Early evolutionary divergence between papillary and anaplastic thyroid cancers.

Background: Papillary thyroid cancer (PTC) is the most common thyroid carcinoma and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer (ATC) is less frequent and is one of the most aggressive cancers usually resistant to conventional treatment. Current hypothesis posits that ATC derives from PTC through the progressive acquisition of a discrete number of genomic alterations and implies that the mutational landscape of ATC resembles that of PTC. However, the clinical behaviour of ATC and PTC is radically different. We decided to address the disconnection between the clinical behaviour of ATC and PTC and the proposed model of the progressive development of ATC from PTC. Patients and methods: We carried out exome sequencing of DNA from 14 ATC specimens including three cases of concomitant ATC and PTC as well as their corresponding normal DNA from 14 patients. The sequencing results were validated using droplet digital PCR. We carried out immunohistochemistry and immunofluorescence studies of the concomitant ATC and PTC cases. In addition, we integrated our sequencing results with the existing TCGA data. Results: Most of the somatic mutations identified in the ATC component differed from the ones in PTC in the cases of concomitant ATC and PTC. The trunks of the phylogenetic trees representing the somatic mutations were short with long branches. In one case of concomitant PTC and ATC specimens, we observed an infiltration of PTC cells within the ATC component. Moreover, we integrated our results with data obtained from TCGA and observed that the most frequent mutations found in ATC presented high cancer cell fraction values and were significantly different from the PTC ones. Conclusion: ATC diverge from PTC early in tumour development and both tumour types evolve independently. Our work allows the understanding of the relationship between ATC and PTC facilitating the clinical management of these malignancies.

Rediscovering contact inhibition in the embryo.

The cellular reaction called contact inhibition of locomotion was initially characterised by Michael Abercrombie more than 60 years ago. In his most general definition, it is defined as the stopping of the continued locomotion of a cell in the direction which has produced a collision with another cell. This deceptively simple response has been widely studied in vitro in a number of cell types over the years, yet it is still often misunderstood by the scientific community. Abercrombie spent much of his life studying the failure of the response shown by cancer cell types and how this might lead to malignant invasion of normal tissue. However, since Abercrombie's time, a role for this response in living organisms has been left to the realm of speculation. Here, we discuss the history of contact inhibition research, clarify some of the misconceptions about the response and reclaim misused terminology. We will also highlight our recent work, which for the first time elucidates a functional role for contact inhibition in vivo during embryogenesis.

Short-term outcome of psychogenic non-epileptic seizures after communication of the diagnosis.

We previously described a communication strategy for the delivery of the diagnosis of psychogenic non-epileptic seizures (PNES) that was acceptable and effective at communicating the psychological cause of PNES. This prospective multicenter study describes the short-term seizure and psychosocial outcomes after the communication of the diagnosis and with no additional treatment. Participants completed self-report measures at baseline, two and six months after the diagnosis (seizure frequency, HRQoL, health care utilization, activity levels, symptom attributions and levels of functioning). Thirty-six participants completed the self-report questionnaires. A further eight provided seizure frequency data. After six months, the median seizure frequency had dropped from 10 to 7.5 per month (p=0.9), 7/44 participants (16%) were seizure-free, and an additional 10/44 (23%) showed greater than 50% improvement in seizure frequency. Baseline questionnaire measures demonstrated high levels of impairment, which had not improved at follow-up. The lack of change in self-report measures illustrates the need for further interventions in this patient group.

Attention deficit hyperactivity disorder increases the risk of having abnormal eating behaviours in obese adults.

OBJECTIVE: To determine the rate of abnormal eating behaviours in obese adult patients with attention deficit hyperactivity disorder (ADHD) in comparison with obese adult patients without ADHD. METHOD: This case-control study includes: obese adult patients defined by a body mass index (BMI) ≥30 kg/m², screening positive in the adult ADHD self-report scale-V1.1. (ASRS-V1.1), attending the Nutrition Section, as cases; and obese adult patients screening negative, as controls. Weight, height and BMI were determined in all the participants. The rate of abnormal eating behaviours was determined using an eating pattern questionnaire. RESULTS: Forty-five out of 51 (88.2%) cases vs 127 out of 179 (70.9%) controls had abnormal eating behaviours (p=0.01). Eating between-meal snacks was found in 39 (76.5%) cases vs 107 (59.8%) controls (p=0.03), going on binge eating episodes in 28 (54.9%) vs 42 (23.5%) (p=0.00), waking up at night to eat in 11 (21.6%) vs 16 (8.9%) (p=0.01), eating large amounts of food in 13 (25.5%) vs 38 (21.2%) (p=0.52), and eating in secret in 11 (21.6%) vs 16 (8.9%) (p=0.01), respectively. CONCLUSION: This is the first study that determines the rate of these abnormal eating behaviours in obese adult patients with ADHD in comparison with obese adult patients without ADHD. A high rate of abnormal eating behaviours was observed in obese patients with ADHD. Our results suggest that ADHD is a risk factor for the development of these abnormal eating behaviours, which may be contributing factors of obesity and the unsuccessful treatment of obese patients.

[High percentage of adrenergic symptoms in extraadrenal chromaffin tumors]. / Manifestaciones adrenérgicas de los tumores del tejido cromafín extraadrenal.

UNLABELLED: Descriptive retrospective study of 14 patients with paragangliomas (PGL) attended in the University Hospital of Vigo (Pontevedra) during the last 25 years to evaluating their characteristics and neuroendocrine potential. RESULTS: 71.4% were diagnosed due to mass tumoral effect, 21.4% due to adrenergic symptoms and 7.1% incidentally. Regarding to symptoms and signs 66.7% of PGL Simpatic (PGLS) and 40% of PGL Parasimpatic (PGLPS) presented adrenergic symptoms. Urine catecholamine analysis was carried out to 4 PGLS and high levels were found in all patients. The tumoral size reached a mean value of 37.8+/-18.9 mm, there were not differences found between both types of tumors. Inmunohistoquimia showed positive Chromogranine A stain in all patients. Two PGLS were maligns. Eleven patients had positive outcome, 2 PGLS died, and 1 PGLPS remains not cured. CONCLUSIONS: High percentage of patients had clinical manifestations related to catecholamine hyperproduction. We believe that due to the risk related to surgical treatment, malignance, multiple location and family associations, it would be advisable to carry out a complete examination prior to surgery.

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease.

Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease.

[High frequency of non-specific eating disorders in obese persons]. / Alta frecuencia de trastornos de la conducta alimentaria inespecíficos en personas obesas.

OBJECTIVES: Determine frequency of Eating Disorders and Non-Specific Eating Disorders and pathological behaviour in obese patients. SUBJECTS AND METHODS: The study includes fifty-four obese patients (BMI > or = 30) consecutively attended at the Nutrition Section of the University Hospital of Vigo. Aged 37.5 +/- 11.1. Range 18-58, 45 female and 9 male. CONTROL GROUP: 15 adult normal-weight subjects (11 female, 4 male), aged 35,3 +/- 9,2 años. Frequency of Eating Disorders was determined by a lifestyle clinical interview and the following questionnaires: Eating Attitudes Test 26 (EAT26), Bulimic Investigatory Test Edimburgh (BITE) and Questionnaire Eating Weight Patterns Revised (QEWP-R). RESULTS: Twelve out of 54 (20.6%) patients showed Pathological Behavior, while 5 (4.1%) and 3 (2.5%) had Non- Specific Eating Disorders and Classic Eating Disorders respectively, whereas in the control group non subjects showed psychological anomalies. When we divided obese patients by the degree of obesity, differences in the frequencies of the Eating Disorders was no observed. CONCLUSIONS: In our obese patients, Pathological Behavior was the most frequent finding followed for Non-Specific Eating Disorders and Classic Eating Disorders.

[Rate of undernutrition and response to specific nutritional therapy in Crohn's disease]. / Tasa de desnutrición y respuesta al tratamiento nutricional específico en la enfermedad de Crohn.

OBJECTIVES: to determine the rate of malnutrition in patients with Crohn's disease in our area (Substudy A). We assess in long-term the response of malnourished patients to treatment of nutritional supplement with TGF-beta2 (Substudy B). SUBJECTS: ninety-eight (51% females) patients with Crohn's disease without selection, ages: 39.2 +/- 15.19 years, range: 18-81 years were included in Substudy A. In Substudy B thirty-nine malnourished patients (52% females) were included with an average age of 36.41 +/- 5.2 years and range: 19-45 (Substudy B). METHODS: the design of the Substudy A was an observational and cross sectional study. Whereas, the Substudy B was a longitudinal, open intervention study with active (historical) control. The variables were anthropometric parameters, electrical bioimpedance, biochemical measures, index of disease activity, subjective global assessment and the kind of treatment that every patient has received. MAIN RESULTS: the malnutrition rate was 52%, being the most frequent the caloric malnutrition, followed by mixed malnutrition. Thirty four per cent of the patients had iron deficiency. Twelve months of nutritional therapy with supplement specifically enriched in TGF-beta2 improved the evolution of the disease determined by a decrease in CDAI. CONCLUSIONS: The rate of malnutrition was similar to that of previous studies realized in Spain. Our study confirms the high rate of iron deficiency that the patients suffer with Crohn's disease. The response to the treatment is favorable, especially regarding the natural history of the disease.

Four years' follow up at a smoking cessation clinic.

UNLABELLED: Smoking is an important cause of pulmonary pathology and this addiction can be regarded as a chronic, recurrent disease. The benefits of smoking cessation are unquestionable and all physicians should become more active and assertive in recommending it. AIM: To characterise the population seeking medical support for smoking cessation and understand why some successfully stop smoking and others do not. MATERIAL AND METHODS: Retrospective analysis of medical records of outpatients in follow-up between January 2003 and June 2006. Age, gender, age at smoking initiation, smoking burden (number of pack-years), associated diseases, degree of dependence (Fagerström test for nicotine addiction), prior attempts at and motivation for smoking cessation, need for cognitive/behavioural support and success and abandonment rates were evaluated. RESULTS: Five hundred and twenty six patients were studied, 50% male with an average age of 45.5+/-11.4 years. Almost half (43.1 %; n=227) of the patients started smoking before the age of 15. Average smoking burden was 35.8+/-20 pack-years although 21.4% (n=113) smoked more than 50 pack-years. Respiratory disease was present in 52.1% (COPD, 39.9% and others, 12.2%) and cardiovascular disease in 14.6% of the patients. In 46% of patients (n=242) a relevant psychiatric disorder was identified; depression (21.4%), anxiety disorder (19.4%), other dependencies (2.1%) bipolar disorder (1.5%) and schizophrenia (0.6%). The evaluation of degree of addiction revealed maximum level in 69.7% of the patients (n=380). Many patients (72.2%; n=380) reported prior attempts to quit smoking. The strongest reasons for giving up smoking were concern over health (83.5%), financial issues (8.2%) and search for better quality of life (5.7%). Most patients (81.7%; n=430) had undergone nicotine replacement therapy; skin patches (53.3%), chewing gum (1.1%) or both (45.6%). Psychopharmacological treatment included administration of sedative-hypnotics (86.5%), bupropion hydrochloride (2.3%) and antidepressants (0.6%). Seventy six patients (14%) benefited from cognitive/ behavioural support. Two hundred and twenty three patients (42.4%) were successful in giving up smoking while 219 (41.6%) abandoned follow up, the majority after the first appointment. Most patients that abandoned follow up reported lack of motivation and the price of therapy. CONCLUSIONS: The population under study had a high rate of psychiatric disorders and a high level of dependence and lack of motivation that might justify the drop-out rate. Successful treatment was associated with close follow up, behavioural support and pharmacological therapy.