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Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways
Get PDFLung cancer is one of the most common cancers in the world with a high mortality rate. We analyzed 45 surgical samples of the adenocarcinoma, 13 with lymph node metastasis. APC, BCL2, chromogranin A, CK 5/6/18 (LP34), CK20, CK7, cyclin D1, EGFR, ERCC1, HER2, Ki67, LRP, MRP, P53, RB and TTF1 expressions were evaluated by immunohistochemistry (IHC). Higher Ki67, APC, ERCC1 expressions and lower TTF1 expression were identified in advanced stages (IIA and IIIA) of adenocarcinomas, which reflect a more aggressive, less differentiated, possibly a non-TRU adenocarcinoma. Acinar, micropapillary and BA/lepidic adenocarcinoma patterns were the most similar patterns and papillary was the most different pattern followed by solid pattern, according to expression of these markers. Different adenocarcinoma patterns are engaged with different molecular pathways for carcinogenesis, based on the differences of expression. Acinar, BA/lepidic and micropapillary showed higher TTF1 expression (type TRU), and papillary and solid patterns revealed less TTF1 expression, exhibiting a non-TRU/bronchial phenotype. Solid pattern revealed lower HER2 and higher EGFR and ERCC1 (this compared to papillary) expression; papillary higher HER2 and lower ERCC1 expressions; micropapillary higher RB expression; and acinar lower ERCC1 and higher EGFR expressions. Ciclin D1 seems to have more importance in acinar and BA/lepidic patterns than in micropapillary. ERCC1 protein expression in micropapillary, solid and BA/lepidic patterns may indicate DNA repair activation. Inhibition of apoptosis could be explained by BCL2 overexpression, present in all adenocarcinoma patterns. MRP-1 and LRP were overexpressed in all patterns, which may have implications for drug resistance. Further studies are needed to interpret these data regarding to therapy response in advanced staged bronchial-pulmonary carcinomas.info:eu-repo/semantics/publishedVersio
Linfoma de Hodgkin e Autoimunidade: Existirá uma Relação?
Get PDFINTRODUCTION:
The relationship between lymphomas and autoimmune diseases has been reported as bi-directional, however there is a few data in pediatric population. The aim of this work is to evaluate the prevalence of autoimmune diseases in children and adolescents with Hodgkin's lymphoma followed in a Pediatric Oncology Unit.
MATERIAL AND METHODS:
By reviewing Hodgkin's lymphomas data from the past 16 years (collected prospectively), an apparently large incidence of autoimmune diseases, mostly in female patients, was noted. We decided to do this retrospective study with an update on follow-up. Data analyzed: age, gender, autoimmune disease, temporal relation with lymphoma, lymphoma's stage, histologic subtype and treatment.
RESULTS:
Fifty-two cases were included, 7 (13.5%) of which, all female, had an autoimmune disease diagnosed previously, simultaneously or after lymphoma. Autoimmune diseases were: juvenile idiopathic arthritis, inflammatory bowel disease, Behçet's disease, autoimmune hepatitis, systemic erythematosus lupus, Hashimoto's thyroiditis and idiopathic thrombocytopenic purpura. The diagnosis was made after lymphoma in 4 patients, before in 2 and simultaneously in 1 patient. All cases, except the one with simultaneous diagnosis, are out of treatment and without oncologic disease relapse. No deaths were registered.
DISCUSSION:
There was an important prevalence of autoimmune diseases in girls with Hodgkin's lymphoma. We present data and discuss the possible causes based on a literature review.
CONCLUSIONS:
This relationship should be invoked, requiring more studies, especially in pediatric age.info:eu-repo/semantics/publishedVersio
Morbilidade Neonatal e Cesariana Electiva em Recém-Nascidos de Termo
Get PDFINTRODUCTION:
International guidelines suggest that non-urgent planned deliveries be scheduled at or after 39 weeks. Despite this recommendation elective cesarean often occurs before 39 weeks. Some research has demonstrated that elective cesarean before 39 weeks poses a greater risk to the infants than at or after 39 weeks.
OBJECTIVE:
To evaluate neonatal morbidity in term newborns born by elective cesarean section.
MATERIAL AND METHODS:
Retrospective study of all term elective cesarean sections (scheduled and without labor) performed in level III maternity, in the last 11 years (2003 - 2013). High risk pregnancies were excluded: twins, premature rupture of membranes, preeclampsia, poorly controlled diabetes mellitus, Rh isoimmunization and congenital malformations. Two groups of newborns with gestational age less than 39 weeks and equal or greater than 39 weeks gestational age were compared.
RESULTS:
In our sample, 45% of elective caesarean sections were performed before 39 weeks. Infants born before 39 weeks were more frequently admitted in neonatal intensive care, odds ratio 2.4 [1.4 - 4.1] p = 0.001, had more respiratory morbidity, odds ratio 2.4 [1.6 - 3.8] p < 0.001, more hyperbilirubinaemia odds ratio 2.3 [1.5 - 3.7] p < 0.001, more hypoglycaemia and/or feeding difficulties odds ratio 1.6 [1.2 - 2.4] p = 0.006, and longer admissions (more than five days), odds ratio 2.0 [1.4 - 3] p < 0.001.
DISCUSSION:
As in other studies 'early term' had higher respiratory and metabolic morbidity and consequently had a longer hospital stay.
CONCLUSION:
These findings support recommendations to delay elective cesarean delay until 39 weeks of gestation.info:eu-repo/semantics/publishedVersio
Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study
Get PDFType 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.info:eu-repo/semantics/publishedVersio
Elbow Arthroplasty in a patient with Juvenile Idiopathic Arthritis
No full textIntroduction: Juvenile Idiopathic Arthritis (JIA) is an autoimmune systemic chronic inflammatory disease that affects the joints as a chronic inflammatory synovitis. It appears before the 16 years old and there are many disease types, like the oligoarticular, polyarticular, systemic, etc. The orthopedic treatment and prognosis are defined by the joint sequelae grades, affecting mostly the hips, knees, ankles, elbows and wrists.
Objectives: Case report of a patient with JIA which conservative treatment was ineffective. A new stage of treatment was proposed, with bone preservation total elbow prosthesis. A good function, increasing range of motion and pain relief was achieved.
Methods: We present a clinical case of a 35 year-old female with diagnosis of a polyarticular JIA with evolution of 30 years. The disease stadium is the articular sequelae phase, affecting the vertebral column, hips, knees, shoulders, elbows and hands. The patient is referred to our centre because of intense pain and progressive amplitudes loss of the left elbow, with 5 years evolution. The plain radiograph of the left elbow shows bone erosions and diffuse osteopenia, signs of inflammatory active process at this joint. At this time, the patient is treated non surgically with disease modifying anti-rheumatoid, anti-inflammatory and pain killer drugs. After six months, the elbow pain and stiffness are worse, so the patient is submitted to a surgical arthrolisis, with no improvement. After 6 months, it is performed another arthrolisis, with the same unsuccessful results. The symptoms became incapacitating, with intense pain and crepitation of the joint, and severe limitation of the daily activities. The Mayo Score was 15. The movement arc was 90º of flexion and 20º of extension. At this time, the x-ray shows a grade 4 elbow arthrosis, with numerous osteophytes and an almost complete disappearance of the interarticular space. Being aware of the age of the patient and the severe limitation and prejudice on the life quality, it is performed a total elbow arthroplasty. The intraoperative findings were extense synovitis and aderences and a total juxtaposition of the articular surfaces, conditioning severe joint stiffness. It was used a bone preservation total elbow prosthesis.
Results: The surgery had no intercurrences and during the first 3 weeks it was done a cast immobilization with 90º elbow flexion. After this time, the patient began psychiatric rehabilitation programs that lead to progressive gain of joint amplitudes. One month after the joint replacement, the patient has 120º flexion and 15º extension, with no signs of joint instability and pain only at the movement limits. The patient was satisfied with the recuperation and at the third postoperative month the Mayo Sore was 100.
Conclusions: JIA can result in extreme situations of incapacitating osteoarthosis, frequently of the elbow joint. This disease affecting a young active patient is an indication to total elbow arthroplasty, that in the inflammatory arthritis generally results in pain relief and an important function recuperation of the joint amplitudes movements
Morphologic and Molecular Features of Hepatocellular Adenoma with Gadoxetic Acid-enhanced MR Imaging
Get PDFPurpose To evaluate the diagnostic performance of imaging features of gadoxetic acid-enhanced magnetic resonance (MR) imaging to differentiate among hepatocellular adenoma (HCA) subtypes by using the histopathologic results of the new immunophenotype and genotype classification and to correlate the enhancement pattern on the hepatobiliary phase (HBP) with the degrees of expression of organic anion transporting polypeptide (OATP1B1/3), multidrug resistance-associated protein 2 (MRP) (MRP2), and MRP 3 (MRP3) transporters. Materials and Methods This retrospective study was approved by the institutional review board, and the requirement for informed consent waived. MR imaging findings of 29 patients with 43 HCAs were assessed by two radiologists independently then compared with the histopathologic analysis as the standard of reference. Receiver operating characteristic curves and Spearman rank correlation coefficient were used to test the diagnostic performance of gadoxetic acid-enhanced MR imaging features, which included the retention or washout at HBP and degree of transporter expression. Interreader agreement was assessed by using the κ statistic with 95% confidence interval. Results The area under the curve for the diagnosis of inflammatory HCA was 0.79 (95% confidence interval: 0.64, 0.90); for the steatotic type, it was 0.90 (95% confidence interval: 0.77, 0.97); and for the β-catenin type, it was 0.87 (95% confidence interval: 0.74, 0.95). There were no imaging features that showed a significant statistical correlation for the diagnosis of unclassified HCAs. On immunohistochemical staining, OATP1B1/3 expression was the main determinant for the retention, whereas MRP3 was the key determinant for washout of gadoxetic acid at HBP (P < .001). MRP2 appeared to have no role. Conclusion Gadoxetic acid-enhanced MR imaging features may suggest the subtype of HCA. The degree of OATP1B1/3 and MRP3 expression correlated statistically with gadoxetic acid retention and washout, respectively, in the HBP. (©) RSNA, 2015 Online supplemental material is available for this article
Imbalance in habitual versus goal directed neural systems during symptom provocation in obsessive-compulsive disorder
Get PDFIntrusive thoughts and compulsive urges to perform stereotyped behaviours are typical symptoms of obsessive-compulsive disorder. Emerging evidence suggests a cognitive bias towards habit formation at the expense of goal-directed performance in obsessive-compulsive disorder. In this study, we test this hypothesis using a novel individualized ecologically valid symptom provocation design: a live provocation functional magnetic resonance imaging paradigm with synchronous video-recording of behavioural avoidance responses. By pairing symptom provocation with online avoidance responses on a trial-by-trial basis, we sought to investigate the neural mechanisms leading to the compulsive avoidance response. In keeping with the model of habit formation in obsessive-compulsive disorder, we hypothesized that this disorder would be associated with lower activity in regions implicated in goal-directed behaviours and higher activity in regions implicated in habitual behaviours. Fifteen patients with obsessive-compulsive disorder and 15 healthy control volunteers participated in this functional magnetic resonance imaging study. Online stimuli were individually tailored to achieve effective symptom provocation at neutral, intermediate and strong intensity levels. During the symptom provocation block, the participant could choose to reject or terminate the provoking stimuli resulting in cessation of the symptom provocation. We thus separately analysed the neural correlates of symptom provocation, the urge to avoid, rejection and relief. Strongly symptom-provoking conditions evoked a dichotomous pattern of deactivation/activation in patients, which was not observed either in control conditions or in healthy subjects: a deactivation of caudate-prefrontal circuits accompanied by hyperactivation of subthalamic nucleus/putaminal regions. This finding suggests a dissociation between regions engaged in goal-directed and habitual behaviours. The putaminal hyperactivity during patients' symptom provocation preceded subsequent deactivation during avoidance and relief events, indicating a pivotal role of putamen in regulation of behaviour and habit formation in obsessive-compulsive disorder. Effective connectivity analysis identified the ventromedial prefrontal cortex/orbitofrontal cortex as the main structure in this circuitry involved in the modulation of compulsivity in obsessive-compulsive disorder. These findings suggest an imbalance in circuitry underlying habitual and goal-directed action control, which may represent a fundamental mechanism underlying compulsivity in obsessive-compulsive disorder. Our results complement current models of symptom generation in obsessive-compulsive disorder and may enable the development of future therapeutic approaches that aim to alleviate this imbalance