RESUMO
OBJECTIVES: Residual airspace following thoracic resections is a common clinical problem. Persistent air leak, prolonged drainage time, and reduced hemostasis extend hospital stay and morbidity. We report a trial of pharmacologic-induced diaphragmatic paralysis through continuous paraphrenic injection of lidocaine to reduced residual airspace. The objectives were confirmation of diaphragmatic paralysis and possible procedure related complications. METHODS: Six eligible patients undergoing resectional surgery (lobectomy or bilobectomy) were included. Inclusion criteria consisted of: postoperative predicted FEV1 greater than 1300 ml, right-sided resection, absence of parenchymal lung disease, no class III antiarrhythmic therapy, absence of hypersensitivity reactions to lidocaine, no signs of infection, and informed consent. Upon completion of resection an epidural catheter was attached in the periphrenic tissue on the proximal pericardial surface, externalized through a separate parasternal incision, and connected to a perfusing system injecting lidocaine 1% at a rate of 3 ml/h (30 mg/h). Postoperative ICU surveillance for 24h and daily measurement of vital signs, drainage output, and bedside spirometry were performed. Within 48 h fluoroscopic confirmation of diaphragmatic paralysis was obtained. The catheter removal coincided with the chest tube removal when no procedural related complications occurred. RESULTS: None of the patients reported respiratory impairment. Diaphragmatic paralysis was documented in all patients. Upon removal of catheter or discontinuation of lidocaine prompt return of diaphragmatic motility was noticed. Two patients showed postoperative hemodynamic irrelevant atrial fibrillation. CONCLUSION: Postoperative paraphrenic catheter administration of lidocaine to ensure reversible diaphragmatic paralysis is safe and reproducible. Further studies have to assess a benefit in terms of reduction in morbidity, drainage time, and hospital stay, and determine the patients who will profit.
Assuntos
Anestésicos Locais/uso terapêutico , Diafragma/efeitos dos fármacos , Lidocaína/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Pulmonares , Idoso , Ar , Drenagem , Estudos de Viabilidade , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Paralisia Respiratória/induzido quimicamente , Capacidade Vital/fisiologiaRESUMO
OBJECTIVE: The objective of this prospective study was to compare the clinical value of procalcitonin (PCT) and C-reactive protein (CrP) plasma concentrations in their postoperative course after decortication. METHODS: Twenty-two patients requiring surgery for pleural empyema were chosen for this prospective study. Routine blood samples including CrP and PCT plasma concentrations were taken before the operation and on the 1st, 2nd, 3rd, and 7th postoperative day. RESULTS: Due to infection PCT and CrP were elevated preoperatively. In the postoperative course both PCT and CrP reached peak-levels on day 2 with values up to 43.55 ng/ml and 384.00 mg/l, respectively. In PCT the rise was followed by a clear decrease in 20 (90.9 %) patients until day 7. In contrast the CrP levels decreased slowly and only seven (54.5%) patients had values of 100 mg/l or below on day 7. PCT showed a better correlation with the clinic in case of septic course than CrP does. CONCLUSIONS: PCT reflects postoperative clinical course more accurately than CrP. Therefore, PCT is a more appropriate laboratory parameter to monitor patients after surgery for pleural empyema.
Assuntos
Proteína C-Reativa/análise , Calcitonina/sangue , Empiema Pleural/cirurgia , Precursores de Proteínas/sangue , Infecção da Ferida Cirúrgica/sangue , Reação de Fase Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Empiema Pleural/microbiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Período Pós-Operatório , Estudos Prospectivos , Estatísticas não Paramétricas , Toracotomia , Resultado do TratamentoRESUMO
OBJECTIVES: Tumour infiltration, or gross infectious involvement of the thoracic aortic wall, poses a significant intraoperative risk for fatal bleeding and therefore could compromise adequate resection or efficient surgical management of pleural infection in a considerable amount of cases. We present 3 successful cases of off-label thoracic aortic endografting to safeguard thoracic aortic wall integrity. METHODS: After all patients received thoracic stent grafts through femoral access into the descending aorta, the first patient underwent a resection of a locally advanced squamous cell carcinoma of the left inferior lobe cT4cN0-1cM0 after neoadjuvant chemoradiation, which had infiltrated the descending aortic wall. The second case was video-assisted thoracoscopic bilateral pleural decortication for empyema with aortic ulcers of the distal thoracic aorta in a patient with pancreatic intrathoracic fistula in a necrotizing pancreatitis. The third patient was operated for a locally advanced squamous cell carcinoma of the left inferior lobe initial stage cT4 cN1-2 cM0 after neoadjuvant chemoradiation, which had broad contact to the descending aorta at the level of thoracic vertebrae 7 and 8 on a circumference of circa 180°. Regional ethics committee approval according the Swiss Federal Human Research Act was obtained according to regulations. RESULTS: Preventive stent graft placement resulted in complication-free resection and significantly minimized the risk of fatal intraoperative bleeding. Patients were thus not exposed to complications associated with aortic cross-clamping, possible prosthetic replacement and extracorporeal circulation techniques. CONCLUSIONS: In carefully selected patient populations, the resection of locally advanced tumours or infectious processes involving the aortic wall can be facilitated by thoracic endovascular aortic repair prior to resection.
Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/prevenção & controle , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Complicações Pós-Operatórias/prevenção & controle , Stents , Procedimentos Cirúrgicos Torácicos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Pneumonectomia/efeitos adversosRESUMO
The CACNA2D2 gene, a new subunit of the Ca(2+)-channel complex, was identified in the homozygous deletion region of chromosome 3p21.3 in human lung and breast cancers. Expression deficiency of the CACNA2D2 in cancer cells suggests a possible link of it to Ca(2+) signaling in the pathogenesis of lung cancer and other cancers. We investigated the effects of overexpression of CACNA2D2 on intracellular Ca(2+) contents, mitochondria homeostasis, cell proliferation, and apoptosis by adenoviral vector-mediated wild-type CACNA2D2 gene transfer in 3p21.3-deficient nonsmall cell lung cancer cell lines. Exogenous expression of CACNA2D2 significantly inhibited tumor cell growth compared with the controls. Overexpression of CACNA2D2 induced apoptosis in H1299 (12.5%), H358 (13.7%), H460 (22.3%), and A549 (50.1%) cell lines. Levels of intracellular free Ca(2+) were elevated in AdCACNA2D2-transduced cells compared with the controls. Mitochondria membrane depolarization was observed prior to apoptosis in Ad-CACNA2D2 and Adp53-transduced H460 and A549 cells. Release of cyt c into the cytosol, caspase 3 activation, and PARP cleavage were also detected in these cells. Together, these results suggest that one of the pathways in CACNA2D2-induced apoptosis is mediated through disruption of mitochondria membrane integrity, the release of cyt c, and the activation of caspases, a process that is associated with regulation of cytosolic free Ca(2+) contents.
Assuntos
Apoptose/fisiologia , Canais de Cálcio/fisiologia , Sinalização do Cálcio/fisiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Mitocôndrias/metabolismo , Animais , Sequência de Bases , Cálcio/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Caspase 3 , Caspases/metabolismo , Divisão Celular/fisiologia , Grupo dos Citocromos c/metabolismo , Primers do DNA , Ativação Enzimática , Humanos , Membranas Intracelulares/metabolismo , Membranas Intracelulares/fisiologia , Neoplasias Pulmonares/metabolismo , Potenciais da Membrana , Mitocôndrias/enzimologia , Mitocôndrias/fisiologia , Poli(ADP-Ribose) Polimerases/metabolismo , Células Tumorais Cultivadas , Regulação para CimaRESUMO
BACKGROUND: The issue of phrenic nerve preservation during pneumonectomy is still an unanswered question. So far, its direct effect on immediate postoperative pulmonary lung function has never been evaluated in a prospective trial. METHODS: We conducted a prospective crossover study including 10 patients undergoing pneumonectomy for lung cancer between July 2011 and July 2012. After written informed consent, all consecutive patients who agreed to take part in the study and in whom preservation of the phrenic nerve during operation was possible, were included in the study. Upon completion of lung resection, a catheter was placed in the proximal paraphrenic tissue on the pericardial surface. After an initial phase of recovery of 5 days all patients underwent ultrasonographic assessment of diaphragmatic motion followed by lung function testing with and without induced phrenic nerve palsy. The controlled, temporary paralysis of the ipsilateral hemidiaphragm was achieved by local administration of lidocaine 1% at a rate of 3 mL/h (30 mg/h) via the above-mentioned catheter. RESULTS: Temporary phrenic nerve palsy was accomplished in all but 1 patient with suspected catheter dislocation. Spirometry showed a significant decrease in dynamic lung volumes (forced expiratory volume in 1 second and forced vital capacity; p < 0.05) with the paralyzed hemidiaphragm. Blood oxygen saturation levels did not change significantly. CONCLUSIONS: Our results show that phrenic nerve palsy causes a significant impairment of dynamic lung volumes during the early postoperative period after pneumonectomy. Therefore, in these already compromised patients, intraoperative phrenic nerve injury should be avoided whenever possible.
Assuntos
Diafragma/inervação , Doenças do Sistema Nervoso Periférico/complicações , Nervo Frênico/lesões , Pneumonectomia/efeitos adversos , Recuperação de Função Fisiológica/fisiologia , Paralisia Respiratória/etiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/prevenção & controle , Nervo Frênico/fisiopatologia , Complicações Pós-Operatórias , Período Pós-Operatório , Prognóstico , Estudos Prospectivos , Paralisia Respiratória/fisiopatologia , Paralisia Respiratória/prevenção & controle , Capacidade VitalRESUMO
PRINCIPLES: Trimodal therapy results in long term survival in a small fraction of patients with malignant pleural mesothelioma, particularly in patients having epithelial histology, R0-resection and no nodal involvement. This study analyses the outcome after trimodal therapy including extrapleural pneumonectomy. METHODS: From 2000 to 2005 41 patients with histologically verified malignant pleural mesothelioma were included. Diagnosis and nodal status were confirmed by surgery. 21 patients (51%) underwent trimodal therapy with 655 days (63-2,567 days) of median follow-up. Postoperative complications, mortality, long term survival and recurrence rates were analysed retrospectively. RESULTS: Neoadjuvant chemotherapy consisted of a combination of platinum based agents (n = 19) with gemcitabine (n = 15) or pemetrexed (n = 4). Extrapleural pneumonectomy was the standard procedure for surgery. 13 patients (62%) had postoperative complications. 16 patients (76%) received postoperative adjuvant radiotherapy. There was a 30-day mortality of 4.8% in the trimodal group. Survival rates in the trimodal group were 71% after one, 28% after two and 10% after five years. There were no significant differences regarding age, tumour stage, cell type or lymph node involvement. Tumour recurrence occurred after one and two years in 44% and in 83% respectively. CONCLUSIONS: The majority of patients considered for surgical resection of malignant pleural mesothelioma have regionally advanced disease. In those receiving trimodal therapy long term survival is achieved only in a minority of patients. In view of the time consuming and intensive treatment it should be offered only in carefully selected patients as new surgical approaches such as pleurectomy/decortication have shown high efficacy rates regarding patients' survival.
Assuntos
Mesotelioma/mortalidade , Mesotelioma/terapia , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Adulto , Idoso , Quimiorradioterapia Adjuvante/métodos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Guanina/uso terapêutico , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pemetrexede , Compostos de Platina/uso terapêutico , Pneumonectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , GencitabinaRESUMO
Malignant pleural mesothelioma (MPM) is a lethal cancer of the mesothelium with high chemotherapeutic resistance via unknown mechanisms. A prevailing hypothesis states that cancer stem cells (CSCs) persist in tumors causing relapse after chemotherapy, thus, rendering these cells as critical targets responsible for tumor resistance and recurrence. We selected candidate CSC markers based on expansion under hypoxic conditions, a hallmark for the selection of chemoresistant cells; and investigated the expression of CSC markers: CD133, Bmi-1, uPAR and ABCG2 in three MPM cell lines and normal mesothelial cells by quantitative RT-PCR. Furthermore, we evaluated the chemotherapeutic resistance associated with each CSC marker by determining the change in CSC marker-mRNA levels as an index of drug-resistance following treatment with either cisplatin or pemetrexed. We demonstrate the expression of CSC markers: CD133, Bmi-1, uPAR and ABCG2 in both normal and MPM cell lines. Bmi-1+, uPAR+ and ABCG2+ cells show a distinct role in conferring chemoresistance to cisplatin and pemetrexed in the malignant setting. By contrast, these markers have no apparent participation in chemoresistance to drug treatments in normal mesothelial cells. Intriguingly, CD133 revealed chemoresistant properties in both normal mesothelial and malignant pleural mesothelioma cells. This study provides evidence of putative CSCs conferring drug-resistance to cisplatin and pemetrexed in MPM cell lines. Specific targeting of these drug-resistant cells, while considering the functional heterogeneity of the MPM subtypes, may contribute to more focused and effective chemotherapeutic regimens for malignant pleural mesothelioma.
Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Glutamatos/farmacologia , Guanina/análogos & derivados , Mesotelioma/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Pleurais/patologia , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Epitélio/metabolismo , Epitélio/fisiologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Guanina/farmacologia , Humanos , Células-Tronco Neoplásicas/patologia , Pemetrexede , Células Tumorais CultivadasRESUMO
Tissue transglutaminase (TG2) is implicated in cellular processes such as apoptosis and cell migration. Its acyl transferase activity cross-links certain proteins, among them transcription factors were described. We show here that the TG2 inhibitor KCC009 reversed resistance to tumor necrosis factor-related apoptosis-inducing factor (TRAIL) in lung cancer cells. Sensitization required upregulation of death receptor 5 (DR5) but not of death receptor 4. Upregulation of DR5 involved the first intron of the DR5 gene albeit it was independent from p53 and nuclear factor kappa B. In conclusion, inhibition of tissue transglutaminase provides an interesting strategy for sensitization to TRAIL-induced apoptosis in p53-deficient lung cancer cells.