Publications by authors named "Francisco Pérez Rodríguez"

18 Publications

  • Page 1 of 1

Diagnostic accuracy of two commercial SARS-CoV-2 antigen-detecting rapid tests at the point of care in community-based testing centers.

PLoS One 2021 31;16(3):e0248921. Epub 2021 Mar 31.

Division of Infectious Disease, Geneva University Hospitals, Geneva, Switzerland.

Objectives: Determine the diagnostic accuracy of two antigen-detecting rapid diagnostic tests (Ag-RDT) for SARS-CoV-2 at the point of care and define individuals' characteristics providing best performance.

Methods: We performed a prospective, single-center, point of care validation of two Ag-RDT in comparison to RT-PCR on nasopharyngeal swabs.

Results: Between October 9th and 23rd, 2020, 1064 participants were enrolled. The PanbioTM Covid-19 Ag Rapid Test device (Abbott) was validated in 535 participants, with 106 positive Ag-RDT results out of 124 positive RT-PCR individuals, yielding a sensitivity of 85.5% (95% CI: 78.0-91.2). Specificity was 100.0% (95% CI: 99.1-100) in 411 RT-PCR negative individuals. The Standard Q Ag-RDT (SD Biosensor, Roche) was validated in 529 participants, with 170 positive Ag-RDT results out of 191 positive RT-PCR individuals, yielding a sensitivity of 89.0% (95%CI: 83.7-93.1). One false positive result was obtained in 338 RT-PCR negative individuals, yielding a specificity of 99.7% (95%CI: 98.4-100). For individuals presenting with fever 1-5 days post symptom onset, combined Ag-RDT sensitivity was above 95%. Lower sensitivity of 88.2% was seen on the same day of symptom development (day 0).

Conclusions: We provide an independent validation of two widely available commercial Ag-RDTs, both meeting WHO criteria of ≥80% sensitivity and ≥97% specificity. Although less sensitive than RT-PCR, these assays could be beneficial due to their rapid results, ease of use, and independence from existing laboratory structures. Testing criteria focusing on patients with typical symptoms in their early symptomatic period onset could further increase diagnostic value.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248921PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011749PMC
April 2021

Inactivation of Hepatitis A Virus and Human Norovirus in Clams Subjected to Heat Treatment.

Front Microbiol 2020 12;11:578328. Epub 2021 Jan 12.

Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain.

Bivalve mollusk contamination by enteric viruses, especially human noroviruses (HuNoV) and hepatitis A virus (HAV), is a problem with health and economic implications. The aim of the study was the evaluation of the effect of heat treatment in clams () experimentally contaminated with HuNoV using a PMA-viability RTqPCR assay to minimize measurement of non-infectious viruses, and used HAV as a model to estimate infectivity loss. Spiked clams were immersed in water at 90°C to ensure that internal meat temperature was maintained above 90°C for at least 5 min. The treatment resulted in >3.89 ± 0.24 log TCID/g reduction of infectious HAV, confirming inactivation. For HuNoV, RTqPCR assays showed log reductions of 2.96 ± 0.79 and 2.56 ± 0.56, for GI and GII, respectively, and the use of PMA resulted in an additional log reduction for GII, providing a better correlation with risk reduction. In the absence of a cell culture system which could be used to determine HuNoV infectivity reduction, a performance criteria based on PMA-RTqPCR log reduction could be used to evaluate food product safety. According to data from this study, heat treatments of clams which cause reductions >3.5 log for GII as measured by PMA-RTqPCR assay may be regarded as an acceptable inactivation treatment, and could be set as a performance criterion to test the effectiveness of other time-temperature inactivation processes.
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http://dx.doi.org/10.3389/fmicb.2020.578328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835484PMC
January 2021

Normal tissue content impact on the GBM molecular classification.

Brief Bioinform 2020 Jul 7. Epub 2020 Jul 7.

Brain Tumour Laboratory, Scientific Director at Vithas Hospitals, Managing Director at Fundación Vithas and Professor at the Medial School of Francisco de Vitoria University.

Molecular classification of glioblastoma has enabled a deeper understanding of the disease. The four-subtype model (including Proneural, Classical, Mesenchymal and Neural) has been replaced by a model that discards the Neural subtype, found to be associated with samples with a high content of normal tissue. These samples can be misclassified preventing biological and clinical insights into the different tumor subtypes from coming to light. In this work, we present a model that tackles both the molecular classification of samples and discrimination of those with a high content of normal cells. We performed a transcriptomic in silico analysis on glioblastoma (GBM) samples (n = 810) and tested different criteria to optimize the number of genes needed for molecular classification. We used gene expression of normal brain samples (n = 555) to design an additional gene signature to detect samples with a high normal tissue content. Microdissection samples of different structures within GBM (n = 122) have been used to validate the final model. Finally, the model was tested in a cohort of 43 patients and confirmed by histology. Based on the expression of 20 genes, our model is able to discriminate samples with a high content of normal tissue and to classify the remaining ones. We have shown that taking into consideration normal cells can prevent errors in the classification and the subsequent misinterpretation of the results. Moreover, considering only samples with a low content of normal cells, we found an association between the complexity of the samples and survival for the three molecular subtypes.
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http://dx.doi.org/10.1093/bib/bbaa129DOI Listing
July 2020

Fecal Components Modulate Human Astrovirus Infectivity in Cells and Reconstituted Intestinal Tissues.

mSphere 2019 12 18;4(6). Epub 2019 Dec 18.

Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.

Human astroviruses (HAstV) are among the most common causative agents of viral gastroenteritis, especially in children, and extraintestinal manifestations have also been described. These viruses are transmitted by the fecal-oral route, implying that stool composition and the gut microbiota may impact their ability to remain infectious. For some enteric viruses, individual bacterial envelope components and other polysaccharide-containing molecules, which are abundant in stools, have been shown to enhance capsid stability. However, the role of the complex stool environment and, most importantly, the role of interindividual differences have been poorly studied. We used HAstV as a model to investigate how the stool environment in itself, its interindividual variability, and some specific stool components could affect HAstV stability and infectivity. Using two different HAstV genotypes, we found that stools as a whole modulate astrovirus infectivity not only in an individual-dependent manner but also in a manner that depends on the viral genotype. A virus-protective effect was observed after incubation with various Gram-positive and Gram-negative bacteria as well as with bacterial components, such as lipopolysaccharide and peptidoglycan. These results were further confirmed in human intestinal tissues, a more physiologically relevant system. Astrovirus infectivity was also preserved by mucin, a major component of intestinal mucus. We further confirmed that these components stabilize the viral capsid. These results show that although HAstV benefits from the stabilizing effect of fecal components, the complexity and variability of the stool composition and the multiple potential interactions may explain the interindividual differences in viral transmission observed in real life. To ensure transmission, enteric viruses must maintain their infectivity during the various environmental challenges that they face in transit within and between hosts. Increased knowledge of the factors affecting enteric virus survival may help to control their transmission. This study reveals that specific fecal bacterial components preserve classic human astrovirus infectivity by stabilizing viral particles. However, the outcomes of stool-virus interactions are very variable, ranging from protection to a reduction of viral infectivity, depending on the viral genotype and the individual from whom the stool has been collected. We show that the transmissibility of enteric viruses is dependent on the intestinal contents of the infected individual and highlight the complex multiple interactions that could explain the stochastic nature of enteric virus transmission in humans.
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http://dx.doi.org/10.1128/mSphere.00568-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920511PMC
December 2019

Detection of dicistroviruses RNA in blood of febrile Tanzanian children.

Emerg Microbes Infect 2019 ;8(1):613-623

a Division of Infectious Diseases and Laboratory of Virology , University of Geneva Hospitals Geneva , Switzerland.

Fever is the leading cause of paediatric outpatient consultations in Sub-Saharan Africa. Although most are suspected to be of viral origin, a putative causative pathogen is not identified in over a quarter of these febrile episodes. Using a de novo assembly sequencing approach, we report the detection (15.4%) of dicistroviruses (DicV) RNA in sera collected from 692 febrile Tanzanian children. In contrast, DicV RNA was only detected in 1/77 (1.3%) plasma samples from febrile Tanzanian adults, suggesting that children could represent the primary susceptible population. Estimated viral load by specific quantitative real-time RT-PCR assay ranged from < 1.32E3 to 1.44E7 viral RNA copies/mL serum. Three DicV full-length genomes were obtained, and a phylogenetic analyse on the capsid region showed the presence of two clusters representing tentative novel genus. Although DicV-positive cases were detected throughout the year, a significantly higher positivity rate was observed during the rainy season. This study reveals that novel DicV RNA is frequently detected in the blood of Tanzanian children, paving the way for further investigations to determine if DicV possibly represent a new agent in humans.
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http://dx.doi.org/10.1080/22221751.2019.1603791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493270PMC
June 2019

Glass Wool Concentration Optimization for the Detection of Enveloped and Non-enveloped Waterborne Viruses.

Food Environ Virol 2019 06 21;11(2):184-192. Epub 2019 Mar 21.

Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain.

An extremely affordable virus concentration method based on adsorption-elution to glass wool and subsequent reconcentration through polyethylene glycol 6000 (PEG) precipitation was optimized to recover not only non-enveloped viruses but also enveloped viruses. Hepatitis A virus (HAV) and transmissible gastroenteritis virus (TGEV) were employed as surrogates for naked and enveloped viruses, respectively, to set up the methodology. Initial experimentation in small-volume samples showed that both types of particles readily adsorbed to the positively charged glass wool but were poorly detached from it through standard elution with 0.05 M glycine with 3% of beef extract buffer, pH 9.5, with elution efficiencies of 7.2% and 2.6%, for HAV and TGEV, respectively. To improve the recovery of enveloped viruses, several modifications in the elution were assayed: increasing the elution pH, extending glass wool and eluent contact time, adding a detergent, or performing the elution by recirculation or under agitation. Considering practicability and performance, recircularization of the eluent at pH 11.0 for 20 min was the elution procedure of choice, with efficiencies of 25.7% and 18.8% for HAV and TGEV in 50 L of water. Additionally, employing 20% PEG instead of 10% for virus reconcentration improved recoveries up to 47% and 51%, respectively. The optimized procedure was applied to detect naturally occurring HAV and coronaviruses in surface water of Wadi Hanifa, Riyadh. HAV was detected in 38% of the samples, while one sample was positive for an alphacoronavirus. This cheap virus detection system enables the comprehensive surveillance of viruses present in water samples.
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http://dx.doi.org/10.1007/s12560-019-09378-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090506PMC
June 2019

Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature.

PLoS Pathog 2018 04 9;14(4):e1006962. Epub 2018 Apr 9.

University of Geneva Faculty of Medicine, Department of Microbiology and Molecular Medicine, 1 Rue Michel-Servet, Geneva, Switzerland.

Despite their genetic similarities, enteric and respiratory enteroviruses (EVs) have highly heterogeneous biophysical properties and cause a vast diversity of human pathologies. In vitro differences include acid sensitivity, optimal growth temperature and tissue tropism, which reflect a preferential in vivo replication in the respiratory or gastrointestinal tract and are thus key determinants of EV virulence. To investigate the underlying cause of these differences, we generated chimeras at the capsid-level between EV-D68 (a respiratory EV) and EV-D94 (an enteric EV). Although some chimeras were nonfunctional, EV-D94 with both the capsid and 2A protease or the capsid only of EV-D68 were both viable. Using this latter construct, we performed several functional assays, which indicated that capsid proteins determine acid sensitivity and tropism in cell lines and in respiratory, intestinal and neural tissues. Additionally, capsid genes were shown to also participate in determining the optimal growth temperature, since EV-D94 temperature adaptation relied on single mutations in VP1, while constructs with EV-D68 capsid could not adapt to higher temperatures. Finally, we demonstrate that EV-D68 maintains residual binding-capacity after acid-treatment despite a loss of infectivity. In contrast, non-structural rather than capsid proteins modulate the innate immune response in tissues. These unique biophysical insights expose another layer in the phenotypic diversity of one of world's most prevalent pathogens and could aid target selection for vaccine or antiviral development.
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http://dx.doi.org/10.1371/journal.ppat.1006962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908207PMC
April 2018

Recurrent Cardiac Fibroelastoma. Is It Really a Benign Tumor?

Rev Esp Cardiol (Engl Ed) 2018 Aug 11;71(8):685-687. Epub 2017 Jul 11.

Servicio de Cardiología, Hospital Universitario Madrid Montepríncipe, Boadilla del Monte, Madrid, Spain.

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http://dx.doi.org/10.1016/j.rec.2017.04.031DOI Listing
August 2018

Improving virus production through quasispecies genomic selection and molecular breeding.

Sci Rep 2016 11 3;6:35962. Epub 2016 Nov 3.

Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.

Virus production still is a challenging issue in antigen manufacture, particularly with slow-growing viruses. Deep-sequencing of genomic regions indicative of efficient replication may be used to identify high-fitness minority individuals suppressed by the ensemble of mutants in a virus quasispecies. Molecular breeding of quasispecies containing colonizer individuals, under regimes allowing more than one replicative cycle, is a strategy to select the fittest competitors among the colonizers. A slow-growing cell culture-adapted hepatitis A virus strain was employed as a model for this strategy. Using genomic selection in two regions predictive of efficient translation, the internal ribosome entry site and the VP1-coding region, high-fitness minority colonizer individuals were identified in a population adapted to conditions of artificially-induced cellular transcription shut-off. Molecular breeding of this population with a second one, also adapted to transcription shut-off and showing an overall colonizer phenotype, allowed the selection of a fast-growing population of great biotechnological potential.
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http://dx.doi.org/10.1038/srep35962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093897PMC
November 2016

Massive Intrabile Duct Invasion Caused by a Fatal Progression of Colonic Adenocarcinoma: Abdominal Computed Tomography Findings and Cholangiography Correlation.

J Clin Diagn Res 2016 Apr 1;10(4):XD04-XD05. Epub 2016 Apr 1.

Department of Pathology, Hospital Universitario Montepríncipe , Boadilla Del Monte, Madrid, Spain .

In this report, we present an unusual case of jaundice in a patient with advanced colorectal cancer due to intraductal tumour invasion of the intra- and extrahepatic biliary tree. This complication proved to be fatal despite aggressive therapeutic management. A correct diagnosis of this type of involvement was achieved by a combination of diagnostic and therapeutic cholangiography. Despite adequate biliary decompression, the patient died from liver failure and biliary sepsis.
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http://dx.doi.org/10.7860/JCDR/2016/16951.7681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866233PMC
April 2016

Hepatitis A virus genotype distribution during a decade of universal vaccination of preadolescents.

Int J Mol Sci 2015 Mar 25;16(4):6842-54. Epub 2015 Mar 25.

Enteric Virus Laboratory, Department of Microbiology and Institute of Nutrition and Food Safety, University of Barcelona, Diagonal 643, 08028 Barcelona, Spain.

A universal vaccination program among preadolescents was implemented in Catalonia, Spain, during the period of 1999-2013 and its effectiveness has been clearly demonstrated by an overall significant attack rate reduction. However, reductions were not constant over time, and increases were again observed in 2002-2009 due to the occurrence of huge outbreaks. In the following years, in the absence of large outbreaks, the attack rate decreased again to very low levels. However, an increase of symptomatic cases in the <5 age group has recently been observed. This is an unexpected observation since children younger than 6 are mostly asymptomatic. Such a long vaccination campaign offers the opportunity to analyze not only the effectiveness of vaccination, but also the influence of the circulating genotypes on the incidence of hepatitis A among the different age groups. This study has revealed the emergence of genotype IC during a foodborne outbreak, the short-lived circulation of vaccine-escape variants isolated during an outbreak among the men-having-sex-with-men group, and the association of genotype IIIA with the increase of symptomatic cases among the very young. From a public health perspective, two conclusions may be drawn: vaccination is better at an early age, and the vaccination schedule must be complete and include all recommended vaccine doses.
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http://dx.doi.org/10.3390/ijms16046842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424991PMC
March 2015

Molecular basis of the behavior of hepatitis a virus exposed to high hydrostatic pressure.

Appl Environ Microbiol 2014 Oct 8;80(20):6499-505. Epub 2014 Aug 8.

Enteric Virus Laboratory, Department of Microbiology, School of Biology, University of Barcelona, Barcelona, Spain Enteric Virus Laboratory, Institute of Nutrition and Food Safety, Campus Torribera, University of Barcelona, Santa Coloma de Gramenet, Spain

Food-borne hepatitis A outbreaks may be prevented by subjecting foods at risk of virus contamination to moderate treatments of high hydrostatic pressure (HHP). A pretreatment promoting hepatitis A virus (HAV) capsid-folding changes enhances the virucidal effect of HHP, indicating that its efficacy depends on capsid conformation. HAV populations enriched in immature capsids (125S provirions) are more resistant to HHP, suggesting that mature capsids (150S virions) are more susceptible to this treatment. In addition, the monoclonal antibody (MAb) K24F2 epitope contained in the immunodominant site is a key factor for the resistance to HHP. Changes in capsid folding inducing a loss of recognition by MAb K24F2 render more susceptible conformations independently of the origin of such changes. Accordingly, codon usage-associated folding changes and changes stimulated by pH-dependent breathings, provided they confer a loss of recognition by MAb K24F2, induce a higher susceptibility to HHP. In conclusion, the resistance of HAV to HHP treatments may be explained by a low proportion of 150S particles combined with a good accessibility of the epitope contained in the immunodominant site close to the 5-fold axis.
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http://dx.doi.org/10.1128/AEM.01693-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178634PMC
October 2014

Hepatitis A virus adaptation to cellular shutoff is driven by dynamic adjustments of codon usage and results in the selection of populations with altered capsids.

J Virol 2014 May 19;88(9):5029-41. Epub 2014 Feb 19.

Enteric Virus Laboratory, Department of Microbiology, School of Biology, University of Barcelona, Barcelona, Spain.

Unlabelled: Hepatitis A virus (HAV) has a highly biased and deoptimized codon usage compared to the host cell and fails to inhibit host protein synthesis. It has been proposed that an optimal combination of abundant and rare codons controls the translation speed required for the correct capsid folding. The artificial shutoff host protein synthesis results in the selection of variants containing mutations in the HAV capsid coding region critical for folding, stability, and function. Here, we show that these capsid mutations resulted in changes in their antigenicity; in a reduced stability to high temperature, low pH, and biliary salts; and in an increased efficacy of cell entry. In conclusion, the adaptation to cellular shutoff resulted in the selection of large-plaque-producing virus populations.

Importance: HAV has a naturally deoptimized codon usage with respect to that of its cell host and is unable to shut down the cellular translation. This fact contributes to the low replication rate of the virus, in addition to other factors such as the highly inefficient internal ribosome entry site (IRES), and explains the outstanding physical stability of this pathogen in the environment mediated by a folding-dependent highly cohesive capsid. Adaptation to artificially induced cellular transcription shutoff resulted in a redeoptimization of its capsid codon usage, instead of an optimization. These genomic changes are related to an overall change of capsid folding, which in turn induces changes in the cell entry process. Remarkably, the adaptation to cellular shutoff allowed the virus to significantly increase its RNA uncoating efficiency, resulting in the selection of large-plaque-producing populations. However, these populations produced much-debilitated virions.
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http://dx.doi.org/10.1128/JVI.00087-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993836PMC
May 2014

Standardized multiplex one-step qRT-PCR for hepatitis A virus, norovirus GI and GII quantification in bivalve mollusks and water.

Food Microbiol 2014 Jun 30;40:55-63. Epub 2013 Dec 30.

Enteric Virus Laboratory of the Department of Microbiology, University of Barcelona, Barcelona, Spain; Institute of Nutrition and Food Safety, University of Barcelona, Barcelona, Spain. Electronic address:

A quadruplex Real-Time RT-PCR assay for the simultaneous quantitative detection of hepatitis A virus (HAV), norovirus (NoV) GI and GII, and mengovirus (used as process control for determination of the virus/nucleic acid extraction efficiency) has been developed. This multiplex assay has been comparatively evaluated with the individual monoplex assays and showed to be slightly less sensitive, with average ΔCq values of 0.90, 0.28 and 0.44 for HAV, NoV GI and NoV GII, respectively, in standard curves of viral RNA, or 0.32, 0.37 and 0.51 for the same viruses respectively, in naturally-contaminated samples. These ΔCq values were mostly negligible since it represented, in the worst case scenario, a loss of 0.43 log in genome copy numbers. The quadruplex assay shows similar theoretical detection limits than the monoplex assay for NoV GII, and 10 times higher for HAV and NoV GI. However, when naturally-contaminated food and water samples were tested, these theoretical detection thresholds were often exceeded and very low genome copy numbers (below the limit of detection) could be quantified. The quadruplex assay fulfills the requirements of the method developed by the European Committee on Standardization (CEN) for virus detection in selected foodstuffs with significant advantages in labor and reagent costs.
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http://dx.doi.org/10.1016/j.fm.2013.12.003DOI Listing
June 2014

Hepatitis A virus evolution and the potential emergence of new variants escaping the presently available vaccines.

Future Microbiol 2012 Mar;7(3):331-46

Enteric Virus Laboratory, School of Biology, University of Barcelona, Barcelona, Spain.

Hepatitis A is the most common infection of the liver worldwide and is fecal-orally transmitted. Its incidence tends to decrease with improvements in hygiene conditions but at the same time its severity increases. Hepatitis A virus is the causative agent of acute hepatitis in humans and belongs to the Hepatovirus genus in the Picornaviridae family, and it has very unique characteristics. This article reviews some molecular and biological properties that allow the virus to live in a very quiescent way and to build an extremely stable capsid that is able to persist in and out of the body. Additionally, the relationship between the genomic composition and the structural and antigenic properties of the capsid is discussed, and the potential emergence of antigenic variants is evaluated from an evolutionary perspective.
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http://dx.doi.org/10.2217/fmb.12.5DOI Listing
March 2012

Isolated recurrence of distal adenocarcinoma of the extrahepatic bile duct on a draining sinus scar after curative resection: case report and review of the literature.

World J Surg Oncol 2009 Dec 14;7:96. Epub 2009 Dec 14.

Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain.

Background: Surgical resection remains the gold standard for the treatment of localized adenocarcinoma of the extrahepatic bile ducts. Yet, treatment of loco-regional recurrences is not well defined.

Case Presentation: We present an unusual case of distal adenocarcinoma of the extrahepatic bile ducts that was treated with surgery and relapsed two years later with a solitary recurrence on the tract of a previous Redon drain. In addition, a review of the literature on management of loco regional relapses is presented.

Conclusions: The ideal management of these patients still remains undefined. Decisions are made based on clinical parameters from retrospective series, such as tumor grade, surgical margins or lymph node involvement. Prospective studies, that include molecular and genetic markers, are needed to improve patient selection and outcomes on this population.
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http://dx.doi.org/10.1186/1477-7819-7-96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801668PMC
December 2009

Gene expression profiling reveals overexpression of TSPAN13 in prostate cancer.

Int J Oncol 2009 Feb;34(2):457-63

Universidad Francisco de Vitoria, Facultad de CC. Biosanitarias, Departamento de Bioquímica y Biotecnología, and Hospital Universitario de Madrid-Monteprincipe, Departamento de Anatomía Patológica, Madrid, Spain.

Prostate cancer is one of the most frequent malignancies in the Western world. The identification of additional molecular markers is needed to refine the diagnosis of prostate cancer and to develop more effective therapies. In order to identify molecular abnormalities involved in prostate cancer progression, we performed gene expression analysis of prostate cancer samples compared to matched normal tissue from the same patient using a cancer-related microarray. Amplified RNA was hybridized to a cDNA microarray containing 6386 genes and tissue microarrays were used to study protein expression levels. Using significance analysis of microarrays, we identified >1300 genes differentially expressed in prostate cancer compared to normal tissue. Forty-two of these genes were highly upregulated in prostate cancer while 169 were highly repressed. We found that the gene coding for tspan13 was upregulated >2-fold in 75% of the samples analyzed. Immunohistochemistry analysis of prostate cancer tissue microarrays showed that tspan13 is overexpressed in 80% of prostate cancer samples analyzed. We found that tspan13 expression inversely correlates with Gleason score (p=0.01) and PSA preoperative levels (p=0.11) and directly correlates with presence of prostatic intraepithelial neoplasia in tumor tissue (p=0.04). Moreover, we detected tspan13 expression in low-grade prostatic intraepithelial neoplasia. Thus, our results show that tspan13 is overexpressed in prostate cancer and its expression correlates with factors of favourable outcome. Therefore we suggest that tspan13 may have an important role in the progression of prostate cancer.
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February 2009