RESUMEN
BACKGROUND: This phase 1 clinical trial was conducted to determine the safety, maximum-tolerated dose (MTD), and pharmacokinetics of imatinib, bevacizumab, and metronomic cyclophosphamide in patients with advanced colorectal cancer (CRC). METHODS: Patients with refractory stage IV CRC were treated with bevacizumab 5 mg kg(-1) i.v. every 2 weeks (fixed dose) plus oral cyclophosphamide q.d. and imatinib q.d. or b.i.d. in 28-day cycles with 3+3 dose escalation. Response was assessed every two cycles. Pharmacokinetics of imatinib and cyclophosphamide and circulating tumour, endothelial, and immune cell subsets were measured. RESULTS: Thirty-five patients were enrolled. Maximum-tolerated doses were cyclophosphamide 50 mg q.d., imatinib 400 mg q.d., and bevacizumab 5 mg kg(-1) i.v. every 2 weeks. Dose-limiting toxicities (DLTs) included nausea/vomiting, neutropaenia, hyponatraemia, fistula, and haematuria. The DLT window required expansion to 42 days (1.5 cycles) to capture delayed toxicities. Imatinib exposure increased insignificantly after adding cyclophosphamide. Seven patients (20%) experienced stable disease for >6 months. Circulating tumour, endothelial, or immune cells were not associated with progression-free survival. CONCLUSION: The combination of metronomic cyclophosphamide, imatinib, and bevacizumab is safe and tolerable without significant drug interactions. A subset of patients experienced prolonged stable disease independent of dose level.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/farmacocinética , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacocinética , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas/efectos adversos , Benzamidas/farmacocinética , Bevacizumab , Ciclofosfamida/efectos adversos , Ciclofosfamida/farmacocinética , Esquema de Medicación , Femenino , Humanos , Mesilato de Imatinib , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Células Neoplásicas Circulantes/efectos de los fármacos , Piperazinas/efectos adversos , Piperazinas/farmacocinética , Pirimidinas/efectos adversos , Pirimidinas/farmacocinética , Resultado del TratamientoRESUMEN
BACKGROUND: Temozolomide (TMZ) is widely used for chemotherapy of metastatic melanoma. We hypothesized that epigenetic modulators will reverse chemotherapy resistance, and in this article, we report studies that sought to determine the recommended phase 2 dose (RP2D), safety, and efficacy of decitabine (DAC) combined with TMZ. PATIENTS AND METHODS: In phase I, DAC was given at two dose levels: 0.075 and 0.15 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m(2) qd for weeks 2-5 of a 6-week cycle. The phase II portion used a two-stage Simon design with a primary end point of objective response rate (ORR). RESULTS: The RP2D is DAC 0.15 mg/kg and TMZ 75 mg/m(2). The phase II portion enrolled 35 patients, 88% had M1c disease; 42% had history of brain metastases. The best responses were 2 complete response (CR), 4 partial response (PR), 14 stable disease (SD), and 13 progressive disease (PD); 18% ORR and 61% clinical benefit rate (CR + PR + SD). The median overall survival (OS) was 12.4 months; the 1-year OS rate was 56%. Grade 3/4 neutropenia was common but lasted >7 days in six patients. CONCLUSIONS: The combination of DAC and TMZ is safe, leads to 18% ORR and 12.4-month median OS, suggesting possible superiority over the historical 1-year OS rate, and warrants further evaluation in a randomized setting.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Azacitidina/análogos & derivados , Dacarbazina/análogos & derivados , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/antagonistas & inhibidores , Azacitidina/administración & dosificación , Azacitidina/efectos adversos , Azacitidina/farmacocinética , Dacarbazina/administración & dosificación , Dacarbazina/farmacocinética , Decitabina , Supervivencia sin Enfermedad , Esquema de Medicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inducido químicamente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Cutáneas/patología , TemozolomidaRESUMEN
BACKGROUND: Isolated hepatic perfusion (IHP) with melphalan is an established approach for patients with unresectable metastatic liver lesions. This study determined the safety and maximum tolerated dose (MTD) of 5-FU with oxaliplatin via IHP. METHODS: Standard 3 × 3 Phase I design. Subjects with unresectable isolated CRC liver metastases scheduled for HAI pump were eligible. IHP used fixed-dose oxaliplatin with escalating 5-FU doses. Toxicity (CTCAE v 4.0) and response (RECIST), progression-free survival, and overall survival (OS) were assessed. Systemic and IHP plasma PK of 5-FU, anabolites, and platinum were determined. RESULTS: All 12 patients had received ≥ 1 line of pre-IHP chemotherapy. There were 4 grade 3 serious adverse events (33.3 %) and 1 grade 4 event (8.3 %). Also, 2 dose-limiting toxicities occurred at DL2 at 300 mg/m(2), resulting in expansion of DL1 at 200 mg/m(2) 5-FU, the eventual MTD. At 6-month follow-up, 9 patients (82 %) demonstrated partial response, while 2 (18 %) exhibited stable disease. Also, 64 % of patients demonstrated a >50 % decrease in CEA. The 1- and 2-year OS probabilities were 90.9 and 71.6 %, respectively, with median follow-up of 24 months. IHP exposures (AUC0-60 min) were 10.9 ± 4.5 µgPt h/mL, 49.3 ± 30.7 µg h/mL 5-FU (DL1), and 70.5 ± 35.5 µg h/mL 5-FU (DL2). Systemic exposure (AUC0-inf) relative to IHP exposure was negligible for both platinum (1.1 ± 1.5 %) and 5-FU (0.09 ± 0.10 %). CONCLUSIONS: The MTD for IHP was 200 mg/m(2) 5-FU with 40 mg/m(2) oxaliplatin. Systemic exposure to the agents was minimal during IHP. The response and survival observed warrants assessment in a larger phase II trial.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Dosis Máxima Tolerada , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Área Bajo la Curva , Antígeno Carcinoembrionario/sangre , Quimioterapia del Cáncer por Perfusión Regional/efectos adversos , Neoplasias Colorrectales/sangre , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/farmacocinética , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/farmacocinética , OxaliplatinoRESUMEN
Intestinal organoids are three-dimensional structures derived from tissue-resident adult stem cells. These organoids recapitulate key aspects of epithelial biology and can be used to study homeostatic turnover of the corresponding tissue. Organoids can be enriched for the various mature lineages which allows studies of the respective differentiation processes and of the diverse cellular functions. Here we describe mechanisms of intestinal fate specification and how these can be exploited to drive mouse and human small intestinal organoids into each of the functionally mature lineages.
Asunto(s)
Células Madre Adultas , Intestino Delgado , Adulto , Humanos , Animales , Ratones , Diferenciación Celular , Homeostasis , OrganoidesRESUMEN
BACKGROUND: Determining the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of sorafenib (S) plus imatinib (IM) in castration-resistant prostate cancer (CRPC) patients. METHODS: Refractory CRPC patients were enrolled onto this 3+3 dose escalation designed study. Imatinib pharmacokinetics (PK) were determined on day 15, 4 h post dose with a validated LC-MS assay. RESULTS: Seventeen patients were enrolled; 10 evaluable (6 at 400 mg S qd with 300 mg IM qd (DL0) and 4 at 400 mg S bid with 300 mg IM qd (DL1)); inevaluable patients received <1 cycle. The median age was 73 (57-89); median prostatic serum antigen was 284 ng ml(-1) (11.7-9027). Median number of prior non-hormonal therapies was 3 (1-12). Dose-limiting toxicities were diarrhoea and hand-foot syndrome. Maximum tolerated dose was 400 mg S and 300 mg IM both daily. No biochemical responses were observed. Two patients had stable disease by RECIST. Median time to progression was 2 months (1-5). Median OS was 6 months (1-30+) with 3/17 patients (17%) alive at 21 months median follow-up. Ten patients had PK data suggesting that S reduced IM clearance by 55%, resulting in 77% increased exposure (P=0.005; compared with historical data). CONCLUSION: This is the first report showing that S+IM can be administered in CRPC at a dose of 400 mg S and 300 mg IM, daily.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencenosulfonatos/administración & dosificación , Piperazinas/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Piridinas/administración & dosificación , Pirimidinas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas , Castración , Esquema de Medicación , Humanos , Mesilato de Imatinib , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piperazinas/farmacocinética , Pirimidinas/farmacocinética , Retratamiento , Sorafenib , Insuficiencia del TratamientoRESUMEN
Trabectedin is a novel anticancer drug active against soft tissue sarcomas. Trabectedin is a substrate for P-glycoprotein (P-gp), which is encoded by mdr1a/1b in rodents. Plasma and tissue distribution, and excretion of [(14)C]-trabectedin were evaluated in wild-type and mdr1a/1b(-/-) mice. In parallel, we investigated the toxicity profile of trabectedin by serial measurements of blood liver enzymes and general pathology. [(14)C]-trabectedin was extensively distributed into tissues, and rapidly converted into a range of unknown metabolic products. The excretion of radioactivity was similar in both genotypes. The plasma clearance of unchanged trabectedin was not reduced when P-gp was absent, but organs under wild type circumstances protected by P-gp showed increased trabectedin concentrations in mdr1a/1b(-/-) mice. Although hepatic trabectedin concentrations were not increased when P-gp was absent, mdr1a/1b(-/-) mice experienced more severe liver toxicity. P-gp plays a role in the in vivo disposition and toxicology of trabectedin.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/deficiencia , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Dioxoles/farmacocinética , Dioxoles/toxicidad , Tetrahidroisoquinolinas/farmacocinética , Tetrahidroisoquinolinas/toxicidad , Animales , Área Bajo la Curva , Dioxoles/química , Dioxoles/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Masculino , Dosis Máxima Tolerada , Ratones , Ratones Noqueados , Tetrahidroisoquinolinas/química , Tetrahidroisoquinolinas/metabolismo , Distribución Tisular/efectos de los fármacos , TrabectedinaRESUMEN
We reported that p62 (sequestosome 1) serves as a signaling hub in bone marrow stromal cells (BMSCs) for the formation of signaling complexes, including NFκB, p38MAPK and JNK, that are involved in the increased osteoclastogenesis and multiple myeloma (MM) cell growth induced by BMSCs that are key contributors to multiple myeloma bone disease (MMBD), and demonstrated that the ZZ domain of p62 (p62-ZZ) is required for BMSC enhancement of MMBD. We recently identified a novel p62-ZZ inhibitor, XRK3F2, which inhibits MM cell growth and BMSC growth enhancement of human MM cells. In the current study, we evaluate the relative specificity of XRK3F2 for p62-ZZ, characterize XRK3F2's capacity to inhibit growth of primary MM cells and human MM cell lines, and test the in vivo effects of XRK3F2 in the immunocompetent 5TGM1 MM model. We found that XRK3F2 induces dramatic cortical bone formation that is restricted to MM containing bones and blocked the effects and upregulation of tumor necrosis factor alpha (TNFα), an osteoblast (OB) differentiation inhibitor that is increased in the MM bone marrow microenvironment and utilizes signaling complexes formed on p62-ZZ, in BMSC. Interestingly, XRK3F2 had no effect on non-MM bearing bone. These results demonstrate that targeting p62 in MM models has profound effects on MMBD.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Mieloma Múltiple/tratamiento farmacológico , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/química , Anciano , Animales , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/fisiología , Ratones , Ratones Endogámicos C57BL , Mieloma Múltiple/patología , Osteoclastos/fisiología , Proteína Sequestosoma-1 , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
This paper describes the aims, study design, and patient accrual and characteristics from an ongoing randomized controlled trial evaluating a surgeon- and dentist-delivered smoking cessation intervention for head and neck cancer patients. Subjects (n = 186) accrued into the trial are profiled in terms of demographics, medical and treatment descriptors, smoking history and behavior at enrollment, and related psychosocial variables (mood, adherence indicators, and alcohol consumption). These patients have long histories of tobacco use, moderate to high levels of nicotine dependence, and a lack of overt mood disturbance and are receptive to behavioral change.
Asunto(s)
Carcinoma de Células Escamosas/complicaciones , Neoplasias de Cabeza y Cuello/complicaciones , Educación del Paciente como Asunto/métodos , Proyectos de Investigación , Cese del Hábito de Fumar/métodos , Prevención del Hábito de Fumar , Afecto , Anciano , Carcinoma de Células Escamosas/diagnóstico , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Conductas Relacionadas con la Salud , Humanos , Masculino , Prótesis Maxilofacial , Persona de Mediana Edad , Otolaringología , Cooperación del Paciente , Educación del Paciente como Asunto/normas , Estudios Prospectivos , Fumar/psicología , Cese del Hábito de Fumar/psicologíaRESUMEN
Eighty-three episodes of osteoradionecrosis are reported. Of those episodes affecting the mandible (78), 23 (29.5%) required radical resection. The most common precipitating factors were postradiation extractions (22/83), periodontal disease (19/83), and preradiation extractions (17/83). Those episodes initially located within the zone of attached mucosa fared well with conservative measures while those initially located beyond the zone of attached mucosa fared poorly. In bone necroses where the external radiation dose to the affected bone exceeded 7,000 rad, the mandibular resection rate was high (44%). The most effective way of resolving advanced bone necroses was achieved with a course of hyperbaric oxygen therapy combined with a surgical sequestrectomy.
Asunto(s)
Enfermedades Mandibulares/terapia , Osteorradionecrosis/terapia , Traumatismos por Radiación/terapia , Terapia Combinada , Femenino , Humanos , Oxigenoterapia Hiperbárica , Masculino , Mandíbula/cirugía , Enfermedades Mandibulares/cirugía , Osteorradionecrosis/cirugía , Enfermedades Periodontales/complicaciones , Dosificación Radioterapéutica , Colgajos Quirúrgicos , Extracción DentalRESUMEN
Studies were done with 120 patients submitting to preradiation dental extraction within the radiation treatment volume. Bone necroses developed at the extraction sites in 17 patients (14.1%). The risk of bone necrosis in these patients is primarily dependent upon the size of the radiation treatment volume, radiation dose to mandibular bone, and healing time for the extraction wounds. Of the 13 mandibular bone necroses occurring at preradiation extraction sites, only two have not responded favorably to conservative management. Our data indicates that a policy of selected tooth removal, before radiation treatment, will minimize the risk of osteoradionecrosis. Mandibular molars with advanced chronic periodontal bone loss, residing within the proposed radiation field should be considered for removal before commencement of radiation treatment.
Asunto(s)
Mandíbula/efectos de la radiación , Enfermedades Mandibulares/prevención & control , Neoplasias de la Boca/radioterapia , Osteorradionecrosis/prevención & control , Traumatismos por Radiación/prevención & control , Extracción Dental , Animales , Perros , Humanos , Enfermedades Mandibulares/complicaciones , Enfermedades Mandibulares/etiología , Neoplasias de la Boca/complicaciones , Osteorradionecrosis/complicaciones , Osteorradionecrosis/etiología , Dosificación Radioterapéutica , Ratas , Riesgo , Extracción Dental/efectos adversosRESUMEN
This is the first article in a two-part series dealing with the effects and manifestations in the oral cavity of radiation therapy of head and neck tumors. In this section, oral mucous membranes, taste buds, edema and trismus, diet, salivary glands, bone, periodontium, teeth, and composition of oral flora are discussed. Dental management of the dentulous patient is then approached; criteria for preradiation extraction are delineated. In the next issue of Head & Neck Surgery, the final article in this series will discuss preradiation and postradiation extractions and will elaborate on the dental management (fluoride treatments, follow-up, and restorative care) of the dentulous patient. Dental management of the edentulous patient will also be presented.
Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Enfermedades de la Boca/etiología , Boca/efectos de la radiación , Traumatismos por Radiación/etiología , Bacterias/citología , Humanos , Maxilares/efectos de la radiación , Boca/microbiología , Mucosa Bucal/efectos de la radiación , Higiene Bucal , Periodoncio/efectos de la radiación , Dosificación Radioterapéutica , Glándulas Salivales/efectos de la radiación , Papilas Gustativas/efectos de la radiación , Diente/efectos de la radiación , Extracción Dental , Trismo/etiologíaRESUMEN
This report outlines our experiences involving 72 episodes of postradiation dental extraction over an 11-year period. Bone exposures of 3 months or longer developed following 16 of the 72 postradiation extraction episodes (22%). The necrosis rate in the mandible was 29% (13 of 45) and in the maxilla was 11% (3 of 27). The risk of bone necrosis increased when the dose to bone exceeded 6,500 rad, and when 75% or more of the body of the mandible was within the radiation treatment volume. Five of the 13 mandibular bone necroses precipitated by postradiation extractions eventually required radical resection of the affected portion of the mandible. The remaining eight mandibular episodes healed with conservative measures. When possible, given the two above conditions, root canal therapy rather than dental extraction should be employed to resolve mandibular dental infection within the radiation field after radiotherapy.
Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Osteorradionecrosis/etiología , Traumatismos por Radiación/etiología , Extracción Dental , Relación Dosis-Respuesta en la Radiación , Humanos , Enfermedades Mandibulares/etiología , Enfermedades Maxilares/etiología , Factores de Tiempo , Enfermedades Dentales/etiologíaRESUMEN
This is the concluding portion of a two-part series dealing with the effects and manifestations in the oral cavity of radiation therapy of head and neck tumors. Preradiation and postradiation extractions in dentulous patients, as well as dental maintenance of such patients (including fluoride treatments follow-up, and restorative care), are discussed. Guidelines for the dental management of edentulous patients are also presented at length (this section covers risk of bone necrosis, soft liners, timing of denture placement, dentures and preexisting bone necrosis, soft-tissue necrosis and dentures, morbidity, and prosthodontic procedures). The article concludes with a brief discussion of osteoradionecrosis and soft-tissue necrosis.
Asunto(s)
Atención Dental para la Persona con Discapacidad , Neoplasias de Cabeza y Cuello/radioterapia , Enfermedades Mandibulares/terapia , Neoplasias de la Boca/radioterapia , Osteorradionecrosis/prevención & control , Osteorradionecrosis/terapia , Traumatismos por Radiación/prevención & control , Traumatismos por Radiación/terapia , Caries Dental/prevención & control , Dentadura Completa/efectos adversos , Fluoruros Tópicos/uso terapéutico , Humanos , Oxigenoterapia Hiperbárica , Enfermedades Mandibulares/prevención & control , Boca Edéntula/rehabilitación , Necrosis/etiología , Extracción DentalRESUMEN
This study assesses the success rate of osseous integrated implantation in assisting the prosthetic obturation of maxillectomy defects. Twenty-three patients received a total of 85 osseous integrated implants used for retaining maxillary obturators between 1985 and 1993. Defects include 13 radical maxillectomies, 5 premaxillary resections, 4 subtotal maxillectomies, and 1 soft-palate resection. Thirteen patients (50 implants) received a radiation dose ranging from 5,040 to 7,940 cGy. Implants can be placed at the time of ablation or subsequently. Efforts were made to spare uninvolved segments of the maxilla, especially premaxillary segments and tuberosities, at the time of ablation. Following a 6-month period of integration, implants were uncovered and utilized in prosthetic rehabilitation. Specific implant sites reveal variable success rates, with the anterior maxilla being 86% successful compared with the posterior maxilla being 57% successful. Radiation reduces the success rate from 80% to 55%, although it does not eliminate a patient from being a candidate for implantation. Prosthetic rehabilitation of large maxillary defects can be greatly facilitated with the use of osseous integrated implants in the remaining midfacial skeleton.
Asunto(s)
Maxilar/cirugía , Prótesis Maxilofacial , Prótesis e Implantes , Pérdida de Hueso Alveolar/complicaciones , Trasplante Óseo , Humanos , Enfermedades Maxilares/complicaciones , Neoplasias Maxilares/complicaciones , Neoplasias Maxilares/radioterapia , Neoplasias Maxilares/cirugía , Resultado del TratamientoRESUMEN
Advanced tumors of the midfacial region often require removal of the nose, upper lip, portions of the maxilla, and other adjacent structures. When the resultant defects do not lend themselves to surgical reconstruction, prosthetic appliances may be used successfully to restore the functions of speech and swallowing to near-normal levels. The degree of success depends upon the nature of the previous treatment, the existing surgical defect, and the adaptability of the patient. The most important anatomical consideration is the form and amount of the remaining maxilla. Recent advances in the development of the polyurethanes have resulted in lighter, more flexible, and, therefore, better tolerated prostheses. Close cooperation between the surgeon and the prosthodontist is necessary if successful rehabilitation of these patients is to be achieved.
Asunto(s)
Neoplasias Faciales/cirugía , Prótesis e Implantes , Anciano , Materiales Biocompatibles , Deglución , Neoplasias Faciales/rehabilitación , Femenino , Humanos , Masculino , Masticación , Persona de Mediana Edad , Diseño de Prótesis , HablaRESUMEN
Improper implant angulation is one of the most difficult problems to overcome in the fabrication of implant-supported and implant-retained restorations. Several techniques using the "UCLA" abutment have been developed to solve these problems. The creation of large screw-access holes for moderate angulation and the fabrication of telescopic copings and overlay castings for severe angulation problems are discussed.
Asunto(s)
Implantación Dental Endoósea/métodos , Implantación Dental Endoósea/instrumentación , Implantes Dentales , Diseño de Equipo , HumanosRESUMEN
Three different types of commercially available dental implants (Nobelpharma, IMZ, and Integral) were implanted in the edentulous mandibles of seven adult mongrel dogs. Twenty-one implants were harvested with block sections after 12 weeks and embedded in polymethyl methacrylate resin. Undecalcified sections were prepared with the sectioning-grinding technique. The percentage of bone contacting the implant surface was measured with a self-designed histomorphometry method using a millimeter grid in a stereomicroscope. The results demonstrated a significantly higher percentage of bone along the hydroxyapatite-coated implant than that seen with the titanium-surfaced implant types.
Asunto(s)
Proceso Alveolar/patología , Implantes Dentales , Hidroxiapatitas , Oseointegración , Titanio , Animales , Diseño de Prótesis Dental , Perros , MandíbulaRESUMEN
Twenty patients with microvascular fibula flap reconstruction of oromandibular defects were selected for implant-retained prosthodontic rehabilitation. A total of 71 osseointegrated implants were placed within the grafted fibulas. Four patients had immediate implant placement at the time of their reconstructive surgery, and the remaining 16 patients had implants placed secondarily. One patient received postoperative radiation therapy (5910 cGy) 6 weeks following reconstruction and immediate implant placement. No implants were placed in previously irradiated flaps. A minimum 6-month period of osseointegration was allowed prior to second stage surgery. Fifty-four of the 71 implants were uncovered; 46 of these implants were functional, and 3 were in the process of being restored. Among the 54 implants (15 patients) that were uncovered, only 1 failed to osseointegrate, 2 implants were reburied, and 2 were removed. The follow-up period ranged from 1 to 49 months since second stage surgery. Although a number of prosthodontic designs were used, 11 of the 15 patients were restored with removable overlay prostheses. Only those implants exposed to postoperative radiation demonstrated radiographic bone loss following functional loading.
Asunto(s)
Peroné/trasplante , Mandíbula/cirugía , Oseointegración , Colgajos Quirúrgicos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
From 1987 to 1990, 28 patients were treated with titanium implants (Brånemark flange fixtures) in the craniofacial area for the support of craniofacial prosthesis or anchorage of bone-conduction hearing aids in the Orofacial Implant Center at the University of California, Los Angeles (UCLA). A total of 88 implants were placed, of which 22 were placed in previously irradiated areas. Twenty-three of the implants were placed in the orbital area, 37 in the mastoid area, 20 in the nasal area, and eight in various other craniofacial regions. Seven implants were lost in four different patients. The proper location and positioning of implants in specific areas of the craniofacial regions, as well as soft-tissue complications and management, are discussed.
Asunto(s)
Huesos Faciales/cirugía , Apófisis Mastoides/cirugía , Prótesis e Implantes , Cirugía Plástica/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Irradiación Craneana/efectos adversos , Oído Externo , Femenino , Estudios de Seguimiento , Audífonos , Humanos , Masculino , Prótesis Maxilofacial , Persona de Mediana Edad , Hueso Nasal/cirugía , Nariz , Órbita/cirugía , Oseointegración/efectos de la radiación , Prótesis e Implantes/efectos adversos , Diseño de Prótesis , Falla de Prótesis , Infecciones Relacionadas con Prótesis , TitanioRESUMEN
Restoration of facial symmetry is the goal in rehabilitation of an orbit disfigured by trauma or tumor extirpation. Successful rehabilitation may require replacement of repositioning of the orbital walls and/or construction of a complex orbital prosthesis. Preoperative communication among the head and neck surgeon, ophthalmologist, and maxillofacial prosthodontist is essential.