Explorando la opinión de los especialistas españoles acerca de la utilidad de la radiómica en el área oncológica / Exploring the opinion of Spanish medical specialists about the usefulness of radiomics in oncology

Objetivo Describir el conocimiento y la opinión de los profesionales sanitarios relacionados con la oncología acerca de la radiómica. Métodos Se elaboró un cuestionario de 12 preguntas (respuestas de selección múltiple, de escala tipo Likert y respuesta abierta), dirigido a profesionales relacionados con el diagnóstico/tratamiento de enfermedades oncológicas (oncología, radiodiagnóstico, medicina nuclear, oncología-radioterápica, hematooncología, radiofísica y anatomía patológica). Los participantes se clasificaron en dos grupos según su grado de formación: adjuntos y residentes. Resultados Un total de 114 profesionales completaron la encuesta (54% residentes, principalmente de las especialidades medicina nuclear y radiodiagnóstico). Los adjuntos obtuvieron un mejor desempeño en el área de conocimiento respecto a los residentes. En ambos grupos los encuestados respondieron estar de acuerdo con la utilidad de la radiómica para ayudar a realizar diagnósticos más precisos, facilitando el trabajo de los equipos médicos. Las ideas más frecuentes relacionadas con las desventajas del uso de la radiómica se relacionaron con la falta de sistematización en la adquisición de imágenes y la extracción de parámetros, la necesidad de entrenamiento de los profesionales y la inquietud sobre el reemplazo del trabajo humano por herramientas tecnológicas. Conclusiones La radiómica es un campo de estudio novedoso, cuyos aspectos más generales son conocidos por los profesionales sanitarios. Los profesionales encuestados son optimistas en cuanto a los beneficios que entregan esta y otros tipos de herramientas. El principal problema detectado fue la falta de sistematización en su implementación. El reemplazo de los profesionales y la pérdida de trabajo es una preocupación presente, pero menos prevalente y que puede responder a un fenómeno generacional (AU)

Aim To describe the knowledge and opinion of health professionals regarding the usefulness of radiomics in oncology. Methods A 12-question questionnaire (multiple-choice responses, Likert-type scale, and open response) was developed and sent to professionals related to diagnosis/treatment of oncological diseases (Oncology, Radiodiagnosis, Nuclear Medicine, Radiation Oncology, Hematology-Oncology, Radiophysics and Pathology). Participants were classified into two groups according to their level of training: attending physicians and residents. Results 114 professionals completed the survey (54% residents, mostly from Nuclear Medicine and Radiodiagnostic specialties). Attending physicians obtained a better performance in the area pf knowledge compared to residents. Both groups of respondents agreed regarding the usefulness of radiomics to help make more accurate diagnoses and promoting the work of medical teams and the most frequent disadvantages were related to the lack of systematization in the acquisition of images and extraction of parameters, the need for the training of professionals and concern about the replacement of human work by technological tools. Conclusions Radiomics is a novel field and the most general aspects are known by health professionals. The professionals surveyed were optimistic about the benefits provided by radiomics and other types of tools. The main problem detected was the lack of systematization in its implementation. The replacement of professionals and job loss is a concern, albeit less prevalent, and may respond to a generational phenomenon (AU)

Frecuencia y características de la encefalopatia hipertensiva secundaria a glomerulonefritis posinfecciosa en pacientes internados en un hospital de referencia nacional

Introducción: La glomerulonefritis aguda pos infecciosa (GNPI) puede cursar con complicaciones como la encefalopatía hipertensiva en 7-11% de los casos. Objetivo : determinar la frecuencia y características de la encefalopatía hipertensiva (EH) secundaria a GNPI en pacientes internados en el Departamento de Pediatría del Hospital Nacional en el periodo enero/2000-diciembre/2018. Materiales y Métodos : Estudio observacional, descriptivo, retrospectivo de pacientes con síndrome nefrítico (SN) con C3 disminuido y normalización a los tres meses, con hipertensión arterial (HTA) severa acompañada de manifestaciones neurológicas (cefalea, náuseas, vómitos, alteración de conciencia, convulsiones), que cedieron al regularizarse la HTA. Se estudiaron las características sociodemográficas (edad, sexo, procedencia, escolaridad de los padres, número de hijos) y clínicas (edema periférico, edema agudo de pulmón, hematuria, y manifestaciones neurológicas). Los datos fueron analizados utilizando estadística descriptiva mediante EPIINFO (CDC, Atlanta), expresando las variables cuantitativas como mediana y rango intercuartílico (RIC) y las cualitativas como frecuencia absoluta y porcentual. Resultados: 27 /160 (16,8%) pacientes, desarrollaron EH. La edad varió entre 3 a 16 años (mediana: 10 años; RIC: 5); el antecedente infeccioso más frecuente fue piodermitis (40,7%), seguido de faringitis aguda (37%). Todos los pacientes presentaron edema periférico y cefalea intensa. La duración de la HTA tuvo una mediana de 5 días (RIC: 4) y los días de internación una mediana de 7 (RIC: 6). Ningún paciente requirió diálisis ni quedó con secuelas, no se registraron óbitos. Conclusión: en pacientes con EH debe considerarse el diagnóstico de GNPI, investigando antecedentes infecciosos y valorando adecuadamente la volemia.

Introduction: Acute post-infectious glomerulonephritis (APGN) can present with complications such as hypertensive encephalopathy in 7-11% of cases. Objective: to determine the frequency and characteristics of hypertensive encephalopathy (HE) secondary to APGN in patients admitted to the Department of Pediatrics of the National Hospital from January/2000 to December/2018. Materials and Methods: This was an observational, descriptive and retrospective study of patients with nephritic syndrome (NS) with decreased C3 and normalization at three months, with severe arterial hypertension (AHT) accompanied by neurological manifestations (headache, nausea, vomiting, altered consciousness, seizures), which subsided when the AHT was controlled. Sociodemographic (age, sex, place of residence, parental education level, number of children in home) and clinical (peripheral edema, acute pulmonary edema, hematuria, and neurological manifestations) characteristics were studied. The data were analyzed using descriptive statistics through EPI INFO (CDC, Atlanta), expressing the quantitative variables as median and interquartile range (IQR) and the qualitative ones as absolute frequency and percentage. Results: 27/160 (16.8%) patients developed HE. Age ranged from 3 to 16 years (median: 10 years; IQR: 5); the most frequent infectious history was pyodermitis (40.7%), followed by acute pharyngitis (37%). All patients presented peripheral edema and severe headache. The duration of AHT had a median of 5 days (IQR: 4) and the days of hospitalization a median of 7 (IQR: 6). No patient required dialysis or was left with sequelae, no deaths were recorded. Conclusion: in patients with HE, the diagnosis of APGN should be considered, a history of infections obtained and adequately assessing fluid status.

Progreso y utilidad actual de la radiómica dentro del estudio PET/TC en cáncer de mama no metastásico: una revisión sistemática / Progress and current utility of radiomics in PET/CT study of non-metastatic breast cancer: A systematic review

Objetivo Sintetizar la evidencia actual sobre la utilidad de la radiómica en el análisis de la imagen PET/TC en cáncer de mama local o localmente avanzado y evaluar la calidad metodológica de los estudios radiómicos publicados al respecto. Material y métodos Revisión sistemática de artículos en distintas bases de datos hasta 2021 utilizando los términos «PET», «radiomics», «texture», «breast». Se seleccionaron solo artículos con datos humanos y que incluyeran una imagen de PET en su análisis. Se excluyeron estudios con datos de pruebas y menos de 20 pacientes. De cada artículo se extrajo el tamaño muestral, el radiotrazador utilizado, la técnica de imagen y las características de imagen extraídas. Se determinó la calidad metodológica de los estudios mediante el instrumento QUADAS-2. Resultados Se seleccionaron 18 artículos. El diseño retrospectivo fue el más utilizado. La característica radiómica más estudiada fue el SUVmax. Diversos parámetros radiómicos se correlacionaron con la caracterización tumoral, y la heterogeneidad tumoral demostró utilidad para predecir el curso de la enfermedad y la respuesta al tratamiento. La mayoría de los artículos mostraron un alto riesgo de sesgo, derivado principalmente de la selección de pacientes. Conclusiones Se observó una alta probabilidad de sesgo en los artículos publicados. La radiómica es un campo aún en desarrollo y son necesarios más estudios para demostrar su utilidad en la práctica clínica habitual. La herramienta QUADAS-2 permite la valoración crítica de la calidad metodológica de la evidencia disponible. Pese a las limitaciones, la radiómica se muestra como una herramienta que puede ayudar a conseguir un manejo oncológico personalizado en el cáncer de mama (AU)

Aim To synthesize the current evidence of the usefulness of radiomics in PET/CT image analysis in local and locally advanced breast cancer. Also, to evaluate the methodological quality of the radiomic studies published. Methods Systematic review of articles in different databases until 2021 using the terms «PET», «radiomics», «texture», «breast». Only articles with human data and that included a PET image were included. Studies with simulated data and with less than 20 patients were excluded. The sample size, radiotracer used, imaging technique, and radiomics characteristics were extracted from each article. The methodological quality of the studies was determined using the QUADAS-2 tool. Results Eighteen articles were selected. The retrospective design was the most used. The most studied radiomic characteristic was SUVmax. Several radiomic parameters were correlated with tumor characterization, and tumor heterogeneity proved useful for predicting disease course and response to treatment. Most articles showed a high risk of bias, mainly from the patient selection. Conclusions A high probability of bias was observed in most of the published articles. Radiomics is a developing field and more studies are needed to demonstrate its usefulness in routine clinical practice. The QUADAS-2 tool allows critical assessment of the methodological quality of the available evidence. Despite its limitations, radiomics is shown to be an instrument that can help to achieve personalized oncologic management of breast cancer (AU)

Exploring the opinion of Spanish medical specialists about the usefulness of radiomics in oncology.

AIM: To describe the knowledge and opinion of health professionals regarding the usefulness of radiomics in oncology. METHODS: A 12-question questionnaire (multiple-choice responses, Likert-type scale, and open response) was developed and sent to professionals related to diagnosis/treatment of oncological diseases (Oncology, Radiodiagnosis, Nuclear Medicine, Radiation Oncology, Hematology-Oncology, Radiophysics and Pathology). Participants were classified into two groups according to their level of training: attending physicians and residents. RESULTS: 114 professionals completed the survey (54% residents, mostly from Nuclear Medicine and Radiodiagnostic specialties). Attending physicians obtained a better performance in the area pf knowledge compared to residents. Both groups of respondents agreed regarding the usefulness of radiomics to help make more accurate diagnoses and promoting the work of medical teams and the most frequent disadvantages were related to the lack of systematization in the acquisition of images and extraction of parameters, the need for the training of professionals and concern about the replacement of human work by technological tools. CONCLUSIONS: Radiomics is a novel field and the most general aspects are known by health professionals. The professionals surveyed were optimistic about the benefits provided by radiomics and other types of tools. The main problem detected was the lack of systematization in its implementation. The replacement of professionals and job loss is a concern, albeit less prevalent, and may respond to a generational phenomenon.

Progress and current utility of radiomics in PET/CT study of non-metastatic breast cancer: A systematic review.

AIM: To synthesize the current evidence of the usefulness of radiomics in PET/CT image analysis in local and locally advanced breast cancer. Also, to evaluate the methodological quality of the radiomic studies published. METHODS: Systematic review of articles in different databases until 2021 using the terms "PET", "radiomics", "texture", "breast". Only articles with human data and that included a PET image were included. Studies with simulated data and with less than 20 patients were excluded. Were extracted sample size, radiotracer used, imaging technique, and radiomics characteristics from each article. The methodological quality of the studies was determined using the QUADAS-2 tool. RESULTS: 18 articles were selected. The retrospective design was the most used. The most studied radiomic characteristic was SUVmax. Several radiomic parameters were correlated with tumor characterization, and tumor heterogeneity proved useful for predicting disease course and response to treatment. Most articles showed a high risk of bias, mainly from the patient selection. CONCLUSIONS: A high probability of bias was observed in most of the published articles. Radiomics is a developing field and more studies are needed to demonstrate its usefulness in routine clinical practice. The QUADAS-2 tool allows critical assessment of the methodological quality of the available evidence. Despite its limitations, radiomics is shown to be an instrument that can help to achieve personalized oncologic management of breast cancer.

Computational Analysis of the Global Effects of Ly6E in the Immune Response to Coronavirus Infection Using Gene Networks.

Gene networks have arisen as a promising tool in the comprehensive modeling and analysis of complex diseases. Particularly in viral infections, the understanding of the host-pathogen mechanisms, and the immune response to these, is considered a major goal for the rational design of appropriate therapies. For this reason, the use of gene networks may well encourage therapy-associated research in the context of the coronavirus pandemic, orchestrating experimental scrutiny and reducing costs. In this work, gene co-expression networks were reconstructed from RNA-Seq expression data with the aim of analyzing the time-resolved effects of gene Ly6E in the immune response against the coronavirus responsible for murine hepatitis (MHV). Through the integration of differential expression analyses and reconstructed networks exploration, significant differences in the immune response to virus were observed in Ly6E Δ H S C compared to wild type animals. Results show that Ly6E ablation at hematopoietic stem cells (HSCs) leads to a progressive impaired immune response in both liver and spleen. Specifically, depletion of the normal leukocyte mediated immunity and chemokine signaling is observed in the liver of Ly6E Δ H S C mice. On the other hand, the immune response in the spleen, which seemed to be mediated by an intense chromatin activity in the normal situation, is replaced by ECM remodeling in Ly6E Δ H S C mice. These findings, which require further experimental characterization, could be extrapolated to other coronaviruses and motivate the efforts towards novel antiviral approaches.

Indications and practice of diverting ileostomy after colorectal resection and anastomosis in ovarian cancer cytoreduction.

OBJECTIVE: To determine the factors related with diverting ileostomy performance after colorectal resection and anastomosis, in advanced ovarian cancer cytoreductive surgery. METHODS: We have previously demonstrated the risk factors associated with anastomotic leak after colorectal anastomosis: Advanced age at surgery, low serum albumin level, additional bowel resections, manual anastomosis and distance of the anastomosis from the anal verge. However, use of diverting ileostomy is strongly variable and depends on individual surgeon preferences and training. Eight hospitals participated in this retrospective study. Data of 695 patients operated for ovarian cancer with primary colorectal anastomosis were included (January 2010-June 2018). Fourteen pre-/intraoperatively defined variables were identified and analysed as justification factors for use of diverting ileostomy. RESULTS: The rate of diverting ileostomy in the entire cohort was 19.13% (133/695; range within individual centers 4.6-24.32%). Previous treatment with bevacizumab [OR 2.8 (1.3-6.1); p=0.01]; additional bowel resections [OR 3.0 (1.8-5.1); p<0.001]; extended operating time [OR 1.005 (1.003-1.006); p<0.001] and intra-operative red blood transfusion [OR 2.7 (1.4-5.3); p<0.001] were found to be independently associated with diverting ileostomy performance. Assuming a 7% AL rate cut-off, up to 51.8% of DI presented an AL risk below 7% and might have been spared. CONCLUSIONS: The risk factors that drive the gynecologic oncology surgeons to perform a diverting ileostomy, seem to differ from the actual risk factors that we have identified to be associated with postoperative anastomotic leak. Broader awareness of the risk factors that contribute to a higher perioperative risk profile, will facilitate a better risk stratification process and possibly avoid unnecessary stoma formation in ovarian cancer patients.

Short-course versus long-course antibiotic therapy for complicated appendicitis: A meta-analysis

OBJECTIVE@#To compare the efficacy of short-course versus longcourse antibiotic therapy among patients undergoing appendectomy for complicated appendicitis.@*METHODS@#The authors conducted an electronic search of PubMed, Cochrane Library, and EBSCOHost for studies from 2000 to January, 2000 to September, 2018 comparing short-course versus long-course antibiotic therapy in adults undergoing appendectomy for complicated appendicitis. The outcomes considered were the incidence of superficial surgical site infection and intra-abdominal abscess, and duration of hospital stay. Meta-analysis was performed using Review Manager software.@*RESULTS@#A total of 360 patients in two studies were analyzed. Superficial surgical site infection was identified in 5 out of 123 patients in the short-course antibiotic group (4%), and 5 out of 237 patients in the long-course antibiotic group (2.1%) (95% CI 0.38, 5.51, p=0.58). There was a decrease in the incidence of intra-abdominal abscess in the short-course antibiotic group (6.5%), but the difference was not statistically significant (95% CI 0.32, 1.77, p=0.52). The duration of hospital stay was significantly less in the short-course antibiotic group (3.95 days) compared to the long-course antibiotic group (4.6 days) (95% CI -0.66, -0.21; p<0.001). @*CONCLUSION@#No difference between the <5-day and ≥5-day antibiotic course in terms of surgical site infection and intra-abdominal abscess was detected. However, the hospital stay of the <5-day group was shorter.

Risk factors for anastomotic leakage after colorectal resection in ovarian cancer surgery: A multi-centre study.

OBJECTIVE: To determine pre-/intraoperative risk factors for anastomotic leak after modified posterior pelvic exenteration (MPE) or colorectal resection in ovarian cancer and to create a practical instrument for predicting anastomotic leak risk. BACKGROUND: In advanced ovarian cancer surgery, there is rather limited published evidence, drawn from a small sample, providing information about risk factors for anastomotic leak. METHODS: Eight hospitals participated in this retrospective study. Data on 695 patients operated for ovarian cancer with primary anastomosis were included (January 2010-June 2018). Twelve pre-/intraoperative variables were analysed as potential independent risk factors for anastomotic leak. A predictive model was created to stablish the risk of anastomotic leak for a given patient. RESULTS: The anastomotic leak rate was 6.6% (46/695; range 1.7%-12.5%). A total of 457 patients were included in the final multivariate analysis. The following variables were found to be independently associated with anastomotic leakage: age at surgery (OR 1.046, 95% CI 1.013-1.080, p = 0.005), serum albumin level (OR 0.621, 95% CI 0.407-0.948, p = 0.027), one or more additional small bowel resections (OR 3.544, 95% CI 1.228-10.23, p = 0.019), manual anastomosis (OR 8.356, 95% CI 1.777-39.301, p = 0.007) and distance of the anastomosis from the anal verge (OR 0.839, 95% CI 0.726-0.971, p = 0.018). CONCLUSIONS: Due to the low incidence of AL in ovarian cancer patients, a restrictive stoma policy based on the presence of risk factors should be the actual recommendation. Hand-sewn anastomosis should be avoided.

Clinical application of the sentinel lymph node technique in early ovarian cancer: a pilot study.

INTRODUCTION: There is limited evidence favoring the use of the sentinel lymph node technique in ovarian cancer, and no standardized approach has been studied. The objective of the present pilot study is to determine the feasibility of the sentinel lymph node technique by applying a clinical algorithm. METHODS: Patients with confirmed ovarian cancer were included. 99mTc and indocyanine green were injected into the ovarian and infundubulo-pelvic ligament stump. A gamma probe and near-infrared fluorescence imaging were used for sentinel lymph node detection. RESULTS: The sentinel lymph node technique was performed in nine patients with a detection rate in the pelvic and/or para-aortic region of 100%. The tracer distribution rates of sentinel lymph nodes in the pelvic and para-aortic regions were 87.5% and 70%, respectively. CONCLUSION: The detection of sentinel lymph nodes in early-stage ovarian cancer appears to be achievable. Based on these results, a clinical trial entitled SENTOV (SENtinel lymph node Technique in OVarian cancer) will be performed.

Optimization of surgical treatment of advanced ovarian cancer: a Spanish expert perspective.

BACKGROUND: Optimal upfront treatment of patients with advanced ovarian cancer is complex and requires the adequate function of a multidisciplinary team. Specific standard of quality of care needs to be taken into consideration. METHODS: A literature search in PubMed was performed using the following criteria: ("ovarian neoplasms"[MeSH Terms] OR ("ovarian"[All Fields] AND "neoplasms"[All Fields]) OR "ovarian neoplasms"[All Fields] OR ("ovarian"[All Fields] AND "cancer"[All Fields]) OR "ovarian cancer"[All Fields])"[Date - Publication]: "2018/01/14"[Date - Publication]). RESULTS: This article describes how to optimize the surgical management of advanced ovarian cancer, to achieve the best results in terms of survival and quality of life. For this purpose, this document will cover aspects related to pre-, intra- and postoperative care of newly diagnosed advanced ovarian cancer patients. CONCLUSION: Optimizing upfront treatment of patients with advanced ovarian cancer is complex and requires a structured quality management program including the wise judgment of a multidisciplinary team. Surgeries performed by gynecologic oncologists with formal training in cytoreductive techniques at referral centers are crucial factors to obtain better clinical and oncological outcomes. However, other factors such as the patient's clinical status, the hospital infrastructure and equipment, as well as the tumor biology of each individual patient should also be taken into account before deciding on an initial therapeutic strategy for advanced-stage ovarian cancer to offer patients the best quality of care.

Structure Optimization for Large Gene Networks Based on Greedy Strategy.

In the last few years, gene networks have become one of most important tools to model biological processes. Among other utilities, these networks visually show biological relationships between genes. However, due to the large amount of the currently generated genetic data, their size has grown to the point of being unmanageable. To solve this problem, it is possible to use computational approaches, such as heuristics-based methods, to analyze and optimize gene network's structure by pruning irrelevant relationships. In this paper we present a new method, called GeSOp, to optimize large gene network structures. The method is able to perform a considerably prune of the irrelevant relationships comprising the input network. To do so, the method is based on a greedy heuristic to obtain the most relevant subnetwork. The performance of our method was tested by means of two experiments on gene networks obtained from different organisms. The first experiment shows how GeSOp is able not only to carry out a significant reduction in the size of the network, but also to maintain the biological information ratio. In the second experiment, the ability to improve the biological indicators of the network is checked. Hence, the results presented show that GeSOp is a reliable method to optimize and improve the structure of large gene networks.

Pancreatic resections in renal failure patients: is it worth the risk?

Background. Chronic kidney disease affects 20 million US patients, with nearly 600,000 on dialysis. Long-term survival is limited and the risk of complex pancreatic surgery in this group is questionable. Previous studies are limited to case reports and small case series and a large database may help determine the true risk of pancreatic surgery in this population. Methods. The American College of Surgeons National Surgical Quality Improvement Program database was queried (2005-2011) for patients who underwent pancreatic resection. Renal failure was defined as the clinical condition associated with rapid, steadily increasing azotemia (rise in BUN) and increasing creatinine above 3 mg/dL. Operative trends and short-term outcomes were reviewed for those with and without renal failure (RF). Results. In 18,533 patients, 28 had RF. There was no difference in wound infections, neurologic or cardiovascular complications. Compared to non-RF patients, those with RF had more unplanned intubation (OR 4.89, 95% CI 1.85-12.89), bleeding requiring transfusion (OR 3.12, 95% CI 1.37-14.21), septic shock (OR 8.86, 95% CI 3.75-20.91), higher 30-day mortality (21.4% versus 2.3%, P < 0.001) and longer hospital stay (23 versus 12 days, P < 0.001). Conclusions. RF patients have much higher morbidity and mortality after pancreatic resections and surgeons should consider this before proceeding.

Clinical outcome, fertility and uterine artery Doppler scans in women with obstetric bilateral internal iliac artery ligation or embolisation.

The objective of our study was to report on the clinical outcome, fertility and uterine artery Doppler scans in patients with major postpartum haemorrhage, treated with bilateral internal iliac artery ligation or embolisation. We performed an observational analysis of successful bilateral internal iliac artery ligation or embolisation for postpartum haemorrhage in a tertiary hospital between 2001 and 2006. Clinical data and other medical/ surgical manoeuvres were recorded. Fertility data, menstrual cycle characteristics and uterine artery Doppler scans were assessed. Our success rate in bleeding control was 81%. Three patients got pregnant again 13, 16 and 23 months after the procedure. The one patient whose uterine artery was not identified in the Doppler scan was the only one who presented with secondary infertility. Three patients presented with secondary dysmenorrhoea. We concluded that internal iliac artery occlusion is an effective fertility-sparing procedure for postpartum haemorrhage. The absence of uterine revascularization could be a negative factor in future reproduction. Due to our limited sample size, larger studies are required to confirm these findings.

DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas.

BACKGROUND: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours. METHODS: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non-BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features. RESULTS: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours. CONCLUSION: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitors.

Phenotypic characterization of hereditary epithelial ovarian cancer based on a tissue microarray study.

The pathologic and immunohistochemical features of familial epithelial ovarian cancers are not well understood. We have carried out a comprehensive immunohistochemical study of familial ovarian carcinomas from women with and without BRCA1 or BRCA2 mutations, in order to identify specific and/or common features among these different familial case groups (BRCA1, BRCA2 and non-BRCA1/2) and to identify markers of diagnostic value that might help to select more specific treatments. 73 familial primary ovarian carcinomas were analyzed for the expression of 40 antibodies involved in different genetic pathways using a tissue microarray. Serous carcinomas comprised the majority of all three familial case groups. On the other hand, BRCA1 and BRCA2 carcinomas have similar histopathologic features; i.e. they are often high-grade and are usually diagnosed at a more advanced FIGO stage than non-BRCA1/2 carcinomas. In our series, BRCA1 carcinomas had better clinical evolution and they also more frequently over-expressed PR and P53 than BRCA2 and non-BRCA1/2 carcinomas. Unsupervised cluster analysis and survival analysis identified ERCC1 as a potential marker of better clinical outcome for hereditary epithelial ovarian cancer.

CarGene: characterisation of sets of genes based on metabolic pathways analysis.

The great amount of biological information provides scientists with an incomparable framework for testing the results of new algorithms. Several tools have been developed for analysing gene-enrichment and most of them are Gene Ontology-based tools. We developed a Kyoto Encyclopedia of Genes and Genomes (Kegg)-based tool that provides a friendly graphical environment for analysing gene-enrichment. The tool integrates two statistical corrections and simultaneously analysing the information about many groups of genes in both visual and textual manner. We tested the usefulness of our approach on a previous analysis (Huttenshower et al.). Furthermore, our tool is freely available (http://www.upo.es/eps/bigs/cargene.html).