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AIM: To evaluate the Prostate Imaging Reporting and Data System, version 2.1 (PIRADS V2.1) criteria for seminal vesicle invasion (SVI) and examine whether the timing of last ejaculation influences the detection of SVI. MATERIALS AND METHODS: The study population consisted of 68 patients (34 with SVI, 34 without SVI, matching groups by age and prostate volume) who underwent PIRADS V2.1-compliant multiparametric magnetic resonance imaging (MRI; 34 at 1.5 T, 34 at 3 T). Before the examination, the time of last ejaculation (38/68 ≤ 5 days, 30/68 > 5 days) was collected via a questionnaire. The five PIRADS V2.1 criteria for SVI with subsequent overall assessment were evaluated retrospectively by two independent examiners (examiner 1 with >10 years of experience, examiner 2 with 6 months of experience) in a single-blinded fashion for all patients using a questionnaire and a six-point scale (0 = no, 1 = very likely not, 2 = probably not, 3 = possible, 4 = probable, 5 = certain). RESULTS: E1 achieved high specificity (100%) and positive predictive value (PPV; 100%) in the overall assessment, independent of the time of last ejaculation (sensitivity = 76.5%, negative predictive value [NPV] = 81%). The area under the curve (AUC) value was 0.882; for E2, it was 0.765. At ≤5 days, the AUC values of E1 and E2 differed significantly (0.867 versus 0.681, p=0.016), as did the diffusion restriction criterion (0.833 versus 0.681, p=0.028). E1 showed high AUC values independent of time. E2 had better values for all criteria at >5 days than at ≤5 days. There were no significant differences between the examiners in all observations at >5 days. CONCLUSION: The PIRADS V2.1 criteria are well suited for an experienced examiner to detect SVI independent of time point. An inexperienced examiner will benefit from patients being abstinent >5 days prior to MRI.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Glândulas Seminais/diagnóstico por imagem , Estudos Retrospectivos , Ejaculação , Neoplasias da Próstata/patologia , Invasividade Neoplásica/patologia , Imageamento por Ressonância Magnética/métodos , Estadiamento de NeoplasiasRESUMO
Several N-vinyl compounds are produced in high volumes and are widely employed in the production of copolymers and polymers used in chemical, pharmaceutical, cosmetic and food industry. Hence, information on their genotoxicity and carcinogenicity is requisite. This review presents hitherto available information on the carcinogenicity and genotoxicity of N-vinyl compounds as well as their metabolism potentially generating genotoxic and carcinogenic derivatives. The genotoxicity and carcinogenicity of the investigated N-vinyl compounds vary widely from no observed carcinogenicity tested in lifetime bioassays in two rodent species (up to very high doses) to carcinogenicity in rats at very low doses in the absence of apparent genotoxicity. Despite of the presence of the vinyl group potentially metabolized to an epoxide followed by covalent binding to DNA, genotoxicity was observed for only one of the considered N-vinyl compounds, N-vinyl carbazole. Carcinogenicity was investigated only for two, of which one, N-vinyl pyrrolidone was carcinogenic (but not genotoxic) and ranitidine was neither carcinogenic nor genotoxic. As far as investigated, neither a metabolically formed epoxide nor a therefrom derived diol has been reported for any of the considered N-vinyl compounds. It is concluded that the information collected in this review will further the understanding of the carcinogenic potentials of N-vinyl compounds and may eventually allow approaching their prediction and prevention. A suggestion how to prevent genotoxicity in designing of N-vinyl compounds is presented. However, the available information is scarce and further research especially on the metabolism of N-vinyl compounds is highly desirable.
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Carcinógenos/toxicidade , Dano ao DNA/efeitos dos fármacos , Compostos de Vinila/toxicidade , Animais , Testes de Carcinogenicidade , Carcinógenos/química , Humanos , Camundongos , Testes de Mutagenicidade , Ratos , Compostos de Vinila/químicaRESUMO
Partial nephrectomy (PN) for small renal masses is common, but outcomes are not reported in a standard manner. Traditionally, parameters such as 90-day mortality, blood loss, transfusion rates, length of stay, nephrometry scoring and complications are published but their collective impact on warm ischemia time (WIT) and post-surgery GFR is rarely determined. Thus, our aim was to assess if "Trifecta" and "Pentafecta" outcomes could be used as useful surgical outcome markers. A prospective database of 252 Robotic-Assisted PN (RAPN) cases (2008-2019) was analysed. "Pentafecta" was defined as achievement of "Trifecta" (negative surgical margin, no postoperative complications and WIT of < 25 min) plus over 90% estimated GFR preservation and no CKD stage upgrading at 1 year. Binary logistic regression analysis was conducted to predict factors which may prevent achieving a Trifecta/Pentafecta. Median tumour size was 3 cm and mean WIT was 15 min. Positive surgical margins (PSM) occurred in 2 cases. Overall, the intra-operative complication rate was 7%. One recurrence conferred 5-year cancer-free survival of 97%. Trifecta outcome was achieved in 169 (67%) and Pentafecta in 141 (56%) of cases. At logistic regression analysis, intraoperative blood loss was the only factor to affect Trifecta achievement (p = 0.018). Advanced patient age negatively impacted Pentafecta achievement (p = 0.010). The Trifecta and Pentafecta outcomes are easily applicable to PN data, and offer an internationally comparable PN outcome, quality measure. We recommend applying this standardization to national data collection to improve the quality of reporting and ease of interpretation of surgeon/centres' outcomes.
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Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia , Nefrectomia , Padrões de Referência , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
Acute pancreatitis is a prevalent disease, with variable clinical course: several patients recover quickly and uneventfully, while others require treatment in critical care units with long hospital stay and even with a considerable mortality. The patient's symptoms, laboratory tests and radiological images allow diagnosis without major difficulties. However, early identification of more severe cases can be difficult, and it determines the adequate selection of the hospitalization unit and the quick initiation of the appropriate therapy. In this paper we give some practical treatment guidelines for the everyday clinical practice: immediate severity stratification, fluid replacement and pain control. Early enteral nutrition, monitorization of severe cases in critical care units, adequate therapeutic but no prophylactic use of antibiotics assures the best treatment results. (AU)
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/terapia , Pancreatite/classificação , Pancreatite/complicaçõesRESUMO
A diversity of T helper (Th) subsets (Th1, Th2, Th17) has been identified in the human tumor microenvironment. In breast cancer, the role of Th subsets remains controversial, and a systematic study integrating Th subset diversity, T cell inflammation, breast cancer molecular subtypes, and patient prognosis, is lacking. In primary untreated breast cancer samples, we analyzed 19 Th cytokines at the protein level. Eight were T cell-specific, and subsequently measured in 106 prospectively-collected untreated samples. The dominant Th cytokines across all breast cancer samples were IFN-γ and IL-2. Th2 cytokines (IL-4, IL-5, IL-13) were expressed at low levels and not associated with any breast cancer subtype. Th17 cytokines (IL-17A and IL-17F) were up-regulated in triple negative breast cancer (TNBC), specifically in T cell non-inflamed tumors. In order to get insight into prognosis, we exploited the METABRIC transcriptomic dataset. We derived Th1, Th2, and Th17 metagenes based on manually curated Th signatures, and found that a high Th17 metagene was of good prognosis in T cell non-inflamed TNBC. Multivariate Cox modeling selected the Nottingham Prognostic Index (NPI), Th2 and Th17 metagenes as additive predictors of breast cancer-specific survival, which defined novel and highly distinct prognostic groups within TNBC. Our results reveal that Th17 is a novel prognostic composite biomarker in T cell non-inflamed TNBC. Integrating immune cell and tumor molecular diversity is an efficient strategy for prognostic stratification of cancer patients.
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BACKGROUND: As there are limited data about the clinical practice of catheter ablation in asymptomatic children and adolescents with ventricular preexcitation on ECG, we performed the multicenter "CASPED" (Catheter ablation in ASymptomatic PEDiatric patients with Ventricular Preexcitation) study. METHODS AND RESULTS: In 182 consecutive children and adolescents aged between 8 and 18 years (mean age 12.9 ± 2.6 years; 65% male) with asymptomatic ventricular preexcitation, a total of 196 accessory pathways (APs) were targeted. APs were right sided (62%) or left sided (38%). The most common right-sided AP location was the posteroseptal region (38%). Ablation was performed using radiofrequency (RF) energy (93%), cryoablation (4%) or both (3%). Mean procedure time was 137.6 ± 62.0 min with a mean fluoroscopy time of 15.6 ± 13.8 min. A 3D mapping or catheter localization system was used in 32% of patients. Catheter ablation was acutely successful in 166/182 patients (91.2%). Mortality was 0% and there were no major periprocedural complications. AP recurrence was observed in 14/166 patients (8.4%) during a mean follow-up time of 19.7 ± 8.5 months. A second ablation attempt was performed in 20 patients and was successful in 16/20 patients (80%). Overall, long-term success rate was 92.3%. CONCLUSION: In this retrospective multicenter study, the outcome of catheter ablation for asymptomatic preexcitation in children and adolescents irrespective of antegrade AP conduction properties is summarized. The complication rate was low and success rate was high, the latter mainly depending on pathway location. The promising results of the study may have future impact on the ongoing risk-benefit discussion regarding catheter ablation in the setting of asymptomatic preexcitation in children and adolescents.
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Feixe Acessório Atrioventricular , Ablação por Cateter , Criocirurgia , Síndrome de Wolff-Parkinson-White/cirurgia , Potenciais de Ação , Adolescente , Fatores Etários , Doenças Assintomáticas , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Criança , Criocirurgia/efeitos adversos , Criocirurgia/mortalidade , Feminino , Alemanha , Frequência Cardíaca , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , Suíça , Fatores de Tempo , Resultado do Tratamento , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/mortalidade , Síndrome de Wolff-Parkinson-White/fisiopatologiaRESUMO
Hepatopancreaticobiliary tumours are often diagnosed at an advanced disease stage, in which encasement or invasion of local biliary or vascular structures has already occurred. Irreversible electroporation (IRE) is an image-guided tumour ablation technique that induces cell death by exposing the tumour to high-voltage electrical pulses. The cellular membrane is disrupted, while sparing the extracellular matrix of critical tubular structures. The preservation of tissue integrity makes IRE an attractive treatment option for tumours in the vicinity of vital structures such as splanchnic blood vessels and major bile ducts. This article reviews current data and discusses future trends of IRE for hepatopancreaticobiliary tumours.
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Técnicas de Ablação/métodos , Eletroporação/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Pancreáticas/cirurgia , Humanos , Fígado/cirurgia , Pâncreas/cirurgiaRESUMO
BACKGROUND: In 2015, the German Federal Ministry of Education and Research initiated a large data integration and data sharing research initiative to improve the reuse of data from patient care and translational research. The Observational Medical Outcomes Partnership (OMOP) common data model and the Observational Health Data Sciences and Informatics (OHDSI) tools could be used as a core element in this initiative for harmonizing the terminologies used as well as facilitating the federation of research analyses across institutions. OBJECTIVE: To realize an OMOP/OHDSI-based pilot implementation within a consortium of eight German university hospitals, evaluate the applicability to support data harmonization and sharing among them, and identify potential enhancement requirements. METHODS: The vocabularies and terminological mapping required for importing the fact data were prepared, and the process for importing the data from the source files was designed. For eight German university hospitals, a virtual machine preconfigured with the OMOP database and the OHDSI tools as well as the jobs to import the data and conduct the analysis was provided. Last, a federated/distributed query to test the approach was executed. RESULTS: While the mapping of ICD-10 German Modification succeeded with a rate of 98.8% of all terms for diagnoses, the procedures could not be mapped and hence an extension to the OMOP standard terminologies had to be made.Overall, the data of 3 million inpatients with approximately 26 million conditions, 21 million procedures, and 23 million observations have been imported.A federated query to identify a cohort of colorectal cancer patients was successfully executed and yielded 16,701 patient cases visualized in a Sunburst plot. CONCLUSION: OMOP/OHDSI is a viable open source solution for data integration in a German research consortium. Once the terminology problems can be solved, researchers can build on an active community for further development.
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Comportamento Cooperativo , Implementação de Plano de Saúde , Hospitais Universitários , Avaliação de Resultados em Cuidados de Saúde , Alemanha , Humanos , Inquéritos e Questionários , VocabulárioRESUMO
BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes. RESULTS: A median of 2 (range: 0-10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis. CONCLUSION: These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.
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Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Amplificação de Genes , Perfilação da Expressão Gênica/métodos , Neoplasias de Cabeça e Pescoço/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Transcriptoma , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Distribuição de Qui-Quadrado , Ciclina D1/genética , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p18/genética , Variações do Número de Cópias de DNA , Feminino , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Tempo , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética , Adulto JovemRESUMO
Background: Atrophic gastritis (AG) and intestinal metaplasia (IM) are stages that appear in the process of gastric carcinogenesis. Their presence requires programmed endoscopic vigilance. Objectives: To determine the frequency of AG and IM in gastric biopsies (GB) taken according to Sydney Protocol and to correlate them with endoscopic findings. Methods: Retrospective descriptive analysis of 233 upper gastrointestinal endoscopies with GB per Sydney Protocol. OLGA (Operative Link for Gastritis Assessment) and OLGIM (Operative Link for Gastric Intestinal Metaplasia Assessment) scores were calculated based on the GB description. Endoscopic findings were analyzed for atypical findings and compared to the GB report. Statistic analysis for Kappa and ANOVA was performed via Stata 12. Results: Mean age of patients was 58 ± 12 years. 69% were women. The frequency of AG and IM was 44% and 33% in the antrum, 31% and 20% in the angular incisure and 14% and 9% in the body, respectively. AG and IM were more frequent in the antrum (p < 0.05). AG and IM were more severe in the angular incisure and body (p < 0.05). We were unable to calculate OLGA and OLGIM in 6% and 9% of cases, respectively, due to absence of severity description in GB. 53% were OLGA 0, 42% OLGA I-II and 5% OLGA III-IV. 70% were OLGIM 0, 25% OLGIM I-II and 5% OLGIM III-IV. Agreement between endoscopic and histological findings was best for IM in the antrum (75.5%, Kappa 0.4). Sensitivity and specificity of endoscopic findings were 39% and 70% for AG, and 30% and 85% for IM, respectively. Conclusion: AG and IM are frequent findings in our patients. Due to the low endoscopic sensitivity for AG and IM, we suggest a systematic GB sampling using Sydney Protocol in patients over 40 years old.
Introducción: La gastritis crónica atrófica (GCA) y la metaplasia intestinal (MI) son etapas en el proceso de carcinogénesis gástrica, su presencia requiere control endoscópico programado. Objetivos: Determinar la frecuencia de GCA y MI en biopsias gástricas (BG) por protocolo de Sydney y relacionarlas con el hallazgo endoscópico. Métodos: Estudio descriptivo mediante revisión de 233 endoscopias digestivas altas con BG por Protocolo Sydney. Se graduó puntaje OLGA (Operative Link for Gastritis Assessment) y OLGIM (Operative Link for Gastric Intestinal Metaplasia Assessment) según la descripción de la BG. Se definió el hallazgo endoscópico según su informe y se comparó con BG como patrón de referencia. Estadística: Stata 12 para Kappa y ANOVA. Resultados: Edad promedio 58 ± 12 años, 69% mujeres. La frecuencia de GCA y MI en antro fue de 44 y 33%, en ángulo 31 y 20% y en cuerpo 14 y 9%, respectivamente. Hubo mayor frecuencia de GCA y MI en antro (p < 0,05). La graduación de GCA y MI fue mayor en ángulo y cuerpo (p < 0,05). No se obtuvo OLGA en 6% y OLGIM en 9% por ausencia de graduación. La frecuencia de OLGA 0 fue de 53%, OLGA I-II 42%, OLGA III-IV 5%, OLGIM O 70%, OLGIM I-II 25% y OLGIM III-IV 5%. La mejor correlación se observó entre la MI antral endoscópica con la histológica (75,5%, Kappa 0,4). La sensibilidad y especificidad endoscópica fue de 39 y 70% para GCA y 30 y 85% para MI. Conclusión: GCA y MI son hallazgos frecuentes en nuestros pacientes. Por la baja sensibilidad endoscópica en la identificación de GCA y MI sugerimos la toma sistemática de BG por protocolo de Sydney en pacientes mayores de 40 años.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/epidemiologia , Metaplasia/diagnóstico , Metaplasia/epidemiologia , Lesões Pré-Cancerosas/patologia , Biópsia/métodos , Chile/epidemiologia , Protocolos Clínicos , Programas de Rastreamento/métodos , Epidemiologia Descritiva , Prevalência , Estudos Retrospectivos , Análise de Variância , Endoscopia Gastrointestinal , Sensibilidade e Especificidade , Mucosa Gástrica/patologia , Gastrite Atrófica/patologia , Metaplasia/patologiaRESUMO
Pancreas divisum (PD) is the most common congenital anatomical variant of the pancreas. Its etiological implication in recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) has been recurrently questioned. Normal anatomy and variants: 80-90% of the population has normal anatomy, with excretion of exocrine pancreatic secretion to the duodenum by the major papilla. Three anatomical variants of PD have been described: classic PD with visible ventral duct, but total absence of fusion; PD with absence of ventral duct; and incomplete PD, with a rudimentary connection between the ventral and dorsal ducts. Clinical implication: This anatomical variant is symptomatic in less than 5% of the carriers, being associated to higher prevalence in patients with RAP However, the relationship between PD and RAP is considered probable, only in cases of association with mutation of the CFTR gene. Obstructive CP can develop in the segment drained by the dorsal duct. Diagnosis: Magnetic resonance cholangiopancreatography (MRCP) is the most sensitive diagnostic method. Other non-invasive diagnostic methods are endosonography and computed tomography (CT), the latter with lower performance. Treatment: The current trend in acute pancreatitis (AP) where PD is assumed as an etiological factor, is endoscopic resolution, with papillotomy with or without a pancreatic stent.
El páncreas divisum (PD) es la variante anatómica congénita más frecuente del páncreas. Su implicancia etiológica en pancreatitis aguda recurrente (PAR) y pancreatitis crónica (PC) ha sido frecuentemente cuestionada. Anatomía normal y variantes: 80-90% de la población presenta anatomía normal, con salida de secreción pancreática exocrina al duodeno por la papila mayor. Se han descrito 3 variantes anatómicas: PD clásico con conducto ventral visible, pero ausencia total de fusión; PD con ausencia de conducto ventral; y PD incompleto, con conexión rudimentaria entre los conductos ventral y dorsal. Implicancia clínica: Esta variante anatómica da síntomas en menos de 5% de los portadores, asociándose a mayor prevalencia en pacientes con PAR. Sin embargo, se considera probable la relación entre PD y PAR, solo en casos de asociación con mutación del gen CFTR. Pancreatitis crónica (PC) obstructiva se puede desarrollar en el segmento drenado por el conducto dorsal. Diagnóstico: La colangiopancreatografía por resonancia magnética (CPRM) es el método diagnóstico más sensible. Otros métodos diagnósticos no invasivos son la endosonografía y tomografía computada (TC), este último de menor rendimiento. Tratamiento: La tendencia actual en PA donde se asume PD como factor etiológico, es la resolución endoscópica, con papilotomía con o sin stent.
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Humanos , Pâncreas/anormalidades , Pancreatopatias/fisiopatologia , Pancreatite/fisiopatologia , Pancreatopatias/cirurgia , Pancreatopatias/diagnóstico , Pancreatite/cirurgia , Pancreatite/diagnóstico , Recidiva , Doença Aguda , Colangiopancreatografia por Ressonância Magnética , Variação AnatômicaRESUMO
Essentials Tumor cells circulating in blood (CTC) may favor thrombotic events in cancer patients. We assessed the impact of CTC on the risk of thrombosis in metastatic breast cancer. Baseline CTC detection was the only independent factor associated with the risk of thrombosis. CTC detection under therapy may be the hidden link between tumor progression & thrombosis. SUMMARY: Background Circulating tumor cell (CTC) count is a major prognostic factor in metastatic breast cancer (MBC) and has been reported to be associated with thrombosis in short-term studies on MBC patients. Objective To assess whether CTC detection (CellSearch® ) before first-line chemotherapy impacts the risk of thrombosis throughout the course of MBC. Patients/Methods Among patients included before first-line chemotherapy for MBC in the prospective IC2006-04 CTC detection study (NCT00898014), the electronic medical files of those patients treated at Institut Curie (Paris, France) were searched in silico and manually checked for incident venous or arterial thrombotic events (TE) in the course of MBC. Univariate and multivariate analyses were performed using Cox and Fine-Gray models, adjusted for age and Khorana score. Results/Conclusions With a median follow-up of 64 months (25-81 months), among the 142 patients included, 34 (24%) experienced a TE (incidence rate, 8 TE/100 patient-years). The TE incidence rate was 13 TE/100 patient-years for the 80 patients with ≥ 1 CTC/7.5 mL of blood before initiating first-line chemotherapy, vs. only 4 TE/100 patient-years for the 62 CTC-negative patients. Fine-Gray multivariate analysis (with death as competing event) included age, Khorana score and baseline lactate dehydrogenase and CTC levels: detectable CTC was the only factor significantly associated with an increased risk of TE (sub-distribution hazard ratio [SHR] for patients with [1-4] CTC = 3.1, 95% CI [1.1; 8.6], SHR for patients with ≥ 5 CTC = 1.4, 95% CI [0.5; 4.6]). This study shows that CTC detection before starting first-line chemotherapy is an independent risk factor for TE in MBC patients.
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Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Células Neoplásicas Circulantes/patologia , Trombose/sangue , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/secundário , Contagem de Células , Registros Eletrônicos de Saúde , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Paris/epidemiologia , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Trombose/epidemiologia , Fatores de TempoRESUMO
Deep hypothermia therapy (HT) is a standard method for neuroprotection during complex pediatric cardiac surgery involving extracorporeal circulation and deep hypothermic cardiac arrest. The procedure, however, can provoke systemic inflammatory response syndrome (SIRS), one of the most severe side effects associated with pediatric cardiac surgery. To date, the cellular inflammatory mechanisms induced by deep HT remain to be elucidated. Therefore, we investigated the effects of deep HT (17°C) and rewarming on the inflammatory response in lipopolysaccharide (LPS) stimulated BV-2 murine microglia. Additionally, we also investigated the application of Stattic, a signal transducer and activator of transcription 3 (STAT3) activation inhibitor, as an alternative to physical cooling to attenuate the LPS-induced inflammatory response. Deep HT had no cytotoxic effect but attenuated microglia migration. IκBα degradation was delayed by deep HT resulting in the attenuation of pNF-κB p65 migration into the nucleus and significant decreases in pro-inflammatory IL-6, TNF-α, and MCP-1 expressions and secretions, as well as decreased anti-inflammatory IL-10 and SOCS3 expressions. Additionally, pStat3 was significantly down regulated under deep hypothermic conditions, also corresponding with the significant reduction in IL-6 and TNF-α expressions. Similar to the effects of HT, the application of Stattic under normothermic conditions resulted in significantly reduced IL-6 and TNF-α expressions. Moreover, attenuation of the inflammatory response resulted in decreased apoptosis in a direct co-culture of microglia and neurons. HT reduces the inflammatory response in LPS-stimulated BV-2 microglial cells, alluding to a possible mechanism of therapeutic hypothermia-induced neuroprotection. In the future, attenuating the phospho-STAT3 pathway may lead to the development of a neuroprotectant with greater clinical efficacy.
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Hipotermia Induzida/métodos , Lipopolissacarídeos/toxicidade , Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Anexina A5/metabolismo , Linhagem Celular Transformada , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Técnicas de Cocultura , Óxidos S-Cíclicos/farmacologia , Relação Dose-Resposta a Droga , Interleucina-10/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Fatores de TempoRESUMO
BACKGROUND: Rating the response of melanoma to immune checkpoint blockade (ICB) by conventional CT proves to be difficult, since response patterns and kinetics differ from the classical responses seen with other therapies. Hence, immune-related response criteria were developed. However, they are mainly based on the alteration of the diameter of lesions over time but do not include metabolic activity. OBJECTIVE: The aim of this study was to search for additional criteria to improve the interpretation of the radiologic images of patients with metastatic melanoma after ICB. MATERIALS AND METHODS: We retrospectively analysed 7 patients with metastatic melanoma over a period of 13-41 months after treatment with ICB using contrast enhanced CT scans from the neck region to the lower abdomen and compared the results in the follow ups with 18F-FDG PET/CT. RESULTS: Metastatic lesions in 5 of 7 patients rated as stable disease (SD) in CT staging showed no metabolic activity in 18F-FDG PET/CT. The size of these lesions did not increase or show metabolic activity in the further follow-up, even after discontinuation of ICB. In contrast, tumor lesions in the other 2 patients rated as SD in CT staging showed metabolic activity in 18F-FDG PET/CT. These tumor lesions expanded significantly in the further course of the disease. CONCLUSION: In addition to the size of a tumor lesion, its metabolic activity adds important information regarding treatment response. Thus, we propose that the metabolic activity assessed with 18F-FDG-PET/CT should be included in the immune response criteria. No FDG uptake in a lesion should be rated as inactive tumor rather than SD and further treatment may not be required.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunoterapia/normas , Ipilimumab/uso terapêutico , Melanoma/terapia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Feminino , Fluordesoxiglucose F18 , Humanos , Imunoterapia/efeitos adversos , Ipilimumab/efeitos adversos , Ipilimumab/farmacologia , Masculino , Melanoma/diagnóstico por imagem , Melanoma/patologia , Melanoma/secundário , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
The term Choledocholithiasis refers to the presence of biliary stones in the extrahepatic bile ducts, which are found in 5 to 10% of patients undergoing cholecystectomy for gallstones. Nowadays, with the adoption of the laparoscopic cholecystectomy(LC) as a standard, multiple minimally invasive treatment options for bile duct stones are feasible, with no consensus to date on the procedure of choice. The two stage endoscopic techniques involve the use of Endoscopic Retrograde Cholangiopancreatography(ERCP) before or after performing a LC, which has the main advantage of separating the bile duct procedure from the LC. However, the need for two separate anesthesia times, the possibility of blank or failed ERCP, and the chance for calculi migration between procedures increase the length of hospital stay and associated costs. The single stage procedures include the Laparoscopic Bile Duct Exploration (LBDE), and more recently, the performance of a laparoscopy guided intraoperative ERCP(Rendez Vous). The LBDE, when performed by an experienced surgical team, is an effective and safe technique. Nonetheless, it is considered a technically demanding procedure, whose results cannot be extrapolated to the general surgical community. Recently, the Rendez Vous has become a treatment alternative that simplifies both the surgical and the endoscopic procedures, decreases morbidity, and requires a single anesthesia time. On the downside, Rendez Vous technique involves complex operating room (OR) logistics, requiring both a trained surgical and endoscopic team at the same time. (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Coledocolitíase/terapia , Coledocolitíase/cirurgia , Coledocolitíase/fisiopatologia , ColecistolitíaseRESUMO
Chronic pancreatitis (CP) is defined by chronic inflammation of the pancreas with progressive replacement by fibrosis that produces characteristic morphological changes. The clinical picture is variable, being the main problem the pain and relapses of pancreatitis with possible local complications. Over time, the result is the development of exocrine and endocrine failure. In the initial phase, flare-ups of CP can not be distinguished from recurrent acute pancreatitis (RAP). If there are intraductal stones in the duct of Wirsung, endoscopic extraction of obstructive stones may be the first step to prevent new relapses and complications. We present the case of a patient with five episodes of acute pancreatitis (AP), three of them in the past five months. The patient was referred for study and management of RAP. His recent imaging study already showed dilatation of the main pancreatic duct, calcifications and pancreatic stones, compatible with CP. Although the hypertriglyceridemia participated in the etiology of AP, the last two episodes already occurred with normal values of triglycerides. Another possible etiologic factor was not found. His laboratory results did not show endocrine or exocrine insufficiency. The patient was treated with papillotomy, pancreatic stone extraction and installation of terapeutic pancreatic stent. He has been asymptomatic, free from new episodes of AP in the past six months. In conclusion, the CP is one of the possible causes of RAP. Endoscopic treatment by obstructive stone extraction is an efficient therapy to avoid new relapse.
La pancreatitis crónica (PC) se define por la inflamación crónica del páncreas con reemplazo progresivo por fibrosis que produce cambios morfológicos característicos. El cuadro clínico es variable, siendo el principal problema el dolor, reagudizaciones de pancreatitis con eventuales complicaciones locales. Con el tiempo, el resultado final es el desarrollo de insuficiencia exocrina y endocrina. En la fase inicial, no se puede distinguir las reagudizaciones de la PC de una pancreatitis aguda recurrente (PAR). Si se encuentran cálculos intraductales en el conducto de Wirsung, la extracción endoscópica de cálculos obstructivos puede ser el primer paso para prevenir nuevas recaídas y complicaciones. Se presenta el caso de un paciente con cinco episodios de pancreatitis aguda (PA), tres de ellos en los últimos cinco meses. El paciente fue derivado para estudio y manejo de PAR. Su estudio imagenológico reciente ya demostró dilatación del conducto pancreático principal, calcificaciones y cálculos pancreáticos, compatible con PC. Aunque la hipertrigliceridemia participó en la etiología de las PA, los últimos dos episodios ocurrieron con valores normales de triglicéridos. No se encontró otro factor etiológico posible. Su estudio de laboratorio no mostró insuficiencia exocrina ni endocrina. El paciente fue tratado mediante papilotomía, extracción de cálculos pancreáticos e instalación de prótesis pancreática terapéutica. Ha estado asintomático, libre de nuevos episodios de PA en los seis meses transcurridos. En conclusión, la PC es una de las posibles causas de PAR. El tratamiento endoscópico mediante extracción de cálculos obstructivos es una terapia eficiente para evitar nuevas recaídas.
Assuntos
Humanos , Masculino , Adulto , Cálculos/cirurgia , Endoscopia do Sistema Digestório/métodos , Pancreatite Crônica/prevenção & controle , Recidiva , Cálculos/etiologia , Cálculos/diagnóstico por imagem , Pancreatite Crônica/cirurgia , Pancreatite Crônica/complicações , Prevenção SecundáriaRESUMO
Autoimmune pancreatitis (AIP) is an inflammatory disease of the pancreas. The mechanism of the disease is not completely known. However, AIP shows cellular and humoral immunity elements, the most important being helper and regulatory T lymphocytes as well as B-lymphocytes and plasmocytes, participating in the fibroinflammatory process. Two histologic types have been described with different clinical characteristics. Type 1 AIP is part of a systemic condition associated with an increase of IgG4, while type 2 is a pancreatic disease, frequently associated with inflammatory bowel disease. From the clinical point of view, a third category is described when the classification is not possible at the moment of the diagnosis. The most important differential diagnosis of AIP is pancreatic cancer and it can be difficult, because current diagnostic methods used, including biopsy, have low specificity and sensitivity. AIP patients recover rapidly after steroid therapy, which can be useful even in differential diagnosis. Long-term prognosis is good: more than half of type 1 and almost all cases of type 2 patients have favorable outcome without recurrence and without severe consequences.
La pancreatitis autoinmune (PAI) es una enfermedad inflamatoria del páncreas. El mecanismo fisiopatológico no es completamente conocido. Sin embargo, presenta elementos de inmunidad celular y humoral, siendo de mayor importancia los linfocitos T-helper, T-reguladores, linfocitos B y plasmocitos, que participan en el desarrollo de la enfermedad. Se reconocen dos tipos histológicos con características clínicas también distintas. El tipo 1 forma parte de una enfermedad sistémica relacionada a aumento de IgG4, mientras el tipo 2 es una enfermedad pancreática, aunque con frecuencia asociada a enfermedad inflamatoria intestinal. Desde el punto de vista clínico, existe una tercera categoría, que se presenta cuando en el momento del diagnóstico de PAI la tipificación clínicamente no es posible. El diagnóstico diferencial más importante de la PAI es el cáncer de páncreas y puede ser clínicamente difícil. Los métodos actuales de diagnóstico incluyen la biopsia pero tienen un rendimiento bajo. La PAI responde rápidamente al tratamiento con esteroides, hecho que puede ser útil aún en el diagnóstico diferencial. Su pronóstico a largo plazo es bueno: más de la mitad de los casos tipo 1 y casi todos los casos tipo 2 evolucionan sin recaída y sin consecuencias graves a largo plazo.
Assuntos
Humanos , Doenças Autoimunes/diagnóstico , Prednisona/uso terapêutico , Pancreatite Autoimune/diagnóstico , Pancreatite Autoimune/terapia , Pancreatite/diagnóstico , Pancreatite/imunologia , Prednisona/administração & dosagem , Pancreatite Autoimune/fisiopatologia , Pancreatite Autoimune/tratamento farmacológicoRESUMO
Background: Chronic pancreatitis (CP) is a rare disease in Chile, without a clear explanation for this low prevalence. Aim: To analyze the characteristics of our patients with pancreatitis. Material and Methods: Retrospective analysis of a database of patients with pancreatitis of a clinical hospital. Morphological proof of diagnosis (calcifications/calculi, alterations of ducts, local complication or histology) was obtained for every patient. History of acute pancreatitis was recorded and exocrine-endocrine function was assessed. Results: We retrieved information of 121 patients with pancreatitis (86 males) in a period of 20 years. The number of cases increased markedly every five years. The calculated incidence and prevalence was 0.8/100,000/year and 6/100,000, respectively. Pancreatic calcifications were initially observed in 93 patients and became evident during the follow-up in another six patients. Severe pain or local complications occurred in 27 patients, requiring surgery in 10 or endoscopic treatment in 15. During the years of follow-up, 55 patients were free of symptoms. Exocrine and endocrine insufficiency was demonstrated and treated in 81 and 67 patients, respectively. Alcoholic etiology was evident in 40% of patients. In 29% no etiology was identified. Mapuche origin was exceptional. Conclusions: Late diagnosis of CP is common, since most of our patients presented with advanced stages. Even though CP is increasingly diagnosed in our hospitals, the number of cases is still far fewer when compared to other countries. Underdiagnosis alone cannot explain this difference and genetic factors might be of importance.