Is hospital discharge administrative data an appropriate source of information for cancer registries purposes? Some insights from four Spanish registries

<p>Abstract</p> <p>Background</p> <p>The use of hospital discharge administrative data (HDAD) has been recommended for automating, improving, even substituting, population-based cancer registries. The frequency of false positive and false negative cases recommends local validation.</p> <p>Methods</p> <p>The aim of this study was to detect newly diagnosed, false positive and false negative cases of cancer from hospital discharge claims, using four Spanish population-based cancer registries as the gold standard. Prostate cancer was used as a case study.</p> <p>Results</p> <p>A total of 2286 incident cases of prostate cancer registered in 2000 were used for validation. In the most sensitive algorithm (that using five diagnostic codes), estimates for Sensitivity ranged from 14.5% (CI95% 10.3-19.6) to 45.7% (CI95% 41.4-50.1). In the most predictive algorithm (that using five diagnostic and five surgical codes) Positive Predictive Value estimates ranged from 55.9% (CI95% 42.4-68.8) to 74.3% (CI95% 67.0-80.6). The most frequent reason for false positive cases was the number of prevalent cases inadequately considered as newly diagnosed cancers, ranging from 61.1% to 82.3% of false positive cases. The most frequent reason for false negative cases was related to the number of cases not attended in hospital settings. In this case, figures ranged from 34.4% to 69.7% of false negative cases, in the most predictive algorithm.</p> <p>Conclusions</p> <p>HDAD might be a helpful tool for cancer registries to reach their goals. The findings suggest that, for automating cancer registries, algorithms combining diagnoses and procedures are the best option. However, for cancer surveillance purposes, in those cancers like prostate cancer in which care is not only hospital-based, combining inpatient and outpatient information will be required.</p

Telomerase reverse transcriptase promoter mutations in bladder cancer: High frequency across stages, detection in urine, and lack of association with outcome

Background Hotspot mutations in the promoter of the gene coding for telomerase reverse transcriptase (TERT) have been described and proposed to activate gene expression. Objectives To investigate TERT mutation frequency, spectrum, association with expression and clinical outcome, and potential for detection of recurrences in urine in patients with urothelial bladder cancer (UBC). D

Risk Prediction Scores for Recurrence and Progression of Non-Muscle Invasive Bladder Cancer: An International Validation in Primary Tumours

Abstract Objective: We aimed to determine the validity of two risk scores for patients with non-muscle invasive bladder cancer in different European settings, in patients with primary tumours. Methods: We included 1,892 patients with primary stage Ta or T1 non-muscle invasive bladder cancer who underwent a transurethral resection in Spain (n = 973), the Netherlands (n = 639), or Denmark (n = 280). We evaluated recurrence-free survival and progression-free survival according to the European Organisation for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) risk scores for each patient and used the concordance index (c-index) to indicate discriminative ability. Results: The 3 cohorts were comparable according to age and sex, but patients from Denmark had a larger proportion of patients with the high stage and grade at diagnosis (p,0.01). At least one recurrence occurred in 839 (44%) patients and 258 (14%) patients had a progression during a median follow-up of 74 months. Patients from Denmark had the highest 10- year recurrence and progression rates (75% and 24%, respectively), whereas patients from Spain had the lowest rates (34% and 10%, respectively). The EORTC and CUETO risk scores both predicted progression better than recurrence with c-indices ranging from 0.72 to 0.82 while for recurrence, those ranged from 0.55 to 0.61. Conclusion: The EORTC and CUETO risk scores can reasonably predict progression, while prediction of recurrence is more difficult. New prognostic markers are needed to better predict recurrence of tumours in primary non-muscle invasive bladder cancer patients.This research received funding from the European Community's Seventh Framework program FP7/2007-2011 under grant agreement 201663 (Uromol project, http://www.uromol.eu/

Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis

Introduction: Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods: We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998–2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results: Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value#0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value$0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05–1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion: We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.This work was supported by the Fondo de Investigacion Sanitaria, Spain (grant numbers 00/0745, PI051436, PI061614, G03/174); Red Tematica de Investigacion Cooperativa en Cancer (grant number RD06/0020-RTICC), Spain; Marato TV3 (grant number 050830); European Commission (grant numbers EU-FP7-HEALTH-F2-2008-201663-UROMOL; US National Institutes of Health (grant number USA-NIH-RO1-CA089715); and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USA; Consolider ONCOBIO (Ministerio de Economia y Competitividad, Madrid, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer

Funder: Fundación Científica Asociación Española Contra el Cáncer (ES)Funder: Cancer Focus Northern Ireland and Department for Employment and LearningFunder: Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, USAAbstract: Background: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. Methods: We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. Results: We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E−06 in 1D approach and a Local Moran’s Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8—a lncRNA associated with pancreatic carcinogenesis—with a lowest p value = 6.91E−05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1—a major regulator of the ER stress and unfolded protein responses in acinar cells—identified by 3D; all of them with a strong in silico functional support. Conclusions: This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases

Impacto de la inmigración sobre la asistencia hospitalaria: frecuentación, casuística y repercusión económica Impact of immigration on hospital care: utilization, case-mix, and economic effects

Objetivos: Establecer el impacto de la inmigración sobre los servicios sanitarios, analizando la frecuentación hospitalaria, la casuística y su repercusión económica, comparadas con las de la población autóctona. Métodos: Estudio longitudinal retrospectivo de los ingresos en hospitales de agudos de la Región de Murcia notificados al Conjunto Mínimo Básico de Datos al Alta Hospitalaria (CMBD-AH) durante 2004 y 2005. Los grupos de comparación, establecidos atendiendo al país de nacimiento, son «España», «Europa-25» y «resto de países». Los motivos de ingreso se codificaron con la CIE-9-MC y se agruparon mediante AP-GRD-v18. Se calcularon las tasas de frecuentación ajustadas al tiempo de aseguramiento y el impacto económico mediante los pesos de los grupos relacionados por el diagnóstico (GDR) de 2004. Resultados: Se contabilizaron 196.275 altas, con 2.590.376 años de seguimiento y una frecuentación del 75,8‰ entre los españoles, el 64,3‰ entre los de Europa-25 y el 73,8‰ entre los del resto de los países. Las causas de ingreso más frecuentes se deben a embarazo, parto y puerperio. El coste por ingreso es de 3.529 € para los españoles, 3.231 € para los de Europa-25 y 2.423 € para los del resto de los países. El coste medio por año de aseguramiento estandarizado y truncado es de 263 € para los españoles, 217 € para los de Europa-25 y 219 € para los del resto de los países. Conclusiones: La frecuentación y los costes por ingreso y por año de seguimiento de los españoles son superiores a los de los inmigrantes, especialmente a los del grupo «resto de países»; la casuística también difiere en este grupo.Objectives: To identify the impact of immigration on health services by comparing hospital discharges, case-mix, and economic effects between immigrants and the native population. Methods: We performed a retrospective longitudinal study of acute-care hospital admissions in Murcia (Spain) registered in the Minimum Data Set from 2004-2005. The groups to be compared, established on the basis of country of birth, were «Spain», «Europe-25» and «remaining countries». Diagnoses were codified using the ICE-9-CM and were grouped by means of the All Patient-Diagnosis Related Groups (AP-DRG) version 18. Utilization rates were calculated by the time of medical insurance. Economic effects were calculated through DRG weights for 2004. Results: There were 196,275 discharges, with 2,590,376 person-years of insurance. The frequency of discharges was 75.8‰ among Spaniards, 64.3‰ among immigrants from Europe-25 and 73.8‰ among immigrants from the remaining countries. The most frequent causes of admission were related to pregnancy, childbirth and the puerperium. Cost per admission was 3,529 € in Spaniards, 3,231 € in persons from Europe-25 and 2,423 € in persons from the remaining countries. The average cost per year of insurance was 263 € for Spaniards, 217 € for immigrants from Europe-25 and 219 € for those from the remaining countries. Conclusions: Hospital utilization and costs per admission and for person-year of insurance are higher in Spaniards than in immigrants, especially the group from «the remaining countries». In this group, case-mix is also different

Validación de los códigos diagnósticos de cáncer de colon y recto del Conjunto Mínimo Básico de Datos Validation of colorectal cancer diagnostic codes in a hospital administration data set

Objetivo: Validar la capacidad del Conjunto Mínimo Básico de Datos (CMBD) para detectar casos incidentes de cáncer de colon y recto utilizando como estándar de referencia el Registro de Cáncer de Murcia (RCM) y medir la concordancia entre el CMBD y el registro de cáncer en tumores colorrectales. Material y método: Estudio de validación transversal del CMBD del Hospital Virgen de la Arrixaca de Murcia. La población de estudio son los casos incidentes de colon-recto del año 2000 del RCM y los casos del CMBD en el citado hospital para el mismo año con algún código diagnóstico CIE-9 entre 153.0 y 154.1 eliminando reingresos. Durante el proceso se van a realizar 2 análisis: sólo con el diagnóstico principal y con todos los diagnósticos. Se calcula la sensibilidad, la especificidad, el valor predictivo positivo (VPP) y negativo (VPN) y la concordancia con sus intervalos de confianza (IC) del 95%. Resultados: Con sólo el primer diagnóstico, el CMBD detecta el 80% de los casos incidentes de cáncer colorrectal con un VPP del 75%; considerando todos los diagnósticos, detecta el 85% con un VPP del 64%. La concordancia en la codificación es elevada tanto con 3 dígitos (índice kappa del 88% (IC del 95%, 0,79-0,97) en primer diagnóstico, y del 89% (IC del 95%, 0,80-0,97) en todos los diagnósticos) como de 4 dígitos (índice kappa del 77% (IC del 95%, 0,68-0,85) en el primer diagnóstico, y del 78% (IC del 95%, 0,70-0,86) en todos diagnósticos) en ambos análisis. Conclusiones: El CMBD es una buena fuente para detectar casos incidentes de cáncer al presentar una elevada sensibilidad. La alta concordancia encontrada en las localizaciones tumorales de colon-recto contribuye a consolidar el CMBD como fuente de datos para los registros de cáncer.<br>Objectives: To validate the ability of a hospital administration data set (minimum data set [MDS]) to detect incident cases of colorectal cancer using the Murcia Cancer Registry (MCR) as the gold standard and to measure agreement between the MDS and registration of colorectal cancer. Material and method: A cross sectional validation study of the MDS of the main hospital in the region of Murcia (Spain) was conducted. The study population consisted of incident cases of colorectal cancer in 2000 obtained from the MCR and cases in the MDS of the above-mentioned hospital for the same year with an ICD-9 diagnostic code between 153.0 and 154.1, eliminating readmissions. During the process, two analyses were performed: one analysis with the principal diagnosis only and another with all the diagnostic codes. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and agreement was calculated with their 95% confidence intervals (CI). Results: With the first diagnosis only, the MDS detected 80% of the incident cases of colorectal cancer with a PPV of 75%. With all the diagnoses, the MDS detected 85% of the cases with a PPV of 64%. The agreement in codification was high at three digits (kappa 88% (95% CI, 0.79-0.97) first diagnosis, 89% (95% CI, 0.80-0.97) all diagnoses) as well as at four digits (kappa 77% (IC, 0.68-0.85) first diagnosis, 78% (95% CI, 0.70-0.86) all diagnoses) in both analyses. Conclusions: Because of its high sensitivity, the MDS is a good source for detecting incident cases of cancer. The high agreement found in the site of colorectal cancer helps to consolidate the MDS as a data source for cancer registration

Framework for the Integration of Genomics, Epigenomics and Transcriptomics in Complex Diseases

Different types of '-omics' data are becoming available in the post-genome era; still a single -omics assessment provides limited insights to understand the biological mechanism of complex diseases. Genomics, epigenomics and transcriptomics data provide insight into the molecular dysregulation of neoplastic diseases, among them urothelial bladder cancer (UBC). Here, we propose a detailed analytical framework necessary to achieve an adequate integration of the three sets of -omics data to ultimately identify previously hidden genetic mechanisms in UBC.status: publishe

Framework for the Integration of Genomics, Epigenomics and Transcriptomics in Complex Diseases

Depto. de Estadística y Ciencia de los DatosFac. de Estudios EstadísticosTRUEpu