Comprehensive Genomic Profiling of Central Giant Cell Lesions Identifies Clinically Relevant Genomic Alterations.

PURPOSE: Comprehensive genomic profiling (CGP) can simultaneously detect clinically relevant genomic alterations (CRGAs) in hundreds of cancer-related genes and direct treatment toward patient-specific therapy options for many tumors. This pilot study aimed to use CGP to describe CRGAs present in central giant cell lesions (CGCLs) to characterize any possible underlying genomic drivers of CGCLs. MATERIALS AND METHODS: With institutional review board approval, electronic medical records were searched for patients with histologically confirmed CGCLs who underwent biopsy at Mayo Clinic from 2000 through 2014. Clinical characteristics were recorded from the medical records. At least 50 ng of DNA was extracted from formalin-fixed paraffin-embedded archival CGCL specimens by use of hybridization-capture, adaptor ligation-based libraries targeting all exons from 315 cancer-related genes plus select introns from 28 genes commonly rearranged in cancer. Samples were sequenced to high, uniform coverage and assessed for all 4 classes of genomic alterations: base substitutions, small insertions and deletions, rearrangements, and copy number alterations. RESULTS: Of 8 CGCL specimens, 3 (37.5%) harbored CRGAs, including base substitutions in BRAF, GNAS, and KRAS that are predicted to be oncogenic. In 1 sample, focal high-level amplification of the MITF gene was detected. Rearrangement in the PDGFRB gene was identified in a fourth sample, although the significance of this alteration is uncertain. CONCLUSIONS: This pilot study shows that a relatively high frequency of CRGAs (37.5%) can be identified in CGCLs by use of CGP. Furthermore, 25% of CGCLs analyzed had somatic mutations predicted to activate the mitogen-activated protein kinase signaling pathway, suggesting it may be a driver of the aggressive behavior of these lesions. On the basis of this study, genomic profiling of a larger cohort of CGCLs to validate these observations, as well as correlate mutations with aggressive versus nonaggressive biological behavior and therapeutic responses, appears warranted.

Higher perioperative fluid administration is associated with increased rates of complications following head and neck microvascular reconstruction with fibular free flaps.

PURPOSE: The purpose of this study is to evaluate the impact of perioperative fluid administration on the rates of postoperative complications following head and neck reconstruction with fibular free flaps (FFF). METHODS: A retrospective cohort study of subjects undergoing head and neck reconstruction with FFF was completed. The primary predictor variable was the total volume of perioperative fluids administered on the day of surgery. The primary outcome variable was the presence of medical and surgical complications occurring within 30 days of surgery. Medical and surgical complications were stratified as major or minor based on severity level. Basic demographic information, comorbidity indices, and intraoperative parameters were abstracted as covariates. Univariable and multivariable models were developed to assess for associations between total fluid volume administered on the day of surgery and postoperative medical/surgical complications occurring within 30 days of surgery. RESULTS: In 154 subjects, the partial flap failure rate was 3% and there were no complete flap failures. Total fluid volume was significantly associated with the presence of postoperative medical/surgical complications (OR = 1.21; 95% CI: 1.02-1.44; p = 0.032). A cutpoint for total fluid volume predicting any severity level of postoperative complication was identified at 5,500 mL. A cutpoint for total fluid volume predicting major postoperative complications was identified at 7,000 mL. CONCLUSIONS: The results of this study suggest that liberal fluid administration is associated with increased rates of medical/surgical complications following head and neck reconstruction with FFF. © 2016 Wiley Periodicals, Inc. Microsurgery 37:128-136, 2017.

Orthognathic Surgery in Patients With Congenital Myopathies and Congenital Muscular Dystrophies: Case Series and Review of the Literature.

PURPOSE: This case series examined preoperative findings and the surgical, anesthetic, and postoperative management of 6 patients with congenital myopathies (CMs) and congenital muscular dystrophies (CMDs) treated at a tertiary medical institution with orthognathic surgery over 15 years to describe pertinent considerations for performing orthognathic surgery in these complex patients. MATERIALS AND METHODS: According to the institutional review board-approved protocol, chart records were reviewed for all orthognathic surgical patients with a clinical, genetic, or muscle biopsy-proved diagnosis of CM or CMD. RESULTS: Six patients (5 male, 1 female) qualified, and they were treated by 4 surgeons in the division of oral and maxillofacial surgery from 1992 through 2007. Average age was 19.5 years at the time of orthognathic surgery. Five patients had Class III malocclusions and 1 patient had Class II malocclusion. All 6 patients had apertognathia with lip incompetence. Nasoendotracheal intubation with a difficulty of 0/3 (0=easiest, 3=most difficult) was performed in all cases. Routine induction and maintenance anesthetics, including halogenated agents and nondepolarizing muscle relaxants, were administered without malignant hyperthermia. All 6 patients underwent Le Fort level osteotomies; 4 also had mandibular setback surgery with or without balancing mandibular inferior border osteotomies. Five patients required planned intensive care unit care postoperatively (average, 18.4 days; range, 4 to 65 days). Postoperative respiratory complications resulting in major blood oxygen desaturations occurred in 5 patients; 4 of these patients required reintubation during emergency code response. Five patients required extended postoperative intubation (average, 4.2 days; range, 3 to 6 days) and ventilatory support. Average hospital length of stay was 21.8 days (range, 6 to 75 days). Average postoperative follow-up interval was 29.8 weeks (range, 6 to 128 weeks). CONCLUSIONS: Patients with CMs or CMDs often have characteristic dentofacial malocclusions that contribute to functional problems with feeding and drooling and psychosocial problems. Orthognathic surgery, usually bimaxillary, can be judiciously considered in these patients; these procedures typically require multidisciplinary pre- and postoperative evaluation and care over lengthy hospital stays with a high risk of respiratory complications that bear consideration in treatment planning.

Impact of Perioperative Fluid Administration on Postoperative Morbidity and Length of Hospital Stay Following Maxillomandibular Advancement for Obstructive Sleep Apnea.

PURPOSE: The purpose of this study was to evaluate whether the volume of perioperative fluids administered to patients undergoing maxillomandibular advancement (MMA) for treatment of obstructive sleep apnea (OSA) is associated with an increased incidence of postoperative complications and prolonged length of hospital stay. MATERIALS AND METHODS: A retrospective cohort study design was implemented and patients undergoing MMA for OSA at the Mayo Clinic were identified from 2001 through 2014. The primary predictor variable was the total volume of intravenous fluids administered during MMA. The primary outcome variable was length of hospital stay in hours. Secondary outcome variables included the presence of complications incurred during postoperative hospitalization. Additional covariates abstracted included basic demographic data, preoperative body mass index, preoperative apnea-hypopnea index, preoperative Charlson comorbidity index, preoperative American Society of Anesthesiologists score, type of intravenous fluid administered, surgical complexity score, duration of anesthesia, duration of surgery, and the use of planned intensive care unit admission. Univariate and multivariable models were developed to assess associations between the primary predictor variable and covariates relative to the primary and secondary outcome variables. RESULTS: Eighty-eight patients undergoing MMA for OSA were identified. Total fluid volume was significantly associated with increased length of stay (odds ratio [OR] = 1.34, 95% confidence interval [CI], 1.05-1.71; P = .020) in univariate analysis. Total fluid volume did not remain significantly associated with increased length of hospital stay in stepwise multivariable modeling. Total fluid volume was significantly associated with the presence of postoperative complications (OR = 1.69; 95% CI, 1.08-2.63; P = .021) in univariate logistic regression. CONCLUSION: Fluid administration was not found to be significantly associated with increased length of hospital stay after MMA for OSA. Increased fluid administration might be associated with the presence of postoperative complications after MMA; however, future large multicenter studies will be required to more comprehensively assess this association.

Pode-se usar tomografia de feixe em cone para medições periodontais de nível de inserção? / Does CBCT have potential as a diagnostic tool for measuring Periodontal Attachment Levels?

Objetivos: Pode-se usar tomografia de feixe em cone (TFC) para medições periodontais de nível de inserção (NI)? Este projeto avalia a precisão e reproducibilidade das medidas de NI usando TFC. Introdução: O meio de sondagem periodontal mesmo tendo pouca validade e métodos trabalhosos reconhecida por décadas, continua sendo o padrão-ouro para medidas de NI. O método de TCF pode ser automatizado e elimina a necessidade da medida clínica trabalhosa e longa. Métodos: 57 participantes tiveram TFC e medidas clínicas de NI para este estudo aprovado pelo Conselho de Revisão Institucional (IRB). Um scanner de TFC Hitachi CB Mercu Ray modificado foi usado com os parâmetros 120 kVp e 15 mA num tamanho de imagem de 15cm. Um examinador independente, cegado e previamente calibrado mediu a distância entre a junção esmalte cemento até a crista óssea alveolar (JEC-COA) em 4 faces por dente (total de 4.798 faces), usando um computador. A JEC foi estabelecida pela mudança relativa de densidade existente entre as estruturas dentais. As medidas feitas na TFC foram correlacionadas com as medidas clínicas. Resultados: Os coeficientes de Correlação de Intraclasses (ICC) para as medidas JEC-COA variaram entre 0,923 to 0,979, p<0,001, n=33. A correlação Spearman (rho) entre JEC-COA e NI para todas as faces foi 0,127, p=0,004, α=0,05, n=498. Nos molares rho=0,338, p<0,001, α=0,05, n=145. No premolares rho=0,195, p=0,013, α=0,05, n=162. No dentes anteriores rho=-0,059, p=0,414, α=0,05, n=191. Exibiu-se uma tendência clínica de se subestimar as medidas de NI de forma general, com uma tendência menor nas regiões dos molares do que nos premolares. Esta tendência foi no máximo 0,6 mm, menor que a resolução capaz de uma sonda periodontal, e portanto clinicamente insignificante. Conclusão: As medidas de NI feitas com TFC são reproduzíveis, e precisas. O protocolo de medida NI TFC tem um potencial na habilidade de medir NI clínicos. Mesmo não podendo ser utilizado atualmente como um método...

Objectives: Does Cone Beam Computed Tomography (CBCT) have potential as a diagnostic instrument for Periodontal Attachment Loss (PAL) measurement? This project assesses accuracy and reliability of automatable CBCT based PAL measurement instrument. Background: Even though, low validity and tedious procedure of clinical probing has been recognized for decades, it remains the gold standard measurement for PAL. CBCT is automatable and bypasses need for tedious clinical measurement. Methods: 57 participants underwent CBCT and clinical PAL measurement for this IRB approved study. A customized CB MercuRay was used at 120kVp and 15mA with a 6 inch field of view (FOV). A blinded examiner measured the distance from the CEJ to the crest of alveolar bone (CEJ-BM) at four sites per tooth (4,798 total sites). (The CEJ was determined by change in relative density between apical end of enamel and cementum or dentin.) CBCT measurements were correlated with the clinical measurements. Results: Intraclass Correlation Coefficients for measurement protocol (CEJ-BM) ranged from 0.923 to 0.979, p<0.001, n=33. Spearman’s Correlation Coefficient (rho) for CEJ-BM and PAL for all sites was 0.127, p=0.004, α=0.05, n=498. At molar sites, rho=0.338, p<0.001, α=0.05, n=145. At premolar sites, rho=0.195, p=0.013, α=0.05, n=162. At anterior sites, rho=-0.059, p=0.414, α=0.05, n=191. There is a clinically insignificant tendency to underestimate PAL overall, with a lesser tendency for underestimation in molar sites than in premolar sites. This tendency is at most 0.6mm, less than the resolution of a periodontal probe and therefore clinically insignificant. Conclusion: CBCT PAL measurement is reliable, and protocol accuracy correlates with PAL gold standard. CBCT PAL measurement protocol is promising in the ability to record clinical attachment levels. Although it cannot yet be used as a diagnostic screening tool in light of radiation concerns, current data suggest that it...