RESUMO
BACKGROUND: African Americans (AA) are at high risk for Colorectal Cancer (CRC). Studies report a 30-60% increase in CRC risk with physical inactivity, obesity and metabolic syndrome. Activation of the WNT/ß-catenin (CTNNB1) signaling pathway plays a critical role in colorectal carcinogenesis. Accumulating evidence also indicates a role of WNT-CTNNB1 signaling in obesity and metabolic diseases. AIM: To examine the association between obesity, ß-Catenin expression and colonic lesions in African Americans. METHODS: We reviewed the pathology records of 152 colorectal specimens from 2010 to 2012 (46 CRCs, 74 advanced adenomas and 32 normal colon tissues). Tissue Microarrays (TMA) were constructed from these samples. Immunohistochemistry (IHC) for CTNNB1 (ß-Catenin; clone ß-Catenin-1) was performed on the constructed TMAs. The IHC results were evaluated by 2 pathologists and the nuclear intensity staining was scored from 0 to 4. BMI, sex, age, location of the lesion and other demographic data were obtained. RESULTS: Positive nuclear staining in normal, advanced adenoma and CRC was 0, 24 and 41%, respectively (P < 0.001). CRC was asso ciated with positive status for nuclear CTNNB1 intensity (adjusted OR: 3.40, 95%CI = 1.42-8.15, P = 0.006 for positive nuclear staining) compared to non-CRC samples (Normal or advanced adenoma). Nuclear staining percentage has a fair diagnostic ability for CRC with an AUC of 0.63 (95%CI = 0.55-0.71). Overweight/obese patients (BMI > 25) did not show a significant difference in (p = 0.3) nuclear CTNNB1 staining (17% positive in normal weight vs. 27% positive in overweight/obese). The association between nuclear intensity and CRC was not different between normal and overweight patients (P for interaction = 0.6). The positive nuclear CTNNB1status in CRC stage III and IV (35% of all CRC) was not different from stage I and II (50% vs. 36%, respectively, P = 0.4). CONCLUSION: In our study, advanced adenoma and CRC were associated with activation of ß-catenin in physically fit, overweight and obese patients. Thus, obesity and WNT/ß-Catenin pathway seem to be independent in African American patients. WNT/ß-Catenin signaling pathway has a potential to be used as an effector in colon carcinogenic transformation. Whether or not BMI is a modifier of this pathway needs to be investigated further.
Assuntos
Neoplasias Colorretais , beta Catenina , Negro ou Afro-Americano , Humanos , Obesidade/complicações , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: Colorectal and endometrial lesions increase with age. It is not known if these two precursor lesions in sporadic cases associate with each other. AIM: To determine the association between colorectal polyps and endometrial polyps (EP) in African Americans. METHODS: We reviewed records of patients referred to gynecology clinics and had colonoscopy at Howard University Hospital from January 2004 to December 2015. We defined cases as all patients who had EP and underwent colonoscopy. For controls, we used EP-free patients who underwent colonoscopy. Logistic regression analysis was used to assess the association between colon polyps and EP. RESULTS: The median age was 60 years in 118 Cases and 57 years in 664 Controls. The overall colorectal polyps prevalence in the two groups was not statistically different (54% in controls vs. 52% in cases, P = 0.60). Sessile serrated adenoma/polyps (SSPs) were more frequent in cases (8% vs. 2% in controls, P = 0.003). Sigmoid and rectal locations were more prevalent in controls than cases. In multivariate analysis and after adjusting for age, diabetes mellitus (DM), and BMI, SSPs were associated with EP occurrence with an odds ratio of 4.6 (CI 1.2-16.7, P = 0.022). CONCLUSION: Colorectal polyp prevalence was similar in EP patients compared to EP-free controls. However, we observed a significant association between higher-risk SSPs in patients with EP. The prevalence of smoking and DM was higher in these patients. Females with EP might benefit from a screening for colonic lesions in an age-independent manner.
Assuntos
Negro ou Afro-Americano , Pólipos do Colo/etnologia , Neoplasias Colorretais/etnologia , Pólipos/etnologia , Doenças Uterinas/etnologia , Idoso , Pólipos do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , Diabetes Mellitus/etnologia , Feminino , Humanos , Pessoa de Meia-Idade , Pólipos/diagnóstico , Prevalência , Fatores Raciais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Fumar/etnologia , Doenças Uterinas/diagnósticoRESUMO
BACKGROUND: Up to 30% of colorectal cancers develop through the serrated pathway. African Americans (AAs) suffer a disproportionate burden of colorectal cancer. The aim of this study was to evaluate clinicopathological features of AA patients diagnosed with sessile serrated polyps (SSPs). METHODS: We conducted a retrospective study of all colonoscopies (n = 12,085) performed at Howard University Hospital, from January 1st, 2010 to December 31st, 2015, of which 83% were in AA patients, (n = 10,027). Among AAs, pathology reports confirmed 4070 patients with polyps including 252 with SSPs. Demographic and clinical variables (i.e. sex, age, BMI, anatomic location, clinical symptoms, polyp size, and clinical indications were collected at colonoscopy. RESULTS: In the AA population, the median age was 56 with interquartile range (IQR) of 51 to 62 years, 54% were female, and 48% had a BMI > 30. The most common reason for colonoscopy was screening (53%), whereas the prevalent reasons for diagnostic colonoscopies were changes in bowel habits (18%) and gastrointestinal bleeding (17%). The total number of SSPs among the 252 AA (diagnosed with SSPs) was 338. Of these, 9% (n = 29/338) had some degree of cytological dysplasia, primarily in the ascending colon (n = 6/42, 14%), Transverse colon (n = 2/16, 13%) and rectosigmoid (n = 19/233, 8%). About 24% of patients had more than 2 polyps. Most patients (76%) had distal SSPs (rectal and rectosigmoid), in comparison to 14% of proximal polyps and 10% of bilateral locations. Median SSA/P size for all locations was 0.6 cm. CONCLUSION: The prevalence of SSPs accounts for 6% of all polyps in AA patients and was diagnosed in 2.5% of all colonoscopies (n = 252/10,027), which is higher than Caucasians in the US. SSPs were predominantly located in the left side, as compared to published literature showing the predominance in the right side of the colon. Screening of CRC will have the chance to detect high risk SSA/P in this population.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Pólipos do Colo/etnologia , Pólipos do Colo/patologia , Neoplasias Colorretais/etnologia , Disparidades nos Níveis de Saúde , Idoso , Colo Ascendente , Colo Sigmoide , Colo Transverso , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reto , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Epigenetic plays an important role in colorectal neoplasia process. There is a need to determine sound biomarkers of colorectal cancer (CRC) progression with clinical and therapeutic implications. Therefore, we aimed to examine the role and methylation status of Glyco Protein Non-Metastatic GPNM B (GPNMB) gene in normal, adenoma and CRC in African American (AA) patients. METHODS: The methylation status of 13 CpG sites (chr7: 23287345-23,287,426) in GPNMB gene's promoter, was analyzed by pyrosequencing in human CRC cell lines (HCT116, SW480, and HT29) and microdissected African American paraffin embedded samples (20 normal, 21 non-advanced adenoma (NA), 48 advanced adenoma (AD), and 20 cancer tissues. GPNMB expression was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMA). Correlations between GPNMB methylation and expression with clinicopathological features were analyzed. GPNMB functional analysis was performed in triplicates using cell proliferation, migration and invasion assays in HCT116 colon cell line after stable transfection with a GPNMB-cDNA expression vector. RESULTS: GPNMB methylation was lower in normal mucosa compared to CRC samples (1/20 [5%] vs. 18/20 [90%]; P < 0.001). AD also had a significantly higher GPNMB methylation frequency than normal colon samples (42/48 [88%] vs 1/20 [5%]; P < 0.001). GPNMB was more frequently methylated in AD than in matched normal mucosa from three patients (3/3 [100%] vs 1/3 [33.3%]; P < 0.001). The frequency of GPNMB methylation in NA differed significantly from that in the normal mucosa (16/21 [76%] vs 1/20 [5%]; P = 0.008). There was statistically significant correlation of higher methylation at advanced stages and lower methylation at stage 1 CRCs (P < 0.05). In agreement with these findings, GPNMB protein expression decreased in CRC tissues compared with AD and NA colon mucosa (p < 0.05). GPNMB overexpression in HCT116 colon cancer cell line decreased cell proliferation [(24 h, P = 0.02), (48 h, P < 0.001, 72 h, P = 0.007)], invasion (p < 0.05) and migration (p > 0.05) compared to the mock-transfected cells. CONCLUSION: Our data indicate a high methylation profile leading to a lower GPNMB expression in adenoma and CRC samples. The functional analysis established GPNMB as a potential tumor suppressor gene. As such, GPNMB might be useful as a biomarker of adenomas with high carcinogenic potential.
Assuntos
Adenoma/genética , Neoplasias do Colo/genética , Metilação de DNA/genética , Glicoproteínas de Membrana/genética , Adenoma/diagnóstico , Adenoma/patologia , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Ilhas de CpG/genética , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras GenéticasRESUMO
BACKGROUND AND AIM: Several factors involved in the development of liver fibrosis in African-American patients with chronic hepatitis C have not been well studied. We aimed to evaluate some of these risk factors. METHODS: We reviewed pathology and medical records of 603 African-Americans with chronic hepatitis C virus (HCV) infection at Howard University Hospital from January 2004 to December 2013. Among the clinical and pathological data collected were HIV (human immunodeficiency virus), HCV genotype, hepatitis B virus (HBV), diabetes mellitus (DM), hypertension (HTN), body mass index (BMI), and hepatic steatosis. RESULTS: The frequency of DM, HTN, HIV, and HBV was 22, 16, 11, and 4%, respectively. Median BMI was 27.3 kg/m2. The frequency of fibrosis stages 0, 1, 2, 3, and 4 was 2, 48, 28, 11, and 11%, respectively. In multivariate logistic regression, we found a significant association between liver fibrosis stage (3-4 vs. 0-2) and HIV infection (OR 2.4, P = 0.026), HTN (OR 3.0, P = 0.001), age (OR 2.6 for every 10 years, P < 0.001), weight (OR 1.1 for every 10 lb increase, P = 0.002), and steatosis grade (OR 1.6, P = 0.002). The frequency of liver steatosis was 73%. In an ordinal logistic regression, significant risk factors for steatosis were female gender (OR 1.5, P = 0.034) and inflammation grade (P = 0.001). CONCLUSION: This study shows that steatosis is independently associated with fibrosis in African-American patients with HCV infection. Female patients were at higher risk of steatosis.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Fígado Gorduroso/virologia , Hepacivirus , Hepatite C Crônica/complicações , Cirrose Hepática/virologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Fígado Gorduroso/patologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Fatores Sexuais , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Colorectal cancer is a preventable disease if caught at early stages. This disease is highly aggressive and has a higher incidence in African Americans. Several biomarkers and mutations of aggressive tumor behavior have been defined such as metastasis-associated in colon cancer 1 (MACC1) that was associated with metastasis in colorectal cancer patients. Here, we aim to assess colon tissue MACC1 protein and circulating MACC1 transcripts in colon preneoplastic and neoplastic African American patients. METHODS: Patients' tissue samples (n = 143) have been arranged on three tissue microarrays for normal (n = 26), adenoma (n = 68) and cancer (n = 49) samples. Immunohistochemistry was used to detect MACC1 expression. Blood samples (n = 93) from normal (n = 45), hyperplastic (n = 15) and tubular adenoma (n = 33) patients were used to assess MACC1 transcripts using qRT-PCR. Distribution of continuous variables was tested between different diagnoses with Kruskal-Wallis test. Categorical variables were tested by Chi square test. We assessed the prognostic ability of IHC staining by calculating area under receiver operating characteristics curve (ROC) for adenoma and cancer separately. Differences between groups in terms of MACC1 transcript levels in plasma were calculated by using non-parametric (exact) Wilcoxon-Mann-Whitney tests. We performed all calculations with SPSS, version 21. RESULTS: In patient tissues, there was a statistically significant difference in MACC1 expression in normal vs. adenoma samples (p = 0.004) and normal vs. cancer samples (p < 0.001). There was however no major difference in MACC1 expression between adenoma vs. cancer cases or tubular adenomas vs tubulovillous adenomas. The area under the curve for both normal vs. adenoma and normal vs. cancer cases were 70 and 67 %, respectively. MACC1 expression was not correlated to age, gender or anatomical sample location. In patient plasma, MACC1 transcripts in adenoma patients were significantly higher than in plasma from normal patients (p = 0.014). However, the difference between normal and hyperplastic plasma MACC1 transcripts was not statistically significant. CONCLUSION: Metastasis-associated in colon cancer 1 is expressed at early stages of colorectal oncogenesis within the affected colonic tissue in this patient cohort. The plasma transcripts can be used to stratify African American patients at risk for potential malignant colonic lesions.
Assuntos
Adenoma/sangue , Adenoma/diagnóstico , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Fatores de Transcrição/sangue , Adenoma/genética , Idoso , Neoplasias Colorretais/genética , Demografia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hiperplasia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Risco , Análise Serial de Tecidos , Transativadores , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: The purpose of this study was to identify genome-wide single nucleotide variants and mutations in African American patients with colorectal cancer (CRC). There is a need of such studies in African Americans, because they display a higher incidence of aggressive CRC tumors. METHODS: We performed whole exome sequencing (WES) on DNA from 12 normal/tumor pairs of African American CRC patient tissues. Data analysis was performed using the software package GATK (Genome Analysis Tool Kit). Normative population databases (eg, 1000 Genomes SNP database, dbSNP, and HapMap) were used for comparison. Variants were annotated using analysis of variance and were validated via Sanger sequencing. RESULTS: We identified somatic mutations in genes that are known targets in CRC such as APC, BRAF, KRAS, and PIK3CA. We detected novel alterations in the Wnt pathway gene, APC, within its exon 15, of which mutations are highly associated with CRC. CONCLUSIONS: This WES study in African American patients with CRC provides insight into the identification of novel somatic mutations in APC. Our data suggest an association between specific mutations in the Wnt signaling pathway and an increased risk of CRC. The analysis of the pathogenicity of these novel variants may shed light on the aggressive nature of CRC in African Americans.
Assuntos
Adenocarcinoma/genética , Proteína da Polipose Adenomatosa do Colo/genética , Negro ou Afro-Americano/genética , Neoplasias Colorretais/genética , Exoma , Mutação , Análise de Sequência de DNA/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/etnologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etnologia , Variações do Número de Cópias de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Transdução de Sinais , Proteínas ras/genéticaRESUMO
BACKGROUND: Lymph nodes' examination in colorectal cancer (CRC) resection specimens is an important determinant that aids in the accuracy of CRC staging and treatment outcomes. Current guidelines call for the examination of at least 12 lymph nodes (LN) in resected specimens in order to establish accurate staging. AIM: To investigate lymph nodes' examination protocol as it relates to accurate CRC staging. METHODS: We reviewed 216 African American CRC patients from 1996-2013 who underwent CRC resection and met inclusion criteria for this study. The number of retrieved LNs, length of resected specimens, tumor grade, stage, location, size and histology were examined. RESULTS: The cohort study was made of 49% males, median age was 63 years and 45% of patients were at stage III and IV. The median (IQR) number of examined LNs was 15 (10-22) and the rate of patients with more than 12 examined LNs was 64%. There was a gradual increase in the percentage of patients with adequate number (>12) of examined LNs during the study period (from 60% in 1996-2000 to 84% in 2010-2013 period, P=0.014). Adequate LNs resection was neither associated with shift of stage from II to III (P=0.3) nor with the changes from stage IIIa to IIIc (P=0.9). Metastatic LNs were observed in 8% of samples with LNs (>12) vs. 13% of samples with <12 examined LNs (P=0.1). Patients that had pre-surgical treatment (chemotherapy and radiotherapy) before surgery had <12 LNs examined. There was also a trend of having more examined lymph nodes in large tumors. CONCLUSIONS: Our study shows that there has been an increase in the number of lymph nodes examined in CRC resections since the advent of the current quality initiative. However this increase does not seem to affect the stage or percentage of metastatic lymph nodes' detection in CRC patients.
Assuntos
Neoplasias Colorretais/patologia , Excisão de Linfonodo/métodos , Metástase Linfática/patologia , Estadiamento de Neoplasias/métodos , Patologia Clínica/métodos , Negro ou Afro-Americano , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: It is unclear whether there is a shared pathway in the development of diverticular disease (DD) and potentially neoplastic colorectal lesions since both diseases are found in similar age groups and populations. AIM: To determine the association between DD and colorectal pre-neoplastic lesions in an African-American urban population. METHODS: Data from 1986 patients who underwent colonoscopy at the Howard University Hospital from January 2012 through December 2012 were analyzed for this study. The presence of diverticula and polyps was recorded using colonoscopy reports. Polyps were further classified into adenoma or hyperplastic polyp based on histopathology reports. Multiple logistic regression was done to analyze the association between DD and colonic lesions. RESULTS: Of the 1986 study subjects, 1,119 (56%) were females, 35% had DD and 56% had at least one polyp. There was a higher prevalence of polyps (70 vs. 49%; OR = 2.3; 95% CI: 1.9-2.8) and adenoma (43 vs. 25%; OR = 2.0; 95% CI: 1.7-2.5) in the diverticular vs. non-diverticula patients. Among patients who underwent screening colonoscopy, the presence of diverticulosis was associated with increased odds of associated polyps (OR = 9.9; 95% CI: 5.4-16.8) and adenoma (OR = 5.1; 95% CI: 3.4-7.8). CONCLUSION: Patients with DD are more likely to harbor colorectal lesions. These findings call for more vigilance on the part of endoscopists during colonoscopy in patients known to harbor colonic diverticula.
Assuntos
Adenoma/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Pólipos do Colo/epidemiologia , Diverticulose Cólica/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Saúde da População Urbana/estatística & dados numéricos , Adenoma/patologia , Idoso , Pólipos do Colo/patologia , Colonoscopia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Análise Multivariada , Lesões Pré-Cancerosas/patologia , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Chromodomain helicase DNA binding protein 5 (CHD5) is a family member of chromatin remodeling factors. The epigenetic silencing mechanisms of CHD5 in colorectal cancer have not been well studied. METHODS: Here we analyzed CHD5 methylation and mRNA expression in vitro and in clinical samples from African American patients. DNA and RNA were isolated from formalin fixed paraffin embedded (FFPE) colon tissues. DNA was tested for methylation using methylation-specific polymerase chain reation (PCR) and bisulfite sequencing. RNA was used for mRNA quantification using qRT-PCR. The RKO cell line was treated with 5-Aza-dC and SAHA. RKO cells were also stably transfected with a CHD5-expressing vector. The transcriptional activity was studied in the 1 kb upstream region of the CHD5 promoter using the dual reporter assay. We performed cell proliferation, migration, and invasion assays using the RKO cell line. RESULTS: In most adenoma samples, CHD5 expression was not detected in contrast to normal tissues. In RKO cells, CHD5 silencing was associated with DNA methylation and repressive histone modifications. CHD5 expression was restored after treatment with 5-Aza-dC and SAHA. CHD5 reactivation reduced cell proliferation, migration, and invasion. The reporter assay indicated that the main regulatory region of the CHD5 promoter is encompassed in the -489 to -823 region with important transcriptional regulatory sites (TCF/LEF, SP1, and AP-2). CONCLUSIONS: The CHD5 gene is repressed in all types of adenomas, either epigenetically or by chromosomal deletion. CHD5 activity is regulated by DNA methylation and repressive histone modifications. CHD5 likely acts as a tumor-suppressor gene in early colorectal carcinogenesis.
Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , DNA Helicases/genética , Epigênese Genética , Genes Supressores de Tumor , Proteínas do Tecido Nervoso/genética , Adenoma/patologia , Negro ou Afro-Americano/genética , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células , Neoplasias Colorretais/patologia , Metilação de DNA , Decitabina , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Inibidores de Histona Desacetilases/farmacologia , Histonas/genética , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Regiões Promotoras Genéticas , VorinostatRESUMO
BACKGROUND: African Americans have disproportionately higher incidence and death rates of colorectal cancer among all ethnic groups in the United States. Several lifestyle factors (e.g. diet, physical activity and alcohol intake) have been suggested as risk factors for colorectal cancer. Stressful life events have also been identified as risk factors for colorectal cancer. The association between stressful life events and colon polyps, which are precursors of colorectal cancer, has yet to be determined. METHODS: In this cross-sectional study, 110 participants were recruited from a colon cancer screening program at Howard University Hospital. Participants completed an 82-item Life Events Questionnaire (Norbeck 1984), assessing major events that have occurred in the participants' life within the past 12 months. Participants also reported whether the event had a positive or negative impact. Three scores were derived (total, positive, and negative). RESULTS: Total life events scores were higher (Median [M] = 29 and Interquartile range [IQR] = 18-43) in patients with one or more polyps compared to patients without polyps (M, IQR = 21,13-38; P = 0.029). Total, positive or negative Life Events scores did not differ significantly between normal and adenoma patients. Total, negative and positive Life Events scores did not differ between patients who underwent diagnostic colonoscopy (symptomatic) and patients who underwent colonoscopy for colon cancer screening (asymptomatic) and patients for surveillance colonoscopies due to a personal history of colon polyps. Linear regression analysis indicated that male gender is associated with 9.0 unit lower total Life Events score (P = 0.025). CONCLUSION: This study suggests that patients who experienced total life events may be at higher risk of having colon polyps and adenomas which indicates an association between stress and the development of colorectal polyps.
Assuntos
Adenoma/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Pólipos do Colo/etnologia , Neoplasias Colorretais/etnologia , Estilo de Vida , Estresse Psicológico/complicações , Adenoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Estudos Transversais , Dieta , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Atividade Motora , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Multiple primary malignant neoplasms (MPMNs) or multiple primary malignancies are defined as two or more histologically distinct malignancies present in the same individual. While second or higher-order malignancies account for approximately 18% of all cancers in the United States, it is reasonable to presume that MPMNs are now occurring more frequently than previously reported. Underserved groups such as blacks and Hispanics may represent a high proportion of these underreported cases due to well-established health disparities. Although the role of health disparities has been well established in single primary malignancies, less is known on racial differences in patients with multiple primaries. In comparing MPMNs by race, blacks have lower survival rates compared to white patients. Moreover, despite the lower overall incidence of MPMNs in blacks compared to white patients, when broken down by the specific types of cancers and gender, there are significant racial disparities in the incidence of prostate cancer and possibly other cancers. Further research and case reports are required to explore the risk factors of developing MPMNs in these groups. Our case series explores three African American patients with MPMNs that are rarely described in the literature and outlines the management challenges of treating multiple malignancies.
RESUMO
OBJECTIVES: This study was undertaken to evaluate the diagnostic performance of the BinaxNOW COVID-19 Ag Card rapid antigen assay (Abbott; Chicago, IL, USA) in the detection of COVID-19 infection compared to the reference standard of PCR testing. METHODS: We evaluated the BinaxNOW COVID-19 Ag Card rapid antigen assay relative to a standard reference PCR test. We tested 3810 nasal swabs from symptomatic and asymptomatic adults undergoing surveillance COVID-19 testing at Howard University using one swab for each nostril. One swab was tested using the rapid antigen assay and the other using the PCR test. RESULTS: The sensitivity of the BinaxNOW COVID-19 Ag Card rapid antigen assay was 91.84% (95% confidence interval (CI): 80.40-97.73%) and the specificity was 99.95% (95% CI: 99.81-99.99%). The range of Ct values for the N gene was 10.74-34.90 (M = 26.88, SD=4.86). Fourteen (28.6%) samples had an N gene Ct value > 30. The average N gene Ct value for rapid test negative (i.e. false negative) samples was 31.92. CONCLUSIONS: The sensitivity of the test in our symptomatic and asymptomatic cohort was lower than the manufacturer's reported sensitivity in a symptomatic cohort (97.1%). Despite their relatively lower sensitivity (especially in asymptomatic individuals), rapid tests have undeniable benefits (i.e., ease of use and rapid results) that make them a helpful tool in the control of the SARS-CoV-2 pandemic. Given the diagnostic accuracy of these tests as evidenced by this study, rapid tests can be thoughtfully employed in situations where swift results are critical.
Assuntos
COVID-19 , Adulto , Antígenos Virais , Teste para COVID-19 , Testes Diagnósticos de Rotina , Humanos , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
Of the four subtypes of cutaneous melanoma, acral lentiginous melanoma (ALM) is atypical in its presentation. ALM is a rare melanoma subtype that presents on the volar surfaces of the hand and foot. The difficulty of making an early diagnosis of ALM is highlighted by the case seen in our institution. The dire prognosis associated with ALM is postulated to be not only related to its destructive nature, but also due to a lack of patient awareness and vigilance, inadequate physician awareness, and disparity in healthcare access. We present this as a unique account of an ALM lesion in a 76 year old African-American male presenting originally in the left foot that went misdiagnosed for several years. The original lesion was considered to be an ulcerating left great toe lesion with signs typical of osteomyelitis. These clinical findings were corroborated by radiological x-ray evidence. Upon amputation and biopsy for suspected worsening osteomyelitis five years later, the pathological diagnosis of melanoma was finally made.
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Melanoma , Osteomielite , Neoplasias Cutâneas , Idoso , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/patologia , Prognóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Melanoma Maligno CutâneoRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) disproportionately affected African Americans (AA) and Hispanics (HSP). AIM: To analyze the significant effectors of outcome in African American patient population and make special emphasis on gastrointestinal (GI) symptoms, laboratory values and comorbidities. METHODS: We retrospectively evaluated the medical records of 386 COVID-19 positive patients admitted at Howard University Hospital between March and May 2020. We assessed the symptoms, including the GI manifestations, comorbidities, and mortality, using logistic regression analysis. RESULTS: Of these 386 COVID-19 positive patients, 257 (63.7%) were AAs, 102 (25.3%) HSP, and 26 (6.45%) Whites. There were 257 (63.7%) AA, 102 (25.3%) HSP, 26 (6.45%) Whites. The mean age was 55.6 years (SD = 18.5). However, the mean age of HSP was the lowest (43.7 years vs 61.2 for Whites vs 60 for AAs). The mortality rate was highest among the AAs (20.6%) and lowest among HSP (6.9%). Patients with shortness of breath (SOB) (OR2 = 3.64, CI = 1.73-7.65) and elevated AST (OR2 = 8.01, CI = 3.79-16.9) elevated Procalcitonin (OR2 = 8.27, CI = 3.95-17.3), AST (OR2 = 8.01, CI = 3.79-16.9), ferritin (OR2 = 2.69, CI = 1.24-5.82), and Lymphopenia (OR2 = 2.77, CI = 1.41-5.45) had a high mortality rate. Cough and fever were common but unrelated to the outcome. Hypertension and diabetes mellitus were the most common comorbidities. Glucocorticoid treatment was associated with higher mortality (OR2 = 5.40, CI = 2.72-10.7). Diarrhea was prevalent (18.8%), and GI symptoms did not affect the outcome. CONCLUSION: African Americans in our study had the highest mortality as they consisted of an older population and comorbidities. Age is the most important factor along with SOB in determining the mortality rate. Overall, elevated liver enzymes, ferritin, procalcitonin and C-reactive protein were associated with poor prognosis. GI symptoms did not affect the outcome. Glucocorticoids should be used judiciously, considering the poor outcomes associated with it. Attention should also be paid to monitor liver function during COVID-19, especially in AA and HSP patients with higher disease severity.
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Carcinoma ex pleomorphic adenoma, an uncommon neoplasm of the parotid gland, accounts for less than 4% of salivary gland tumors. It arises from a benign pleomorphic adenoma presenting in the sixth to eighth decades of life. We present this as a unique account of a primary parotid gland carcinoma, arising from myoepithelial cells, without a known precursor lesion, in a 28-year-old woman. This presentation seeks to provide familiarity of an unusual presentation of an unexpected rare pathology in a young female patient and the tools utilized for an accurate diagnosis.
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Chronic hepatitis C virus (HCV) infection disproportionately affects African-Americans (AAs) and is a major contributor to liver failure and mortality. Genetic factors may not be the only cause in outcome disparity. We retrospectively investigated whether genetic host factors, viral genotypes, and treatment compliance in AA patients impacted the efficacy and the sustained virological response (SVR) rate of the interferon (IFN)-based treatment regimen. The medical chart review included 76 African-American patients (age ranging from 26 to 76) with varying levels of hepatitis condition. Fifty-seven (75%) of them had a clinically verifiable HCV infection and were followed by a hepatologist for 2 years at Howard University Hospital in Washington, DC. Both comprehensive metabolic profile and complete blood count analyses were performed. Among the 57 patients whose viral and IL28B genotypes were determined, sixty-eight percent (68%) were infected with viral genotype 1 and 71% harbored the CT allele of the IL28B gene. Among the 12 patients who completed treatment with IFN-based dual or triple therapy, 58% had achieved SVR 12 weeks following completion of treatment; 33% had a partial response with under 6000 viral count after 16 weeks of treatment; and there was one patient with viral genotype 1a and CT allele who did not respond to the medications. The results of this study prove that the PEG IFN-based regimen was effective in treating HCV-infected AA patients despite the current availability of new direct-acting antivirals. The major obstacles contributing to a low reduction in HCV infection and outcome in the AA community were avoidance or lack of treatment or compliance; contraindications, medication side effects, non-adherence, and payer eligibility restrictions.
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Antivirais/uso terapêutico , Negro ou Afro-Americano , Hepatite C Crônica/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Alelos , Antivirais/administração & dosagem , Índice de Massa Corporal , Feminino , Genótipo , Hepatite C Crônica/genética , Humanos , Interferons/genética , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Resposta Viral Sustentada , Carga ViralRESUMO
BACKGROUND: Few studies have analyzed progressive demethylation in the path to cancer. This is of utmost importance, especially in populations such as African Americans, who display aggressive tumors at diagnosis, and for whom markers of early neoplastic transformation are needed. Here, we determined hypomethylated targets in the path to colorectal cancer (CRC) using Reduced Representation Bisulfite Sequencing (RRBS). METHODS: DNA was extracted from fresh frozen tissues of patients with different colon lesions (normal, tubular adenoma, tubulovillous adenoma, and five cancers). RRBS was performed on these DNA extracts to identify hypomethylated gene targets. Alignment, mapping, and methylation analyses were performed. Pathways affected by the hypomethylated gene targets were determined using Ingenuity Pathway Analysis (IPA). RESULTS: Pairwise analyses of samples led to the identification of the following novel hypomethylated genes: ELMO3 (Engulfment and cell motility 3), SLC6A2 (Solute carrier family 6 member 2), SYNM (Synemin), and HMX2 (Homeobox 2). The ELMO3 promoter was significantly hypomethylated at five CpG sites, SYNM at two CpG sites, SLC6A2 at one CpG site, and the HMX2 gene at one CpG site. IPA placed these genes within important carcinogenic pathways. CONCLUSIONS: This work provides insight into the role of hypomethylation in colon carcinogenesis in African Americans. The identified targets affected many important pathways, as demonstrated through IPA. These targets might serve as biomarkers for early diagnosis and potential targets for therapy.
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Hepatoid adenocarcinoma (HAC) is a rare extrahepatic tumor distinguished by having both hepatoid and adenomatous features, which can make the diagnosis challenging. Although it mostly originates in the stomach, several other sites of origin have been reported. We report a case of HAC originating in the duodenum, a very unusual location. We also discuss an approach to the diagnosis of HAC using morphological and immunohistochemical features, and explore possible therapeutic options.
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Background and Aims. Many studies have focused on the determination of methylated targets in colorectal cancer. However, few analyzed the progressive methylation in the sequence from normal to adenoma and ultimately to malignant tumors. This is of utmost importance especially in populations such as African Americans who generally display aggressive tumors at diagnosis and for whom markers of early neoplasia are needed. We aimed to determine methylated targets in the path to colon cancer in African American patients using Reduced Representation Bisulfite Sequencing (RRBS). Methods. Genomic DNA was isolated from fresh frozen tissues of patients with different colon lesions: normal, a tubular adenoma, a tubulovillous adenoma, and five cancers. RRBS was performed on these DNA samples to identify hypermethylation. Alignment, mapping, and confirmed CpG methylation analyses were performed. Preferential hypermethylated pathways were determined using Ingenuity Pathway Analysis (IPA). Results. We identified hypermethylated CpG sites in the following genes: L3MBTL1, NKX6-2, PREX1, TRAF7, PRDM14, and NEFM with the number of CpG sites being 14, 17, 10, 16, 6, and 6, respectively, after pairwise analysis of normal versus adenoma, adenoma versus cancer, and normal versus cancer. IPA mapped the above-mentioned hypermethylated genes to the Wnt/ß-catenin, PI3k/AKT, VEGF, and JAK/STAT3 signaling pathways. Conclusion. This work provides insight into novel differential CpGs hypermethylation sites in colorectal carcinogenesis. Functional analysis of the novel gene targets is needed to confirm their roles in their associated carcinogenic pathways.