RESUMEN
OBJECTIVE: The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC. METHODS: Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for (a) the AJCC/UICC pathologic staging, (b) newly published clinical staging for non-surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based, "HPVpath" staging system that combines features of the primary tumor and nodal metastases. RESULTS: A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (⩽4 versus ⩾5) yielded three groups: stages I (pT1-T2, ⩽4 nodes), II (pT1-T2, ⩾5 nodes; pT3-T4, ⩽4 nodes), and III (pT3-T4, ⩾5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort. CONCLUSIONS: Three loco-regional "HPVpath" stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to establish prognosis and guide adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.
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Alphapapillomavirus/aislamiento & purificación , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Anciano , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virología , Supervivencia sin Enfermedad , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/virología , Humanos , Persona de Mediana Edad , Pronóstico , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
OBJECTIVE: With good loco-regional control, disease failure in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) mainly results from distant metastasis (DM). Our objective was to characterize the patterns and clinical outcomes of DM in p16-positive OPSCC and compare these to patients with p16-negative disease. METHODS: Primary OPSCC patients who developed DM after completing surgical or non-surgical treatment were identified and p16 status was evaluated. Patterns of DM and post-DM progression-free (PFS) and disease-specific survival (DSS) were assessed. RESULTS: Forty-one of the 66 (62%) patients with DM were p16-positive. DM patterns were not statistically different by p16 status. However, p16-positive patients developed DM later in their course and had longer survival. All p16-negative patients either had progression or died within 24 months of DM detection whereas the 2-year post-DM PFS in the p16-positive group was 20% (95% CI: 8-32.5%, p=0.003). The 3-year post-DM disease-specific survival (DSS) estimate in the p16-positive patients was 16% (95% CI: 7-18%) while all p16-negative patients died within 34 months (p<0.001). p16-negativity, loco-regional disease, and no/palliative versus curative intent treatment were all associated with reduced post-DM DSS in multivariate analysis. CONCLUSIONS: The DM pattern did not differ remarkably between p16-positive and negative OPSCC patients in our practice. In p16-positive OPSCC with pulmonary oligometastatic disease, curative intent treatment and optimized locoregional control for the index primary prolonged survival.
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Carcinoma de Células Escamosas/patología , Genes p16 , Neoplasias Orofaríngeas/patología , Adulto , Anciano , Carcinoma de Células Escamosas/genética , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/genéticaRESUMEN
There is no good surgical, medical or prosthetic solution to the problems faced by those with a larynx whose function is irreversibly damaged by tumor or trauma. Over the past 10 years, the pace of research designed to establish laryngeal transplantation as a therapeutic option for these persons has increased steadily. The biggest milestone in this field was the world's first true laryngeal transplant performed in Cleveland, Ohio in 1998. The recipient's graft continues to function well, in many respects, even after 7 years. However, it has also highlighted the remaining barriers to full-scale clinical trials. Stimulated by these observations, several groups have accumulated data which point to answers to some of the outstanding questions surrounding functional reinnervation and immunomodulation. This review seeks to outline the progress achieved in this field by 2005 and to point the way forward for laryngeal transplantation research in the 21st century.
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Enfermedades de la Laringe/cirugía , Nervios Laríngeos/cirugía , Laringe/trasplante , Animales , Rechazo de Injerto/prevención & control , Humanos , Terapia de Inmunosupresión , Nervios Laríngeos/anatomía & histología , Laringe/anatomía & histología , Laringe/lesiones , Soluciones Preservantes de Órganos , Daño por Reperfusión/prevención & controlRESUMEN
OBJECTIVE: We undertook this study of free flap reconstruction of the head and neck to stratify patients and procedures, to determine how donor site preference changed over time, to assess medical and surgical outcomes, and to identify variables associated with complications. METHODS: We analyzed computerized medical records from 236 patients who underwent a total of 241 reconstructions at a tertiary academic medical center in St. Louis between 1989 and 1998. We created a more detailed retrospective database of 141 of those patients by using 48 perioperative variables and 7 adverse outcome measures. Multivariate statistical models were used to analyze associations between variables and outcomes. RESULTS: The fibula became the preferred donor site for mandibular reconstruction, and the radial forearm became the preferred donor site for pharyngoesophageal reconstruction. For the 241 procedures, the mortality rate was 2.1%, the median length of stay was 11 days, and the flap survival rate was 95%. Administration of more than 7 L of crystalloid during surgery and age over 55 were associated with major medical complications. Blood transfusion, prognostic comorbidity, and number of surgeons correlated with length of stay. Cigarette smoking and receipt of more than 7 L of crystalloid during surgery were associated with overall flap complications, and weight loss of more than 10% before surgery, more than one operating surgeon, and cigarette smoking were associated with major flap complications. CONCLUSIONS: Risk to patients and transferred tissue is low in free flap head and neck reconstruction. Age, smoking history, and weight loss should be considered during patient selection. Fluid balance should be considered during and after surgery. Division of labor for patient care should be carefully delineated among surgeons in a teaching setting.
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Neoplasias de Cabeza y Cuello/cirugía , Cabeza/cirugía , Cuello/cirugía , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estética , Femenino , Estudios de Seguimiento , Cabeza/fisiopatología , Neoplasias de Cabeza y Cuello/patología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cuello/fisiopatología , Complicaciones Posoperatorias , Estudios Retrospectivos , Donantes de Tejidos , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the impact of delayed regional metastases, distant metastases, and second primary tumors on the therapeutic outcomes in squamous cell carcinomas of the larynx and hypopharynx. STUDY DESIGN: Chart review and statistical analysis. METHODS: A retrospective tumor registry analysis was made of patients with squamous cell carcinomas of the larynx and hypopharynx who were treated with curative intent in the Department of Otolaryngology-Head and Neck Surgery and the Radiation Oncology Center of the Washington University School of Medicine (St. Louis, MO) between January 1971 and December 1991 and developed delayed regional metastases (2 y after treatment), distant metastases, and second primary malignancies. RESULTS: In 2550 patients, the mean age (59.8 y), sex (8.5 male patients and 1 female patient), and tumor differentiation did not affect the incidence of delayed distant, regional, or second primary malignancies. The overall incidence of delayed regional metastases was 12.4% (317/2550 patients); distant metastases, 8.5% (217/2550); and second primary tumors, 8.9% (228/2550), with a 5-year disease-specific survival of 41%, 6.4%, and 35%, respectively. Second primary malignancies were not statistically related to the origin of the primary tumor, tumor staging, or delayed regional and distant metastases (P =.98). Delayed regional metastases and distant metastases were related to advanced primary disease (T4 stage), lymph node metastases (node positive [N+]), tumor location (hypopharynx), and locoregional tumor recurrence (P < or =.028). Advanced regional metastases at initial diagnosis (N2 and N3 disease) increased the incidence of delayed and distant metastases threefold (P =.017). These two metastatic parameters were significantly greater in hypopharyngeal tumors than in laryngeal tumors (P =.037). The incidences of delayed regional metastases by anatomical location of the primary tumor were as follows: glottic, 4.4%; supraglottic, 16%; subglottic, 11.5%; aryepiglottic fold, 21.9%; pyriform sinus, 31.1%; and posterior hypopharyngeal wall, 18.5%. The incidences of distant metastases were as follows: glottic, 4%; supraglottic, 3.7%; subglottic, 14%; aryepiglottic fold, 16%; pyriform fossa, 17.2%; and posterior hypopharyngeal wall, 17.6%. Seventeen hypopharyngeal tumors (2%) presented with M1 disease. Delayed regional metastases to the ipsilateral treated neck had a significantly worse survival prognosis than delayed metastases to the contralateral nontreated neck (P =.001). CONCLUSIONS: Conclusions are as follows: 1) The incidence of second primary tumors is independent from the primary tumor staging and distant and delayed regional metastases. The highest incidence occurred in patient groups with the highest disease-free survival rates (P =.0378). 2) Highest incidence of delayed and distant metastases occurred in hypopharyngeal tumors and was three times greater than in laryngeal cancers (P =.028). 3) Salvage therapeutic rates were poor for delayed metastases to the ipsilateral treated nodes and distant metastases as compared with contralateral neck metastases and second primary tumors (P =.001). 4) Delayed and distant lymph node metastases were significantly higher in advanced primary disease (T4 stage), locoregional recurrences, and regional disease (N2 and N3) (P =.028) in both the larynx and hypopharynx. 5) The higher incidence of delayed and distant metastatic disease was related to more advanced initial tumor presentation in hypopharyngeal cancer as compared with laryngeal cancer (P =.039). 6) Incidence of distant metastases was greatest between 1.5 and 6 years after initial treatment with a mean incidence being less than or equal to 3.2 years.
Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Hipofaríngeas/patología , Neoplasias Laríngeas/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Secundarias/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Causas de Muerte , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hipofaríngeas/mortalidad , Neoplasias Hipofaríngeas/terapia , Hipofaringe/patología , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/terapia , Laringe/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/terapia , Estudios Retrospectivos , Terapia Recuperativa , Tasa de SupervivenciaRESUMEN
BACKGROUND: The therapeutic outcomes for voice preservation in Stage I (T1 N0 M0) glottic carcinoma, treated with conservation surgery, radiation therapy, and endoscopic resection, are controversial. METHODS: A retrospective tumor registry retrieval of data on patients treated with curative intent at Washington University Medical Center-Barnes Hospital between January 1971 and December 1990 for the surgical group, January 1971 to December 1985 for the low-dose radiation group, and January 1986 to January 1995 for the high-dose radiation group, was performed. RESULTS: The 659 patients with Stage I (T1 N0 M0) glottic carcinoma treated with curative intent were subdivided into four groups: (1) 90 patients received low-dose radiation (mean dose 58 Gy, range 55-65 Gy, daily fractionation 1.5-1.8 Gy); (2) 104 patients received high-dose radiation (mean dose 66.5 Gy, range 65-70 Gy, daily fractionation 2-2.25 Gy); (3) 404 patients underwent conservation surgery; and (4) 61 patients had endoscopic resection. T1A (85%) and T1B (15%) disease was equally distributed among the groups. The anterior commissure was involved in 38 patients in the radiation therapy groups and 56 patients in the surgical groups. The overall local control was 89%. The overall local salvage was 84%. The overall unaided laryngeal voice preservation was 90%. The overall 5-year disease specific and actuarial survival rates were 95% and 81%, respectively. Prevalence of 2% regional metastases, 1.2% distant metastases, and 14% second primary malignancies were documented. The cure rate was 69% for regional metastases, 13% for distant metastases, and 44% for second primary malignancies. There were 5 complication deaths (0.1%), and 38 (6%) patients died of intercurrent disease. The use and dose of tobacco products was significantly increased in patients who died of intercurrent disease (p = 0.004) or developed second primary malignancies (p = 0.024). No significant difference was observed among the four therapeutic groups in the 5-year cause-specific survival rate (p, 0.68). Actuarial survival was significantly decreased in the low-dose radiation therapy group as compared with the other three therapeutic groups (p = 0.04). Initial local control was poorer for the endoscopic (77%) and low-dose radiation (78%) groups as compared with the high-dose radiation (89%) and conservation surgery (92%) groups (p = 0.02) but significant differences were not found for ultimate local control following salvage treatment. Unaided laryngeal voice preservation was similar for high-dose radiation (89%), conservation surgery (93%) and endoscopic resection (90%), but significantly poorer for low-dose radiation (80%; p = 0.02). T1B disease (N = 94) had similar local control and voice preservation with conservation surgery (87%) and high-dose radiation (88%) but lower results with low-dose radiation and endoscopic resections (67% unaided laryngeal voice preservation; p = 0.02). CONCLUSION: (1)The four therapeutic groups achieved similar rates of disease specific survival and ultimate local control. (2) Low-dose radiation was associated with significantly lower overall actuarial survival and unaided laryngeal voice preservation. (3) Endoscopic resection was associated with a significantly lower initial local control rate, but following salvage therapy achieved equivalent results to the other treatment methods. (4) Patients with (T1 N0 M0) glottic carcinoma had similar survival, local control, and unaided laryngeal voice preservation rates with high-dose radiation, conservation surgery, and endoscopic resections, but not with low-dose radiation therapy. (c) 1999 John Wiley & Sons, Inc. Head Neck 21: 707-717, 1999.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias Laríngeas/terapia , Adulto , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Glotis , Humanos , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/patología , Laringectomía , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , VozRESUMEN
INTRODUCTION: Reconstruction of the tongue with existing methods of tissue transfer often leaves glossectomy patients with significant deficits in speech and swallowing. The critical role of the tongue is implied by its unique structure and function. This paper reports the development of an animal model of hemitongue allotransplantation and documents functional and anatomic outcomes of this procedure. METHODS: Ten pairs of unmatched dogs underwent reciprocal exchange of the left hemitongue with microneurovascular replantation. The unoperated hemitongue acted as the control. Under cyclosporine immunosuppression, animals surviving long term underwent clinical observation, before electromyography, force transduction studies, and histological evaluation being euthanized. RESULTS: Five animals survived between 6 and 13 months for long-term evaluation. The remaining group were euthanized because of or died of overwhelming infection or uncontrollable transplant rejection. The latter sometimes resulted from difficulty in the delivery of the cyclosporine. Clinical recovery of tongue function was observed, as well as resumption of motor unit potential activity on electromyography. Contractile force recovery of the transplanted tongue averaged 68% of control (range, 47%-97%), and histological study of the hypoglossal and lingual nerves demonstrated anatomic evidence of reinnervation. Preservation of muscle, mucosal, and stromal ultrastructure was seen with light microscopy of the transplanted tongue. CONCLUSIONS: Allotransplantation of the hemitongue and associated neurovascular apparatus is possible in a large mammalian model, with long-term survival of tissue being accompanied by partial recovery of contractile properties. Anatomical and clinical evidence also points to sensory recovery. These data support the future possibility of employing a similar technique in glossectomy patients.
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Lengua/trasplante , Animales , Ciclosporina/uso terapéutico , Perros , Electromiografía , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Nervio Hipogloso/fisiología , Nervio Hipogloso/cirugía , Inmunosupresores/uso terapéutico , Nervio Lingual/fisiología , Nervio Lingual/cirugía , Masculino , Regeneración Nerviosa/fisiología , Lengua/fisiopatología , Trasplante HomólogoRESUMEN
The authors report a case of an aggressive chordoma in the cervical spine of a 15-year-old girl who underwent radical resection followed by reconstruction using an anterior vascularized fibular strut graft and posterior arthrodesis prior to receiving immediate postoperative radiation therapy. The patient had successful graft incorporation 4 months postoperatively. The authors review the advantages of using vascularized fibular strut grafts for the treatment of multilevel cervical spine neoplastic disease and discuss the theoretical advantages of using vascularized grafts that tolerate therapeutic levels of radiation.
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Vértebras Cervicales/cirugía , Cordoma/cirugía , Peroné/trasplante , Fusión Vertebral/métodos , Neoplasias de la Columna Vertebral/cirugía , Adolescente , Cordoma/radioterapia , Femenino , Peroné/irrigación sanguínea , Humanos , Imagen por Resonancia Magnética , Radioterapia Adyuvante , Neoplasias de la Columna Vertebral/radioterapia , Tomografía Computarizada por Rayos X , Trasplante AutólogoRESUMEN
This study evaluated long-term reinnervation of an end-to-side neurorraphy and the resultant functional recovery in a rat model. The divided distal posterior tibial nerve was repaired to the side of an intact peroneal nerve. Control groups included a cut-and-repair of the posterior tibial nerve and an end-to-end repair of the peroneal nerve to the posterior tibial nerve. Evaluations included walking-track analysis, nerve conduction studies, muscle mass measurements, retrograde nerve tracing, and histologic evaluation. Walking tracks indicated poor recovery of posterior tibial nerve function in the experimental group. No significant difference in nerve conduction velocities was seen between the experimental and control groups. Gastrocnemius muscle mass measurements revealed no functional recovery in the experimental group. Similarly, retrograde nerve tracing revealed minimal motor neuron staining in the experimental group. However, some sensory staining was seen within the dorsal root ganglia of the end-to-side group. Histologic study revealed minimal myelinated axonal regeneration in the experimental group as compared with findings in the other groups. These results suggest that predominantly sensory regeneration occurs in an end-to-side neurorraphy at an end point of 6 months.
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Anastomosis Quirúrgica/métodos , Regeneración Nerviosa/fisiología , Nervio Peroneo/cirugía , Nervio Tibial/cirugía , Potenciales de Acción/fisiología , Animales , Axones/fisiología , Axones/ultraestructura , Colorantes , Modelos Animales de Enfermedad , Estudios de Evaluación como Asunto , Estudios de Seguimiento , Ganglios Espinales/fisiología , Ganglios Espinales/ultraestructura , Estudios Longitudinales , Masculino , Neuronas Motoras/fisiología , Neuronas Motoras/ultraestructura , Músculo Esquelético/anatomía & histología , Músculo Esquelético/inervación , Vaina de Mielina/fisiología , Conducción Nerviosa/fisiología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Neuronas Aferentes/fisiología , Neuronas Aferentes/ultraestructura , Nervio Peroneo/anatomía & histología , Nervio Peroneo/fisiología , Distribución Aleatoria , Ratas , Ratas Endogámicas Lew , Nervio Tibial/anatomía & histología , Nervio Tibial/fisiología , Caminata/fisiologíaRESUMEN
Frequent allelic loss at a genetically polymorphic locus in tumors is an established marker for the presence of a tumor suppressor gene in the neighboring chromosomal region. This technique can be used to identify novel tumor suppressor genes and to monitor their status before the cloning of the gene itself. We have used the polymerase chain reaction and microsatellite loci on all 39 nonacrocentric autosomal chromosomal arms to identify sites of frequent allelic loss in squamous cell carcinomas of the supraglottic larynx. Our allelotype identified seven chromosomal arms (3p, 5q, 8p, 9p, 9q, 13q, and 17p) likely to contain tumor suppressor genes frequently inactivated during squamous tumorigenesis in the larynx. We tested for associations between allelic losses on these chromosomal arms and the clinical and histopathologic features of these tumors. There were no correlations with either T or N classifications. Allelic loss on chromosomal arm 13q is significantly associated with a number of histopathologic features characteristic of poorly differentiated or histologically aggressive tumors. Allelic loss on this arm also exhibits statistical trends toward association with early tumor recurrence and poor survival. The association with survival was substantiated by a multivariate Cox proportional hazards model.
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Alelos , Carcinoma de Células Escamosas/genética , Glotis , Neoplasias Laríngeas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Genes Supresores de Tumor/fisiología , Glotis/patología , Humanos , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/patología , Repeticiones de Microsatélite , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Estadística como AsuntoRESUMEN
This study evaluated reinnervation of an end-to-side neurorrhaphy and the resultant functional recovery in a rat model. The cut distal posterior tibial nerve was repaired to the side of an intact peroneal nerve. In one group, the epineurium of the peroneal nerve was left intact; in another group, the epineurium was stripped; in the third experimental group, a perineurial slit was created. Evaluations included walking track analysis, nerve conduction studies, muscle mass measurements, retrograde nerve tracing, and histologic evaluation. Walking tracks indicated poor functional recovery. No significant difference in nerve conduction between the experimental and control groups was seen. Gastrocnemius muscle mass measurements revealed no functional recovery in the end-to-side groups. Retrograde nerve tracing revealed minimal staining of motor neurons. However, sensory neuronal staining of the dorsal root ganglia occurred in all groups. Histology revealed minimal myelinated axonal regeneration. These results suggest that predominantly sensory neural regeneration occurs in an end-to-side neurorrhaphy at an end point of 16 weeks.
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Axones/fisiología , Regeneración Nerviosa/fisiología , Transferencia de Nervios/métodos , Estilbamidinas , Anastomosis Quirúrgica , Animales , Colorantes Fluorescentes/análisis , Ganglios Espinales/citología , Peroxidasa de Rábano Silvestre/análisis , Masculino , Músculo Esquelético/inervación , Conducción Nerviosa/fisiología , Nervio Peroneo/cirugía , Ratas , Ratas Endogámicas Lew , Degeneración Retrógrada/fisiología , Nervio Tibial/cirugía , Nervio Tibial/ultraestructuraRESUMEN
Thyroidectomy procedures are the mainstay treatment for thyroid cancer and are safe and effective when they are performed by experienced surgeons. Preoperative evaluation of patients with suspected thyroid cancer consists of ultrasonography, radioisotope scanning, and computed tomography scans. Postoperative complications of thyroidectomy procedures include hemorrhage, edema of the glottis, muscle rigidity and spasm (ie, tetany), acute thyrotoxicosis, and damage to the laryngeal nerve. Most surgical patients are discharged home within three days after surgery, and many patients require lifelong thyroid hormone replacement to prevent hypothyroidism.
Asunto(s)
Carcinoma Papilar/enfermería , Carcinoma Papilar/cirugía , Enfermería Perioperatoria , Neoplasias de la Tiroides/enfermería , Neoplasias de la Tiroides/cirugía , Tiroidectomía/enfermería , Carcinoma Papilar/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Pruebas de Función de la Tiroides , Glándula Tiroides/fisiología , Neoplasias de la Tiroides/clasificación , Neoplasias de la Tiroides/diagnóstico , Tiroidectomía/efectos adversosRESUMEN
BACKGROUND: Loss of genetic heterogeneity (allelic loss or loss of heterozygosity) on chromosome arm 8p is frequent in squamous cell carcinomas of the head and neck and has been associated with poor prognosis. We have previously demonstrated that there are three minimal regions of allelic loss on this chromosome arm. The location of each region is marked by a microsatellite locus: D8S264 (8p23), D8S552 (8p23-p22), and D8S133 (8p21). These findings imply the existence of at least three putative tumor suppressor genes on this chromosome arm that may become inactivated during the progression of squamous cell carcinoma. PURPOSE: We used allelic loss data from these three loci to determine if inactivation of these putative suppressors is associated with poor prognosis for patients with squamous cell carcinoma of the supraglottic larynx. We also used multivariate statistics to compare the prognostic power of allelic loss at these genetic markers with that of demographic, clinical, and histopathologic parameters. METHODS: We examined the D8S264, D8S552, and D8S133 microsatellites in tumors from a retrospective population of 59 patients. All patients had histologically confirmed squamous cell carcinoma of the supraglottic larynx and had been treated surgically. DNA was extracted from matched sets of normal and microdissected tumor tissue and used for polymerase chain reaction amplification of the microsatellite markers. Reaction products were separated by denaturing gel electrophoresis and visualized by autoradiography. Patient data were obtained from the original pathology report and from the tumor registry of the Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO. Histopathologic data were obtained by reviewing the portion of the resection specimen used for DNA extraction. Parameters whose association with reduced disease-free interval and reduced disease-specific survival was statistically significant were identified by use of the Kaplan-Meier method and the logrank statistic. Multivariate Cox proportional hazards models were used to identify independent predictors of poor prognosis. All statistical tests were two-sided. RESULTS: In this patient population, allelic loss at the D8S264 locus was associated with both shorter disease-free interval (logrank P = .028) and reduced disease-specific survival (logrank P = .004). Allelic loss at the next most centromeric locus, D8S552, had a statistically significant association with only reduced disease-specific survival (logrank P = .034), whereas allelic loss at the most centromeric region, D8S133, showed no statistically significant association with reductions in either interval. Multivariate Cox models suggested that D8S264 was the only 8p marker of the three microsatellites with a statistically significant and independent association with shortened disease-free interval (relative risk [RR] = 3.38; P = .0107) and reduced disease-specific survival (RR = 3.41; P = .0105). CONCLUSIONS: Allelic loss in the p23 region of chromosome 8 appears to be a statistically significant, independent predictor of poor prognosis in patients with supraglottic squamous cell carcinoma.
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Carcinoma de Células Escamosas/genética , Deleción Cromosómica , Cromosomas Humanos Par 8 , Neoplasias Laríngeas/genética , Alelos , Carcinoma de Células Escamosas/patología , ADN de Neoplasias/genética , Supervivencia sin Enfermedad , Femenino , Glotis , Heterocigoto , Humanos , Neoplasias Laríngeas/patología , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo Genético , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Numerous clinical parameters have been suggested as predictors of outcome for patients with head and neck carcinoma treated with radiation therapy, but their applicability remains controversial. Inactivation of the p53 tumor suppressor results in radioresistance in experimental systems and might predict treatment failure in human patients. We have tested this hypothesis by comparing the predictive power of nuclear accumulation of p53 protein with that of clinical and histopathologic markers in patients with glottic carcinoma treated with primary radiotherapy. METHODS: Clinical charts were reviewed for 165 patients with glottic squamous cell carcinoma treated with radiation therapy. One hundred and twenty-one patients with T1 or T2 classified tumors were determined to have received adequate treatment and to have adequate follow-up data for further study. Archival pretreatment tumor biopsies from a subpopulation of patients were examined for p53 protein by immunohistochemistry. The influence of clinical and histopathologic variables and p53 nuclear protein on tumor recurrence was studied by bivariate and multivariate analysis. RESULTS: The recurrence rate was lowest for patients with moderately to poorly differentiated tumors (P < 0.05). This was the only significant predictor of outcome in this patient population. The presence of immunohistochemically detectable p53 antigen was not predictive of tumor recurrence in 70 patients for whom there was both p53 and sufficient follow-up data. CONCLUSIONS: Histologic differentiation was prognostic for tumor recurrence in this population of patients with glottic carcinoma treated with radiation therapy. In contrast, nuclear accumulation of p53 protein was not predictive of tumor response or recurrence in this population.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/radioterapia , Proteína p53 Supresora de Tumor/análisis , Anciano , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Neoplasias Laríngeas/química , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , PronósticoRESUMEN
The mutational inactivation of suppressor genes, a process required for cancer progression, generates new genetic subclones within a tumor. The allelic losses that frequently unmask these mutations serve not only as markers of the chromosomal locations of these genes but also as clonal fingerprints of the shifting relationships between these genetically heterogeneous cell populations. The rise of the metastasis-competent subclone to dominance within the primary tumor should be reflected in the similarity of the genetic fingerprints of the primary tumor and its resultant metastases. We have tested this hypothesis by comparing the patterns of allelic loss of individual primary laryngeal squamous cell carcinomas and their resultant cervical lymph node metastases at 16 different genetically polymorphic loci on 15 chromosome arms. Although primary tumors and metastases both frequently lose heterozygosity on the same chromosome arms (3p, 9p, 9q, 13q, and 17p), five of the 12 metastases differed from their primary tumors at one or two of the loci examined. Discordance between the two tumor cell populations from the same patient is suggestive of either subclone heterogeneity within the primary tumor at the time of establishment of the metastasis or further clonal evolution of both tumors after metastasis.
Asunto(s)
Carcinoma de Células Escamosas/genética , Deleción Cromosómica , Cromosomas Humanos , Eliminación de Gen , Genes Supresores de Tumor , Neoplasias Laríngeas/genética , Metástasis Linfática/genética , Metástasis de la Neoplasia/genética , Alelos , Carcinoma de Células Escamosas/patología , Mapeo Cromosómico , ADN de Neoplasias/análisis , Humanos , Neoplasias Laríngeas/patología , Reacción en Cadena de la PolimerasaRESUMEN
Gender differences in the incidence and mortality rates for cancers of the lung, colon, and larynx have previously been noted. The goal of this project was to identify gender differences in prognostic variables for survival and recurrence for patients with cancer of the larynx. The medical records of 193 patients with cancer of the larynx treated initially between 1973 and 1985 were examined retrospectively. A total of 151 men and 42 women were included. A majority of men developed glottic cancers, whereas a majority of women developed supraglottic cancers. Age was prognostically important for both genders; however, comorbidity, symptom severity, anatomic subsite, and TNM stage all had different impacts on survival and recurrence in men and women. No gender difference in initial treatment was found. This study suggests that when designing and analyzing the results from clinical studies of cancer of the larynx, it is important to employ stratification based on gender.
Asunto(s)
Neoplasias Laríngeas/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Factores de Edad , Anciano , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Tasa de Supervivencia , Factores de TiempoRESUMEN
Reconstructive options following total laryngopharyngectomy include thin, pliable free tissue segments, approximating the natural thickness of the pharyngeal wall. The authors have investigated outcomes in the following clinical series, emphasizing speech and swallowing. Twelve cancer patients underwent laryngopharyngectomy with or without glossectomy. Eight jejunal, 1 radial forearm, and 3 innervated latissimus dorsi flaps were used for vibratory segment (VS) reconstruction, and all 12 patients underwent tracheoesophageal puncture (TEP). Eleven patients achieved intelligible speech, with a median intelligibility of 93%. The vibrating segments showed fluttering of the free flap tissue when studied by videopharyngography. Vocal quality was lower pitched and softer than "conventional" TEP speech. All patients achieved oral intake as their primary mode of nutrition. Free flaps are a successful option for VS reconstruction in patients undergoing laryngopharyngectomy or glossopharyngolaryngectomy, obviating the need for written or electrolarynx communication.