RESUMEN
BACKGROUND: Despite the importance of tumor-infiltrating T lymphocytes (TILs) in cancer biology, the relationship between TIL phenotypes and their prognostic relevance for localized non-small-cell lung cancer (NSCLC) has not been well established. PATIENTS AND METHODS: Fresh tumor and normal adjacent tissue was prospectively collected from 150 patients with localized NSCLC. Tissue was comprehensively characterized by high-dimensional flow cytometry of TILs integrated with immunogenomic data from multiplex immunofluorescence, T-cell receptor sequencing, exome sequencing, RNA sequencing, targeted proteomics, and clinicopathologic features. RESULTS: While neither the magnitude of TIL infiltration nor specific TIL subsets were significantly prognostic alone, the integration of high-dimensional flow cytometry data identified two major immunotypes (IM1 and IM2) that were predictive of recurrence-free survival independent of clinical characteristics. IM2 was associated with poor prognosis and characterized by the presence of proliferating TILs expressing cluster of differentiation 103, programmed cell death protein 1, T-cell immunoglobulin and mucin-domain containing protein 3, and inducible T-cell costimulator. Conversely, IM1 was associated with good prognosis and differentiated by an abundance of CD8+ T cells expressing cytolytic enzymes, CD4+ T cells lacking the expression of inhibitory receptors, and increased levels of B-cell infiltrates and tertiary lymphoid structures. While increased B-cell infiltration was associated with good prognosis, the best prognosis was observed in patients with tumors exhibiting high levels of both B cells and T cells. These findings were validated in patient tumors from The Cancer Genome Atlas. CONCLUSIONS: Our study suggests that although the number of infiltrating T cells is not associated with patient survival, the nature of the infiltrating T cells, resolved in distinct TIL immunotypes, is prognostically relevant in NSCLC and may inform therapeutic approaches to clinical care.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Linfocitos T CD8-positivos , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Linfocitos Infiltrantes de Tumor/patología , PronósticoRESUMEN
BACKGROUND: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. METHODS: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. RESULTS: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). CONCLUSION: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.
Asunto(s)
Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Anciano , Quimioradioterapia Adyuvante , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Terapia RecuperativaRESUMEN
The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.
Asunto(s)
Quimioradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Complicaciones Posoperatorias , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Terapia Combinada/métodos , Terapia Combinada/estadística & datos numéricos , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía/efectos adversos , Esofagectomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Evaluación de Procesos y Resultados en Atención de Salud , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Terapia Recuperativa/métodos , Terapia Recuperativa/estadística & datos numéricosRESUMEN
BACKGROUND: The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. PATIENTS AND METHODS: Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. RESULTS: Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. CONCLUSION: Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia , Selección de Paciente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Curva ROC , Factores de RiesgoRESUMEN
BACKGROUND: Chemoradiation followed by surgery is the preferred treatment of localized gastroesophageal cancer (GEC). Surgery causes considerable life-altering consequences and achievement of clinical complete response (clinCR; defined as postchemoradiation [but presurgery] endoscopic biopsy negative for cancer and positron emission tomographic (PET) scan showing physiologic uptake) is an enticement to avoid/delay surgery. We examined the association between clinCR and pathologic complete response (pathCR). PATIENTS AND METHODS: Two hundred eighty-four patients with GEC underwent chemoradiation and esophagectomy. The chi-square test, Fisher exact test, t-test, Kaplan-Meier method, and log-rank test were used. RESULTS: Of 284 patients, 218 (77%) achieved clinCR. However, only 67 (31%) of the 218 achieved pathCR. The sensitivity of clinCR for pathCR was 97.1% (67/69), but the specificity was low (29.8%; 64/215). Of the 66 patients who had less than a clinCR, only 2 (3%) had a pathCR. Thus, the rate of pathCR was significantly different in patients with clinCR than in those with less than a clinCR (P < 0.001). CONCLUSIONS: clinCR is not highly associated with pathCR; the specificity of clinCR for pathCR is too low to be used for clinical decision making on delaying/avoiding surgery. Surgery-eligible GEC patients should be encouraged to undergo surgery following chemoradiation despite achieving a clinCR.
Asunto(s)
Quimioradioterapia , Neoplasias Esofágicas/terapia , Neoplasias Gástricas/terapia , Estudios de Cohortes , Terapia Combinada , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Inducción de Remisión , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The contribution of induction chemotherapy (IC) before preoperative chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC would increase the rate of pathologic complete response (pathCR). METHODS: Trimodality-eligibile patients were randomized to receive no IC (Arm A) or IC (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted â¼5-6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality, overall survival (OS), and toxic effects were assessed. Bayesian methods and Fisher's exact test were used. RESULTS: One hundred twenty-six patients were randomized dynamically to balance the two arms for histology, baseline stage, gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months [95% confidence interval (CI), 27.63-NA], with median OS 45.62 months (95% CI 25.56-NA) in Arm A and 43.68 months (95% CI 27.63-NA) in Arm B (P = 0.69). The pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided Fisher's exact test, P = 0.094). Safety was similar in both arms. CONCLUSIONS: These data suggest that IC produces non-significant increase in the pathCR rate and does not prolong OS. Further development of IC before chemoradiation may not be beneficial. Clinical trial no.: NCT 00525915 (www.clinicaltrials.gov).
Asunto(s)
Quimioradioterapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Quimioterapia de Inducción , Adulto , Anciano , Teorema de Bayes , Cisplatino/administración & dosificación , Terapia Combinada , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Periodo Preoperatorio , Inducción de RemisiónRESUMEN
BACKGROUND: Approximately 25% of patients with esophageal cancer (EC) who undergo preoperative chemoradiation, achieve a pathologic complete response (pathCR). We hypothesized that a model based on clinical parameters could predict pathCR with a high (≥60%) probability. PATIENTS AND METHODS: We analyzed 322 patients with EC who underwent preoperative chemoradiation. All the patients had baseline and postchemoradiation positron emission tomography (PET) and pre- and postchemoradiation endoscopic biopsy. Logistic regression models were used for analysis, and cross-validation via the bootstrap method was carried out to test the model. RESULTS: The 70 (21.7%) patients who achieved a pathCR lived longer (median overall survival [OS], 79.76 months) than the 252 patients who did not achieve a pathCR (median OS, 39.73 months; OS, P = 0.004; disease-free survival, P = 0.003). In a logistic regression analysis, the following parameters contributed to the prediction model: postchemoradiation PET, postchemoradiation biopsy, sex, histologic tumor grade, and baseline (EUS)T stage. The area under the receiver-operating characteristic curve was 0.72 (95% confidence interval [CI] 0.662-0.787); after the bootstrap validation with 200 repetitions, the bias-corrected AU-ROC was 0.70 (95% CI 0.643-0.728). CONCLUSION: Our data suggest that the logistic regression model can predict pathCR with a high probability. This clinical model could complement others (biomarkers) to predict pathCR.
Asunto(s)
Neoplasias Esofágicas/patología , Terapia Combinada , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Humanos , Análisis Multivariante , Análisis de SupervivenciaRESUMEN
High body mass index (H-BMI; ≥25 kg/m(2) ) is common in US adults. In a small cohort of esophageal cancer (EC) patients treated with surgery, H-BMI and diagnosis of early stage EC appeared associated. We evaluated a much larger cohort of EC patients. From a prospectively maintained database, we analyzed 925 EC patients who had surgery with or without adjunctive therapy. Various statistical methods were used. Among 925 patients, 69% had H-BMI, and 31% had normal body mass index (<25 kg/m(2) ; N-BMI). H-BMI was associated with men (P<0.001), Caucasians (P=0.064; trend), lower esophageal localization (P<0.001), adenocarcinoma histology (P<0.001), low baseline cT-stage (P=0.003), low baseline overall clinical stage (P=0.003), coronary artery disease (P=0.036), and diabetes (P<0.001). N-BMI was associated with weight loss (P<0.001), alcohol abuse (P=0.056; trend), ever/current smoking (P=0.014), and baseline cN+ (P=0.018). H-BMI patients with cT1 tumors (n=110) had significantly higher rates of gastresophageal reflux disease symptoms (P<0.001), gastresophageal reflux disease history (P<0.001), and Barrett's esophagus history (P<0.001) compared with H-BMI patients with cT2 tumors (n=114). Median survival of N-BMI patients was 36.66 months compared with 53.20 months for H-BMI patients (P=0.005). In multivariate analysis, older age (P<0.001), squamous histology (P=0.002), smoking (P=0.040), weight loss (P=0.002), high baseline stage (P<0.001), high number of ypN+ (P=0.005), high surgical stage (P<0.001), and American Society of Anesthesia scores, three out of four (P<0.001) were independent prognosticators for poor overall survival. We were able to perform propensity-based analysis of surgical complications between H-BMI and N-BMI patients. A comparison of fully matched 376 patients (188 with H-BMI and 188 with N-BMI) found no significant differences in the rate of complications between the two groups. This larger data set confirms that a fraction of H-BMI patients with antecedent history is diagnosed with early baseline EC. Upon validation of our data in an independent cohort, refinements in surveillance of symptomatic H-BMI patients are warranted and could be implemented. Our data also suggest that H-BMI patients do not experience higher rate of surgical complications compared with N-BMI patients.
Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Sobrepeso/complicaciones , Adenocarcinoma/complicaciones , Adenocarcinoma/patología , Factores de Edad , Anciano , Índice de Masa Corporal , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Obesidad/complicaciones , Estudios Retrospectivos , Factores Sexuales , Tasa de Supervivencia , Factores de TiempoRESUMEN
During inflammation, neutrophils migrate from the vascular lumen into extravascular sites. In vitro assays have suggested that platelet-endothelial cell adhesion molecule-1 [PECAM-1 (CD31)], a member of the immunoglobulin superfamily, is required for the transmigration of neutrophils across endothelial monolayers. Antibody to human PECAM-1, which cross-reacts with rat PECAM-1, was found to block not only in vivo accumulation of rat neutrophils into the peritoneal cavity and the alveolar compartment of the lung but also neutrophil accumulation in human skin grafts transplanted onto immunodeficient mice. On the basis of these findings in three different models of inflammation, it appears that PECAM-1 is required for neutrophil transmigration in vivo and may thus be a potential therapeutic target.
Asunto(s)
Antígenos de Diferenciación Mielomonocítica/fisiología , Moléculas de Adhesión Celular/fisiología , Glicoproteínas de Membrana/fisiología , Neutrófilos/fisiología , Animales , Anticuerpos/farmacología , Antígenos de Diferenciación Mielomonocítica/inmunología , Moléculas de Adhesión Celular/inmunología , Movimiento Celular/fisiología , Quimiotaxis de Leucocito/fisiología , Endotelio/inmunología , Humanos , Enfermedades del Complejo Inmune/inmunología , Glicoproteínas de Membrana/inmunología , Ratones , Ratones SCID , Cavidad Peritoneal/citología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta , Ratas , Trasplante de Piel/inmunología , Trasplante Heterólogo/inmunologíaRESUMEN
Human umbilical vein endothelial cells have recently been shown to respond to C5a with increases in intracellular Ca2+, production of D-myo-inositol 1,4,5-triphosphate and superoxide anion generation. In the current studies, C5a had been found to cause in a time- and dose-dependent manner rapid expression of endothelial P-selectin, secretion of von Willebrand factor, and adhesiveness for human neutrophils. The effects of C5a in P-selectin expression and adhesiveness of neutrophils were similar to the effects of histamine and thrombin on endothelial cells. The adhesiveness of C5a-stimulated endothelium for neutrophils was blocked by anti-P-selectin, but not by antibodies to intercellular adhesion molecule 1, E-selectin, or CD18. A cell-based ELISA technique has confirmed upregulation of P-selectin in endothelial cells exposed to C5a. Binding of C5a to endothelial cells has been demonstrated, with molecules bound being approximately 10% of those binding to neutrophils. By a reverse transcriptase-PCR technique, endothelial cells have been shown to contain mRNA for the C5a receptor. These data suggest that C5a may be an important inflammatory mediator for the early adhesive interactions between neutrophils and endothelial cells in the acute inflammatory response.
Asunto(s)
Complemento C5a/farmacología , Endotelio Vascular/fisiología , Glicoproteínas de Membrana Plaquetaria/biosíntesis , Receptores de Complemento/biosíntesis , Adhesión Celular/fisiología , Moléculas de Adhesión Celular/biosíntesis , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Ensayo de Inmunoadsorción Enzimática , Expresión Génica , Histamina/farmacología , Humanos , Cinética , Neutrófilos/fisiología , Selectina-P , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Receptor de Anafilatoxina C5a , Proteínas Recombinantes/farmacología , Venas Umbilicales , Factor de von Willebrand/análisis , Factor de von Willebrand/biosíntesisRESUMEN
Neutrophil adherence to endothelial monolayers in multi-well plates can be rapidly quantitated, using a fluorescent plate reader. The number of adherent neutrophils which have been labeled with biscarboxyethyl carboxyfluorescein (BCECF) was calculated by comparing fluorescence of endothelial monolayers to a reference standard curve determined by fluorescence intensity of suspensions of labeled neutrophils. The limit of sensitivity approached 100 cells, which is similar to that achieved by the most sensitive of alternate techniques. The assay, after isolation of the neutrophils, can be completed in 1.5 h. The ability to utilize microwell plates permits the use of large numbers of samples. This method has the advantage of being relatively simple and rapid while maintaining a sensitivity comparable to alternate approaches which employ radioactive labeling or counting of adherent or non-adherent cells.
Asunto(s)
Adhesión Celular , Endotelio Vascular/fisiología , Neutrófilos/fisiología , Adhesión Celular/efectos de los fármacos , Recuento de Células , Células Cultivadas , Fluoresceínas , Fluorescencia , Humanos , Acetato de Tetradecanoilforbol/farmacología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
OBJECTIVE: Primary sarcomas involving the chest wall requiring full-thickness excision are rare. We reviewed our experience with these lesions in a tertiary referral cancer center by using multidisciplinary approaches. METHODS: A 10-year retrospective study identified 51 patients referred with primary sarcomas of the chest wall: 40 for initial treatment and 11 after previous unsuccessful surgical excisions elsewhere (secondary referral). Presenting symptoms were pain alone in 23 (45%) of 51 patients, pain with an associated mass in 8 (16%) patients, and an asymptomatic mass alone in 13 (25%) patients. Median symptom duration was 241 days in the primary group and 225 days in the recurrent group. Tumor locations were the sternum (n = 11), the rib alone (n = 36), and the posterior rib with extension into vertebral bodies (n = 4). Histologic types included the following: chondrosarcomas (n = 15), malignant fibrous histiocytomas (n = 9), osteosarcomas (n = 4), Ewing sarcomas (n = 3), desmoid tumors (n = 7), and other types (n = 13). The median tumor volume of those referred initially was 311 cm(3) compared with 84 cm(3) in patients with recurrent lesions. RESULTS: Twenty-six (51%) of 51 patients received treatment before resection, including chemotherapy alone (n = 22), radiation alone (n = 3), and combined chemotherapy and radiation therapy (n = 1). The complete sternum was removed in 6 of 11 patients, and the average number of ribs requiring resection was 3.8. Four patients had vertebral body resections. Prosthetic meshes alone were required in 16 of 51 patients, and meshes with methylmethacrylate were required in 18 of 51 patients. Muscle flap reconstructions by plastic surgery were required in 24 patients. Negative margins were obtained in 47 of 51 patients. There were no perioperative deaths with morbidities occurring in 12 (24%) of 51 patients (wound [n = 3], prolonged air leak [n = 1], prolonged ventilator requirement [n = 1], arrhythmias [n = 3], doxorubicin (Adriamycin)-induced cardiomyopathy [n = 1], and other [n = 3]). Postoperative treatment was administered to 13 patients (chemotherapy alone, n = 9; chemotherapy with radiation therapy, n = 4). The cumulative 5-year survival of all patients was 64% (initial referral, 61.3%; secondary referral, 72.7%). The average follow-up is 44.7 months. CONCLUSIONS: A combined aggressive multidisciplinary approach to primary sarcomas of the chest wall resulted in no treatment-related deaths and a cumulative 5-year survival of 64% in patients referred to our tertiary care cancer center.
Asunto(s)
Sarcoma/terapia , Neoplasias Torácicas/terapia , Procedimientos Quirúrgicos Torácicos/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Sarcoma/diagnóstico por imagen , Sarcoma/mortalidad , Sarcoma/patología , Tasa de Supervivencia , Texas/epidemiología , Neoplasias Torácicas/diagnóstico por imagen , Neoplasias Torácicas/mortalidad , Neoplasias Torácicas/patología , Procedimientos Quirúrgicos Torácicos/mortalidad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Development of non-small cell lung carcinoma (NSCLC) in patients previously treated for small cell carcinoma (SCLC/NSCLC) is well described; however, little is known about clinical outcome. METHODS: A single-institution 20-year review was performed. Patient characteristics and survival for SCLC/ NSCLC patients were compared with those for control patients matched for stage, resection, and previous malignancy. RESULTS: One thousand four hundred four patients with small cell carcinoma were identified, and 29 underwent therapy for metachronous NSCLC: 11 of 29 patients underwent surgical resection, 10 of these 11 (90%) were stage I. Compared with surgically treated stage I NSCLC patients, SCLC/NSCLC patients were more likely to have squamous histology (70% versus 35%, p = 0.026); and subanatomic resection (90% versus 17.4%, p < 0.0005). The SCLC/NSCLC patients had significantly poorer survival when compared with stage I NSCLC patients undergoing any resection (24.53 versus 74.43 months, p = 0.003) and stage I NSCLC patients receiving wedge resection (24.53 versus 58.39 months, p = 0.006). Survival was similar to NSCLC patients with a history of previous treated extrathoracic solid malignancy. CONCLUSIONS: Surgical resection for SCLC/NSCLC patients is feasible, but poorer prognosis is noted when compared with stage-matched control patients. Surgical candidates should be carefully chosen, and alternative local control modalities considered.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neoplasias Primarias Secundarias/cirugía , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Pequeñas/mortalidad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/mortalidad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Preoperative chemotherapy (C+S) for non-small cell lung cancer (NSCLC) has increased in an attempt to improve survival. Patients receiving C+S potentially may have an increase in postoperative morbidity and mortality compared with surgery alone (S). We reviewed our experience with C+S and S in a tertiary referral center. METHODS: Three hundred eighty consecutive patients underwent lobectomy or greater resection for NSCLC between August 1, 1996, and April 30, 1999: 335 patients (259 S; 76 C+S) were analyzed; 45 additional patients were excluded for prior NSCLC, other chemotherapy for other malignancy, or radiation. We compared morbidity and mortality overall, and by subset analysis (clinical stage, pathological stage, procedure, and by protocol use) for both C+S and S patients. RESULTS: Demographics, comorbidities, and spirometry were similar. We noted no significant difference in overall or subset mortality or morbidity including pneumonia, acute respiratory distress syndrome, reintubation, tracheostomy, wound complications, or length of hospitalization. CONCLUSIONS: C+S did not significantly affect morbidity or mortality overall, based on clinical stage, postoperative stage, or extent of resection. The potential for enhanced survival in resectable NSCLC justifies continued study of C+S.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Neumonectomía/mortalidad , Vinblastina/análogos & derivados , Anciano , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neumonectomía/métodos , Cuidados Posoperatorios , Premedicación , Valores de Referencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificación , VinorelbinaRESUMEN
BACKGROUND: Previous studies have shown that a chronic indwelling pleural catheter (PC) safely and effectively relieved dyspnea, maintained quality of life, and reduced hospitalization in patients with malignant pleural effusions. Outpatient management of malignant pleural effusion with a PC may reduce length of stay and early (7-day) charges compared with inpatient management with chest tube and sclerosis. METHODS: A retrospective review of consecutive PC patients (n = 100; 60 outpatient, 40 inpatient) were treated from July 1, 1994 to September 2, 1998 and compared with 68 consecutive inpatients treated with chest tube and sclerosis between January 1, 1994 and December 31, 1997. Hospital charges were obtained from date of insertion (day 0) through day 7. RESULTS: Demographics were similar in both groups. Pretreatment cytology was positive in 126 of 168 patients (75%), negative in 21 (12.5%), and unknown in 21 (12.5%). Primary histology included lung (n = 61, 36%), breast (n = 39, 23%), lymphoma (n = 12, 7%), or other (n = 56, 34%). Median survival was 3.4 months and did not differ significantly between treatment groups. Overall median length of stay was 7.0 days for inpatient chest tube and inpatient PC versus 0.0 days for outpatient Pleurx. No mortality occurred related to the PC. Eighty-one percent (81/100) of PC patients had no complications. One or more complications occurred in 19 patients (19%). Patients treated with outpatient PC (n = 60) had early (7-day) mean charges of $3,391 +/- $1,753 compared with inpatient PC (n = 40, $11,188 +/- $7,964) or inpatient chest tube (n = 68, $7,830 +/- $4,497, SD) (p < 0.001). CONCLUSIONS: Outpatient PC may be used effectively and safely to treat malignant pleural effusions. Hospitalization is not required in selected patients. Early (7-day) charges for malignant pleural effusion are reduced in outpatient PC patients compared with inpatient PC patients or chest tube plus sclerosis patients.
Asunto(s)
Derrame Pleural Maligno/terapia , Anciano , Atención Ambulatoria , Catéteres de Permanencia , Drenaje , Femenino , Precios de Hospital , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Derrame Pleural Maligno/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Texas , Toracostomía , Factores de TiempoAsunto(s)
Moléculas de Adhesión Celular/fisiología , Endotelio Vascular/fisiología , Leucocitos/fisiología , Neumonía/fisiopatología , Enfermedad Aguda , Animales , Antígenos CD/fisiología , Modelos Animales de Enfermedad , Humanos , Integrinas/fisiología , Molécula 1 de Adhesión Intercelular , Neumonía/etiologíaRESUMEN
The purpose of this study was to identify gender-dependent differences in presentation at baseline and therapy outcome in esophageal carcinoma patients treated with preoperative chemoradiotherapy (CTRT). We stratified patients according to gender and statistically compared pretreatment clinical stage, post-CTRT effect on carcinoma in the resected specimen, overall survival (OS), and patterns of failure. Of the 235 patients who underwent preoperative CTRT, 203 were men and 32 were women. Carcinomas in women correlated significantly with clinical stage II classification (78%vs. 55%) while cancers in men correlated significantly with clinical stage III classification (39%vs. 16%; P = 0.02). Carcinomas in women also correlated significantly with lower clinical N classification; more women had cN0 (52%) compared to men (28%; P = 0.01). Similarly, in the surgical specimens, more women had pN0 (78%) compared to men (64%; P = 0.06). At a median follow-up of 37 months, 10% more women than men remain alive (63%vs. 53%; P = 0.3). Distant metastases-free survival time was longer for women than men. Our results suggest that localized esophageal carcinoma is diagnosed in more advanced stages in men than in women. The reasons for these differences remain unclear and further expansion of these observations and study of biologic differences that might exist are warranted.
Asunto(s)
Quimioterapia Adyuvante , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/terapia , Terapia Neoadyuvante , Radioterapia Adyuvante , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores Sexuales , Resultado del TratamientoRESUMEN
There is evidence for a tumor necrosis factor alpha (TNF alpha)-initiated and CD11b/CD18-dependent burst of superoxide anion (O2-) and hydrogen peroxide production by human polymorphonuclear leukocytes which are adherent to surfaces bearing a variety of proteins. In the current studies neutrophils were stimulated with opsonized (by fresh human serum) zymosan particles in the presence of cytochalasin B, to prevent internalization of particles and to simulate the interaction of neutrophils with protein-bearing surfaces. Under these conditions, the cells demonstrated 2.9-fold greater production of O2- when compared to nonopsonized zymosan particles. Heat inactivation or cobra venom factor treatment of human serum prior to opsonization resulted in 98% and 66% reductions, respectively, in O2- responses. C3 and factor B were required for this response, since sera deficient in either component caused 56 and 68% reductions, respectively, in O2- production. Sera deficient in Clq, C2, C4, C5, C6, C7 or C9 showed no defect in their ability to enhance O2- responses to zymosan particles. Monoclonal antibody to iC3b, but not monoclonal antibodies to C3c or C3d, caused a 29% reduction (p < 0.01) in O2- generation. Antibodies to CD18 (R15.7) or CD11b (CL44 and 60.1) reduced the incremental production of O2- by 76, 71 and 77%, respectively. Two antibodies directed against CD11a as well as the isotype-matched control (MOPC 21) were without effects. These data suggest that, in this model of neutrophil activation, the pathway for O2- generation is a Mac-1 (but not LFA-1)-dependent pathway and also requires iC3b. These findings may be relevant to complement-mediated, neutrophil-dependent vascular injury in vivo.
Asunto(s)
Complemento C3b/fisiología , Antígeno de Macrófago-1/fisiología , Neutrófilos/metabolismo , Superóxidos/metabolismo , Citocalasina B/farmacología , Calor , Humanos , Neutrófilos/efectos de los fármacos , Fagocitosis/efectos de los fármacosRESUMEN
Lung injury following deposition of IgG immune complexes is neutrophil-dependent and requires both tumor necrosis factor alpha (TNF alpha) and CD18. In the current studies, we have evaluated the relationship between TNF alpha and expression of intracellular adhesion molecule-1 (ICAM-1) in vitro and in vivo. In both rat pulmonary artery endothelial cells and human umbilical vein endothelial cells, TNF alpha induced an early (within 60 minutes) increase in ICAM-1 expression, followed by a peak at 6 to 8 hours, with relatively stable expression at 24 hours. Expression of E-selectin did not show the early phase (within 60 minutes) of up-regulation, peaked at 4 hours, and then declined thereafter. Using a radioimmunochemical assay in vivo, it was demonstrated that intrapulmonary deposition of IgG immune complexes caused a progressive increase in ICAM-1 expression in lung over an 8-hour period. In animals pretreated with antibody to TNF alpha, the intrapulmonary expression of ICAM-1 was significantly reduced. These results were confirmed by immunoperoxidase analysis of lung tissue. It was also shown that airway instillation of TNF alpha caused up-regulation of ICAM-1 in lung. These data support the concept that deposition of IgG immune complexes in lung induces intrapulmonary up-regulation of ICAM-1 in a manner that is TNF alpha-dependent.
Asunto(s)
Moléculas de Adhesión Celular/análisis , Pulmón/química , Factor de Necrosis Tumoral alfa/fisiología , Análisis de Varianza , Animales , Anticuerpos/inmunología , Anticuerpos/farmacología , Complejo Antígeno-Anticuerpo/metabolismo , Antígenos CD/fisiología , Antígenos CD18 , Moléculas de Adhesión Celular/metabolismo , Selectina E , Endotelio Vascular/química , Endotelio Vascular/metabolismo , Humanos , Inmunoglobulina G/metabolismo , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular , Pulmón/citología , Pulmón/metabolismo , Masculino , Microscopía Electrónica , Radioinmunoensayo , Ratas , Factores de Tiempo , Factor de Necrosis Tumoral alfa/inmunología , Venas Umbilicales/citología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Recombinant murine IL-4 and IL-10 have been used in two models of inflammatory lung injury in rats after intrapulmonary deposition of IgG or IgA immune complexes. These models have contrasting requirements for cytokines, phagocytic cells, and adhesion molecules. In these two models of lung injury, IL-4 and IL-10 were individually coinstilled into the airways with the IgG or IgA antibodies, whereas the Ag were injected intravenously. Injury was quantitated by increases in permeability (leakage of 125I-BSA) and by hemorrhage (extravasation of 51Cr-RBC). In the model of IgG immune complex-induced lung injury, IL-4 and IL-10 were each highly protective when given in nanogram amounts. These protective effects were dose dependent. IL-4 and IL-10 caused substantial reductions in lung content of myeloperoxidase and parallel reductions in neutrophil content in bronchoalveolar lavage (BAL) fluids. The protective effects of IL-4 and IL-10 were associated with profound reductions of TNF-alpha in the BAL fluids and complete inhibition in the up-regulation of pulmonary vascular ICAM-1. In the IgA immune complex model of lung injury IL-4 had no protective effects, whereas IL-10 was highly protective. These protective effects correlated with diminished retrieval of alveolar macrophages in BAL fluids. These data suggest that IL-4 and IL-10 have significant protective effects in lung inflammatory injury, presumably achieving these effects by various mechanisms.