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.

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.

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.

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.

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.

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.

Gene association analysis: a survey of frequent pattern mining from gene expression data.

Establishing an association between variables is always of interest in genomic studies. Generation of DNA microarray gene expression data introduces a variety of data analysis issues not encountered in traditional molecular biology or medicine. Frequent pattern mining (FPM) has been applied successfully in business and scientific data for discovering interesting association patterns, and is becoming a promising strategy in microarray gene expression analysis. We review the most relevant FPM strategies, as well as surrounding main issues when devising efficient and practical methods for gene association analysis (GAA). We observed that, so far, scalability achieved by efficient methods does not imply biological soundness of the discovered association patterns, and vice versa. Ideally, GAA should employ a balanced mining model taking into account best practices employed by methods reviewed in this survey. Integrative approaches, in which biological knowledge plays an important role within the mining process, are becoming more reliable.

A biclustering algorithm for extracting bit-patterns from binary datasets.

MOTIVATION: Binary datasets represent a compact and simple way to store data about the relationships between a group of objects and their possible properties. In the last few years, different biclustering algorithms have been specially developed to be applied to binary datasets. Several approaches based on matrix factorization, suffix trees or divide-and-conquer techniques have been proposed to extract useful biclusters from binary data, and these approaches provide information about the distribution of patterns and intrinsic correlations. RESULTS: A novel approach to extracting biclusters from binary datasets, BiBit, is introduced here. The results obtained from different experiments with synthetic data reveal the excellent performance and the robustness of BiBit to density and size of input data. Also, BiBit is applied to a central nervous system embryonic tumor gene expression dataset to test the quality of the results. A novel gene expression preprocessing methodology, based on expression level layers, and the selective search performed by BiBit, based on a very fast bit-pattern processing technique, provide very satisfactory results in quality and computational cost. The power of biclustering in finding genes involved simultaneously in different cancer processes is also shown. Finally, a comparison with Bimax, one of the most cited binary biclustering algorithms, shows that BiBit is faster while providing essentially the same results. AVAILABILITY: The source and binary codes, the datasets used in the experiments and the results can be found at: http://www.upo.es/eps/bigs/BiBit.html CONTACT: dsrodbae@upo.es SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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.

New approaches to female fertility preservation.

Survival rates have been improved in young cancer patients due to advances in oncologic treatments. It is necessary to focus on the consequences of cancer treatments and try to elude or at least prevent them. Menopause and infertility are two of the main causes for concern to those patients who survive cancer. When a solution is offered to these patients, their quality of life and self-esteem can be dramatically increased after therapy. Results observed in vitrified oocytes are similar to those achieved with fresh oocytes, giving this method great potential. Recommendations on fertility preservation should be focused on the oocyte vitrification method, which should be considered as the first option. Limitations of this approach are the need for ovarian stimulation, which means a 2-3 week period prior to chemotherapy and the possibility of high oestradiol levels when tumours are hormone dependent.

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.

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.

Design, manufacture and evaluation of a NiTi stent for colon obstruction.

We have designed, manufactured and evaluated a prototype of a new stent based on the superelasticity of the NiTi alloy for colon obstruction, which is the first clinical manifestation of colorectal cancer in up to 29% of cases. The stent is auto-expandable diamond cell type, manufactured from a NiTi tube with 4.5 mm in diameter, in which longitudinal grooves were performed by cutting laser technique. The expansion process to the final shape was made by deformation in the martensite state. The stent reaches a high free expansion rate of 7, with a longitudinal variable radial strength and a bell-shaped profile in the extremes in order to avoid migration. Finite elements models were used for simulating the mechanical behaviour. The prototype was evaluated by implantation in a colon stenosis model of 6 mm in diameter performed in a porcine speciment. The stent gave a good deployment, fixation and capability to open the gap up to 15 mm in diameter.

Antibiotic treatment induces an increase of the specific antibody levels in Brucella melitensis infected mice.

The effects of doxycycline (DOX) and streptomycin (SM) treatment of Brucella melitensis infected mice on humoral immune response were examined. In female BALB/c mice, DOX was administered at a dose of 50 mg/kg/12 h, for 21 or 45 consecutive days, alone or combined with SM (10 mg/kg/12 h) for 14 days. All treatments induced a significant increase in specific IgG levels (ELISA and CIEP) against LPS and cytosolic antigens of Brucella during treatment. This was not related with therapeutic failure or relapse since all treatments induced a significant reduction in the degree of infection.

The reactions of myoglobin, normal adult hemoglobin, sickle cell hemoglobin and hemin with hydroxyurea.

The kinetics of the reaction of hydroxyurea (HU) with myoglobin (Mb), hemin, sickle cell hemoglobin (HbS), and normal adult hemoglobin (HbA) were determined using optical absorption spectroscopy as a function of time, wavelength, and temperature. Each reaction appeared to follow pseudo-first order kinetics. Electron paramagnetic resonance spectroscopy (EPR) experiments indicated that each reaction produced an FeNO product. Reactions of hemin and the ferric forms of HbA, HbS, and myoglobin with HU also formed the NO adduct. The formation of methemoglobin and nitric oxide-hemoglobin from these reactions may provide further insight into the mechanism of how HU benefits sickle cell patients.

Inadequate azithromycin activity against Brucella melitensis in mice with acute or chronic infections.

The activities of therapeutic regimens with azithromycin (AZI) and doxycycline combined with streptomycin (DOX-SM) were compared in Brucella melitensis infected mice. In a chronic model, AZI given over 10, 14 or 21 consecutive days (50 mg/kg/24 h) significantly reduced the infection (1.3-1.6 logs, day 48 post-infection). However, the effectiveness of DOX (21 days, 50 mg/kg/12 h) was higher than AZI (3.4 logs of reduction, day 48 post-infection). Besides, when DOX was administered for 45 days, it "cured" all the animals from day 78. Similar results were obtained in an acute model infection. One single dose of DOX or DOX-SM, starting one day after lethal challenge, was able to protect 83% of the mice. In contrast, only 25% of the mice treated with AZI (50-200 mg/Kg) survived the challenge. Our findings demonstrate that AZI, in contrast to DOX-SM, does not cure experimental brucellosis.