RESUMO
OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.
Assuntos
Colo do Útero/patologia , Histerectomia/efeitos adversos , Laparoscopia/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Colo do Útero/cirurgia , Conização/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Neoplasia Residual , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/estatística & dados numéricos , Fatores de Proteção , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Carga Tumoral , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.
Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/mortalidade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
The authors describe a rare case of primary ovarian fibrosarcoma and the latest trends in diagnosis and therapy. The rarity of this dis-ease and the scarce number of reported cases pose serious problems in differentiating it from other fibrous forms. A 58-year-old woman presented intermittent pelvic pain and a demarcated, mobile, and solid lump in the right adnexa. Diagnostic imaging revealed a solid- cystic inhomogeneous mass occupying the right adnexa and the CA125 level was elevated. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy. Histological findings with immunomarkers led to the final diagnosis of low-grade malignant mesenchymal neoplasm derived from the ovarian stroma compatible with fibrosarcoma. Twenty-four months follow-up showed no recurrence of disease. Ovarian fibrosarcoma is very uncommon neoplasm with a poor prognosis. Despite the efforts of several authors in reporting morphological, histological, and immunohistochemical features of this neoplasm, nowadays, the diagnosis, treatment, and prognosis are unresolved issues. The present case highlights the important role of immunohistochemistry to define histological type and differential diagnosis. As demonstrated by the authors' experience, they believe that surgery is curative in the early stages with low immunohistochemical positivity for ki67 and that chemotherapy should be reserved in advanced stages with regimens in use for the treatment of sarcomas.
Assuntos
Fibrossarcoma/diagnóstico , Neoplasias Ovarianas/diagnóstico , Feminino , Fibrossarcoma/patologia , Fibrossarcoma/terapia , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapiaRESUMO
The human genome encodes a gene for an enzymatically active chitinase (CHIT1) located in a single copy on Chromosome 1, which is highly expressed by activated macrophages and in other cells of the innate immune response. Several dysfunctional mutations are known in CHIT1, including a 24-bp duplication in Exon 10 causing catalytic deficiency. This duplication is a common variant conserved in many human populations, except in West and South Africans. Thus it has been proposed that human migration out of Africa and the consequent reduction of exposure to chitin from environmental factors may have enabled the conservation of dysfunctional mutations in human chitinases. Our data obtained from 85 indigenous Amerindians from Peru, representative of populations characterized by high prevalence of chitin-bearing enteroparasites and intense entomophagy, reveal a very high frequency of the 24-bp duplication (47.06%), and of other single nucleotide polymorphisms which are known to partially affect enzymatic activity (G102S: 42.7% and A442G/V: 25.5%). Our finding is in line with a founder effect, but appears to confute our previous hypothesis of a protective role against parasite infection and sustains the discussion on the redundancy of chitinolytic function.
Assuntos
Quitina/química , Hexosaminidases/genética , Imunidade Inata/genética , Animais , Quitina/genética , Dieta , Hexosaminidases/deficiência , Humanos , Indígenas Sul-Americanos , Macrófagos/metabolismo , Macrófagos/parasitologia , Mutação , Parasitos/química , Parasitos/metabolismo , Peru , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Despite the efficiency of venom immunotherapy, the effects on basophils and mast cells remain incompletely understood and probably vary according to the treatment phase. OBJECTIVES: To study the effect of build-up and maintenance venom immunotherapy on individual basophils. METHODS: Intracellular histamine and its release was analyzed flow cytometrically by a new enzyme-affinity method using diamine oxidase conjugated to laser-excitable fluorochromes. Phenotyping of cells included flow cytometric quantification of CD63 and CD203c. Analyses of basophil activation experiments were performed before the start of treatment, after build-up therapy and during maintenance therapy. RESULTS: Before the start of therapy, patients demonstrated significantly higher numbers of basophils when compared with stung control individuals. At the end of build-up therapy a decrease of basophil numbers was observed, whereas during maintenance therapy basophil counts returned to pretreatment values. Before the start of therapy, the intracellular histamine content per cell in patients was significantly higher when compared with stung control individuals. During maintenance therapy intracellular histamine content decreased to values observed in stung control individuals. In addition, maintenance therapy lowered the net release of histamine per cell in response to optimal stimulation with wasp venom. CONCLUSIONS: We introduce a novel technique that enables to assess the effects of venom immunotherapy on basophils. This new technique may help to monitor treatment effects in individual patients and could aid in the development of more efficient and better tolerated immunotherapy protocols.
Assuntos
Basófilos/metabolismo , Liberação de Histamina/efeitos dos fármacos , Histamina/sangue , Hipersensibilidade/terapia , Venenos de Vespas/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Criança , Dessensibilização Imunológica/métodos , Feminino , Citometria de Fluxo/métodos , Expressão Gênica , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/imunologia , Pirofosfatases/genética , Pirofosfatases/imunologia , Tetraspanina 30/genética , Tetraspanina 30/imunologia , VespasRESUMO
AIM: The prevalence of respiratory diseases has been assessed in community based epidemiological studies. General practice is the ideal position to intercept chronic respiratory illness and manage the first level of follow up as well. Aim of this study was to obtain General Practitioners (GPs) data about management and clinical setting of patients with respiratory diseases. METHODS: This is a prospective observational study; 272 Italian GPs were involved and equally distributed on the Italian territory. The interviews were performed by means of a questionnaire consisting in which consisted of 25 questions regarding individual demographics, catchment area, professional behavior, health attitudes. RESULTS: Each GP reported that about 13% of the pooled patients had a respiratory disease. Concerning as for chronic respiratory illnesses, spirometry was frequently prescribed and in these patients 63% of the interviewed GPs thought that the lung functional test was fundamental. GPs also reported the importance of improving health education, well aware of its importance in the prevention of respiratory diseases; and furthermore in improving the current health system organization. As for with regard to cigarette smoke, interviewed GPs reported that the 26% of their assisted subjects were smokers and the commitment to discouraging the smoking habit was very high. CONCLUSION: This is a large National survey that involved GPs and real life data about management of patients with respiratory diseases. The role of GPs in the management of chronic respiratory patients represents an important tool valuable in increasing primary care identification, education and treatment of respiratory diseases.
Assuntos
Medicina Geral , Clínicos Gerais , Pneumopatias/terapia , Padrões de Prática Médica , Atitude do Pessoal de Saúde , Doença Crônica , Feminino , Medicina Geral/estatística & dados numéricos , Clínicos Gerais/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Itália/epidemiologia , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Abandono do Hábito de Fumar , Espirometria , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Epidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma. OBJECTIVES: To determine the effects of experimental hookworm infection in asthma. METHODS: Thirty-two individuals with asthma and measurable airway responsiveness to adenosine monophosphate (AMP) were randomized and double blinded to cutaneous administration of either ten Necator americanus larvae, or histamine solution (placebo), and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce forced expiratory volume in 1 s by 20% (PD(20)AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitivity and the occurrence of adverse effects. RESULTS: Mean PD(20)AMP improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD; 95% confidence interval: -1.79 to 2.80; P=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitization. Infection was generally well tolerated. CONCLUSIONS: Experimental infection with ten hookworm larvae in asthma did not result in significant improvement in bronchial responsiveness or other measures of asthma control in this study. However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken.
Assuntos
Asma/complicações , Asma/terapia , Necator americanus , Necatoríase/complicações , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Administração por Inalação , Adulto , Animais , Asma/imunologia , Asma/prevenção & controle , Testes de Provocação Brônquica , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Larva/imunologia , Larva/fisiologia , Masculino , Necator americanus/crescimento & desenvolvimento , Necator americanus/imunologia , Necator americanus/fisiologia , Necatoríase/diagnóstico , Necatoríase/parasitologia , Placebos , Segurança , Testes CutâneosRESUMO
BACKGROUND: Epidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration. OBJECTIVE: To determine whether hookworm larval migration through the lungs increases airway responsiveness in allergic individuals with measurable airway responsiveness but not clinical asthma, and investigate the general tolerability of infection and effect on allergic symptoms. METHODS: Thirty individuals with allergic rhinoconjunctivitis and measurable airway responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed asthma were randomized, double-blind to cutaneous administration of either 10 hookworm larvae or histamine placebo, and followed for 12 weeks. The primary outcome was the maximum fall from baseline in provocative dose of inhaled AMP required to reduce 1-s forced expiratory volume by 10% (PD(10)AMP) measured at any time over the 4 weeks after active or placebo infection. Secondary outcomes included peak flow variability in the 4 weeks after infection, rhinoconjunctivitis symptom severity and adverse effect diary scores over the 12-week study period, and change in allergen skin test responses between baseline and 12 weeks. RESULTS: Mean maximum change in PD(10)AMP from baseline was slightly but not significantly greater in the hookworm than the placebo group (-1.67 and -1.16 doubling doses; mean difference -0.51, 95% confidence interval -1.80 to 0.78, P=0.42). Symptom scores of potential adverse effects were more commonly reported in the hookworm group, but infection was generally well tolerated. There were no significant differences in peak-flow variability, rhinoconjunctivitis symptoms or skin test responses between groups. CONCLUSION: Hookworm infection did not cause clinically significant exacerbation of airway responsiveness and was well tolerated. Suitably powered trials are now indicated to determine the clinical effectiveness of hookworm infection in allergic rhinoconjunctivitis and asthma.
Assuntos
Hiper-Reatividade Brônquica/etiologia , Infecções por Uncinaria/complicações , Monofosfato de Adenosina/efeitos adversos , Adolescente , Adulto , Asma/terapia , Testes de Provocação Brônquica , Conjuntivite Alérgica/terapia , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Seguimentos , Volume Expiratório Forçado , Infecções por Uncinaria/parasitologia , Humanos , Masculino , Placebos , Rinite Alérgica Sazonal , Segurança , Testes Cutâneos , Reino Unido , Adulto JovemRESUMO
BACKGROUND: Basophils are increasingly utilized as indicators of allergic inflammation and as primary allergic effector cells to study signalling pathways. However, until the present, their enrichment has been time consuming, costly and limited to relatively few specialized laboratories. OBJECTIVE: We have therefore devised a reproducible and rapid method for the purification of human basophils from small quantities of peripheral blood within 1.5 h, which does not require the use of specialized equipment such as elutriators. METHODS: Human basophils were obtained from healthy volunteers undergoing venipuncture. Heparinized or K3-ethylenediaminetetraacetic acid blood samples were first subjected to centrifugation in Hetasep, directly followed by negative selection using immunomagnetic beads. Basophil morphology and purity were assessed by May-Grünwald staining of cytospins. IgE-mediated histamine release was analysed spectrofluorometrically and IL-4 and IL-13 production by quantitative RT-PCR. CD203c and CD63 surface expression was measured using flow cytometry before and after activation with anti-IgE. RESULTS: Using this protocol, basophils were enriched close to homogeneity in most cases with a mean purity of 99.34+/-0.88% (range 97-100%, n=18) and a mean recovery of 75.6 (range 39-100%, n=8). Basophil viability following purification was 99.6+/-0.89% using Trypan blue exclusion. The purification procedure gave rise to basophils with normal functional responses to anti-IgE regarding histamine release as well as IL-4 and IL-13 mRNA expression. Moreover, constitutive cell-surface CD203c/CD63 expressions were not elevated before anti-IgE stimulation. CONCLUSION: The rapidity, simplicity and reproducibility of this method will facilitate the employment of basophils in high-output ex vivo studies.
Assuntos
Basófilos , Células Sanguíneas , Separação Celular/métodos , Anticorpos Anti-Idiotípicos/farmacologia , Antígenos CD/metabolismo , Basófilos/metabolismo , Basófilos/fisiologia , Células Sanguíneas/fisiologia , Membrana Celular/metabolismo , Separação Celular/normas , Sobrevivência Celular , Liberação de Histamina/efeitos dos fármacos , Humanos , Imunoglobulina E/imunologia , Interleucina-13/genética , Interleucina-4/genética , Diester Fosfórico Hidrolases/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Pirofosfatases/metabolismo , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Tetraspanina 30 , Fatores de TempoRESUMO
BACKGROUND: Little is known about the long-term natural history of asthma and the long-term clinical and functional consequences in non-smoking patients. From a functional point of view, non-smoking asthmatic patients may have a significantly greater decline in forced expiratory volume in one second (FEV1) compared with non-asthmatic subjects and may develop chronic irreversible (fixed) airflow limitation. This has been related to the physiological consequences of chronic airway inflammation causing airway remodeling. However these lesions are all potentially reversible and there is little radiological evidence indicating lung destruction (pulmonary emphysema), which is potentially irreversible, in non-smoking asthmatics. Severe chronic respiratory failure is the major cause of mortality in patients with severe chronic lung diseases. Domiciliary long-term oxygen therapy (LTOT) is an accepted treatment for patients with severe chronic respiratory failure. Our reasoning, therefore, was that if asthma is a cause of severe chronic respiratory failure in non-smokers we should be able to find non-smoking asthmatics within a large population of patients on LTOT. The aim of our study (Asthma and Long-term Oxygen Therapy, "ALOT") was to investigate the prevalence of non-smoking asthmatics in patients on LTOT in a multi-centre, cross-sectional study. METHODS: Between June and September 2003 we screened all subjects on long-term domiciliary oxygen therapy in three different hospitals in the North-East area of Italy (within the provinces of Ferrara and Bologna). Taken collectively, we have found one-hundred and eighty-four patients on LTOT. We have reviewed their clinical data (age, sex, smoking, history and physical examination, arterial blood gas analysis, pulmonary function). RESULTS: 114 patients (all smokers) fulfilled the diagnostic criteria for COPD. Seventy patients (all smokers) had other diseases. We were unable to find any non-smokers in our screened population of subjects on long-term domiciliary oxygen therapy. Furthermore, there was no past history of asthma and/or acute wheezing episodes in either of the patient groups. CONCLUSIONS: This data suggests that asthma is an uncommon cause of severe chronic respiratory failure necessitating long-term domiciliary oxygen therapy in non-smokers and supports the current consensus that asthma and COPD are different diseases with differing stages of severity and the concept that long-term avoidance of active smoking is fundamental for the prevention of severe chronic respiratory failure.
Assuntos
Asma/complicações , Insuficiência Respiratória/etiologia , Idoso , Dióxido de Carbono/sangue , Doença Crônica , Estudos Transversais , Feminino , Volume Expiratório Forçado/fisiologia , Serviços de Assistência Domiciliar , Humanos , Estudos Longitudinais , Masculino , Oxigênio/sangue , Oxigenoterapia , Exame Físico , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Insuficiência Respiratória/terapia , Fumar/efeitos adversos , Fumar/fisiopatologia , Capacidade Pulmonar Total/fisiologia , Capacidade Vital/fisiologiaRESUMO
Infections with the helminth parasite Brugia malayi share many key features with Th2-mediated allergic diseases, including recruitment of eosinophils. We have investigated the dynamics of inflammatory cell recruitment under type 2 cytokine conditions in mice infected with B. malayi. Among the cells recruited to the site of infection is a novel population of "alternatively activated" macrophages that ablate cell proliferation and enhance Th2 differentiation. By profiling gene expression in this macrophage population, we found a dramatic up-regulation of a recently described eosinophil chemotactic factor, eosinophil chemotactic factor-L/Ym1, representing over 9% of clones randomly selected from a cDNA library. Because B. malayi is known to secrete homologs (Bm macrophage migration inhibitory factor (MIF)-1 and -2) of the human cytokine MIF, we chose to investigate the role this cytokine mimic may play in the development of the novel macrophage phenotype observed during infection. Strikingly, administration of soluble recombinant Bm-MIF-1 was able to reproduce the effects of live parasites, leading both to the up-regulation of Ym1 by macrophages and a marked recruitment of eosinophils in vivo. Because activity of Bm-MIF-1 is dependent upon an amino-terminal proline, this residue was mutated to glycine; the resultant recombinant (Bm-MIF-1G) was unable to induce Ym1 transcription in macrophages or to mediate the recruitment of eosinophils. These data suggest that macrophages may provide a crucial link between helminth parasites, their active cytokine mimics, and the recruitment of eosinophils in infection.
Assuntos
Brugia Malayi , Eosinófilos/fisiologia , Filariose/imunologia , Fatores Inibidores da Migração de Macrófagos/fisiologia , Macrófagos/fisiologia , beta-N-Acetil-Hexosaminidases , Animais , Movimento Celular , Perfilação da Expressão Gênica , Lectinas/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBARESUMO
Diarrhoea, T-CD4+ lymphopenia and bilateral patchy pulmonary infiltrates developed in a male 60 yrs of age, who was treated with oxaliplatinum and 5-fluorouracil for unresectable rectum carcinoma. The findings from transbronchial lung biopsy and bronchoalveolar lavage (BAL) were consistent with an organizing diffuse alveolar damage pattern. Once extensive microbiological studies proved negative, corticosteroids were given and a complete remission of clinical and radiological abnormalities was achieved. It is concluded that the aforementioned pathological manifestations were due to chemotherapy and included a pulmonary adverse reaction, a feature never previously associated with oxaliplatinum and 5-fluorouracil regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fluoruracila/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Fibrose Pulmonar/induzido quimicamente , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/administração & dosagem , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Neoplasias Retais/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND AIM OF THE WORK: The studies on late-onset non-infectious respiratory complications after allogeneic bone marrow transplantation (allo-BMT) have been mainly focused on bronchiolitis obliterans to date. The aim of this work was to analyze the incidence, clinico-pathologic characteristics and outcome of the entire spectrum of entities falling into the group of delayed non-infectious lung disease (DLD). METHODS: Retrospective chart review was carried out of 112 patients who underwent allo-BMT for hematologic malignancies between April 1995 and November 1998 at a single Institution. The categorization of the pulmonary disease was made by analyzing clinical data, bronchoalveolar lavage (BAL), high-resolution computed tomography (HRCT) and histology when possible. RESULTS: DLD occurred in 10 (10%) out of 97 recipients who survived at least 100 days following allo-BMT and was defined as bronchiolitis obliterans (BO; 4 cases), acute lung injury (ALI; 1 case) and subacute cellular interstitial pneumonia (SCIP; 5 cases). The BAL-profile was characterized by a marked increase of the neutrophil percentage in BO cases and of the lymphocyte (predominantly CD8+) percentage in parenchymal DLDs (SCIP, ALI). HRCT proved to be helpful to correctly identify BO cases, whereas histology was always needed to better define DLD presenting with an interstitial and/or alveolar pattern. The predominant airway involvement as well as the acute-onset of a respiratory illness with histological evidence of diffuse alveolar damage were associated with a worse prognosis because of a poor response to the immunosuppressive treatment. CONCLUSIONS: DLDs represent a group of entities heterogeneous in regard to variables such as onset and clinical behaviour (acute, subacute or chronic), predominant pattern of lung involvement (airway or parenchymal), response to treatment. Although immunopathologic mechanisms related to c-GVHD probably have a relevant pathogenic importance in this setting, the possible role of associated events (eg, drug toxicity and infections) at least in priming the lung damage need to be better clarified for its therapeutical implications.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , Pneumopatias/etiologia , Adolescente , Adulto , Lavagem Broncoalveolar , Feminino , Humanos , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoAssuntos
Basófilos/fisiologia , Hipersensibilidade/imunologia , Adulto , Alérgenos/imunologia , Anticorpos Monoclonais/imunologia , Basófilos/efeitos dos fármacos , Basófilos/metabolismo , Cálcio/fisiologia , Sinalização do Cálcio/efeitos dos fármacos , Diferenciação Celular , Linhagem da Célula , Separação Celular/métodos , Quimiotaxia de Leucócito , Citocinas/farmacologia , Grânulos Citoplasmáticos/metabolismo , Sangue Fetal/citologia , Previsões , Substâncias de Crescimento/farmacologia , Helmintíase/imunologia , Helmintíase/patologia , Fatores de Crescimento de Células Hematopoéticas/farmacologia , Liberação de Histamina/efeitos dos fármacos , Humanos , Hipersensibilidade/patologia , Hipersensibilidade Tardia/imunologia , Hipersensibilidade Tardia/patologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/patologia , Imunoglobulina E/imunologia , Recém-Nascido , Inflamação/imunologia , Inflamação/patologia , Interleucina-13/metabolismo , Interleucina-3/farmacologia , Interleucina-3/fisiologia , Interleucina-4/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Modelos Imunológicos , Fosfatidilinositol 3-Quinases/fisiologia , Fosforilação , Proteína Quinase C/fisiologia , Proteínas Quinases/fisiologia , Processamento de Proteína Pós-Traducional , Receptores de IgE/fisiologia , Transdução de Sinais , Células Tumorais CultivadasRESUMO
The purpose of this study was to describe the clinical features at onset and outcome and the diagnostic approach in subjects with bronchiolitis obliterans-organizing pneumonia (BOOP). Over a 7-year period we observed 78 cases of biopsy-proven bronchiolitis obliterans-organizing pneumonia, in which well documented clinical and radiographic data were available. The final diagnosis of BOOP was validated when patients presented: (i) negative microbiological analysis on BAL fluid; (ii) a well documented improvement either spontaneous, or after steroid treatment or (iii) cases with progressive respiratory failure and increasing radiographic shadows, an open lung biopsy or autopsy that excluded other entities. There were 42 males and 36 females; the mean age was 61+/-12 years (range 12-85 years). Forty-two (54%) patients were current smokers, 25 (32%) had never smoked and 11 (14%) were ex-smokers. The clinical pattern at presentation of BOOP was more frequently similar to classical acute or sub-acute infectious pneumonia. Fever (63%), dyspnoea (58%) and dry cough (53%) were the typical symptoms on admission. A flu-like syndrome preceeding BOOP was observed in 21 cases (27%). Inspiratory crackles (78%) were the most typical finding at physical examination. However, 13% of the patients were asymptomatic and an abnormal chest X-ray film was the reason for seeking medical attention. Radiographically the most frequent pattern of BOOP was a unilateral consolidation (44%) with lower field predominance. A migratory behaviour was present in 22% of the cases. High-resolution computed tomographic (HR-CT) scan when performed, was more sensitive in detecting ground glass infiltrates, sub-pleural or peri-bronchovascular distribution or the presence of nodules or cavitation. Most patients (68%) were classified as having idiopathic BOOP. However, the same clinical-roentgenological pattern was observed in patients after radiotherapy for ductal breast carcinoma (6%), in collagen-vascular diseases (6%), related to drugs (9%), to infections serologically documented (4%), and to graft vs. host disease (4%). Four patients (all of whom had idiopathic BOOP) presented a rapid progressive respiratory failure needing mechanical ventilation. In another two cases respiratory failure appeared after a long period during which patients experienced exertional dyspnoea and low grade fever. BAL profile was characterized by lymphocytosis with a reduction of the CD4/CD8 ratio, associated with a slight increase of neutrophils and eosinophils and scattered mast cells. However in two cases we had an increased CD4/CD8 ratio and in one case the presence of a significant 12% of polyclonal B cells. In a few cases atypical (cytokeratin-positive cells) epithelial cells were detected: these cells were constantly present in the BAL fluid of patients with rapidly progressive respiratory failure. From the diagnostic point of view this series documents that transbronchial lung biopsy (coupled with BAL) can be the first diagnostic step. However, therapy can be started on the basis of BAL data (when a characteristic morphological and phenotypical profile is evident) in cases in which the clinical presentation is suggestive and a biopsy cannot be made. Most patients showed a rapid and good response to steroid therapy. However, three patients died (4%) in spite of steroid therapy (two cases) and steroid and cyclophosphamide therapy (one case). In conclusion, although clinical findings, chest X-ray film and CT Scan findings usually suggest the diagnosis a definite confirmation requires transbronchial lung biopsy and BAL and, less frequently, open lung biopsy.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Pneumonia em Organização Criptogênica/diagnóstico , Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Relação CD4-CD8 , Criança , Tosse/etiologia , Pneumonia em Organização Criptogênica/tratamento farmacológico , Dispneia/etiologia , Feminino , Febre/etiologia , Humanos , Itália , Estudos Longitudinais , Linfocitose/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Catepsinas/genética , Toxocara canis/genética , Sequência de Aminoácidos , Animais , Catepsina K , Catepsina Z , Catepsinas/química , Sequência Consenso , Regulação Enzimológica da Expressão Gênica , Humanos , Larva/enzimologia , Larva/genética , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Toxocara canis/classificação , Toxocara canis/enzimologiaRESUMO
BACKGROUND: Growing evidence indicates that unilateral lung irradiation for breast cancer may "prime" the development of migratory lung infiltrates with histologic features of bronchiolitis obliterans organizing pneumonia. OBJECTIVE: Our purpose was to evaluate the cytologic and immunocytologic features of bronchoalveolar lavage in this condition. METHODS: We analyzed the profile bronchoalveolar lavage cell differentials and lymphocyte subpopulations of 11 women with bronchiolitis obliterans organizing pneumonia syndrome after radiation therapy for breast cancer in comparison to 9 healthy women. RESULTS: The bronchoalveolar lavage analysis demonstrated a significant increase in the percentage of lymphocytes (36.7% +/- 5.4% vs 8.6% +/- 1.1%, P =.0002), neutrophils (3.8% +/- 1.2% vs 0.6% +/- 0.2%, P =.005), eosinophils (2.4% +/- 1% vs 0.3% +/- 0.1%, P =.01), and mast cells (1.4% +/- 0.6% vs 0.1% +/- 0.02%, P =.05) with a significant decrease in the percentage of macrophages (56.1% +/- 6% vs 90.3% +/- 1.4%, P =.0002) in patients with bronchiolitis obliterans organizing pneumonia compared with the control subjects. The percentage of CD3(+) cells was significantly increased in patients with bronchiolitis obliterans organizing pneumonia (93.7% +/- 1.3% vs 70.9% +/- 4%, P =.0004), with a significant decrease in CD4(+) cells (32.7% +/- 4.7% vs 55.4% +/- 2. 6%, P =.002) and a significant increase in CD8(+) cells (61.2% +/- 4. 8% vs 37.5% +/- 2.9%, P =.003) in comparison to control subjects. The CD4/CD8 ratio was significantly reduced in patients with bronchiolitis obliterans organizing pneumonia compared with control subjects (0.6% +/- 0.1% vs 1.5% +/- 0.1%, P =.001). CONCLUSION: These data add to the view that unilateral lung irradiation for breast cancer may "prime" the development of a syndrome quite similar to idiopathic bronchiolitis obliterans organizing pneumonia.
Assuntos
Neoplasias da Mama/radioterapia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Pneumonia em Organização Criptogênica/etiologia , Lesões por Radiação/etiologia , Idoso , Lavagem Broncoalveolar , Pneumonia em Organização Criptogênica/imunologia , Pneumonia em Organização Criptogênica/patologia , Feminino , Humanos , Pulmão/fisiopatologia , Pulmão/efeitos da radiação , Contagem de Linfócitos/efeitos da radiação , Subpopulações de Linfócitos/efeitos da radiação , Pessoa de Meia-Idade , Lesões por Radiação/imunologia , Lesões por Radiação/patologia , Testes de Função RespiratóriaRESUMO
Photodynamic therapy (PDT) is an effective modality that can be used in the treatment of bronchogenic squamous cancer. PDT can be curative in cases of early-stage central type lung cancer and, for this reason, is an alternative to surgery in patients with in situ carcinoma or minimally invasive squamous cell carcinoma. PDT was performed in 26 early bronchogenic cancers in 23 patients, and 16 complete remissions and 10 partial remissions were obtained. It is concluded that photodynamic therapy is effective in the treatment of superficial lung cancer in which complete remission can be expected. The combination of different endoscopic therapeutic modalities and trials comparing endoscopic therapy with surgical resection are anticipated.
Assuntos
Carcinoma Broncogênico/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Fotoquimioterapia , Carcinoma Broncogênico/patologia , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Pulmonares/patologia , Resultado do TratamentoRESUMO
In order to assess the diagnostic yield of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBB) in pulmonary diseases with a ground-glass and/or alveolar pattern on high-resolution computed tomography (HRCT) scan, a prospective study was undertaken. Thirty-six patients (17 males, 19 females), mean age 53 yrs, selected on the basis of the presence of an alveolar and/or ground-glass pattern on chest HRCT scan, were submitted to fibreoptic bronchoscopy. All patients underwent BAL. TBBs were performed in 33 cases. A specific diagnosis was achieved, taking into account data obtained by means of serology, microbiology, cytology and histopathology in appropriate clinical settings. Twelve (33%) patients only had the appearance of a ground-glass opacity, whereas 24 (67%) had associated areas of airspace consolidation. BAL was performed in all cases and gave a definitive diagnosis in 21 (58%). The diagnostic yield of BAL in patients with only ground-glass opacities was no different from that in those patients also showing areas of alveolar consolidation (58 versus 58%). In eight patients (six with ground-glass opacity and two with alveolar consolidation), BAL provided useful but not definitive information. In these patients, a definitive diagnosis was achieved by means of TBB in seven cases and by open lung biopsy in one case. TBB was performed in 33 out of 36 patients and gave positive results in 25 (76%). The diagnostic yield of TBB in patients showing areas of alveolar consolidation was significantly higher than in those with pure ground-glass opacity, i.e. 95% (21 of 22) and 36% (4 of 11) respectively (p < 0.001). BAL and TBB were performed during the same bronchoscopy in 33 patients, and an accurate diagnosis was achieved in 30 (91%). Overall, the diagnostic yield of TBB (76%) and BAL (56%) did not differ significantly in the whole patient group (p = 0.12), or in patients with a ground-glass opacification (58 versus 36%, p = 0.3). However, in patients with areas of alveolar consolidation, the diagnostic sensitivity of TBB (95%) was significantly greater than the diagnostic sensitivity of BAL (54%) (p = 0.03). In conclusion this study shows that high-resolution computed tomography can be helpful in predicting the diagnostic accuracy of bronchological procedures, in particular of bronchoalveolar lavage and transbronchial biopsy, and that alveolar and/or ground-glass are favourable patterns for these diagnostic tools.