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1.
J Stomatol Oral Maxillofac Surg ; 125(5S1): 101959, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38964469

RESUMEN

PURPOSE: The aim of the present study was to determine the methodological quality of systematic reviews that evaluated the effectiveness of pentoxifylline and tocopherol (PENTO) in the treatment of osteoradionecrosis of the jaw (ORNJ) and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Searches were performed in Databases including PubMed, Scopus, LILACS, DARE, Cochrane Library, and SIGLE through OpenGrey until March 2024, were evaluated by two independent reviewers to answer the following question: Is the use of PENTO protocol effective in the treatment of ORNJ or for the treatment of MRONJ? RESULTS: A total of 256 articles were initially identified; however, following the use of appropriate inclusion and exclusion criteria, five systematic reviews were identified for detailed analysis. The final study sample comprised 588 patients: 397 patients with ORN and 197 patients with MRONJ who were treated with PENTO. The total recovery of individuals who used the PENTO protocol was 62,2 % for ORN and 100 % for MRONJ, with a follow-up period of 1 month to 10 years. The methodological quality of the studies was assessed using the AMSTAR 2 tool, in which four were of low quality and 1 moderate quality. CONCLUSION: The treatment of ORN and MRONJ with pentoxifylline and tocopherol has shown good results in the studies presented, with a partial or total reduction in bone exposure. However, the low quality of the relevant reports highlights the need for primary and secondary studies with better methodological rigor to reduce bias and provide reassurance for this treatment option.


Asunto(s)
Osteorradionecrosis , Pentoxifilina , Tocoferoles , Humanos , Enfermedades Maxilomandibulares/terapia , Enfermedades Maxilomandibulares/tratamiento farmacológico , Enfermedades Maxilomandibulares/inducido químicamente , Enfermedades Maxilomandibulares/diagnóstico , Osteorradionecrosis/tratamiento farmacológico , Osteorradionecrosis/terapia , Osteorradionecrosis/etiología , Osteorradionecrosis/patología , Pentoxifilina/uso terapéutico , Pentoxifilina/administración & dosificación , Tocoferoles/uso terapéutico , Tocoferoles/administración & dosificación , Resultado del Tratamiento , Revisiones Sistemáticas como Asunto
2.
Indian J Pathol Microbiol ; 67(1): 162-165, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38358211

RESUMEN

Extranodal Natural Killer/T Cell Lymphoma Nasal Type (EN-NK/T-CL-NT) is a non-Hodgkin extranodal lymphoma of unfavorable prognosis due to its aggressive nature. This neoplasm mainly affects the paranasal sinuses, nasopharynx, oropharynx, oral cavity, palate, and rarely intestinal, gastric and skin regions. 50-year-old female with a history of lymphoma in nasal and pelvic region. At four years of tumors-free, has facial asymmetry, accompanied by sub-palpebral, nasal and lip edema. Intraoral examination revealed a large ulceration suggestive of osteoradionecrosis. Gum biopsy shows Extranodal NK/T Cell Lymphoma Nasal Type (EN-NK/T-CL-NT). In this case we highlight the characteristics of EN-NK/T-CL-NT with a presentation of osteoradionecrosis-like. Unfortunately, the nature of this tumor led to the patient's death. Clinical follow-up of patients with cancer is imperative to mend and/or decrease treatment complications, as well as to identify second primary tumors or the spread of the underlying disease.


Asunto(s)
Linfoma Extranodal de Células NK-T , Osteorradionecrosis , Femenino , Humanos , Persona de Mediana Edad , Osteorradionecrosis/diagnóstico , Osteorradionecrosis/patología , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/radioterapia , Linfoma Extranodal de Células NK-T/patología , Pronóstico , Pelvis , Células Asesinas Naturales/patología
3.
Support Care Cancer ; 29(6): 3311-3317, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33106977

RESUMEN

BACKGROUND: The aim of the present study was to evaluate the efficacy of pentoxifylline and tocopherol for the management of osteoradionecrosis of the jaws. METHODS: Twenty-five patients diagnosed with osteoradionecrosis of the jaws treated with pentoxifylline 400 mg + tocopherol 400 mg three times daily (tid) were evaluated. Clinical records and image tests were reviewed. All patients were previously submitted to head and neck radiation therapy and presented with a clinical and radiographic diagnosis of osteoradionecrosis of the jaws. RESULTS: Following therapy with pentoxifylline and tocopherol, 76% (19/25) of the patients showed complete mucosal healing, in which 47.3% (9/19) did not undergo sequestrectomy. From this particular group, 77.7% (7/9) were in stage I and 33.3% (3/9) used the protocol for up to 3 months. Among those who underwent to sequestrectomy, complete mucosal healing was observed in 52.7% (10/19). Among these, 60% (6/10) were in stage I and 100% of the patients were using the protocol for more than 3 months. In all other patients, partial healing of the mucosa was observed since they presented advanced disease. These represented 24% of the sample (6/25), 66.6% (4/6) were in stage III, and 60% (4/6) used the protocol for over 6 months. CONCLUSION: Pentoxifylline and tocopherol may provide effective management of osteoradionecrosis of the jaws, and the association with sequestrectomy may avoid major surgical procedures.


Asunto(s)
Antioxidantes/uso terapéutico , Maxilares/patología , Osteorradionecrosis/tratamiento farmacológico , Osteorradionecrosis/cirugía , Pentoxifilina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tocoferoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antioxidantes/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteorradionecrosis/patología , Pentoxifilina/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Tocoferoles/farmacología
4.
Braz Oral Res ; 32: e23, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29723337

RESUMEN

It is largely known that some oral diseases can be diagnosed based upon their clinical manifestation combined with the patient's medical history and generally not depending on examination. This is the case of some bone diseases such as osteoradionecrosis of the jaw (ORNJ), osteomyelitis of the jaw (OMJ), and medication-related osteonecrosis of the jaw (MRONJ). The present study aimed to analyze the histopathological features of these specific bone diseases in order to evaluate similarities and differences. Forty-four bone specimens resected from each bone disease (22 cases of ORNJ, 6 cases of OMJ, and 16 cases of MRONJ) were analyzed by two experienced oral pathologists without prior knowledge of the diagnosis, considering bone tissue condition, inflammation, vascularization, and the presence of microorganisms. In addition, the examiners formulated a diagnostic hypothesis for each specimen. Many histopathological similarities were found among the diseases, especially considering the presence of necrotic bone, inflammation, and microorganisms. Statistically significant differences were detected in empty bone lacunae, which was decreased in ORN (p = 0.042), and considering neutrophil count, which was low in the MRONJ group (p ≤ 0.001). The Kappa coefficient was calculated and agreement was detected based on the histopathological parameters, but not for diagnostic suggestion (p=0.23). In conclusion, histopathological aspects of ORNJ, OMJ, and MRONJ do not permit a conclusive diagnosis, emphasizing the necessity of a detailed clinical report.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Osteomielitis/patología , Osteorradionecrosis/patología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Osteomielitis/diagnóstico , Osteorradionecrosis/diagnóstico , Estudios Retrospectivos , Factores Sexuales , Estadísticas no Paramétricas
5.
J Appl Oral Sci ; 26: e20170172, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29791570

RESUMEN

BACKGROUND: Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa. METHODS: We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years. RESULTS: 100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa. CONCLUSION: LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ.


Asunto(s)
Antiinfecciosos/uso terapéutico , Quimioradioterapia Adyuvante/métodos , Enfermedades Maxilomandibulares/terapia , Terapia por Luz de Baja Intensidad/métodos , Osteorradionecrosis/terapia , Fotoquimioterapia/métodos , Adulto , Anciano , Relación Dosis-Respuesta en la Radiación , Femenino , Homeostasis/efectos de los fármacos , Homeostasis/efectos de la radiación , Humanos , Enfermedades Maxilomandibulares/patología , Masculino , Persona de Mediana Edad , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/efectos de la radiación , Osteorradionecrosis/patología , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del Tratamiento , Cicatrización de Heridas/efectos de la radiación
6.
J. appl. oral sci ; J. appl. oral sci;26: e20170172, 2018. tab, graf
Artículo en Inglés | LILACS, BBO - Odontología | ID: biblio-893733

RESUMEN

Abstract Background: Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa. Methods: We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years. Results: 100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa. Conclusion: LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Osteorradionecrosis/terapia , Fotoquimioterapia/métodos , Enfermedades Maxilomandibulares , Terapia por Luz de Baja Intensidad/métodos , Quimioradioterapia Adyuvante/métodos , Antiinfecciosos/uso terapéutico , Osteorradionecrosis/patología , Factores de Tiempo , Cicatrización de Heridas/efectos de la radiación , Enfermedades Maxilomandibulares/patología , Estudios Prospectivos , Reproducibilidad de los Resultados , Resultado del Tratamiento , Relación Dosis-Respuesta en la Radiación , Homeostasis/efectos de los fármacos , Homeostasis/efectos de la radiación , Persona de Mediana Edad , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/efectos de la radiación
7.
Braz. oral res. (Online) ; 32: e23, 2018. tab, graf
Artículo en Inglés | LILACS | ID: biblio-889482

RESUMEN

Abstract It is largely known that some oral diseases can be diagnosed based upon their clinical manifestation combined with the patient's medical history and generally not depending on examination. This is the case of some bone diseases such as osteoradionecrosis of the jaw (ORNJ), osteomyelitis of the jaw (OMJ), and medication-related osteonecrosis of the jaw (MRONJ). The present study aimed to analyze the histopathological features of these specific bone diseases in order to evaluate similarities and differences. Forty-four bone specimens resected from each bone disease (22 cases of ORNJ, 6 cases of OMJ, and 16 cases of MRONJ) were analyzed by two experienced oral pathologists without prior knowledge of the diagnosis, considering bone tissue condition, inflammation, vascularization, and the presence of microorganisms. In addition, the examiners formulated a diagnostic hypothesis for each specimen. Many histopathological similarities were found among the diseases, especially considering the presence of necrotic bone, inflammation, and microorganisms. Statistically significant differences were detected in empty bone lacunae, which was decreased in ORN (p = 0.042), and considering neutrophil count, which was low in the MRONJ group (p ≤ 0.001). The Kappa coefficient was calculated and agreement was detected based on the histopathological parameters, but not for diagnostic suggestion (p=0.23). In conclusion, histopathological aspects of ORNJ, OMJ, and MRONJ do not permit a conclusive diagnosis, emphasizing the necessity of a detailed clinical report.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Osteomielitis/patología , Osteorradionecrosis/patología , Factores de Edad , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico , Diagnóstico Diferencial , Variaciones Dependientes del Observador , Osteomielitis/diagnóstico , Osteorradionecrosis/diagnóstico , Estudios Retrospectivos , Factores Sexuales , Estadísticas no Paramétricas
8.
J Oral Maxillofac Surg ; 74(1): 190-9, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26253013

RESUMEN

PURPOSE: Surgery of irradiated tissue has an increased complication rate because of the development of hypovascular, hypocellular, and hypoxic tissue. This study was undertaken to perform histopathologic and histomorphometric analyses of irradiation tissue injury in bone and the surrounding soft tissues. MATERIAL AND METHODS: The histopathologic findings of 40 human mandibular bones and the surrounding soft tissue specimens obtained from different patients who underwent surgical procedures for treatment of osteoradionecrosis of the jaws were reviewed. RESULTS: Histopathologic examination showed 7 processes in the following order of appearance: hyperemia, endarteritis, thrombosis, cell loss, hypovascularity, increase of fat in the bone marrow cavity, and fibrosis. Histomorphometric analysis showed significant hypocellularity (P = .007), hypovascularity (P < .001), and fibrosis (P < .001) in irradiated specimens compared with control specimens. CONCLUSION: These results showed that radiation injuries affect the bone and surrounding soft tissues. However, the irradiation-induced injuries, such as cellular loss (hypocellularity) and fibrosis, were more expressive in bone tissue than in the surrounding soft tissues.


Asunto(s)
Enfermedades Mandibulares/patología , Osteorradionecrosis/patología , Periodoncio/efectos de la radiación , Tejido Adiposo/efectos de la radiación , Antígenos CD34/análisis , Médula Ósea/efectos de la radiación , Muerte Celular/efectos de la radiación , Endarteritis/patología , Endotelio Vascular/efectos de la radiación , Fibrosis , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Hiperemia/patología , Microvasos/efectos de la radiación , Dosificación Radioterapéutica , Radioterapia de Alta Energía/métodos , Trombosis/patología
9.
Arthroscopy ; 20(6): 632-6, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15241316

RESUMEN

The purpose of this report is to describe a case of osteonecrosis that occurred after arthroscopic meniscectomy associated with a radiofrequency device. The patient developed increasing knee pain and disability 6 months after arthroscopic meniscectomy. Magnetic resonance imaging showed subchondral osteonecrosis of both femoral condyles with cyst formation.


Asunto(s)
Artroscopía/efectos adversos , Electrocoagulación/efectos adversos , Fémur/patología , Meniscos Tibiales/cirugía , Osteonecrosis/etiología , Osteorradionecrosis/etiología , Ondas de Radio/efectos adversos , Fémur/efectos de la radiación , Humanos , Traumatismos de la Rodilla/cirugía , Imagen por Resonancia Magnética , Masculino , Meniscos Tibiales/patología , Persona de Mediana Edad , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/patología , Osteorradionecrosis/diagnóstico por imagen , Osteorradionecrosis/patología , Radiografía , Estrés Mecánico
10.
São Paulo; s.n; 2002. 108 p. tab.
Tesis en Portugués | LILACS, Inca | ID: lil-553385

RESUMEN

O manejo de pacientes irradiados para tratamento de carcinoma de cabeça e pescoço representa um desafio para as equipes multidisciplinares, pois a radioterapia resulta em lesões celulares e vasculares nos tecidos... Este estudo tem como objetivos analisar a efetividade da cirurgia associada à oxigenação hiperbárica adjuvante no tratamento da ORN refratária de mandíbula e maxila, bem como avaliar as alterações histopatológicas e histomorfométricas da radiação no osso mandibular e na mucosa bucal adjacente. Material e Métodos. O presente estudo analisou 18 pacientes submetidos ao tratamento de cirurgia e oxigenação hiperbárica adjuvante, os quais mostraram-se refratários ao tratamento conservador para osteorradionecrose. Para a análise histopatológica utilizou-se 55 amostras irradiadas de osso mandibular e mucosa bucal, resultantes de cirurgias de resgate em pacientes portadores de carcinoma de boca previamente irradiados, e de tratamento de osteorradionecrose de mandíbula... Conclusão. Os resultados deste estudo mostram que a cirurgia associada à oxigenação hiperbárica é bastante efetiva no tratamento da osteorradionecrose refratária de mandíbula e maxila. Os resultados histopatológicos mostram que as lesões teciduais da radiação afetam tanto o osso mandibular como também o tecido mole adjacente. Estas alterações foram observadas nas células, no tecido conjuntivo e no sistema vascular dos tecidos irradiados. Todas amostras irradiadas mostraram reduzida capacidade de recuperação tecidual após a radioterapia. As alterações teciduais da radiação parecem progressivas após a radioterapia...


Asunto(s)
Humanos , Mandíbula , Maxilar , Osteorradionecrosis , Osteorradionecrosis/diagnóstico , Osteorradionecrosis/patología , Oxigenoterapia Hiperbárica , Neoplasias de Cabeza y Cuello , Radioterapia
11.
In. Parise Junior, Orlando. Câncer de boca: aspectos básicos e terapêuticos. Säo Paulo, Sarvier, 2000. p.212-9, ilus. (BR).
Monografía en Portugués | LILACS, BBO - Odontología | ID: lil-298370
12.
Cir. & cir ; Cir. & cir;67(4): 129-32, jul.-ago. 1999. tab, ilus
Artículo en Español | LILACS | ID: lil-254668

RESUMEN

La osteorradionecrosis (ORN) es la pérdida de hueso viable, posterior a terapia con radiación. Este daño es el resultado directo de la radiación sobre osteocitos y el endotelio vascular. El proceso patológico subyacente, originalmente llamado ®osteítis¼, es una necrosis avascular lentamente progresiva, desencadenada por una endarteritis obliterativa. El diagnóstico de ORN de hueso temporal es histopatológico, aunque clínicamente puede presentarse como otomastoiditis crónica, pérdida auditiva y la presencia de secuestros óseos, la tomografía computada es útil para delimitar la destrucción ósea. El tratamiento está basado en la extensión del hueso temporal involucrado, en la forma localizada el manejo es conservador; la forma más difusa de la enfermedad puede requerir desbridación quirúrgica agresiva con remoción completa de todo el tejido necrótico. Presentamos el caso clínico de paciente femenino de 70 años de edad con ORN de hueso temporal izquierdo, la cual se diagnosticó 17 años después de recibir radioterapia debido a un tumor maligno de parótida, la paciente cursó con destrucción importante de la porción ósea del conducto auditivo externo y la mastoides, manifestándose como proceso infeccioso crónico de oído. Se presentan las características clínicas del caso, su evolución, los hallazgos radiológicos, así como su confirmación histológica y tratamiento


Asunto(s)
Humanos , Femenino , Anciano , Osteorradionecrosis/diagnóstico , Osteorradionecrosis/patología , Osteorradionecrosis/terapia , Radioterapia/efectos adversos , Hueso Temporal/patología , Tomografía Computarizada por Rayos X
13.
Radiol. bras ; Radiol. bras;32(3): 147-50, maio-jun. 1999. ilus
Artículo en Portugués | LILACS | ID: lil-254458

RESUMEN

Resumo: A osterradionecrose após radioterapia para as neoplasias de cabeça e pescoço tem incidência variável. A mandíbula é o osso mais frequentemente afetado, sendo a osterradiocrese de clavícula uma rara ocorrência. O presente trabalho apresenta três pacientes com osteorradionecrose de clavícula subsequente a tratamento cirúrgico e radioterapia para neoplasias de cabeça e pescoço. Os três pacientes foram submetidos a esvaziamento cervical, rotaçäo de retalho miocutâneo de músculo peitoral maior e irradiaçäo dos leitos tumorais com campos se estendendo às cadeias e fossas supraclaviculares. Desenvolveram a osteorradionecrose após períodos de noves meses, três anos e sete anos após a radioterapia. Enfatizamos os principais mecanismos envolvidos na produçäo da necrose óssea, os fatores comumente implicados no seu desencadeamento, bem como assinalamos as formas terapêuticas. Embora a osterradionecrose clavicluar apresente baixa incidência, ela deve ser caracterizada em pacientes tratados com grandes ressecçöes cirúrgicas e rotaçöes de retalhos muicutâneos.


Asunto(s)
Humanos , Masculino , Adulto , Persona de Mediana Edad , Clavícula/efectos de la radiación , Osteorradionecrosis , Osteorradionecrosis/diagnóstico , Osteorradionecrosis/epidemiología , Osteorradionecrosis/patología , Osteorradionecrosis/terapia
14.
São Paulo; s.n; 1999. 73 p. ilus, tab, graf.
Tesis en Portugués | Sec. Munic. Saúde SP, HSPM-Acervo | ID: sms-2951

RESUMEN

A actinomicose pode, ocasionalmente, infectar de maneira oportunista, pacientes portadores de osteorradionecrose (ORN) de mandíbula e maxila. O estudo retrospectivo (1992-1997) constituiu-se de 50 pacientes portadores de ORN de mandíbula e maxila, tratados com medidas conservadoras, cirurgia e oxigenação hiperbárica. Foram avaliados a incidência de actinomicose nestes pacientes e sua significância clínica no tratamento da ORN. A actinomicose foi diagnosticada em 12% (6 casos) dos casos de ORN. Dos 50 pacientes, 36 casos evoluíram com cura e resolução completa da ORN após as terapias empregadas. A duração média do tratamento da ORN nos pacientes portadores de actinomicose (29,7 meses) foi significantemente maior que nos pacientes sem actinomicose (13,4 meses) (P=0,007). Concluindo, nos casos de ORN com resposta insatisfatória às terapias especificamente empregadas, deve-se considerar a biópsia de tecido ósseo, com o objetivo de identificar uma possível actinomicose oportunista


Asunto(s)
Humanos , Osteorradionecrosis/patología , Osteorradionecrosis/cirugía , Osteorradionecrosis/terapia , Actinomicosis/terapia , Oxigenoterapia Hiperbárica
15.
Acta odontol. venez ; 35(2): 77-81, mayo-ago. 1997. ilus
Artículo en Español | LILACS | ID: lil-230970

RESUMEN

Se presenta la revisión de la literatura acerca de los cuidados preventivos y de los tratamientos de la osteorradionecrosis de los maxilares. Se establece un protocolo de trabajo para la atención de estos pacientes ya que se presentan con relativa frecuencia en el Servicio de Postgrado de la Facultad de Odontología de la UCV.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Extracción Dental/normas , Neoplasias de Cabeza y Cuello/radioterapia , Osteorradionecrosis/complicaciones , Osteorradionecrosis/terapia , Caries Dental/etiología , Osteorradionecrosis , Osteorradionecrosis/patología , Osteorradionecrosis/prevención & control , Planificación de Atención al Paciente , Profilaxis Antibiótica/métodos , Radioterapia/efectos adversos
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