A multicentre retrospective clinico-histopathological review of 250 patients after parotidectomy.

A clinicopathological review of parotid tumours treated surgically in two oral and maxillofacial surgery departments was conducted. The performance of fine needle aspiration cytology (FNAC) was also assessed. This retrospective study included 250 consecutive patients treated surgically for parotid gland-related tumours. Benign tumours (n=211, 84.4%) were more prevalent than malignancies (n=39, 15.6%). A predominance of pleomorphic adenoma (48.8%) was identified, and epithelial-myoepithelial carcinoma (3.6%) was the most common malignant tumour. Overall, the sensitivity and specificity of FNAC were 64% and 99%, respectively. Subgrouping resulted in sensitivity and specificity of 50% and 100% for clinically assisted FNAC versus, 72% and 99% for ultrasound guidance. Surgically, 31.6% underwent complete superficial parotidectomy and 28.4% underwent extracapsular dissection. Overall, facial nerve palsy was the most prevalent postoperative complication, affecting 29.2% (70/240); loss of function was transient in 21.2% (51/240) and permanent in 7.9% (19/240). Extracapsular dissection and superficial parotidectomy with facial nerve preservation were the treatments of choice when a benign tumour was suspected. Facial nerve palsy was quite frequent; treatment options however are scarce. Preoperative diagnostic workup using imaging and ultrasound-guided FNAC was essential in identifying malignancy so that surgical planning could be adapted.

Incidence of medication-related osteonecrosis of the jaw in patients treated with both bone resorption inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Several case reports and small case series have suggested a higher incidence of medication-related osteonecrosis of the jaw (MRONJ) in patients treated concomitantly with bone resorption inhibitors (BRIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), as compared to patients treated with BRIs alone. We aimed to assess ONJ-incidence in patients exposed concomitantly to BRIs and VEGFR-TKIs. PATIENTS AND METHODS: We reviewed the records of all patients who received VEGFR-TKIs concomitantly with BRIs. Patients, who were treated with BRIs without VEGFR-TKI, served as a control group. Endpoints of the study were total MRONJ-incidence, MRONJ-incidence during the first and second year of exposure, and time-to-ONJ-incidence. RESULTS: Ninety patients were treated concomitantly with BRIs and VEGFR-TKIs with a median BRI-exposure of 5.0 months. Total MRONJ-incidence was 11.1%. During the first year of BRI-exposure (with a median concomitant exposure of 4.0 months), 6 out of 90 patients (6.7%) developed a MRONJ, compared to 1.1% in the control group (odds ratio 5.9; 95%CI 2.0-18.0; p = 0.0035). In Kaplan-Meier estimates, time-to-ONJ-incidence was significantly shorter in patients treated with BRIs and VEGFR-TKIs compared to BRIs alone (hazard ratio 9.5; 95%CI 3.1-29.6; p < 0.0001). MRONJs occurred earlier in patients treated concomitantly compared to patients treated with BRIs only (after a median exposure of 4.5 and 25.0 months, respectively; p = 0.0033). CONCLUSION: With a global MRONJ-incidence of 11%, patients receiving concomitant treatment with VEGFR-TKIs and BRIs have a five to ten times higher risk for development of MRONJ compared to patients treated with BRIs alone.

Medication-related osteonecrosis of the jaw in oncological patients with skeletal metastases: conservative treatment is effective up to stage 2.

There is currently no widespread strategy for treating medication-related osteonecrosis of the jaw (MRONJ), so our aim was to evaluate retrospectively the outcome of a minimally invasive treatment protocol for patients with both MRONJ and cancer. We designed a retrospective cohort study of patients with cancer who had been diagnosed with MRONJ after treatment with denosumab or bisphosphonates given intravenously. Primary outcome measures were improvement in the clinical stage of MRONJ and the time course to its resolution. Secondary outcome measures included the incidence of risk factors and patterns of treatment. Seventy-nine patients with 109 lesions were enrolled, and their characteristics, presentation of the lesions, complications, and relations to previous oral interventions were recorded. Treatment depended on the stage of disease, and included conservative medical, and minimally-invasive surgical, procedures. There was complete healing and resolution of disease in 38/57 stage 1 lesions, 30/47 stage 2 lesions, and 3/5 stage 3 lesions. The symptoms improved in 16/47 stage 2 lesions, and 2/5 stage 3 lesions. Fifteen of the stage 1 lesions, and one of the stage 2 lesions, failed to respond. Despite the possibility of an aggressive approach to the treatment of MRONJ, conservative treatment remains the first line of defence as regression is obvious, with evidence of no evolution to a higher stage. In our experience surgical intervention is recommended in persistent stage 3 MRONJ that has failed to respond to conservative treatment.

Novel IRF6 Mutations Detected in Orofacial Cleft Patients by Targeted Massively Parallel Sequencing.

Common variants in interferon regulatory factor 6 ( IRF6) have been associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) as well as with tooth agenesis (TA). These variants contribute a small risk towards the 2 congenital conditions and explain only a small percentage of heritability. On the other hand, many IRF6 mutations are known to be a monogenic cause of disease for syndromic orofacial clefting (OFC). We hypothesize that IRF6 mutations in some rare instances could also cause nonsyndromic OFC. To find novel rare variants in IRF6 responsible for nonsyndromic OFC and TA, we performed targeted multiplex sequencing using molecular inversion probes (MIPs) in 1,072 OFC patients, 67 TA patients, and 706 controls. We identified 3 potentially pathogenic de novo mutations in OFC patients. In addition, 3 rare missense variants were identified, for which pathogenicity could not unequivocally be shown, as all variants were either inherited from an unaffected parent or the parental DNA was not available. Retrospective investigation of the patients with these variants revealed the presence of lip pits in one of the patients with a de novo mutation suggesting a Van der Woude syndrome (VWS) phenotype, whereas, in other patients, no lip pits were identified.

Osteoradionecrosis and medication-related osteonecrosis of the jaw: similarities and differences.

The purpose of this study was to compare medication-related osteonecrosis of the jaw (MRONJ) with osteoradionecrosis (ORN). Group 1 comprised 74 MRONJ patients (93 lesions) and group 2 comprised 59 ORN patients (69 lesions). Patient characteristics, clinical presentation of the lesions, the presence of complications, and the relationship with previous dental extractions were analyzed for both groups. Significant differences were found between the groups with regard to the characteristics of the patient populations, extraction as the precipitating event, the type of initial complaint, the prevalence of pain, and the location of the lesions. In the ORN group, significantly more patients complained of pain (P=0.0108) compared with the MRONJ group. Furthermore, significantly more pathological fractures (P<0.0001) and skin fistulae (P<0.0001) occurred in the ORN group. The treatment was more often conservative in the MRONJ group than in the ORN group (61.3% vs. 36.2%). Despite similarities in terms of imaging, risk factors, prevention, and treatment, MRONJ and ORN are two distinct pathological entities, as highlighted by the differences in patient characteristics, the initial clinical presentation, course of the disease, and outcome.

Review: Facial endophenotypes in non-syndromic orofacial clefting.

Cleft lip and/or palate (CL/P) is one of the most frequent congenital malformations, with a frequency of 1 in 700 live births. Non-syndromic orofacial clefting is a multifactorial condition, with both a genetic and an environmental component. Although numerous studies have been published addressing the genetic etiology of CL/P, this factor remains incompletely understood. A promising approach to find candidate gene regions for CL/P is the investigation of endophenotypes, which are characteristics associated with a certain condition and that can be an expression of underlying susceptibility genes. This review focuses on the known facial endophenotypes in CL/P (such as distortion of the orbicularis oris muscle and facial features in non-affected relatives of patients with CL/P) and genes that could be associated with these characteristics. Possibilities for further endophenotype-related studies in the field of non-syndromic CL/P are discussed.

Surgery for velopharyngeal insufficiency: The outcomes of the University Hospitals Leuven.

OBJECTIVES: We reviewed the outcomes of patients who underwent a velopharyngoplasty and subsequent speech therapy for velopharyngeal insufficiency (VPI) to determine possible prognostic variables. METHODS: During the period 2002-2010, 91 patients with VPI underwent a velopharyngoplasty (either the Honig velopharyngoplasty, the modified Honig velopharyngoplasty or the Hynes pharyngoplasty). Of these, 62 had complete data for long-term evaluation of speech outcome and analysis of variables potentially influencing this outcome. Speech outcome was assessed using five criteria that were evaluated pre- and postoperatively: hypernasality, nasal emission, facial grimacing, retro-articulation and glottal stops. The former two variables were transformed into a semi-objective nasality index (NI), the latter three variables were assembled to form a subjective articulation index (AI). Prognostic variables for outcome that were studied included age at velopharyngoplasty, associated 22q11.2 deletion syndrome, intervention type, primary or secondary surgery and pre-intervention speech therapy. RESULTS: Before surgery, based on the NI, 15 patients had mild VPI and 44 patients had moderate to severe VPI. Postoperatively at 12 months, 46 patients had a good speech outcome (normal or mild VPI), 13 patients had moderate VPI and no more severe VPI was observed. The overall success rate of 78% after one year increased to 90% in the long-term (median 27 months) with further speech therapy. Patients without the diagnosis of 22q11.2 deletion syndrome had better speech outcomes than patients with the syndrome. No statistically significant effect of the age at velopharyngoplasty on speech outcome was found. No cases of sleep apnea syndrome were reported. CONCLUSIONS: Our protocol of patient tailored surgical interventions and further postoperative speech therapy results in good speech outcomes, with no or only mild remaining VPI for the majority of patients. The correction of VPI is more difficult for the subgroup of patients with 22q11.2 deletion syndrome.

Pierre Robin sequence: Management of respiratory and feeding complications during the first year of life in a tertiary referral centre.

OBJECTIVES: To review early clinical manifestations of Pierre Robin sequence (PRS) and their management during the first year of life in the University Hospitals Leuven. METHODS: Retrospective series of 48 patients with PRS born between 2001 and 2011 and treated at a tertiary referral hospital. Review of the current literature about management of respiratory and breathing difficulties in the early life of PRS patients. RESULTS: Of our cleft palate patients 15.3% presented with PRS. A syndrome was diagnosed in 14.6%, associated anomalies without a syndromic diagnosis in 56.3% and isolated PRS in 29.2% of the cases. Mortality rate directly related to PRS was 2.1%. Respiratory difficulties were observed in 83.3% and feeding difficulties in 95.6% of the patients. Respiratory problems were addressed in a conservative way in 75%, in a non-surgical invasive way in 42.5% and in a surgical way in 12.5%. A statistically significant relationship between the association of a syndrome or other anomalies, and a higher need for resuscitation and invasive treatment were found (chi-square test, p-values=0.019 and 0.034). Feeding difficulties were managed conservatively in 91.3%, invasively in 80.4% and surgically in 15.2%. CONCLUSIONS: PRS is frequently associated with other abnormalities or syndromes. Therefore routine screening for associated anomalies in neonates with PRS is recommendable. Respiratory and feeding complications are highly frequent and possibly severe, particularly in patients with associated anomalies or syndromes, and should be recognized and addressed appropriately in an early stage. There is a potential role for the nasopharyngeal airway in reducing the need for the more traditional surgical interventions for respiratory problems.

Evaluation of transverse maxillary expansion after a segmental posterior subapical maxillary osteotomy in cleft lip and palate patients with severe collapse of the lateral maxillary segments.

Objective : The purpose of this longitudinal retrospective study was to evaluate transverse maxillary expansion after a Schuchardt or segmental posterior subapical maxillary osteotomy (SPSMO) in patients with cleft lip and palate (CLP). A second aim was to compare these data with data for adult patients without CLP who were receiving a surgical assisted rapid palatal expansion (SARPE). Method : The study group comprised 19 patients with CLP and a severe transversally collapsed maxilla who were treated with SPSMO followed by hyrax expansion at the University Hospitals Leuven. Dental casts of the 19 patients were analyzed before treatment, at maximum expansion, during orthodontic treatment, at the completion of orthodontic treatment. and 2 years after orthodontic treatment and were measured at the canine, premolar, and molar levels. Adult patients without CLP who were enrolled in a prospective study served as the control group. Results : Maxillary expansion within the study group was significantly greater (P < .05) at all measured levels compared with the maxillary arch before treatment. No significant relapse was measured in the study group 2 years after orthodontic treatment. When comparing the study and control groups, the only statistical difference was that canine expansion was significantly greater in the study group. Conclusion : SPSMO followed by maxillary expansion and orthodontic treatment is an appropriate treatment option to correct a severe transversally collapsed maxilla in patients with CLP. The overall treatment effect of SPSMO expansion is comparable with the effects of SARPE, although canine expansion was greater in the SPSMO group.

Evaluation of Transverse Maxillary Expansion After a Segmental Posterior Subapical Maxillary Osteotomy in Cleft Lip and Palate Patients With Severe Collapse of the Lateral Maxillary Segments.

Objective : The purpose of this longitudinal retrospective study was to evaluate transverse maxillary expansion after a Schuchardt or segmental posterior subapical maxillary osteotomy (SPSMO) in patients with cleft lip and palate (CLP). A second aim was to compare these data with data for adult patients without CLP who were receiving a surgical assisted rapid palatal expansion (SARPE). Method : The study group comprised 19 patients with CLP and a severe transversally collapsed maxilla who were treated with SPSMO followed by hyrax expansion at the University Hospitals Leuven. Dental casts of the 19 patients were analyzed before treatment, at maximum expansion, during orthodontic treatment, at the completion of orthodontic treatment. and 2 years after orthodontic treatment and were measured at the canine, premolar, and molar levels. Adult patients without CLP who were enrolled in a prospective study served as the control group. Results : Maxillary expansion within the study group was significantly greater (P < .05) at all measured levels compared with the maxillary arch before treatment. No significant relapse was measured in the study group 2 years after orthodontic treatment. When comparing the study and control groups, the only statistical difference was that canine expansion was significantly greater in the study group. Conclusion : SPSMO followed by maxillary expansion and orthodontic treatment is an appropriate treatment option to correct a severe transversally collapsed maxilla in patients with CLP. The overall treatment effect of SPSMO expansion is comparable with the effects of SARPE, although canine expansion was greater in the SPSMO group.

Cranio-maxillofacial, orthodontic and dental treatment in three patients with Apert syndrome.

BACKGROUND: Apert syndrome is a severe developmental malformation, clinically characterised by craniosynostosis, midface hypoplasia, a cone-shaped calvarium, ocular manifestations, typical dental findings and syndactyly of the hands and feet. Early craniosynostosis of the coronal suture, the cranial base and agenesis of the sagittal suture are prodromal characteristics for the typical craniofacial appearance in patients with Apert syndrome. CASE REPORTS: The aim of this report was to describe the maxillofacial and orthodontic management of three patients with Apert syndrome who attended the Craniofacial, Maxillofacial and Orthodontic clinics of the University Hospitals of the KU Leuven (Belgium). The typical clinical features, the general orthognathic treatment approach as well as individual approaches of three patients with Apert syndrome are being highlighted. FOLLOW-UP: The three patients with Apert syndrome have been followed up very closely by all involved specialised departments as well as by multidisciplinary teams from birth. CONCLUSION: This report demonstrated that a combined orthodontic and orthognathic surgical treatment plan could significantly improve the occlusal function as well as the facial and occlusal aesthetics in patients with Apert syndrome.

Enamel defects on the maxillary premolars in patients with cleft lip and/or palate: a retrospective case-control study.

AIM: The purpose of this study was to investigate the presence of developmental defects of enamel on maxillary premolars in patients with cleft lip and/or palate. In addition, the relationship with the surgical technique of soft palate closure was studied. Such a relationship could be suspected since formation of enamel occurs around the same time period as soft palate closure. MATERIALS AND METHODS: The study consisted of three groups. Patients from the first group (n = 123) were recruited from the Cleft Lip and Palate Team of the University Hospitals Leuven (CLPT-UHL). The second group (n = 81) consisted of patients consulting the Cleft Lip and Palate Team of the Radboud University Medical Centre Nijmegen (CLPT-UMCN). Healthy non-cleft lip and/or palate patients (n = 100) recruited from a private orthodontic practice were enrolled in group 3. All maxillary premolars were examined. RESULTS: Out of the total sample, 43 patients showed developmental defects on one or more premolars. All defects occurred in patients of group 1 who received surgical closure by the CLPT-UHL. None of the patients from group 2 and 3 showed defects. CONCLUSIONS: It can be suggested that the surgical technique, used by the CLPT-UHL for soft palate closure, causes these defects. It is postulated that the technique used by the CLPT-UHL leads to interference with the blood supply of the developing premolar at a critical stage of tooth enamel development. More research is needed to confirm these findings.

Cyclophosphamide, doxorubicin, and cisplatin in advanced salivary gland cancer.

OBJECTIVES: Advanced salivary gland cancer is a rare disease that comprises different histopathological tumour types; correspondingly, data on palliative systemic treatment are scarce. Combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) has been reported to induce a reasonable response rate, although fewer than 100 cases have been described. We conducted a retrospective review of advanced salivary gland cancer patients treated with CAP. METHODOLOGY: Fifteen consecutive patients with recurrent, locally advanced, or metastatic progressive salivary gland cancer treated with CAP were identified over a five-year period. The mean age at start of treatment was 53.5 years, and the male/female ratio was 11/4. The most common histological subtypes were adenoid cystic carcinoma and adenocarcinoma not otherwise specified (NOS), with the parotid gland as the most frequently affected anatomical site. RESULTS: A response rate of 60% was achieved, with one complete and eight partial responses and six stable diseases according to RECIST criteria. No patient progressed under treatment. An average of 5.4 treatment cycles were administered; median time to progression after ending CAP was 6.6 months, and median overall survival was 15.1 months. Patients with adenocarcinoma NOS appeared to benefit more than patients with adenoid cystic carcinoma, but had a shorter time to progression. Except for neutropenia with neutropenic fever and alopecia, no NCI-CTC grade III or IV toxicity was observed. CONCLUSION: This retrospective study confirms the clinically meaningful efficacy of CAP in advanced adenocarcinomas NOS of the salivary gland in routine practice, with acceptable safety levels.

Syndrome of Hajdu-Cheney: three case reports of orofacial interest.

Hajdu-Cheney syndrome is a rare, probably autosomal dominant connective tissue disorder with a variable expressivity. It is characterized by an osteoporotic skeleton, acro-osteolysis, a proportionate short stature, and distinctive orofacial anomalies. The aim of this article is to focus on the orofacial manifestations in two sporadic cases and one familial case with Hajdu-Cheney syndrome. Several common dental and craniofacial features are described. In contrast to earlier proposed diagnostic features, these patients show persisting deciduous teeth, problematic tooth eruption, and tendency toward a Class III malocclusion.

Unique approach to secondary cleft-lip rhinoplasty in facial plastic surgery.

Rhinoplasty occupies a unique position in facial plastic surgery due to the central position of the nose in the face and the vital functions of the nose. Among facial plastic surgeons, secondary rhinoplasty in adult cleft-lip patients is considered to be one of the most challenging surgical interventions due to the congenital distortion of the cartilaginous and bony nasal pyramid, with consequences for both nasal aesthetics and breathing. In spite of the challenging nature of the procedure, post-operative satisfaction is high, matching that of non-cleft-lip patients, as long as appropriate surgical techniques are applied. Specific rhinoplasty methods are used in unilateral or bilateral cleft-lip patients with extensive grafting, combined efforts for aligning the nasal dorsum and the creation of symmetry in the nasal tip, medialisation of the anterior nasal spine with augmentation of the premaxilla, correction of nasal vestibulum stenosis and specific post-operative care with a nasal vestibulum device. This review aims to address some specific surgical issues relating to cleft-lip rhinoplasty, resulting in the high subjective satisfaction rate reported by cleft patients operated upon in the University Hospitals Leuven.

[Dentomaxillary and -facial problems in cleidocranial dysplasia]. / Dentomaxillaire en -faciale problemen bij cleidocraniale dysplasie.

A 14-year old boy with cleidocranial dysplasia was referred because of an almost complete presence of the deciduous dentition. Diagnostics by means of a panoramic radiograph, lateral headfilm, CT scan and 3D computer images of the dentomaxillary complex showed 7 supernumerary permanent teeth: 13', 11', 21', 23', 28', 35' and 45'. A combined orthodontic-surgical treatment was started. The supernumary teeth were removed surgically and the impacted teeth are exposed. The closed eruption technique was used to extrude these teeth orthodontically.

The Leuven staged supraperiosteal retropositioning repair: long-term velopharyngeal function in non-syndromic cleft palate.

BACKGROUND: From 1989 to 1993, 113 previously untreated patients were admitted to the Multi-disciplinary Cleft Lip and Palate Team of the University Hospitals Leuven. Palate repair was performed in our centre by one surgeon (FO) in 88 patients. Our current surgical technique consists of a single-stage supraperiosteal retropositioning (modified Veau-Wardill-Kilner) for patients with a soft cleft palate only (SCP) or a soft cleft palate with up to 1 cm of the hard palate (HSCPpa). Patients with a larger or complete cleft of the secondary hard palate (HSCP) and patients with unilateral (UCLP) or bilateral (BCLP) cleft lip and palate undergo two surgical stages for palate closure: a supra-periosteal retropositioning is performed around 12 months of age, and a modified Langenbeck closure of the hard palate around 60 months of age. AIM: To assess velopharyngeal function with speech as outcome measure. PATIENTS AND METHODS: Velopharyngeal function was assessed in two ways. In one assessment, a "hard" outcome measure was the number of patients undergoing pharyngoplasty following palate repair in our centre (n = 88). In the other assessment, velopharyngeal function was evaluated in a homogeneous sub-population of 44 non-syndromic cleft patients with normal to slight impairment of the following functions: mental development, language development, and hearing. In this group, prospectively collected data about hypernasality and nasal emission were analysed retrospectively using a semi-objective nasality index (NI). Articulation was evaluated using a subjective articulation index (AI) representing articulation errors (retro-articulation, glottal stops and facial grimacing) associated with velopharyngeal insufficiency (VPI). Mean follow-up was 114 months. RESULTS: Despite rigid assessment by a phoniatrician and speech pathologist, only 1 patient out of 88 patients with soft palate surgery in our institution was thought to need pharyngoplasty. In the sub-cohort of 44 non-syndromic patients, nobody needed a pharyngoplasty. In the latter cohort, at the age of about eight years, 27 patients (61.5%) had undetectable nasality, 13 patients (29.5%) had an NI of 1 or "mild" nasality, and 4 patients (9%) had moderate nasality. At this point in time, articulation errors associated with VPI were noted in 14% of patients. CONCLUSION: In this subgroup of cleft palate patients treated following the Leuven protocol, there was no need for secondary pharyngoplasty. Ninety-one per cent of patients had no, or only mild, rhinolalia aperta by the age of eight years, and 84% did not display VPI-related articulation disorders. This suggests that velopharyngeal function in patients treated by this protocol is excellent compared to results in the literature.

Brown tumour: presenting symptom of primary hyperparathyroidism.

The skeletal lesions of primary hyperparathyroidism, including brown tumour, are rare nowadays, with the practice of checking serum calcium levels leading to an earlier diagnosis of hyperparathyroidism. Clinical, laboratory, radiographic and histological investigations can lead to a correct diagnosis. Treatment of brown tumour focuses on the hyperparathyroidism, and is usually followed by a regression of the brown tumour. The diagnosis of hyperparathyroidism and brown tumour should be considered in patients with hypercalcaemia and an osteolytic expansive bone lesion. We present a patient where a brown tumour of the mandible was the presenting symptom of primary hyperparathyroidism.

Treatment of hemifacial microsomia in a growing child: the importance of co-operation between the orthodontist and the maxillofacial surgeon.

The treatment of patients with hemifacial microsomia (HM) always requires an interdisciplinary approach including at least maxillofacial surgery and orthodontics. Co-operation not only within the team, but also with the patients and their family is essential in order to achieve the best results. In the case history of the 10-(1/2) year old female patient reported here, three surgical interventions (two with costo-chondral bone grafts) and a 3-year orthodontic treatment have taken place. A harmonious facial and occlusal result was finally reached.