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1.
BMC Med Genomics ; 15(1): 45, 2022 03 04.
Article in English | MEDLINE | ID: mdl-35246124

ABSTRACT

BACKGROUND: DNA methylation (DNAm) age metrics have been widely accepted as an epigenetic biomarker for biological aging and disease. The purpose of this study is to assess whether or not individuals carrying Lynch Syndrome-associated mutations are affected in their rate of biological aging, as measured by the epigenetic clock. METHODS: Genome-wide bisulfite DNA sequencing data were generated using DNA from CD4 + T-cells obtained from peripheral blood using 27 patient samples from Lynch syndrome families. Horvath's DNAm age model based on penalized linear regression was applied to estimate DNAm age from patient samples with distinct clinical and genetic characteristics to investigate cancer mutation-related aging effects. RESULTS: Both Lynch mutation carriers and controls exhibited high variability in their estimated DNAm age, but regression analysis showed steeper slope for the Lynch mutation carriers. Remarkably, six Lynch Syndrome-associated mutation carriers showed a strong correlation to the control group, and two sisters carrying Lynch Syndrome-associated mutations, with no significant difference in lifestyle and similar chronological age, were assigned very different DNAm age. CONCLUSIONS: Future studies will be required to explore, in larger patient populations, whether specific epigenetic age acceleration is predictive of time-to-cancer development, treatment response, and survival. Epigenetic clock DNAm metrics may be affected by the presence of cancer mutations in the germline, and thus show promise of potential clinical utility for stratified surveillance strategies based on the relative risk for imminent emergence of tumor lesions in otherwise healthy Lynch Syndrome-associated mutation carriers.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis , DNA Methylation , Acceleration , Aging/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Epigenesis, Genetic , Humans , Mutation
2.
Adv Chronic Kidney Dis ; 26(5): 369-375, 2019 09.
Article in English | MEDLINE | ID: mdl-31733721

ABSTRACT

In systemic lupus erythematosus, nephrotic-range proteinuria typically signals the presence of a proliferative lupus nephritis (class III/IV) and/or membranous lupus nephritis (class V, with or without concomitant class III or IV lesions). However, in rare instances, systemic lupus erythematosus patients with nephrotic syndrome have kidney biopsy findings of normal glomeruli or focal segmental glomerulosclerosis lesions, with or without mesangial proliferation, on light microscopy; the absence of subepithelial or subendothelial deposits on immunofluorescence and electron microscopy; and diffuse foot process effacement on electron microscopy. This pattern, termed lupus podocytopathy, is a unique form of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis and represents approximately 1% of lupus nephritis biopsies. Here we review the clinical features, histological manifestations, diagnostic criteria and classification, pathogenesis, treatment, and prognosis of lupus podocytopathy.


Subject(s)
Kidney Glomerulus , Lupus Erythematosus, Systemic/complications , Lupus Nephritis , Podocytes/pathology , Disease Management , Humans , Kidney Glomerulus/diagnostic imaging , Kidney Glomerulus/pathology , Lupus Nephritis/etiology , Lupus Nephritis/pathology , Lupus Nephritis/physiopathology , Lupus Nephritis/therapy , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/etiology
3.
Eur J Surg Oncol ; 45(10): 1876-1881, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31189513

ABSTRACT

INTRODUCTION: 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. STUDY METHOD: 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. RESULTS: 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. CONCLUSIONS: The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups.


Subject(s)
Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Mass Screening , Neoplasm Staging , Aged , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/metabolism , Female , Follow-Up Studies , Humans , Immunohistochemistry , Incidence , Male , Middle Aged , Prospective Studies , Spain/epidemiology , Survival Rate/trends
4.
Tumour Biol ; 42(4): 1010428319835684, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30957671

ABSTRACT

We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour samples from a prospective cohort of patients with colorectal cancer were examined and tumour biology markers were determined as follows: percentage of apoptotic cells, by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling technique; Ki-67 antigen, as a cell proliferation marker and density of microvessels (as a marker of angiogenesis). An increase in the percentage of cellular apoptosis is significantly related to the presence of poorly differentiated tumours, with vascular invasion (p < 0.001). The CD105 angiogenesis marker is not related to any clinical-pathological parameter except that of higher frequency in older patients (p = 0.03). Ki-67 is more frequently expressed in tumours with less nervous invasion (p = 0.05). Neither apoptosis nor angiogenesis present any significant association with short-term survival. The only marker clearly related to 2-year survival is Ki-67, which is shown to be a good prognostic factor in the multivariate analysis (hazard ratio = 0.49; 95% confidence interval = 0.27-0.90). Therefore, in a prospective cohort of colorectal cancer patients, only Ki-67 is a marker of good prognosis in short-term follow-up.


Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Ki-67 Antigen/genetics , Neovascularization, Pathologic/genetics , Adult , Aged , Apoptosis/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Disease-Free Survival , Endoglin/genetics , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neovascularization, Pathologic/epidemiology , Neovascularization, Pathologic/pathology , Prognosis
5.
Oncol Lett ; 12(5): 3127-3134, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27899972

ABSTRACT

Aflibercept is a recombinant fusion protein that acts by inhibiting tumoural angiogenesis. Efficacy data obtained in the VELOUR randomised study has contributed to the approval of aflibercept as a second-line metastatic colorectal cancer (mCRC) treatment following an oxaliplatin-based regimen. The present study reports a case series of five patients with mCRC, who were treated in two centres since 2011 in the Compassionate Use Program for aflibercept. All patients had a KRAS mutation and previously received palliative fluoropyrimidine-oxaliplatin-based chemotherapy with bevacizumab. A doublet with irinotecan combined with aflibercept was administered until progression of disease. The majority of patients received a greater number of aflibercept cycles than the median reported in the VELOUR study (12 vs. 7 cycles), with manageable and reversible toxicity. The most frequent adverse events observed were diarrhoea, neutropenia, fatigue, proteinuria and hypertension. Most cases obtained a progression-free survival greater than the median reported in the VELOUR study (11 vs. 6.9 months) and, in a subgroup of patients previously treated with bevacizumab, and a median survival time of ~47 months was reached from the initial treatment of the disease. The present study contrasts the efficacy and safety results obtained from the pivotal VELOUR trial, and confirms that aflibercept, used in routine clinical practice outside of the clinical trial environment, is active and well-tolerated following bevacizumab treatment.

6.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 34(7): 400-405, ago.-sept. 2016. graf, tab
Article in Spanish | IBECS | ID: ibc-155483

ABSTRACT

INTRODUCCIÓN: La neoplasia intraepitelial anal de alto grado (NIAAG) está en aumento en determinados grupos de riesgo y en su etiopatogenia están implicados algunos genotipos del virus del papiloma humano (VPH). El cribado de la NIAAG contempla el uso sistemático de la citología anal y más recientemente el genotipado de VPH. Nuestro objetivo fue determinar la sensibilidad y especificidad de ambas herramientas diagnósticas en la identificación de NIAAG. MATERIAL Y MÉTODO: Estudio de correlación entre los hallazgos citológicos y microbiológicos con respecto a la biopsia anal de una cohorte de pacientes con conductas de riesgo de desarrollar neoplasia intraepitelial anal atendidos en la consulta de infecciones de transmisión sexual del área de Dermatología del Hospital Costa del Sol desde enero de 2008 a diciembre de 2014. RESULTADOS: De los 151 pacientes sometidos al cribado, se seleccionaron aquellos pacientes con las tres pruebas de cribado realizadas (citología anal, genotipado y biopsia guiada por anoscopia), 92 en total, de los que el 62% presentaban infección por VIH. La sensibilidad y especificidad para identificar NIAAG fue 52,8 y 85,7% para la citología anal (k: 0,328), y 78 y 62,8% de la presencia de dos o más genotipos oncogénicos VPH (k: 0,417). La detección de VPH oncogénicos permitió clasificar correctamente 23 casos de NIAAG confirmados por biopsia guiada por anoscopia e infradiagnosticados con la citología anal, 14 de ellos con al menos 3 genotipos de riesgo. CONCLUSIÓN: La citología anal ha mostrado una sensibilidad insuficiente para la detección de NIAAG. El genotipado del VPH, aunque como única herramienta de cribado daría lugar a un sobrediagnóstico, es una herramienta que puede complementar el procedimiento de cribado, especialmente con el objetivo de identificar los casos de NIAAG


INTRODUCTION: The incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. MATERIALS AND METHODS: This is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. RESULTS: Of the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. CONCLUSION: Anal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure


Subject(s)
Humans , Anus Neoplasms/diagnosis , Papillomaviridae/pathogenicity , Genotyping Techniques/methods , Cytological Techniques/methods , Carcinoma in Situ/diagnosis , Sensitivity and Specificity , Biopsy/methods , Risk Factors , Mass Screening/methods
7.
Virchows Arch ; 469(4): 385-94, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27447172

ABSTRACT

Stage I-II (pN0) colorectal cancer patients are surgically treated although up to 25 % will eventually die from disease recurrence. Lymph node (LN) status is an independent prognostic factor in colorectal cancer (CRC), and molecular tumour detection in LN of early-stage CRC patients is associated with an increased risk of disease recurrence and poor survival. This prospective multicentre study aimed to determine the relationship between LN molecular tumour burden and conventional high-risk factors in stage I-II colon cancer patients. A total of 1940 LN from 149 pathologically assessed pN0 colon cancer patients were analysed for the amount of tumour cytokeratin 19 (CK19) messenger RNA (mRNA) with the quantitative reverse transcription loop-mediated isothermal amplification molecular assay One-Step Nucleic Acid Amplification. Patient's total tumour load (TTL) resulted from the sum of all CK19 mRNA tumour copies/µL of each positive LN from the colectomy specimen. A median of 15 LN were procured per case (IQR 12;20). Molecular positivity correlated with high-grade (p < 0.01), mucinous/signet ring type (p = 0.017), male gender (p = 0.02), number of collected LN (p = 0.012) and total LN weight per case (p < 0.01). The TTL was related to pT stage (p = 0.01) and tumour size (p < 0.01) in low-grade tumours. Multivariate logistic regression showed independent correlation of molecular positivity with gender, tumour grade and number of fresh LN [AUC = 0.71 (95 % CI = 0.62-0.79)]. Our results show that lymph node CK19 mRNA detection correlates with classical high-risk factors in stage I-II colon cancer patients. Total tumour load is a quantitative and objective measure that may help to better stage early colon cancer patients.


Subject(s)
Colonic Neoplasms/pathology , Lymph Nodes/pathology , Neoplasm Recurrence, Local/pathology , Aged , Colonic Neoplasms/diagnosis , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Staging/methods , Prospective Studies , Risk Factors , Tumor Burden
8.
Enferm Infecc Microbiol Clin ; 34(7): 400-5, 2016.
Article in Spanish | MEDLINE | ID: mdl-26976378

ABSTRACT

INTRODUCTION: The incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. MATERIALS AND METHODS: This is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. RESULTS: Of the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. CONCLUSION: Anal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure.


Subject(s)
Anus Neoplasms/diagnosis , Anus Neoplasms/virology , Carcinoma in Situ/diagnosis , Carcinoma in Situ/virology , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis , Adult , Anus Neoplasms/pathology , Carcinoma in Situ/pathology , Cross-Sectional Studies , Female , Genotype , Genotyping Techniques , Humans , Male , Sensitivity and Specificity , Spain
9.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 32(9): 560-564, nov. 2014. tab, graf
Article in Spanish | IBECS | ID: ibc-129883

ABSTRACT

INTRODUCCIÓN: La incidencia de la neoplasia intraepitelial anal está en aumento en determinados grupos con conductas de riesgo, y en su etiopatogenia está implicada la infección por el virus del papiloma humano (VPH). Dentro de los programas de cribado implementados en las últimas décadas se encuentra el uso sistemático de la citología anal y, más recientemente, la detección del VPH mediante captura de híbridos y genotipado. MATERIAL Y MÉTODO: Estudio de cohortes retrospectivo de la población con conductas de riesgo de desarrollar neoplasia intraepitelial anal atendida en la consulta de Infecciones de Transmisión Sexual del área de Dermatología del Hospital Costa del Sol desde enero de 2010 a diciembre de 2012, a la que se le realizó cribado de neoplasia intraepitelial anal mediante toma de citología anal y genotipado de VPH. RESULTADOS: El 50% de la población estudiada tenía infección por VIH. Se encontró una alta frecuencia de displasia anal y presencia de VPH en la citología (82,1%) y genotipado (79%). Se obtuvo una asociación estadísticamente significativa (p < 0,005) entre la presencia de genotipos de VPH de alto riesgo y la presencia de displasia de alto grado en la segunda citología dirigida. El genotipado de VPH permitió identificar 17 casos (22%) de displasia severa infradiagnosticados en la primera citología. CONCLUSIÓN: La citología anal a ciegas puede infradiagnosticar casos de displasia de alto grado. La detección de VPH puede complementar este procedimiento, permitiéndonos identificar aquellos pacientes con mayor riesgo de desarrollar displasia anal de alto grado


INTRODUCTION: The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades. MATERIAL AND METHODS: A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping. RESULTS: Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P < .005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology. CONCLUSION: Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia


Subject(s)
Humans , Papillomavirus Infections/diagnosis , Early Detection of Cancer/methods , Anus Neoplasms/epidemiology , Papillomaviridae/isolation & purification , Risk-Taking , Mass Screening , Neoplasms, Glandular and Epithelial/epidemiology , HIV Infections/complications , False Negative Reactions , Retrospective Studies
10.
Enferm Infecc Microbiol Clin ; 32(9): 560-4, 2014 Nov.
Article in Spanish | MEDLINE | ID: mdl-24908497

ABSTRACT

INTRODUCTION: The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades. MATERIAL AND METHODS: A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping. RESULTS: Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P<.005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology. CONCLUSION: Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia.


Subject(s)
Anus Neoplasms/virology , Carcinoma in Situ/virology , Early Detection of Cancer/methods , Papillomavirus Infections/diagnosis , Tumor Virus Infections/diagnosis , Adult , Anus Neoplasms/epidemiology , Anus Neoplasms/pathology , Anus Neoplasms/prevention & control , Carcinoma in Situ/epidemiology , Carcinoma in Situ/pathology , Carcinoma, Squamous Cell/prevention & control , Female , Genotype , Humans , Male , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomaviridae/pathogenicity , Papillomavirus Infections/epidemiology , Retrospective Studies , Risk , Risk-Taking , Sexual Behavior , Sexually Transmitted Diseases/epidemiology , Single-Blind Method , Spain/epidemiology , Tumor Virus Infections/epidemiology
11.
BMC Clin Pathol ; 13(1): 24, 2013 Oct 10.
Article in English | MEDLINE | ID: mdl-24106912

ABSTRACT

BACKGROUND: Alterations to apoptosis are a common occurrence in human tumours. The aim of our study was to determine the influence of apoptotic variations on the carcinogenesis and prognosis of colorectal carcinomas (CRCs). METHODS: A TUNEL assay was performed on archival material from 103 colorectal carcinomas, 26 adenomas and 20 samples of normal epithelia. RESULTS: The number of apoptotic cells was higher in CRCs (1.09 ± 0.13) than in adenomas (0.38 ± 0.23, p = 0.059) and normal epithelium (0.06 ± 0.04, p = 0.001). In addition, the apoptotic index (AI) was greater in metastatic disease (stage IV) than in other stages (p = 0.017). No relationship was found between apoptotic rates and age, gender or tumour grade. However, patients with tumours that showed higher AI values had a significantly lower disease-free survival (DFS) and overall survival (OS) than those with tumours that had lower AIs (p = 0.020 and p = 0.027). In a multivariate Cox proportional hazards model, AI remained a significant independent predictor of survival. CONCLUSIONS: We conclude that disregulated apoptosis is an important event during CRC development and progression. Higher AIs are associated with more aggressive tumours and a poorer prognosis for patients with CRC.

12.
BMC Cancer ; 12: 604, 2012 Dec 17.
Article in English | MEDLINE | ID: mdl-23244222

ABSTRACT

BACKGROUND: The aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences. METHODS: For this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors. RESULTS: After adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RR = 0.43, CI = 0.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (OR = 3.38, CI = 1.72-6.63 and OR = 3.44, CI = 1.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (OR = 1.77, CI = 1.01-3.23 and OR = 0.64, CI = 0.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (OR = 2.84, CI = 1.05-7.69), were less likely to be HER2/neu positive (OR = 0.22, CI = 0.08-0.61) and presented lower Ki67 expression (OR = 0.36, CI = 0.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RR = 4.88, CI = 1.12-21.19). CONCLUSIONS: Incident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/mortality , Early Detection of Cancer/methods , Mammography , Case-Control Studies , Disease Progression , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Prognosis , Proportional Hazards Models
13.
Support Care Cancer ; 17(5): 595-9, 2009 May.
Article in English | MEDLINE | ID: mdl-18841396

ABSTRACT

INTRODUCTION: This study evaluates clinical-pathological characteristics and survival rates associated with emergency admission and delays in diagnosis and treatment of 411 consecutive breast cancer patients. MATERIALS AND METHODS: Emergency admission and first symptom-first hospital visit delay were significantly associated with advanced tumor stages but only in the former case with short disease-free survival (RR 2.5, CI 95% 1.5-4.2). RESULTS: Brief diagnostic delays were significantly associated with advanced disease stage and poor survival rates (RR 2.04; CI 95% 1.08-3.82) probably because sicker patients receive prompt medical attention.


Subject(s)
Breast Neoplasms/diagnosis , Emergency Service, Hospital/statistics & numerical data , Patient Admission/statistics & numerical data , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm Staging , Prognosis , Spain , Survival Rate , Time Factors
14.
Diagn Pathol ; 3: 20, 2008 Apr 29.
Article in English | MEDLINE | ID: mdl-18445254

ABSTRACT

This short report discusses a case of solitary colonic polypoid ganglioneuroma associated with melanosis coli in a woman with no systemic manifestations. To our knowledge this is the first ganglioneuroma reported in the literature in association with melanosis coli. The nature and significance of this event remains unclear, although this may be coincidental due to the laxative intake. Further investigation is necessary to clarify this point. The interest of this case lies moreover in the rarity of this entity and its endoscopic and histologic resemblance to sessile polyps frequent in the clinical practice.

15.
Diagn Pathol ; 2: 30, 2007 Aug 21.
Article in English | MEDLINE | ID: mdl-17711572

ABSTRACT

Chromophobe renal cell carcinoma (CHRC) is a neoplasm of the kidney with clinicopathologic peculiarities that seems to be of better prognosis than conventional renal cell carcinoma. Classical and eosinophilic types are the two histological variants recorded. Also, it has been described in association with carcinoma of collecting ducts, conventional renal cell carcinoma and sarcomatoid renal cell carcinoma. Squamous renal carcinoma is a very rare neoplasm with a malignant course. We describe a case of simultaneous chromophobe renal cell carcinoma with squamous cell carcinoma, finding which, to the best of our knowledge, has not previously been reported.

16.
J Infect ; 47(1): 73-6, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12850166

ABSTRACT

Neutrophil-rich CD30+ anaplastic large-cell lymphoma (ALCL) is a rare pathological entity without distinct clinical behavior. Twelve cases of neutrophil-rich CD30+ anaplastic large-cell lymphoma (ALCL) have been reported, three of them were HIV-infected patients. All these reports stressed the presence of neutrophil infiltration as a new morphologic feature of CD30+ ALCL. Only one case of cutaneous involvement presented with microabscess formation. We describe a case of neutrophil-rich CD30+ ALCL in an AIDS patient with a clinical picture determined by the massive neutrophil infiltration of the tumor without necrosis nor local infection, but with the formation of abscesses.


Subject(s)
Abscess/complications , Ki-1 Antigen/analysis , Lymphoma, Large B-Cell, Diffuse/pathology , Neutrophils/pathology , Adult , Diagnosis, Differential , Fatal Outcome , Humans , Ilium , Lymphoma, AIDS-Related/complications , Lymphoma, Large B-Cell, Diffuse/complications , Male
18.
Oncogene ; 21(53): 8173-7, 2002 Nov 21.
Article in English | MEDLINE | ID: mdl-12444553

ABSTRACT

Pituitary tumor-transforming gene (pttg) is a distinct proto-oncogene which is expressed in certain normal tissues with high proliferation rate and in a variety of tumors. PTTG is the vertebrate analog of yeast securins Pds1 and Cut2 with a key role in the regulation of sister chromatid separation during mitosis. Impairment of PTTG regulated functions is expected to lead to chromosomal instability and aneuploidy. Human pttg (hpttg) is abundantly expressed in Jurkat T lymphoblastic lymphoma cells but not in normal peripheral blood leukocytes. To obtain additional data on the potential role of hpttg in lymphomagenesis we selected 150 cases of lymphoid tumors for the assessment of hpttg expression in tumor tissues. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissues revealed hPTTG in 38.8% of B-cell lymphomas, 70.2% of T-cell lymphomas, and 73.1% of Hodgkin's lymphomas. Among B-cell lymphomas, the most frequently immunostained tumors were plasma cell tumors, diffuse large cell lymphomas, and follicle center cell lymphomas. In Hodgkin's disease, immunoreactivity was mainly noted in Reed-Sternberg cells. In conclusion, the frequent overexpression of hpttg in many histological subtypes of lymphoma suggests the involvement of this proto-oncogene in lymphomagenesis.


Subject(s)
Lymphoma/chemistry , Neoplasm Proteins/analysis , Blotting, Northern , Gene Expression Regulation, Neoplastic , Hodgkin Disease/genetics , Hodgkin Disease/metabolism , Humans , Immunoenzyme Techniques , Lymphoma/genetics , Lymphoma, B-Cell/chemistry , Lymphoma, B-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/chemistry , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, T-Cell/chemistry , Lymphoma, T-Cell/genetics , Neoplasm Proteins/genetics , Neoplasm Proteins/physiology , Proto-Oncogene Mas , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , RNA, Neoplasm/analysis , RNA, Neoplasm/biosynthesis , Reed-Sternberg Cells/chemistry , Securin
19.
Radiographics ; 22(4): 775-84, 2002.
Article in English | MEDLINE | ID: mdl-12110709

ABSTRACT

Synovial plicae are normal anatomic structures of the knee that sometimes become symptomatic. Magnetic resonance (MR) imaging and MR arthrography are useful tools in the evaluation of synovial plicae and allow differentiation of these entities from other causes of knee pain. At MR imaging, synovial plicae appear as bands of low signal intensity within the high-signal-intensity joint fluid. Gradient-echo T2-weighted and fat-suppressed T2-weighted or proton density-weighted MR images are optimal for the evaluation of plicae. Plica syndrome, the painful impairment of knee function in which the only finding that helps explain the symptoms is the presence of a thickened and fibrotic plica, should be included in the differential diagnosis of internal derangement of the knee. A diffusely thickened synovial plica, perhaps associated with synovitis or erosion of the articular cartilage of the patella or femoral condyle, in a patient with no other significant MR imaging findings suggests the diagnosis of plica syndrome. Once the diagnosis has been made, nonsurgical treatment is preferable initially. Failure of the patient to improve with conservative treatment leaves arthroscopic excision of the pathologic plica as the treatment of choice.


Subject(s)
Knee Joint/pathology , Magnetic Resonance Imaging , Synovial Membrane/pathology , Humans , Knee Joint/anatomy & histology , Pain/etiology , Syndrome , Synovial Membrane/anatomy & histology
20.
Radiographics ; 22(1): 105-21, 2002.
Article in English | MEDLINE | ID: mdl-11796902

ABSTRACT

Impaction syndromes related to ulnar-sided pain include ulnar impaction syndrome, ulnar impingement syndrome, ulnocarpal impaction syndrome secondary to nonunion of the ulnar styloid process, ulnar styloid impaction syndrome, and hamatolunate impingement syndrome. The most common of these, ulnar impaction syndrome, is a degenerative condition of the ulnar side of the wrist related to excessive load bearing across the ulnar carpus, triangular fibrocartilage (TFC) complex, and ulnar head. In an adequate clinical setting, characteristic osseous findings at radiography include positive ulnar variance in ulnar impaction syndrome, a short ulna in ulnar impingement syndrome, nonunion of the ulnar styloid process in ulnar impaction syndrome secondary to ulnar styloid nonunion, an excessively long ulnar styloid process in ulnar styloid impaction syndrome, and type II lunate bone in hamatolunate impingement syndrome. Nevertheless, confirmation of clinical and conventional radiographic findings with magnetic resonance (MR) imaging is often necessary to exclude other entities with similar clinical manifestations. MR imaging allows earlier detection of an abnormality in the TFC complex, cartilage, or bone marrow of carpal bones and is helpful in formulating the extensive differential diagnosis in patients with ulnar wrist pain and limitation of motion.


Subject(s)
Magnetic Resonance Imaging , Pain/diagnosis , Ulna/pathology , Wrist/pathology , Carpal Bones/pathology , Cartilage Diseases/diagnosis , Cartilage Diseases/pathology , Cartilage, Articular/pathology , Diagnosis, Differential , Humans , Pain/etiology , Syndrome , Ulna/injuries , Wrist Injuries/diagnosis , Wrist Injuries/pathology
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