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AIM: This study evaluated the bias and accuracy of the CKD-EPI/CKiD and EKFC equations compared with the reference exogenous tracer-based assessment of glomerular filtration rate (GFR) in adult and pediatric patients according to their renal transplant status. METHODS: We assessed the bias and P30 accuracy of the CKD-EPI/CKiD and EKFC equations compared with iohexol-based GFR measurement. RESULTS: In the overall population (n = 59), the median age was 29 years (IQR, 16.0-46.0) and the median measured GFR was 73.9 mL/min/1.73m2 (IQR, 57.3-84.6). Among non-kidney transplant patients, the median was 77.7 mL/min/1.73m2 (IQR, 59.3-86.5), while among kidney transplant patients, it was 60.5 mL/min/1.73m2 (IQR, 54.2-66.8). The bias associated with the EKFC and CKD-EPI/CKiD equations was significantly higher among kidney transplant patients than among non-kidney transplant patients, with a difference between medians (Hodges-Lehmann) of +10.4 mL/min/1.73m2 (95% CI, 2.2-18.9; p = .02) for the EKFC and +12.1 mL/min/1.73m2 (95% CI, 4.2-21.4; p = .006) for the CKD-EPI/CKiD equations. In multivariable analysis, kidney transplant status emerged as an independent factor associated with a bias of >3.4 mL/min/1.73m2 (odds ratio, 7.7; 95% CI, 1.4-43.3; p = .02) for the EKFC equation and a bias of >13.4 mL/min/1.73m2 (odds ratio, 15.0; 95% CI, 2.6-85.7; p = .002) for the CKD-EPI/CKiD equations. CONCLUSION: In our study, which included adolescent and young adult kidney transplant patients, both the CKD-EPI/CKiD and EKFC equations tended to overestimate the measured glomerular filtration rate, with the EKFC equation exhibiting less bias. Renal transplant status significantly influenced the degree of estimation bias.
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BACKGROUND: The assessment of phosphate homeostasis in clinical practice relies not only on circulating phosphate levels but also on phosphate tubular reabsorption, ideally assessed using the tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR). TmP/GFR reference values were established before the onset of isotope-dilution mass spectrometry-standardized (IDMS) creatinine assays and thus need to be updated. Our objective is to provide reference values for TmP/GFR from childhood to adulthood, using the gold-standard of GFR assessment and IDMS-standardized creatinine values. METHODS: We retrospectively analysed all the inulin and iohexol clearances [measured glomerular filtration rate (mGFR)] performed in children and in adults screened for a living-donation in our unit since the beginning of IDMS-creatinine assays. TmP/GFR was calculated on a fasting sample, using the conventional formula without correction for tubular reabsorption of phosphate (TRP) in subjects below 19 years of age. RESULTS: A total of 2051 subjects (1711 children, 340 adults), aged from 1.9 to 73.4 years with normal GFR, normal phosphate and normal calcium levels, were included for TmP/GFR analysis. As expected, there was a progressive decrease along puberty in both genders of plasma phosphate and TmP/GFR, the decrease occurring earlier in girls. After the age of 19 years, there was a stabilization of plasma phosphate and TmP/GFR levels until the age of 55 years, phosphate levels and TmP/GFR being slightly lower in men than in women. CONCLUSION: We present the largest cohort describing TmP/GFR reference values in the era of IDMS-standardized creatinine assays. We believe that these data will help physicians to better diagnose and manage patients with abnormal phosphate metabolism in daily clinical routine.
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Yohexol , Fosfatos , Humanos , Niño , Adulto , Femenino , Masculino , Adolescente , Adulto Joven , Creatinina , Inulina , Estudios Retrospectivos , Calcio , Tasa de Filtración Glomerular , IsótoposRESUMEN
INTRODUCTION: Gastroenteropancreatic neuroendocrine carcinomas (GEPNEC) are characterized by a heterogeneous molecular profile and a poor prognosis. Circulating tumour DNA (ctDNA) analysis may be useful for NEC management. This study aimed at describing ctDNA mutations, to assess their predictive value for response to chemotherapies, and their change according to disease progression. METHODS: The CIRCAN-NEC study included patients with GEPNEC or NEC from an unknown primary, scheduled to begin first- or second-line chemotherapy. Blood samples were collected prior to chemotherapy initiation, at first evaluation, and during disease progression. ctDNA was sequenced by next-generation sequencing (NGS). Molecular response was defined as a decrease of at least 30% of the mutant allele fraction. RESULTS: All 24 patients included received platinum-etoposide first-line chemotherapy; 19 received a FOLFIRI-based post-first-line regimen. Twenty-two patients had at least one driver mutation: TP53 (n = 21), RB1 (n = 2), KRAS (n = 4), and BRAF (n = 3). Ten (42%) had an "adenocarcinoma-like" profile. Five of 6 patients with matching ctDNA/tissue NGS harboured at least one concordant mutation (44% concordance at the gene level). The concordance rate between ctDNA mutation/immunohistochemistry profile was 64% (7/11) for TP53/p53+ and 14% (1/7) for RB1/pRb-. In this pilot study including few patients by subgroups, patients with KRAS (HR = 3.60, 95% CI [1.06-12.04]) and BRAF (HR = 4.25, 95% CI [1.11-16.40]) mutations had shorter progression-free survival (PFS) under platinum-etoposide, while the 2 patients with RB1 mutations had shorter PFS under FOLFIRI-based chemotherapy. Twenty-eight periods of treatment were assessed: 10 patients had a molecular response (7/10 had a morphological response), which was associated with longer PFS (HR = 0.37, 95% CI [0.15; 0.91]). CONCLUSION: This pilot study shows a high sensitivity of ctDNA assessment, which is encouraging for the future management of GEPNEC (tumour molecular diagnosis and evaluation of disease progression).
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Antineoplásicos/farmacología , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/secundario , ADN Tumoral Circulante/genética , Neoplasias Intestinales/patología , Neoplasias Primarias Desconocidas/patología , Tumores Neuroendocrinos/patología , Evaluación de Resultado en la Atención de Salud , Neoplasias Pancreáticas/patología , Neoplasias Gástricas/patología , Adulto , Anciano , Antineoplásicos/administración & dosificación , Carcinoma Neuroendocrino/tratamiento farmacológico , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
OBJECTIVES: The one-compartment iohexol plasma clearance has been proposed as a reliable alternative to renal inulin clearance. However, this method's performance depends on the formula used to calculate glomerular filtration rate (GFR). This study reports on performance comparisons between various mathematical formulas proposed for iohexol plasma clearance vs. inulin urinary clearance. METHODS: GFR was simultaneously determined by inulin and iohexol clearance in 144 participants (age: 10-84 years; glomerular filtration rate: 15-169 mL/min/1.73 m2). A retrospective cross-sectional study evaluated the performance of four formulas proposed to calculate plasma iohexol clearance (Brøchner-Mortensen, Fleming et al., Jødal-Brøchner-Mortensen, and Ng-Schwartz-Munoz). The performance of each formula was assessed using bias, precision (standard deviation of the bias), accuracy (percentage iohexol within 5, 10, and 15%), root mean square error, and concordance correlation coefficient vs. renal inulin clearance as reference. RESULTS: Regarding accuracy, there was no difference in root mean square error (RMSE), P5, P10, or P15 between the four formulas. The four concordance correlation coefficients (CCC) between the value from each formula and in-GFR were high and not significantly different. At in-GFR ≥90 mL/min/1.73 m2, Ng-Schwartz-Munoz formula performed slightly better than other formulas regarding median bias (-0.5; 95% CI [-3.0 to 2.0] and accuracy P15 (95.0; 95% CI [88.0-100.0]). CONCLUSIONS: The studied formulas were found equivalent in terms of precision and accuracy, but the Ng-Schwartz-Munoz formula improved the accuracy at higher levels of in-GFR.
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Tasa de Filtración Glomerular , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Creatinina , Humanos , Inulina , Yohexol , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
The identification of novel regulators of tumor progression is a key challenge to gain knowledge on the biology of small intestinal neuroendocrine tumors (SI-NETs). We recently identified the loss of the axon guidance protein semaphorin 3F as a protumoral event in SI-NETs. Interestingly the expression of its receptor neuropilin-2 (NRP-2) was still maintained. This study aimed at deciphering the potential role of NRP-2 as a contributor to SI-NET progression. The role of NRP-2 in SI-NET progression was addressed using an approach integrating human tissue and serum samples, cell lines and in vivo models. Data obtained from human SI-NET tissues showed that membranous NRP-2 expression is present in a majority of tumors, and is correlated with invasion, metastatic abilities, and neovascularization. In addition, NRP-2 soluble isoform was found elevated in serum samples from metastatic patients. In preclinical mouse models of NET progression, NRP-2 silencing led to a sustained antitumor effect, partly driven by the downregulation of VEGFR2. In contrast, its ectopic expression conferred a gain of aggressiveness, driven by the activation of various oncogenic signaling pathways. Lastly, NRP-2 inhibition led to a decrease of tumor cell viability, and sensitized to therapeutic agents. Overall, our results point out NRP-2 as a potential therapeutic target for SI-NETs, and will foster the development of innovative strategies targeting this receptor. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Carcinoma Neuroendocrino/metabolismo , Neoplasias Intestinales/metabolismo , Intestino Delgado/metabolismo , Neuropilina-2/metabolismo , Anciano , Animales , Antineoplásicos/farmacología , Apoptosis , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/secundario , Línea Celular Tumoral , Movimiento Celular , Everolimus/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Intestinales/tratamiento farmacológico , Neoplasias Intestinales/genética , Neoplasias Intestinales/patología , Intestino Delgado/patología , Masculino , Ratones Desnudos , Invasividad Neoplásica , Neovascularización Patológica , Neuropilina-2/sangre , Neuropilina-2/genética , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: International organizations require from medical laboratories a quantitative statement of the uncertainty in measurement (UM) to help interpret patient results. The French accreditation body (COFRAC) recommends an approach (SH GTA 14 IQC/EQA method) using both internal quality control (IQC) and external quality assessment (EQA) data. The aim of this work was to validate an alternative way to quantify UM using only EQA results without any need for IQC data. This simple and practical method, which has already been described as the long-term evaluation of the UM (LTUM), is based on linear regression between data obtained by participants in EQA schemes and target values. We used it for 43 routine analytes covering biochemistry, immunoassay, and hemostasis fields. METHODS: Data from 50 laboratories participating in ProBioQual (PBQ) EQA schemes over 25 months were used to obtain estimates of the median and 90th percentile LTUM and to compare them to the usual analytical goals. Then, the two UM estimation methods were compared using data from 20 laboratories participating in both IQC and EQA schemes. RESULTS: Median LTUMs ranged from 2.9% (sodium) to 16.3% (bicarbonates) for biochemistry analytes, from 12.6% (prothrombin time) to 18.4% (factor V) for hemostasis analytes when using the mean of all participants, and were around 10% for immunoassays when using the peer-group mean. Median LTUMs were, in most cases, slightly lower than those obtained with the SH GTA 14 method, whatever the concentration level. CONCLUSIONS: LTUM is a simple and convenient method that gives UM estimates that are reliable and comparable to those of recommended methods. Therefore, proficiency testing (PT) organizers are allowed to provide participants with an additional UM estimate using only EQA data and which could be updated at the end of each survey.
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Hemostasis , Inmunoensayo , Garantía de la Calidad de Atención de Salud/métodos , Incertidumbre , Humanos , Modelos Lineales , Control de CalidadRESUMEN
Background: Vasoactive intestinal peptide (VIP)-secreting tumors (VIPomas) are digestive neuroendocrine tumors in which the hormonal secretion is life-threatening. Biological confirmation is obtained by demonstrating an elevation in plasma VIP, usually using radioimmunoassay (RIA). In some cases, analytical interference is suspected. We developed 3 different techniques to detect interference in VIP RIA. Methods: Three techniques were used: RIA after Sephadex column chromatography separation, RIA after polyethylene glycol precipitation, and 125I-labeled VIP binding test. We included patients with suspicion of false positive VIP (FPV) elevation. We then compared results with those of a group of "real," proven VIPoma (RV). Results: A total of 15 patients with FPV elevation and 9 RV patients were included. Interference was detected in all FPV patients vs none in RV. Clinical and biochemical parameters did not differ between FPV and RV patients, but VIP concentration in RIA was significantly higher in FPV patients than in RV patients (228â pmol/L vs 66â pmol/L, P = .038). Using a 125I-labeled VIP binding test, median proportion of radioactivity in the pellet was significantly higher in FPV than in RV patients (53% vs 13%, P < .0001). A 20.5% threshold presented excellent performances (sensitivity 100% [79.6-100], specificity 100% [70.1-100]). Conclusion: We developed 3 different laboratory techniques to reveal interference in RIA VIP assays. The diagnostic performance of all 3 was excellent. These techniques must be employed in cases of discordance between VIP elevation and clinical presentation.
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Neuropilin 2 (NRP2), a transmembrane non-tyrosine kinase receptor, has been described as a potential critical player in the tumourigenesis of several solid cancers and particularly in neuroendocrine neoplasms (NENs). A soluble form of NRP2 (sNRP2) has been previously described and corresponds to a truncated splice isoform. Its prognostic value has never been studied in NEN. NRP2 expression was studied by immunochemistry on tissue microarrays (n = 437) and on circulating tumour cells (CTCs, n = 5 patients with neuroendocrine carcinoma, NEC). We described the levels of sNRP2 in 229 patients with NEN using the ELISA method to identify the factors associated with sNRP2 levels and to evaluate its prognostic role; 90 blood donors represented the healthy control group. NRP2 was found in 97% of neuroendocrine tumours (396/410) and in 74% of NEC (20/27). NRP2 was also expressed in CTC of all the studied patients. The receiver operating characteristic (ROC) analysis showed that sNRP2 had a weak capacity to discriminate between NEN patients and healthy controls (area under curve (AUC) = 0.601, P = 0.053). Abnormal sNRP2 levels were associated with inflammatory syndrome, bone and peritoneal metastases, and abnormal chromogranin A levels. Patients with high sNRP2 levels (sNRP2Q3-Q4) had significantly poorer overall survival in multivariate analysis (HR 0.16, 95% CI (0.04-0.67), P = 0.015). In conclusion, the present study found that sNRP2 and NRP2 could represent a new prognostic biomarker and a therapeutic target, respectively, particularly in aggressive NEN.
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Biomarcadores de Tumor , Tumores Neuroendocrinos , Neuropilina-2 , Humanos , Femenino , Neuropilina-2/metabolismo , Neuropilina-2/genética , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/sangre , Anciano , Adulto , Biomarcadores de Tumor/metabolismo , Pronóstico , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Anciano de 80 o más Años , Adulto JovenRESUMEN
OBJECTIVE: To evaluate morphological and perfusion changes in liver metastases of neuroendocrine tumours by contrast-enhanced ultrasound (CEUS) after transarterial embolisation with bead block (TAE) or trans-arterial chemoembolisation with doxorubicin-eluting beads (DEB-TACE). METHODS: In this retrospective study, seven patients underwent TAE, and ten underwent DEB-TACE using beads of the same size. At 1 day before embolisation, 2 days, 1 month and 3 months after the procedure, a destruction-replenishment study using CEUS was performed with a microbubble-enhancing contrast material on a reference tumour. Relative blood flow (rBF) and relative blood volume (rBV) were obtained from the ratio of values obtained in the tumour and in adjacent liver parenchyma. Morphological parameters such as the tumour's major diameter and the viable tumour's major diameter were also measured. A parameter combining functional and morphological data, the tumour vitality index (TVI), was studied. The Wilcoxon rank-sum test and Fisher's test were used to compare treatment groups. RESULTS: At 3 months rBF, rBV and TVI were significantly lower (P = 0.005, P = 0.04 and P = 0.03) for the group with doxorubicin. No difference in morphological parameters was found throughout the follow-up. CONCLUSIONS: One parameter, TVI, could evaluate the morphological and functional response to treatments.
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Embolización Terapéutica/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neovascularización Patológica/terapia , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/secundario , Ultrasonografía/métodos , Anciano , Medios de Contraste , Femenino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/terapia , Fosfolípidos , Estudios Retrospectivos , Hexafluoruro de Azufre , Resultado del TratamientoRESUMEN
INTRODUCTION: Point of care (POC) analyzers are an integral part of the patient care. Transfuse can be an emergency decision, not being a benign act, it is necessary to ensure that the hemoglobin value measured by the POC are comparable with the reference analyzer. The objective is to compare the analytical performance of three POCs: ABL800 Flex, Hemocue and iSTAT and a central laboratory analyzer: XN-10 and the impact on the transfusion decision. METHODS: An in vitro study was performed in 50 patients for whom a hemogram had been prescribed on the XN-10, the hemoglobin determination was performed in parallel on the three POCs. Then, retrospective study was performed to compare the hemoglobin values returned for matched samples in routine practice, 5505 for ABL800 Flex, 55 for Hemocue and 70 for iSTAT were analyzed. RESULTS: In vitro study shows systematic biases in the measurement of hemoglobin between the different analyzers, overestimation for the ABL800 Flex and the Hemocue, underestimation for the iSTAT. These biases are accentuated in current practice for iSTAT but decreased for ABL800 Flex. In the transfusion decision range from 70 to 100 g/L, there were 8.6% of clinically discordant results between the reference method and ABL, 34.8% for Hemocue and 21.4% for iSTAT. CONCLUSION: In addition to systematic biases, many additional factors may be involved for variation in hemoglobin measurement with POC. Thus, in the case of urgent transfusion decisions, sending a hemogram on a central laboratory analyzer seems to be essential, while being compatible with a life-threatening emergency.
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Pruebas Hematológicas , Pruebas en el Punto de Atención , Humanos , Estudios Retrospectivos , Análisis de los Gases de la Sangre/métodos , Sistemas de Atención de Punto , Hemoglobinas/análisisRESUMEN
Summary: We report a case of metastatic pancreatic neuroendocrine carcinoma associated with paraneoplastic Cushing's syndrome, successively treated with five lines of treatment (platin-etoposide, LV5FU2-dacarbazine, FOLFIRINOX, pembrolizumab, and paclitaxel) and anti-secretory treatment. Circulating-free DNA (cfDNA) was analysed at each morphological evaluation starting from the second-line treatment. cfDNA changes were well correlated with the disease course, and cfDNA may be used as a predictive marker and/or as an early marker of response. In addition, the absolute count of atypical cells was elevated upon disease progression. Learning points: cfDNA changes were well correlated with the Cushing's syndrome course and with the tumour burden changes assessed by laboratory markers and by RECIST criteria.cfDNA analysis was used to determine the pharmacogenetic patterns of the present patient.An elevated number of atypical circulating cells was noticed upon disease progression.
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Abetalipoproteinemia (ABL; OMIM 200100) is an inherited disorder resulting from mutations in the microsomal triglyceride transfer protein gene and characterized by a major lipid malabsorption leading to extremely low plasma cholesterol and triglyceride levels and fat-soluble vitamins deficiencies. We report two novel mutations (c.59del17 and c.582C>A) and the long-term follow-up of four ABL subjects treated with vitamin E. The good outcome of the early-treated patients contrasts with severe ataxia and retinopathy observed in the patient with delayed treatment. In conclusion, early diagnosis and early management are essential to prevent the manifestations following the fat-soluble vitamin deficiencies.
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Abetalipoproteinemia/genética , Proteínas Portadoras/genética , Codón sin Sentido , Mutación del Sistema de Lectura , Abetalipoproteinemia/fisiopatología , Adolescente , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Linaje , Penetrancia , Deficiencia de Vitamina E/genéticaRESUMEN
BACKGROUND: Reference intervals for arterial and venous umbilical cord blood gas (UCBG) parameters are scarce, are mainly focused on pH, pO2, pCO2 and base deficit, and are usually assessed using parametric tests, despite a generally skewed data distribution. Here, the purpose is to determine reference percentiles for nine parameters of concomitant arterial and venous UCBG (CAV-UCBG) from neonates at birth, using nonparametric tests. METHODS: Results of CAV-UCBG, assayed over a 4.5-year period, were extracted from a hospital laboratory database for pH, pCO2, pO2, oxygen saturation, concentration of total oxygen, total carbon dioxide, hydrogen carbonate, total haemoglobin, and acid-base excess. Exclusion criteria were: a venous-arterial pH difference <0.02, an arterial-venous pCO2 <0.7 kPa, and a venous pCO2 <2.9 kPa. Nonparametric bivariate kernel density estimations were used for the selection of plots within the 95% percentile surface of the pCO2-to-pH relationship (NBKDE-95P). Outliers from skewed data were removed using an adjusted-Tukey method, and percentiles were calculated according to the CLSI EP28-A3 nonparametric method. RESULTS: Overall, 31% (5033/16164) of CAV-UCBG were discarded using the three exclusion criteria. Then, 6% (670/11131) of CAV-UCBG were excluded from the NBKDE-95P, and 0.1 to 3.5% outliers were subsequently removed. Depending on the parameter, the 2.5th and 97.5th percentiles from the whole group were similar or slightly narrower compared to reference intervals from other studies, while those from female and male neonates did not differ substantially. CONCLUSIONS: Using an indirect nonparametric approach, this study proposes new percentiles for parameters from concomitant arterial and venous umbilical cord blood gases.
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Dióxido de Carbono/sangre , Sangre Fetal/metabolismo , Oxígeno/sangre , Arterias Umbilicales , Venas Umbilicales , Femenino , Humanos , Concentración de Iones de Hidrógeno , MasculinoRESUMEN
Direct measurement methods of glomerular filtration rate (GFR) are considered as the gold standard to assess kidney function. Following the withdrawal of the Proinuline Serb® specialty by the French National Health Surveillance Agency, iohexol remains the most suitable marker to replace inulin as the marker for GFR in France. The assay is performed by high performance liquid chromatography (HPLC) coupled with ultraviolet (UV) detection or by mass spectrometry. Plasma clearance measurement is the protocol of choice: single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations to improve accuracy. In some cases, urinary clearance protocols may be proposed. National and international recommendations suggest using a GFR measurement as a confirmatory test in cases where the creatinine-based estimated GFR is inappropriate, ie clinical situations characterized by a significant alteration of muscle mass or volume distribution. The indications retained by the working group were graded according to the level of recommendations. The essential indications are the evaluation of living kidney donor, the monitoring of kidney allograft function at one year post-transplantation, drugs with narrow therapeutic range (anticoagulant, chemotherapy) in patients with inadequate estimation of GFR by creatinine and clinical research.
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Tasa de Filtración Glomerular , Pruebas de Función Renal , Biomarcadores/análisis , Biomarcadores/metabolismo , Creatinina/sangre , Francia , Humanos , Internacionalidad , Yohexol/análisis , Yohexol/metabolismo , Enfermedades Renales/sangre , Enfermedades Renales/diagnóstico , Pruebas de Función Renal/métodos , Pruebas de Función Renal/normas , Estándares de ReferenciaRESUMEN
CONTEXT: Biogenic amines such as 5-hydroxy-indole acetic acid (5HIAA) the main metabolite of serotonin or metanephrines (catecholamines metabolites) are used as biomarkers of neuroendocrine tumours. OBJECTIVE: To re-evaluate the recommendations for urinary sampling (preservatives, diet, drugs, etc.) as many of the reported analytical interferences supporting these recommendations are related to obsolete assays. METHODS: Bibliographic analysis of old and modern assays concerning preservation, extraction, assay and interferences. RESULTS: 5HIAA may degrade as soon as urine is excreted. Thus, acids as preservatives (hydrochloric or acetic acid) have to be immediately added. Care should be taken not to decrease the pH under 2. Urine preservative for metanephrine assays is not mandatory. Diets including serotonin-, tryptophan- and dopamine-rich foods have to be avoided depending on the biomarkers investigated (bananas, plantain, nuts, etc.). Tryptophan-rich over-the-counter formulas have to be prohibited when 5HIAA has to be assayed. Acetaminophen may interfere with electrochemical detection depending on high-pressure liquid chromatography (HPLC) parameters. No interference is known with mass spectrometric assays but with the one described for metanephrines determination. Some drugs interfere however with serotonin and catecholamines secretion and/or metabolism (monoamine oxidase inhibitors, serotonin or dopamine recapture inhibitors, etc.). CONCLUSION: Revisited recommendations are provided for the diet, the drugs and the preservatives before HPLC coupled with electrochemical and mass spectrometry assays.
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Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are a very aggressive type of cancer, for which prognostic factors are lacking. We analysed clinical and histomorphological prognostic markers of overall survival (OS), completed with a record of biological and haematological data of patients diagnosed between December 2002 and December 2015. The median OS was 16 months (95% CI 13.9-18.1). After univariate analysis, performance status (PS) ≥ 2 and stage IV were associated with a worse outcome (9 months and 14 months, respectively), as well as patients with lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels ≥ 2 ULN (9 months and 8 months, respectively). After multivariate analysis, LDH and AST levels were the only factors that remained significantly associated with better survival: HR 0.36 (p = 0.04) and 0.31 (p = 0.03), respectively. When patients had elevated LDH and AST levels, OS was 20 months, when they had high LDH or AST levels, 13 months and 8 months in the group with low LDH and AST levels (p < 0.001). Therefore, biological data appeared to be more relevant prognostic factors than usual factors described in other studies (PS, stage, and Ki-67). Considering LDH and AST levels at diagnosis could help physicians to predict survival and to stratify patients for clinical trials.
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Biomarcadores de Tumor/metabolismo , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/patología , Adulto , Anciano , Carcinoma Neuroendocrino/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
OBJECTIVES: Inappropriate calcitonin (CT) release, a major feature of medullary thyroid cancer (MTC), may occur in neuroendocrine tumors (NETs). The aims of this retrospective study were to assess i) the characteristics and prognosis of CT-producing NETs, and ii) the value of CT monitoring during follow-up. METHODS: All patients with NETs in whom serum CT was assayed between 2010 and 2012 were included. MTCs were excluded. Clinical, biological, and histological characteristics were studied. RESULTS: Twenty-one (12%) of 176 patients in whom serum CT was systematically assayed had concentrations >100 âng/l, with tumours predominantly of bronchial or pancreatic origin (P<0.0001), and of high grade (P=0.0006). Poor prognosis was linked to high CT levels, poor differentiation, and grade 3. In a total group of 24 patients with serum CT >100 âng/l, symptoms potentially attributable to CT were recorded in eight, with occasional overlap with the carcinoid syndrome among other secretory syndromes. Immunohistochemistry could be performed in six tumor specimens, CT being detected in five. In 11 patients with five or more successive CT assays, hormone levels were fairly well correlated with clinical courses. CONCLUSION: Serum CT levels may be raised in some patients with NETs, especially from foregut origin, and of high grade. The suggested value of CT monitoring during follow-up must be confirmed in further studies.
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Neoplasias de los Bronquios/metabolismo , Calcitonina/metabolismo , Neoplasias Gastrointestinales/metabolismo , Tumores Neuroendocrinos/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Bronquios/patología , Neoplasias de los Bronquios/terapia , Calcitonina/sangre , Cromogranina A/sangre , Estudios de Cohortes , Femenino , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/terapia , Humanos , Inmunohistoquímica , Masculino , Síndrome Carcinoide Maligno/sangre , Persona de Mediana Edad , Clasificación del Tumor , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
INTRODUCTION: Chromogranin A (CgA) is the principal tumour marker for gastroenteropancreatic neuroendocrine tumours (GEPNET). Combining serum CgA and pancreatic polypeptide (PP) levels may increase the sensitivity of tumour markers in the diagnosis of GEPNET. OBJECTIVES: (1) To evaluate the sensitivity of PP and CgA in GEPNET. (2) To compare changes in serum CgA and PP levels with the morphological evolution of the tumours. PATIENTS AND METHODS: Sixty-six pancreatic and 49 gastrointestinal NET, with at least one serum determination of CgA and PP at the same time were retrieved from an institutional data base. Secondly, the variations in serum CgA or PP at successive determinations were compared to Response Evaluation Criteria in Solid Tumours (RECIST) criteria in 57 patients (112 follow-up visits) with high serum CgA levels and in 21 patients (37 follow-up visits) with high serum PP levels. RESULTS: Among the 115 patients included in the study group, an increase in serum CgA (normal <98 µg/L) or PP (normal <100 pmol/L) was found in respectively 79 (69%) and 36 (31%) cases. Seven patients had normal CgA and elevated PP levels. Both markers were significantly more elevated in metastatic disease (74% versus 51% for CgA and 37% versus 18% for PP). The concordance rates between serum markers and RECIST criteria were 51% for CgA and 54% for PP. CONCLUSIONS: Serum PP determination identify few false-negative results of serum CgA determination in GEPNET. Our study does not validate the use of CgA or PP as surrogate markers for detecting changes in tumour burden.
Asunto(s)
Cromogranina A/sangre , Neoplasias Gastrointestinales/sangre , Neoplasias Gastrointestinales/diagnóstico , Tumores Neuroendocrinos/sangre , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico , Polipéptido Pancreático/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Femenino , Neoplasias Gastrointestinales/patología , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Adulto JovenRESUMEN
INTRODUCTION: Endocrine tumors of Meckel's diverticulum are rare. Their clinical and pathological characteristics are not well known, making it difficult to assess the best strategy for therapeutic management. MATERIALS AND METHODS: Eight cases of endocrine tumors of Meckel's diverticulum, submitted to surgical resection in our institution between 1977 and 2009, were studied. Clinical charts were reviewed; classification, grading, and staging were performed according to recent international recommendations. Five cases, including two associated with the carcinoid syndrome, were revealed by mesenteric mass or liver metastases; three cases were diagnosed incidentally at laparotomy or laparoscopy. RESULTS: All cases presented as typical well-differentiated midgut endocrine tumors. Five cases were associated with mesenteric lymph node metastases; three presented with liver metastases. Seven cases were classified as well-differentiated endocrine carcinomas, one as well-differentiated endocrine tumor of benign behavior. DISCUSSION: All tumors >1 cm, but one, had regional or distant disease. All patients had complete surgical resection of the primary. One patient deceased after 25 months; the others were alive after 12-101 months. CONCLUSION: In conclusion, endocrine tumors of Meckel's diverticulum are rarely symptomatic and often diagnosed at an advanced stage. All tumors measuring more than 1 cm in diameter must be resected according to oncological principles.