Eppo B. Wolvius

The Generation R Study: Biobank update 2015

The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. In total, 9,778 mothers were enrolled in the study. Data collection in children and their parents include questionnaires, interviews, detailed physical and ultrasound examinations, behavioural observations, Magnetic Resonance Imaging and biological samples. Efforts have been conducted for collecting biological samples including blood, hair, faeces, nasal swabs, saliva and urine samples and generating genomics data on DNA, RNA and microbiome. In this paper, we give an update of the collection, processing and storage of these biological samples and available measures. Together with detailed phenotype measurements, these biological samples provide a unique resource for epidemiological studies focused on environmental exposures, genetic and genomic determinants and their interactions in relation to growth, health and development from fetal life onwards.

Long-term functional outcome in 167 patients with syndromic craniosynostosis; defining a syndrome-specific risk profile

OBJECTIVE Little is known about the long-term prevalence of elevated intracranial pressure (ICP), obstructive sleep apnoea (OSA), level of education, language and motor skills, impaired sight and hearing in craniosynostosis syndromes. The objective of this study was to define the prevalence per syndrome of elevated ICP, OSA, impaired sight and impaired hearing. METHODS A retrospective study was undertaken on 167 consecutive patients diagnosed with Apert, Crouzon, Pfeiffer, Muenke or Saethre-Chotzen syndrome, aged 1-25 years and treated between 1983 and 2008. The mean age at time of referral and review was 1 years and 2 months and 10 years and 3 months, respectively. RESULTS Patients with Apert and Crouzon/Pfeiffer syndromes had the highest prevalence of elevated ICP (33% and 53%, respectively) and OSA (31% and 27%, respectively), while Saethre-Chotzen syndrome was also associated with a fair risk for elevated ICP (21%). The prevalence of impaired sight (61%) and hearing (56%) was high in all syndromes. CONCLUSION Based on these data, a syndrome-specific risk profile with suggestions for screening and treatment is presented.

Stability, tipping and relapse of bone-borne versus tooth-borne surgically assisted rapid maxillary expansion; a prospective randomized patient trial

This study evaluated stability, tipping and relapse after surgically assisted rapid maxillary expansion (SARME), comparing bone-borne and tooth-borne devices, in skeletally matured non-syndromal patients with transverse maxillary hypoplasia. The study is a randomized, open-label, clinical trial. Patients were randomized to bone-borne (n=25) and tooth-borne (n=21) groups. The surgical technique for corticotomy was the same in both groups. Expansion was performed using a bone-borne or tooth-borne device. Dental study casts, lateral and postero-anterior cephalograms were taken before treatment, after the distraction phase and at 12-month follow up. Stability, segmental maxillary tipping and relapse were studied. 23 bone-borne and 19 tooth-borne patients were analyzed. There were no significant differences between the two groups. Widening was comparable at canine, premolar and molar level. Relapse was not significant and at follow up the significant increase in distance was sustained. A significant increase in palatal width, at premolar and molar level, occurred in both groups. The maxilla moves slightly downward in SARME. Segmental maxillary tipping occurred in both groups and did not affect relapse. There is no significant difference between the two groups. In SARME, the widening achieved at dental level is stable after 12 months. Over-correction is not necessary. Tipping of the maxillary segments and increases in the retention period are equal in both groups.

Advancement of the midface, from conventional Le Fort III osteotomy to Le Fort III distraction: review of the literature

Since its introduction in about 1950, the Le Fort III (LF III) procedure has become a widely accepted treatment for correction of midface hypoplasia and related functional and esthetic problems. As long-term surgical experience grows and improvements are made in technique, equipment and peri-operative care, the number of LF III procedures performed worldwide is increasing. A number of fundamental questions concerning the technique remain unclear, and large, conclusive studies are lacking owing to the relative rarity of severe midface hypoplasia. This literature review aims to address problems, such as the indication field, timing of surgery, rate of relapse and the use of distraction osteogenesis. An overview of the history and technique of LF III osteotomy and distraction is provided, together with a comprehensive review of the available clinical data.

Obstructive sleep apnea in children with syndromic craniosynostosis: long-term respiratory outcome of midface advancement

Almost 50% of patients with Apert, Crouzon or Pfeiffer syndrome develop obstructive sleep apnea (OSA), mainly due to midface hypoplasia. Midface advancement is often the treatment of choice, but the few papers on long-term outcome report mixed results. This paper aimed to assess the long-term respiratory outcome of midface advancement in syndromic craniosynostosis with OSA and to determine factors contributing to its efficacy. A retrospective study was performed on 11 patients with moderate or severe OSA, requiring oxygen, continuous positive airway pressure (CPAP), or tracheostomy. Clinical symptoms, results of polysomnography, endoscopy and digital volume measurement of the upper airways on CT scan before and after midface advancement were reviewed. Midface advancement had a good respiratory outcome in the short term in 6 patients and was ineffective in 5. In all patients without respiratory effect or with relapse, endoscopy showed obstruction of the rhino- or hypopharynx. The volume measurements supported the clinical and endoscopic outcome. Despite midface advancement, long-term dependence on, or indication for, CPAP or tracheostomy was maintained in 5 of 11 patients. Pharyngeal collapse appeared to play a role in OSA. Endoscopy before midface advancement is recommended to identify airway obstruction that may interfere with respiratory improvement after midface advancement.

How does obstructive sleep apnoea evolve in syndromic craniosynostosis? A prospective cohort study

Objective To describe the course of obstructive sleep apnoea syndrome (OSAS) in children with syndromic craniosynostosis. Design Prospective cohort study. Setting Dutch Craniofacial Centre from January 2007 to January 2012. Patients A total of 97 children with syndromic craniosynostosis underwent level III sleep study. Patients generally undergo cranial vault remodelling during their first year of life, but OSAS treatment only on indication. Main outcome measures Obstructive apnoea-hypopnoea index, the central apnoea index and haemoglobin oxygenation-desaturation index derived from consecutive sleep studies. Results The overall prevalence of OSAS in syndromic craniosynostosis was 68% as defined by level III sleep study. Twenty-three patients were treated for OSAS. Longitudinal profiles were computed for 80 untreated patients using 241 sleep studies. A mixed effects model showed higher values for the patients with midface hypoplasia as compared to those without midface hypoplasia (Omnibus likelihood ratio test=7.9). In paired measurements, the obstructive apnoea-hypopnoea index (Z=−3.4) significantly decreased over time, especially in the first years of life (Z=−3.3), but not in patients with midface hypoplasia (Z=−1.5). No patient developed severe OSAS during follow-up if it was not yet diagnosed during the first sleep study. Conclusions OSAS is highly prevalent in syndromic craniosynostosis. There is some natural improvement, mainly during the first 3 years of life and least in children with Apert or Crouzon/Pfeiffer syndrome. In the absence of other co-morbid risk factors, it is highly unlikely that if severe OSAS is not present early in life it will develop during childhood. Ongoing clinical surveillance is of great importance and continuous monitoring for the development of other co-morbid risk factors for OSAS should be warranted.

Discrimination between oral cancer and healthy tissue based on water content determined by Raman spectroscopy.

Tumor-positive resection margins are a major problem in oral cancer surgery. High-wavenumber Raman spectroscopy is a reliable technique to determine the water content of tissues, which may contribute to differentiate between tumor and healthy tissue. The aim of this study was to examine the use of Raman spectroscopy to differentiate tumor from surrounding healthy tissue in oral squamous cell carcinoma. From 14 patients undergoing tongue resection for squamous cell carcinoma, the water content was determined at 170 locations on freshly excised tongue specimens using the Raman bands of the OH-stretching vibrations (3350-3550 cm(-1)) and of the CH-stretching vibrations (2910-2965 cm(-1)). The results were correlated with histopathological assessment of hematoxylin and eosin stained thin tissue sections obtained from the Raman measurement locations. The water content values from squamous cell carcinoma measurements were significantly higher than from surrounding healthy tissue (p-value < 0.0001). Tumor tissue could be detected with a sensitivity of 99% and a specificity of 92% using a cutoff water content value of 69%. Because the Raman measurements are fast and can be carried out on freshly excised tissue without any tissue preparation, this finding signifies an important step toward the development of an intraoperative tool for tumor resection guidance with the aim of enabling oncological radical surgery and improvement of patient outcome.

Hyperbaric oxygen therapy in the management of radiation-induced injury in the head and neck region: a review of the literature.

PURPOSE Radiotherapy is generally used in the treatment of malignant tumors in the head and neck region. It causes a hypoxic, hypocellular, and hypovascular environment that leads to injury to surrounding normal tissue, both acute and chronic, ranging from xerostomia to osteoradionecrosis. These side effects are debilitating and greatly influence quality of life in these patients. Hyperbaric oxygen (HBO) therapy is clinically used to prevent or treat these side effects by enhancing oxygen pressure and thereby regeneration. Although this therapy is widely applied, its mechanism of action is still poorly understood, and controversy exists in the literature about its clinical use. This review therefore aims to analyze the existing experimental and clinical research on this topic. MATERIALS AND METHODS A systematic search was performed in PubMed for experimental and clinical studies conducted regarding the use of HBO therapy in previously irradiated tissue, in the period from January 1990 to June 2009. RESULTS Experimental research is scarce, and clinical studies are especially lacking in terms of randomized controlled studies. Although discussions on the subject are ongoing, most studies suggest a beneficial role for HBO in previously irradiated tissue. CONCLUSION Further research, both experimental and clinical, is necessary to unravel the working mechanism of HBO therapy and validate its clinical use.

Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause

This cohort study in 35 patients (13 children) evaluates the prevalence, severity and anatomical cause of obstructive sleep apnoea syndrome (OSAS) in patients with Treacher Collins syndrome. Ambulatory polysomnography was performed cross-sectionally to determine OSAS prevalence and severity. All upper airway related surgical interventions were evaluated retrospectively. In 11 patients, sleep endoscopy, and flexible and rigid endoscopy were applied to determine the level of anatomical obstruction of the upper airway. The overall prevalence of OSAS in Treacher Collins patients was 46% (54% in children; 41% in adults). Thirty-eight upper airway related surgical interventions were performed in 17 patients. Examination of the upper airway revealed various anatomical levels of obstruction, from the nasal septum to the trachea. Most significant obstruction was found at the level of the oro/hypopharynx. OSAS in Treacher Collins patients is an important problem so all patients should be screened for OSAS by polysomnography. Endoscopy of the upper airways was helpful in determining the level of obstruction. Surgical treatment at one level will not resolve OSAS in most patients because OSAS in Treacher Collins has a multilevel origin. Non-invasive ventilation (continuous positive airway pressure or bilevel positive airway pressure) or tracheotomy should be considered as a treatment modality.

Mandibular reconstruction in the growing patient with unilateral craniofacial microsomia: a systematic review

The purpose of this systematic review is to provide an overview of the surgical correction of the mandible in unilateral craniofacial microsomia (UCM) performed in the growing patient, and its long-term outcome and stability. The following databases were searched: PubMed, Embase, Cochrane, and Web of Science. Articles reporting prospective and retrospective studies of patients not older than 16 years (N ≥ 4) who had undergone surgical correction of a craniofacial microsomia spectrum condition using grafts, osteotomies, distraction, or combinations of these, were reviewed. The period of follow-up was selected to be ≥1 year. After inclusion, the articles were evaluated on short- and long-term outcomes, relapse, and any increase in asymmetry following treatment. Thirty of 1611 articles were included in the qualitative synthesis. Analysis of the surgical mandibular correction of UCM showed that the outcome is not so much treatment-dependent, but patient-dependent, i.e. deformity gradation-dependent. The type I-IIa Pruzansky-Kaban patient had the best results with regard to minimal relapse and/or minimal increase in asymmetry. Single-stage correction of the asymmetry should be postponed until the permanent dentition stage. It can be concluded that in the treatment of the severely hypoplastic mandible, the patient will benefit from a multi-stage treatment protocol if indicated for functional or psychological problems.