Parents' Perception of the Benefit of Receiving a Patient Information Leaflet Prior to Attending a Craniofacial Multidisciplinary Team Appointment.

OBJECTIVE: To investigate how a patient information leaflet describing what to expect during a craniofacial multidisciplinary team (MDT) appointment is experienced by parents of children with craniofacial anomalies (CFAs) and whether it helps with preparation for the appointment. DESIGN: Combination of qualitative and quantitative design. SETTING: Norwegian National Unit for Craniofacial Surgery. PARTICIPANTS: Thirty-three parents of children with CFAs completed the questionnaire and fourteen were subsequently interviewed. INTERVENTIONS: A patient information leaflet, sent to all parents before their MDT appointment. MAIN OUTCOME MEASURES: Descriptive questionnaire data and interview data. RESULTS: All parents (N = 33, 100%) found the leaflet easy to understand, while 31 (93.9%) found it provided helpful information. However, many first-time attendees still found the MDT setting overwhelming. CONCLUSIONS: A leaflet may be helpful for parents when preparing for their child's MDT appointment. However, some parents may need additional support and information related to their child's treatment pathway.

Long-term outcome of patients treated for craniopharyngioma: a single center experience.

PURPOSE: Treatment of craniopharyngiomas (CP) is challenging due to their proximity to critical neural structures, risk of serious complications and impaired quality of life after treatment. Recurrences may occur many years after surgical resection. However, long-term outcome data are still scarce. The purpose of this retrospective study was therefore to assess the long-term results after treatment of patients with CP. MATERIAL AND METHOD: Patients surgically treated for a histologically verified CP at Oslo University Hospital between 1992 and 2015 and with at least a 5-year follow-up were included. Patients' medical records and radiological studies were reviewed. RESULTS: Sixty-one patients (mean age 35.8 ± 22.2 years) were included; 18 patients (30%) were children <18 years of age. The incidence for the study period and the referral population was 1.1 cases/million/year, with trimodal peak incidence at 6, 32 and 59 years of age. The commonest presenting symptoms were visual disturbances (62%), headache (43%) and endocrine dysfunction (34%). The transcranial approach was utilized in 79% of patients. Gross total resection (GTR) was achieved in 59%. The surgical complication rate was 20%. Three patients (5%) received radiotherapy or radiosurgery after primary resection. The mean follow-up was 139 ± 76 months, with no patients lost to follow-up. Postoperatively, 59% of patients had panhypopituitarism and 56% diabetes insipidus. Eighteen patients (30%) developed tumour recurrence after a mean follow-up of 26 ± 25 months. The 10-year overall survival (OS) rate was 75%, whereas the disease-specific survival (DSS) rate was 84%, and recurrence-free survival (RFS) 61%. Subtotal resection (STR) (p = .01) and systemic comorbidity (p = .002) were associated with worse DSS. CONCLUSION: Surgical treatment of CP, even though combined with adjuvant radiotherapy in only selected cases, provides good long-time OS and DSS, and relatively good functional outcome in long-term survivors despite postoperative morbidity, particularly endocrine dysfunction. Systemic comorbidity and STR are individual negative prognostic factors.

Intraoperative DNA methylation classification of brain tumors impacts neurosurgical strategy.

BACKGROUND: Brain tumor surgery must balance the benefit of maximal resection against the risk of inflicting severe damage. The impact of increased resection is diagnosis-specific. However, the precise diagnosis is typically uncertain at surgery due to limitations of imaging and intraoperative histomorphological methods. Novel and accurate strategies for brain tumor classification are necessary to support personalized intraoperative neurosurgical treatment decisions. Here, we describe a fast and cost-efficient workflow for intraoperative classification of brain tumors based on DNA methylation profiles generated by low coverage nanopore sequencing and machine learning algorithms. METHODS: We evaluated 6 independent cohorts containing 105 patients, including 50 pediatric and 55 adult patients. Ultra-low coverage whole-genome sequencing was performed on nanopore flow cells. Data were analyzed using copy number variation and ad hoc random forest classifier for the genome-wide methylation-based classification of the tumor. RESULTS: Concordant classification was obtained between nanopore DNA methylation analysis and a full neuropathological evaluation in 93 of 105 (89%) cases. The analysis demonstrated correct diagnosis in 6/6 cases where frozen section evaluation was inconclusive. Results could be returned to the operating room at a median of 97 min (range 91-161 min). Precise classification of the tumor entity and subtype would have supported modification of the surgical strategy in 12 out of 20 patients evaluated intraoperatively. CONCLUSION: Intraoperative nanopore sequencing combined with machine learning diagnostics was robust, sensitive, and rapid. This strategy allowed DNA methylation-based classification of the tumor to be returned to the surgeon within a timeframe that supports intraoperative decision making.

The role of pulsatile and static intracranial pressure measurements in the management of children with craniosynostosis-an institutional experience from 49 patients.

BACKGROUND: Although measurement of intracranial pressure (ICP) has occasionally been utilized in children with craniosynostosis (CSS), data on parameters of pulsatile ICP in CSS are still lacking, and the role of pulsatile ICP measurements in the management of CSS is not well established. METHODS: From our department's database, we retrieved the data from children in whom the measurement of static and pulsatile ICP was a part of the diagnostic work-up in different clinical situations related to CSS. Both clinical and ICP data were retrospectively reviewed and analyzed. RESULTS: We identified 49 children with CSS, median age 4.4 years (range 0.2-18.9), in whom a total of 67 diagnostic ICP measurements were undertaken between 2002 and 2014. The CSS was syndromal in 23 cases. The rationale for ICP measurement was a question of indication for cranial vault expansion surgery (CVES) in 12 patients (Group 1), of its timing in 10 patients (Group 2), of suspected abnormally elevated ICP or hydrocephalus in 11 patients (Group 3), of indication for repeated CVES in 13 patients (Group 4), or shunt dysfunction in three patients (Group 5). The average mean ICP for the whole cohort was 15.1 ± 5.5 mmHg and mean wave amplitude (MWA) 5.3 ± 2.2 mmHg. There was no significant difference in ICP parameters when compared between Groups 1-5. Fundoscopy revealed papilledema in five out of 32 children (15.6%). There were significantly higher parameters of pulsatile ICP (MWA) in patients with papilledema, but no statistically significant difference in parameters of static ICP. CONCLUSIONS: In this cohort of pediatric patients with CSS presenting with various diagnostic challenges, we found the diagnostic measurement of static and pulsatile ICP useful in selecting the optimal treatment modality and timing of surgery. Papilledema was associated with elevated pulsatile ICP, a parameter that in previous studies has been shown to correlate with impaired intracranial compliance.

Epidemiology of craniosynostosis in Norway.

OBJECTIVE: The authors present population-based epidemiological data for craniosynostosis regarding incidence, age at diagnosis, sex differences, and frequency of syndromic and familial cases. METHODS: The prospective registry of the Norwegian National Unit for Craniofacial Surgery was used to retrieve data on all individuals with craniosynostosis treated between 2003 and 2017. The cohort was divided into three 5-year groups based on year of birth: 2003-2007, 2008-2012, and 2013-2017. RESULTS: The authors identified 386 individuals with craniosynostosis. Of these, 328 (85%) consented to be registered with further information. The incidence increased significantly during the study period and was 5.5 per 10,000 live births (1/1800) in the last 5-year period. The increase was seen almost exclusively in the nonsyndromic group. Syndromic craniosynostosis accounted for 27% of the cases, and the incidence remained stable throughout the three 5-year periods. Both syndromic and nonsyndromic craniosynostosis were highly suture specific. There was a male preponderance (male/female ratio 2:1), and males accounted for 75% of the individuals with midline synostosis. Overall, 9.5% were index individuals in families with more than one affected member; of these, 73% were nonsyndromic cases. CONCLUSIONS: The incidence of craniosynostosis increased during the study period, and the observed incidence is among the highest reported. The authors attribute this to increasing awareness among healthcare professionals. The number of syndromic cases was high, likely due to a broader definition compared to the majority of earlier reports. The study revealed a high number of familial cases in both syndromic and nonsyndromic craniosynostosis, thus highlighting the importance of genetics as an underlying cause of craniosynostosis.

Medical Stress Reactions and Personal Growth in Parents of Children With a Rare Craniofacial Condition.

BACKGROUND: The birth of a child with a congenital craniofacial anomaly (CFA) can have a profound psychological impact on the family. Despite the complexity and variability in treatment for these rare conditions, few studies have been conducted into parents' emotional responses to health-care experiences. The aim of the present study was to investigate parents' subjective experiences of their child's condition and treatment using an in-depth qualitative approach. METHODS: Individual semistructured interviews were conducted in person or over the telephone with 48 parents of children with a range of rare CFAs. Interviews were transcribed verbatim, translated into English, and analyzed using inductive thematic analysis. RESULTS: Participants reported physical and psychological symptoms that could be indicative of medical traumatic stress in relation to their child's diagnosis and treatment. Participants described feelings of powerlessness and the weight of being responsible for their child's care. Yet, participants also reported that as a result of their experiences, their perspective on life had changed and they had grown in self-confidence. CONCLUSIONS: The findings provide insight into the complex physical and psychological effects experienced by parents in response to their child's diagnosis and medical treatment, as well as an understanding of how these experiences may also result in personal growth over time. Implementation of trauma-informed evidence-based resources should be considered in craniofacial care and future research, particularly in regard to prevention and treatment of psychological distress.

Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival.

BACKGROUND: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. MATERIAL AND METHODS: Data from patients aged 0-20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. RESULTS: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P =  0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P =  0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P =  0.048). CONCLUSION: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

Intracranial volume versus static and pulsatile intracranial pressure values in children with craniosynostosis.

OBJECTIVE: Reduced intracranial volume (ICV) and raised intracranial pressure (ICP) are assumed to be principal pathophysiological mechanisms in childhood craniosynostosis. This study examined the association between ICV and ICP and whether ICV can be used to estimate the ICP. METHODS: The authors analyzed ICV and ICP measurements from children with craniosynostosis without concurrent hydrocephalus and from age-matched individuals without craniosynostosis who underwent diagnostic ICP measurement. RESULTS: The study included 19 children with craniosynostosis (mean age 2.2 ± 1.9 years) and 12 reference individuals without craniosynostosis (mean age 2.5 ± 1.6 years). There was no difference in ICV between the patient and reference cohorts. Both mean ICP (17.1 ± 5.6 mm Hg) and mean wave amplitude (5.9 ± 2.6 mm Hg) were higher in the patient cohort. The results disclosed no significant association between ICV and ICP values in the patient or reference cohorts, and no association was seen between change in ICV and ICP values after cranial vault expansion surgery (CVES) in 5 children in whom ICV and ICP were measured before and after CVES. CONCLUSIONS: In this cohort of children with craniosynostosis, there was no significant association between ICV and ICP values prior to CVES and no significant association between change in ICV and ICP values after CVES in a subset of patients. Therefore, ICV could not reliably estimate the ICP values. The authors suggest that intracranial hypertension in childhood craniosynostosis may not be caused by reduced ICV alone but rather by a distorted relationship between ICV and the volume of intracranial content (brain tissue, CSF, and blood).

Abnormally wide eustachian tubes involving the sphenoid bone: A collection.

OBJECTIVES: To present nine patients with an abnormal widened bony Eustachian tube running anteriorly in the skull base through the sphenoid bone. METHODS: Patients with a particular anomaly in the bony Eustachian tube incidentally found on CT examinations were registered consecutively over a period of four years. RESULTS: Nine patients had the anomaly, eight unilaterally and one bilaterally. All our patients had additional anomalies involving the outer, middle, and/or inner ear. CONCLUSION: The consequences of this anomaly remain unknown, but the presence of the widened, bony ET should increase the awareness for complex temporal bone deformities and vice versa. LEVEL OF EVIDENCE: 4.

Outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) - a retrospective analysis spanning 40 years of treatment.

BACKGROUND: Medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor of the central nervous system (CNS-PNET) are among the most common pediatric brain tumors. The diagnosis, treatment, and outcome of MB/CNS-PNET patients treated during the last four decades at Oslo University Hospital (OUH) are described. MATERIAL AND METHODS: All patients younger than 20 years of age diagnosed and treated for MB/CNS-PNET at OUH between 1 January 1974 and 31 December 2013 were identified. RESULTS: We found 175 patients. In 13 of them, the diagnosis was changed upon histopathological review and in 4 patients part of the treatment was administered at other hospitals. Thus, 158 patients were included for further analysis. Eight patients did not receive adjuvant therapy because of a dismal clinical condition. The overall 5-year survival rate for MB and CNS-PNET was 54%, for MB 57%, and for CNS-PNET 41%. Gross total resection (GTR) was achieved in 118 patients and 5-year overall survival for patients with GTR versus those with non-GTR differed significantly with 64% versus 22%. Cytological examination of the cerebrospinal fluid was performed in 52 patients. A total of 126 patients received radiotherapy as part of the primary treatment and 24 did not due to young age. Median time from surgery to start of radiotherapy was 33 days. Duration of radiotherapy was more than 48 days in 22% of patients. At the time of analysis, 63 patients were alive and disease-free, one alive with disease, and 94 patients were deceased; 84 of these due to MB/CNS-PNET and 10 due to supposed late effects from the treatment. CONCLUSIONS: Survival was comparable to data from other population-based studies. The importance of GTR for survival was corroborated. Reporting real-world data remains crucial to know the true outcome of patients treated outside clinical trials.

Cerebrospinal fluid (CSF) shunting and ventriculocisternostomy (ETV) in 400 pediatric patients. Shifts in understanding, diagnostics, case-mix, and surgical management during half a century.

OBJECTIVE: To characterize shifts from the 1960s to the first decade in the 21st century as to diagnostics, case-mix, and surgical management of pediatric patients undergoing permanent CSF diversion procedures. METHODS: One hundred and thirty-four patients below 15 years of age were the first time treated with CSF shunt or ETV for hydrocephalus or idiopathic intracranial hypertension (IIH) in 2009-2013. This represents our current practice. Our previously reported cohorts of shunted children 1967-1970 (n = 128) and 1985-1988 (n = 138) served as backgrounds for comparison. RESULTS: In the 1960s, ventriculography and head circumference measurements were the main diagnostic tools; ventriculoatrial shunt was the preferred procedure (94 %), neural tube defect (NTD) was the leading etiology (33 %), and overall 2-year survival rate was 76 % (non-tumor survival 84 %). In the 1980s, computerized tomography (CT) was the preferred diagnostic imaging tool; ventriculoperitoneal shunt (VPS) had become standard (91 %), the proportion of NTD children declined to 17 %, and the 2-year survival rate was 91 % (non-tumor survival 95 %). Hydrocephalus caused by intracranial hemorrhage had, on the other hand, increased from 7 to 19 %. In the years 2009-2013, when MRI and endoscopic third ventriculocisternostomy (ETV) were matured technologies, 73 % underwent VPS, and 23 % ETV as their initial surgical procedure. The most prevalent etiology was CNS tumor (31 %). The proportion of NTD patients was yet again halved to 8 %, while intracranial hemorrhage was also reduced to 12 %. In this last period, six children were treated with VPS for Idiopathic Intracranial Hypertension (IIH) due to unsatisfactory response to medical treatment. They all had headache, papilledema, and visual disturbances and responded favorably to treatment. The 2 years of survival was 92 % (non-tumor survival 99 %). In contrast to the previous periods, there was no early shunt related mortality (2 years). Aqueductal stenosis was a small but distinctive group in all cohorts with 5, 6 and 3 % respectively. CONCLUSIONS: The case-mix in pediatric patients treated with permanent CSF diversion has changed over the last half-century. With the higher proportion of children with CNS tumor patients and inclusion of the IIH children, the median age at initial surgery has shifted substantially from 3.2 to 14 months. Between the 1960s and the current cohort, 2 years of all-cause mortality fell from 24 to 8 %. Prolonged asymptomatic periods, extending 15 years, were relatively common. Nevertheless, 18 patients experienced shunt failure more than 15 years after last revision, and first-time shunt failure has been observed 29 years after initial treatment. This underscores the importance of life-long follow-up.

Patients with focal cerebellar lesions show reduced auditory cortex activation during silent reading.

Functional neuroimaging studies consistently report language-related cerebellar activations, but evidence from the clinical literature is less conclusive. Here, we attempt to bridge this gap by testing the effect of focal cerebellar lesions on cerebral activations in a reading task previously shown to involve distinct cerebellar regions. Patients (N=10) had lesions primarily affecting medial cerebellum, overlapping cerebellar regions activated during the presentation of random word sequences, but distinct from activations related to semantic prediction generation and prediction error processing. In line with this pattern of activation-lesion overlap, patients did not differ from matched healthy controls (N=10) in predictability-related activations. However, whereas controls showed increased activation in bilateral auditory cortex and parietal operculum when silently reading familiar words relative to viewing letter strings, this effect was absent in the patients. Our results highlight the need for careful lesion mapping and suggest possible roles for the cerebellum in visual-to-auditory mapping and/or inner speech.

Surgical mortality and selected complications in 273 consecutive craniotomies for intracranial tumors in pediatric patients.

BACKGROUND: In order to weigh the risks of surgery against the presumed advantages, it is important to have specific knowledge about complication rates. Contemporary reports on complications following craniotomy for tumor resection in pediatric patients are scarce. OBJECTIVE: To study the surgical mortality and rate of hematomas, infections, meningitis, infarctions, and cerebrospinal fluid (CSF) leaks, as well as neurological morbidity, after craniotomy for pediatric brain tumors in a large, contemporary, single-institution consecutive series. METHODS: All pediatric patients (< 18 years) from a well-defined population of 3.0 million inhabitants who underwent craniotomies for intracranial tumors at Oslo University Hospital, Rikshospitalet, during 2003 to 2009 were included. The patients were identified from our prospectively collected database, and all charts were reviewed to validate the database entries. RESULTS: Included in the study were 273 craniotomies, performed on 211 patients. Mean age was 8.5 years (range, 0-18). Follow-up was 100%. One hundred ninety-nine cases (72.9%) were primary craniotomies, while 74 cases (27.1%) were secondary craniotomies. Surgical approach was supratentorial in 194 (71.1%) and infratentorial in 79 (28.9%). Surgical mortality within 30 days was 0.4% (n = 1). Complication rates were intracerebral hemorrhage 0.4%, chronic subdural hematoma 1.1%, meningitis 1.8%, cerebral infarctions 1.5%, and postoperative CSF leak 7.3%. Neurological deficit rates were no change or improvement 87.2%, minor or moderate new deficits 9.5%, and severe new neurological deficits 2.9%. CONCLUSION: Overall, the complication rates are low and compare favorably with similar data from adult series. The authors' data could be used as a baseline for future studies.

Comparison of perioperative morbidity after LeFort III and monobloc distraction osteogenesis.

We have compared distraction by monobloc and LeFort III osteotomy in the treatment of midfacial retrusion. We treated 14 patients with midface distraction (Crouzon syndrome (n = 9), Apert disease (n = 3), and other (n = 2)), 7 of whom had monobloc distraction and 7 who had LeFort III osteotomy. We compared duration of operation, peroperative blood loss, and complications. The two groups were comparable with respect to diagnosis, type of distraction (internal or external device), and duration of distraction. The operating time was longer in the monobloc than in the LeFort III group, but not significantly so (p = 0.09). The weight-adjusted blood losses were significantly different (66 ml/kg and 34 ml/kg, respectively (p = 0.05). The two groups had similar numbers of complications (p = 0.3), and similar duration of hospital stay. Both techniques seem safe. The choice of operation, therefore, should be tailored to the individual patient and the monobloc procedure should be used if indicated.

Audits can improve neurosurgical practice--illustrated by endoscopic third ventriculostomy.

OBJECTIVE: A single-center, retrospective study was performed to evaluate the effect of audit on the patient selection for endoscopic third ventriculostomy (ETV). MATERIALS AND METHODS: Between 01.01.99 and 07.31.01, 134 patients underwent ETV (group 1). During this period, there was no consensus within the neurosurgical community as to patient selection criteria for ETV. A review of our clinical practice in August 2001 demonstrated significantly lower ETV success rates for patients <6 months of age, patients with communicating hydrocephalus (HC) and for patients with prior shunt surgery. Thus, stricter patient selection criteria were established. Between 08.01.01 and 12.31.02, 54 patients were operated (group 2). The two groups were compared with respect to age, type of HC, previous shunt surgeries and ETV success rates. The primary outcome event was ETV malfunction, defined as symptoms and/or signs of increased intracranial pressure leading to repeat ETV or shunt implantation. Follow-up was done through outpatient clinics and telephone interviews. Average follow-up time was 12 months (range 0-44 months). No patient was lost to follow-up. RESULTS: The overall 1-year ETV success rate in group 2 (65%) was significantly higher than in group 1 (53%) (p < 0.04). Group 2 had a significantly higher proportion of patients >6 months of age (p = 0.013) and with obstructive HC (p = 0.001). CONCLUSION: Patient selection criteria critically affect the overall ETV success rate. An audit of our results led to a significant change in clinical practice, thereby improving the ETV success rates and patient care.

Le Fort III distraction osteogenesis in syndromal craniosynostosis.

Midface distraction osteogenesis has become a valuable technique. Although outcome data are available from several craniofacial centers, information regarding perioperative and immediate postoperative course is scarce. This report describes seven children, aged 4 to 17 years, with syndromal craniosynostosis in need of midface advancements. Most were rather complex cases with several previous craniofacial surgeries (mean 4.4 times, range 1-8). The Modular Internal Distraction System (Howmedica Leibinger, Inc., Rutherford, NJ) was used for the gradual Le Fort III advancements. The average midface advancement obtained was 23 mm (range 15-30 mm), resulting in improved facial profile, normalized or improved dental occlusion, reduced exophthalmos, and cessation or a significant decrease in preoperative respiratory problems. The mean length of operation was 354 minutes (range 300-535 minutes), and the mean amount of perioperative blood transfusion needed was 1251 mL (range 450-1800 mL) or 46.0 mL/kg (range 8.2-121.4 mL/kg). Complications included subcutaneous infections inferolaterally to the eye (N = 3) and forehead (N = 1). One patient had worsening of her facial profile and underwent a subsequent fronto-orbital advancement. One patient developed a deviation of the nasal septum and needed a corrective rhinoplasty. One patient developed marked trismus and one needed reoperation and trimming of the anchoring titanium plate on the malar process. In one patient, the lacrimal sac was lacerated, leading to transient epiphora. In most patients, Le Fort III distraction led to a significant improvement in the facial profile. However, surgery is still a major undertaking, with several potential complications. In our hands, the rate of complications is not less than for monobloc advancement. Thus, the choice of operation method is not based on which method is the least risky but on which is best suited for the individual patient.

Monobloc distraction osteogenesis in pediatric patients with severe syndromal craniosynostosis.

The management of the hypoplastic midface in syndromic craniosynostosis remains a great challenge. Frequently, patients have to be operated on numerous times to achieve a satisfactory end result, partially because of the limited skeletal advancement possible when using traditional surgical techniques. During the last decade, however, methods for gradual midfacial distraction have been presented, whereby greater advancements can be obtained. We present four children aged 17 months to 15 years with severe syndromal craniosynostosis in need of midface advancements because of severe respiratory obstruction or severe exophthalmos. These patients were complex cases with several previous craniofacial surgeries (mean of three times, range of two to six times) that yielded insufficient skeletal advancements. They were operated on with gradual monobloc advancements using the Modular Internal Distraction System. The mean length of operations was 370 minutes (range: 240-455 minutes), and the mean amount of perioperative blood transfusion needed was 1,300 ml (range: 280-2,700 ml) or 66.9 ml/kg (range: 31.1-94.9 ml/kg). The patient with the greatest number of previous operations also had the longest operation time as well as the most blood loss. The average midface advancement obtained was 25 mm (range: 20-30 mm), resulting in cessation or a significant decrease of preoperative respiratory problems, reduced exophthalmos, and improved facial profile. Apart from a local infection in one patient with a connective tissue disorder and several previous wound infections, no major postoperative complications were recorded. Distraction osteogenesis has become a versatile and safe technique that allows for large advancements of the midface.