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Yi-Ju Liao,1 Tzu-Hung Hsiao,2– 4 Ching-Heng Lin,2,3,5,6 Chun-Sheng Hsu,7– 10 Yen-Lin Chang,1,8 Yu-Wei Chen,11 Chiann-Yi Hsu,2,12 Yi-Ming Chen,2,10,13– 15,* Ming-Fen Wu1,* 1Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan; 4Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan; 5Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; 6Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; 7Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung, Taiwan; 8Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan; 9School of Medicine, National Defense Medical Center, Taipei, Taiwan; 10Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 11Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan; 12Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan; 13Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 14Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 15School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Yi-Ming ChenDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Xitun Dist., Taichung, 407, Taiwan, Tel +886-4-2359-2525 ext. 4400, Fax +886-4-2359-2705, Email ymchen1@vghtc.gov.twPurpose: Clopidogrel is widely used in coronary artery, peripheral arterial, and cerebrovascular disease. We aimed to study the association of the CYP2C19 phenotype with cardiovascular outcomes and interventional procedures in a hospital-based population.Patients and Methods: This cross-sectional, retrospective study enrolled patients with prior exposure to clopidogrel at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI). Data on the CYP2C19 phenotype, drug-prescription profile, comorbidities, vascular intervention procedures, and hospitalization due to acute myocardial infarction (AMI) or stroke of clopidogrel users were analyzed.Results: From the 32,728 patients in the TCVGH-TPMI cohort, we selected 2687 clopidogrel users. A total of 400 (14.9%) clopidogrel poor metabolizers (PMs), 1235 (46.0%) intermediate metabolizers (IMs), and 1052 (39.2%) extensive metabolizers (EMs) were identified. The predominant loss-of-function allele is *2. In 2687 patients with clopidogrel exposure, the CYP2C19 PM phenotype was unassociated with hospitalization due to AMI or stroke after adjusting for comorbidities and carotid angiographies. Among the 1554 clopidogrel users who underwent cardiovascular intervention, 193 (12.4%) received two or more types of interventional procedures. Compared with non-PMs, patients with the PM phenotype had a higher risk of multiple carotid interventions (OR: 3.13, 95% CI: 1.19– 8.22).Conclusion: In this hospital-wide cohort, 8.2% were clopidogrel users, of which 14.9% were CYP2C19 PMs. The result of this study does not support universal genotyping of CYP2C19 in all clopidogrel users to identify risks for stroke and AMI. CYP2C19 PMs are more likely to undergo multiple carotid interventions than non-PMs. Prospective studies to investigate the association of the CYP2C19 genotype and carotid interventions and outcomes are needed to validate our results.Keywords: pharmacogenomics, clopidogrel, CYP2C19, Taiwan precision medicine initiative, TPMI, carotid intervention

Chloroplasts are the sites for photosynthesis, and two Golden2-like factors act as transcriptional activators of chloroplast development in rice (Oryza sativa L.) and maize (Zea mays L.). Rice OsGLK1 and OsGLK2 are orthologous to maize ZmGLK1 (ZmG1) and ZmGLK2 (ZmG2), respectively. However, while rice OsGLK1 and OsGLK2 act redundantly to regulate chloroplast development in mesophyll cells, maize ZmG1 and ZmG2 are functionally specialized and expressed in different cell-specific manners. To boost rice chloroplast development and photosynthesis, we generated transgenic rice plants overexpressing ZmG1 and ZmG2, individually or simultaneously, with constitutive promoters (pZmUbi::ZmG1 and p35S::ZmG2) or maize promoters (pZmG1::ZmG1, pZmG2::ZmG2, and pZmG1::ZmG1/pZmG2::ZmG2). Both ZmG1 and ZmG2 genes were highly expressed in transgenic rice leaves. Moreover, ZmG1 and ZmG2 showed coordinated expression in pZmG1::ZmG1/pZmG2::ZmG2 plants. All Golden2-like (GLK) transgenic plants had higher chlorophyll and protein contents, Rubisco activities and photosynthetic rates per unit leaf area in flag leaves. However, the highest grain yields occurred when maize promoters were used; pZmG1::ZmG1, pZmG2::ZmG2, and pZmG1::ZmG1/pZmG2::ZmG2 transgenic plants showed increases in grain yield by 51%, 47%, and 70%, respectively. In contrast, the pZmUbi::ZmG1 plant produced smaller seeds without yield increases. Transcriptome analysis indicated that maize GLKs act as master regulators promoting the expression of both photosynthesis-related and stress-responsive regulatory genes in both rice shoot and root. Thus, by promoting these important functions under the control of their own promoters, maize GLK1 and GLK2 genes together dramatically improved rice photosynthetic performance and productivity. A similar approach can potentially improve the productivity of many other crops.

Distracted driving refers to multisensory integration and attention shifts between attentional driving and different interferences from different modalities, including visual and auditory stimuli. Here, we compared the behavioral performance with interacting multisensory distractors during attentional driving. Then, the independent component analysis (ICA) and event-related spectral perturbation (ERSP) were applied to investigate the neural oscillation changes. The behavioral results showed that the response times (RTs) increased when distractors appeared in response to attentional driving. Moreover, the RTs were longer when the distractor interference was presented in the auditory modality compared with the visual modality. Eye movement intervals showed shorter tracking saccades under distractor interference. These results may indicate that attentional driving performance was impaired under the exposure to multisensory distractor interference. The ERSPs under visual and auditory distraction exposure showed decreased beta power in the frontal area, increased theta and delta power in the central area, and decreased alpha power in the parietal area. During this process, distracted driving under cross-modal sensory interference required more neural oscillation involvement. Moreover, the visual modality showed increased gamma power in the frontal, central, parietal and occipital areas, while the auditory modality showed decreased gamma power in the frontal area, indicating that auditory interference could intervene in top-down attentional processing.

Chang-Wei Wu,1 Ching-Yao Yang,1 Yih-Leong Chang,2 Jin-Yuan Shih1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; 2Department of Pathology, National Taiwan University Cancer Center, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, TaiwanCorrespondence: Jin-Yuan ShihDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, TaiwanTel +886-2-23562905Fax +886-2-23582867Email jyshih@ntu.edu.twAbstract: Pulmonary pleomorphic carcinoma (PPC) generally lacks actionable driver mutations such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase or c-ros oncogene 1 (ROS1) rearrangements. The response to crizotinib, ceritinib, brigatinib, and lorlatinib in ROS1-positive advanced non-small cell lung carcinoma is well established; however, there is little mention of their successful administration in pulmonary pleomorphic carcinoma cases. We report a case of a stage II PPC with recurrence after surgical resection and developed multiple distant metastasis. The tumor was refractory to chemotherapy and immunotherapy with progressive disease. EZR-ROS1 fusion was detected by next-generation sequencing and showed a good response to serial ROS1 inhibitors combined with surgery and radiotherapy. Now under lorlatinib, all her lesions responded well during the follow-up with sustained partial remission for more than 18 months. A sustainable treatment effect can be achieved in pulmonary pleomorphic carcinoma with driver mutations with tyrosine kinase inhibitor treatment. Driver mutations should be regularly tested in pulmonary pleomorphic carcinomas.Keywords: pulmonary pleomorphic carcinoma, lung cancer, ROS1-rearranged, tyrosine kinase inhibitor, lorlatinib

Yenlin Huang,1,2 Chieh Lin,3 Huang-Kai Kao,2,4 Shao-Yu Hung,4 Hung-Ju Ko,2 Yu-Chen Huang,5 Yu-Liang Chang,5 Kai-Ping Chang2,6 1Department of Anatomic Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Department of Oral & Maxillofacial Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Kai-Ping ChangDepartment of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, No. 5, Fu-Hsing Street, Kwei-Shan, Taoyuan 333005, TaiwanTel +886-3-3281200 ext 3972Fax +886-3-3979361Email dr.kpchang@gmail.comPurpose: The presence of CD8+ tumor-infiltrating lymphocytes (TILs) has been reported to be associated with treatment outcomes in many types of solid tumors. However, the results vary due to the various methods of visual estimation and subjective interpretation. The current study is the first to use digital image analyses to evaluate the density of CD8+/CD3+ TILs in tongue squamous cell carcinoma (TSCC).Patients and Methods: From 2005 to 2015, a cohort of 258 TSCC patients were consecutively enrolled in this study. After immunohistochemistry on representative sections, the density of CD8+/CD3+ TILs at tumor invasive margins was evaluated by digital image analysis. The subjects were stratified by the median values of CD3+ cell density, CD8+ cell density, CD8/CD3, and scores (0, 1, and 2) to demonstrate the association with various clinicopathological manifestations.Results: Low CD8+ TIL counts were associated with advanced tumor stages (p=0.034), and low CD8/CD3 ratios were associated with perineural invasion (p=0.043). Both parameters were also associated with increased tumor depths (p=0.034 and 0.004, respectively). Univariate analyses revealed that advanced tumor stages, perineural invasion, extranodal extension, tumor depth, lower CD8 counts, and lower scores (score 0 vs 2) were associated with poorer overall survival, and multivariate analysis further indicated that extranodal extension and low scores (score 0 vs 2) were both independent factors for overall survival (p < 0.0001 and p = 0.0369, respectively).Conclusion: The use of digital image analysis to assess CD8+ TILs at the invasive margins provides an objective indicator of prognoses including overall survival.Keywords: oral cavity, squamous cell carcinoma, oral cancer, SCC, tumor-infiltrating lymphocyte, TIL

The U.S. welfare reform of 1996 brought about highly decentralized Welfare-to-Work (WTW) programs, granting discretion to states and local governments to implement policies. Previous research has emphasized racial disparities in WTW sanction rates, by focusing on state/county characteristics or frontline-workers' biases. There is a dearth of research focusing on different understandings of equity or equality and corresponding practices embedded within WTW programs at the state and local levels. This knowledge is important to better understand how race disparities in WTW may be shaped. Our case is California's comparatively generous and highly devolved WTW program and its implementation in two most different counties. Descriptive analysis of administrative data reveals racial disparities in WTW sanctions and exemptions at the state-level and contrasting racial disparity patterns across two counties. Drawing on an equity framework, critical discourse analysis (CDA) of policy documents and interviews at the state level reveals conflicting discourses and practices around equity and equality, leaving room for interpretation at local agencies. CDA of county-level documents and interviews with county administrators showcases contrasting discourses and practices: while one county operates on an equality discourse that does not challenge existing disparities, the other county adopts an equity-related discourse of providing better treatment towards some historically disadvantaged groups. The observed discourses and practices help to understand the different racial disparity patterns. We conclude that in the absence of a clear equity framework at the state level, decentralization in WTW complicates the manner in which equity discourses and practices play out at the local level.

Tenofovir disoproxil fumurate (TDF) therapy during late pregnancy in highly viremic mothers can reduce residual overt hepatitis B virus (HBV) infections of their infants that occur despite immunoprophylaxis.1,2 Occult HBV infection (OBI) has been defined as the presence of HBV DNA in liver or sera in subjects seronegative for hepatitis B surface antigen (HBsAg).3 OBI has been found in varying proportions of immunized infants born to HBsAg-positive mothers.4-6 We aimed to investigate the impact of maternal TDF therapy during pregnancy on vertically acquired OBI.

This paper addresses a gap in welfare reform literature by investigating the social constructions of poor people in state policymaking within the context of diminishing General Assistance (GA) after the Great Recession. Using social construction and policy design theory and thematic content analysis of Washington State’s legislative archives, I found that the negative constructions of GA recipients as deviants with undesired psychological and behavioral problems were associated with the reform direction toward a regulated, punitive model. These constructions, intersecting with the ideologies of personal responsibility and work ethic, contribute to the dismantling of the social safety net for Washington’s poorest residents.

Bih-Ru Wang,1,2,* Yuh-Lih Chang,1,2,* Tzeng-Ji Chen,3,4 Jen-Hwey Chiu,5,6 Jing Chong Wu,7 Min-Shan Wu,1 Chia-Lin Chou,1 Yueh-Ching Chou1,2,81Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; 3Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan; 5Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; 6Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Traditional Medicine Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 8College of Pharmacy, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workBackground: Many female breast cancer (FBC) patients take Chinese herbal medicine (CHM) and Western medication (WM) concurrently in Taiwan. Despite the possibility of interactions between the CHM and WM mentioned in previous studies, the pattern of these coprescriptions in FBC patients remains unclear. Hence, the aim of the present study is to investigate the utilization of coprescriptions of CHM and WM among the FBC patients in Taiwan.Methods: The study was a cross-sectional survey using the sampled cohort in 2009 obtained from the National Health Insurance Research Database in Taiwan. There were 3,507 FBC patients identified from the registry for catastrophic illness patients. Ambulatory visit records, corresponding prescriptions, and the data of beneficiaries belonging to the FBC patients were further extracted. A total of 1,086 FBC patients used CHM at least once. CHM and WM prescribed within any overlapping duration were defined as coprescriptions.Results: There were 868 (80.0%) patients simultaneously receiving CHM and WM. A total of 4,927 CHM prescriptions and 6,358 WM prescriptions were prescribed concurrently. Among these coprescriptions, the most frequently used CHM was jia-wei-xiao-yao-san (21.2%), and the most frequently coprescribed WM was acetaminophen (38.9%), followed by tamoxifen (25.5%). There were 346 patients using systemic adjuvant therapy and CHM concurrently. The most commonly coprescribed CHM with chemotherapy, endocrine therapy, and trastuzumab was xiang-sha-liu-jun-zi-tang, jia-wei-xiao-yao-san, and zhi-gan-cao-tang, respectively.Conclusion: The combined use of CHM with WM is prevalent. The main purpose of combining CHM with systemic cancer treatment is to alleviate the treatment-related adverse effects. However, the combination may result in the potential risk of drug–herb interactions. Further clinical studies are needed to evaluate the efficacy and safety of the CHM and WM coprescriptions for FBC patients.Keywords: drug utilization patterns, complementary and alternative medicine, pharmacoep-idemiology

ΔNp63, the N-terminal truncated isoform of p63, has been found to be overexpressed in several human epithelial cancers, including nasopharyngeal carcinomas (NPCs), suggesting a function in carcinogenesis. Trans-resveratrol (RSV) has been shown to exert proapoptotic activities through a p53-dependent or p53-independent pathway in various cancer cells. However, the effects of RSV on NPC are still unexplored. In this study, we investigated the apoptotic effects of RSV on ΔNp63-overexpressing NPC cell lines. We showed that RSV (12-100 μ) induced dose-dependent growth suppression, cell-cycle arrest in the S phase and caspase-dependent apoptosis in NPC-TW076 and NPC-TW039 cells. The RSV effect was accompanied by the downregulation of ΔNp63 and the upregulation of p53 protein in a dose-dependent manner. By using small-interfering RNA (siRNA) technology, we found that the targeted silencing of ΔNp63 induced apoptosis and sensitized the NPC cells to RSV-induced apoptosis through caspase-3 activation, whereas suppression of p53 by siRNA did not inhibit RSV-induced apoptosis. Furthermore, transfection with p53 siRNA or pretreatment with caspase inhibitors (Z-VAD-fmk or Z-DEVD-fmk) had no influence on the RSV downregulation of ΔNp63. Interestingly, ecoptic expression of ΔNp63 did not significantly block RSV-induced cell death and was also downregulated after RSV treatment. Downregulation of ΔNp63 by RSV was shown to occur at the mRNA transcript and post-translational levels. Importantly, RSV enhanced chemotheraptic drug-induced apoptosis in NPC and two human carcinoma cell lines, HT1376 and Hep3B cells. These results suggested that ΔNp63, but not p53, is a molecular target of RSV-induced apoptosis and the regulation of ΔNp63 expression by RSV may provide a therapeutic effect of RSV in human NPC.

There are no antivirals or vaccines available to treat Enterovirus 71 (EV71) infections. Although the type I interferon response, elicited upon virus infection, is critical to establishing host antiviral innate immunity, EV71 fails to induce this response efficiently. Here we provide new insights into potential anti-EV71 therapy by showing that neutralization of EV71-induced miR-146a prevents death in mice by restarting the production of type I interferon. EV71 infection upregulates miR-146a, which targets IRAK1 and TRAF6 involved in TLR signalling and type I interferon production. We further identify AP1 as being responsible for the EV71-induced expression of miR-146a. Surprisingly, knocking out miR-146a or neutralizing virus-induced miR-146a by specific antagomiR restores expressions of IRAK1 and TRAF6, augments IFNβ production, inhibits viral propagation and improves survival in the mouse model. Our results suggest that enterovirus-induced miR-146a facilitates viral pathogenesis by suppressing IFN production and provide a clue to developing preventive and therapeutic strategies for enterovirus infections. © 2014 Macmillan Publishers Limited. All rights reserved.

Objectives The aims of this study were to examine the expression of androgen receptors (AR) in oral squamous cell carcinoma (OSCC) cells and tumors and to determine the role of AR in regulating OSCC cell growth. Materials and Methods Four OSCC cell lines were used for analyzing AR expression and transcriptional activity. The effects of AR knockdown on the growth and tumorigenicity of OSCC cells were examined. A series of 11 benign, 22 premalignant, and 21 malignant lesions of the oral cavity were used for analyzing AR expression. Results OSCC cells expressed AR proteins with differential activities. Stimulation of AR by dihydrotestosterone in OSCC cells caused an increase in cyclin D1 expression and promoted cell growth, whereas treatment with bicalutamide led to decreased cyclin D1 expression and inhibited cell growth. Knockdown of AR expression in OSCC cells resulted in decreased proliferation, increased apoptosis, and inhibited tumorigenicity. Results from immunohistochemical studies showed that AR immunoreactivity was found in 27% (3/11) of benign lesions, while 68% (15/22) of premalignant and 67% (14/21) of malignant lesions showed positive AR staining. Conclusion Our data suggest that OSCC cells express functional AR proteins which are critical for promoting cell growth and causing malignant disease.

We report on a female term neonate who presented with a huge cystic hygroma of the right neck associated with intraventricular haemorrhage as demonstrated by computerized tomography and magnetic resonance imaging studies. She underwent extraventricular drainage and excision of the neck mass with stable postoperative condition. Psychomotor retardation was found thereafter. To our knowledge, the association of a large cystic hygroma of the neck with intracranial haemorrhage has not been reported previously. The possible mechanism of the occurrence of the haemorrhage is discussed.

Objective: To evaluate the effectiveness of salvage neck dissection as part of a multidisciplinary treatment approach in persistent or recurrent metastatic nasopharyngeal carcinoma, after failure of initial radiotherapy at the regional site. Design: A retrospective study of 31 patients treated during a 14-year period from March 1981 through May 1995, with a maximum follow-up of 152 months. Factors evaluated include patients' sex, age, and initial stage of tumor, mobility and number of nodal recurrences, surgical and pathological findings, and postoperative irradiation. Setting: Academic tertiary referral center. Patients: Twenty-six men and 5 women were studied; one patient had neck dissection to both sides of the neck on separate occasions, for a total of 32 operations. All patients had pathologically proved nasopharyngeal carcinoma and had been previously treated at the primary site and both sides of the neck with definitive radiotherapy. Intervention: Patients underwent a radical, modified radical, or level I—sparing radical neck dissection. Main Outcome Measure: Surgical morbidity, time to recurrence at the regional site, and survival time. Results: Clinically, there was a disease predilection of 81% at levels II and V. Surgical morbidity was minimal. Regional control was achieved in 20 (65%) of the patients, and the overall 5-year survival was 67%. Tumor involvement of the posterior triangle musculature and spinal accessory nerve was associated with failure to control neck disease. Extracapsular nodal extension correlated with a poor survival outcome. Conclusion: Control of regional disease by salvage neck dissection when radiotherapy has failed is both safe and effective in properly selected patients. Arch Otolaryngol Head Neck Surg. 1997;123:725-729

This study delineated the distribution of reactivity of malignant human lymphoid cells with monoclonal antibodies Leu 1 and OKT1, and correlated this expression with that of conventional lymphoid cell markers. The presence of Leu 1 on benign lymph nodal T-cells and its absence from benign lymph nodal B-cells was confirmed. Twenty-two T-cell neoplasms, expressing a variety of intrathymic and mature peripheral phenotypes, expressed Leu 1, but this expression was heterogeneous with respect to percent-positive cells and antigenic density, and appeared to correlate with stages of T-cell differentiation. This study demonstrated the expression of Leu 1 by 33 of 36 cases of B-CLL, by 10 of 15 cases of the closely allied small lymphocytic cell lymphoma, and by 9 of 29 follicular center-cell lymphomas. This included B-cell malignancies of each surface immunoglobulin isotype, and some cases associated with a monoclonal protein spike. Leu 1 was not expressed by myeloma plasma cells, and was absent from non-B, non-T acute lymphoblastic leukemia cells in each of 15 cases studied. Finally, Leu 1 and OKT1 were expressed in parallel, with respect to percent-positive cells and staining intensity, on benign and malignant T-cells, and on malignant B-cells, wherever studied. Possible explanations for this shared antigen are the existence of a minor Leu 1+ B-cell subset, a transformation-associated event, or glycosylation.

Severe hand trauma caused by an industrial accident resulted in composite tissue loss in the basal joint area of the right hand. The crushed metacarpal bone was replaced, and ligamentous and capsular reconstruction was performed with flexor carpi radialis tendon and additional tendon graft. We present our experience, with a follow-up of one year and eight months.

Background 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. Methods 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. Results 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. Conclusions 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.