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Currently, less than thirty cases of primary malignant melanoma of the lung have been reported in the literature. Thus, strict criteria for diagnosis have been published and include: malignant melanoma associated with bronchial epithelial changes; a solitary lung tumor; no prior history of skin, mucous membrane, intestinal or ocular melanoma; and absence of any other detectable tumor at the time of diagnosis. In this article we present a case of melanoma of the lung without evidence of extra-pulmonary disease.
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INTRODUCTION: In lung cancer surgery, large tidal volume and elevated inspiratory pressure are known risk factors of acute lung (ALI). Mechanical ventilation with low tidal volume has been shown to attenuate lung injuries in critically ill patients. In the current study, we assessed the impact of a protective lung ventilation (PLV) protocol in patients undergoing lung cancer resection. METHODS: We performed a secondary analysis of an observational cohort. Demographic, surgical, clinical and outcome data were prospectively collected over a 10-year period. The PLV protocol consisted of small tidal volume, limiting maximal pressure ventilation and adding end-expiratory positive pressure along with recruitment maneuvers. Multivariate analysis with logistic regression was performed and data were compared before and after implementation of the PLV protocol: from 1998 to 2003 (historical group, n = 533) and from 2003 to 2008 (protocol group, n = 558). RESULTS: Baseline patient characteristics were similar in the two cohorts, except for a higher cardiovascular risk profile in the intervention group. During one-lung ventilation, protocol-managed patients had lower tidal volume (5.3 +/- 1.1 vs. 7.1 +/- 1.2 ml/kg in historical controls, P = 0.013) and higher dynamic compliance (45 +/- 8 vs. 32 +/- 7 ml/cmH2O, P = 0.011). After implementing PLV, there was a decreased incidence of acute lung injury (from 3.7% to 0.9%, P < 0.01) and atelectasis (from 8.8 to 5.0, P = 0.018), fewer admissions to the intensive care unit (from 9.4% vs. 2.5%, P < 0.001) and shorter hospital stay (from 14.5 +/- 3.3 vs. 11.8 +/- 4.1, P < 0.01). When adjusted for baseline characteristics, implementation of the open-lung protocol was associated with a reduced risk of acute lung injury (adjusted odds ratio of 0.34 with 95% confidence interval of 0.23 to 0.75; P = 0.002). CONCLUSIONS: Implementing an intraoperative PLV protocol in patients undergoing lung cancer resection was associated with improved postoperative respiratory outcomes as evidence by significantly reduced incidences of acute lung injury and atelectasis along with reduced utilization of intensive care unit resources.
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Lesión Pulmonar Aguda/prevención & control , Cuidados Intraoperatorios/métodos , Neoplasias Pulmonares/cirugía , Respiración con Presión Positiva/métodos , Anciano , Protocolos Clínicos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Volumen de Ventilación Pulmonar/fisiología , Resultado del TratamientoRESUMEN
Freshly isolated, starch-elicited mouse peritoneal macrophages (Mø) attached very efficiently to type I collagen in vitro, if collagen molecules were arranged in ordered supra-molecular assemblies corresponding to the precursor native fibrils. After 6-20h of incubation, the collagen-bound cells were observed to secrete fibronectin, which presumably enhanced cell-collagen interaction associated with cellular differentiation. Mø attachment to collagen could be temporarily inhibited by addition of the linear tri-peptide Arg-Gly-Asp (RGD) to the culture media. This inhibition was much more pronounced when using the cyclic RGD-containing peptide cGRGDSPA. Similarly, cells could be easily detached from the fibrillar collagen layers within 20 min at 37 degrees C by RGDS, GRGDS or cGRGDSPA but not by the glutamate-containing RGES peptide. Using antibodies to known collagen receptors, attachment of Mø to type I collagen fibers was best inhibited by antibodies directed against the alpha2 and beta1 integrin subunits. The presence of these integrins on Mø was confirmed by immunofluorescence. Binding of the alpha2beta1 integrin on collagen was divalent cation-dependent and was supported by magnesium but not by calcium. Cells recovered by RGD-mediated detachment from collagen were highly phagocytic and synthesized DNA when exposed to growth factors. These cells could be activated for cytotoxicity by treatment with interferon-gamma and lipopolysaccharide. Comparative in vitro assays performed on macrophages cultured on plastic and on collagen allowed the detection of NO production by activated macrophages followed by spontaneous deactivation for cells cultivated on collagen. These findings suggest that Mø can recognize native collagen of type I through functional interactions with their specific triple helix-binding integrin receptors indicating that integrins other than those directed to fibronectin may also occupy active focal points on the cell at the initial phase of attachment.
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Técnicas de Cultivo de Célula , Colágeno Tipo I/metabolismo , Macrófagos Peritoneales/fisiología , Animales , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , Proliferación Celular/efectos de los fármacos , Colágeno Tipo I/ultraestructura , Integrinas/metabolismo , Interferón gamma/farmacología , Lipopolisacáridos/farmacología , Antígeno de Macrófago-1/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Óxido Nítrico/metabolismo , Oligopéptidos/farmacología , Péptidos Cíclicos/farmacología , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiologíaRESUMEN
BACKGROUND: Outcome after lung transplantation (LTx) is affected by the onset of bronchiolitis obliterans syndrome (BOS) and lung function decline. Reduced health-related quality of life (HRQL) and physical mobility have been shown in patients developing BOS, but the impact on the capacity to walk is unknown. We aimed to compare the long-term HRQL and 6-minute walk test (6MWT) between lung recipients affected or not by BOS Grade > or =2. METHODS: Fifty-eight patients were prospectively followed for 5.6 +/- 2.9 years after LTx. Assessments included the St George's Respiratory Questionnaire (SGRQ) and the 6MWT, which were performed yearly. Moreover, clinical complications were recorded to estimate the proportion of the follow-up time lived without clinical intercurrences after transplant. Analyses were performed using adjusted linear regression and repeated-measures analysis of variance. RESULTS: BOS was a significant predictor of lower SGRQ scores (p < 0.01) and reduced time free of clinical complications (p = 0.001), but not of 6MWT distance (p = 0.12). At 7 years post-transplant, results were: 69.0 +/- 21.8% vs 86.9 +/- 5.6%, p < 0.05 (SGRQ); 58.5 +/- 21.6% vs 88.7 +/- 11.4%, p < 0.01 (proportion of time lived without clinical complications); and 82.2 +/- 10.9% vs 91.9 +/- 14.2%, p = 0.27 (percent of predicted 6MWT), respectively, for patients with BOS and without BOS. CONCLUSIONS: Despite significantly less time lived without clinical complications and progressive decline of self-reported health status, the capacity to walk of patients affected by BOS remained relatively stable over time. These findings may indicate that the development of moderate to severe BOS does not prevent lung recipients from walking independently and pursuing an autonomous life.
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Bronquiolitis Obliterante/complicaciones , Tolerancia al Ejercicio , Trasplante de Pulmón/fisiología , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Caminata/fisiología , Adulto , Análisis de Varianza , Bronquiolitis Obliterante/fisiopatología , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
We report a case of a massive haemothorax following bilateral surgical resection of apical bullae. Occult bleeding was not recognized until the onset of a life-threatening circulatory collapse associated with metabolic acidosis and a fall in haemoglobin level. Using a thoracotomy, large amounts of blood were evacuated from the thoracic cavity and bleeding originating from ruptured pleural adhesion was easily controlled. Thrombotic material with talc particles was found to obstruct the 19-French 4-channel Blake drain. Although this new silastic Blake tube has been recommended in cardiac surgical patients, extending its indication in thoracic surgery, particularly when talc pleurodesis is used, should be questioned given the enhanced postoperative prothrombotic state and risk of drain obstruction. In conclusion, caution should be exercised when new small-sized material is introduced in clinical practice, especially after talc pleurodesis following thoracic surgery.
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Tubos Torácicos/efectos adversos , Hemorragia Posoperatoria/etiología , Choque/etiología , Adulto , Falla de Equipo , Hemotórax/diagnóstico por imagen , Hemotórax/etiología , Humanos , Masculino , Pleurodesia/efectos adversos , Cuidados Posoperatorios/efectos adversos , Cuidados Posoperatorios/instrumentación , Hemorragia Posoperatoria/diagnóstico por imagen , Radiografía , Talco/administración & dosificación , ToracotomíaRESUMEN
BACKGROUND: Smoking is a common risk factor for chronic obstructive pulmonary disease (COPD), cardiovascular disease, and lung cancer. In this observational study, we examined the impact of COPD severity and time-related changes in early outcome after lung cancer resection. METHODS: Over a 15-year period, we analyzed an institutional registry including all consecutive patients undergoing surgery for lung cancer. Using the receiver-operating characteristic (ROC) curve, we analyzed the relationship between forced expiratory volume in 1 second (FEV1) and postoperative mortality and respiratory morbidity. Multiple regression analysis has also been applied to identify other risk factors. RESULTS: A preoperative FEV1 less than 60% was a strong predictor for respiratory complications (odds ratio [OR] = 2.7, confidence interval [CI]: 1.3 to 6.6) and 30-day mortality (OR = 1.9, CI: 1.2 to 3.9), whereas thoracic epidural analgesia was associated with lower mortality (OR = 0.4; CI: 0.2 to 0.8) and respiratory complications (OR = 0.6; CI: 0.3 to 0.9). Mortality was also related to age greater than 70 years, the presence of at least three cardiovascular risk factors, and pneumonectomy. From the period 1990 to 1994, to 2000 to 2004, we observed significant reductions in perioperative mortality (3.7% versus 2.4%) and in the incidence of respiratory complications (18.7% versus 15.2%), that was associated with a higher rate of lesser resection (from 11% to 17%, p < 0.05) and increasing use of thoracic epidural analgesia (from 65% to 88%, p < 0.05). CONCLUSIONS: Preoperative FEV1 less than 60% is a main predictor of perioperative mortality and respiratory morbidity. Over the last 5-year period, diagnosis of earlier pathologic cancer stages resulting in lesser pulmonary resection as well as provision of continuous thoracic epidural analgesia have contributed to improved surgical outcome.
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Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/cirugía , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Anciano , Femenino , Volumen Espiratorio Forzado , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neumonectomía , Curva ROC , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Fumar/epidemiología , Toracotomía , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the influence of recipient's and donor's factors as well as surgical events on the occurrence of reperfusion injury after lung transplantation. DESIGN AND SETTING: Retrospective study in the surgical intensive care unit (ICU) of a university hospital. METHODS: We collected data on 60 lung transplantation donor/recipient pairs from June 1993 to May 2001, and compared the demographic, peri- and postoperative variables of patients who experienced reperfusion injury (35%) and those who did not. RESULTS: The occurrence of high systolic pulmonary pressure immediately after transplantation and/or its persistence during the first 48 h after surgery was associated with reperfusion injury, independently of preoperative values. Reperfusion injury was associated with difficult hemostasis during transplantation (p=0.03). Patients with reperfusion injury were more likely to require the administration of catecholamine during the first 48 h after surgery (p=0.014). The extubation was delayed (p=0.03) and the relative odds of ICU mortality were significantly greater (OR 4.8, 95% CI: 1.06, 21.8) in patients with reperfusion injury. Our analysis confirmed that preexisting pulmonary hypertension increased the incidence of reperfusion injury (p<0.01). CONCLUSIONS: Difficulties in perioperative hemostasis were associated with reperfusion injury. Occurrence of reperfusion injury was associated with postoperative systolic pulmonary hypertension, longer mechanical ventilation and higher mortality. Whether early recognition and treatment of pulmonary hypertension during transplantation can prevent the occurrence of reperfusion injury needs to be investigated.
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Trasplante de Pulmón , Daño por Reperfusión/etiología , Adulto , Estudios de Cohortes , Cuidados Críticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Perioperativa , Daño por Reperfusión/epidemiología , Daño por Reperfusión/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Suiza/epidemiologíaRESUMEN
OBJECTIVES: To compare long-term health-related quality of life (HRQL) in single and bilateral lung transplant recipients independent of the underlying disease, and in a subset of patients with native pulmonary emphysema. METHODS: Forty-four lung transplant recipients (mean [+/- SD] age, 44.8 +/- 11.6 years) were followed up for > 2 years after single lung transplantation (LTx) [14 recipients] or bilateral LTx (30 recipients). Data were prospectively collected, before undergoing LTx and annually after undergoing LTx, measuring FEV1, 6-min walk test (6MWT) results, and quality of life using the St. George respiratory questionnaire (SGRQ) and a visual analog scale (VAS). The SGRQ addresses three domains, namely, respiratory symptoms, accomplishment of routine activities, and disease impact on daily life. RESULTS: Statistically significant correlation coefficients were found comparing the SGRQ and the VAS (r = 0.812; p < 0.0001), the SGRQ and the 6MWT (r = 0.610; p < 0.0001), and the SGRQ and the FEV1 (r = 0.523; p < 0.0001) in all patients. Significant improvements on the FEV1, 6MWT, and SGRQ were observed after LTx in both single and bilateral LTx recipients. Increased risk for the development of bronchiolitis obliterans syndrome (BOS) [relative risk, 2.86; 95% confidence interval, 1.22 to 6.67; p = 0.03] and significantly lower FEV1 values were observed in patients following a single graft, compared to that in patients following a bilateral graft (p < 0.01). In contrast, the 6MWT and the SGRQ scores were not significantly different between recipients of single and double LTx. The same patterns of results were observed in comparisons between single and bilateral lung recipients with prior pulmonary emphysema. CONCLUSIONS: Despite poorer FEV1 recovery and increased risk of BOS after LTx, single lung transplant recipients had comparable long-term exercise tolerance and quality-of-life scores as patients who received bilateral transplants. These results suggest the limited influence of functional performance on objective and subjective markers of HRQL recovery after LTx.
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Trasplante de Pulmón/métodos , Enfisema Pulmonar/cirugía , Calidad de Vida , Adulto , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Recuperación de la FunciónRESUMEN
BACKGROUND: Alveolar macrophages (AMs) are known to be poor antigen-presenting cells, and lack the accessory molecules such as CD40, CD80 or CD86 to activate T cells. The question raised is about the potential changes in phenotypes after lung transplantation, particularly during acute rejection episodes. METHODS: The present study analyzed the phenotype of AMs longitudinally in 45 lung transplant patients, between August 1997 and April 2002, with a follow-up period of 27.2 +/- 2.5 (mean +/- SEM) months. There were 7.7 +/- 0.6 bronchoalveolar lavage (BAL) assessments performed per patient (i.e., 345 BALs), simultaneously with transbronchial biopsies. Transplantation was soon followed by a progressive upregulation of CD40 on 49.7 +/- 8% of AMs during the first month, and this marker remained elevated at 60 +/- 8% after 5 years. RESULTS: Both CD86 and CD80, as well as CD83, a marker of dendritic cells, were enhanced for most AMs during Grade A2 and A3 rejection episodes. A correlation was found between expression of CD83 and CD86, but not between CD1a and CD86. Immunohistology confirmed that CD40-positive cells in the alveoli corresponded to AMs and to some dendritic cells in the basal layers of the airways. In vitro studies showed that harvested AMs with these enhanced accessory molecules remained poor stimulators of allogeneic cells, a phenomenon that may be related to the ongoing immunosuppressive treatments. CONCLUSIONS: AM phenotypes showed marked changes during early or late acute rejection episodes, acquiring CD80, CD83 and CD86, while CD40 expression was further enhanced. This finding may provide clues on how to monitor the tolerance of transplanted lungs and may also provide new insights into the pathophysiology of lung transplantation.
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Antígenos CD/análisis , Antígeno B7-2/análisis , Antígenos CD40/análisis , Inmunoglobulinas/análisis , Trasplante de Pulmón/inmunología , Macrófagos Alveolares/citología , Glicoproteínas de Membrana/análisis , Inmunología del Trasplante/fisiología , Adulto , Anciano , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Inmunohistoquímica , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Sensibilidad y Especificidad , Regulación hacia Arriba , Antígeno CD83RESUMEN
When right ventricular failure develops secondary to primary pulmonary hypertension, right-left ventricular interaction may lead to severe impairment of left ventricular function. In such cases, many experts favor combined heart-lung transplantation by fear that the left ventricle may not recover after transplantation of the lungs alone. We report a case of primary pulmonary hypertension with severely diminished right and left ventricular function. The patient was rendered amenable to isolated pulmonary transplantation with the endothelin-receptor antagonist bosentan. The medication improved right and left ventricular function to the point that heart transplantation no longer appeared necessary. After double-lung transplantation the patient's cardiac function made a full recovery. This approach might be particularly welcome considering both the current donor organ shortage and the limited number of surgical teams with expertise in heart-lung transplantation.
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Antihipertensivos/uso terapéutico , Hipertensión Pulmonar/terapia , Trasplante de Pulmón , Sulfonamidas/uso terapéutico , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Derecha/etiología , Adulto , Bosentán , Terapia Combinada , Humanos , Hipertensión Pulmonar/complicaciones , Masculino , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Parathyroid carcinoma (PC) mimics benign primary hyperparathyroidism (PHP), but the diagnosis of PC is seldom available at the time of the first operation. Because PC is plagued by recurrences usually beyond cure, one may wonder whether some of these could be prevented by more extensive resections initially, i.e., if the diagnosis of PC were available at that time. METHODS: Over a 25-year period, 311 consecutive patients with PHP underwent operation in our department: 302 had benign disease (adenomas or hyperplasias), and 9 had PC. Several clinical parameters, serum calcium and parathyroid hormone (PTH) levels, and the weight of the parathyroid tumor removed were compared in both groups. Receiver operating characteristic curves and logistical regression analyses were used to distinguish PC from benign PHP. RESULTS: Eight of 9 patients with PC had symptoms, versus 238 (79%) of 302 with benign PHP (not significant). In the PC subgroup, serum calcium and PTH levels and the tumor weights of the parathyroid glands removed were significantly higher than in the benign PHP cohort, even if these three parameters were regularly flawed by low positive predictive values (14%, 20%, and 15%, respectively). CONCLUSIONS: Serum calcium, PTH levels, and tumor weights were significantly greater in the PC subgroup, even if not invariably in a discriminatory way. However, when PTH is <4 times the upper limit of normal and tumor weight is <1.9 g, the probability of PC is nil.
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Hiperparatiroidismo/cirugía , Neoplasias de las Paratiroides/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Calcio/sangre , Femenino , Humanos , Hiperparatiroidismo/etiología , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Hormona Paratiroidea/sangre , Neoplasias de las Paratiroides/sangre , Neoplasias de las Paratiroides/cirugía , Paratiroidectomía , Valor Predictivo de las PruebasRESUMEN
This study reports the establishment of three major subtypes of human mesothelioma cells in tissue culture, i.e. the epithelioid, sarcomatoid and biphasic forms, and compares their phenotypic and biological characteristics. Primary cells isolated from biopsies or pleural exudates were subcultured for over 50 passages. We evaluated immunoreactivity using various mesothelial markers related to histological patterns of these cell lines. For epithelioid cells, calretinin and cytokeratin were found to be useful and easily interpretable markers as for control mesothelial cells. The biphasic form was only partially positive and the sarcomatoid type negative. Vimentin was expressed by all cell lines. BerEP4, a specific marker for adenocarcinoma, was negative. Interestingly, while the macrophage marker CD14 was negative, immunoreactivity for a mature macrophage marker (CD68) was expressed by all cell types, suggesting that this marker might constitute an additional tool useful in the differential diagnosis of mesothelioma. At the ultrastructural level, a cell surface rich in microvilli confirmed their mesothelial origin. PCR analysis revealed that none of the cell lines contained SV40 DNA. Karyotypic analyses showed more complex abnormalities in the epithelioid subtype than in the sarcomatoid form. These cell lines may be useful in the study of cellular, molecular and genetic aspects of the disease.
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Biomarcadores de Tumor/metabolismo , Técnicas de Cultivo de Célula/métodos , Mesotelioma/patología , Derrame Pleural Maligno/patología , Neoplasias Pleurales/patología , Línea Celular Tumoral , Proliferación Celular , ADN Viral/análisis , Citometría de Flujo , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Cariotipificación , Mesotelioma/genética , Mesotelioma/metabolismo , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurales/genética , Neoplasias Pleurales/metabolismo , Reacción en Cadena de la Polimerasa , Infecciones por Polyomavirus/complicaciones , Virus 40 de los Simios/genética , Virus 40 de los Simios/aislamiento & purificación , Infecciones Tumorales por Virus/complicacionesRESUMEN
OBJECTIVE: Lung transplantation has evolved from an experimental procedure to a viable therapeutic option in many countries. In Switzerland, the first lung transplant was performed in November 1992, more than ten years after the first successful procedure world-wide. Thenceforward, a prospective national lung transplant registry was established, principally to enable quality control. PATIENTS: The data of all patients transplanted in the two Swiss Lung Transplant centres Zurich University Hospital and Centre de Romandie (Geneva-Lausanne) were analysed. RESULTS: In 10 years 242 lung transplants have been performed. Underlying lung diseases were cystic fibrosis including bronchiectasis (32%), emphysema (32%), parenchymal disorders (19%), pulmonary hypertension (11%) and lymphangioleiomyomatosis (3%). There were only 3% redo procedures. The 1, 5 and 9 year survival rates were 77% (95% CI 72-82), 64% (95% CI 57-71) and 56% (95% CI 45-67), respectively. The 5 year survival rate of patients transplanted since 1998 was 72% (95% CI 64-80). Multivariate Cox regression analysis revealed that survival was significantly better in this group compared to those transplanted before 1998 (HR 0.44, 0.26-0.75). Patients aged 60 years and older (HR 5.67, 95% CI 2.50-12.89) and those with pulmonary hypertension (HR 2.01, 95% CI 1.10-3.65) had a significantly worse prognosis The most frequent causes of death were infections (29%), bronchiolitis obliterans syndrome (25%) and multiple organ failure (14%). CONCLUSION: The 10-year Swiss experience of lung transplantation compares favourably with the international data. The best results are obtained in cystic fibrosis, pulmonary emphysema and parenchymal disorders.
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Trasplante de Pulmón/mortalidad , Trasplante de Pulmón/estadística & datos numéricos , Sistema de Registros , Adolescente , Adulto , Factores de Edad , Anciano , Causas de Muerte , Niño , Femenino , Humanos , Hipertensión Pulmonar/complicaciones , Enfermedades Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Reoperación/estadística & datos numéricos , Tasa de Supervivencia , Suiza/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Early-stage breast cancer is increasing and consequently the use of breast-conserving surgery (BCS). We examined the effect of mastectomy and BCS on overall and breast cancer survival in routine health care in Geneva, Switzerland. PATIENTS AND METHODS: We included all stage I breast cancers treated by surgery (n=1046) recorded at the Geneva Cancer Registry between 1988 and 1999. The effect of treatment type was evaluated by Cox models, which accounted for confounders. RESULTS: Overall, 780 (75%) women had BCS with radiotherapy, 57 (5%) BCS alone and 209 (20%) mastectomy. The overall 10-year survival was 86, 56, and 72%, respectively. The effect of BCS with radiotherapy was similar to that of mastectomy for both breast cancer mortality (adjusted hazard ratio (HR), 0.67; 95%CI, 0.31-1.38) and other causes of mortality (HR, 0.79; 95%CI, 0.49-1.28). Women with BCS alone had higher mortality from breast cancer (HR, 3.95; 95%CI, 1.59-9.84). CONCLUSIONS: This retrospective study shows that BCS plus radiotherapy is the predominant treatment in routine practice for stage I breast cancer in Geneva, with the same effect on survival as mastectomy. In this data set the addition of radiotherapy to BCS substantially reduces mortality from breast cancer without increasing other causes of mortality after 10 years of follow-up.
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Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Anciano , Neoplasias de la Mama/mortalidad , Terapia Combinada , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
UNLABELLED: Acute lung injury (ALI) may complicate thoracic surgery and is a major contributor to postoperative mortality. We analyzed risk factors for ALI in a cohort of 879 consecutive patients who underwent pulmonary resections for non-small cell lung carcinoma. Clinical, anesthetic, surgical, radiological, biochemical, and histopathologic data were prospectively collected. The total incidence of ALI was 4.2% (n = 37). In 10 cases, intercurrent complications (bronchopneumonia, n = 5; bronchopulmonary fistula, n = 2; gastric aspiration, n = 2; thromboembolism, n = 1) triggered the onset of ALI 3 to 12 days after surgery, and this was associated with a 60% mortality rate (secondary ALI). In the remaining 27 patients, no clinical adverse event preceded the development of ALI-0 to 3 days after surgery-that was associated with a 26% mortality rate (primary ALI). Four independent risk factors for primary ALI were identified: high intraoperative ventilatory pressure index (odds ratio, 3.5; 95% confidence interval, 1.7-8.4), excessive fluid infusion (odds ratio, 2.9; 95% confidence interval, 1.9-7.4), pneumonectomy (odds ratio, 2.8; 95% confidence interval, 1.4-6.3), and preoperative alcohol abuse (odds ratio, 1.9; 95% confidence interval, 1.1-4.6). In conclusion, we describe two clinical forms of post-thoracotomy ALI: 1). delayed-onset ALI triggered by intercurrent complications and 2). an early form of ALI amenable to risk-reducing strategies, including preoperative alcohol abstinence, lung-protective ventilatory modes, and limited fluid intake. IMPLICATIONS: In an observational study including all patients undergoing lung surgery, we describe two clinical forms of acute lung injury (ALI): a delayed-onset form triggered by intercurrent complications and an early form associated with preoperative alcohol consumption, pneumonectomy, high intraoperative pressure index, and excessive fluid intake over the first 24 h.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Lesión Pulmonar , Neoplasias Pulmonares/cirugía , Pulmón/cirugía , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Torácicos/efectos adversos , Enfermedad Aguda , Factores de Edad , Anciano , Alcoholismo/complicaciones , Estudios de Cohortes , Complicaciones de la Diabetes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonectomía , Complicaciones Posoperatorias/mortalidad , Pruebas de Función Respiratoria , Estudios Retrospectivos , Factores de Riesgo , Procedimientos Quirúrgicos Torácicos/mortalidadRESUMEN
Galectin-3 has been extensively studied as an immunohistochemical marker of thyroid malignancy, and a high diagnostic accuracy has been reported even for difficult pathological diagnoses, such as minimal invasive follicular carcinoma. We consequently hypothesized that the quantitative analysis of galectin-3 mRNA rather than the more observer-dependent immunohistological determination might enhance the diagnostic workup of ambiguous thyroid lesions. In the present study, we set out to validate this approach by analyzing concomitantly the expression and production of galectin-3 in benign and malignant thyroid tumors by means of quantitative PCR and immunohistochemistry. Twenty-eight benign and 31 malignant thyroid samples were quantified by real-time PCR for the mRNA levels of galectin-3 and thyroglobulin. Galectin-3 protein expression was examined by immunohistochemistry in 13 benign and 14 malignant thyroid samples. There was a significant increase in galectin-3 at both the mRNA (12/20) and protein levels in papillary cancer (8/8), although the mRNA values overlapped partly with benign lesions. Surprisingly, only a focal and discrete galectin-3 immunoreactivity was seen in follicular cancer (1/5); no augmentation of the mRNA was found. The expression of the thyroid-specific gene thyroglobulin was highly variable in benign and malignant thyroid tissue. These results suggest that the quantitative measurement of galactin-3 mRNA is unlikely to be clinically useful and underscore the need for searching for novel markers for thyroid malignancies.
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Adenocarcinoma Folicular/metabolismo , Carcinoma Papilar/metabolismo , Galectina 3/metabolismo , Glándula Tiroides/metabolismo , Neoplasias de la Tiroides/metabolismo , Estudios de Casos y Controles , Galectina 3/genética , Humanos , Inmunohistoquímica , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Tiroglobulina/genéticaAsunto(s)
Espasmo Bronquial/inducido químicamente , Desinfectantes/efectos adversos , Hipersensibilidad a las Drogas/fisiopatología , Hipotensión/inducido químicamente , Complicaciones Posoperatorias/inducido químicamente , Adulto , Aerosoles , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Espasmo Bronquial/fisiopatología , Desinfectantes/administración & dosificación , Hipersensibilidad a las Drogas/diagnóstico , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Hipotensión/fisiopatología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Intubación Intratraqueal , Neoplasias Pulmonares/cirugía , Pruebas CutáneasRESUMEN
PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Metástasis Linfática/patología , Paclitaxel/análogos & derivados , Taxoides , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Cisplatino/administración & dosificación , Docetaxel , Femenino , Humanos , Infusiones Intravenosas , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Pronóstico , Sobrevida , Resultado del TratamientoRESUMEN
Pharmacologic interactions and absorption disturbances after transplantation may induce serologic fluctuation of immunosuppression and adversely affect outcome. We present data showing that trough levels of mycophenolic acid decreased by 50% during combined mycophenolate mofetil (MMF) and cyclosporine therapy compared with levels during combined MMF and tacrolimus therapy. In addition, cystic fibrosis patients required 30% higher doses of MMF to achieve the therapeutic levels of recipients without cystic fibrosis.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Inmunosupresores/farmacocinética , Trasplante de Pulmón/inmunología , Ácido Micofenólico/farmacocinética , Adulto , Inhibidores de la Calcineurina , Ciclosporina/farmacocinética , Ciclosporina/uso terapéutico , Fibrosis Quística/cirugía , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Quimioterapia Combinada , Humanos , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Tacrolimus/farmacocinética , Tacrolimus/uso terapéuticoRESUMEN
BACKGROUND: Both undernutrition and overnutrition can affect the quality of life and survival of patients with pulmonary disease and lead to quantitative and functional alterations of fat-free mass (FFM). This longitudinal study determines the changes in weight, FFM, and body fat before and up to 4 years after lung transplant (LTR). METHODS: Height, weight, and body composition measurements (bioelectrical impedance) were obtained in 37 LTR patients. FFM and body fat were measured before and at 1, 3, 6, 9, 12, 18, 24, 36, and 48 months after LTR. RESULTS: Weight changed by +16.6%, +3.2%, -0.2%, and -3.2% and FFM by +14.0%, +2.5%, -0.3%, and -1.0% during years 1, 2, 3, and 4, respectively. A diagnosis of obliterative bronchiolitis after LTR was associated with loss of body weight, FFM, and body fat, compared with stable weight or gain in weight, FFM, and body fat in obliterative bronchiolitis-negative subjects; 76.2% and 85.7%, and 28% and 38% of men and women, respectively, demonstrated low FFM at 1 month and at 2 years after LTR, respectively. The FFM change was higher (39% of weight) during year 1 than during year 2 (25%) or year 3 (21%). CONCLUSIONS: After LTR, patients gained weight, FFM, and body fat, and two-thirds reached normal levels of FFM by year 2. A weight increase resulted in an FFM increase. Contrary to studies after heart or liver transplantation, our results suggest that despite posttransplant infections and grafts rejection, LTR permits FFM recovery.