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1.
J Oral Maxillofac Surg ; 80(9): 1544-1549, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35679901

RESUMEN

We describe a method for performing mandibular resection and vascularized tissue transfer via an intraoral and contralateral submandibular approach to minimize the risk of wound complications in a radiated field. Surgery on radiated tissue associated with osteoradionecrosis of the mandible can present with oral cutaneous fistulas, dense fibrotic skin, and altered tissue planes to make dissection through this tissue tedious and can place the marginal mandibular nerve at increased risk of injury. The use of custom plates allows surgeons to minimize incisions and depend less on anatomic/visual cues during surgery to obtain an accurate result. Our experience in 8 patients has shown a predictable method for resection and reconstruction of the mandible, while minimizing the potential complications associated with previously radiated and operated patients.


Asunto(s)
Colgajos Tisulares Libres , Osteorradionecrosis , Procedimientos de Cirugía Plástica , Colgajos Tisulares Libres/cirugía , Cabeza/cirugía , Humanos , Mandíbula/cirugía , Osteorradionecrosis/etiología , Osteorradionecrosis/cirugía , Procedimientos de Cirugía Plástica/efectos adversos
2.
Proc Natl Acad Sci U S A ; 116(14): 6954-6963, 2019 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-30886100

RESUMEN

Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry without the addition of exogenous growth factors or cells. To translate this technology, we investigated its success in reconstructing a mandibular defect of physiologically relevant size in sheep. We fabricated and implanted 3D-printed in vivo bioreactors against rib periosteum and utilized biomaterial-based space maintenance to preserve the native anatomical mandibular structure in the defect site before reconstruction. Nine weeks after bioreactor implantation, the ovine mandibles were repaired with the autologous bony tissue generated from the in vivo bioreactors. We evaluated tissues generated in bioreactors by radiographic, histological, mechanical, and biomolecular assays and repaired mandibles by radiographic and histological assays. Biomaterial-aided mandibular reconstruction was successful in a large superior marginal defect in five of six (83%) sheep. Given that these studies utilized clinically available biomaterials, such as bone cement and ceramic particles, this strategy is designed for rapid human translation to improve outcomes in patients with large mandibular defects.


Asunto(s)
Sustitutos de Huesos , Mandíbula , Traumatismos Mandibulares , Periostio , Impresión Tridimensional , Ingeniería de Tejidos , Animales , Reactores Biológicos , Femenino , Mandíbula/metabolismo , Mandíbula/patología , Traumatismos Mandibulares/metabolismo , Traumatismos Mandibulares/patología , Traumatismos Mandibulares/terapia , Periostio/metabolismo , Periostio/patología , Ovinos
3.
J Oral Maxillofac Surg ; 77(4): 874.e1-874.e13, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30615849

RESUMEN

The complex 3-dimensional anatomy of the facial skeleton creates a unique challenge for surgical reconstruction. Even more difficult is the precise reconstruction of the maxilla owing to its lack of solid bony support after large resections. Virtual surgical planning (VSP) technology has many applications in head and neck surgery, such as preoperative planning, fabrication of cutting guides and stereolithographic models, and fabrication of custom implants. We present the case of a patient who had undergone surgical resection of a mucoepidermoid carcinoma of the maxilla and immediate reconstruction with a vascularized free fibula flap using VSP. Using a custom 3-dimensional, titanium printed plate, which corresponded precisely with the surgical defect, the maxilla and midface were reconstructed to ideal dimensions with no unplanned surgical manipulation and a shorter overall operating time. We have described the technique and reviewed the pertinent reported data.


Asunto(s)
Trasplante Óseo , Colgajos Tisulares Libres/trasplante , Reconstrucción Mandibular/instrumentación , Procedimientos de Cirugía Plástica/instrumentación , Impresión Tridimensional , Carcinoma Mucoepidermoide/cirugía , Diseño Asistido por Computadora , Femenino , Peroné , Humanos , Maxilar/cirugía , Neoplasias Maxilares/cirugía , Persona de Mediana Edad , Titanio
4.
J Oral Maxillofac Surg ; 75(10): 2254-2260, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28399392

RESUMEN

PURPOSE: The purpose of this review is to 1) evaluate our early experience with urinary bladder matrix as a dressing for the management of complex wounds subsequent to fasciocutaneous or osteocutaneous vascularized tissue harvests, 2) assess coverage of exposed tendons and the duration of granulation and epithelial coverage, and 3) assess esthetic and functional outcomes compared with traditional means for the management of vascularized tissue harvest sites. PATIENTS AND METHODS: This prospective study consisted of 8 consecutive patients in whom a substantial cutaneous component was harvested as part of a vascularized tissue reconstruction, which did not permit for primary closure (n = 7) or had skin graft failure (exposed tendon) that required additional treatment (n = 1). RESULTS: Functional and esthetic outcomes were comparable to those of traditional methods of donor site closure as determined by clinical evaluation and subjective assessment by the patient. In all patients, no additional grafting was required to achieve full coverage. Irregularities of the wound achieved a level plane with granulation tissue an average of 3 to 4 weeks after surgery, followed by an additional 5 to 8 weeks for epithelialization. Wound care was minimal and included twice-daily wet-to-dry dressings. It was noted that complete wound healing was delayed in the urinary bladder matrix group, which required more attention during wound care when compared with published data. Advantages included facilitation of a robust granulation layer that leveled wound irregularities and avoidance of an additional skin graft site. CONCLUSIONS: The use of urinary bladder matrix is a viable option for the rehabilitation of donor sites of vascularized tissue that include skin. Benefits include the avoidance of an additional skin graft donor site, facilitation of epithelialization over exposed tendons, leveling of the donor site texture, and an equivalent esthetic result compared with current practices for wound coverage. The success of this technique may be limited by the cost of materials and the protracted course for wound epithelialization.


Asunto(s)
Colgajos Tisulares Libres , Sitio Donante de Trasplante/cirugía , Vejiga Urinaria/trasplante , Fascia/trasplante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplante de Piel , Cicatrización de Heridas
5.
J Oral Maxillofac Surg ; 75(4): 828-838, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27810548

RESUMEN

PURPOSE: Reconstruction of hard tissue continuity defects caused by ablative tumor surgery has been traditionally reconstructed with autogenous bone grafts or microvascular free flaps. Although results have been predictable from these 2 methods of reconstruction, the morbidity associated with bone harvest is quite serious for the patient. Predictable results have been obtained with using a combination of 100% cadaver bone, bone marrow aspirate concentrate (BMAC), and recombinant human bone morphogenic protein in immediate reconstruction for benign tumor extirpations through the extraoral approach. In light of these successful outcomes, the same combination was evaluated with an intraoral approach. This study evaluated the success of immediate mandibular reconstruction through the intraoral approach without any autogenous bone harvesting. PATIENTS AND METHODS: The aim of this retrospective study was to share the authors' experience with the use of 100% allogeneic bone in combination with bone morphogenic protein and BMAC through the transoral approach for immediate reconstruction of continuity defects that resulted from benign tumor surgery. A retrospective chart review was performed of all patients undergoing bone graft reconstruction at the University of Texas Health Sciences Center at Houston (UTHealth) Department of Oral and Maxillofacial Surgery from December 2014 through January 2016. Inclusion criteria were biopsy-proven benign tumors, American Society of Anesthesiologists I or II health status, and adequate intraoral soft tissue for primary closure determined during initial consultation. RESULTS: Five patients who underwent this procedure at the UTHealth Department of Oral and Maxillofacial Surgery from December 2014 through January 2016 are presented. The success rate was 100%. All patients showed excellent bone quality clinically and radiographically for endosseous dental implant placement. With the transoral approach and no autogenous bone harvesting, the average operating time was 3.4 hours and the hospital stay was 2.4 days. CONCLUSIONS: Composite allogeneic tissue engineering is an effective and predictable technique for immediate reconstruction of continuity defects from ablative benign tumor surgery. Overall, there was no donor site morbidity, the intraoperative time was shorter, there were fewer admission days, and total costs overall were lower compared with traditional methods.


Asunto(s)
Trasplante Óseo/métodos , Neoplasias Mandibulares/cirugía , Reconstrucción Mandibular/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Neoplasias Mandibulares/patología , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
6.
J Oral Maxillofac Surg ; 74(9): 1898.e1-9, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27244274

RESUMEN

Recurrent invasive ameloblastoma of the infratemporal fossa is an uncommonly encountered phenomenon in the practice of oral and maxillofacial surgery and presents many surgical challenges for the practitioner. This case report describes a patient who underwent previous resection of a mandibular ameloblastoma with multiple recurrences. The patient was diagnosed with a recurrent ameloblastoma of the infratemporal fossa that was subsequently resected and reconstructed using an anterolateral thigh (ALT) free tissue transfer. There are few reported cases of recurrent ameloblastomas in the infratemporal fossa and none that describe surgical resection and reconstruction of such a lesion. Owing to the uniqueness of the surgical defect, an ALT flap was used to correct the temporal hollowing. There have been multiple reported cases of reconstruction of temporal hollowing defects using autogenous fat or allograft; however, none have described the use of a de-epithelialized ALT microvascular reconstruction of a temporal hollowing defect. This case report describes a unique clinical situation of surgical resection and reconstruction that resulted in a satisfactory outcome for the patient.


Asunto(s)
Ameloblastoma/patología , Ameloblastoma/cirugía , Colgajos Tisulares Libres , Neoplasias Mandibulares/patología , Neoplasias Mandibulares/cirugía , Reconstrucción Mandibular/métodos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Hueso Temporal/patología , Hueso Temporal/cirugía , Adulto , Ameloblastoma/diagnóstico por imagen , Humanos , Masculino , Neoplasias Mandibulares/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Hueso Temporal/diagnóstico por imagen , Muslo/irrigación sanguínea , Tomografía Computarizada por Rayos X
7.
J Oral Maxillofac Surg ; 74(8): 1678-86, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26902710

RESUMEN

PURPOSE: Buccal squamous cell carcinoma is an aggressive form of oral carcinoma with a high recurrence rate. Injury to the parotid duct is often unavoidable when surgically treating buccal squamous cell carcinoma because of the intimate anatomic relation among the buccal mucosa, Stensen duct, and parotid gland. It is often difficult to achieve negative margins and preserve the integrity of the parotid duct. Sialocele formation is a frequent and untoward complication owing to extravasation of saliva into the surgical defect, which delays healing, creates fistulas, and produces painful facial swelling. Currently, no consensus exists regarding the management of a parotid sialocele. Multiple investigators have described different modalities of treatment, such as repeated percutaneous needle aspiration, pressure dressings, antisialagogue therapy, radiotherapy, botulinum toxin, and surgical techniques, including duct repair, diversion, ligation, drain placement, and parotidectomy. MATERIALS AND METHODS: With approval from the institutional review board of the University of Texas Health Sciences Center at Houston, 3 cases of parotid sialocele and nonhealing fistulas successfully treated with Botox (onabotulinumtoxinA) after tumor extirpation, neck dissection, and reconstruction with a microvascular free flap are presented. RESULTS: At the University of Texas Health Sciences Center at Houston, the radiation oncologist prefers not to start adjunctive radiation treatment with a nonhealing wound or a drain in the field of radiation. Ideally, a standard timing of adjuvant radiotherapy is 6 to 8 weeks after surgery and 60 cGy should be completed before 7 months. CONCLUSIONS: With the use of Botox, the nonhealing wound resolved and the drain was removed at least 2 weeks before the initiation of adjunctive radiotherapy, thus minimizing the delay in adjuvant treatment.


Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Carcinoma de Células Escamosas/terapia , Quistes/tratamiento farmacológico , Fístula/tratamiento farmacológico , Colgajos Tisulares Libres/irrigación sanguínea , Fármacos Neuromusculares/uso terapéutico , Enfermedades de las Parótidas/tratamiento farmacológico , Neoplasias de la Parótida/terapia , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/tratamiento farmacológico , Adulto , Anciano , Terapia Combinada , Quistes/diagnóstico por imagen , Fístula/diagnóstico por imagen , Humanos , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
8.
Adv Exp Med Biol ; 881: 57-78, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26545744

RESUMEN

Over the past decades, there has been a substantial amount of innovation and research into tissue engineering and regenerative approaches for the craniofacial region. This highly complex area presents many unique challenges for tissue engineers. Recent research indicates that various forms of implantable biodegradable scaffolds may play a beneficial role in the clinical treatment of craniofacial pathological conditions. Additionally, the direct delivery of bioactive molecules may further increase de novo bone formation. While these strategies offer an exciting glimpse into potential future treatments, there are several challenges that still must be overcome. In this chapter, we will highlight both current surgical approaches for craniofacial reconstruction and recent advances within the field of bone tissue engineering. The clinical challenges and limitations of these strategies will help contextualize and inform future craniofacial tissue engineering strategies.


Asunto(s)
Sustitutos de Huesos/metabolismo , Procedimientos Quirúrgicos Orales/métodos , Ingeniería de Tejidos/métodos , Andamios del Tejido , Enfermedades Óseas/fisiopatología , Enfermedades Óseas/cirugía , Regeneración Ósea/efectos de los fármacos , Regeneración Ósea/fisiología , Humanos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Anomalías Maxilofaciales/fisiopatología , Anomalías Maxilofaciales/cirugía , Procedimientos Quirúrgicos Orales/tendencias , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Medicina Regenerativa/métodos , Medicina Regenerativa/tendencias , Ingeniería de Tejidos/tendencias
9.
COPD ; 12 Suppl 1: 2-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25938284

RESUMEN

Individuals with Alpha-1 antitrypsin deficiency (AATD) have mutations in the SERPINA1 gene causing genetic susceptibility to early onset lung and liver disease that may result in premature death. Environmental interactions have a significant impact in determining the disease phenotype and outcome in AATD. The aim of this study was to assess the impact of smoke exposure on the clinical phenotype of AATD in Ireland. Clinical demographics and available thoracic computerised tomography (CT) imaging were detected from 139 PiZZ individuals identified from the Irish National AATD Registry. Clinical information was collected by questionnaire. Data was analysed to assess AATD disease severity and evaluate predictors of clinical phenotype. Questionnaires were collected from 107/139 (77%) and thoracic CT evaluation was available in 72/107 (67.2%). 74% of respondents had severe Chronic Obstructive Pulmonary Disease (COPD) (GOLD stage C or D). Cigarette smoking was the greatest predictor of impairment in FEV1 and DLCO (%predicted) and the extent of emphysema correlated most significantly with DLCO. Interestingly the rate of FEV1 decline was similar in ex-smokers when compared to never-smokers. Passive smoke exposure in childhood resulted in a greater total pack-year smoking history. Radiological evidence of bronchiectasis was a common finding and associated with increasing age. The Irish National AATD Registry facilitates clinical and basic science research of this condition in Ireland. This study illustrates the detrimental effect of smoke exposure on the clinical phenotype of AATD in Ireland and the benefit of immediate smoking cessation at any stage of lung disease.


Asunto(s)
Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfisema Pulmonar/etiología , Enfermedades Raras/complicaciones , Fumar/efectos adversos , Contaminación por Humo de Tabaco/efectos adversos , Deficiencia de alfa 1-Antitripsina/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Bronquiectasia/diagnóstico , Bronquiectasia/etiología , Estudios Transversales , Progresión de la Enfermedad , Femenino , Encuestas Epidemiológicas , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfisema Pulmonar/diagnóstico , Enfermedades Raras/diagnóstico , Enfermedades Raras/genética , Enfermedades Raras/fisiopatología , Sistema de Registros , Factores de Riesgo , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos X , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/genética , Deficiencia de alfa 1-Antitripsina/fisiopatología
10.
J Oral Maxillofac Surg ; 72(1): 169-77, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23911143

RESUMEN

PURPOSE: The purposes of this study were 1) to estimate and compare the 1-month survival rates of patients with acute malnutrition (low prealbumin level) and patients who are not malnourished (normal prealbumin level) and 2) to identify risk factors associated with microvascular free flap failure. MATERIALS AND METHODS: To address the research purposes, we designed a retrospective cohort study and enrolled a sample composed of patients who underwent head and neck microvascular reconstruction and had prealbumin levels measured in the perioperative period. The primary predictor variable was nutritional status (low vs normal prealbumin level). The primary outcome variable was flap survival. One-month survival rates were estimated by use of Kaplan-Meier survival analyses. Risk factors for free flap failure were identified by use of multivariate marginal Cox proportional hazards modeling. RESULTS: The sample was composed of 162 patients who underwent microvascular free tissue transfer during the study enrollment period. The 1-month survival estimates for patients who were and were not malnourished were 76.5% (95% confidence interval [CI], 48.8% to 90.5%) and 95.2% (95% CI, 90.1% to 97.7%), respectively (P = .002). In the adjusted Cox hazards proportions model, acute malnutrition was associated with a 4-fold increased risk of failure (P = .04) in comparison with those patients with a normal nutritional status. CONCLUSIONS: Acute malnutrition in patients undergoing microvascular free flap reconstruction in the head and neck region was associated with an increased risk for free flap failure.


Asunto(s)
Colgajos Tisulares Libres/trasplante , Supervivencia de Injerto/fisiología , Prealbúmina/análisis , Anciano , Consumo de Bebidas Alcohólicas , Índice de Masa Corporal , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/complicaciones , Complicaciones de la Diabetes , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Hipertensión/complicaciones , Masculino , Desnutrición/sangre , Desnutrición/fisiopatología , Persona de Mediana Edad , Estado Nutricional , Enfermedades Vasculares Periféricas/complicaciones , Modelos de Riesgos Proporcionales , Embolia Pulmonar/complicaciones , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Factores de Riesgo , Fumar , Resultado del Tratamiento , Trombosis de la Vena/complicaciones
11.
NPJ Precis Oncol ; 8(1): 130, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851780

RESUMEN

Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.

12.
Artículo en Inglés | MEDLINE | ID: mdl-36529672

RESUMEN

OBJECTIVES: The purpose of this manuscript is to review the current literature on osteoradionecrosis of the cervical spine (C-ORN) and to summarize the risk factors, presenting symptoms and management strategies of this rare condition. STUDY DESIGN: A systematic review of the literature on C-ORN was completed using PubMed. Nineteen articles met criteria; 97 patient cases were identified. Statistical analysis was completed from the patient cases. RESULTS: Of the analyzed patients, 72% are male and 28% are female with an average age of 57.7 years. Nasopharyngeal carcinoma was the most common initial diagnosis (72%). Thyroid and other lower neck cancers were associated with a later onset of C-ORN compared with other cancers. C-ORN more commonly occurred in the clivus to C2 (55.3%, P = .004). Onset of C-ORN significantly differed for men (n = 6.99 years) and women (n = 17.5 years) (P = .022). CONCLUSION: C-ORN can be a devastating complication of head and neck radiation therapy. C-ORN is associated with nasopharyngeal carcinoma, and most commonly affects the area of the clivus to cervical vertebrae C2. Cancers of the lower neck and female sex are associated with later onset. Initial presentation ranges from asymptomatic to severe neurologic deficits; the degree of intervention should be congruent with the severity of presenting symptoms. As long-term survival of patients with head and neck cancer increase, this complication may become more prevalent.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Nasofaríngeas , Osteorradionecrosis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vértebras Cervicales/patología , Neoplasias de Cabeza y Cuello/patología , Carcinoma Nasofaríngeo/complicaciones , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/radioterapia , Osteorradionecrosis/etiología , Osteorradionecrosis/patología , Estudios Retrospectivos
13.
PLoS One ; 18(2): e0280481, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36827358

RESUMEN

Craniofacial defects require a treatment approach that provides both robust tissues to withstand the forces of mastication and high geometric fidelity that allows restoration of facial architecture. When the surrounding soft tissue is compromised either through lack of quantity (insufficient soft tissue to enclose a graft) or quality (insufficient vascularity or inducible cells), a vascularized construct is needed for reconstruction. Tissue engineering using customized 3D printed bioreactors enables the generation of mechanically robust, vascularized bony tissues of the desired geometry. While this approach has been shown to be effective when utilized for reconstruction of non-load bearing ovine angular defects and partial segmental defects, the two-stage approach to mandibular reconstruction requires testing in a large, load-bearing defect. In this study, 5 sheep underwent bioreactor implantation and the creation of a load-bearing mandibular defect. Two bioreactor geometries were tested: a larger complex bioreactor with a central groove, and a smaller rectangular bioreactor that were filled with a mix of xenograft and autograft (initial bone volume/total volume BV/TV of 31.8 ± 1.6%). At transfer, the tissues generated within large and small bioreactors were composed of a mix of lamellar and woven bone and had BV/TV of 55.3 ± 2.6% and 59.2 ± 6.3%, respectively. After transfer of the large bioreactors to the mandibular defect, the bioreactor tissues continued to remodel, reaching a final BV/TV of 64.5 ± 6.2%. Despite recalcitrant infections, viable osteoblasts were seen within the transferred tissues to the mandibular site at the end of the study, suggesting that a vascularized customized bony flap is a potentially effective reconstructive strategy when combined with an optimal stabilization strategy and local antibiotic delivery prior to development of a deep-seated infection.


Asunto(s)
Osteotomía Mandibular , Procedimientos de Cirugía Plástica , Humanos , Animales , Ovinos , Ingeniería de Tejidos , Colgajos Quirúrgicos/cirugía , Mandíbula/cirugía , Trasplante Óseo
14.
Oral Maxillofac Surg Clin North Am ; 34(4): 545-554, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36224071

RESUMEN

The pursuit of fellowship training stems from one's desire to master a focused area of surgery. Successful applicants tend to have published articles and participated in other scholarly activities. They commonly have a mentor within the subspecialty of their interest. Selection of the program is generally based on the breadth of experience available followed by faculty reputation and location. Advantages to the successful fellowship graduate include the experience and confidence to provide specialized and efficient care to patients. Enhancements to an academic department with a fellowship program include mentorship for residents and guidance toward fellowship, as well as an increased level of scholarly activity.


Asunto(s)
Internado y Residencia , Cirugía Bucal , Humanos , Educación de Postgrado en Medicina , Becas
15.
Nat Commun ; 13(1): 4829, 2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-35977936

RESUMEN

Despite therapeutic advancements, oral cavity squamous cell carcinoma (OCSCC) remains a difficult disease to treat. Systemic platinum-based chemotherapy often leads to dose-limiting toxicity (DLT), affecting quality of life. PRV111 is a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles, that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. Here we evaluate PRV111 using animal models of oral cancer, followed by a clinical trial in patients with OCSCC. In vivo, PRV111 results in elevated cisplatin retention in tumors and negligible systemic levels, compared to the intravenous, intraperitoneal or intratumoral delivery. Furthermore, PRV111 produces robust anti-tumor responses in subcutaneous and orthotopic cancer models and results in complete regression of carcinogen-induced premalignant lesions. In a phase 1/2, open-label, single-arm trial (NCT03502148), primary endpoints of efficacy (≥30% tumor volume reduction) and safety (incidence of DLTs) of neoadjuvant PRV111 were reached, with 69% tumor reduction in ~7 days and over 87% response rate. Secondary endpoints (cisplatin biodistribution, loco-regional control, and technical success) were achieved. No DLTs or drug-related serious adverse events were reported. No locoregional recurrences were evident in 6 months. Integration of PRV111 with current standard of care may improve health outcomes and survival of patients with OCSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Modelos Animales , Neoplasias de la Boca/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Distribución Tisular
16.
Biomark Res ; 9(1): 90, 2021 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-34930473

RESUMEN

BACKGROUND: Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients. METHODS: Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies. RESULTS: There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11). CONCLUSIONS: Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.

17.
Nucleic Acids Res ; 36(20): e131, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18796527

RESUMEN

The polymerase chain reaction (PCR) is widely used for applications which require a high level of specificity and reliability, such as genetic testing, clinical diagnostics, blood screening, forensics and biodefense. Great improvements to PCR performance have been achieved by the use of Hot Start activation strategies that aim to prevent DNA polymerase extension until more stringent, higher temperatures are reached. Herein we present a novel Hot Start activation approach in PCR where primers contain one or two thermolabile, 4-oxo-1-pentyl (OXP) phosphotriester (PTE) modification groups at 3'-terminal and 3'-penultimate internucleotide linkages. Studies demonstrated that the presence of one or more OXP PTE modifications impaired DNA polymerase primer extension at the lower temperatures that exist prior to PCR amplification. Furthermore, incubation of the OXP-modified primers at elevated temperatures was found to produce the corresponding unmodified phosphodiester (PDE) primer, which was then a suitable DNA polymerase substrate. The OXP-modified primers were tested in conventional PCR with endpoint detection, in one-step reverse transcription (RT)-PCR and in real-time PCR with SYBR Green I dye and Taqman(R) probe detection. When OXP-modified primers were used as substitutes for unmodified PDE primers in PCR, significant improvement was observed in the specificity and efficiency of nucleic acid target amplification.


Asunto(s)
Cartilla de ADN/química , Calor , Reacción en Cadena de la Polimerasa/métodos , Benzotiazoles , Cartilla de ADN/síntesis química , ADN Viral/análisis , ADN Polimerasa Dirigida por ADN/metabolismo , Diaminas , Dimerización , Colorantes Fluorescentes , VIH-1/genética , Humanos , Cinética , Compuestos Orgánicos , Compuestos Organofosforados/síntesis química , Quinolinas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Moldes Genéticos
18.
Biomaterials ; 256: 120185, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32599360

RESUMEN

Mandibular reconstruction requires functional and aesthetic repair and is further complicated by contamination from oral and skin flora. Antibiotic-releasing porous space maintainers have been developed for the local release of vancomycin and to promote soft tissue attachment. In this study, mandibular defects in six sheep were inoculated with 106 colony forming units of Staphylococcus aureus; three sheep were implanted with unloaded porous space maintainers and three sheep were implanted with vancomycin-loaded space maintainers within the defect site. During the same surgery, 3D-printed in vivo bioreactors containing autograft or xenograft were implanted adjacent to rib periosteum. After 9 weeks, animals were euthanized, and tissues were analyzed. Antibiotic-loaded space maintainers were able to prevent dehiscence of soft tissue overlying the space maintainer, reduce local inflammatory cells, eliminate the persistence of pathogens, and prevent the increase in mandibular size compared to unloaded space maintainers in this sheep model. Animals with an untreated mandibular infection formed bony tissues with greater density and maturity within the distal bioreactors. Additionally, tissues grown in autograft-filled bioreactors had higher compressive moduli and higher maximum screw pull-out forces than xenograft-filled bioreactors. In summary, we demonstrated that antibiotic-releasing space maintainers are an innovative approach to preserve a robust soft tissue pocket while clearing infection, and that local infections can increase local and remote bone growth.


Asunto(s)
Mandíbula , Reconstrucción Mandibular , Animales , Antibacterianos/uso terapéutico , Reactores Biológicos , Porosidad , Prótesis e Implantes , Ovinos
19.
Anal Biochem ; 388(2): 266-72, 2009 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-19258004

RESUMEN

Multiplex polymerase chain reaction (PCR), the amplification of multiple targets in a single reaction, presents a new set of challenges that further complicate more traditional PCR setups. These complications include a greater probability for nonspecific amplicon formation and for imbalanced amplification of different targets, each of which can compromise quantification and detection of multiple targets. Despite these difficulties, multiplex PCR is frequently used in applications such as pathogen detection, RNA quantification, mutation analysis, and (recently) next generation DNA sequencing. Here we investigated the utility of primers with one or two thermolabile 4-oxo-1-pentyl phosphotriester modifications in improving multiplex PCR performance. Initial endpoint and real-time analyses revealed a decrease in off-target amplification and a subsequent increase in amplicon yield. Furthermore, the use of modified primers in multiplex setups revealed a greater limit of detection and more uniform amplification of each target as compared with unmodified primers. Overall, the thermolabile modified primers present a novel and exciting avenue for improving multiplex PCR performance.


Asunto(s)
Reacción en Cadena de la Polimerasa/métodos , Cartilla de ADN/química
20.
N Y State Dent J ; 75(5): 41-4, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19882841

RESUMEN

The presentation of cavernous sinus thrombosis can be ominous and, in many cases, lead to death or serious morbidity. Infections from the face can tract via a valveless venous system in a retrograde manner to the cavernous sinus. A case of cavernous sinus thrombosis secondary to a non-operable posterior maxillary sinus wall fracture is reported. This case is of interest because the inciting factor was a fracture in the posterior maxillary wall that created a tract from which bacteria traveled to the pterygoid plexus and, ultimately, to the cavernous sinus. Although cavernous sinus thrombosis is uncommon, we present this case to remind medical and dental professionals of the potential complications of infection and trauma to the face, especially in immunocompromised patients.


Asunto(s)
Trombosis del Seno Cavernoso/etiología , Fracturas Maxilares/complicaciones , Seno Maxilar/lesiones , Sinusitis Maxilar/complicaciones , Infecciones Estafilocócicas/complicaciones , Accidentes por Caídas , Adulto , Anemia Aplásica/complicaciones , Estenosis Carotídea/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Resultado Fatal , Femenino , Humanos , Huésped Inmunocomprometido
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