Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis.

PURPOSE: We aimed to identify a novel genetic cause of tooth agenesis (TA) and/or orofacial clefting (OFC) by combining whole-exome sequencing (WES) and targeted resequencing in a large cohort of TA and OFC patients. METHODS: WES was performed in two unrelated patients: one with severe TA and OFC and another with severe TA only. After deleterious mutations were identified in a gene encoding low-density lipoprotein receptor-related protein 6 (LRP6), all its exons were resequenced with molecular inversion probes in 67 patients with TA, 1,072 patients with OFC, and 706 controls. RESULTS: We identified a frameshift (c.4594delG, p.Cys1532fs) and a canonical splice-site mutation (c.3398-2A>C, p.?) in LRP6, respectively, in the patient with TA and OFC and in the patient with severe TA only. The targeted resequencing showed significant enrichment of unique LRP6 variants in TA patients but not in nonsyndromic OFC patients. Of the five variants in patients with TA, two affected the canonical splice site and three were missense variants; all variants segregated with the dominant phenotype, and in one case the missense mutation occurred de novo. CONCLUSION: Mutations in LRP6 cause TA in humans.Genet Med 18 11, 1158-1162.

Inferior alveolar nerve sensory disturbance after impacted mandibular third molar evaluation using cone beam computed tomography and panoramic radiography: a pilot study.

PURPOSE: To measure sensory disturbances of the inferior alveolar nerve (IAN) after removal of impacted mandibular third molars using cone beam computed tomography (CBCT) and dental panoramic radiography (PAN) for preoperative assessment in a randomized controlled trial and to measure the efficacy of the observers' prediction of IAN exposure at surgery based on CBCT compared with PAN. MATERIALS AND METHODS: The sample consisted of 86 impacted third molars (from 79 consecutive patients) in close relation to the IAN as determined by PAN and judged as showing a "moderate" risk of IAN damage. Cases presenting with no close relation between the IAN and roots and extremely risky cases with an obvious interrelation were excluded. Potential neurosensory disturbances of the lip and chin were assessed before surgery and during the postoperative recall by measuring the function of the IAN with the light-touch sensation method. RESULTS: Postoperative sensory disturbances occurred in 1 patient in the CBCT group and 1 patient in the PAN group. The light-touch sensation test showed no significant differences at the lip (P = .10) and chin (P = .17) levels for CBCT- versus PAN-based surgery. Significant differences in making a correct diagnosis of neurovascular bundle exposure at the extraction of impacted teeth were found between the 2 modalities (P = .029). CONCLUSIONS: Within the limits of the present pilot study, CBCT was not superior to PAN in predicting postoperative sensory disturbances but was superior in predicting IAN exposure during third molar removal in cases judged as having "moderate" risk.

Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors.

Benign peripheral nerve sheath tumors (PNSTs) are a characteristic feature of neurofibromatosis type I (NF1) patients. NF1 individuals have an 8-13% lifetime risk of developing a malignant PNST (MPNST). Atypical neurofibromas are symptomatic, hypercellular PNSTs, composed of cells with hyperchromatic nuclei in the absence of mitoses. Little is known about the origin and nature of atypical neurofibromas in NF1 patients. In this study, we classified the atypical neurofibromas in the spectrum of NF1-associated PNSTs by analyzing 65 tumor samples from 48 NF1 patients. We compared tumor-specific chromosomal copy number alterations between benign neurofibromas, atypical neurofibromas, and MPNSTs (low-, intermediate-, and high-grade) by karyotyping and microarray-based comparative genome hybridization (aCGH). In 15 benign neurofibromas (4 subcutaneous and 11 plexiform), no copy number alterations were found, except a single event in a plexiform neurofibroma. One highly significant recurrent aberration (15/16) was identified in the atypical neurofibromas, namely a deletion with a minimal overlapping region (MOR) in chromosome band 9p21.3, including CDKN2A and CDKN2B. Copy number loss of the CDKN2A/B gene locus was one of the most common events in the group of MPNSTs, with deletions in low-, intermediate-, and high-grade MPNSTs. In one tumor, we observed a clear transition from a benign-atypical neurofibroma toward an intermediate-grade MPNST, confirmed by both histopathology and aCGH analysis. These data support the hypothesis that atypical neurofibromas are premalignant tumors, with the CDKN2A/B deletion as the first step in the progression toward MPNST.

Contribution of three-dimensional images in the planning of cementoblastoma resection.

Cementoblastomas are rare benign tumours that represent less than 1% of all odontogenic tumours. Complete resection is mandatory to avoid recurrence. This case report describes the contribution of three-dimensional imaging and three-dimensional printing in the pre-operative surgical planning of a large cementoblastoma that not only caused substantial compression on the inferior alveolar and mental nerves, but also caused thinning and partial erosion of the lingual and vestibular cortical bone, thus increasing the risk of pre-operative mandibular fracture.

Orthodontic and orthognathic management of a patient with Apert syndrome: a case report.

This case report describes the combined orthodontic and orthognathic management of a 14-year-old girl affected with Apert syndrome. She presented with a severe Class III skeletal relationship, midfacial hypoplasia and an large anterior open bite. Intraorally, she had severe crowding, a narrow maxilla and lateral posterior crossbites. The patient was treated with a combination of removable and fixed appliances, a transpalatal skeletal distractor and Le Fort I surgery. The extraoral characteristics improved and a good occlusal relationship between maxillary and mandibular teeth was achieved.

Dog Bite Injuries in the Head and Neck Region: A 20-Year Review.

Dog bite-related wounds seem to have become a common problem, especially when they relate to the head and neck region. According to Overall and Love, up to 18 per 1,000 people sustain a dog bite every year, of whom 3 need medical attention. Approximately 1 to 2% of bite injuries require hospitalization of the victims. Most of the lacerations are found in the upper lip and the nose regions and they are classified according to severity and concomitant damage to other organs. Bite wounds are considered "dirty" wounds and are prone to infection. When dealing with bite wounds, there is always an indication for antibiotic treatment. Broad-spectrum antibiotics like amoxicillin-clavulanate and/or moxifloxacin cover most of the pathogenic flora and should be administered in every bite wound case at risk of infection. This article would like to present a medical record review: a retrospective analysis of all bite wounds sustained in the head and neck region, treated at the University Hospital of Leuven over the past 20 years. Furthermore, it provides an overview of the current literature and its standings on the treatment of dog bite injuries in the maxillofacial region. We assessed both surgical and medical treatment options, as well as primary management, which includes infection prevention strategies, closure management, and additional vaccination requirements. Secondary management or scar revision methods will be mentioned. After conducting a UZ Leuven database search using keywords such as "dog," "dog bite," "face," "head," "lip," and others, 223 patients were included. Age at the time of injury, location of the injury, treatment method used, and whether secondary infection was present or not were documented. All patients have been divided in age groups. We concluded that 21.52% was 5 years old or younger. Almost half of our patients (49.33%) were 18 years old or younger. Of all patients, 79 were hospitalized (35.43%). Primary closure was the treatment of choice. In 141 patients, the wounds were closed primarily (63.23%), resulting in only 2.24% reported secondary infections. Only one fatality was reported in our center over the course of 20 years (0.45%), a 6-year-old girl who had been attacked by her father's Rottweilers. Most patients who sustained dog bite injuries in the head and neck region seem to be children, specifically toddlers. Due to their height, it is possible they are more prone to dog bite injuries in the head and neck region. It is essential to optimize management of these injuries due to the impact they have on patients. This article provides the epidemiological data and clinical outcome of the approach at our center.

Accuracy of computer-assisted mandibular reconstructions with free fibula flap: Results of a single-center series.

OBJECTIVES: We evaluated the accuracy of computer-assisted mandibular reconstructions. PATIENTS AND METHODS: We retrospectively reviewed data for 26 patients who had mandibular reconstruction with a microvascular free fibula flap, January 2015 to June 2018. Postoperative mandible models were obtained from computed tomography scans. After registering the models to the corresponding preoperative plan, we performed comparative measurements. Patients were grouped by condylar involvement and subdivided based on number of fibular segments used for reconstruction. For each segment, we measured length and osteotomy angles. For the final postoperative outcome, we compared intercoronoid, intergonial, and anteroposterior distances and intersegmental plane shift. RESULTS: Means (SD) for deviation of each osteotomy angle and fibular segment length were 1.98° (2.98) and 1.78 mm (2.69), respectively, remaining constant across subgroups. Other mean values were as follows: intercoronoid distance deviation, 3.86 mm (range, 0.20-11.21 mm); intergonial distance deviation, 3.14 mm (range, 0.05-8.28 mm); anteroposterior distance deviation, 2.92 mm (range, 0.03-8.49 mm); and intersegmental plane shift, 11.00° (range, 2.76-24.15°). Where the condyle was preserved, the intercoronoid and intergonial deviation means differed significantly (respectively 5.02 mm and 4.88 mm, both P < 0.05) for one-segmented and three-segmented fibular reconstructions. Furthermore, reconstructions involving the condylar region compared with condyle preservation showed significantly different intersegmental plane shifts (7.18°; P < 0.05). CONCLUSION: Computer-assisted surgery provides cutting guides for obtaining accurate fibular segments, but current fixation methods lead to inaccuracies and reproducibility errors. In multisegmental transfer with condylar involvement, computer-assisted fixation is recommended to ensure accuracy of the preoperative plan.

Fibula Free Flap in Head and Neck Reconstruction: Identifying Risk Factors for Flap Failure and Analysis of Postoperative Complications in a Low Volume Setting.

The fibula free flap (FFF) has been a workhorse in maxillofacial reconstruction. High success rates of this technique are reported. However, identifying risk factors for flap failure and analyzing complications can open the way to better patient care. A retrospective analysis was conducted of all FFFs performed over a 20-year period at a low-volume single tertiary center to identify risk factors and postoperative complications. A total of 129 FFFs were included (122 mandible, 7 maxilla). Complete flap failure occurred in 12.4% and partial flap failure in 7.8% of patients. A significant relation was found between younger age and flap failure, and most failures were associated with venous thrombosis. In-hospital surgical complications occurred in 60.5%, in-hospital medical complications in 49.6%, and out-of-hospital complications in 77.5% of patients. The in-hospital reintervention rate was 27.1%, and including salvaged flaps, flap survival rate was 87.6%. Osteomyocutaneous FFF failure (complete 12.4%; partial 7.8%) is an important clinical reality in a low-volume head and neck reconstruction center resulting in an in-hospital reintervention rate of 27.1%. Postoperative complications are frequent, both surgical and out-hospital complications. These results provide a better understanding of the limitations of the FFF in a low-volume center and can be used to optimize care in this kind of setting.

Deletions and loss-of-function variants in TP63 associated with orofacial clefting.

We aimed to identify novel deletions and variants of TP63 associated with orofacial clefting (OFC). Copy number variants were assessed in three OFC families using microarray analysis. Subsequently, we analyzed TP63 in a cohort of 1072 individuals affected with OFC and 706 population-based controls using molecular inversion probes (MIPs). We identified partial deletions of TP63 in individuals from three families affected with OFC. In the OFC cohort, we identified several TP63 variants predicting to cause loss-of-function alleles, including a frameshift variant c.569_576del (p.(Ala190Aspfs*5)) and a nonsense variant c.997C>T (p.(Gln333*)) that introduces a premature stop codon in the DNA-binding domain. In addition, we identified the first missense variants in the oligomerization domain c.1213G>A (p.(Val405Met)), which occurred in individuals with OFC. This variant was shown to abrogate oligomerization of mutant p63 protein into oligomeric complexes, and therefore likely represents a loss-of-function allele rather than a dominant-negative. All of these variants were inherited from an unaffected parent, suggesting reduced penetrance of such loss-of-function alleles. Our data indicate that loss-of-function alleles in TP63 can also give rise to OFC as the main phenotype. We have uncovered the dosage-dependent functions of p63, which were previously rejected.

Incidence of osteonecrosis of the jaw in patients with bone metastases treated sequentially with bisphosphonates and denosumab.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a serious adverse event of bone resorption inhibitors (BRIs), such as bisphosphonates and denosumab. Bisphosphonates and denosumab inhibit osteoclast function through different pharmacological effects and bisphosphonates are retained in bone for several months to years. Sequential treatment with bisphosphonates and denosumab might lead to an overlapping treatment effect, due to the addition of the effect of denosumab on the residual bisphosphonate effect. Therefore, the aim of our study was to investigate if switching from denosumab to bisphosphonates is associated with a higher incidence of ONJ. METHODS: We retrospectively reviewed records of patients with solid tumors and bone metastases treated with denosumab after prior treatment with bisphosphonates at the University Hospitals Leuven (sequential group). Patients treated with denosumab or bisphosphonates alone were used as control groups. RESULTS: We identified 110 patients sequentially treated with bisphosphonates and denosumab with a median total BRI exposure of 36 months (sequential group). Median bisphosphonates exposure was 16 months and median denosumab exposure was 13 months. About 299 patients were included in the bisphosphonates control group with a median bisphosphonate exposure 19 months. About 6.7% (20/299) of patients developed ONJ. About 240 patients were included in the denosumab control group with a median denosumab exposure 17.5 months. About 10.0% of patients (24/240) developed ONJ. In the sequential group, 15.5% of patients (17/110) developed ONJ. The incidence of ONJ was 1.8% (2/110), 6.3% (6/99), 4.9% (4/82), 5.6% (3/54), and 3.4% (1/29), respectively in the first, second, third, fourth, and fifth year of BRI exposure, an ONJ-incidence similar to ONJ-incidence in the denosumab control group. In a time-to-ONJ-analysis, the curves of the sequential group and the denosumab control group were overlapping. In the sequential group, most of the ONJs occurred in the first year of denosumab exposure and in a matched control group analysis, with correction for median BRI-exposure, ONJ cases tend to occur earlier in the sequential group compared to ONJ cases in the bisphosphonates group. CONCLUSION: Cancer patients with bone metastases treated with BRIs seem to have a slightly higher risk of ONJ early after switching from bisphosphonates to denosumab compared to patients remaining on bisphosphonates. Nevertheless, based on the global ONJ-incidence, the switch from bisphosphonates to denosumab can be considered as safe as an equivalent exposure to denosumab from the start on.

Retrospective Analysis of Dental Implants Placed Between 2012 and 2014: Indications, Risk Factors, and Early Survival.

PURPOSE: The aim of this study was to review the indications for implant placement, early outcomes, and associated risk factors. MATERIALS AND METHODS: A retrospective cohort study design was used. The study was composed of a group of 509 consecutive patients, which represented the total number of patients treated from 2012 to 2014 in the Department of Oral and Maxillofacial Surgery, University Hospitals Leuven, Belgium. The authors analyzed the indications for implant placement and the potential risk factors for early implant failure. RESULTS: A total of 509 patients received 1,139 dental implants. The group consisted of 240 men and 269 women, with a median age of 58 years. The most frequent indication for implant placement was restoration of a partially edentulous arch (80.1%, n = 408). For 152 implants (13.3%), additional bone-augmentation or sinus elevation procedures were required. Early failures were recorded for 52 (4.6%) implants in 33 patients (6.5%). Smoking, male gender, total edentulism, implant diameter, and bone augmentation surgery were found to be associated with early implant failure. CONCLUSION: Patients referred for implant placement were more likely to be partially edentulous and older than 50 years. Singletooth replacement in the posterior mandible was the most frequent indication (24.4%) for treatment. This study found an early success rate of 95.4% and identified risk factors for early failures.

Wound Healing Problems in the Mouth.

Wound healing is a primary survival mechanism that is largely taken for granted. The literature includes relatively little information about disturbed wound healing, and there is no acceptable classification describing wound healing process in the oral region. Wound healing comprises a sequence of complex biological processes. All tissues follow an essentially identical pattern to complete the healing process with minimal scar formation. The oral cavity is a remarkable environment in which wound healing occurs in warm oral fluid containing millions of microorganisms. The present review provides a basic overview of the wound healing process and with a discussion of the local and general factors that play roles in achieving efficient would healing. Results of oral cavity wound healing can vary from a clinically healed wound without scar formation and with histologically normal connective tissue under epithelial cells to extreme forms of trismus caused by fibrosis. Many local and general factors affect oral wound healing, and an improved understanding of these factors will help to address issues that lead to poor oral wound healing.

Primary intraosseous squamous cell carcinoma of the mandible arising from an infected odontogenic cyst: A case report and review of the literature.

Primary intraosseous squamous cell carcinoma (PIOSCC) derived from a odontogenic cyst is a rare form of odontogenic carcinoma. The incidence of carcinomas arising from odontogenic cysts is particularly uncommon and is reported to occur in 1-2 individuals for every 1,000 cases. The present case describes a 25-year-old man who was initially diagnosed with a chronically infected odontogenic cyst of the mandible. Biopsy and subsequent histology revealed the presence of squamous cell carcinoma. Therefore, neck dissection and hemimandibulectomy were performed. Ultimately, the situation in the mouth healed, though with a severe amount of scarring. Although the development of PIOSCC from an odontogenic cyst is rare, it should be included in the differential diagnosis for jaw bone radiolucency.

Differences in human papillomavirus-positive and -negative head and neck cancers in Belgium: an 8-year retrospective, comparative study.

OBJECTIVES: This study investigated the prevalence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and compared patient profiles and outcomes between HPV-positive and HPV-negative groups. STUDY DESIGN: This retrospective study included all patients treated for OPSCC in the University Hospitals of Leuven between 2004 and 2012. Paraffin-embedded tumor tissue was available for all patients. Patient characteristics, treatment, and follow-up data were retrieved from medical files. HPV status was determined by immunohistochemical staining for the p16 epitope. RESULTS: Among 94 patients, the prevalence of HPV-positive OPSCC was 22.34%. Compared with HPV-negative tumors, HPV-positive tumors were correlated with less smoking and alcohol consumption, tonsillar sublocalization (P < .05), and younger age. HPV-positive OPSCC was associated with better overall survival (62.2%) compared with HPV-negative OPSCC (42.5%; P = .0588). CONCLUSIONS: Among patients with OPSCC, those with HPV exhibited profiles different from those without HPV. HPV-positive OPSCC was associated with better overall survival compared with HPV-negative OPSCC. HPV-positive OPSCC prevalence increased over time.

First evidence of treatment efficacy in metastatic carcinoma of the parotid gland with BRD4/NUT translocation.

BACKGROUND: Nuclear protein in testis (NUT) midline carcinomas (NMC) are characterized by rearrangements of the gene NUT. In the majority of NMCs, a translocation t(15;19), resulting in a BRD4/NUT fusion gene, is present. Nuclear protein in testis midline carcinomas is a rare, but probably underdiagnosed entity due to misdiagnosis. Most cases have been reported in the mediastinum and upper aero-digestive tract. The clinical course of a NMC is extremely aggressive, in spite of intensive chemotherapy and radiotherapy, with an average survival < 1 year. METHODS AND RESULTS: A 32-year-old man presented with a pre-auricular swelling on the left side. After partial parotidectomy, the diagnosis of a NMC was made based on the presence of t(15;19)(q14;p13.1) and BRD4/NUT fusion gene demonstrated by fluorescence in situ hybridization (FISH). During postoperative radiotherapy, the patient developed bone metastases for which chemotherapy consisting of cisplatine, doxorubicine and ifosfamide (PAI) was initiated with remarkable clinical and radiological improvement. Nevertheless, the response was not durable. CONCLUSION: This case illustrates that responses to chemotherapy in the palliative treatment of a t(15;19)-translocated salivary gland carcinoma are possible but not durable.

Secondary cleft rhinoplasty: impact on self-esteem and quality of life.

BACKGROUND: Rhinoplasty is one of the most challenging facial plastic procedures. Although patient satisfaction is the real outcome parameter in rhinoplasty, most authors have studied objective outcomes evaluated by professionals. The purpose of this study was to determine patient satisfaction after rhinoplasty in patients born with a cleft lip compared with outcome assessment by professionals, and to assess the impact of the procedure on appearance-related distress and generic quality of life. METHODS: Patient evaluation of the nose was performed before and 1 year after secondary cleft rhinoplasty (n = 33) using a visual analogue scale for nasal function and shape, and the Rhinoplasty Outcome Evaluation. General sinonasal complaints were evaluated using the Sino-Nasal Outcome Test. Appearance-related psychological distress was measured using the Derriford Appearance Scale. The Sheehan Disability Scale evaluated quality of life. Aesthetic outcome was evaluated by scoring of preoperative and postoperative photographs by two independent surgeons. RESULTS: One year postoperatively, patients showed significantly higher visual analogue scale scores for nasal shape (p < 0.0001) and function (p = 0.005) and higher Rhinoplasty Outcome Evaluation (p < 0.0001) scores. Correspondingly, Sino-Nasal Outcome Test scores were lower (p = 0.006). The appearance-related psychological distress was lower (p < 0.0001), and the generic quality of life was increased after rhinoplasty (p = 0.01). No correlation was found between patient outcome evaluation and surgeons' scores. CONCLUSION: There is high patient satisfaction at 12 months after secondary cleft rhinoplasty, resulting in a significant improvement of self-esteem and generic quality of life.

High patient satisfaction after secondary rhinoplasty in cleft lip patients.

OBJECTIVES: We surveyed the subjective outcome of secondary rhinoplasty in cleft lip patients. METHODS: Questionnaires were sent to 38 patients who had undergone a secondary rhinoplasty. A total of 30 questionnaires were returned and analyzed. Patients were asked to score their preoperative and postoperative nasal function and form. The validated Rhinoplasty Outcome Evaluation (ROE) questionnaire was supplemented with questions on the subjective burden of the procedure and general satisfaction. In parallel, the objective aesthetic outcome was judged by 2 surgeons using preoperative and postoperative photographs. RESULTS: There was a significant subjective improvement in ROE scores (from 39.3 ± 3.1 to 73.1 ± 2.0, p < 0.001), and in specific scores for nasal aesthetical appearance (from 3.6 ± 0.3 to 7.9 ± 0.2, p < 0.0001) and breathing capacity (from 4.9 ± 0.4 to 6.8 ± 0.3, p < 0.01). Subjective improvement in nasal aesthetics was generally evaluated to be better than improvement in nasal breathing. In retrospect, all patients would undergo the procedure again. Patient satisfaction did not correlate with the surgeon's appreciation of the aesthetic outcome of the rhinoplasty. CONCLUSION: Patient satisfaction after secondary rhinoplasty in cleft lip patients is high and comparable to that of non-cleft lip rhinoplasty patients.

Prognostic index for patients with parotid carcinoma: international external validation in a Belgian-German database.

BACKGROUND: Prognostic indices for recurrence-free interval in patients with parotid carcinoma were developed and validated in a nationwide database. International validation would increase generalizability. METHODS: In a Belgian-German database that contained 237 consecutive patients with parotid carcinoma, a pretreatment prognostic index (PS1) and a post-treatment prognostic index (PS2) were validated by calculating both indices for each patient, comparing coefficients, constructing survival curves, calculating the concordance measure C, and performing Wald tests for scale and weight optimization of included variables and for the possible inclusion of new variables. RESULTS: Sixty-nine percent of patients (standard error, 5%) were disease free at 5 years. The defined cutoff points for PS1 resulted in 5-year disease-free rates from 94% (PS1 = 1) to 42% (PS1 = 4), and the cutoff points for PS2 resulted in 5-year disease-free rates from 93% (PS2 = 1) to 40% (PS2 = 4). Concordance measure C was good with 0.74 for both PS1 and PS2. Neither index could be improved statistically using this international database. There was some evidence that additional inclusion of the variable 'number of positive lymph nodes in the neck dissection specimen' could enhance the prognostic power of PS2. CONCLUSIONS: The prognostic indices performed adequately in this validation sample. Prospective generalized use seems to be well supported.

Impact of adding concomitant chemotherapy to hyperfractionated accelerated radiotherapy for advanced head-and-neck squamous cell carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma. METHODS AND MATERIALS: Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m(2)) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 73) treated with the same schedule, but without concomitant Cx, between 2001 and 2004. RESULTS: The locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2-year disease-free survival rates were 74% and 60%, respectively. In comparison with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall survival (p = 0.09) was observed. All patients were treated to full radiation dose according to protocol, although the Cx schedule had to be adjusted in 12 patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3 acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p < 0.001) were significantly higher in the chemoradiotherapy group compared with patients treated with RT alone. CONCLUSION: With this chemoradiotherapy regimen, excellent LRC and survival rates were achieved, with acceptable acute toxicity.

Combined surgical/orthodontic treatment and autotransplantation of a premolar in a patient with unilateral cleft lip and palate.

OBJECTIVE: The treatment of a patient with a complete unilateral left cleft lip and palate, agenesis of the left upper second premolar, and a severely malformed left upper lateral incisor is reported. Treatment included placement of an autologous bone graft from the left iliac crest into the alveolar cleft at 8 years of age and transplantation of a lower premolar into the reconstructed alveolar process at 10 years of age. During the succeeding orthodontic treatment, the dental arches were aligned and corrected toward a Class I molar occlusion. One year after the end of treatment, the status of the transplanted premolar was good.