Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a ...biological level, between the tumours of asymptomatic and symptomatic patients.
Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening.
A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010–2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained.
A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p < 0.05). However, no significant differences were found regarding the markers of tumour biology: Ki67 (proliferation), CD105 (angiogenesis) and the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (apoptosis). The patients with asymptomatic tumours had a lower mortality at five years than those diagnosed presenting symptoms.
The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups.
Although the most common cause for coronary embolism is atrial fibrillation, we should take other conditions into consideration that, despite their low frequency of occurrence, need to be discarded ...to be able to establish a definitive treatment. Arteriovenous malformations like the case presented here are some of these conditions. A 36-year-old woman with Rendu-Osler-Weber syndrome and recurrent and spontaneous epistaxis as the only personal medical history presented to the ER with oppression in her middle chest and pain radiating towards her left upper limb and back with concomitant vegetative symptoms. The electrocardiogram confirmed the presence of a subepicardial lesion in leads V2-V3 with high-sensitive troponin peak values of 9148 pg/mL.
Grafts with subclinical rejection associated with interstitial fibrosis and tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical rejection without IF/TA (SCR). Aiming to ...detect differences among SCR+IF/TA and SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and used a low-density array to determine levels of TH 1 (interleukin IL-2, IL-3, γ-interferon, tumor necrosis factor-α, lymphotoxin-α, lymphotoxin-β, granulocyte-macrophage colony-stimulating factor) and TH 2 (IL-4, IL-5, IL-6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell activation) in 31 protocol biopsies of renal allografts. Here we show that grafts with early IF/TA and SCR can be distinguished from grafts with SCR on the basis of the activation of IL-10 gene expression and of an increased infiltration by B-lymphocytes in a cellular context in which the degree of T-cell activation is similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R mRNA. These results suggest that the up-regulation of the IL-10 gene expression, as well as an increased proportion of B-lymphocytes in the inflammatory infiltrates, might be useful as markers of early chronic lesions in grafts with SCR.
BACKGROUND AND OBJECTIVEMesial temporal lobe epilepsy with hippocampal sclerosis is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, ...surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis and the prognosis, seizures control, side effects and anticonvulsivant drug withdrawal in patients with refractory epilepsy. PATIENTS AND METHODClinical histories and anatomopathological specimens of 228 patients with temporal epilepsy surgically obtained at our hospital between 1993 and 2014 were retrospectively analysed. All patients underwent a standard preoperative evaluation and anterior temporal resection (modified from Spencer). The anatomopathological study included the standard hematoxylin-eosin and immunohistochemical protocol, with special interest in the assessment of neuronal loss with NeuN. Seizure control was assessed according to the scale of results of the ILAE and Engel. The mean follow-up was 8.6 years (2-19). RESULTSAt 10 years after the intervention, 67.9% of patients were seizure-free (ILAE 1) and as many as 77.5% of the patients were seizure-free (Engel 1) at the end of the follow-up. The probability of not having a seizure (ILAE 1) after surgery at 2 (p=.042), 5 (p=.001) and 7 years (p=.22) was higher in classic and severe forms compared to isolated sclerosis CA1 and CA4 forms. Higher neuronal loss measured with the NeuN immunostain in CA1 was associated with better outcome in seizure management (multivariate analysis, p=.08). The presence of a personal history of epilepsy was associated with greater neuronal loss in CA1 (p=.028) and CA3 (p=.034), and the presence of psychic auras was related with greater neuronal loss in CA3 (p=.025). In our case, the probability of medication withdrawal was related to the presence of personal history (p=.003) and, inversely, to neuronal loss in CA1 (p=.036) and CA3 (p=.038). The greatest impairment of verbal memory occurred in those patients with a lower neuronal loss in CA1 (p=.023), CA2 (p=.049) and CA3 (p=.035). CONCLUSIONSThe results indicate that the classical and severe subtypes have a better prognosis in the control of seizures against the atypical forms, validating the clinical and prognostic utility of the classification of histological subtypes of hippocampal sclerosis from the ILAE. The value of the immunohistochemistry in the mesial temporal lobe epilepsy with hippocampal sclerosis has been demonstrated as a key element to determine the neuropsychological prognosis and seizure management of the patients after surgery.
Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation. It is now accepted that inflammation and related events, such as ...activation of NF-κB, are key components in the initiation and progression of epithelial cancer and in particular in the neoplastic transformation of keratinocytes and skin carcinogenesis. Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis. In parp-1−/− mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced. In addition, epidermis of parp-1−/− mice did not show increased proliferation rates after treatment with carcinogen. Deregulated NF-κB is a hallmark for tumorigenesis together with the concomitant release of early inflammatory mediators. In the absence of PARP-1, NF-κB activation and induction κB-target genes did not take place during the promotion of tumor development. These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-κB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
Smoothelin is a cytoskeletal protein of differentiated smooth muscle cells with contractile capacity, distinguishing it from other smooth muscle proteins, such as smooth muscle actin (SMA).
To ...evaluate the expression of smoothelin and SMA in the skin in order to establish specific localizations of smoothelin in smooth muscle cells with high contractile capacity and in the epithelial component of cutaneous adnexal structures.
Immunohistochemical analysis (smoothelin and SMA) was performed in 18 patients with normal skin.
SMA was expressed by the vascular structures of superficial, deep, intermediate and adventitial plexuses, whereas smoothelin was specifically expressed in the cytoplasm of smooth muscle cells of the deepest vascular plexus and in no other plexus of the dermis. The hair erector muscle showed intense expression of smoothelin and SMA. Cells with nuclear expression of smoothelin and cytoplasmic expression of SMA were observed in the outer root sheath of the inferior portion of the hair follicles and intense cytoplasmic expression in cells of the dermal sheath to SMA.
We report the first study of smoothelin expression in normal skin, which differentiates the superficial vascular plexus from the deep. The deep plexus comprises vessels with high contractile capacity, which is important for understanding dermal hemodynamics in normal skin and pathological processes. We suggest that the function of smoothelin in the outer root sheath may be to enhance the function of SMA, which has been related to mechanical stress. Smoothelin has not been studied in cutaneous pathology; however we believe it may be a marker specific for the diagnosis of leiomyomas and leiomyosarcomas of the skin. Also, smoothelin could differentiate arteriovenous malformations of cavernous hemangioma of the skin.
Pediatric acute myeloid leukemia (AML) is a rare and heterogeneous disease that remains the major cause of mortality in children with leukemia. To improve the outcome of pediatric AML we need to gain ...knowledge on the biological bases of this disease. NUP98-KDM5A (NK5A) fusion protein is present in a particular subgroup of young pediatric patients with poor outcome. We report the generation and characterization of human Embryonic Stem Cell (hESC) clonal lines with inducible expression of NK5A. Temporal control of NK5A expression during hematopoietic differentiation from hESC will be critical for elucidating its participation during the leukemogenic process.
Background: Toxic epidermal necrolysis is a severe reaction with skin involvement induced by different drugs and other agents. The mechanisms implicated in the induction of the reaction are poorly ...understood. Objective: Our purpose was to study the involvement of T lymphocytes and other immunocompetent cells in the peripheral blood, blister fluid, and affected skin of 3 patients who had a severe reaction after receiving anticonvulsant medication. Methods: Quantification of T lymphocytes expressing the skin-homing receptor (cutaneous lymphocyte-associated antigen CLA) in peripheral blood, skin, and skin blister fluid and assessment of other adhesion molecules, activation markers, and inflammatory interleukins by flow cytometry, immunohistochemistry, and reverse transcription–PCR. Results: An increase in CD3+CLA+ cells paralleling the severity of the disease was observed in both peripheral blood and skin, tending to normalize as soon as patient’s conditions improved. E-selectin was detected in endothelial vessels in parallel with CLA expression on lymphocytes. An overexpression of TNFα, IFN-γ, and IL-2 was also observed in PBMCs. The expression of the different markers changed over the course of the disease. Conclusions: These data show an increase in activated T cells expressing the skin-homing receptor in both tissue and peripheral blood accompanying clinical symptoms, with a recruitment of macrophages and an overexpression of cytokines. All these results suggest an important role for T cells in the production of toxic epidermal necrolysis. (J Allergy Clin Immunol 2000;105:157-65.)
KDRI / KDPI are tools use in kidney donor evaluation. It has been proposed as a substitute of, or complementary to preimplantation renal biopsy. These scores has not been validated in Spain.
1) To ...investigate the concordance between KDPI and histological scores (preimplantation renal biopsy) and 2) To assess the relationship between KDRI, KDPI and histological score on graft survival in the expanded criteria donors group.
Retrospective cohort study from 1 January 1998 until 31 December 2010.
During the study 120 donors were recruited, that resulted in 220 preimplantation renal biopsies. 144 (65%) grafts were considered suitable for kidney transplantation. 76 (34.5%) were discarded. Median follow up has been 6.4 years (sd 3.9). Median age 63.1 years (sd 8.2), males (145; 65.9%), non-diabetic (191; 86.8%) and without another cardiovascular risk factors (173; 78.6%). 153 (69.5%) donors died of cerebrovascular disease. There were significant differences in KDRI/KDPI score in both groups 1.56/89 (sd 0.22) vs 1.66/93 (sd 0.15), p<0.01). The KDPI showed moderate concordance and correlation with the histological score (AUC 0.64 / correlation coefficient 0.24, p <0.01). KDPI (HR 24.3, p<0.01) and KDRI (HR 23.3, p<0.01) scores were associated with graft survival in multivariate analysis.
1) KPDI and histological scores show moderate concordance. The utility of both scores as combined tools it has to be determined. 2) KDPI score, and especially KDRI score, are valid for estimating graft survival and combined with the biopsy can help to individualized decision making in the expanded criteria donors pool.
Integrin-linked kinase (ILK) is an intracellular effector of cell–matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, ...invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing.
► ILK deletion results in decreased HGF expression and delayed scratch wound repair. ► PI3K/ILK/AKT pathway signals through HGF to regulate wound healing. ► An ILK-dependent increase in HGF expression is responsible for wound healing in vivo. ► ILK-KO mice are used to confirm the requirement for ILK function in wound healing. ► Human HGF treatment restores delayed wound closure in vitro and in vivo.
PDF
