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1.
Clin Transplant ; 37(12): e15122, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37694497

RESUMO

INTRODUCTION: The postoperative hemodynamic management after lung transplant (LUTX) is guided by limited evidence. We aimed to describe and evaluate risk factors and outcomes of postoperative vasoactive support of LUTX recipients. METHODS: In a single-center retrospective analysis of consecutive adult LUTX, two cohorts were identified: (1) patients needing prolonged vasoactive support (>12 h from ICU admission) (VASO+); (2) or not (VASO-). Postoperative hemodynamic characteristics were thoroughly analyzed. Risk factors and outcomes of VASO+ versus VASO- cohorts were assessed by multivariate logistic regression and propensity score matching. RESULTS: One hundred and thirty-eight patients were included (86 (62%) VASO+ versus 52 (38%) VASO-). Vasopressors (epinephrine, norepinephrine, dopamine) were used in the first postoperative days (vasoactive inotropic score at 12 h: 6 [4-12]), while inodilators (dobutamine, levosimendan) later. Length of vasoactive support was 3 [2-4] days. Independent predictors of vasoactive use were: LUTX indication different from cystic fibrosis (p = .003), higher Oto score (p = .020), longer cold ischemia time (p = .031), but not preoperative cardiac catheterization. VASO+ patients showed concomitant hemodynamic and graft impairment, with longer mechanical ventilation (p = .010), higher primary graft dysfunction (PGD) grade at 72 h (PGD grade > 0 65% vs. 31%, p = .004, OR 4.2 [1.54-11.2]), longer ICU (p < .001) and hospital stay (p = .013). Levosimendan as a second-line inodilator appeared safe. CONCLUSIONS: Vasoactive support is frequently necessary after LUTX, especially in recipients of grafts of lesser quality. Postoperative hemodynamic dysfunction requiring vasopressor support and graft dysfunction may represent a clinical continuum with immediate and long-term consequences. Further studies may elucidate if this represents a possible treatable condition.


Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Adulto , Humanos , Estudos Retrospectivos , Simendana/farmacologia , Transplante de Pulmão/efeitos adversos , Norepinefrina , Vasoconstritores/uso terapêutico , Hemodinâmica , Disfunção Primária do Enxerto/etiologia
2.
Transpl Int ; 36: 10690, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846600

RESUMO

Donation after cardiac death (DCD) donors are still subject of studies. In this prospective cohort trial, we compared outcomes after lung transplantation (LT) of subjects receiving lungs from DCD donors with those of subjects receiving lungs from donation after brain death (DBD) donors (ClinicalTrial.gov: NCT02061462). Lungs from DCD donors were preserved in-vivo through normothermic ventilation, as per our protocol. We enrolled candidates for bilateral LT ≥14 years. Candidates for multi-organ or re-LT, donors aged ≥65 years, DCD category I or IV donors were excluded. We recorded clinical data on donors and recipients. Primary endpoint was 30-day mortality. Secondary endpoints were: duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, severe primary graft dysfunction (PGD3) and chronic lung allograft dysfunction (CLAD). 121 patients (110 DBD Group, 11 DCD Group) were enrolled. 30-day mortality and CLAD prevalence were nil in the DCD Group. DCD Group patients required longer MV (DCD Group: 2 days, DBD Group: 1 day, p = 0.011). ICU length of stay and PGD3 rate were higher in DCD Group but did not significantly differ. LT with DCD grafts procured with our protocols appears safe, despite prolonged ischemia times.


Assuntos
Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Doadores de Tecidos , Transplante de Pulmão/métodos , Pulmão , Morte , Morte Encefálica , Isquemia , Perfusão/métodos , Sobrevivência de Enxerto
3.
Artigo em Inglês | MEDLINE | ID: mdl-37522864

RESUMO

A five classes (A-E) aggregate risk score predicting 90-day mortality after video-assisted thoracoscopic lobectomy for lung cancer, including as independent factors male sex (3 points), DLCO <60% (1 point) and operative time >150 minutes (1 point), has been recently published. This study aims to assess the effectiveness and reliability of this risk model in a large, independent cohort of patients, to confirm its generalizability. From the Italian VATS Group Database, we selected 2,209 patients [60% males; median age 69 years (IQR:63-74)] who underwent video-assisted thoracoscopic lobectomy for non-small cell lung cancer. We calculated the aggregate risk score and the corresponding class of 90-day mortality risk for each patient. The correlation between risk classes and mortality rates was tested by Spearman's r-test. Model calibration was evaluated by Hosmer-Lemeshow goodness-of-fit test. Class A-E 90-day mortality rates were 0.33%, 0.51%, 1.39%, 1.31% and 2.56%, respectively. A strong uphill correlation was identified between risk classes and 90-day mortality (r=0.90; p=0.037), showing a positive correlation between increased mortality rate and class A to E. Hosmer-Lemeshow chi-squared value was 67.47 (p<0.001) with overall, Class D and E significantly lower 90-day mortality in our cohort than in the original one [1.04% vs 2.5% (p=0.018), 1.31% vs 5.65% (p=0.005) and 2.56% vs 18.75% (p=0.007), respectively]. Despite our data show a positive correlation between 90-day mortality and risk classes from A to E with modest discriminatory performance, the poor calibration suggests the need for model recalibration using local data to better manage and counsel lung cancer patients eligible for video-assisted thoracoscopic lobectomy.

4.
Transpl Int ; 35: 10450, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431638

RESUMO

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.


Assuntos
Alveolite Alérgica Extrínseca , Doença Enxerto-Hospedeiro , Doenças Pulmonares Intersticiais , Transplante de Pulmão , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/cirurgia , Biópsia , Estudos de Coortes , Humanos , Doenças Pulmonares Intersticiais/patologia , Estudos Retrospectivos
5.
Langenbecks Arch Surg ; 406(5): 1353-1361, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33611653

RESUMO

INTRODUCTION: Gastroesophageal reflux disease (GERD) is frequently seen in patients with systemic sclerosis (SSc). Long-standing GERD may cause esophagitis, long-segment strictures, and Barrett's esophagus and may worsen pre-existing pulmonary fibrosis with an increased risk of end-stage lung disease. Surgical treatment of recalcitrant GERD remains controversial. The purpose of this systematic review was to summarize the current data on surgical treatment of recalcitrant GERD in SSc patients. MATERIALS AND METHODS: A systematic literature review according to PRISMA and MOOSE guidelines. PubMed, EMBASE, and Web of Science databases were consulted. RESULTS: A total of 101 patients were included from 7 studies. The age ranged from 34 to 61 years and the majority were females (73.5%). Commonly reported symptoms were heartburn (92%), regurgitation (77%), and dysphagia (74%). Concurrent pulmonary disease was diagnosed in 58% of patients. Overall, 63 patients (62.4%) underwent open fundoplication, 17 (16.8%) laparoscopic fundoplication, 15 (14.9%) Roux en-Y gastric bypass (RYGB), and 6 (5.9%) esophagectomy. The postoperative follow-up ranged from 12 to 65 months. Recurrent symptoms were described in up to 70% and 30% of patients undergoing fundoplication and RYGB, respectively. Various symptoms were reported postoperatively depending on the type of surgical procedures, anatomy of the valve, need for esophageal lengthening, and follow-up. CONCLUSIONS: The treatment of recalcitrant GERD in SSc patients is challenging. Esophagectomy should be reserved to selected patients. Minimally invasive RYGB appears feasible and safe with promising preliminary short-term results. Current evidence is scarce while a definitive indication about the most appropriate surgical treatment is lacking.


Assuntos
Esôfago de Barrett , Derivação Gástrica , Refluxo Gastroesofágico , Laparoscopia , Escleroderma Sistêmico , Esôfago de Barrett/cirurgia , Feminino , Fundoplicatura , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/cirurgia , Humanos , Escleroderma Sistêmico/complicações , Resultado do Tratamento
6.
Monaldi Arch Chest Dis ; 92(2)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34818884

RESUMO

This study describes the case of an 18-years-old male affected by severe COVID-19, who was receiving bilateral lung transplantation (LT), after 71 days of mechanical ventilation and 55 days of veno-venous extracorporeal membrane oxygenation. From post-operative day 2, early mobilization and physiotherapy treatments were performed. Weaning from mechanical ventilation, the use of non-invasive ventilation and tracheostomy management were included in the treatment. Forty-five days after LT the patient was discharged at home, showing improvements in terms of functional and respiratory parameters, quality of life and mood. While evidences about physiotherapy treatments in lung transplantation post severe COVID-19 remain limited, early approach and a multidisciplinary team may be considered key elements for functional recovery of these subjects.


Assuntos
COVID-19 , Transplante de Pulmão , Adolescente , Estado Terminal/terapia , Humanos , Masculino , Modalidades de Fisioterapia , Qualidade de Vida
7.
Transpl Int ; 33(7): 773-785, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32219887

RESUMO

Outcomes after transplantation of lungs (LuTX) treated with ex-vivo lung perfusion (EVLP) are debated. In a single-center 8 years of retrospective analysis, we compared: donors' and recipients' characteristics, gas exchange and lung mechanics at ICU admission, 3, 6, and 12 months, and patients' survival of LuTX from standard donors compared with EVLP-treated grafts. A total of 193 LuTX were performed. Thirty-one LuTX, out of 50 EVLP procedures, were carried out: 7 from nonheart beating and 24 from extended criteria brain-dead donors. Recipients' characteristics were similar. At ICU admission, compared with standard donors, EVLP patients had worse PaO2 /FiO2 [276 (206; 374) vs. 204 (133; 245) mmHg, P < 0.05], more frequent extracorporeal support (18% vs. 32%, P = 0.053) and longer mechanical ventilation duration [28 days of ventilator-free days: 27 (24; 28) vs. 26 (19; 27), P < 0.05]. ICU length of stay [4 (2; 9) vs. 6 (3; 12) days, P = 0.208], 28-day survival (99% vs. 97%, P = 0.735), and 1-year respiratory function were similar between groups. Log-rank analysis (median follow-up 2.5 years) demonstrated similar patients' survival (P = 0.439) and time free of chronic lung allograft disease (P = 0.484). The EVLP program increased by 16% the number of LuTX. Compared to standard donors, EVLP patients had worse respiratory function immediately after LuTX but similar early and mid-term outcomes.


Assuntos
Transplante de Pulmão , Estudos de Coortes , Humanos , Pulmão , Perfusão , Estudos Retrospectivos , Doadores de Tecidos
8.
Transpl Infect Dis ; 22(6): e13356, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32510771

RESUMO

Limited data are currently available regarding the course of COVID-19 in lung and solid organ transplant recipients. We hereby present four cases of SARS-CoV-2 pneumonia in lung transplant recipients from our center, set in Milan, Italy. We reduced immunosuppressive regimen in all these patients, typically holding the antiproliferative agent and augmenting steroids; everybody received hydroxychloroquine, initial empiric antibiotic treatment with piperacillin/tazobactam, and high-dose low molecular weight heparin. Clinical course seemed favorable in three of our patients, but one of them deteriorated after 10 days of hospitalization, probably due to an acute form of graft dysfunction triggered both by COVID-19 and a nosocomial bacterial infection, and eventually died. Although short-term prognosis could be considered benign in the majority of our patients, we should carefully monitor these individuals in order to detect early sign of clinical deterioration and graft dysfunction in the next few months.


Assuntos
Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Tratamento Farmacológico da COVID-19 , Inibidores Enzimáticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Hidroxicloroquina/uso terapêutico , Transplante de Pulmão , Idoso , Gasometria , COVID-19/imunologia , Fibrose Cística/cirurgia , Desprescrições , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Fibrose Pulmonar Idiopática/cirurgia , Imunossupressores/uso terapêutico , Itália , Doenças Pulmonares Intersticiais/cirurgia , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/cirurgia , SARS-CoV-2 , Resultado do Tratamento
9.
Heart Lung Circ ; 29(11): 1648-1655, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32718900

RESUMO

Primary spontaneous pneumothorax (PSP) is a commonly known condition due to the accumulation of air in the pleural space in otherwise healthy people, without apparent underlying lung disease. To date, the exact pathogenesis of PSP is unclear, but it still represents a public health issue. We performed a review of the literature concerning the epidemiology of PSP, examining age of onset and presentation symptoms, in order to assess the possible correlation between these characteristics and its occurrence. Data concerning age, signs, and symptoms were collected. For description purposes, information regarding aetiological and anthropomorphic data was also gathered. In total, 265 papers were evaluated. Regarding age of onset, PSP is a disease that can occur in a broad age group with a double cluster (15-30 and 40-45 yr). Regarding symptoms, pain and dyspnoea (in its various forms) are the most described in PSP. Pain was recorded in 69.25% (range, 9-100%) of the population studied, whereas dyspnoea was present in an average of 54.55% (range, 27-77.1%). Tobacco exposure seems to play an important role in the early onset of PSP. Concerning age at presentation, this review highlights that PSP can occur over a broad age range. The literature appears to be consistent in reporting PSP occurrence mostly below 45 years of age. Asymptomatic PSP is an almost unseen entity. Finally, of pollutants, cigarette smoking should be considered as the most significant exogenous risk factor in the development of PSP.


Assuntos
Pneumotórax/epidemiologia , Medição de Risco/métodos , Distribuição por Idade , Fatores Etários , Saúde Global , Humanos , Morbidade , Fatores de Risco
11.
Future Oncol ; 14(6s): 23-28, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29664356

RESUMO

This report highlights the results of the Italian video-assisted thoracoscopic surgery (VATS) Group, launched in mid 2013, which now has a website and an established database with over 4000 VATS lobectomy cases recruited from 67 thoracic surgery units across Italy. The year 2016 has been crucial for the following steps: inclusion of a dedicated biostatistician and a 'Survey Analysis & Data Quality Check'; the First Consensus Meeting with statements consequently adopted as Recommendations for the Italian Thoracic Surgery Society and published in a peer-reviewed journal; two papers published under the logo Italian VATS Group and seven abstracts accepted at annual international meetings (European Society of Thoracic Surgeons, European Association of Cardio-Thoracic Surgeons, European Lung Cancer Conference and European Respiratory Society); the institution of a Master Course on VATS lobectomy; the partnership with AME Publishing Company.


Assuntos
Neoplasias Pulmonares/cirurgia , Sistemas On-Line/estatística & dados numéricos , Pneumonectomia/normas , Sistema de Registros/estatística & dados numéricos , Cirurgia Torácica Vídeoassistida/normas , Conferências de Consenso como Assunto , Bases de Dados como Assunto , Humanos , Itália/epidemiologia , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Pneumonectomia/efeitos adversos , Pneumonectomia/economia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/economia , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
12.
Histopathology ; 68(5): 746-51, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26272457

RESUMO

AIMS: The role of tumour metabolic and proliferative indices in predicting non-small-cell lung cancer (NSCLC) patients' prognosis is unclear. We correlated fluorine 18 ((18) F)-fluorodeoxyglucose (FDG)-positron emission tomography (PET) value and Ki67 index to patients' survival, taking into account tumour heterogeneity, disease characteristics and genetic aberrations. METHODS AND RESULTS: A series of 383 NSCLCs was arranged into tissue microarrays and Ki67 staining was analysed by immunohistochemistry. The maximum standardized uptake (SUV(MAX) ) value detected by (18) F-FDG-PET analysis was calculated over a region of interest. Large-cell and squamous cell carcinomas had higher proliferative and metabolic activities than adenocarcinomas, and the two measures were correlated significantly. The hot-spot Ki67 value was correlated with patients' survival and the cut-off to discriminate patients in the survival risk groups was 20%. Ki67 hot-spot values were greater in anaplastic lymphoma kinase (ALK) rearranged tumours. Adenocarcinomas showed the highest intratumour heterogeneity in proliferative activity and the hot-spot Ki67 value predicted only the prognosis of patients in this group. Although tumour metabolic activity was not associated with patients' prognosis, a SUV(MAX) > 2 was related to nodal metastases, tumour size and grade. CONCLUSIONS: Our results highlight how tumour heterogeneity influences evaluation of prognostic biomarkers. Our data support Ki67 evaluation to estimate NSCLC patients' prognosis, particularly for adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Antígeno Ki-67/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Grandes , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos
13.
Int J Cancer ; 136(5): E262-71, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25196286

RESUMO

In lung cancer, the survival of patients with the same clinical stage varies widely for unknown reasons. In this two-phase study, we examined the hypothesis that germline variations influence the survival of patients with lung adenocarcinoma. First, we analyzed existing genotype and clinical data from 289 UK-resident patients with lung adenocarcinoma, identifying 86 single nucleotide polymorphisms (SNPs) that associated with survival (p < 0.01). We then genotyped these candidate SNPs in a validation series of 748 patients from Italy that resulted genetically compatible with the UK series based on principal component analysis. In a Cox proportional hazard model adjusted for age, sex and clinical stage, four SNPs were confirmed on the basis of their having a hazard ratio (HR) indicating the same direction of effect in the two series and p < 0.05. The strongest association was provided by rs2107561, an intronic SNP of PTPRG, protein tyrosine phosphatase, receptor type, G; the C allele was associated with poorer survival in both patient series (pooled analysis loge HR = 0.31; 95% CI: 0.15-0.46, p = 8.5 × 10(-5) ). PTPRG mRNA levels in 43 samples of lung adenocarcinoma were 40% of those observed in noninvolved lung tissue from the same patients. PTPRG overexpression significantly inhibited the clonogenicity of A549 lung carcinoma cells and the anchorage-independent growth of the NCI-H460 large cell lung cancer line. These four germline variants represent promising candidates that, with further study, may help predict clinical outcome. In addition, the PTPRG locus may have a role in tumor progression.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Estudo de Associação Genômica Ampla , Mutação em Linhagem Germinativa/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Polimorfismo de Nucleotídeo Único/genética , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Seguimentos , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Estudos de Validação como Assunto , População Branca
15.
Transpl Int ; 27(6): 553-61, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24628890

RESUMO

This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).


Assuntos
Circulação Extracorpórea/métodos , Transplante de Pulmão/métodos , Transplante de Pulmão/estatística & dados numéricos , Preservação de Órgãos/métodos , Adulto , Análise de Variância , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Modelos Lineares , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Perfusão , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Testes de Função Respiratória , Medição de Risco , Estatísticas não Paramétricas , Fatores de Tempo , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Resultado do Tratamento
16.
Carcinogenesis ; 34(6): 1281-5, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23430818

RESUMO

CHRNA5 gene expression variation may play a role in individual susceptibility to lung cancer. Analysis of CHRNA5 transcripts expressed in normal lung tissue detected the full-length transcript (isoform-1) and four splicing transcripts (isoform-2 to isoform-5), derived from the recognition of other splice sites in exon 5. Isoforms-2, -3 and -4 were found by protein modeling to form a completely folded, potentially functional extracellular domain and were observed at the protein level, whereas isoform-5 lacked a consistent part of the distorted ß sandwich and was not seen at the protein level. Only isoform-1 appeared to encode a complete, functional subunit able to fulfill the ion channel function. We previously reported that CHRNA5 expression is associated with genetic polymorphisms at this locus and that three haplotypes in its promoter region show functional regulation in vitro. Analysis of differential allelic expression (DAE) of three single nucleotide polymorphisms (rs503464, rs55853698 and rs55781567) tagging the expression haplotypes of the CHRNA5 promoter indicated statistically significant DAE at rs55853698 and rs55781567, in both normal lung and lung adenocarcinoma. Overall, our findings provide evidence for the presence of multiple CHRNA5 messenger RNA (mRNA) isoforms that may modulate the multimeric nicotine receptor and cis-regulatory variations in the CHRNA5 locus that act in vivo in the control of CHRNA5 mRNA expression, in normal lung tissue and in lung adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Proteínas do Tecido Nervoso/genética , Isoformas de Proteínas/metabolismo , Receptores Nicotínicos/genética , Adenocarcinoma/metabolismo , Alelos , Processamento Alternativo , Sequência de Aminoácidos , Frequência do Gene , Predisposição Genética para Doença , Variação Genética , Haplótipos/genética , Humanos , Canais Iônicos/genética , Canais Iônicos/metabolismo , Desequilíbrio de Ligação , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Polimorfismo de Nucleotídeo Único , Estrutura Terciária de Proteína , Splicing de RNA , RNA Mensageiro/genética , Receptores Nicotínicos/biossíntese , Alinhamento de Sequência
17.
Carcinogenesis ; 34(12): 2767-73, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23978379

RESUMO

Lung adenocarcinoma patients of similar clinical stage and undergoing the same treatments often have marked interindividual variations in prognosis. These clinical discrepancies may be due to the genetic background modulating an individual's predisposition to fighting cancer. Herein, we hypothesized that the lung microenvironment, as reflected by its expression profile, may affect lung adenocarcinoma patients' survival. The transcriptome of non-involved lung tissue, excised from a discovery series of 204 lung adenocarcinoma patients, was evaluated using whole-genome expression microarrays (with probes corresponding to 28 688 well-annotated coding sequences). Genes associated with survival status at 60 months were identified by Cox regression analysis (adjusted for gender, age and clinical stage) and retested in a validation series of 78 additional cases. RNA-Seq analysis from non-involved lung tissue of 12 patients was performed to characterize the different isoforms of candidate genes. Ten genes for which the loge-transformed hazard ratios expressed the same direction of effect in the discovery (P < 1.0 × 10(-3)) and validation series comprised the gene expression signature associated with survival: CNTNAP1, PKNOX1, FAM156A, FRMD8, GALNTL1, TXNDC12, SNTB1, PPP3R1, SNX10 and SERPINH1. RNA sequencing highlighted the complex expression pattern of these genes in non-involved lung tissue from different patients and permitted the detection of a read-through gene fusion between PPP3R1 and the flanking gene (CNRIP1) as well as a novel isoform of CNTNAP1. Our findings support the hypothesis that individual genetic characteristics, evidenced by the expression pattern of non-involved tissue, influence the outcome of lung adenocarcinoma patients.


Assuntos
Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Transcriptoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética
18.
BMC Infect Dis ; 13: 461, 2013 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-24094042

RESUMO

BACKGROUND: Children make up a significant proportion of the global tuberculosis (TB) caseload, and experience considerable TB-related morbidity and mortality. Unfortunately, it is not easy to diagnose TB in the first years of life because of the diversity of its clinical presentation and the non-specific nature of most of its symptoms. CASE PRESENTATION: A 26-month-old male child was admitted to hospital because of the sudden onset of rapidly increasing swelling of the neck, face and upper trunk a few hours before. Upon admission, his temperature was 36.5°C, pulse rate 120/min, respiratory rate 36/min, and O2 saturation 97% in air. Palpation revealed subcutaneous emphysema (SE) over the swollen skin areas, and an examination of the respiratory system revealed crepitations in the left part of the chest without any significant suggestion of mediastinal shift. Chest radiography showed enlargement of the left lung hilum with pneumomediastinum and diffuse SE. Bronchoscopy was carried out because of the suspicion that the SE may have been due to the inhalation of a peanut. This excluded the presence of a foreign body but showed that the left main bronchus was partially obstructed with caseous material and showed significant signs of granulomatous inflammation on the wall. Contrast-enhanced computed tomography of the lungs confirmed the SE and pneumomediastinum, and revealed bilateral hilum lymph node disease with infiltration of the adjacent anatomical structure and a considerable breach in the left primary bronchus wall conditioning the passage of air in the mediastinum and subcutaneous tissue. As a tuberculin skin test and polymerase chain reaction for Mycobacterium tuberculosis on bronchial material and gastric aspirate were positive, a diagnosis of TB was made and oral anti-TB therapy was started, which led to the elimination of M. tuberculosis and a positive clinical outcome. CONCLUSIONS: This is the first case in which SE was the first relevant clinical manifestation of TB and arose from infiltration of the bronchial wall secondary to caseous necrosis of the hilum lymph nodes. Physicians should be aware of the fact that SE is one of the possible initial signs and symptoms of early TB infection, and act accordingly.


Assuntos
Enfisema Subcutâneo/etiologia , Tuberculose dos Linfonodos/complicações , Pré-Escolar , Humanos , Masculino , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Enfisema Subcutâneo/diagnóstico , Tuberculose dos Linfonodos/microbiologia
19.
Int J Med Sci ; 10(3): 320-30, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23423768

RESUMO

The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs).This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Receptores ErbB/genética , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação
20.
BMC Pulm Med ; 13: 44, 2013 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-23844609

RESUMO

BACKGROUND: Tumors with a massive inflammatory infiltration are described in several organs. There is agreement about considering the inflammatory infiltration as the host's immune response to neoplastic cells; such neoplasms indeed have a better prognostic outcome than non-inflammatory counterparts. Only seventeen cases of pulmonary adenocarcinoma with massive lymphocytic infiltration (AMLI) have been reported in literature so far. CASE PRESENTATION: We present a case of pulmonary adenocarcinoma with massive lymphocytic infiltration occurring in a 71 years old male smoker. He came under our attention because of dyspnea, and underwent a left lower lobectomy. Histological examination showed a moderately differentiated (G2) acinar adenocarcinoma associated with a stromal desmoplastic reaction and a massive inflammatory infiltration, made up mostly of CD3+ lymphocytes. pTNM stage was pT2a, N0 (clinical stage: Ib). CONCLUSIONS: Literature review showed seventeen similar cases, with a 16/1 male/female ratio and a mean age of 70,2 years. In eight out of seventeen cases EBV-infection was demonstrated with immunohistochemical or molecular biology techniques.


Assuntos
Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Linfócitos T/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Idoso , Complexo CD3/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Masculino , Pneumonectomia , Linfócitos T/imunologia , Resultado do Tratamento
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