Significant association between FGFR1 mutation frequency and age in central giant cell granuloma.

Central giant cell granulomas (CGCG) are rare intraosseous osteolytic lesions of uncertain aetiology. Despite the benign nature of this neoplasia, the lesions can rapidly grow and become large, painful, invasive, and destructive. The identification of molecular drivers could help in the selection of targeted therapies for specific cases. TRPV4, KRAS and FGFR1 mutations have been associated with these lesions but no correlation between the mutations and patient features was observed so far. In this study, we analysed 17 CGCG cases of an Italian cohort and identified an interesting and significant (p=0.0021) correlation between FGFR1 mutations and age. In detail, FGFR1 mutations were observed frequently and exclusively in CGCG from young (<18 years old) patients (4/5 lesions, 80%). Furthermore, the combination between ours and previously published data confirmed a significant difference in the frequency of FGFR1 mutations in CGCG from patients younger than 18 years at the time of diagnosis (9/23 lesions, 39%) when compared to older patients (1/31 lesions, 0.03%; p=0.0011), thus corroborating our observation in a cohort of 54 patients. FGFR1 variants in young CGCG patients could favour fast lesion growth, implying that they seek medical attention earlier. Our observation might help prioritise candidates for FGFR1 testing, thus opening treatment options with FGFR inhibitors.

Post-Operative Patients' Satisfaction and Quality of Life Assessment in Adult Patients with Obstructive Sleep Apnea Syndrome (OSAS).

BACKGROUND: The treatment for severe OSAS includes maxillomandibular advancement surgical option in selected cases. The aim of this study was to evaluate the post-operative impact of bimaxillary surgery on satisfaction and consequently the quality of life of these patients. METHODS: This study included 18 patients with severe OSAS who received maxillomandibular advancement surgery. Patients were divided into Group A (operated by CAD/CAM) and Group B (conventional surgery). The impact of bimaxillary surgery on satisfaction and quality of life of these patients was evaluated by utilizing post-operative life quality and Rustemeyer's patient-satisfaction-based survey. RESULTS: A total of 18 adult OSAS patients (Group A: 11 patients, Group B: 7 patients) with a mean age of 44.39 years (SD ± 9.43) were included. Mean follow-up period was 32.64 months (SD ± 21.91). No intra-operative complications were seen in any patients. Post-operative complication was seen in one patient and the mandible did not integrate. According to the results, overall post-operative satisfaction score was 79.72% (SD ± 9.96). There was no significant difference among those in Group A and Group B. CONCLUSIONS: Maxillomandibular advancement surgery seems to be beneficial in terms of patients' satisfaction in severe adult OSAS patients and can be considered as a valuable option in selected cases.

Comparing prognostic utility between the 8th edition of TNM staging system and the lymph node ratio for oral squamous cell carcinoma.

BACKGROUND: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is associated with poor prognosis. The 8th edition of TNM has implemented new nodal staging criteria. We assess the prognostic utility of the lymph node ratio (LNR) and compare it to that of pN in the TNM 8th edition. METHODS: One hundred and forty-two patients with OSCC were retrospectively studied. Nodal staging was performed using the TMN 8th edition and the prognostic value of the LNR in terms of overall survival (OS) and disease-free survival (DFS) was evaluated. RESULTS: Fifty-seven patients were eligible for inclusion. The LNR was independently prognostic of OS (p = 0.02). Instead N classification was not significantly predictive of OS (p = 0.10). High LNRs resulted in decreases in OS of approximately 40% within 6 months after surgery. CONCLUSIONS: The LNR identifies patients with poor outcomes better than N classification. The lack of reliable LNR cutoffs compromises its utility in clinical practice.

Accuracy of Fibula Reconstruction Using Patient-Specific Cad/Cam Plates: A Multicenter Study on 47 Patients.

OBJECTIVES: This prospective study evaluated the accuracy of mandibular reconstruction using free fibular flaps (by comparing virtual plans to the three-dimensional postoperative results), and the extent of bone-to-bone contact after computer-assisted surgery. METHODS: We included 65 patients who underwent partial-continuity mandibular resections from February 2013 to January 2017, and evaluated virtual planning, surgical techniques, and accuracy. RESULTS: Forty-seven patients were analysed. A total of 112 fibular segments received 54 implants. We measured 227 distances between landmarks to assess the accuracy of reconstruction. Postoperative reconstruction accuracy ranged from 0.5 to 3 mm. CONCLUSION: Virtual surgical planning very accurately translated simulation into reality, particularly in patients requiring large, complex mandibular reconstructions using multiple fibular segments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2169-E2175, 2021.

Accuracy of splint vs splintless technique for virtually planned orthognathic surgery: A voxel-based three-dimensional analysis.

PURPOSE: This study compared two transferring methods for virtually planned orthognathic surgery - the CAD/CAM intermediate splint and the customized surgical guide with fixation plates. METHODS: This was a prospective clinical study in which participants were consecutively recruited and underwent bimaxillary orthognathic surgery. They were divided into two groups based on the transferring method used. The pre- and postoperative CBCTs were aligned using voxel-based landmark-free registration, and the discrepancies for selected points were compared with the planned displacement of the virtually planned surgery. The maxilla and mandible were analyzed separately, and translation and rotation movements were considered. RESULTS: A total of 16 patients, divided into two groups of eight patients each, were included in this study. The splintless group was significantly more accurate for the translation movement along the x-axes for points A (p = 0.008; mean absolute error 0.527 ± 0.387 for the splint group and 0.137 ± 0.067 for the splintless group) and Ans (p = 0.045; mean absolute error 0.535 ± 0.446 for the splint group and 0.156 ± 0.002 for the splintless group). For the mandible there was a significant difference in accuracy along the x-axes for points B (p = 0.049; mean absolute errors 1.728 ± 1.181 and 0.697 ± 0.519 for the splint and splintless groups, respectively), LL3 (p = 0.049; mean absolute error 1.629 ± 0.912 and 0.851 ± 0.797 for the splint and splintless groups, respectively), LR3 (p = 0.049; mean absolute error 1.711 ± 0.906 and 0.844 ± 0.780 for the splint and splintless groups, respectively), with the splintless group being more accurate. For the rotation the splintless group was significantly more accurate along the y-axes (p = 0.04; mean absolute error 1.62 ± 0.78 and 0.49 ± 0.31 for the splint and splintless groups, respectively) and z-axes (p = 0.04; mean absolute error 0.63 ± 0.45 and 0.17 ± 0.05 for the splint and splintless groups, respectively) for the maxilla, while no significant difference was found for the mandible. CONCLUSIONS: Overall, the customized fixation plate system is more accurate than the intermediate CAD/CAM splint for transferring the virtual plan into the operation room.

Dental implant-based oral rehabilitation in patients reconstructed with free fibula flaps: Clinical study with a follow-up 3 to 6 years.

BACKGROUND: Oral rehabilitation of patients after maxillofacial reconstructive surgery represents a challenge and stable prosthetic retention can be achieved with the use of dental implants. PURPOSE: This retrospective report aimed to evaluate implant-based oral rehabilitation following maxillofacial reconstruction with free fibula flaps. MATERIALS AND METHODS: A total of 14 patients who had reconstruction with fibula flaps either by CAD/CAM or conventional surgery were included in this study. A total of 56 implants (40 in flaps, 16 in native bone) were evaluated. Follow-up after reconstructive surgery ranged between 3.25 and 6.3 years. Follow-up after implant surgery ranged between 1.5 and 3.8 years. RESULTS: Overall survival rate was 85.7% in free fibula flaps and 85.6% in dental implants. Eight implants were lost in three patients and all of these failures were in dental implants inserted in free flaps. According to the results on patient basis, the implant survival was not influenced by any variable. CONCLUSIONS: The maxillofacial reconstruction with free fibula flap and oral rehabilitation with implant-supported prostheses after ablative surgery can be considered as an effective and safe procedure with successful aesthetic and functional outcomes.

Role of Axial Split Osteotomy of Free Fibula Flap in Mandibular Reconstruction and Dental Rehabilitation.

The fibula free flap (FFF) is regarded as the gold standard in mandibular reconstruction. Dental rehabilitation is important to improve the health-related quality of life of patients undergoing mandibular reconstruction. FFF provides adequate cortical bone osseous tissue for use in dental implantation. The application of "axial split osteotomy" via a double-barrel fibula graft may enable discrepancies between the native mandible and FFF to be avoided, thereby improving the likelihood of early and successful dental rehabilitation.

Computer-Aided Design and Computer-Aided Manufacturing Versus Conventional Free Fibula Flap Reconstruction in Benign Mandibular Lesions: An Italian Cost Analysis.

PURPOSE: The cost of computer-aided design and computer-aided manufacturing (CAD-CAM) technology has created obstacles for its widespread use despite its several advantages. This study compared the cost of CAD-CAM technology with that of the conventional freehand technique in fibula reshaping for mandibular reconstruction. MATERIALS AND METHODS: A retrospective comparative study was conducted at the Maxillofacial and Dental Unit of the Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico (Milan, Italy). The study compared 15 patients in the CAD-CAM group with 10 patients in the conventional freehand group. Only benign pathologic lesions that required at least 3 fibular segments for reconstruction were included. The consumption of resources was estimated using micro-costing analysis (activity-based costing approach). RESULTS: The CAD-CAM group included 15 patients (7 men and 8 women) with a mean age of 42.2 ± 1.5 years, and the conventional freehand group included 10 patients (4 men and 6 women) with a mean age of 40.8 ± 0.9 years. Although CAD-CAM was a statistically expensive procedure in the perioperative phase (P < .0001), no significant difference was shown in total health care costs between the 2 groups (P = .98). CONCLUSION: CAD-CAM technology had a comparable expense to the conventional freehand technique, specifically for defects requiring at least 3 fibular segments.

Phenytoin and gingival mucosa: A molecular investigation.

Several distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers, caused gingival overgrowth. One of the main drugs associated with the gingival overgrowth is the anti-epileptic such as phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. In our study, we evaluate the effect of phenytoin, a drug whose active substance is phenytoin, on gingival fibroblasts of healthy volunteers. Gene expression of 29 genes was investigated in gingival fibroblasts' cell culture treated with phenytoin compared with untreated cells. Among the studied genes, only 13 genes (CXCL5, CXCL10, CCR1, CCR3, CCR5, CCR6, IL-1A, IL-1B, IL-5, IL-7, IL-6R, BMP-2, and TNFSF-10) were statistically significant. All but one gene resulted downregulated after 24 h of treatment with phenytoin. BPM2 was the only, although weakly, up-expressed gene. Probably, we have not highlighted overexpression of the other inflammatory molecules because the study was performed on healthy people. Many studies show that phenytoin induces the overexpression of these cytokines but, probably, in our study, the drug does not have the same effect because we used gingival fibroblasts of healthy people.

Drug-induced gingival hyperplasia: An in vitro study using amlodipine and human gingival fibroblasts.

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast's function in gingival overgrowth. To determine whether amlodipine alters the inflammatory responses, we investigated its effects on gingival fibroblast gene expression as compared with untreated cells. Fragments of gingival tissue of healthy volunteers (11 years old boy, 68 years old woman, and 20 years old men) were collected during operation. Gene expression of 29 genes was investigated in gingival fibroblast cell culture treated with amlodipine, compared with untreated cells. Among the studied genes, only 15 (CCL1, CCL2D, CCL5, CCL8, CXCL5, CXCL10, CCR1, CCR10, IL1A, IL1B, IL5, IL7, IL8, SPP1, and TNFSF10) were significantly deregulated. In particular, the most evident overexpressed genes in treated cells were CCR10 and IL1A. These results seem to indicate a possible role of amlodipine in the inflammatory response of treated human gingival fibroblasts.

Copy number variation analysis of twin pairs discordant for cleft lip with or without cleft palate.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.

Use of CAD-CAM technology to improve orthognathic surgery outcomes in patients with severe obstructive sleep apnoea syndrome.

INTRODUCTION: Although multilevel surgery is the mainstay treatment for severe obstructive sleep apnoea syndrome (OSAS), bi-maxillary surgery (maxillomandibular advancement [MMA]) is the most efficacious single procedure for the expansion of the whole pharyngeal airway. MMA is an alternative to the gold standard of continuous positive airway pressure and is equivalent to tracheotomy. PATIENTS AND METHOD: Computer-aided design/computer-aided manufacturing (CAD-CAM) technology was used to virtually assess the degree of mandibular and/or maxillary advancement and rotation required to obtain adequate posterior airway space (PAS) in eight patients (seven males, one female). The mean age of the patients was 45.5 years (range, 27-51 years), and the average body mass index was 28.9 kg/m2 (range, 21.9-31.8 kg/m2). RESULTS: The study group showed significant mandibular advancement, widening of the PAS, and reduction of the apnoea hypopnea index (p < 0.0001, p < 0.0001, and p < 0.0002, respectively). Moreover, patient satisfaction scores regarding postoperative facial profile changes showed excellent compliance. CONCLUSION: This study demonstrated that bi-maxillary surgery is an efficient single surgical procedure in patients with multilevel OSAS. CAD-CAM technology aided surgeons in performing this operation precisely and enabled patients to expect specific facial profiles.

A novel integrated platform for the identification of surgical margins in oral squamous cell carcinoma: results from a prospective single-institution series.

BACKGROUND: The optimal surgical margins assessment is capital in oral squamous cell carcinoma (OSCC) management. We evaluated the clinical benefits of integrating intraoperative macroscopic margin (MM) assessment and narrow band imaging (NBI). METHODS: Sixteen OSCC patients eligible for surgery were prospectively enrolled. For each patient, 2 to 6 bioptic samples of MM and NBI margins were obtained and histologically analyzed for the presence of dysplasia and lymphocytes. Microvessel density was investigated by CD34 immunohistochemistry. RESULTS: Taken together, 104 specimens were analyzed, including 15% tumors, 33% MM, 33% NBI margins, and 19% MM-NBI overlapping margins. The NBI margins were closer to the lesion in 50% cases, while the same number of MM were more conservative than NBI, irrespective of the tumor site. The rate of histologically positive margins was similar among the two methods, akin to the microvessel density. CONCLUSIONS: MM assessment should be integrated but not replaced with the NBI technology to allow for more conservative surgery.

Evaluation of the Accuracy of Virtual Planning in Orthognathic Surgery: A Morphometric Study.

BACKGROUND: The purpose of this study was to prospectively test the accuracy of computer-aided orthognathic surgery comparing the virtual surgical planning with the three-dimensional (3D) outcome. METHODS: Patients that underwent computer-assisted orthognathic surgery were retrospectively evaluated. The postoperative results were compared with the surgical plan, superimposing the postoperative computed tomography (CT) scan onto the virtual plan. Surface-based superimpositioning of the postoperative CT scan onto the 3D preoperative plan was carried out to visualize the discrepancy between preoperative virtual plan and postoperative 3D CT result. RESULTS: A total of 17 consecutive patients that underwent two-jaw computer-assisted orthognathic surgery were enrolled in the study.The average linear differences for selected points were <1 mm in 12 patients out of 17. In 5 patients out of 17, the average differences for selected points were <2 mm. CONCLUSIONS: An overall high degree of accuracy between the virtual plan and the postoperative result was found.

Donor-Site Morbidity After Osteocutaneous Free Fibula Transfer: Longitudinal Analysis of Gait Performance.

PURPOSE: The purpose was to evaluate donor-site clinical morbidity and changes in kinematic gait parameters after the harvest of a vascularized free fibula flap for facial reconstruction. MATERIALS AND METHODS: We enrolled 14 patients (aged 50 ± 15 years) in a longitudinal study. Every patient underwent a double evaluation in which a presurgical assessment and 6-month postsurgical assessment were performed. Subjective donor-site evaluation was carried out through unstructured clinical questioning about pain, paresthesia, walking ability, and restrictions in activity. Further subjective evaluations were assessed through the Western Ontario and McMaster Universities Osteoarthritis Index and the Point Evaluation System for Lower Extremity Fibulectomy. A clinical evaluation of the donor site assessed muscular deficits, sensibility disturbance, and wound healing. Temporal and spatial kinematic parameters were measured through gait analysis during overground walking at a comfortable speed. RESULTS: Postsurgical clinical examinations detected 1 patient affected by a neurologic disorder and 3 patients with donor-site pain, whereas 10 patients (71%) declared no residual alterations in the operated leg. On average, the Western Ontario and McMaster Universities Osteoarthritis Index score was 367 of 2,400, and the Point Evaluation System for Lower Extremity Fibulectomy score was 19 of 24. Presurgical versus postsurgical gait analysis comparison showed no significant differences in gait parameters except for a 6% reduction in the double-support phase. Stance values were higher for the operated limb in both evaluations (+1.3% before surgery, +1.8% after surgery). No alterations were detected in the range of motion of the lower-limb joints. CONCLUSIONS: Considering the slight modification of the gait pattern, which is not usually perceived by patients, vascularized free fibula flap harvest was generally associated with successful functional and subjective outcomes of the donor site.

Fibula free flap pedicle ossification: Experience of two centres and a review of the literature.

PURPOSE: The osteogenic potential of vascularized periosteum has been described in a few cases in the literature, and many different factors have been pointed out as plausible. Our aim was to review the literature in order to give a complete overview of this topic and to report on our clinical experience. PATIENTS & METHODS: Our experience includes three patients who underwent maxillectomy and FFF reconstruction. A progressive reduction in mouth opening was noticed in the months after surgery, and CT scans showed calcified tissue around the pedicle. Surgical revisions were performed. No recurrences were noticed. A full systematic literature review was conducted, including studies published on or before September 2016. RESULTS: Clinically, free flap pedicle ossification is presented as trismus, hard swelling, and severe pain during movements, although the diagnosis is scarce and often fortuitous. From January 2010 to January 2016 we performed 68 FFF reconstructions, and the incidence of FFF pedicle ossification in our experience was 4.4%. CONCLUSION: Ossification of FFF pedicle is uncommon, but when it occurs, it has dramatic clinical consequences. Follow-up CT scan can be useful in diagnosis. In our experience, surgery should be performed only when the patient is symptomatic.

Resorbable Materials for Reconstruction of the Orbital Floor in Children.

The best treatment of pediatric orbital fractures is debated and different strategies are proposed in the literature. Resorbable materials, due to their features and the specific requirements of the pediatric population, seem a very suitable choice. The authors present their experience by describing 3 cases and explaining their mesh modeling technique. Two fractures were caused by accidental falls, whereas the other resulted from aggression. Clinical and radiological evaluation (computed tomography scanning) was performed before surgery. No complications occurred either immediately after surgery or in the long term (maximum follow-up of 3 y). As there has been little experience of the use of resorbable mesh in maxillofacial pediatric traumatology, the authors describe their technique, which may facilitate the use of this material in orbital fractures.