RESUMO
PURPOSE: The aim of this study was to evaluate the 5-year recurrence rate of pilonidal sinus disease (PSD) after endoscopic sinusectomy and identify risk factors for recurrence. METHODS: All consecutive patients from September 2011 through December 2017 who underwent endoscopic sinusectomy at seven referral centres for pilonidal sinus treatment were retrospectively analysed from a prospectively maintained database. RESULTS: Out of 290 patients (185 males versus 105 female, with a mean age of 25.5±6.9), 73 presented recurrence at 5-year follow-up with a recurrence rate of 25.2%. The number of pilonidal sinus with pits off the midline (p = 0.001) and the mean (SD) distance from the most lateral orifice to the midline (p = 0.001) were higher in the group of patients with recurrence at 5-year follow-up. Multivariate analysis demonstrated that the position of the pits off the midline (p = 0.001) and the distance of the most lateral orifice from the midline (p = 0.001) were independent risk factors for recurrence at 5-year follow-up. Receiver operating characteristic (ROC) curve analysis showed that the distance of lateral orifice from midline predicted an 82.2% possibility of recurrence at 5-year follow-up and Youden's test identified the best cut-off as 2 cm for this variable. Out of 195 cases with the most lateral orifice less than 2 cm from the midline, 13 presented recurrence at 5-year follow-up with a recurrence rate of 6.7%. Out of 95 cases with the most lateral orifice more than 2 cm from midline, 60 showed recurrence at 5-year follow-up with a recurrence rate of 63.2%. CONCLUSIONS: This data may help guide which disease characteristics predict the optimal use of an endoscopic pilonidal sinus technique.
Assuntos
Seio Pilonidal , Dermatopatias , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Seio Pilonidal/cirurgia , Estudos Retrospectivos , Bases de Dados Factuais , Análise MultivariadaRESUMO
BACKGROUND: Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering. METHODS: A population-based case-control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed. RESULTS: One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32-22.38) and 10.48 (95%CI 4.54-24.2) for 0-5 km and 5-10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors. CONCLUSIONS: In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.
Assuntos
Amianto/efeitos adversos , Exposição Ambiental/efeitos adversos , Mesotelioma Maligno/epidemiologia , Neoplasias Pleurais/epidemiologia , Idoso , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise EspacialRESUMO
Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.
Assuntos
Neoplasias Pulmonares , Mesotelioma , Neoplasias Pleurais , Animais , Humanos , Incidência , Itália/epidemiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Mesotelioma/complicações , Mesotelioma/diagnóstico , Mesotelioma/epidemiologia , Mesotelioma/terapia , Mesotelioma Maligno , Derrame Pleural/etiologia , Neoplasias Pleurais/complicações , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/terapia , Saúde Pública , Fatores de RiscoRESUMO
BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma.
Assuntos
Biomarcadores Tumorais/genética , Códon sem Sentido , Inibidor de Quinase Dependente de Ciclina p18/genética , Mutação em Linhagem Germinativa , Melanoma/genética , Mesotelioma/genética , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p18/análise , Análise Mutacional de DNA , Bases de Dados Factuais , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Hereditariedade , Humanos , Imuno-Histoquímica , Itália , Masculino , Melanoma/química , Melanoma/patologia , Mesotelioma/química , Mesotelioma/patologia , Pessoa de Meia-Idade , Linhagem , Fenótipo , Fatores de Risco , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/análise , Ubiquitina Tiolesterase/análise , Adulto JovemRESUMO
The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up-to-date methodology; 4) Necroscopy should be practiced for validation. Expert referral centres could contribute to the definition of uncertain cases. Health surveillance should aim to all asbestos effects. No diagnostic test is recommended for MM screening. Health surveillance should provide information on risks, medical perspective, and smoking cessation. The economic burden associated to MM was estimated in 250,000 Euro per case.
Assuntos
Neoplasias Pulmonares , Mesotelioma , Doenças Profissionais , Neoplasias Pleurais , Amianto/efeitos adversos , Humanos , Itália , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Mesotelioma/epidemiologia , Mesotelioma/etiologia , Mesotelioma Maligno , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Medicina do Trabalho , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/etiologia , Saúde PúblicaRESUMO
BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer death in women. Early detection is essential to reduce cancer mortality. Studying participation in an organised breast cancer screening program is important in order to evaluate the program effectiveness. Breast screening both enables minimally invasive breast surgery and reduces cause-specific mortality. METHODS: The main objective of this study was to evaluate, through the use of a questionnaire, the influence of socio-economic characteristics (age, education, occupational status, participation in other screening programs etc.) on participation in a mammography screening program organized by the local health units (LHU) of Novara and Verbano-Cusio-Ossola, located in the Italian region of Piedmont. A sample of 500 women was identified. Eligible participants included women aged 50-69 years, resident in the area of the LHUs of Novara and Verbano-Cusio-Ossola who had been invited to participate in the screening program 2006-2007. Twenty six women were excluded, leaving 474 women in the final analysis: 23 women were unable to be contacted due to incorrect contact details and 3 women were unable to complete the questionnaire due to neurodegenerative diseases. A postal questionnaire was sent by post during 2008-2009. Two postal reminders were sent to non-responders, followed by a phone call. One group of women received an additional copy of the questionnaire with the first postal reminder and another group received only the reminder letter. The socio-personal profiles and their influence in women's participation in the screening program were evaluated. RESULTS: Among the responders, 93% of the women (348/374) received a mammogram at least once following LHU invitation for check-up. 74.1% of women got a mammogram at least once using the organized screening program, an additional 17.8% got a mammogram in a private clinic, and the type of prevention was unknown for 8.1% of the women. 25.3% began having mammogram for prevention before the age of 45. CONCLUSIONS: A screening program is a sanitary intervention of secondary prevention and the identification of the attitude towards this kind of prevention is quite complex. Some causes of non-participation in this screening program were the belief that mammogram is not necessary, fear of pain, and presence of family problems. This study obtained a higher response than expected and the data also allowed an assessment of the degree of participation of women in the prevention services, identifying that most of them carried out a mammogram using an organized screening program.
Assuntos
Neoplasias da Mama/diagnóstico , Mamografia/estatística & dados numéricos , Programas de Rastreamento/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Idoso , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Prevenção Secundária/métodos , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The Immuknow assay (IKA; Cylex) is a T-cell immune function assay that evaluates immunoreactivity in immunocompromised patients. The aim of this study was to analyze IKA values in a cohort of kidney transplantation (KT) recipients to investigate correlations between single-time point low IKA values and their trend over time with cytomegalovirus (CMV) or BK virus (BKV) reactivation. METHODS: A total of 118 adult patients receiving deceased-donor KT were enrolled (55.6±11.9 years old; 79 [66.9%] male). IKA CMV and BKV viremia determinations and were performed at months 1, 3, and 6 after surgery. RESULTS: Overall, 272 IKA determinations were performed: IKA values significantly decreased from month 1 (422±184 ng/mL) to month 3 (330±159 ng/mL; P<.001) and from month 3 to month 6 (300±128 ng/mL; P=.030). IKA values did not correlate with renal function or viral reactivation at any time. However, patients with either CMV or BKV viremia had a trend to higher IKA values at month 1 and lower IKA values at month 6, even if the difference did not reach a statistical significance (P=.115). CONCLUSIONS: Our study suggests that presence of low immunologic reactivity (IKA<225 ng/mL) is not associated with an increased risk of CMV and BKV reactivation over the 1st 6 months after KT. However, a trend to a more pronounced drop in IKA values over time was observed in patients with viral reactivation. These preliminary results suggests that drop in IKA values within the 1st post-KT months, unlike single-time point immune function assay, may predict the risk of opportunistic viral infections.
Assuntos
Infecções por Citomegalovirus/imunologia , Testes Imunológicos , Transplante de Rim , Infecções Oportunistas/imunologia , Infecções por Polyomavirus/imunologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/sangue , Infecções Oportunistas/diagnóstico , Infecções por Polyomavirus/sangue , Infecções por Polyomavirus/diagnóstico , Complicações Pós-Operatórias , Viremia/diagnóstico , Ativação ViralRESUMO
BACKGROUND: The risk of malignant mesothelioma (MM) increases proportionally to the cumulative exposure, and to the 3rd or 4th power of time since first exposed, to asbestos. However, little is known about the risk of MM after more than 40â years since first exposure because most epidemiological studies do not have follow-up for sufficient periods of time. METHODS: The data from six cohort studies of exposed workers and two cohorts with residential exposure have been pooled. A nested case control design matched cases and controls on calendar period and age. Conditional logistic regression modelled the relationship between time since first exposure and risk of MM. RESULTS: The combined data consisted of 22,048 people with asbestos exposure (5769 women), 707 cases of pleural MM (165 in women) and 155 cases of peritoneal MM (32 in women). Median time since first exposure for pleural MM cases was 38.4â years (IQR 31.3-45.3). Median duration of exposure for pleural MM cases was 3.75â years (IQR 0.7-18.2). The rate and risk of pleural MM increased until 45â years following first exposure and then appeared to increase at a slower power of time since first exposure. The rate of increase in peritoneal MM over the 10-50â years since first exposure continued to increase. CONCLUSIONS: Exposure to asbestos confers a long-term risk of developing pleural and peritoneal mesothelioma which increases following cessation of exposure. While the rate of increase appears to start to level out after 40-50â years no one survives long enough for the excess risk to disappear.
Assuntos
Asbesto Crocidolita/toxicidade , Asbestos Serpentinas/toxicidade , Exposição por Inalação/efeitos adversos , Mesotelioma/epidemiologia , Exposição Ocupacional/efeitos adversos , Neoplasias Peritoneais/epidemiologia , Neoplasias Pleurais/epidemiologia , Adolescente , Adulto , Austrália/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Mesotelioma/etiologia , Pessoa de Meia-Idade , Neoplasias Peritoneais/etiologia , Neoplasias Pleurais/etiologia , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: To date, no study has reported cause-specific Standardized Mortality Ratios (SMR) for asbestos-cement workers at a manufacturing establishment in Broni (Pavia, Italy). This site is among those specifically targeted by Italian Law for reclamation (SIN - Site of National Interest for remediation). OBJECTIVES: To provide cause-specific SMRs for asbestos-cement workers in the Broni (Pavia, Italy) factory, with particular regard to duration of employment and latency. METHODS: Cause-specific SMRs for asbestos-cement workers (1296 workers hired since 1/1/1950 and with follow-up period 1/1/1970-30/06/2004: 1254 males and 42 females, 545 deaths, 523 males and 22 females) were calculated using the cause-specific mortality rates for the Lombardy Region. Similarly, for pleural and peritoneal mesothelioma and lung cancer among male workers, SMRs by duration of employment and latency were calculated. RESULTS: Significantly increased SMRs were observed among male workers for pleural (SMR 17.99, 95% CI 11.75-26.36) and peritoneal (SMR 10.10, 95% CI 4.05-20.77) mesothelioma and lung cancer (SMR 1.26, 95% CI 1.02-1.55) and among female workers for pleural mesothelioma (SMR 68.90, 95% CI 8.33-248.90) and ovarian cancer (SMR 8.56, 95% CI 1.04-30.91). Only among male workers, was a significant risk trend observed for pleural mesothelioma by duration of employment and for lung cancer by latency. Significantly reduced SMRs were observed, among male workers for all causes of death, cardiovascular and respiratory diseases. CONCLUSIONS: The results of this cohort study showed increased SMRs for pleural and peritoneal mesothelioma and lung cancer among male workers and for pleural mesothelioma and ovarian cancer among female workers. These results are consistent with the literature data.
Assuntos
Amianto/efeitos adversos , Materiais de Construção/efeitos adversos , Mesotelioma/mortalidade , Doenças Profissionais/mortalidade , Adulto , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIM: Electromagnetic navigation bronchoscopy (ENB) was reported to increase diagnostic yield in pulmonary nodules (PNs). The aim of this study was to assess if rapid on site evaluation (ROSE) associated with ENB could improve diagnostic accuracy in PNs after non-diagnostic fluoroscopy-guided bronchoscopy added to ROSE. METHODS: Forty patients with PNs suspected for lung cancer underwent to ENB + ROSE after non-diagnostic Fluoroscopy-guided Bronchoscopy + ROSE. Each lesion was studied with reference to size, location, presence of bronchus sign on CT. All lesions were sampled by needle and brush; if negative, by forceps and bronchoalveolar lavage. All patients were followed-up until achievement of definitive diagnosis. RESULTS: Twenty-nine out of 41 lesions (70.7%) had a definitive diagnosis. ENB sensitivity for malignancy was 76.5%, with higher rate in presence of bronchus sign on CT (86.2%) and in case of lesions located in the upper and middle lobes (87.5%). CONCLUSION: ENB is a useful tool in the evaluation of PNs. High diagnostic accuracy may be related to sampling (transbronchial needle aspiration), ROSE, location and presence of bronchus sign.
Assuntos
Broncoscopia/métodos , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/cirurgia , Idoso , Fenômenos Eletromagnéticos , Feminino , Fluoroscopia , Humanos , Masculino , Estudos Retrospectivos , Cirurgia Assistida por Computador , Fatores de TempoRESUMO
OBJECTIVES: Leukaemia is the most common cancer in children, but its aetiology is still poorly understood. We tested the hypothesis that traffic-related air pollution is associated with paediatric leukaemia because of chronic exposure to several potential carcinogens. METHODS: The Italian SETIL study (Study on the aetiology of lymphohematopoietic malignancies in children) was conducted in 14 Italian regions. All incident cases of leukaemia in children aged ≤10 years from these regions (period 1998-2001) were eligible for enrolment. Two controls per case, matched on birth date, gender and region of residence were randomly selected from the local population registries. Exposure assessment at birth residence included traffic indicators (distance to main roads and length of main roads within 100 m) and estimates of pollutants concentrations (particulate matter -PM2.5 and PM10- and gases -NO2 and O3-) from national dispersion model and land use regression models. The association between the exposure variables and leukaemia was assessed by logistic regression analyses. RESULTS: Participation rates were 91.4% among cases and 69.2% in controls; 620 cases (544 acute lymphocytic and 76 acute non-lymphocytic leukaemia) and 957 controls were included. Overall, when considering the residence at birth, 35.6% of cases and 42.4% of controls lived along busy roads, and the mean annual PM10 levels were 33.3 (SD=6.3) and 33.4 µg/m(3) (SD=6.5), respectively. No association was found, and all ORs, independent of the method of assessment and the exposure windows, were close to the null value. CONCLUSIONS: Using various exposure assessment strategies, air pollution appears not to affect the incidence of childhood leukaemia.
Assuntos
Poluição do Ar/efeitos adversos , Carcinógenos Ambientais/toxicidade , Leucemia/etiologia , Emissões de Veículos/toxicidade , Automóveis/estatística & dados numéricos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Itália/epidemiologia , Leucemia/epidemiologia , Masculino , Exposição Ocupacional/efeitos adversos , Material Particulado/toxicidade , Características de Residência/estatística & dados numéricosRESUMO
The aim of this study was twofold. The first aim was to estimate the diagnostic reliability of urinary cytology for detection and management of urothelial neoplasms by using a specific preserving fluid for sample collection, and the liquid-based thin layer method for specimen preparation, the estimate was based on the correlation between the cytological findings of 10,000 non-hospitalized patients, and their histological diagnoses. A second aim was to compare the reliability of two instruments for thin-layer preparation, i.e., TP2000, TP3000, capable of processing the specimens at very different rates. The preservation of cell structure is ameliorated by the procedure of sample collection and treatment here described. This allows a more accurate reading of LBC slides as shown by: (a) the significant concordance between cytological and histological diagnosis (92%); (b) the significant number of low-grade urothelial carcinomas (20.5%) revealed by urinary cytology and validated by histologic diagnosis; (c) the low rate (8%) of misjudgement of cytological diagnosis reached in this study. The quality of performances of the two instruments tested for thin-layer preparation, i.e., TP2000 and TP3000, is statistically comparable. We recommend the procedure that makes use of preserving fluid for sample collection (cytolyt™) and treatment (preservcyt ™) as here described. We also recommend the use of thin-layer method for specimen preparation since it allows a more uniform distribution of the cells on the support with reduction of overlapping phenomena. Finally, economic considerations suggest the preferential use of Thin Prep 3000.
Assuntos
Neoplasias Uretrais/diagnóstico , Urinálise/métodos , Urina/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Citodiagnóstico/instrumentação , Citodiagnóstico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Uretrais/patologia , Urinálise/instrumentação , Coleta de Urina/métodosRESUMO
PURPOSE: The aim of this study was to evaluate the effect of different clinical covariates on tacrolimus dose requirements in adult kidney transplant patients with a specific focus on drug interactions. PATIENTS: Tacrolimus dosing requirement, normalized by drug levels and expressed as the concentration/dose (C/D) ratio as a surrogate index of tacrolimus bioavailability, was employed to identify four categories of tacrolimus dosing requirement, namely, very high, high, small, and very-small, in very fast, fast, slow, and very slow metabolizers, respectively. Steroid weight-based doses were analyzed instead of fixed doses, and genetic analysis of cytochrome P450 (CYP) 3A5*1/*3 and multi-drug resistance 1 (MDR1) C3435T and C1236T polymorphisms were performed RESULTS: Multivariate analysis on 450 adult transplant patients identified six risk factors for being slow metabolizers and therefore requiring small tacrolimus doses: male sex (OR 1.615, p = 0.020); age >60 years (OR 2.456, p = 0.0005); body mass index ≥ 25 (OR 1.546, p = 0.046), hepatitis C virus positivity (OR 2.800, p = 0.0004); low steroid dose <0.06 mg/kg (OR 3.101, p < 0.0001). Patients with a small tacrolimus requirement were at increased risk for multiple infections (OR 1.533, p = 0.0008) and higher systolic blood pressure (OR 1.385, p = 0.022) and showed a significant association with the CYP3A5*3/*3 genotype adjusted by MDR1 polymorphisms C3435T and C1236T (OR 8.104, p = 0.0001). CONCLUSIONS: Our results demonstrate the importance of the interaction among genetic and clinical factors in conditioning tacrolimus disposition, with corticosteroid weight-based dose being the only modifiable risk factor for tacrolimus requirement. As the tacrolimus dosing requirement increases with increasing tacrolimus clearance through concomitant steroid use, undesirable changes in tacrolimus levels may occur when steroid doses are tapered, predominantly in slow metabolizers. This often neglected drug interaction has to be monitored to optimize tacrolimus exposure in kidney transplant patients.
Assuntos
Índice de Massa Corporal , Glucocorticoides/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim/imunologia , Polimorfismo Genético , Tacrolimo/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Fatores Etários , Disponibilidade Biológica , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Interações Medicamentosas , Monitoramento de Medicamentos , Feminino , Estudos de Associação Genética , Glucocorticoides/uso terapêutico , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Caracteres Sexuais , Tacrolimo/sangue , Tacrolimo/farmacocinética , Tacrolimo/uso terapêuticoRESUMO
Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.
Assuntos
Proteínas de Ligação a DNA/genética , Endonucleases/genética , Mesotelioma/genética , Polimorfismo de Nucleotídeo Único , Amianto/toxicidade , Sequência de Bases , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
BACKGROUND: Chrysotile from the mine in Balangero, Italy is considered to be free of tremolite. In a cohort study of miners and millers only two pleural cancers were reported, a finding considered to indicate that chrysotile has a low potency for inducing mesothelioma. However, follow-up ended in 1987 and white-collar workers and the employees of subcontractors were not studied. METHODS: To complete the case ascertainment, the study searched the Registry of Malignant Mesotheliomas of Piedmont for records of cases of pleural mesothelioma among the following: mine employees; employees of subcontractors or of other firms transporting or refining Balangero asbestos, asbestos ore or mine tailings; individuals exposed to air pollution from the mine or living with mine employees; and individuals exposed to mine tailings from Balangero. RESULTS: The study identified four new cases of pleural mesothelioma among blue-collar workers in the mine, in addition to the two reported in the cohort study. Thus, six mesotheliomas occurred, compared to the 1.5 expected (p<0.01). The study also identified three mesothelioma cases among white-collar employees at the mine, five in workers in the mine hired by subcontracting firms, and three among workers processing Balangero chrysotile outside the mine. Finally, 10 additional cases due to non-occupational exposure or exposure to re-used mine tailings were identified. CONCLUSIONS: The cluster of 14 mesothelioma cases among workers who were active in the mine and 13 among other people exposed to Balangero chrysotile provides further evidence that tremolite-free chrysotile is carcinogenic.
Assuntos
Asbestos Serpentinas/efeitos adversos , Mesotelioma/etiologia , Doenças Profissionais/etiologia , Neoplasias Pleurais/etiologia , Idoso , Humanos , Itália/epidemiologia , Masculino , Mesotelioma/epidemiologia , Pessoa de Meia-Idade , Mineração , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Neoplasias Pleurais/epidemiologiaRESUMO
PURPOSE: The aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study. METHODS: Individual data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943-2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed. RESULTS: We observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99) for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). CONCLUSION: This population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour.
Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
OBJECTIVES: We aimed to study mortality for asbestos related diseases and the incidence of mesothelioma in a cohort of Italian asbestos cement workers after cessation of asbestos exposure. METHODS: The Eternit factory operated from 1907 to 1986. The cohort included 3434 subjects active in 1950 or hired in 1950-86, ascertained from company records, without selections. Local reference rates were used for both mortality and mesothelioma incidence. RESULTS: Mortality was increased in both sexes for all causes (overall 1809 observed (obs) vs 1312.3 expected (exp); p<0.01), pleural (135 obs vs 3.6 exp; p<0.01) and peritoneal (52 vs 1.9; p<0.01) malignancies and lung cancer (249 vs 103.1; p<0.01). In women, ovarian (9 vs 4.0; p<0.05) and uterine (15 vs 5.8; p<0.01) malignancies were also in excess. No statistically significant increase was found for laryngeal cancer (16 obs vs 12.2 exp). In Poisson regression analyses, the RR of death from pleural neoplasm linearly increased with duration of exposure, while it showed a curvilinear increase with latency and time since cessation of exposure. RR for peritoneal neoplasm continued to increase by latency, duration and time since cessation of exposure. RR for lung cancer showed a reduction after 15 years since cessation of exposure and levelled off after 40 years of latency. CONCLUSION: This study of a cohort of asbestos exposed workers with very long follow-up confirmed the reduction in risk of death from lung cancer after the end of exposure. It also suggested a reduction in risk for pleural mesothelioma with over 40 years of latency, while risk for peritoneal mesothelioma showed a continuing increase.