective: To compare if watchful waiting is noninferior to elective repair in men aged 50 years and older with mildly symptomatic or asymptomatic inguinal hernia.

Background: The role of watchful waiting in older male patients with mildly symptomatic or asymptomatic inguinal hernia is still not well-established.

Methods: In this noninferiority trial, we randomly assigned men aged 50 years and older with mildly symptomatic or asymptomatic inguinal hernia to either elective inguinal hernia repair or watchful waiting. Primary endpoint was the mean difference in a 4-point pain/discomfort score at 24 months of follow-up. Using a 0.20-point difference as a clinically relevant margin, it was hypothesized that watchful waiting was noninferior to elective repair. Secondary endpoints included quality of life, event-free survival, and crossover rates.

Results: Between January 2006 and August 2012, 528 patients were enrolled, of whom 496 met the inclusion criteria: 234 were assigned to elective repair and 262 to watchful waiting. The mean pain/discomfort score at 24 months was 0.35 [95% confidence interval (CI) 0.28-0.41)] in the elective repair group and 0.58 (95% CI 0.52-0.64) in the watchful waiting group. The difference of these means (MD) was -0.23 (95% CI -0.32 to -0.14). In the watchful waiting group, 93 patients (35·4%) eventually underwent elective surgery and 6 patients (2·3%) received emergent surgery for strangulation/incarceration. Postoperative complication rates and recurrence rates in these 99 operated individuals were comparable with individuals originally assigned to the elective repair group (8.1% vs 15.0%; P = 0.106, 7.1% vs 8.9%; P = 0.668, respectively).

Conclusions: Our data could not rule out a relevant difference in favor of elective repair with regard to the primary endpoint. Nevertheless, in view of all other findings, we feel that our results justify watchful waiting as a reasonable alternative compared with surgery in men aged 50 years and older.
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http://dx.doi.org/10.1097/SLA.0000000000002243DOI Listing
January 2018

Insulin therapy in hyperglycemic children with severe acute asthma.

J Asthma 2015 Sep 18;52(7):681-6. Epub 2015 May 18.

a Department of Pediatric Intensive Care .

Objectives: The aim of this study was to assess the effect of intravenous (IV) insulin administration in children with severe acute asthma (SAA) and hyperglycemia on IV salbutamol consumption and length of stay (LOS) in a pediatric intensive care unit (PICU).

Methods: Retrospective, descriptive study of the clinical course before and after implementation of an insulin protocol for the treatment of hyperglycemia (i.e. blood glucose >8 mmol/L or 144 mg/dL, respectively) in the PICU of a tertiary care university hospital. Admissions between 1994 and 2010 were reviewed. The insulin protocol was introduced in 2006.

Results: A total of 131 pediatric patients with SAA complicated by hyperglycemia requiring IV salbutamol were included. Severity of illness before and after implementation of the insulin protocol did not significantly differ. The insulin-treated patient group had significantly higher maximum blood glucose levels and higher cumulative IV salbutamol dose than the non-treated group. There were no differences between these groups in the duration of IV salbutamol administration and LOS.

Conclusions: In view of the lack of difference in outcomes and considering that the insulin protocol is labor-intensive, the question is whether this protocol is efficacious for the treatment of pediatric SAA associated with hyperglycemia.
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http://dx.doi.org/10.3109/02770903.2015.1008139DOI Listing
September 2015

Reversibility of trapped air on chest computed tomography in cystic fibrosis patients.

Eur J Radiol 2015 Jun 21;84(6):1184-90. Epub 2015 Feb 21.

Department of Radiology, Erasmus MC, The Netherlands; Department of Computer Science, University of Copenhagen, Denmark; Department of Medical Informatics, Erasmus MC, The Netherlands.

Purpose: To investigate changes in trapped air volume and distribution over time and compare computed tomography (CT) with pulmonary function tests for determining trapped air.

Methods: Thirty children contributed two CTs and pulmonary function tests over 2 years. Localized changes in trapped air on CT were assessed using image analysis software, by deforming the CT at timepoint 2 to match timepoint 1, and measuring the volume of stable (TAstable), disappeared (TAdisappeared) and new (TAnew) trapped air as a proportion of total lung volume. We used the difference between total lung capacity measured by plethysmography and helium dilution, residual volume to total lung capacity ratio, forced expiratory flow at 75% of vital capacity, and maximum mid-expiratory flow as pulmonary function test markers of trapped air. Statistical analysis included Wilcoxon's signed rank test and Spearman correlation coefficients.

Results: Median (range) age at baseline was 11.9 (5-17) years. Median (range) of trapped air was 9.5 (2-33)% at timepoint 1 and 9.0 (0-25)% at timepoint 2 (p=0.49). Median (range) TAstable, TAdisappeared and TAnew were respectively 3.0 (0-12)%, 5.0 (1-22)% and 7.0 (0-20)%. Trapped air on CT correlated statistically significantly with all pulmonary function measures (p<0.01), other than residual volume to total lung capacity ratio (p=0.37).

Conclusion: Trapped air on CT did not significantly progress over 2 years, may have a substantial stable component, and is significantly correlated with pulmonary function markers.
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http://dx.doi.org/10.1016/j.ejrad.2015.02.011DOI Listing
June 2015

The influence of mechanical bowel preparation on long-term survival in patients surgically treated for colorectal cancer.

Am J Surg 2015 Jul 21;210(1):106-10. Epub 2015 Jan 21.

Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands.

Background: In this study, we evaluated long-term survival in patients treated with and without mechanical bowel preparation (MBP) before colorectal surgery for cancer.

Methods: Long-term outcome of patients of 2 main participating hospitals in a prior multicenter randomized trial comparing clinical outcome of MBP versus no MBP was reviewed. Primary endpoint was cancer-related mortality and secondary endpoint was all-cause mortality.

Results: A total of 382 patients underwent potentially curative surgery for colorectal cancer. One hundred seventy-seven (46%) patients were treated with MBP and 205 (54%) were not before surgery. Median follow-up was 7.6 years (mean 6.6, range .01 to 12.73). There was no significant difference in both cancer-related mortality and all-cause mortality in patients treated with MBP and without MBP (P = .76 and P = .36, respectively). Multivariate analysis, taking account of age, sex, AJCC cancer stage, and ASA classification, also showed no survival difference.

Conclusions: Our results indicate that MBP does not seem to influence long-term survival in patients surgically treated for colorectal cancer.
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http://dx.doi.org/10.1016/j.amjsurg.2014.10.022DOI Listing
July 2015

The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia.

Haematologica 2014 Nov 22;99(11):1716-21. Epub 2014 Aug 22.

Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands

We prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase in relation to levels of asparaginase activity in children with acute lymphoblastic leukemia. We also evaluated the incidence of pancreatitis, thrombosis, hyperammonemia and central neurotoxicity and their association with asparaginase activity levels. Eighty-nine patients were treated according to the Dutch Childhood Oncology Group Acute Lymphoblastic Leukemia 10 medium-risk intensification protocol, which includes 15 doses of PEGasparaginase (2,500 IU/m(2)) over 30 weeks. Erwinia asparaginase (20,000 IU/m(2)) was administered when allergy to or silent inactivation of PEGasparaginase occurred. Triglyceride, cholesterol and ammonia levels increased rapidly in children treated with PEGasparaginase and remained temporarily elevated, but normalized after administration of the last asparaginase dose. Among the patients treated with PEGasparaginase, hypertriglyceridemia and hypercholesterolemia (grade 3/4) were found in 47% and 25%, respectively. The correlation between PEGasparaginase activity levels and triglyceride levels was strongest at week 5 (Spearman correlation coefficient = 0.36, P = 0.005). The triglyceride levels were higher in children ≥ 10 years old than in younger patients (<10 years old) after adjustment for type of asparaginase preparation: median 4.9 mmol/L versus 1.6 mmol/L (P<0.001). In patients receiving Erwinia asparaginase, triglyceride levels increased in the first weeks as well, but no grade 3/4 dyslipidemia was found. Hyperammonemia (grade 3/4) was only found in patients treated with Erwinia asparaginase (9%). Thrombosis occurred in 4.5%, pancreatitis in 7%, and central neurotoxicity in 9% of patients using either of the two agents; these toxicities were not related to levels of asparaginase activity or to triglyceride levels. In conclusion, severe dyslipidemia occurred frequently, but was temporary and was not associated with relevant clinical events and should not, therefore, be considered a reason for modifying asparaginase treatment. Dyslipidemia was the only toxicity related to levels of asparaginase activity.
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http://dx.doi.org/10.3324/haematol.2014.109413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222477PMC
November 2014

Incisional hernia after liver transplantation: risk factors and health-related quality of life.

Clin Transplant 2014 Jul 12;28(7):829-36. Epub 2014 Jun 12.

Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.

The aim of this cross-sectional study was to analyze the incidence of incisional hernia after liver transplantation (LT), to determine potential risk factors for their development, and to assess their impact on health-related quality of life (HRQoL). Patients who underwent LT through a J-shaped incision with a minimum follow-up of three months were included. Follow-up was conducted at the outpatient clinic. Short Form 36 (SF-36) and body image questionnaire (BIQ) were used for the assessment of HRQoL. A total of 140 patients was evaluated. The mean follow-up period was 33 (SD 20) months. Sixty patients (43%) were diagnosed with an incisional hernia. Multivariate analysis revealed surgical site infection (OR 5.27, p = 0.001), advanced age (OR 1.05, p = 0.003), and prolonged ICU stay (OR 1.54, p = 0.022) to be independent risk factors for development of incisional hernia after LT. Patients with an incisional hernia experienced significantly diminished HRQoL with respect to physical, social, and mental aspects. In conclusion, patients who undergo LT exhibit a high incidence of incisional hernia, which has a considerable impact on HRQoL. Development of incisional hernia was shown to be related to surgical site infection, advanced age, and prolonged ICU stay.
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http://dx.doi.org/10.1111/ctr.12386DOI Listing
July 2014

Daily interruption of sedation in critically ill children: study protocol for a randomized controlled trial.

Trials 2014 Feb 13;15:55. Epub 2014 Feb 13.

Intensive Care, Erasmus MC - Sophia Children's Hospital, Dr, Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.

Background: In adult patients who are critically ill and mechanically ventilated, daily interruption of sedation (DSI) is an effective method of improving sedation management, resulting in a decrease of the duration of mechanical ventilation, the length of stay in the intensive care unit (ICU) and the length of stay in the hospital. It is a safe and effective approach and is common practice in adult ICUs. For critically ill children it is unknown if DSI is effective and feasible. The aim of this multicenter randomized controlled trial is to evaluate the safety and efficacy of daily sedation interruption in critically ill children.

Methods/design: Children between 0 and 18 years of age who require mechanical ventilation, with an expected duration of at least 48 h and need for sedative infusion, will be included. After enrollment patients will be randomly assigned to DSI in combination with protocolized sedation (intervention group) or protocolized continuous sedation (control group). A sedation protocol that contains an algorithm for increasing and weaning of sedatives and analgesics will be used. The sedative infusion will be restarted if the patient becomes uncomfortable or agitated according to the sedation protocol. The primary endpoint is the number of ventilator-free days at 28 days.

Trial Registration: NTR2030.
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http://dx.doi.org/10.1186/1745-6215-15-55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928607PMC
February 2014

A double blind randomized controlled trial comparing primary suture closure with mesh augmented closure to reduce incisional hernia incidence.

BMC Surg 2013 Oct 28;13:48. Epub 2013 Oct 28.

Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.

Background: Incisional hernia is the most frequently seen long term complication after laparotomy causing much morbidity and even mortality. The overall incidence remains 11-20%, despite studies attempting to optimize closing techniques. Two patient groups, patients with abdominal aortic aneurysm and obese patients, have a risk for incisional hernia after laparotomy of more than 30%. These patients might benefit from mesh augmented midline closure as a means to reduce incisional hernia incidence.

Methods/design: The PRImary Mesh Closure of Abdominal Midline Wound (PRIMA) trial is a double-blinded international multicenter randomized controlled trial comparing running slowly absorbable suture closure with the same closure augmented with a sublay or onlay mesh. Primary endpoint will be incisional hernia incidence 2 years postoperatively. Secondary outcomes will be postoperative complications, pain, quality of life and cost effectiveness.A total of 460 patients will be included in three arms of the study and randomized between running suture closure, onlay mesh closure or sublay mesh closure. Follow-up will be at 1, 3, 12 and 24 months with ultrasound imaging performed at 6 and 24 months to objectify the presence of incisional hernia. Patients, investigators and radiologists will be blinded throughout the whole follow up.

Disccusion: The use of prosthetic mesh has proven effective and safe in incisional hernia surgery however its use in a prophylactic manner has yet to be properly investigated. The PRIMA trial will provide level 1b evidence whether mesh augmented midline abdominal closure reduces incisional hernia incidence in high risk groups.

Trial Registration: Clinical trial.gov NCT00761475.
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http://dx.doi.org/10.1186/1471-2482-13-48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840708PMC
October 2013

A prospective study on drug monitoring of PEGasparaginase and Erwinia asparaginase and asparaginase antibodies in pediatric acute lymphoblastic leukemia.

Blood 2014 Mar 21;123(13):2026-33. Epub 2014 Jan 21.

Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands;

This study prospectively analyzed the efficacy of very prolonged courses of pegylated Escherichia coli asparaginase (PEGasparaginase) and Erwinia asparaginase in pediatric acute lymphoblastic leukemia (ALL) patients. Patients received 15 PEGasparaginase infusions (2500 IU/m(2) every 2 weeks) in intensification after receiving native E coli asparaginase in induction. In case of allergy to or silent inactivation of PEGasparaginase, Erwinia asparaginase (20 000 IU/m(2) 2-3 times weekly) was given. Eighty-nine patients were enrolled in the PEGasparaginase study. Twenty (22%) of the PEGasparaginase-treated patients developed an allergy; 7 (8%) showed silent inactivation. The PEGasparaginase level was 0 in all allergic patients (grade 1-4). Patients without hypersensitivity to PEGasparaginase had serum mean trough levels of 899 U/L. Fifty-nine patients were included in the Erwinia asparaginase study; 2 (3%) developed an allergy and none silent inactivation. Ninety-six percent had at least 1 trough level ≥100 U/L. The serum asparagine level was not always completely depleted with Erwinia asparaginase in contrast to PEGasparaginase. The presence of asparaginase antibodies was related to allergies and silent inactivation, but with low specificity (64%). Use of native E coli asparaginase in induction leads to high hypersensitivity rates to PEGasparaginase in intensification. Therefore, PEGasparaginase should be used upfront in induction, and we suggest that the dose could be lowered. Switching to Erwinia asparaginase leads to effective asparaginase levels in most patients. Therapeutic drug monitoring has been added to our ALL-11 protocol to individualize asparaginase therapy.
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http://dx.doi.org/10.1182/blood-2013-10-534347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968389PMC
March 2014

Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol.

Bone 2014 Feb 25;59:223-8. Epub 2013 Nov 25.

Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands; Dutch Childhood Oncology Group, The Hague, The Netherlands. Electronic address:

Purpose: To elucidate incidence and risk factors of bone mineral density and fracture risk in children with Acute Lymphoblastic Leukemia (ALL).

Methods: Prospectively, cumulative fracture incidence, calculated from diagnosis until one year after cessation of treatment, was assessed in 672 patients. This fracture incidence was compared between subgroups of treatment stratification and age subgroups (Log-Rank test). Serial measurements of bone mineral density of the lumbar spine (BMDLS) were performed in 399 ALL patients using dual energy X-ray absorptiometry. We evaluated risk factors for a low BMD (multivariate regression analysis). Osteoporosis was defined as a BMDLS≤-2 SDS combined with clinical significant fractures.

Results: The 3-year cumulative fracture incidence was 17.8%. At diagnosis, mean BMDLS of ALL patients was lower than of healthy peers (mean BMDLS=-1.10 SDS, P<0.001), and remained lower during/after treatment (8months: BMDLS=-1.10 SDS, P<0.001; 24months: BMDLS=-1.27 SDS, P<0.001; 36months: BMDLS=-0.95 SDS, P<0.001). Younger age, lower weight and B-cell-immunophenotype were associated with a lower BMDLS at diagnosis. After correction for weight, height, gender and immunophenotype, stratification to the high risk (HR)-protocol arm and older age lead to a larger decline of BMDLS (HR group: β=-0.52, P<0.01; age: β=-0.16, P<0.001). Cumulative fracture incidences were not different between ALL risk groups and age groups. Patients with fractures had a lower BMDLS during treatment than those without fractures. Treatment-related bone loss was similar in patients with and without fractures (respectively: ΔBMDLS=-0.36 SDS and ΔBMDLS=-0.12 SDS; interaction group time, P=0.30). Twenty of the 399 patients (5%) met the criteria of osteoporosis.

Conclusion: Low values of BMDLS at diagnosis and during treatment, rather than the treatment-related decline of BMDLS, determine the increased fracture risk of 17.8% in children with ALL.
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http://dx.doi.org/10.1016/j.bone.2013.11.017DOI Listing
February 2014

Closure of midline laparotomies by means of small stitches: practical aspects of a new technique.

Surg Technol Int 2013 Sep;23:34-8

Department of Surgery Erasmus University Medical Center Rotterdam, Netherlands.

Randomized studies support the closure of midline incisions with a suture length to wound length ratio (SL:WL) of more than 4, accomplished with small tissue bites and short stitch intervals to decrease the risk of incisional hernia and wound infection. We investigated practical aspects of this technique possibly hampering the introduction of this technique. Patient data, operative variables and SL:WL ratio were collected at two hospitals: Sundsvall Hospital (SH) and Erasmus University Medical Center (EMC). A structured implementation of the technique had been performed at SH but not at EMC. Personnel were interviewed by questionnaire. At each hospital, 18 closures were analyzed. Closure time was significantly longer (p = 0.023) at SH (median 18 minutes, range: 9-59) than at EMC (median 13 minutes, range: 5-23). An SL:WL ratio of more than 4 was achieved in 8 of 18 cases at EMC and in all 18 cases at SH. We conclude that calculation of an SL:WL ratio is easily performed. Suturing with the small bite-short stitch interval technique of SH required 5 minutes extra, outweighing the morbidity of incisional hernia. Without a structured implementation to suture with an SL:WL ratio of more than 4, a lower ratio is often achieved.
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September 2013

Emotional distress in 652 Dutch very long-term survivors of childhood cancer, using the hospital anxiety and depression scale (HADS).

J Pediatr Hematol Oncol 2013 Oct;35(7):525-9

*Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital †Department of Obstetrics and Gynaecology, Division of Reproductive Medicine ‡Department of Biostatistics §Department of Internal Medicine/Endocrinology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Background: After a more successful treatment of pediatric cancer, the number of childhood cancer survivors is progressively increasing. Consequently, awareness of psychological late sequelae is important.

Procedure: The Hospital Anxiety and Depression Scale (HADS) was used as a screening tool for emotional distress in a single center cohort of 652 childhood cancer survivors (median age 23 y [range, 15 to 46 y], median follow-up time 15 y [range, 5 to 42 y]). Results were compared with a control group of 440 Dutch subjects. A higher HADS score linearly reflect a higher level of emotional distress, and a score ≥15 is indicative of clinically significant emotional distress.

Results: Mean HADS score of the childhood cancer survivors was not different from the control group (P=0.38). Survivors exposed to global central nervous system (CNS) irradiation had a significantly higher HADS score than the control group (8.3±6.6; P=0.05) as well as other survivors (P=0.01). Forty-three survivors (7%) had a HADS score ≥15. Survivors with a HADS score ≥15 were variously spread over the diagnostic-related and treatment-related subgroups. Linear regression analysis showed that high educational achievement (β=-1.28; P<0.01) and age at the time of the study (β=0.08; P=0.03) were both significantly associated with the HADS score.

Conclusions: Emotional distress does not occur more often in childhood cancer survivors than in the normal population. No disease-related or treatment-related variable was independently associated with emotional distress.
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http://dx.doi.org/10.1097/MPH.0b013e31829f2799DOI Listing
October 2013

The current state of active third stage management to prevent postpartum hemorrhage: a cross-sectional study.

Acta Obstet Gynecol Scand 2013 Nov 16;92(11):1277-83. Epub 2013 Sep 16.

Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Objective: To investigate the implementation of the International Confederation of Midwives/International Federation of Gynecology and Obstetrics (ICM/FIGO) guideline on active third stage management in vaginal deliveries in daily clinical practice.

Design: Observational, cross-sectional study.

Setting: One tertiary and one teaching hospital in the Netherlands.

Population: Women undergoing vaginal deliveries.

Methods: A case record form was completed after every vaginal delivery. Primary outcome was adequate guideline adherence, defined as initial administration of 10 IU oxytocin, performance of controlled cord traction and uterine massage. Adequate guideline adherence was a priori estimated to be 10%. With a sample size of 600, i.e. 300 women per hospital, the standard error of the resulting percentage would be less than 2% for each hospital.

Results: Six hundred and twenty six women were included. Guideline adherence was adequately performed in 48% of vaginal deliveries. Oxytocin was administered after birth in 98% of deliveries and in 80% the correct dose was used. Controlled cord traction was performed in 63% and uterine massage in 93%; however, the latter was performed as advised (at least eight times) in only 8%. The amount of blood loss was not associated with the use of either 5 or 10 IU oxytocin (p = 0.818). Controlled cord traction and uterine massage were more frequently performed when blood loss exceeded 500 mL (p < 0.001).

Conclusions: Active third stage management according to the ICM/FIGO guideline is adequately performed in only 48% of all vaginal deliveries. Results of this study call for training programs to increase adherence to the ICM/FIGO guideline.
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http://dx.doi.org/10.1111/aogs.12238DOI Listing
November 2013

Acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: a 14-year cohort study.

Crit Care 2013 Jul 24;17(4):R151. Epub 2013 Jul 24.

Introduction: Newborns in need of extracorporeal membrane oxygenation (ECMO) support are at high risk of developing acute kidney injury (AKI). AKI may occur as part of multiple organ failure and can be aggravated by exposure to components of the extracorporeal circuit. AKI necessitates adjustment of dosage of renally eliminated drugs and avoidance of nephrotoxic drugs. We aimed to define systematically the incidence and clinical course of AKI in critically ill neonates receiving ECMO support.

Methods: This study reviewed prospectively collected clinical data (including age, diagnosis, ECMO course, and serum creatinine (SCr)) of all ECMO-treated neonates within our institution spanning a 14-year period. AKI was defined by using the Risk, Injury, Failure, Loss of renal function, and End-stage renal disease (RIFLE) classification. SCr data were reviewed per ECMO day and compared with age-specific SCr reference values. Accordingly, patients were assigned to RIFLE categories (Risk, Injury, or Failure as 150%, 200%, or 300% of median SCr reference values). Data are presented as median and interquartile range (IQR) or number and percentage.

Results: Of 242 patients included, 179 (74%) survived. Median age at the start of ECMO was 39 hours (IQR, 26 to 63); median ECMO duration was 5.8 days (IQR, 3.9 to 9.4). In total, 153 (64%) patients had evidence of AKI, with 72 (30%) qualifying as Risk, 55 (23%) as Injury, and 26 (11%) as Failure. At the end of the study period, only 71 (46%) patients of all 153 AKI patients improved by at least one RIFLE category. With regression analysis, it was found that nitric oxide ventilation (P = 0.04) and younger age at the start of ECMO (P = 0.004) were significant predictors of AKI. Survival until intensive care unit discharge was significantly lower for patients in the Failure category (35%) as compared with the Non-AKI (78%), Risk (82%), and Injury category (76%), with all P < 0.001, whereas no significant differences were found between the three latter RIFLE categories.

Conclusions: Two thirds of neonates receiving ECMO had AKI, with a significantly increased mortality risk for patients in the Failure category. As AKI during childhood may predispose to chronic kidney disease in adulthood, long-term monitoring of kidney function after ECMO is warranted.
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http://dx.doi.org/10.1186/cc12830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057448PMC
July 2013

Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: an observational study.

PLoS Med 2013 14;10(5):e1001444. Epub 2013 May 14.

Department of Paediatric Infectious Diseases and Immunology, Erasmus MC-Sophia, Rotterdam, The Netherlands.

Background: Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods.

Methods And Findings: This study was conducted at the Erasmus MC-Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%-25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%-20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo.

Conclusions: Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.
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http://dx.doi.org/10.1371/journal.pmed.1001444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653782PMC
October 2013

Long-term follow-up after two years of asthma treatment guided by airway responsiveness in children.

Respir Med 2013 Jul 11;107(7):981-6. Epub 2013 May 11.

HAGA Teaching Hospital/Juliana Children's Hospital, Department of Pediatric Respiratory Medicine, Sportlaan 600, 2566 MJ The Hague, The Netherlands.

Introduction: Children with persistent asthma may have diminished lung function in early adulthood. In our previous study ('CATO') we showed preservation of lung function in asthmatic children, during 2 years of treatment that was guided by airway hyperresponsiveness (AHR). The aim of the present prospective follow up study was to investigate whether the positive effect of the AHR strategy on lung function had persisted beyond the duration of the intervention study, after several years of usual care by paediatrician and general practitioner.

Methods: With a mean interval of 4.4 y after the last visit, 137 subjects (67% of the original CATO population) participated in this follow-up study. Evaluation consisted of spirometry (n = 137), a methacholine challenge test (n = 83), data on inhaled steroid treatment and asthma exacerbations (n = 137), and an asthma symptom diary during 6 weeks (n = 90).

Results: At follow-up, lung function, % symptom-free days and exacerbation rates of both treatment strategy groups was similar. The mean dose of inhaled corticosteroids had diminished from 550 μg/day at the end of CATO to 235 μg/day at follow-up. The decrease in AHR measured at the end of CATO was maintained at follow-up for both treatment strategy groups.

Conclusion: The beneficial effect on lung function of 2 years treatment guided by AHR was lost after 3-7 years of usual care. This suggests that an AHR-guided treatment strategy may need to be sustained in order to preserve lung function.
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http://dx.doi.org/10.1016/j.rmed.2013.03.008DOI Listing
July 2013

Perception of bronchoconstriction: a complementary disease marker in children with asthma.

J Asthma 2013 Aug 20;50(6):560-4. Epub 2013 May 20.

Department of Pediatrics Respiratory Medicine, Haga Hospital/Juliana Children's Hospital, The Hague, The Netherlands.

Introduction: Asthma guidelines use symptoms as the most important aspect of asthma control. Symptom perception varies widely between individuals. Over-perception as well as underperception of bronchoconstriction could have a negative effect on asthma management. We hypothesized that perception of bronchoconstriction in childhood asthma is not related to common measures of disease control. For that reason, we examined the clinical determinants of the perception of bronchoconstriction and the repeatability of perception measurements.

Patients And Methods: In school-age children with moderately severe atopic asthma, we measured the perception of bronchoconstriction (decrease in forced expiratory volume in 1 second (FEV(1)) during methacholine bronchoprovocation challenges. The perception of bronchoconstriction was assessed as the slope of the relation between FEV(1) and Borg score, and as the Borg score at a 20% decrease in FEV(1) from baseline during the provocation test (PS(20)). Data from subjects who had a 20% or more decrease in FEV(1) (n = 112) were used for the analysis. Fifty-four children repeated the test after 3 months. Symptoms, use of rescue medication, and peak expiratory flows were scored in diaries during the 2 weeks before testing.

Results: Symptom perception was significantly better in children without (PD(20) > 1570 μg, n = 28) than in children with airway hyperresponsiveness (PD(20) ≤ 1570 μg, n = 112), slope 0.22 versus 0.13 respectively (p < .001). Borg scores correlated with PD(20) (p = .01), baseline FEV(1) (only for slope, p = .04), and use of rescue beta agonist (p = .01), but not with other aspects of asthma control. Repeatability of Borg scores was good (slope: R = 0.59, PS(20): R = 0.52).

Conclusion: Poorer symptom perception in asthmatic children correlated with hyperresponsiveness, and was associated with lower baseline FEV(1) and less use of rescue bronchodilators. This suggests that the measurement of symptom perception should be taken into account in individual management plans for children with asthma.
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http://dx.doi.org/10.3109/02770903.2013.792347DOI Listing
August 2013

Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

J Allergy Clin Immunol 2013 Aug 4;132(2):353-60.e2. Epub 2013 May 4.

Institute for Medical Technology Assessment, Department of Health Economics (iMTA), Erasmus University, Rotterdam, The Netherlands.

Background: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects.

Objective: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation.

Methods: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate.

Results: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent.

Conclusion: Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance.
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http://dx.doi.org/10.1016/j.jaci.2013.03.013DOI Listing
August 2013

Chronic anal and perianal pain resolved with MRI.

AJR Am J Roentgenol 2013 May;200(5):1034-41

Department of Radiology, University Hospital Rotterdam, Rotterdam, The Netherlands.

Objective: The purpose of this study was to assess the diagnostic value of anorectal MRI in the care of patients with chronic anal and perianal pain but without findings of abnormalities in the clinical workup.

Materials And Methods: Patients referred from a tertiary department of colorectal surgery to the MRI unit with clinically occult chronic anal and perianal pain were included. MRI of the anorectum was performed with an endoanal or pelvic phased-array coil. The images from all examinations were read by two radiologists. MRI findings were correlated with clinical follow-up data.

Results: The study group (103 patients) was stratified into patients with no history of anorectal disease (n = 60) and those who had a history of surgery for anorectal disease (n = 43). MRI findings suggested the final diagnoses in 40 patients (39%). These diagnoses were 28 cases of suppurative lesions (27%), 11 cases of painful scarring of the anus (11%), and one case of metastasis to the sacrum (1%). Suppurative lesions were surgically proved with marked relief of pain after surgery. In the other patients the final diagnoses were 37 cases of levator ani syndrome (36%) and 26 cases of unspecified functional anorectal pain (25%). No MRI abnormalities were found in 33 of the patients with levator ani syndrome and 26 of the patients with unspecified anorectal pain. The two readers had very good agreement (κ = 0.92). The patients with a history of anorectal disease had significantly more MRI findings of abnormalities (60%) than did patients without a history of anorectal disease (23%). The positive predictive value of MRI was 91%, and the negative predictive value was 100%.

Conclusion: In 39% of patients, MRI showed abnormalities that were clinically confirmed as the final diagnosis. Surgical treatment will especially benefit patients with suppurative lesions, resulting in relief of pain.
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http://dx.doi.org/10.2214/AJR.12.8813DOI Listing
May 2013

Enzyme replacement therapy and fatigue in adults with Pompe disease.

Mol Genet Metab 2013 Jun 3;109(2):174-8. Epub 2013 Apr 3.

Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Background: Pompe disease is a hereditary metabolic myopathy, for which enzyme replacement therapy (ERT) has been available since 2006. We investigated whether ERT reduces fatigue in adult patients with Pompe disease.

Methods: In this prospective international observational survey, we used the Fatigue Severity Scale (FSS) to measure fatigue. Repeated measures ANOVA was used to analyze the data over time. In a subgroup of patients, we also evaluated muscle strength using the Medical Research Council Scale, measured pulmonary function as Forced Vital Capacity, and assessed depression using the Hospital Anxiety and Depression Scale.

Results: We followed 163 patients for a median period of 4 years before ERT and for 3 years during ERT. Before ERT, the mean FSS score remained stable at around 5.3 score points; during ERT, scores improved significantly by 0.13 score points per year (p < 0.001). Fatigue decreased mainly in women, in older patients and in those with shorter disease duration. Patients' improvements in fatigue were moderately correlated with the effect of ERT on depression (r 0.55; CI 95% 0.07 to 0.70) but not with the effect of ERT on muscle strength or pulmonary function.

Conclusions: Fatigue is a common and disabling problem in patients with early and advanced stages of Pompe disease. Our finding that ERT helps to reduce fatigue is therefore important for this patient population, irrespective of the mechanisms underlying this effect.
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http://dx.doi.org/10.1016/j.ymgme.2013.03.016DOI Listing
June 2013

Small-airways deposition of dornase alfa in children with asthma and persistent airway obstruction.

J Allergy Clin Immunol 2013 Aug 28;132(2):482-5.e10. Epub 2013 Mar 28.

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http://dx.doi.org/10.1016/j.jaci.2013.02.006DOI Listing
August 2013

Up to five years experience with 11 mucopolysaccharidosis type VI patients.

Mol Genet Metab 2013 May 4;109(1):70-6. Epub 2013 Mar 4.

Erasmus MC Center for Lysosomal and Metabolic Diseases, Sophia's Children's Hospital, Rotterdam, The Netherlands.

Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is a rare progressive metabolic disorder characterized by coarse facial features, hepatosplenomegaly, restrictive pulmonary function, cardiac abnormalities and stiff joints. The disease is caused by a deficiency of the lysosomal enzyme N-acetyl galactosamine 4-sulfatase which leads to glycosaminoglycan (GAG) storage in various tissues. It presents as a clinical spectrum with varying disease progressions and severities. While the phases I/II/III studies proved the effectiveness of enzyme-replacement therapy (ERT) with recombinant human arylsulfatase B, long-term data are still scarce. Over treatment periods ranging from 1.3 to 5.4 years, this prospective open-label follow-up study in 11 Dutch mucopolysaccharidosis type VI patients (age 2-18 years) showed that ERT had significant positive effects on cardiac-wall diameters (IVSd and LVMI), left and right shoulder flexions (p<0.001), liver size and spleen size (p<0.001), urinary GAG excretion (p<0.001), and the scales of quality of life (motor functioning and body functioning). ERT did not affect cardiac valve regurgitation or hearing function; HRQoL decreased slightly in two domains ('anxiety' and 'negative emotions'), and patients with the rapid and slow progressive forms of the disease differed with regard to baseline GAG excretion and GAG decrease during treatment. In conclusion, ERT had an effect on several clinical parameters. This effect was established in an open cohort of young mucopolysaccharidosis type VI patients.
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http://dx.doi.org/10.1016/j.ymgme.2013.02.013DOI Listing
May 2013

A comparative assessment of surgeons' tracking methods for surgical site infections.

Surg Infect (Larchmt) 2013 Apr 13;14(2):181-7. Epub 2013 Mar 13.

Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: The incidence of surgical site infections (SSI) is considered increasingly to be an indicator of quality of care. We conducted a study in which daily inspection of the surgical incision was performed by an independent, trained team to monitor the incidence of SSI using U.S. Centers for Disease Control and Prevention (CDC) definitions, as a gold-standard measure of care. In the department of surgery, two registration systems for SSI were used routinely by the surgeon: An electronic and a plenary tracking system. The results of the independent team were compared with the outcomes provided by two registration systems for SSI, so as to evaluate the reliability of these systems as a possible alternative for indicating quality of care.

Methods: The study was an incidence study conducted from May 2007 to January 2009 that included 1,000 adult patients scheduled to undergo open abdominal surgery in an academic teaching hospital. Surgical incisions were inspected daily to check for SSI according to definitions of health care-associated infections established by the CDC. Follow-up after discharge was done at the outpatient clinic of the hospital by telephone or letter in combination with patient diaries and reviews of patient charts, discharge letters, electronic files, and reported complications. Univariate and multivariable analyses were done to identify putative risk factors for missing registrations.

Results: Of the 1,000 patients in the study, 33 were not evaluated. Surgical site infections were diagnosed in 26.8% of the 967 remaining patients, of which 18.0% were superficial incisional infections, 5.4% were deep incisional infections, and 3.4% were organ/space infections. More than 60% of SSIs were unreported in either of the department's two tracking systems for such infections. For these two systems, independent major risk factors for missing registrations were (1) the lack of occurrence of an SSI, (2) transplantation surgery, and (3) admission to non-surgical departments.

Conclusions: Most SSIs were not tracked with the department's two systems. These systems proved poor alternatives to the gold-standard method of quantifying the incidence of Surgical Site Infection SSI and, therefore, the quality of care. Both protocolized wound assessment and on-site documentation are mandatory for realistic quantification of the incidence of SSI.
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http://dx.doi.org/10.1089/sur.2012.045DOI Listing
April 2013

Reply to letter: "End-to-end versus end-to-side esophagogastrostomy after esophageal cancer resection: a prospective randomized study".

Ann Surg 2014 Jan;259(1):e7

Department of Surgery Erasmus University Medical Centre Rotterdam's-Gravendijkwal 230, Rotterdam 3015 CE, The Netherlands

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http://dx.doi.org/10.1097/SLA.0b013e31827b9d21DOI Listing
January 2014

Urinary eosinophil protein X in childhood asthma: relation with changes in disease control and eosinophilic airway inflammation.

Mediators Inflamm 2013 15;2013:532619. Epub 2013 Jan 15.

Department of Pediatric Respiratory Medicine, Juliana Children's Hospital, HAGA Teaching Hospital, P.O. Box 60605, 2506 LP, The Hague, The Netherlands.

The aim of this study was to assess cross-sectional and longitudinal correlations between uEPX and other markers of asthma control and eosinophilic airway inflammation. Methods. We measured uEPX at baseline, after 1 year and after 2 years in 205 atopic asthmatic children using inhaled fluticasone. At the same time points, we assessed symptom scores (2 weeks diary card), lung function (forced expiratory volume in one second (FEV(1))), airway hyperresponsiveness (AHR), and percentage eosinophils in induced sputum (% eos). Results. We found negative correlations between uEPX and FEV(1) at baseline (r = -0.18, P = 0.01), after 1 year (r = -0.25, P < 0.01) and after 2 years (r = -0.21, P = 0.02). Within-patient changes of uEPX showed a negative association with FEV(1) changes (at 1 year: r = -0.24, P = 0.01; at 2 years: r = -0.21, P = 0.03). Within-patient changes from baseline of uEPX correlated with changes in % eos. No relations were found between uEPX and symptoms. Conclusion. In this population of children with atopic asthma, uEPX correlated with FEV(1) and % eos, and within-subjects changes in uEPX correlated with changes in FEV(1) and % eos. As the associations were weak and the scatter of uEPX wide, it seems unlikely that uEPX will be useful as a biomarker for monitoring asthma control in the individual child.
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http://dx.doi.org/10.1155/2013/532619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557635PMC
August 2013

Orbital aspects following monobloc advancement in syndromic craniosynostosis.

J Craniomaxillofac Surg 2013 Oct 24;41(7):e146-53. Epub 2013 Jan 24.

Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center Rotterdam, Netherlands. Electronic address:

The monobloc advancement with distraction is a treatment modality for syndromic craniosynostosis, to correct exorbitism, upper airway compromise and malocclusion. In this report orbital volume and movements of (peri-)orbital structures and globes of seven patients following monobloc distraction are evaluated. In preoperative and postoperative CT-scans orbital volume was assessed and a 3D coordinate system with eleven landmarks was used to measure the movements of orbital structures and globes and to measure the change of exorbitism. Correlation between orbital volume, movements of the orbital structures and change in exorbitism was studied. The orbital volume increased by 49.9% (left) and 50.4% (right). The average anterior movement of the bone was 13.6 mm (left) and 13.9 mm (right). The mean anterior movement of the left globe was 5.8 mm and of the right globe 5.3 mm. The ratio of globe/bone movement was 0.4. Exorbitism decreased with 7.8 mm (left) and 8.1 mm (right). Differences between left and right for orbital volume, for movements and for the decrease in exorbitism were not significant. Volume enlargement and decrease in exorbitism were correlated (p ≤ 0.05). Following monobloc advancement orbital volume increases, (peri-)orbital structures and the globe move forward and exorbitism diminishes.
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http://dx.doi.org/10.1016/j.jcms.2012.12.002DOI Listing
October 2013

Gonadal function recovery in very long-term male survivors of childhood cancer.

Eur J Cancer 2013 Apr 5;49(6):1280-6. Epub 2013 Jan 5.

Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.

Background: Although gonadal toxicity has been reported, no data are available on recovery of gonadal function in very long-term survivors of childhood cancer. Inhibin B is a novel reliable serum marker which has been shown to be of value in childhood cancer survivor studies to identify risk groups for impaired gonadal function, but consecutive long-term follow-up studies using serum inhibin B as a marker are not available.

Objective: To evaluate possible recovery of gonadal dysfunction over time in adult male survivors of childhood cancer.

Methods: In this retrospective study, adult male long-term childhood cancer survivors (n=201) who visited our outpatient late effects clinic were included and we used inhibin B as a surrogate marker for gonadal function.

Results: Median age at diagnosis was 5.9 years (range 0.0-17.5) and discontinuation of treatment was reached at a median age of 8.2 years (range 0.0-20.8). Inhibin B levels were first measured after a median follow-up time of 15.7 years (range 3.0-37.0). Median interval between the first (T1) and second measurement (T2) was 3.3 years (range 0.7-11.3). Median inhibin B level was 127 ng/L (range 5-366) at T1 and 155 ng/L (range 10-507) at T2. The prediction model suggests that inhibin B levels do not normalise in survivors with a very low Inhibin B level at T1.

Conclusions: Our results suggest that recovery of gonadal function is possible even long after discontinuation of treatment. However, this recovery does not seem to occur in survivors who already reached critically low inhibin B levels after discontinuation of treatment.
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http://dx.doi.org/10.1016/j.ejca.2012.12.007DOI Listing
April 2013

Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome.

J Am Soc Nephrol 2013 Jan;24(1):149-59

Department of Pediatrics, Division of Nephrology, Erasmus University Medical Centre—Sophia Children’s Hospital, Rotterdam, The Netherlands.

Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo (n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months. Both groups received equal cumulative doses of prednisolone (approximately 3360 mg/m(2)). Among the 126 children who started trial medication, relapses occurred in 48 (77%) of 62 patients who received 3 months of prednisolone and 51 (80%) of 64 patients who received 6 months of prednisolone. Frequent relapses, according to international criteria, occurred with similar frequency between groups as well (45% versus 50%). In addition, there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and/or other immunosuppressive therapy (50% versus 59%), steroid dependence, or adverse effects. In conclusion, in this trial, extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not benefit clinical outcome in children with nephrotic syndrome. Previous findings indicating that prolonged treatment regimens reduce relapses most likely resulted from increased cumulative dose rather than the treatment duration.
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http://dx.doi.org/10.1681/ASN.2012070646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537218PMC
January 2013

Respiratory morbidity and growth after open thoracotomy or thoracoscopic repair of esophageal atresia.

J Pediatr Surg 2012 Nov;47(11):1975-83

Intensive Care and Department of Pediatric Surgery, Erasmus Medical Centre/Sophia Children's Hospital, Rotterdam, The Netherlands.

Background: Respiratory morbidity has been described in patients who underwent repair of esophageal atresia as a neonate. We compared the influence of open thoracotomy or thoracoscopy on lung function, respiratory symptoms, and growth.

Methods: Functional residual capacity (FRC(p)), indicative of lung volume, and maximal expiratory flow at functional residual capacity (V'max(FRC)), indicative of airway patency, of 37 infants operated for esophageal atresia were measured with Masterscreen Babybody at 6 and 12 months. SD scores were calculated for V'max(FRC).

Results: Repair was by thoracotomy in 21 cases (57%) and by thoracoscopy in 16 cases (43%). Lung function parameters did not differ between the types of surgery (FRC(p); P = .384 and V'max(FRC); P = .241). FRC(p) values were in the upper normal range and increased from 6 to 12 months (22.5 and 25.4 mL/kg respectively, P = .010). Mean (SD) V'max(FRC) was below the norm without significant change in SD scores from 6 to 12 months (-1.9 and -2.3, respectively, P = .248). Neither lung function nor type of repair was associated with clinical evolution up to 2 years.

Conclusion: Lung function during the first year was similar in EA infants repaired by thoracotomy or thoracoscopy. Ongoing follow-up including pulmonary function testing is needed to determine whether differences occur at a later age in this cohort.
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http://dx.doi.org/10.1016/j.jpedsurg.2012.07.044DOI Listing
November 2012