Julio Acero

The behaviour of titanium as a biomaterial: microscopy study of plates and surrounding tissues in facial osteosynthesis

Titanium has become the biomaterial of choice for facial osteosynthesis. Titanium is considered a highly biocompatible and corrosion resistant material, although the ultrastructural behaviour of titanium in human tissues after bone fixation is not well documented. A prospective scanning electron microscopy study was carried out on 37 commercially pure titanium miniplates which were removed from 23 patients who had undergone surgery for maxillofacial trauma or deformity. Twenty two cases were used as a control group. Implant-bone specimens were excised using tungsten burs and studied with a scanning electron microscope (Jeol JSM-T-300). Findings at the bone-titanium interface were analyzed, as well as the presence of contaminating bodies on the specimen surface. Biopsies were also obtained from the soft tissues adjacent to 20 miniplates, then sectioned and stained with Haematoxilin-Eosin for histological evaluation by light microscopy. The results showed good ultrastructural osseointegration of the osteosynthesis material in most cases (81.8%). Mobility was found upon removal in 80% of plates which showed clinical complications. A significant correlation was found between the degree of microscopical osseointegration and macroscopic fixation of the plate. Microscopical contamination was found in 100% of the nine plates with intraoral exposure, while only 36% of the 22 miniplates of the control group had contaminating elements (P < 0.001). Thirty-five point one percent of the plates showed hole-like substance loss images, whose size ranged from 10-25 mu. Light microscopy showed granular deposits in soft tissues surrounding the plates in 80% of the 20 specimens investigated. Our findings suggest a higher development of corrosion in titanium than previously reported. These findings are not correlated, however with the clinical complications.

NID2 and HOXA9 Promoter Hypermethylation as Biomarkers for Prevention and Early Detection in Oral Cavity Squamous Cell Carcinoma Tissues and Saliva

Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance, we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and quantitative methylation specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage design consisting of discovery and prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the discovery screen. HOXA9 had 68% sensitivity, 100% specificity, and a 0.81 Area Under the Curve (AUC). NID2 had 71% sensitivity, 100% specificity, and a 0.79 AUC. In the prevalence screen, HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity, and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity, and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity, and a 0.97 AUC. In saliva, from OSCC cases and controls, HOXA9 had 75% sensitivity, 53% specificity, and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity, and a 0.73 AUC. This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies. Cancer Prev Res; 4(7); 1061–72. ©2011 AACR.

Infratemporal-Preauricular-Cervical Approach for Resection of a Cavernous Intramasseteric Hemangioma: A Case Report

1. Engevall S, Fischer K: Dislocation of the mandibular condyle into the middle cranial fossa: Review of literature and report of a case. J Oral Maxillofac Surg 50:524, 1992 2. Bradley P: Injuries of the condylar and coronoid process, in Rowe NL, Williams JLL (eds): Maxillofacial Injuries. New York, NY, Churchill Livingstone, 1985, pp 337-362 3. Musgrove BT: Dislocation of the mandibular condyle into the middle cranial fossa. Br J Oral Maxillofac Surg 24:22, 1986 4. Seymour RL, Irby WB: Dislocation of the condyle into middle cranial fossa. J Oral Surg 34:180, 1976 5. Clauser L, Tieghi R, Polito J, et al: Dislocation of the mandibular condyle into the middle cranial fossa. J Craniofac Surg 17:590, 2006 6. Kapila BK, Lata J: Superolateral dislocation of an intact mandibular condyle into the temporal fossa: A case report. J Trauma 41:351, 1996 7. Barron RP, Kainulainen VT, Gusenbauer AW, et al: Fracture of glenoid fossa and traumatic dislocation of mandibular condyle into middle cranial fossa. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93:640, 2002

Sliding osteotomies in mandibular reconstruction.

The aim of this article is to describe a few simple and atraumatic methods for mandibular reconstruction following the ablation of tumors or traumas. These reconstruction techniques are indicated for rebuilding short mandibular defects (less than 4 cm) or for patients in poor general condition with larger defects that cannot be remedied using longer and more complicated procedures. Five types of osteotomies were used: “C,” single, double, bilateral sliding, and sagittal sliding. Osteotomies were performed on 14 patients, 13 with malignant tumors and one with a gunshot wound. Good results were obtained in 10 patients, total failure occurred in two, and complications without failure of the reconstruction arose in the other two. (Plast. Reconstr. Surg. 107: 1107, 2001.)

Microsurgical reconstruction of the head and neck region: Current concepts of maxillofacial surgery units worldwide

INTRODUCTION Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the surveys on current reconstructive practice in German-speaking countries and Europe, this paper presents the third phase of the project when the survey was conducted globally. METHODS The DOESAK questionnaire has been developed via a multicenter approach with maxillofacial surgeons from 19 different hospitals in Germany, Austria and Switzerland. It was distributed in three different phases to a growing number of maxillofacial units in German-speaking clinics, over Europe and then worldwide. RESULTS Thirty-eight units from Germany, Austria and Switzerland, 65 remaining European OMFS-departments and 226 units worldwide responded to the survey. There is wide agreement on the most commonly used flaps, intraoperative rapid sections and a trend towards primary bony reconstruction. No uniform concepts can be identified concerning osteosynthesis of bone transplants, microsurgical techniques, administration of supportive medication and postoperative monitoring protocols. Microsurgical reconstruction is the gold standard for the majority of oncologic cases in Europe, but worldwide, only every second unit has access to this technique. CONCLUSION The DOESAK questionnaire has proven to be a valid and well accepted tool for gathering information about current practice in reconstructive OMFS surgery. The questionnaire has been able to demonstrate similarities, differences and global inequalities.

I Conferencia Nacional de Consenso sobre el Injerto Óseo del Seno Maxilar

Resumen Objetivo El objetivo de la I Conferencia Espanola de Consenso sobre el Injerto Oseo Sinusal era intentar llegar a puntos de acuerdo sobre las principales controversias de esta tecnica, aplicada de forma muy variada y con el empleo de materiales muy diversos, y conseguir plasmar los mismos en un documento resumen consensuado por todos los autores. Material y metodo Durante los dias 17 y 18 de octubre de 2008 se celebro en Oviedo la citada conferencia, auspiciada por la Sociedad Espanola de Cirugia Oral y Maxilofacial. En ella se dieron cita un total de 50 ponentes de reconocido prestigio nacional e internacional que repasaron en 6 mesas de trabajo las principales controversias sobre los injertos oseos sinusales. Tras las conferencias de los ponentes, los moderadores establecian las principales conclusiones de cada mesa y se abria un turno de debate donde participaban todos los asistentes. Resultado Este documento y sus conclusiones emanan de las presentaciones realizadas por los ponentes y de las deliberaciones y acuerdos de cada mesa de trabajo. Ambos han sido aprobados tras varias correcciones por todos los autores antes de ser enviados para su publicacion. Ademas, han obtenido el reconocimiento cientifico oficial de la Sociedad Espanola de Cirugia Oral y Maxilofacial y deben servir como base para futuros estudios y reuniones cientificas. Conclusiones El objetivo fundamental cuando se realiza un injerto oseo sinusal es la formacion de hueso vital en el seno maxilar, para conseguir la supervivencia a largo plazo de los implantes tras su carga protesica. Para ello, la tecnica y la secuencia de tratamiento deben orientarse a conseguir resultados predecibles y estables en el tiempo, aunque esto suponga un mayor tiempo de espera hasta la colocacion de la protesis. La estabilidad inicial del implante es el factor clave para la osteointegracion y debe ser el principal criterio para indicar implantes simultaneos o diferidos en el seno maxilar.

A worldwide comparison of the management of T1 and T2 anterior floor of the mouth and tongue squamous cell carcinoma – Extent of surgical resection and reconstructive measures

INTRODUCTION Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the results on general aspects of current reconstructive practice in German-speaking countries, Europe and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T1/T2 squamous cell carcinoma (SCC) of the anterior floor of the mouth and tongue. METHODS The DOESAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated. RESULTS A total of 188 OMFS units from 36 different countries documented their treatment strategies for T1/T2 anterior floor of the mouth squamous cell carcinoma and tongue carcinoma. For floor of mouth carcinoma close to the mandible, a wide variety of concepts are presented: subperiosteal removal of the tumor versus continuity resection of the mandible and reconstruction ranging from locoregional closure to microvascular bony reconstruction. For T2 tongue carcinoma, concepts are more uniform. CONCLUSION These results demonstrate the lack of evidence and the controversy of different guidelines for the extent of safety margins and underline the crucial need of global prospective randomized trials on this topic to finally obtain evidence for a common guideline based on a strong community of OMFS units.

Reoperative Midface Reconstruction

Reoperative reconstruction of the midface is a challenging issue because of the complexity of this region and the severity of the aesthetic and functional sequela related to the absence or failure of a primary reconstruction. The different situations that can lead to the indication of a reoperative reconstructive procedure after previous oncologic ablative procedures in the midface are reviewed. Surgical techniques, anatomic problems, and limitations affecting the reoperative reconstruction in this region of the head and neck are discussed.

A worldwide comparison of the management of surgical treatment of advanced oral cancer

INTRODUCTION Microvascular surgery following tumor resection has become an important field of oral and maxillofacial surgery (OMFS). Following the results from management of T1/T2 floor-of-mouth and tongue squamous cell carcinoma (SCC) in German-speaking countries, Europe, and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T3/T4 SCC of the maxillary and mandibular alveolar process and tongue. METHODS The DÖSAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated. RESULTS A total of 188 OMFS units from 36 different countries documented their treatment strategies for T3/T4 maxillary and mandibular alveolar process and tongue SCC. The extent of surgical resections and subsequent reconstructions is more consistent than with T1/T2 tumors, although the controversy surrounding continuity resections and mandible-sparing procedures remains. For continuity resection of the mandible the fibula free flap is the most frequently used bone replacement, whereas maxilla reconstruction concepts are less consistent, ranging from locoregional coverage concepts and different microvascular reconstruction options to treatment via obturator prosthesis. CONCLUSION Results from treatment strategies for T3/T4 tumors underline the limited evidence for the appropriate amount of resection and subsequent reconstruction process, especially in cases involving the mandible. Prospective randomized trials will be necessary in the long term to establish valid treatment guidelines.

Abstract 2924: Genome-wide microarray platforms uncover novel hypermethylated genes in an oral squamous cell carcinoma case-control study: A phase I preclinical biomarker development study

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Introduction: Panels of hypermethylated genes have been proposed as diagnostic markers in primary head and neck squamous cell carcinoma using a pharmacological unmasking expression microarray approach. Such experiments are performed in cancer cell lines, mostly with poor relevance when extrapolating to primary cancers. Objective: To overcome this lack of relevance we used two unbiased genome-wide DNA methylation platforms that represent 28K CpG Islands and the promoter regions of 14K-17K genes to identify hypermethylated genes in Oral Squamous Cell Carcinoma (OSCC), which also exhibited downregulated expression in the Gene Expression Omnibus (GEO) repository. Methods: DNA isolated from normal, premalignant lesions and squamous cell carcinoma lesions of the oral cavity was: a) bisulfite treated and hybridized to Infinium arrays; b) enriched with Methylated DNA Immunoprecipitation (MeDIP) and hybridized to Nimblegen 385K tiling arrays. Bioinformatics strategies were used for background correction, array normalization and data analysis of differentially methylated genomic regions between tumor and normal tissue. Genes identified as hypermethylated in cancer with methylation platforms were cross-validated against expression profiles published in the GEO public data repository. Quantitative Methylation Specific PCR (QMSP) was then used to validate candidate genes that were both, hypermethylated and downregulated in cancer. Results: The two unbiased microarray platforms were successful in identifying three novel genes hypermethylated and down regulated in OSCC: MCAM, EDNRB and CALCA. EDNRB, MCAM and CALCA expression was downregulated in HNSCC when compared to normal tissue. A twofold or higher downregulated expression was seen for EDNRB (59%) than for MCAM (55%) and CALCA (55%). The sensitivity of each gene was higher for EDNRB (82%) than for MCAM (60%) and CALCA (76%). The specificity was also higher for EDNRB (86%) than for CALCA (71%), and MCAM (57%). KIF1a had both high sensitivity (82%) and specificity (86%) but there was no expression data in HNSCC available for this gene in the GEO repository. The Receiver Characteristic Operator Curves (ROC) for individual genes revealed area under the curve values (AUC) for: EDNRB (0.88), CALCA (0.85), KIF1a (0.84), and MCAM (0.61). Methylation of three genes was found in 71% of tumor and 0% of normal tissue. Methylation of two genes was found in 82% of tumor and 29% of normal tissue. Conclusion: We successfully demonstrated that unbiased genome-wide methylation arrays paired with publicly available expression data identify panels of relevant hypermethylated genes in primary OSCC. MCAM, KIF1a, EDNRB and CALCA were identified as hypermethylated in OSSC tumor tissue, when compared to normal tissue. These results should be validated in a Phase II Biomarker Development Study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2924.