[Comparing group educational intervention to individual and self-learning in COPD]. / Comparación de intervención educacional grupal frente a una individual y el autoaprendizaje en EPOC.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is considered a public health issue which affects 10.2% of Spanish population between 40 and 80 years of age. Many patients do not perform well the inhalation technique. Error rates vary between 50-80% depending on the device under study. These values haven been proven to decrease with educational interventions. OBJECTIVE: To ascertain whether a group educational intervention is superior to an individual intervention or to a conventional approach in these patients as regards quality of life measured by means of the total score of the COPD Assessment Test (CAT),of adherence to treatment, exacerbations and hospitalizations. MATERIAL AND METHODS: A multicenter, multidisciplinary cluster-randomized controlled clinical trial with three branches (conventional intervention, individual intervention and group intervention) in a cohort of COPD-patients. Sociodemographic data and risk factors were collected and several questionnaires were completed (CAT, BODEx, Barthel, Lawton y Brody). A descriptive analysis of qualitative and quantitative variables and a multiple linear regression were conducted. OUTCOMES: 149 patients of average age 69.08 (SD 1.26). Significant differences were observed in CAT in the different intervention groups according to the level of severity on BODEx. The rate of patients performing well the inhalation technique was significantly lower at the beginning of the study and the number of exacerbations was lower after the intervention. Last year's exacerbations were linearly related to post-intervention suffering. CONCLUSIONS: Better results are obtained using the traditional and individual interventions. There is a decrease in number of exacerbations, hospitalizations, CAT score and post-intervention inhalation technique.

Disfunción sexual en mujeres diagnosticadas y tratadas de cáncer de mama. Estudio descriptivo longitudinal / Sexual dysfunction in women diagnosed and treated for breast cancer: Descriptive longitudinal study

Objetivo: Describir el estado de la función sexual en mujeres a lo largo de un año tras el diagnóstico de cáncer de mama. Materiales y métodos: Estudio descriptivo longitudinal realizado entre septiembre de 2016 y junio de 2018. Para diagnosticar la disfunción sexual (DSx) en 110 mujeres tratadas de cáncer de mama incluidas se utilizó el Manual Diagnóstico y Estadístico de los Trastornos DSM-5; para describir la función sexual femenina se empleó el índice de la función sexual femenina (FSFI). El FSFI se cumplimentó tras el diagnóstico médico de cáncer de mama (V0); tras el tratamiento médico-quirúrgico (V1); y 12 meses después de la V0. Resultados: El 54,12% declararon no ser sexualmente activas. Mostraron DSx según el DSM-5: en la V0 un 64,86% siendo las más frecuentes los trastornos de interés/excitación (51,35%); orgásmico (35,14%); y dispareunia (32,43%); en la V1 un 77,74% siendo los más frecuentes el de interés/excitación (72,09%); el orgásmico (51,16%); y la dispareunia (41,86%); y 6 meses después de los tratamientos médico-quirúrgicos el 74,07%, siendo los más frecuentes el de interés/excitación (59,26%); la dispareunia (40,74%); y el orgásmico (37,04%). Las DSx más prevalentes según el FSFI, fueron la dispareunia (V0) y el trastorno de deseo sexual (V1, V2). En cuanto a la evolución de las DSx a lo largo del primer año tras la cirugía por cáncer de mama, estas parecen mejorar al año tanto en el valor total del FSFI (p = 0,016), como en el dominio «dolor» (p = 0,008). Conclusiones: Las DSx son frecuentes en mujeres supervivientes de cáncer de mama durante el primer año tras el diagnóstico médico. Los tratamientos médico-quirúrgicos no parecen influir negativamente en la función sexual detectada tras el diagnóstico médico. Las DSx se relacionan significativamente con la posmenopausia y con la linfadenectomía axilar

Objective: To describe the sexual function state in women treated for breast cancer over a year after the diagnosis of breast cancer. Materials and methods: A cross-sectional descriptive study was conducted between September 2016 and June 2018. One hundred and ten women treated for breast cancer were included. The Diagnostic and Statistical Manual of Disorders DSM-5 was used to assess sexual dysfunction (SD), and the Female Sexual Function Index (FSFI) was used to describe female sexual function. The FSFI was assessed after breast cancer diagnosis (V0); after medical-surgical treatment (V1); and 12 months after V0 (V2). Results: 54.12% of women were not sexually active. According to DSM-5, after the V0 assessment, 64.86% of women showed a SD, being the most frequent: interest/excitation disorder (51.35%); orgasmic disorder (35.14%); and dyspareunia (32.43%); at A1, 77.74% of women had a SD, with the most frequent being: interest/excitation disorder (72.09%); orgasmic disorder (51.16%); and dyspareunia (41.86%); and 6 months after medical-surgical treatments (V2), 74.07% of women had a SD, being the most frequent: interest / excitation disorder (59.26%); dyspareunia (40.74%); and orgasmic disorder (37.04%). The most prevalent SDs according to the FSFI, were dyspareunia at V0 and sexual desire disorder at V1 and V2 assessments. Regarding the evolution of the SD throughout the first year, the SD seem to improve after one year of the surgical treatment of breast cancer both in the total value of the FSFI (P = .016) and in the "pain" domain (P = .008). Conclusions: SD is current in breast cancer survivors during the first year after the medical diagnosis. Medical-surgical treatments do not seem to negatively influence the sexual function detected after the medical diagnosis. SD is significantly related to post-menopause and axillary lymphadenectomy

[Diagnostic and therapeutic difficulties in neurocysticercosis: presentation of 6 cases and review of the literature]. / Dificultades diagnósticas y terapéuticas en la neurocisticercosis: presentacion de 6 casos y revisión de la literatura.

INTRODUCTION: The incidence of neurocysticercosis (NCC) is increasing currently in developed countries due to the migration movements from endemic countries. Due to NCC polymorphism, treatment would be individualized in each case. Countries not used to this disease have to deal with. GOALS: To set up diagnostic and therapeutic guidelines in all sorts of NCC and choose the correct treatment would be challenging. PATIENTS AND METHODS: To perform a descriptive and retrospective analysis of six cases of NCC seen in the Neurosurgery Department of the Hospital Clinic de Barcelona from 1992 to 2000 (both included). We have performed a revision of the literature about diagnostic and therapeutic methods. DISCUSSION: Definitive or probable diagnosis of NCC is based on clinical, imaging, immunological, and epidemiological criteria. In patients with inactive disease only symptomatic treatment is indicated. In active parenchymal forms there are not consensus if antiparasitic treatment is indicated. However, in extraparenchymal active disease aggressive treatment with antiparasitic agents and steroids is recommended. In cases of intracranial hypertension, neurological deficits or hydrocephalus surgery is the treatment of choice.

[Diagnosis and staging of carcinoma of the pancreas (I)]. / Diagnóstico y estadificación del carcinoma de páncreas (I).

Carcinoma of the pancreas is a neoplasm with a poor prognosis that is diagnosed in the advanced stages in most patients. Given that surgical resection is the only potentially curative treatment for this disease, it is of the utmost importance to appropriately select the group of patients with initial stage pancreatic tumors that have not extended and can therefore be resected. Several different imaging techniques can be used for this purpose: ultrasonography (US), computed tomography (CT), magnetic resonance (MR), as well as the recent additions of endoscopic ultrasonography (EUS) and positron emission tomography (PET). Other techniques, such as laparoscopy and laparoscopic ultrasonography, also play a role in the diagnosis and staging of these patients. Continual technological developments in each of the above-mentioned techniques have led to reiterated updates in the scientific literature throughout the last two decades. This review aims to evaluate each of these techniques and present diagnostic algorithms reflected in the literature in order to achieve the greatest diagnostic accuracy in determining the extent of the disease so that unnecessary surgery can be avoided in cases not susceptible to resection.

Overexpression of c-myc and loss of heterozygosity on 2p, 3p, 5q, 17p and 18q in sporadic colorectal carcinoma.

AIM: The aim of the present study is to evaluate the prognostic influence of loss of heterozygosity on 2p, 3p, 5q, 17p and 18q, and c-myc overexpression on surgically treated sporadic colorectal carcinoma. METHODS: Tumor and non-tumor tissue samples from 153 patients were analyzed. Fifty-one percent of patients were male, and mean age in the series was 67 years. Tumors were located in the proximal colon in 37 cases, in the distal bowel in 37, and in the rectum in 79 patients. c-myc overexpression was studied by means of Northern blot analysis, and loss of heterozygosity through microsatellite analysis. RESULTS: c-myc overexpression was detected in 25% of cases, and loss of heterozygosity in at least one of the studied regions in 48%. There was no association between clinical and pathologic features, and genetic alterations. The disease-free interval was significantly shorter for patients with both genetic alterations; the presence of both events was an independent prognostic factor for poor outcome in the multivariate analysis (RR: 4.34, p < 0.0001). CONCLUSIONS: The presence of both loss of heterozygosity and overexpression of the c-myc oncogene separates a subset of colorectal carcinoma patients who have a shorter disease-free interval after curative-intent surgery.

Characterization of MDGA1, a novel human glycosylphosphatidylinositol-anchored protein localized in lipid rafts.

We report the characterization of the novel human protein MDGA1 encoded by MDGA1 (MAM domain containing glycosylphosphatidylinositol anchor-1) gene, firstly termed as GPIM. MDGA1 has been mapped to 6p21 and it is expressed in human tissues and tumors. The deduced polypeptide consists of 955 amino acids and exhibits structural features found in different types of cell adhesion molecules (CAMs), such as the presence of both immunoglobulin domains and a MAM domain or the capacity to anchor to the cell membrane by a GPI (glycosylphosphatidylinositol) motif. Our results demonstrate that human MDGA1 (hMDGA1) is localized in the membrane of eukaryotic cells. The protein follows the secretion pathway and finally it is retained in the cell membrane by a GPI anchor, susceptible to be cleavaged by phospholipase C (PI-PLC). Moreover, our results reveal that hMDGA1 is localized specifically into membrane microdomains known as lipid rafts. Finally, as other proteins of the secretory pathway, hMDGA1 undergoes other post-translational modification consisting of N-glycosylation.

Clinical relevance of MMP-9, MMP-2, TIMP-1 and TIMP-2 in colorectal cancer.

The main aim of this study was to evaluate the clinical relevance of Gelatinases in colorectal cancer (CRC). Ninety-five CRCs and their paired normal tissues were investigated to detect total levels of MMP-9, MMP-2, and the tissue inhibitors TIMP-1 and TIMP-2. Also, pro-MMP and MMP activity, and potential associations with clinical parameters were estimated. MMP-9, MMP-2 and TIMP-1 levels were greater in CRCs than in normal tissues, differences being significant for MMP-9 and TIMP-1. However, TIMP-2 showed significantly lower levels in tumour samples. Moreover, significant differences in the state of activation between gelatinases were found. TIMP-1 low levels were significantly associated with poor clinical outcome of patients. According to these data, different roles have to be attributed to MMP-2 and MMP-9 in CRC progression. Moreover, TIMP-1 level evaluation emerges as the main prognostic factor in relation to Gelatinases A and B activity in CRC.

Relationship between 3p deletions and telomerase activity in non-small-cell lung cancer: prognostic implications.

3p deletions and telomerase reactivation are two of the most frequent events described in relation to non-small-cell lung cancer (NSCLC) pathogenesis. Moreover, a number of genes that map on 3p have been proposed as candidates to tumour-suppressor genes of importance in the lung cancer process. In this work, we analysed deletions at different 3p loci in relationship to telomerase activity in 66 NSCLCs obtained from patients who had suffered potentially curative surgery. Also, we evaluated prognostic implications. DNA samples were analysed for 3p deletions using five different polymorphic human dinucleotide repeat DNA markers (D3S1619 at 3p22.2, D3S3623 at 3p22.1, D3S1260 at 3p21.33, D3S3697 at 3p14.3, and D3S3722 at 3p21.2). Telomerase activity was investigated by a TRAP-based method. Possible correlations between the different molecular markers and distributions of disease-free survival were estimated. Our data revealed a significant correlation between telomerase activity and losses of heterozygosity (LOH) on D3S3697 (P=0.040), since all of the tumours showing deletion at this locus were positives for telomerase. Moreover, our results revealed clear associations with poor prognosis of patients, in the case of LOH at D3S1260 and D3S3697 (P=0.005 and 0.005, respectively). According to our data, potential repressors for telomerase may be located in chromosome 3p.

Hereditary subependymal heterotopia associated with mega cisterna magna: antenatal diagnosis with magnetic resonance imaging.

Bilateral nodular subependymal heterotopia has recently been identified as a hereditary disease linked to the X-chromosome. The sonographic findings are very subtle and difficult to observe during the second trimester when the germinal matrix is at its largest. Fetal magnetic resonance imaging facilitates visualization of the periventricular area. We report a case of bilateral nodular heterotopia associated with mega cisterna magna diagnosed by ultrasound and magnetic resonance imaging at 29 weeks' gestation. Magnetic resonance imaging of the brain of the mother revealed similar findings to those observed in the fetus and neonate. This case confirms the association between mega cisterna magna and bilateral periventricular nodular heterotopia and demonstrates that neuroimaging studies of the mother can contribute to the fetal diagnosis.

Loss of heterozygosity at 3p23 is correlated with poor survival in patients with colorectal carcinoma.

BACKGROUND: Loss of heterozygosity (LOH) of chromosome 3p has been observed commonly in carcinomas of various tumor tissues, including colorectal carcinoma (CRC). Because there is no report analyzing 3p deletions in relation to patient prognosis in CRC, the authors investigated the prognostic value of LOH on 3p in 87 patients with sporadic CRC. METHODS: DNA samples from tumor and nontumor tissues were amplified by using polymerase chain reaction (PCR) and were analyzed for LOH on 3p using four different polymorphic human dinucleotide repeat DNA markers that map on this chromosome arm. The correlations with prognosis were established by the Kaplan-Meier method, and the Cox proportional hazards model was used to identify which independent factors jointly had a significant influence on patient survival. RESULTS: Overall, allelic losses were detected in 19.5% of the patients evaluated. Only considering informative tumors, the data indicated that LOH was observed in 17 of 71 (29.4%) informative cases. Results from survival analysis showed a significant correlation between this molecular abnormality and both overall survival and disease free survival (P = 0.02 and P = 0.0005, respectively). The worst prognosis was found for the group of patients with LOH at 3p23: This alteration was an independent prognostic factor according to Cox multivariate analysis. CONCLUSIONS: This study is the first to demonstrate the prognostic significance of LOH at chromosome arm 3p for patients CRC and may help to identify patients who need an intensive postoperative follow-up protocol.

Detection of telomerase activity in human carcinomas using a trap-ELISA method: correlation with hTR and hTERT expression.

We have evaluated telomerase activity in a tumour population of 65 human cancers by using a TRAP-based method, in which detection is performed by an enzyme immunoassay (ELISA). We have corroborated that sensitivity and specificity of this new procedure can be considered similar to that of classical TRAP method, having the advantage of a rapid and reproducible analysis of large pools of samples. Thus, telomerase activity was detected in 83% of the tumours included in our population. Moreover, we found a significant association between enzyme activity and both hTR and hTERT expression (P=0.004 and P=0.04, respectively).

DNA amplification on chromosome 6p12 in non small cell lung cancer detected by arbitrarily primed polymerase chain reaction.

Gene amplification is clearly an important aspect of tumour growth and development and has prognostic significance in certain tumours. The identification and genetic characterisation of new areas of amplification in human malignancy remains an important goal in understanding the underlying genetic lesions within these tissues. In the present work, arbitrarily primed-PCR (AP-PCR) has been applied to detect and characterise amplified DNA fragments in human non small cell lung cancer (NSCLC). Our results show that gains of genomic sequences occur at high frequency (64% of all genomic changes analysed). Moreover, we succeeded in detecting a genomic sequence that is highly amplified in one of the tumours analysed. The amplification intensity of this DNA fragment was also increased in 29 (45%) of the 65 NSCLC patients from our study. The amplified DNA fragment was isolated and identified as a 600 bp sequence mapped to chromosome 6p12. This sequence did not show significant homology with known human DNA sequences. Interestingly, a gene related to cancer processes, the pim-1 oncogene, is placed neighbouring to this region on chromosome 6. Survival studies revealed that disease-free interval of NSCLC patients was shorter in patients bearing the amplified sequence (p = 0.05 by the Breslow test). Our findings suggest that the amplified sequence located on chromosome 6 might be relevant in the pathogenesis of human NSCLC. Int. J. Cancer (Pred. Oncol.), 84:344-349, 1999.

Differential prognosis of replication error phenotype and loss of heterozygosity in sporadic colorectal cancer.

Several distinct genetic alterations have been associated with colorectal tumorigenesis. This study investigated the frequency of microsatellite instability, also known as replication error (RER), and loss of heterozygosity (LOH) at six chromosome regions in sporadic colorectal cancer (CRC). Eighty-six tumour and paired normal mucosa samples were included in the study. A polymerase chain reaction (PCR)-based technique was performed to analyse six (CA)n dinucleotide repeats located near or within regions containing important genes implicated in the complex process of colorectal tumorigenesis (chromosomes 2p, 3p, 5q, 11p, 17p and 18q). Overall, LOH frequency was higher in RER-tumours (25/46, 54.3%) compared with RER+ tumours (9/40, 22.5) (P = 0.04). To investigate prognostic implications, survival analysis was performed for 66 patients. Compared with RER- tumours, patients with RER+ tumours at 2p, 3p, 5q, 11p or 18q were found to have an improved prognosis (overall survival, P = 0.02 and disease-free survival (DFS) P = 0.005) this variable being an independent prognostic factor by multivariate analysis (P = 0.001). Overall survival of patients whose tumours were LOH+ was significantly shorter compared with those without LOH (overall survival, P = 0.008 and DFS, P = 0.01). Thus, tumours displaying RER+ and LOH+ phenotype, as established by microsatellite analysis, show a differential prognosis. These data indicate that this may be a useful tool for the identification of patients at different risks affected by CRC.

p53 exon 7 mutations as a predictor of poor prognosis in patients with colorectal cancer.

We have studied 61 resected colorectal adenocarcinomas in order to investigate p53 mutations as a prognostic factor for this pathology. Mutations in exons 5-9 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing. Our data indicate that p53 exon 7 mutations were prevalent in the latest stages of colorectal carcinogenesis and patients bearing this alteration had the worst prognosis. Therefore, according to our results, mutations affecting exon 7 of the p53 gene could be considered as a useful marker of biological aggressiveness for colorectal cancer.

Genetic abnormalities and microsatellite instability in colorectal cancer.

Our purpose was to investigate different genetic abnormalities, such as K-ras mutations, p53 alterations, and c-myc RNA overexpression, as well as microsatellite instability in 63 colorectal tumors obtained from patients that had undergone surgery. K-ras point mutations were analyzed by PCR-RFLP technique, followed by sequencing; p53 protein accumulation by immunohistochemistry; p53 gene mutations in exons 5-9 were studied by the SSCP and sequencing techniques, and c-myc overexpression by Northern blot. Microsatellite instability was performed at chromosomes 2p, 3p, and 11p by a PCR-based technique. Our data indicate a trend toward a poorer prognosis in patients who had K-ras transversions; besides, we have obtained a prevalence of c-myc RNA overexpression and p53 exon 7 mutations in the latest stages of tumor progression. In conclusion, our findings suggest that the recognition of molecular abnormalities might be used in colorectal cancer as a prognostic indicator or to determine the metastatic potential of colorectal adenocarcinomas.

Prognostic significance of p53 gene mutations in squamous cell carcinoma of the lung.

The aim of the present study was to analyze the prevalence and clinical importance of p53 gene mutations in surgically treated squamous cell lung carcinoma. Sixty patients were included. Fifty-one patients in stages I to IIIa were submitted to radical resection. Twenty-five samples tested positive for the p53 immunohistochemistry assay, and were analyzed for p53 gene mutations. Eleven mutations were found. Patients harboring p53 gene mutations suffered a higher incidence of recurrence and a higher mortality rate. Disease-free interval and overall survival were shorter for patients with mutated p53 gene (p=0.03 and p=0.005, respectively).

Prognostic value of genomic damage in non-small-cell lung cancer.

Genomic alterations have been analysed in 65 non-small-cell lung cancer (NSCLC) tissue samples by using the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting. We have shown that AP-PCR may be applied as a useful and feasible practical method for detection of the genomic alterations that accompany malignancy in NSCLC. Genomic changes detected by us consisted of: allelic losses or gains in anonymous DNA sequences, homozygously deleted DNA sequences and polymorphic DNA sequences. According to these genomic changes, lung tumours evaluated in the present study have been scored into three groups: low, moderate and high genomic damage tumours. The aim of this study was to investigate the effect of genomic damage on patient survival. Survival analysis was carried out in 51 NSCLC patients. Our results revealed that high genomic damage patients showed a poorer prognosis than those with low or moderate genomic damage (P = 0.038). Multivariate Cox regression analysis showed that patients with higher genomic alterations displayed an adjusted-by-stage risk ratio 4.26 times higher than the remaining patients (95% CI = 1.03-17.54). We can conclude that genomic damage has an independent prognostic value of poor clinical evolution in NSCLC.

Comparative survival analysis of p53 gene mutations and protein accumulation in colorectal cancer.

Immunohistochemical reactivity for p53 protein is common in various human malignancies. Increased intracellular concentration of p53, which is frequently, but not systematically, related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 alterations, we screened a series of 72 colorectal carcinomas for overexpression and mutation of the p53 gene. Mutations in exons 5-9 of the p53 gene were assayed by single-strand conformation polymorphism and direct DNA sequencing, whereas p53 protein accumulation was detected in 10-microm frozen tissue by immunostaining using 2 different monoclonal antibodies (PAb 1801 and DO7). Thirty-six tumors (50%) showed p53 overexpression. Nineteen of the 36 tumors which contained high levels of p53 protein were found to have missense point mutations. Using a multivariate survival analysis, stage, differentiation, p53 immunoreactivity and p53 mutation emerged as risk factors, but only the stage was significant. In univariate analysis, stage, differentiation and p53 immunoreactivity were significant prognostic indicators, while p53 mutation was at the borderline of significance.

p53 exon 5 mutations as a prognostic indicator of shortened survival in non-small-cell lung cancer.

Inactivation of the tumour-suppressor gene p53 has been described as one of the most common molecular changes found in lung tumours. Our purpose was to study the prognostic value of p53 alterations and to determine whether some specific mutation type in the p53 gene could be associated with poor clinical evolution in non-small-cell lung cancer (NSCLC) patients. To this end, we studied 81 resected primary NSCLCs in order to detect p53 alterations. p53 protein accumulation was analysed using immunohistochemistry methods; p53 gene mutations in exons 5-9 were studied using polymerase chain reaction-single-strand conformation polymorphism and sequencing techniques. p53 protein was immunodetected in 46.9% of lung carcinomas and 44.7% of p53-immunopositive tumours showed p53 mutations. Survival analysis was performed on 62 patients. No survival differences were found for patients with or without p53 immunopositivity. A shorter survival was found in patients with underlying p53 gene mutations, mainly in patients with squamous cell lung tumours; the worst prognosis was found when mutations were located in exon 5 (P = 0.007). In conclusion, the location of p53 mutations might be considered as a prognostic indicator for the evaluation of poor clinical evolution in NSCLC patients.