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Secondary Event (secondary + event)
Selected AbstractsEffectiveness of routine follow-up of patients treated for T1,2N0 oral squamous cell carcinomas of the floor of mouth and tongueHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2006Matthias Adrianus Wilhelmus Merkx MD Abstract Background. The duration of follow-up after treatment for head and neck cancer, the depth of the routine visits, and the diagnostic tools used are determined on the basis of common acceptance rather than evidence-based practice. Patients with early-stage tumors are more likely to benefit from follow-up programs, because they have the best chance for a second curative treatment after recurrence. The purpose of this study was to determine the benefit of our 10-year follow-up program in patients with stage I and II squamous cell carcinoma (SCC) of the floor of mouth and tongue. Methods. In a longitudinal cohort study involving 102 patients who were treated with curative intent for a pT1,2N0M0 SCC of the floor of mouth and tongue from 1989,1998 with a minimum follow-up of 5 years, we evaluated the effect of routine follow-up. Results. During the follow-up (mean, 61 months; SD, 4 months), 10 patients had a recurrence, and 20 patients had a second primary tumor. No regional lymph node recurrences in the neck were detected. Location, T classification of the primary tumor, choice of therapy, or measure of tumor-free margins in the resection did not significantly affect the occurrence of a secondary event (p , .1). The secondary event was discovered during a patient-initiated visit for complaints in 14 patients and was found during routine follow-up visits in 16 patients. Only seven second primary tumors were detected after 60 months, four on routine follow-up and three on a self-initiated visit. The mean disease-free survival time after treatment of the secondary event was 72 months (SD, 17 months) in the "own initiative" group and 65 months (SD, 13 months) in the routine follow-up group; this difference was not statistically significant (p = .3). Conclusions. The effectiveness of a 10-year routine follow-up, even in patients with early-stage oral SCC, is very limited. These visits on routine basis can be stopped after 5 years. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] HER-2/neu expression in extramammary Paget disease: a clinicopathologic and immunohistochemistry study of 47 cases with and without underlying malignancyJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2009Jose A. Plaza Extramammary Paget disease (EMPD) is an infrequent skin cancer sometimes representing a secondary event caused by extension of an underlying carcinoma. Her-2/neu overexpression in breast cancer is correlated with a more aggressive behavior, but anti-Her-2/neu therapy improves survival in these patients. We investigated Her-2/neu expression by immunohistochemistry in cases of EMPD with and without underlying malignancy to try to correlate with tumor recurrence, progression and possible targeted therapy. Forty-seven cases were analyzed (6 from the scrotum, 7 perianal region, 1 axilla and 33 vulva). Two cases had invasive EMPD (one from vulva and one from scrotum). The overall Her-2/neu expression was 31.9%. Of the noninvasive EMPD of the vulva (32 cases), Her-2/neu was shown in 38%. The case of invasive vulvar EMPD was negative. All six scrotal EMPD lacked Her2/neu expression. Her-2/neu was expressed in two of seven perianal cases (33.3%). The EMPD on the axilla (one case) was negative. Eighteen cases had recurrence, and of these, 44.4% expressed Her-2/neu in the initial lesion. A high proportion of EMPD showed Her-2/neu expression (31.9%), indicating that these patients may benefit from targeted therapy. The proportion of positive cases was higher in lesions that had recurred at last follow up (44.4%), suggesting a more aggressive behavior. [source] Secondary prevention of ischemic stroke: Challenging patient scenarios,JOURNAL OF HOSPITAL MEDICINE, Issue S4 2008Kiwon Lee MD Abstract The risk for recurrent stroke following a stroke or transient ischemic attack (TIA) is high. Prevention of a secondary event is a priority, as the associated morbidity and mortality are great. Antiplatelet agents have been shown to reduce this risk, but the choice of treatment modality depends on a number of factors, including the underlying cause of the stroke and the patient's comorbidities. For example, a cardioembolic stroke is best treated with anticoagulants, whereas one of noncardioembolic origin requires antiplatelet therapy. A number of challenging patient scenarios are explored in this article, and appropriate medical management is discussed, with the goal of examining the most recent trial data and information in the context of an actual case. Eight sample cases are presented: stroke prevention in a patient with recent stent placement, low ejection fraction, intracranial stenosis, carotid stenosis, atherosclerosis of the aortic arch, symptomatic coronary artery disease, antiplatelet failure, and stroke prevention in a patient already on warfarin. Journal of Hospital Medicine 2008;3(4 Suppl):S20,S28. © 2008 Society of Hospital Medicine. [source] Mitochondrial alterations in Parkinson's disease: new cluesJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Miquel Vila Abstract Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). In particular, complex I impairment and subsequent oxidative stress have been widely demonstrated in experimental models of PD and in post-mortem PD samples. A recent wave of new studies is providing novel clues to the potential involvement of mitochondria in PD. In particular, (i) mitochondria-dependent programmed cell death pathways have been shown to be critical to PD-related dopaminergic neurodegeneration, (ii) many disease-causing proteins associated with familial forms of PD have been demonstrated to interact either directly or indirectly with mitochondria, (iii) aging-related mitochondrial changes, such as alterations in mitochondrial DNA, are increasingly being associated with PD, and (iv) anomalies in mitochondrial dynamics and intra-neuronal distribution are emerging as critical participants in the pathogenesis of PD. These new findings are revitalizing the field and reinforcing the potential role of mitochondria in the pathogenesis of PD. Whether a primary or secondary event, or part of a multi-factorial pathogenic process, mitochondrial dysfunction remains at the forefront of PD research and holds the promise as a potential molecular target for the development of new therapeutic strategies for this devastating, currently incurable, disease. [source] Tumor necrosis factor-, mediates polymethylmethacrylate particle-induced NF-,B activation in osteoclast precursor cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2002John C. Clohisy Tumor necrosis factor-, (TNF) is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of implant particle-induced osteolysis. The nuclear transcription factor NF-,B mediates TNF signaling and this transcription complex is necessary for osteoclastogenesis. Because polymethylmethacrylate (PMMA) particles cause osteolysis, we reasoned the PMMA would induce NF-,B activation. In fact, we find that exposure of osteoclast precursors, in the form of colony stimulating factor-1 (CSF-1) dependent murine bone marrow macrophages, to PMMA particles prompts nuclear translocation and activation of NF-,B. Supershift assays confirm the presence of the p50 and p65 NF-,B subunits in the activated transcription factor. Particle-induced NF-,B activation is equal in both wild type and LPS- hyporesponsive cells indicating that the phenomenon does not represent endotoxin contamination. A soluble, competitive inhibitor of TNF (huTNF:Fc) dampens particle-directed NF-,B activation and this response is also abrogated in TNF,/, osteoclast precursors. Thus, PMMA particle activation of NF-,B is a secondary event resulting from enhanced TNF expression and is independent of LPS contamination. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Iron metabolism in Parkinsonian syndromesMOVEMENT DISORDERS, Issue 9 2006Daniela Berg MD Abstract Growing evidence suggests an involvement of iron in the pathophysiology of neurodegenerative diseases. Several of the diseases are associated with parkinsonian syndromes, induced by degeneration of basal ganglia regions that contain the highest amount of iron within the brain. The group of neurodegenerative disorders associated with parkinsonian syndromes with increased brain iron content can be devided into two groups: (1) parkinsonian syndromes associated with brain iron accumulation, including Parkinson's disease, diffuse Lewy body disease, parkinsonian type of multiple system atrophy, progressive supranuclear palsy, corticobasal ganglionic degeneration, and Westphal variant of Huntington's disease; and (2) monogenetically caused disturbances of brain iron metabolism associated with parkinsonian syndromes, including aceruloplasminemia, hereditary ferritinopathies affecting the basal ganglia, and panthotenate kinase associated neurodegeneration type 2. Although it is still a matter of debate whether iron accumulation is a primary cause or secondary event in the first group, there is no doubt that iron-induced oxidative stress contributes to neurodegeneration. Parallels concerning pathophysiological as well as clinical aspects can be drawn between disorders of both groups. Results from animal models and reduction of iron overload combined with at least partial relief of symptoms by application of iron chelators in patients of the second group give hope that targeting the iron overload might be one possibility to slow down the neurodegenerative cascade also in the first group of inevitably progressive neurodegenerative disorders. © 2006 Movement Disorder Society [source] Environmental carcinogens and p53 tumor-suppressor gene interactions in a transgenic mouse model for mammary carcinogenesisENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002Daniel Medina Abstract Mouse mammary tumorigenesis is greatly influenced by a variety of exogenous agents, such as MMTV, chemical carcinogens (i.e., polycyclic aromatic hydrocarbons), and radiation, as well as by endogenous/physiological factors, such as steroid hormones, tumor-suppressor genes (i.e., Brca1/2,p53), and gene products of modifier genes. In the mouse model, the most frequently used chemical carcinogen has been 7,12-dimethylbenz[a]anthracene (DMBA), which activates the Ha- ras gene but does not alter the p53 tumor-suppressor gene. However, on an existing background of p53 gene alteration, low doses of DMBA are strongly cocarcinogenic. Using a transgenic model system, in which the p53 gene was deleted in the mammary gland, we examined the carcinogenic effects of a variety of external agents and internal factors given at either low doses or physiological doses. These agents/factors included DMBA, ,-radiation, Brca2 heterozygosity, and steroid hormones. All agents/factors increased the tumorigenic response of the p53 null mammary cells, even under conditions where no tumorigenic response was observed in the p53 wildtype mammary cell. The strongest cocarcinogenic effect was observed with the steroid hormone progesterone. The majority of tumors were highly aneuploid and composed of nuclear igh-grade cells. The mechanism for the aneuploidy and secondary events associated with high tumorigenicity were examined using array technology. These results demonstrate that, on a background of underlying genetic instability, very low doses of environmental mutagens and mitogens can produce strong cocarcinogenic effects. Environ. Mol. Mutagen. 39:178,183, 2002. © 2002 Wiley-Liss, Inc. [source] Cytogenetic, FISH, and molecular studies in a case of B-cell chronic lymphocytic leukemia with karyotypic evolutionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5-6 2002Christian Chena Abstract:, We report the clinical, cytogenetic, fluorescence in situ hybridization (FISH) and molecular findings in a 54-yr-old male patient diagnosed with B-cell chronic lymphocytic leukemia (B-CLL), who showed progression to a diffuse large B-cell lymphoma (Richter's syndrome). Genetic studies were performed at diagnosis and during the Richter's transformation (RT). A clonal karyotype with two dicentric chromosomes, psu dic(12,21)(q24;q10) and dic(17,18)(p11.2;p11.2), was found. Both rearrangements were confirmed by FISH. Molecular cytogenetics analysis using p53 probe showed monoallelic loss of this tumor suppressor gene in 43.8% and 77.3% of cells for the first and the second studies, respectively). In both studies, deletions of D13S319 (18% and 12% of cells) and D13S25 loci (13% and 12% of cells) at 13q14 were found. Polymerase chain reaction analysis showed the MBR/JH rearrangement of the bcl-2 gene. FISH studies using LSI bcl-2/IgH probe allowed quantifying the clonal cell population with this rearrangement (4% and 6.6% of cells at diagnosis and RT, respectively). To our knowledge, this is the first case with a psu dic(12,21) described in B-CLL. The low percentage of cells with the 13q14 deletion and bcl-2/IgH rearrangement suggests that they were secondary events that resulted from clonal evolution. Our patient had a short survival (9 months) and a clear lack of response to several therapeutic agents, confirming the association of p53 gene deletion and karyotypic evolution with disease progression. [source] Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma: A report from the Children's Oncology GroupGENES, CHROMOSOMES AND CANCER, Issue 8 2009Frederic G. Barr Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer that is related to the skeletal muscle lineage and characterized by recurrent chromosomal translocations. Within the ARMS category, there is clinical and genetic heterogeneity, consistent with the premise that "primary" genetic events collaborate with "secondary" events to give rise to subsets with varying clinical features. Previous studies demonstrated that genomic amplification occurs frequently in ARMS. In the current study, we used oligonucleotide arrays to localize two common amplicons to the 2p24 and 12q13-q14 chromosomal regions. Based on the copy number array data, we sublocalized the minimum common regions of 2p24 and 12q13-q14 amplification to a 0.83 Mb region containing the DDX1 and MYCN genes, and a 0.55 Mb region containing 27 genes, respectively. Using fluorescent in situ hybridization assays to measure copy number of the 2p24 and 12q13-q14 regions in over 100 cases, we detected these amplicons in 13% and 12% of cases, respectively. Comparison with fusion status revealed that 2p24 amplification occurred preferentially in cases positive for PAX3-FOXO1 or PAX7-FOXO1 while 12q13-q14 amplification occurred preferentially in PAX3-FOXO1 -positive cases. Expression studies demonstrated that MYCN was usually overexpressed in cases with 2p24 amplification while multiple genes were overexpressed in cases with 12q13-q14 amplification. Finally, although 2p24 amplification did not have a significant association with clinical outcome, 12q13-q14 amplification was associated with significantly worse failure-free and overall survival that was independent of gene fusion status. © 2009 Wiley-Liss, Inc. [source] Prevention of secondary stroke and transient ischaemic attack with antiplatelet therapy: the role of the primary care physician roleINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2007H. S. Kirshner Summary Background:, Stroke risk is heightened among patients who have had a primary stroke or transient ischaemic attack (TIA). The primary care physician is in the best position to monitor these patients for stroke recurrence. Because stroke recurrence can occur shortly after the primary event, guidelines recommend initiating antiplatelet therapy as soon as possible. Aspirin, with or without extended-release dipyridamole (ER-DP), and clopidogrel are options for such patients. Low-dose aspirin (75,150 mg/day) has the same efficacy as higher doses but with less gastrointestinal bleeding. Clopidogrel remains an option for prevention of secondary events and may benefit patients with symptomatic atherothrombosis, but its combined use with aspirin can harm patients with multiple risk factors and no history of symptomatic cerebrovascular, cardiovascular or peripheral vascular disease. Results:, Low dose aspirin is effective in secondary stroke prevention. Trials assessing aspirin plus ER-DP have shown that the combination is more effective than aspirin monotherapy in preventing stroke, with efficacy increasing among higher risk patients, notably those with prior stroke/TIA. Clopidogrel does not appear to have as much advantage over aspirin in secondary stroke prevention as aspirin plus ER-DP. Smoking cessation and cholesterol, blood glucose and blood pressure control are also important concerns in preventing recurrent stroke. In choosing pharmacological therapy, the physician must consider the individual patient's risk factors and tolerance, as well as other issues, such as use of aspirin among patients with ulcers. Conclusion:, Antiplatelet therapy is effective in secondary stroke prevention. Low dose aspirin can be used first-line, but aspirin plus ER-DP improves efficacy. Clopidogrel is another option in secondary stroke prevention, especially for aspirin-intolerant patients, but it appears to have less advantage over aspirin than aspirin plus ER-DP, and its combined use with aspirin has only marginally better efficacy and increased bleeding risk. [source] Psoriasis under the microscopeJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2006BJ Cribier Abstract Histopathology is a major diagnostic tool in dermatology, particularly in psoriasiform diseases. Morphological studies showed that the initial event in psoriatic lesions is perivascular infiltrate, followed by dilatation of superficial papillary vessels. Proliferation of keratinocytes and neutrophil exocytosis are secondary events. Fully developed psoriasis has a very characteristic pattern, which includes elongation of rete ridges leading to regular acanthosis, oedema of the papillary dermis associated with tortuous dilated vessels, thinning of suprapapillar area, decreased thickness of granular layer, and exocytosis of neutrophils in the spinous layer (Kogoj's pustule) or in the cornified parakeratotic layer (Munro microabscesses). Pustular psoriasis is characterized by large or confluent intra-epidermal multilocular pustules. Whatever the clinical variant of psoriasis, common morphological signs suggest that it is basically a unique pathological process, with many possible presentations according to various factors such as age, size and localization of lesions, or therapy. Similar microscopic elementary lesions indicate that Hallopeau's acrodermatitis continua, Reiter's disease and geographical tongue are variants of psoriasis. Because of the many faces of the disease, psoriasis can resemble many other squamous or pustular disorders. Differential diagnosis by microscopic analysis is based on pattern analysis, PAS (Periodic Acid Schiff) staining to rule out fungal infection, and immunohistochemistry to characterize lymphocytic infiltrate. Psoriasis is one of the most common inflammatory skin diseases. In its characteristic presentation, psoriasis comprises well-circumscribed red scaly papules and plaques. In this form, the disease is generally easy to identify, especially when the elbows, knees and scalp are affected. Nevertheless, the term ,psoriasis' includes more clinical variants than any other inflammatory dermatosis: psoriasis vulgaris vs. pustular, localized vs. generalized, topographic variants, mucous membranes involvement, hair and nail lesions. Although some of these conditions might be extremely different from psoriasis vulgaris, common pathological findings can be identified in all of them. Microscopic analysis of psoriatic lesions may therefore help clinicians to make the diagnosis and to understand that, whatever the clinical presentation, signs and symptoms are mainly due to a unique pathological process. [source] | ||||||||||||||||||||||