Search

Resumen: Objetivo: Describir los primeros resultados del programa de cribado de cáncer colorrectal en Aragón para valorar su implantación. Métodos: Se recogen los datos del programa en el primer año de implantación (2014), basado en la realización de test de sangre oculta en heces inmunoquímico para personas de 60-69 años de edad. Se reportan los indicadores principales de la red nacional de cribado. Resultados: Población invitada tras exclusiones: 12.518 personas. Tasa de participación: 45,28% (intervalo de confianza del 95% [IC95%]: 44,41-46,15). Test inadecuados: 0,21% (IC95%: 0,12-0,37). Test positivos: 10,75% (IC95%: 9,97-11,58). Aceptación de colonoscopia: 95,07% (IC95%: 93,04-96,52). Colonoscopias completas: 97,58% (IC95%: 95,98-98,55). Tasas de detección de adenomas de alto riesgo: 14,7‰ (IC95%: 11.9-18.2); adenomas de bajo riesgo: 5,55‰ (IC95%: 3,9-7,8). Valor predictivo positivo (VVP) para cualquier adenoma: 58,55% (IC95%: 54,49-62,49); VVP para cáncer invasivo: 5,36% (IC95%: 3,8-7,51). Conclusión: El análisis de los indicadores muestra que el programa se está implantando de forma adecuada. Abstract: Objective: To describe preliminary findings from the colorectal cancer screening programme in Aragon (Spain) to evaluate its implementation. Methods: We have collected data from the first year of the program (2014) based on faecal occult blood immunochemical (FOBTi) test in patients 60-69 years old. We report “indicators” defined by the “Red Nacional de Cribado”. Results: Invited population after exclusions: 12,518. Program participation rate: 45.28% (95%CI: 44.41-46.15). Inadequate tests: 0.21% (95%CI: 0.12-0.37); positive FOBTi test 10.75% (95%CI: 9.97-11.58) and colonoscopy acceptance 95.07% (95%CI: 93.04-96.52). Colonoscopy was appropriate and complete in 97.58% (95%CI: 95.98–98.55) of cases. The high- and low-risk adenoma detection rates were 14.7‰ (95%CI: 11.9-18.2) and 5.55‰ (95%CI: 3.9-7.8) respectively. The positive predictive value for any adenoma was 58.55% (95%CI: 54.49-62.49) and for invasive cancer was 5.36% (95%CI: 3.8-7.51). Conclusion: The indicator analysis of the ongoing programme suggests the programme is being implemented correctly in our community. Palabras clave: Cáncer colorrectal, Cribado, Sangre oculta en heces, Keywords: Colorectal cancer, Screening, Faecal occult blood immunochemical test

Background: Liver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria., Methods: Retrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram., Results: A total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement., Conclusions: The nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria., (Copyright © 2024 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Thalassemia is one of the most common genetic diseases and a major health threat worldwide. Accurate, efficient, and scalable analysis of next-generation sequencing (NGS) data is much needed for its molecular diagnosis and carrier screening. We developed NGS4THAL, a bioinformatics analysis pipeline analyzing NGS data to detect pathogenic variants for thalassemia and other hemoglobinopathies. NGS4THAL realigns ambiguously mapped NGS reads derived from the homologous Hb gene clusters for accurate detection of point mutations and small insertions/deletions. It uses a combination of complementary structural variant (SV) detection tools and an in-house database of control data containing specific SVs to achieve accurate detection of the complex SV types. Detected variants are matched with those in HbVar (A Database of Human Hemoglobin Variants and Thalassemia Mutations), allowing recognition of known pathogenic variants, including disease modifiers. Tested on simulation data, NGS4THAL achieved high sensitivity and specificity. For targeted NGS sequencing data from samples with laboratory-confirmed pathogenic Hb variants, it achieved 100% detection accuracy. Application of NGS4THAL on whole genome sequencing data from unrelated studies revealed thalassemia mutation carrier rates for Hong Kong Chinese and Northern Vietnamese that were consistent with previous reports. NGS4THAL is a highly accurate and efficient molecular diagnosis tool for thalassemia and other hemoglobinopathies based on tailored analysis of NGS data and may be scaled for population carrier screening., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Mutation in BRCA1/BRCA2 genes accounts for 20% of familial breast cancers, 5% to 10% of which may be due to other less penetrant genes which are still incompletely studied. Herein, a four-gene panel was used to examine the prevalence of BRCA1, BRCA2, TP53, and PTEN in hereditary breast and ovarian cancers in Southern Chinese population. In this cohort, 948 high-risk breast and/or ovarian patients were recruited for genetic screening by next-generation sequencing (NGS). The performance of our NGS pipeline was evaluated with 80 Sanger-validated known mutations and eight negative cases. With appropriate bioinformatics analysis pipeline, the detection sensitivity of NGS is comparable with Sanger sequencing. The prevalence of BRCA1/BRCA2 germline mutations was 9.4% in our Chinese cohort, of which 48.8% of the mutations arose from hotspot mutations. With the use of a tailor-made algorithm, HomopolymerQZ, more mutations were detected compared with single mutation detection algorithm. The frequencies of PTEN and TP53 were 0.21% and 0.53%, respectively, in the Southern Chinese patients with breast and/or ovarian cancers. High-throughput NGS approach allows the incorporation of control cohort that provides an ethnicity-specific data for polymorphic variants. Our data suggest that hotspot mutations screening such as SNaPshot could be an effective preliminary screening alternative adopted in a standard clinical laboratory without NGS setup., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer. Sanger sequencing has been the gold standard in identifying these mutations. However, 4-28% of inherited BRCA mutations may be due to large genomic rearrangements (LGRs), which could be missed by using Sanger sequencing alone. Our aim is to evaluate the pick-up rate of LGRs in our cohort. A total of 1,236 clinically high-risk patients with breast and/or ovarian cancers were recruited through The Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2014. Full gene sequencing (either Sanger or next generation sequencing) and multiplex ligation-dependent probe amplification (MLPA) were performed. We identified 120 deleterious BRCA mutations: 57 (4.61%) were in BRCA1 and 63 (5.10%) were in BRCA2. LGRs accounted for 6.67% (8 of 120) of all BRCA mutations, whereas 8.77 % (5 of 57) were BRCA1 mutations and 4.76% (3 of 63) were BRCA2 mutations. Through this integrated approach, both small nucleotide variations and LGRs could be detected. We suggest that MLPA should be incorporated into the standard practice for genetic testing to avoid false-negative results, which would greatly affect the management of these high-risk families., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Nutrition is a recognized determinant in 3 (ie, diseases of the heart, malignant neoplasms, cerebrovascular diseases) of the top 4 leading causes of death in the United States. However, many health care providers are not adequately trained to address lifestyle recommendations that include nutrition and physical activity behaviors in a manner that could mitigate disease development or progression. This contributes to a compelling need to markedly improve nutrition education for health care professionals and to establish curricular standards and requisite nutrition and physical activity competencies in the education, training, and continuing education for health care professionals. This article reports the present status of nutrition and physical activity education for health care professionals, evaluates the current pedagogic models, and underscores the urgent need to realign and synergize these models to reflect evidence-based and outcomes-focused education.

Background: This study investigated whether there were differential survival outcomes to first-line tyrosine kinase inhibitors (TKI) in patients with metastatic non-small-cell lung cancer harboring different subtypes of exon 19 and exon 21 mutations on epidermal growth factor receptor (EGFR)., Methods: Of 452 patients with stage IIIB and IV non-small-cell lung cancer, 192 patients (42.5%) harbored EGFR mutation and 170 (37.5%) received TKI as first-line treatment. EGFR mutation analysis was performed by direct sequencing. Survival and response outcome were compared among different subtypes of exon 19 and exon 21 EGFR mutations in these 170 patients., Results: Patients harboring exon 19 18-nucleotide deletion (delL747&#95;P753insS) had the shortest median progression-free survival (PFS) (6.5 months), followed by those with 15-nucleotide deletion (delE746&#95;A750) (12.4 months) and mixed insertion/substitution mutations (22.3 months; p = 0.012). However, patients who had exon 19 deletions starting on codon E746 had better median PFS (14.2 months) than those starting on L747 (6.5 months; hazard ratio, 0.445; 95% confidence interval [0.219-0.903]; p = 0.021). Besides, exon 21 L858R derived a longer median PFS than L861R/L861Q (11.4 months versus 2.1 months, respectively; hazard ratio, 0.298; 95% confidence interval [0.090-0.980]; p = 0.034)., Conclusions: Different subtypes of EGFR exon 19 and 21 mutations exhibited differential survival to first-line TKI therapy. Detailed sequence evaluation of exon 19 deletions may provide important prognostic information on survival outcome after TKI.

Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.

Serial quantitation of BCR-ABL mRNA levels is an important indicator of therapeutic response for patients with chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, but there is substantial variation in the real-time quantitative polymerase chain reaction methodologies used by different testing laboratories. To help improve the comparability of results between centers we sought to develop accredited reference reagents that are directly linked to the BCR-ABL international scale. After assessment of candidate cell lines, a reference material panel comprising 4 different dilution levels of freeze-dried preparations of K562 cells diluted in HL60 cells was prepared. After performance evaluation, the materials were assigned fixed percent BCR-ABL/control gene values according to the International Scale. A recommendation that the 4 materials be established as the first World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL translocation by real-time quantitative polymerase chain reaction was approved by the Expert Committee on Biological Standardization of the World Health Organization in November 2009. We consider that the development of these reagents is a significant milestone in the standardization of this clinically important test, but because they are a limited resource we suggest that their availability is restricted to manufacturers of secondary reference materials.

We describe a 75-year-old Chinese man who presented with three separate tumors in three different lobes of the lung, without evidence of mediastinal or systemic involvement. All three tumors were surgically resected by minimal invasive approach. Based on a differing epidermal growth factor receptor (EGFR) mutation status, the tumors were characterized as synchronous triple primary rather than intrapulmonary metastases. This report highlights the clinical usefulness of molecular cancer biomarkers to determine prognosis and to guide management decision in multiple lung tumors., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular (RV) function is very important for those patients with respiratory and cardiovascular disorders that can result in RV impairments. Because of complex geometry of the chamber, it is difficult to accurately measure the RV volumetric parameters with conventional imaging modalities. The purpose of this study was to evaluate whether the 64-MDCT can assess RV function with high accuracy and reproducibility when compared to the results with those of MRI., Methods: Forty-seven consecutive subjects underwent retrospectively ECG-gated 64-MDCT and MRI for assessing the ventricular function. Right ventricular end diastolic and end-systolic volume, stroke volume, and ejection fraction were measured with dedicated cardiac analysis software on 64-MDCT and compared with values measured on MRI which served as the reference standard. Agreement between two modalities was assessed with Bland and Altman analysis and linear regression analysis. Repeated measurements were performed to determine intraobserver and interobserver variability., Results: No significant differences were revealed in calculated RV volumes and EF between the two modalities. Agreement and correlation were similar for RV-EDV (0.4 ± 8.2 ml; r=0.95), RV-ESV (-0.6 ± 4.8; r=0.95), RV-SV (1.1 ± 6.7 ml; r=0.93), and RV-EF (0.9 ± 4.4; r=0.88). The difference of SV of right and left ventricle with 64-MDCT was not statistically significant (p=0.40) and good correlation was obtained (r=0.96). The variability in 64-MDCT measurements was lower than those in MRI., Conclusions: ECG-gated 64-MDCT can assess the RV function with high accuracy and reproducibility without geometric assumptions about right ventricle., (Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.)

The effect of clarithromycin on the systemic and local inflammatory responses after surgical trauma was investigated using a guinea pig model. There was no statistically significant difference in the body temperature and respiratory rate of the guinea pigs between the clarithromycin and control groups, although there was a trend towards a lower temperature in the first 36 h after the operation, and a trend towards a lower respiratory rate on day 1 and day 2 (P=0.07 and 0.18, respectively) in the clarithromycin group. The total leukocyte count of both groups of animals increased from day -1 to day 4, and the increase was more marked in the control group (P=0.06 on day 1). The neutrophil and monocyte counts of the two groups of animals also increased after the operation. The neutrophil count of the control group was significantly higher than the clarithromycin group on day 1 and 2 (P<0.05 and 0.01, respectively), and the monocyte count of the control group was significantly higher than the clarithromycin group on day 1 (P<0.005). Moreover, the platelet count of the animals also increased after the operation, and the count in the control group was significantly higher than the clarithromycin group on day 1, 2 and 4 (P<0.05, 0.005 and 0.005, respectively). There was no difference between the haemoglobin concentration, lymphocyte count, eosinophil count and basophil count between the two groups of animals. The number of animals with wound discharge was lower in the clarithromycin group than the control group throughout the post-operative period, but the difference was not statistically significant. None of the animals developed signs of wound infection. The present observation suggests that clarithromycin suppressed both the systemic and local inflammatory response after surgical trauma, and it prompts further animal experiments for delineation of the mechanism of action, as well as clinical trials in major surgical procedures., (Copyright 1999 The Italian Pharmacological Society.)