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The subcutaneous implantable cardioverter defibrillator (S-ICD) is often used in young patients such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome due to long-term lead durability issues. Although S-ICD lead dislodgement is rare, we encountered such an incident in a young ARVC patient during the chronic phase following the two-incision technique. Remote monitoring system is useful for early diagnosis of electrode movement (Graphical abstract image). When S-ICD lead dislodgement occurs in active young patients, lead revision using the three-incision technique may be an option.
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Recently, conduction system pacing has been performed in patients with impaired cardiac function. We report a case in which a DF4 implantable cardioverter defibrillator lead was screwed directly into the left bundle branch area with the support of a steerable delivery sheath.
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Pleural empyema often requires surgical intervention; however, surgical invasiveness should be minimized. We utilized the modified Claget procedure as an alternative to thoracoplasty for acute pleural empyema with a dead space. The procedure was performed as follows: first, 500 mg of kanamycin and 500,000 units of polymyxin sulfate dissolved in 10-100 ml saline was instilled intrapleurally via tube thoracostomy. The chest tube was clamped overnight and then removed. The modified Clagett procedure might be effective for acute pleural empyema with a dead space without pulmonary or bronchopleural fistula. We report our successful experience of performing modified Clagett procedure for pleural empyema with a dead space, through a detailed case presentation.
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Fístula Bronquial , Empiema Pleural , Empiema , Enfermedades Pleurales , Humanos , Neumonectomía , Empiema Pleural/cirugía , Tubos Torácicos , Empiema/cirugíaRESUMEN
PURPOSE: Pulmonary artery reconstruction is sometimes utilized as an alternative to pneumonectomy in lung cancer surgery. We herein report our experience of pulmonary artery reconstruction using an expanded polytetrafluoroethylene (ePTFE) patch based on the surgical results and long-term outcome. METHODS: Clinical records of lung cancer patients who underwent patch plasty were reviewed retrospectively. RESULTS: Between 2003 and 2017, pulmonary artery patch plasty were performed in 21 patients [18 males, 3 females; mean age 65 (range 47-79) years]. Induction chemoradiotherapy was performed in three patients. Bronchoplasty was performed in five patients. The pathologic stages were stage I in 3 patients, stage II in 6 and stage III in 12. Pneumonectomy, lobectomy and segmentectomy were performed in 2, 18 and 1 patient, respectively. The left upper lobe was the most frequent origin of lung cancer (15 patients). There was no reconstruction-related morbidity or mortality. The overall survival rate at 5 years was 64.1% with a mean follow-up of 39.5 months, and the survival rates for N0-1 and N2-3 were 80.8% and 28.6%, respectively. CONCLUSION: Patch angioplasty using the ePTFE sheet is a reliable procedure in radical surgery for lung cancer.
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Angioplastia/métodos , Polímeros de Fluorocarbono/uso terapéutico , Neoplasias Pulmonares/cirugía , Procedimientos de Cirugía Plástica/métodos , Arteria Pulmonar/cirugía , Anciano , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonectomía , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSES: To evaluate vertebral artery (VA) dominancy and the risk of brain infarction in T4 lung cancer patients with tumor invasion into the subclavian artery. METHODS: We reconstructed the subclavian artery in 10 patients with T4 non-small cell lung cancer. The histological stages were IIIA in eight patients and IIIB in two patients. We evaluated the VA dominancy by performing a four-vessel study preoperatively and investigated the relationship between the methods of VA treatment and postoperative brain complications, retrospectively. RESULTS: Seven patients had a superior sulcus tumor (SST) and three had direct invasion into the mediastinum. Based on the tumor location, a transmanublial approach was used in five patients and a posterolateral hook incision was used in the other five. All subclavian artery (SA) reconstructions were done using an artificial woven graft. Preoperative angiography of the VA revealed poor development of the contralateral side in two patients. One of these patients suffered a severe brain infarction on postoperative day 2, which proved fatal. In the other patient, the VA was connected to the left SA graft by a side-to-end anastomosis and there was no postoperative brain complication. CONCLUSIONS: Preoperative SA and VA angiography is mandatory for identifying the need for VA reconstruction in lung cancer patients with major arterial invasion.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Procedimientos de Cirugía Plástica , Arteria Subclavia/patología , Arteria Subclavia/cirugía , Neoplasias Vasculares/patología , Neoplasias Vasculares/cirugía , Procedimientos Quirúrgicos Vasculares , Arteria Vertebral/cirugía , Adulto , Anciano , Infarto Encefálico/etiología , Infarto Encefálico/prevención & control , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Riesgo , Arteria Subclavia/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Arteria Vertebral/diagnóstico por imagenRESUMEN
A relationship between serum polyunsaturated fatty acids (PUFAs) and cardiovascular disease has been reported; however, the existence of a relationship between serum PUFAs and extent of vessel disease (VD) in patients with ST elevation myocardial infarction (STEMI) remains unclear.Between July 2011 and June 2015, 866 consecutive STEMI patients underwent emergent percutaneous coronary intervention, 507 of whom were enrolled and classified into three groups according to the initial angiograms: 1VD, 294 patients; 2VD, 110 patients; and 3VD/left main trunk disease (LMTD), 103 patients. Serum levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid, and other laboratory data during hospitalization were evaluated.The serum EPA level in the 3VD/LMTD group was significantly lower than that in the 1VD group (55.5 ± 22.1 versus 66.2 ± 28.7, P = 0.002) and was slightly lower than that in the 2VD group (55.5 ± 22.1 versus 65.2 ± 28.9, P = 0.0167). Multivariate adjustment analysis revealed that age ≥ 70 years (odds ratio, 1.72; 95% confidence interval, 1.03-2.89; P = 0.038) and a low serum EPA level (odds ratio, 0.98; 95% confidence interval, 0.99-1.00; P = 0.023) were independent risk factors for 3VD/LMTD, while a low serum DHA level was not.A low serum EPA level may be more strongly related than a low serum DHA level to the extent of VD in STEMI patients. Age ≥ 70 years and a low serum EPA level may be independent risk factors for 3VD/LMTD.
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Enfermedad de la Arteria Coronaria/sangre , Vasos Coronarios/diagnóstico por imagen , Ácidos Grasos Omega-3/sangre , Infarto del Miocardio con Elevación del ST/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/terapiaRESUMEN
PURPOSE: We conducted a phase III randomized controlled trial (RCT) to investigate the efficacy of postsurgical adjuvant immunotherapy combined with chemotherapy. The immunotherapy targets were residual micrometastases and clones resistant to chemotherapy. PATIENTS AND METHODS: Between April 2007 and July 2012, 103 postsurgical non-small cell lung cancer patients were randomly assigned to receive either chemo-immunotherapy (group A) or chemotherapy (group B). The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients' own regional lymph nodes. RESULTS: The 2-year overall survival rates in groups A and B were 93.4 and 66.0 %, and the 5-year rates were 81.4 and 48.3 %, respectively. The differences were statistically significantly better in group A. The hazard ratio (HR) was 0.229 (p = 0.0013). The 2- and 5-year recurrence-free survival rates were 68.5, 41.4 and 56.8, 26.2 % in groups A and B, respectively. Those differences were also statistically significant (log-rank test p = 0.0020). The HR was 0.423 (p = 0.0027) in favor of group A. As for adverse reactions to immunotherapy, of a total of 762 courses, 52 (6.8 %) were accompanied with chills and shivering, and 47 (6.2 %), with fever (>38 °C). CONCLUSIONS: Immunotherapy has the potential to improve the postsurgical prognosis of lung cancer patients, but a large-scale multi-institutional RCT is awaited for further confirmation of this study.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Células Dendríticas/inmunología , Inmunoterapia , Neoplasias Pulmonares/terapia , Recurrencia Local de Neoplasia/terapia , Linfocitos T Citotóxicos/inmunología , Adenocarcinoma/inmunología , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
PURPOSE: The purpose of this study was to determine the impact of pulmonary fibrosis (PF) on postoperative complications and on long-term survival after surgical resection in lung cancer patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: A retrospective chart review was conducted of 380 patients with COPD who had undergone pulmonary resection for lung cancer at the University Hospital between 1990 and 2005. The definition of COPD was a preoperative forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of less than 70%; PF was defined as obvious bilateral fibrous change in the lower lung fields, confirmed by computed tomography. RESULTS: PF was present in 41 patients (10.8%) with COPD; the remaining 339 patients (89.2%) did not have PF. The preoperative FVC/FEV1 was significantly lower in the group of patients with PF than in the group without (p < 0.05). Acute lung injury and home oxygen therapy were significantly more common in the PF group; however, the 30-day mortality was similar between the groups. The cumulative survival at 3 and 5 years was 53.6 and 36.9%, respectively, in the PF group and 71.4 and 66.1%, respectively, in the non-PF group (p = 0.0009). Increased age, decreased body mass index, advanced pathologic stage, and the existence of PF were identified as independent risk factors for decreased survival. CONCLUSION: PF is a risk factor for decreased survival after surgical treatment in lung cancer patients with COPD.
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Neoplasias Pulmonares/cirugía , Pulmón/cirugía , Neumonectomía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Fibrosis Pulmonar/complicaciones , Anciano , Femenino , Volumen Espiratorio Forzado , Hospitales Universitarios , Humanos , Japón , Estimación de Kaplan-Meier , Pulmón/patología , Pulmón/fisiopatología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Neumonectomía/efectos adversos , Neumonectomía/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Fibrosis Pulmonar/diagnóstico , Fibrosis Pulmonar/mortalidad , Fibrosis Pulmonar/fisiopatología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Capacidad VitalRESUMEN
Primary pericardial synovial sarcoma is a rare disease. We herein report a case of synovial sarcoma that originated in the epicardium. A 13-year-old male visited our hospital with a fever and chest pain. Copious pericardial effusion and a large intrapericardial tumor were detected. An open-chest tumor resection was performed. A solid nodular tumor was observed in the pericardial cavity. The tumor was a polypoid mass that was pedunculated and grew from the inner surface of the pericardium near the origin of the SVC and ascending aorta. Histologically, the tumor cells were uniformly spindle shaped, with an ovoid or oval nucleus, and formed solid, compact sheets and fascicles. A storiform pattern was also observed. Based on the histopathological and immunohistochemical findings, and the fluorescence in situ hybridization detection of rearrangement of the SYT gene, a monophasic synovial sarcoma was diagnosed. We discuss the diagnosis and treatment of this case and review the pertinent literature.
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Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirugía , Pericardio , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/cirugía , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Procedimientos Quirúrgicos Cardíacos , Quimioterapia Adyuvante , Doxorrubicina/administración & dosificación , Reordenamiento Génico , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/patología , Humanos , Ifosfamida/administración & dosificación , Masculino , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Sarcoma Sinovial/genética , Sarcoma Sinovial/patología , Resultado del TratamientoRESUMEN
Although the late cardiac tamponade in leadless pacemaker implantation (LPI) is rare, we encountered such an incident in patient with AVEIR-VR™ system on hemodialysis and warfarinization. When LPI with active fixation system, we should aim for successful single-attempt deployment using electrical premapping to prevent cardiac tamponade including the late phase.
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AIMS: Atrial fibrillation (AF) is frequently associated with heart failure with preserved ejection fraction (HFpEF), but the diagnosis and prediction of the outcomes of HFpEF are difficult. Notably, the Heart Failure Association of the European Society of Cardiology proposed the use of the HFA-PEFF score in the diagnosis of HFpEF. This study aimed to assess the prognostic value of the pre- and post-procedural HFA-PEFF scores in patients with preserved ejection fraction (EF) after catheter ablation (CA) for AF. The primary endpoint was a composite of cardiac hospitalization for cardiovascular events and all-cause mortality. The secondary endpoint was AF recurrence. METHODS AND RESULTS: Overall, 354 patients with AF and preserved EF who underwent CA as well as blood tests and transthoracic echocardiography 2 weeks before and 6 months after CA from January 2018 to December 2019 were retrospectively enrolled in the study. In the 354 participants, univariate analysis showed that the post-procedural HFA-PEFF score was associated with a 3-year risk of the primary endpoint (hazard ratio [HR] = 3.73; 95% confidence interval [CI] = 2.07-6.73; P < 0.001), whereas the pre-procedural HFA-PEFF score was not (HR = 1.24, 95% CI = 0.82-1.86, P = 0.307). Further, the association between the post-procedural HFA-PEFF score and primary endpoint was not modified even after including other relevant variables into the score. Similar to the primary endpoint, the post-procedural HFA-PEFF score was associated with the 3-year risk of AF recurrence (P < 0.001). CONCLUSIONS: In patients with preserved EF undergoing AF ablation, the HFA-PEFF score at 6 months after CA was associated with the primary endpoint and AF recurrence at the 3-year follow-up.
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Background: Cardiac resynchronization therapy (CRT) with biventricular pacing is a well-established therapy. Left bundle branch area pacing (LBBAP) is a safe technique providing physiological pacing, and LBBAP-optimized CRT (LOT-CRT) has been shown to provide better electrical resynchronization than traditional CRT. However, there are few reports on shock lead placement in the left bundle branch area (LBBA) during CRT-defibrillator (CRT-D) implantation. Case summary: A 76-year-old woman with heart failure from dilated cardiomyopathy presented with left bundle branch block pattern (QRS duration, 160 ms). Left ventricular ejection fraction was 21%. Cardiac resynchronization therapy-defibrillator implantation was performed due to worsening symptoms. By reshaping the Agilis HisPro catheter and adding a septal curve, the shock lead was placed deep into the ventricular septum, narrowing QRS duration to 114 ms. Left ventricular activation time was 84 ms. A defibrillation threshold test confirmed successful treatment without adverse events. At 6-month follow-up, left ventricular ejection fraction improved from 21 to 63%, with the patient's condition improving from New York Heart Association class III to class I. Discussion: It was reported that QRS narrowing in CRT was related to long-term mortality, and LOT-CRT further decreased QRS duration as compared with LBBP only or biventricular pacing and increased the response rate. Combining LBBAP with coronary sinus pacing can potentially achieve superior electrical resynchronization. Lack of a suitable tool for direct shock lead placement in LBBA necessitated additional LBBAP lead in conventional LOT-CRT. Our successful LOT-CRT-D procedure with minimal number of leads through Agilis HisPro catheter reshaping enabled direct LBBA shock lead placement.
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Key Clinical Message: Atrial fibrillation ablation, including pulmonary vein isolation immediately after left atrial appendage closure (LAAC), is a rare and challenging issue. Intracardiac echocardiography guidance can help identify the LAAC device position for safe atrial fibrillation ablation without LAAC device-related adverse events even immediately after LAAC device implantation. Abstract: Early phase atrial fibrillation (AF) ablation after left atrial appendage closure (LAAC) is a rare and challenging issue. Here, we present a case illustrating the feasibility of AF ablation under intracardiac echocardiography guidance immediately after LAAC device implantation without LAAC device-related adverse events.
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Background: Patients with atrial fibrillation (AF) who are not suitable for long-term anticoagulant therapy undergo percutaneous left atrial appendage closure (LAAC). The safety and feasibility of left atrial catheter ablation (CA) procedures after LAAC remain unclear. This study aimed to clarify the feasibility and safety of CA after LAAC, including in the early phase within 180 days. Methods: Characteristics and clinical outcomes of 46 patients with AF who had undergone both CA and LAAC within 2 years (mean age, 72 years; 29 men) were compared between those who had undergone CA-first (31 patients) and LAAC-first (15 patients). Results: The mean CHA2DS2-VASc and HAS-BLED scores were 4.8 and 3.3 points, respectively. The LAAC-first strategy was often used in patients with prior major bleeding and LAA thrombosis or sludge. In the LAAC-first group, the mean duration between both procedures was 212 days, and all LAAC-first patients, including seven patients in the early phase, could undergo CA without LAAC device-related complications; moreover, no cardiovascular adverse events were reported after both procedures (mean periods: 420 days). After CA post-LAAC, no device-related adverse events (device-related thrombosis, new peri-device leak appearance, peri-device leak increase, or device dislodgement) were observed, whereas, after LAAC post-CA, 3 new peri-device leak appearance events and 1 peri-device leak increase event were observed, especially patients who underwent LAAC in the early phase post-CA. Conclusion: Based on single-center experience, left atrial CA in the presence of an LAAC device implanted including the early phase was safe and feasible.
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Background: It is unknown whether atrial fibrillation (AF) burden varies by pacing site in patients with reactive atrial antitachycardia pacing (rATP). We aimed to compare AF burden in patients with high atrial septal pacing (HASp) via delivery catheter and right atrial appendage pacing (RAAp) in patients with sick sinus syndrome (SSS). Methods: We retrospectively identified 109 patients with a history of paroxysmal AF and SSS who had received dual-chamber pacemaker implantation between January 2017 and December 2019, of whom 39 and 70 patients had HASp and RAAp, respectively. rATP was initiated after a 1-month post-implantation run-in period. Results: Patients with HASp had a significantly shorter P-wave duration during atrial pacing than those with RAAp (99.3 ± 10.4 vs. 116.0 ± 14.3 ms, p < .001). During the 3-year follow-up period, the incidence of an AF lasting longer than 1 or 7 days was significantly lower (hazard ratio [HR], 0.45; p = .016; HR, 0.24; p = .004) than in those with RAAp. The median time of AF/AT per day in the follow-up periods was significantly shorter in the HASp group than in the RAAp group (10 vs. 18 min/day, p = .018). Atrial lead division did not occur in the HASp group during the follow-up period. Conclusions: HASp via delivery catheter is as safe as RAAp, and HASp combined with rATP is effective for reducing AF burden in patients with SSS and paroxysmal AF.
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PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (Tex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the Tex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the Tex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such Tex clonotypes, mainly from TDLNs.
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Linfocitos T CD8-positivos/efectos de los fármacos , Inhibidores de Puntos de Control Inmunológico/farmacología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Microambiente Tumoral/inmunología , Animales , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral/efectos de los fármacos , Humanos , Linfocitos Infiltrantes de Tumor/metabolismo , Ratones , Receptor de Muerte Celular Programada 1/metabolismo , Microambiente Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: The aim of this study was to evaluate the molecular influence of chronic obstructive pulmonary diseases (COPD) on the pathogenesis of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The methylation profiles of 12 genes, and the epidermal growth factor receptor (EGFR) and KRAS mutations were determined for samples from 229 NSCLC patients. In addition, protein expression of EGFR and HER2 in 116 NSCLCs was analyzed based on the presence or absence of COPD. RESULTS: IL-12Rbeta2 and Wif-1 methylation and HER2 overexpression were more frequent events in the COPD group. Eighty nonmalignant lung tissues had no correlation with any molecular changes between the COPD and the non-COPD group. EGFR mutation was significantly higher in the non-COPD group, while EGFR expression was inversely correlated with %FEV1.0. In the COPD group, unmethylated SPARC and sFRP-2 genes or a negative CpG island methylator phenotype (CIMP) was a negative prognostic factor, while methylation of p16(INK4A) and WNT antagonist genes was a negative prognostic factor in the non-COPD group. CONCLUSIONS: Novel characteristics of COPD-related NSCLC were identified by examination of methylation profiles and alterations of EGFR signaling. In consideration of the high sensitivity to smoking in patients with COPD, NSCLC with COPD might be a distinct population of smoke-related NSCLC, the genetic profile of which is quite different from non-COPD NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Metilación de ADN , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutación/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Transducción de Señal/genética , Adenocarcinoma/complicaciones , Adenocarcinoma/genética , Adenocarcinoma/patología , Anciano , Carcinoma de Células Grandes/complicaciones , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Receptores ErbB/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Pronóstico , Regiones Promotoras Genéticas , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/patología , Tasa de SupervivenciaRESUMEN
Several studies have described p16INK4A and prostaglandin E2 (PGE2) co-alterations in various solid tumors, including non-small cell lung cancer (NSCLC). In this study, we examined the correlation between PGE2 receptor 2 (EP2) expression and p16INK4A methylation in NSCLC, and the association with clinicopathological features and prognostic significance. We retrospectively reviewed 88 NSCLC patients who underwent resection from July 1993 to May 1997. The tumors included 43 adenocarcinomas, 39 squamous cell carcinomas, and 6 large cell carcinomas. EP2 expression was determined by immunostaining, and p16INK4A methylation was analyzed by methylation specific PCR. EP2 was overexpressed in 44% of NSCLC patients, 61% of adenocarcinoma cases, 28% of squamous cell carcinoma cases, and 33% of large cell carcinoma cases. EP2 expression positively correlated with lymph node metastasis (P=0.034), especially in patients with squamous cell carcinoma (P<0.009). Methylation of p16INK4A was detected in 34% of NSCLC patients, 23% of adenocarcinoma cases, 44% of squamous cell carcinoma cases, and 50% of large cell carcinoma cases. In patients with squamous cell carcinoma, EP2 overexpression correlated with poor prognosis with a relative risk of 2.4 (confidence interval 2.1-51.8, P<0.003), and positively correlated with p16INK4A methylation (P<0.024). Adenocarcinoma patients with p16INK4A methylation had poor prognosis with a relative risk of 2.4 (confidence interval 1.8-69.7, P<0.009), but this was not correlated with EP2 expression. In conclusion, EP2 overexpression was common in NSCLCs, especially in adenocarcinomas. Synchronous alteration of p16INK4A and EP2 may accelerate progression of squamous cell carcinomas. These two alterations may differentially affect pathogenesis among subtypes of NSCLC.
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Carcinoma de Células Escamosas/genética , Metilación de ADN , Genes p16 , Neoplasias Pulmonares/genética , Receptores de Prostaglandina E/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Receptores de Prostaglandina E/genética , Receptores de Prostaglandina E/metabolismo , Subtipo EP2 de Receptores de Prostaglandina E , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The efficacy and toxicity of adjuvant chemo-immunotherapy using dendritic cells and activated killer cells are not clear in post-surgical primary lung cancer patients. PATIENTS AND METHODS: Pathologically diagnosed N2 lung cancer patients were selected for postsurgical adjuvant chemo-immunotherapy. The activated killer cells and dendritic cells (AKT-DC) obtained from tissue cultures of tumor-draining lymph nodes (TDLN) or from TDLN co-cultured with peripheral blood lymphocytes (TDLN-Pb) were used for the adoptive transfer of immunotherapy. The patients received 4 courses of chemotherapy along with immunotherapy every 2 months for 2 years. RESULTS: There were 31 N2 patients eligible for the study. Three cases were excluded because of refusal by the patients after 1-2 courses of immunotherapy. For the 28 cases treated, a total of 313 courses of immunotherapy were administered. The main toxicities were fever (78.0%), chill (83.4%), fatigue (23.0%) and nausea (17.0%) on the day of cell transfer. The 2- and 5-year survival rates were 88.9 % (95.9-81.9; 95% confidence interval, C.I.) and 52.9% (76.4-29.4; C.I.). CONCLUSION: Adoptive transfer of activated killer cells and dendritic cells from the tumor-draining lymph nodes of primary lung cancer patients is feasible and safe, and a large-scale multi-institutional study is necessary for evaluation of the efficacy of this treatment.