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1.
Front Genet ; 14: 1231536, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37732318

RESUMO

Over the past few years, a number of studies have revealed that a significant number of men with prostate cancer had genetic defects in the DNA damage repair gene response and mismatch repair genes. Certain of these modifications, notably gene alterations known as homologous recombination (HRR) genes; PALB2, CHEK2 BRCA1, BRCA2, ATM, and genes for DNA mismatch repair (MMR); MLH1, MSH2, MSH6, and PMS2 are connected to a higher risk of prostate cancer and more severe types of the disease. The DNA damage repair (DDR) is essential for constructing and diversifying the antigen receptor genes required for T and B cell development. But this DDR imbalance results in stress on DNA replication and transcription, accumulation of mutations, and even cell death, which compromises tissue homeostasis. Due to these impacts of DDR anomalies, tumor immunity may be impacted, which may encourage the growth of tumors, the release of inflammatory cytokines, and aberrant immune reactions. In a similar vein, people who have altered MMR gene may benefit greatly from immunotherapy. Therefore, for these treatments, mutational genetic testing is indicated. Mismatch repair gene (MMR) defects are also more prevalent than previously thought, especially in patients with metastatic disease, high Gleason scores, and diverse histologies. This review summarizes the current information on the mutation spectrum and clinical significance of DDR mechanisms, such as HRR and MMR abnormalities in prostate cancer, and explains how patient management is evolving as a result of this understanding.

4.
Front Psychiatry ; 13: 821610, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295779

RESUMO

Background: Healthcare workers play a key role in responding to pandemics like the on-going COVID-19 one. Harmful alcohol use among them could result in inefficiencies in health service delivery. This is particularly concerning in sub-Saharan Africa where the health workforce is already constrained. The aim of this study is to document the burden and correlates of harmful alcohol use among healthcare workers at the beginning of the COVID-19 pandemic in Kenya with the aim of informing policy and practice. Methods: This study was a cross-sectional analysis of data obtained from a parent online survey that investigated the burden and factors associated with mental disorders among healthcare workers during the COVID-19 pandemic in Kenya. We analyzed data obtained from a sub-population of 887 participants who completed the Alcohol Use Disorder Identification Test questionnaire. We used descriptive statistics to summarize the socio-demographic characteristics of the participants and multivariate analysis to determine the factors associated with harmful alcohol use. Results: Three hundred and eighty nine (43.9%) participants reported harmful alcohol use. The factors significantly associated with increased odds of endorsing harmful alcohol use were: being male (AOR = 1.56; 95% CI = 1.14, 2.14; p = 0.006), being unmarried (AOR = 2.06; 95% CI = 1.48, 2.89; p < 0.001), having 11-20 years of experience as compared to having 20+ years of experience (AOR = 1.91; 95% CI = 1.18, 3.12; p = 0.009), and being a specialist (AOR = 2.78; CI = 1.64, 4.78; p = < 0.001) or doctor (AOR = 2.82; 95% CI = 1.74, 4.63; p < 0.001) as compared to being a nurse. Conclusions: A high proportion of healthcare workers reported harmful alcohol use at the beginning of the COVID-19 pandemic in Kenya. Males, the unmarried, those with 11-20 years of experience in the health field, doctors and specialists, were more likely to report harmful alcohol use. These findings highlight the need to institute interventions for harmful alcohol use targeting these groups of healthcare workers in Kenya during the COVID-19 pandemic in order to optimize functioning of the available workforce.

5.
Front Psychiatry ; 12: 665611, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366913

RESUMO

Background: Healthcare workers responding to the Corona Virus Pandemic (COVID-19) are at risk of mental illness. Data is scanty on the burden of mental disorders among Kenyan healthcare workers responding to the pandemic that can inform mental health and psychosocial support. The purpose of this study was to establish the frequency and associated factors of worry, generalized anxiety disorder, depression, posttraumatic stress disorder and poor quality of sleep among Kenyan health care workers at the beginning of COVID-19 pandemic. Methods: We conducted an online survey among 1,259 health care workers in Kenya. A researcher developed social demographic questionnaire and several standardized tools were used for data collection. Standardized tools were programmed into Redcap, (Research Electronic Data Capture) and data analysis was performed using R Core Team. In all analysis a p-value < 0.05 was considered significant. Results: 66% of the participants reported experiencing worry related to COVID-19. 32.1% had depression, 36% had generalized anxiety, 24.2% had insomnia and 64.7% scored positively for probable Post Traumatic Stress Disorder (PTSD). Depression was higher among females compared to men (36.5 vs. 26.9%, p = 0.003), workers <35 years old compared to older ones (38.1 vs. 26.4%, p < 0.001), and those who were not married compared to those who were married (40.6 vs. 27.6%, p < 0.001). Generalized anxiety was commoner among workers aged <35 years (43.5 vs. 29.3%, p < 0.001), females (41.7 vs. 29.2%, p < 0.001), those who mere not married compared to the married (45.2 vs. 31.2%, p < 0.001) and those with <10 years working experience (41.6 to 20.5%, p < 0.001). Younger health care professional had a higher proportion of insomnia compared to the older ones (30.3 vs. 18.6%, p < 0.001). Insomnia was higher among those with <10 years' experience compared to those with more than 20 years' experience(27.3 vs. 17.6%, p = 0.043) Conclusion: Many Kenyan healthcare workers in the early phase of COVID-19 pandemic suffered from various common mental disorders with young, female professionals who are not married bearing the bigger burden. This data is useful in informing interventions to promote mental and psychosocial wellbeing among Kenyan healthcare workers responding to the pandemic.

6.
Infect Agent Cancer ; 15(1): 68, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33292364

RESUMO

BACKGROUND: Cervical cancer screening is slowly transitioning from Pappanicolaou cytologic screening to primary Visual Inspection with Acetic Acid (VIA) or HPV testing as an effort to enhance early detection and treatment. However, an effective triage tests needed to decide who among the VIA or HPV positive women should receive further diagnostic evaluation to avoid unnecessary colposcopy referrals is still lacking. Evidence from experimental studies have shown potential usefulness of Squamous Cell Carcinoma Antigen (SCC Ag), Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/mRNA, and DNA methylation biomarkers in detecting premalignant cervical neoplasia. Given the variation in performance, and scanty review studies in this field, this systematic review described the diagnostic performance of some selected assays to detect high-grade cervical intraepithelial neoplasia (CIN2+) with histology as gold standard. METHODS: We systematically searched articles published in English between 2012 and 2020 using key words from PubMed/Medline and SCOPUS with two reviewers assessing study eligibility, and risk of bias. We performed a descriptive presentation of the performance of each of the selected assays for the detection of CIN2 + . RESULTS: Out of 298 citations retrieved, 58 articles were included. Participants with cervical histology yielded CIN2+ proportion range of 13.7-88.4%. The diagnostic performance of the assays to detect CIN2+ was; 1) SCC-Ag: range sensitivity of 78.6-81.2%, specificity 74-100%. 2) M-CSF: sensitivity of 68-87.7%, specificity 64.7-94% 3) VEGF: sensitivity of 56-83.5%, specificity 74.6-96%. 4) MicroRNA: sensitivity of 52.9-67.3%, specificity 76.4-94.4%. 5) p16INKa / ki-67: sensitivity of 50-100%, specificity 39-90.4%. 6) HPV E6/E7/mRNA: sensitivity of 65-100%, specificity 42.7-90.2%, and 7) DNA methylation: sensitivity of 59.7-92.9%, specificity 67-98%. CONCLUSION: Overall, the reported test performance and the receiving operating characteristics curves implies that implementation of p16ink4a/ki-67 assay as a triage for HPV positive women to be used at one visit with subsequent cryotherapy treatment is feasible. For the rest of assays, more robust clinical translation studies with larger consecutive cohorts of women participants is recommended.

8.
BMC Endocr Disord ; 19(1): 77, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331321

RESUMO

BACKGROUND: Chronic inflammation has been associated with dysglycemia among people living with HIV (PLHIV). There is however, limited data regarding this phenomenon in sub-Sahara Africa (SSA). Therefore we assessed the levels of C-reactive protein (CRP) and Interleukin 6 (IL-6) on a cohort of PLHIV and its associations with dysglycemia in Tanzania. METHODS: We conducted a cross-sectional study at the Infectious Disease Clinic (IDC) in Tanzania from March to May 2018. Purposive sampling was used to identify participants who had an undetectable viral load, were on 1st line anti-retroviral therapy (ART) and had an overnight fast. The WHO stepwise approach for non-communicable disease (NCD) surveillance was used to collect data. Fasting blood glucose and blood glucose after 75 g oral glucose load was measured, and Enzyme-linked immunosorbent assay (ELISA) was used to test for inflammatory markers (IL-6 and CRP). Associations were explored using the Chi square test and binary logistic regression was performed to estimate the odds ratios. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 240 participants were enrolled. Forty two percent were overweight/obese (> 25 kg/m2), 89% had a high waist to height ratio. The median ART duration was 8(5-10) years. The prevalence of dysglycemia among our cohort of PLHIV was 32%. High CRP was associated with a 2.05 increased odds of having dysglycemia OR 2.05 (1.15-3.65) (p = 0.01). Taking stavudine was associated with a 1.99 odds of having dysglycemia OR 1.99 (1.04-3.82) (p = 0.03).We did not find a significant association between IL-6 and dysglycemia. CONCLUSION: High CRP and taking stavudine were significantly associated with dysglycemia among PLHIV with undetectable viral load.


Assuntos
Biomarcadores/sangue , Glicemia/análise , Proteína C-Reativa/análise , Intolerância à Glucose/sangue , Infecções por HIV/complicações , HIV/isolamento & purificação , Interleucina-6/sangue , Estudos Transversais , Feminino , Seguimentos , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/virologia , Infecções por HIV/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Tanzânia/epidemiologia
9.
Pan Afr Med J ; 34: 206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32180880

RESUMO

Burkitt's lymphoma (BL) is a frequent childhood B cell non-Hodgkin's lymphoma (NHL) in equatorial Africa associated with infections. Chronic Epstein Barr virus (EBV) infections can lead to host immune stimulation that may trigger genetic translocation(s), neoplastic transformation and proliferation of B cells. We determined EBV immunoglobulin G (IgG) in sera from participants and EBER-1 in tumour sections in confirmed BL cases at Moi Teaching and Referral Hospital (MTRH). A cross sectional study of children with clinical and histology diagnosis of NHL from whom BL status were confirmed by immunohistochemistry (IHC) was carried out. Epstein Barr virus IgG in sera was determine using Enzyme-linked immunosorbant assay, IHC for EBER-1 and MYC protein in tumour sections. Demographic and clinical information were obtained from questionnaires and hospital files respectively. Ninety three percent of sera were EBV IgG positive of which 31.7% were confirmed as BL. All jaw BL tumours and 86.7% of BL tumours carried EBER-1 antigen. Odds ratio of EBER-1 positive was 1.39, 95% CI: 0.16-12.19 in BL tumours regardless of age or gender. EBV infection among the study participants may be associated with BL, however, EBER-1 and MYC negative in BL tumours suggest alternative BL pathogenesis or variant.


Assuntos
Linfoma de Burkitt/diagnóstico , Herpesvirus Humano 4/imunologia , Imunoglobulina G/sangue , RNA Viral/imunologia , Adolescente , Linfoma de Burkitt/imunologia , Linfoma de Burkitt/patologia , Criança , Estudos Transversais , Feminino , Humanos , Quênia , Masculino , Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/imunologia , Neoplasias Mandibulares/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo
11.
J Neurosci Rural Pract ; 9(3): 363-369, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30069093

RESUMO

BACKGROUND: Astrocytomas are primary central nervous system tumors arising from astrocytes and accounting for up to 37.8% of all brain tumors seen in hospital-based studies from Africa. Despite being common, their patterns and short-term outcomes remain poorly studied in Kenya. MATERIALS AND METHODS: A prospective, descriptive study involving consecutive patients with a histological diagnosis of astrocytoma seen in three hospitals located in Eldoret, Kenya. Clinicopathologic characteristics and outcomes were recorded and patients followed up for 12 weeks. RESULTS: Thirty-one patients were recruited over a 1-year period. Majority of them were female (51.6%). Headache (83.9%) and focal neurological deficits (64.5%) were the most common presenting features. Among patients with high-grade tumors, mean duration of illness was 106.03 ± 162.16 days, median functional status was Karnofsky performance status (KPS) score 50, mean tumor size was 110.22 ± 46.16 cm3, and median magnetic resonance imaging (MRI) score was 17. Among patients with low-grade astrocytomas, mean duration of illness was 213.03 ± 344.93 days, median functional status was KPS score 40, mean tumor size was 53.49 ± 54.96 cm3 and median MRI score was 9. Glioblastoma multiforme (GBM) (71%) and diffuse astrocytoma (22.6%) were the predominant histological subtypes. The median Ki-67 proliferative index was 6% for pilocytic astrocytoma, 1.6% for diffuse astrocytoma, and 60% for GBM. Systemic and regional surgical complications occurred in 6.5% and 38.7% of patients, respectively. In-hospital mortality was 19.4% and increased to 25.8% at 12 weeks. The KPS score at discharge was 50 and improved to 60 at 12 weeks. Only 9.7% of patients had acceptable functional status at 12 weeks follow-up. CONCLUSIONS: In this locality, headache, focal neurological deficits, and reduced functional status are the most common presenting features of astrocytomas while GBM is the most common histological subtype. Tumors are highly proliferative and in the short-term, both surgical and functional outcome are suboptimal.

12.
BMC Res Notes ; 10(1): 519, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-29078819

RESUMO

OBJECTIVE: Burkitt's lymphoma (BL) is a common aggressive non-Hodgkin's lymphoma in East and Central Africa among children. Persistent infections with Epstein Barr virus or Plasmodium falciparum are associated with immune hyperstimulation. It is hypothesised that inadvertent cytokine responses to infections indirectly or directly influence B cell neoplastic transformation through c-myelocytomatosis (c-myc) gene translocation. We sought to describe cytokines in children and adolescents with BL. Participants were recruited from western Kenya with parental consent, diagnosis confirmed using histology and consensus panel of immunohistochemistry antibodies. T helper1/2/17A and transforming growth factor-ß1 (TGF-ß1) cytokines were estimated using cytometric bead array in plasma. Complete blood counts (CBC) were determined by Beckman Coulter®. RESULTS: Out of 104 enrolled participants, 32% were confirmed BL and 68% grouped as non-BL. Mean (pg/ml) levels of cytokines in BL and non-BL were: interleukin (IL)-6 100.3 and 39.4 p = 0.152; IL-10 11.5 and 12.5 p = 0.363; IL-17A 17.8 and 64.9 p = 0.094 respectively. Expressions of interferon-γ, IL-2 and tumour necrosis factor-α were low and TGF-ß1 undetectable in both groups. Mean CBC differed between the two groups before and after chemotherapy, WBC being significantly so. Interleukin-6, IL-17A and IL-10 responses to infections in the study area may be associated with pathogenesis and be potential therapeutic targets.


Assuntos
Linfoma de Burkitt/metabolismo , Citocinas/metabolismo , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/genética , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Quênia , Masculino
13.
Trop Med Health ; 45: 19, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28794686

RESUMO

BACKGROUND: Tumors commonly are infiltrated by leukocytes, or tumor infiltrating leukocytes (TILs). It remains unclear, however, if the density and type of individual TILs has a direct or simply correlative role in promoting poor prognosis in breast cancer patients. Breast cancer in Kenyan women is aggressive with presentation at a young age, with advanced grade (grade III), large tumor size (>2.0 cm), and poor prognosis. We previously observed that the tumors were predominantly estrogen receptor positive (ER+) but also included both a high percentage of triple negative tumors and also increased immune cell infiltration within the tumors. We used breast tumor tissues from each patient to make tissue microarrays that were then stained for leukocyte and myeloid markers including CD4, CD8, CD20, CD25, CD68, and CD163 using immunohistochemical techniques. The immune cell infiltration into the cancer tissue included increased numbers of macrophages (CD68+), helper T cells (CD4+), and CD25+ lymphocytes compared to benign tissue. RESULTS: This study characterized the grade, molecular subtypes, and proliferation index of these tumors and determined if TIL density was enriched across any of these factors. We analyzed 49 malignant patient tissue samples for this study. The patient population had a mean age of 51.9 years. The tumors analyzed were heterogeneous by grade: grade I (6%), grade II (47%), and grade III (39%). Most patients presented with large tumors (>2.0 cm) (69%). We classified the tumors into molecular subtypes based on clinical marker expression. Based on this analysis, the molecular subtype distribution was heterogeneous with luminal B (41%), basal/triple negative (TN) (37%), luminal A (14%) and HER2 (8%) breast cancer subtypes. While the basal/TN subtype had a much higher proliferative index (Ki-67+) than did the other molecular subtypes, we did not see a significant correlation between TIL density and either subtype or tumor grade. Therefore, TIL density is independent of molecular subtype and grade. CONCLUSION: This study identified a Kenyan patient cohort that develops large, high-grade tumors primarily of the luminal B and basal molecular subtypes. After analyzing the TILs within these tumors, we found that immune cell infiltration of these tumors correlated with increased proliferation but not grade or molecular subtype. Future research is required to determine if the aberrant recruitment of TILs to tumors contributes to cancer progression and response to cancer treatments.

14.
Case Rep Pediatr ; 2016: 1621827, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27051548

RESUMO

Purpose of Review. The aim of this review is to provide a case driven presentation of the presenting features and diagnostic criteria particularly focusing on the management of FPIES. It also summarises the natural history and resolution of cow's milk induced FPIES. Data Sources. OvidSP Database was used to search for literature using the keywords food protein-induced enterocolitis and FPIES. Recent Findings. The diagnosis of FPIES is often delayed following two or more presentations. Symptoms in the acute form include profuse vomiting usually 2-6 hours following ingestion of food. Vomiting may or may not be accompanied by diarrhoea. Management involves removing the causal food protein from diet. There is some concomitance in cow's milk and soya induced FPIES. Hence extensively hydrolysed formula is the milk of choice unless breast-feeding is carried out in which case that should be continued. Summary. FPIES is a complex form of non-IgE mediated food allergy. More awareness and knowledge of the condition are required to prevent misdiagnosis. Early diagnosis and removal of the culprit food protein improve the outcome. Good nutritional advice and clear management plans are important. More multicentre studies are required to reevaluate and produce consistent oral food challenge criteria and guidelines.

15.
BMC Cancer ; 16: 204, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26964534

RESUMO

BACKGROUND: Breast cancer incidence and mortality vary significantly among different nations and racial groups. African nations have the highest breast cancer mortality rates in the world, even though the incidence rates are below those of many nations. Differences in disease progression suggest that aggressive breast tumors may harbor a unique molecular signature to promote disease progression. However, few studies have investigated the pathology and clinical markers expressed in breast tissue from regional African patient populations. METHODS: We collected 68 malignant and 89 non-cancerous samples from Kenyan breast tissue. To characterize the tumors from these patients, we constructed tissue microarrays (TMAs) from these tissues. Sections from these TMAs were stained and analyzed using immunohistochemistry to detect clinical breast cancer markers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 receptor (HER2) status, Ki67, and immune cell markers. RESULTS: Thirty-three percent of the tumors were triple negative (ER-, PR-, HER2-), 59% were ER+, and almost all tumors analyzed were HER2-. Seven percent of the breast cancer patients were male, and 30% were <40 years old at diagnosis. Cancer tissue had increased immune cell infiltration with recruitment of CD163+ (M2 macrophage), CD25+ (regulatory T lymphocyte), and CD4+ (T helper) cells compared to non-cancer tissue. CONCLUSIONS: We identified clinical biomarkers that may assist in identifying therapy strategies for breast cancer patients in western Kenya. Estrogen receptor status in particular should lead initial treatment strategies in these breast cancer patients. Increased CD25 expression suggests a need for additional treatment strategies designed to overcome immune suppression by CD25+ cells in order to promote the antitumor activity of CD8+ cytotoxic T cells.


Assuntos
Biomarcadores Tumorais/genética , Proliferação de Células/genética , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Idoso , População Negra/genética , Feminino , Humanos , Imuno-Histoquímica , Quênia , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Linfócitos T Citotóxicos/imunologia , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/genética
16.
Afr J Lab Med ; 5(1): 187, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28879100

RESUMO

BACKGROUND: Cancer is becoming a major cause of mortality in low- and middle-income countries. Unlike infectious disease, malignancy and other chronic conditions require significant supportive infrastructure for diagnostics, staging and treatment. In addition to morphologic diagnosis, diagnostic pathways in oncology frequently require immunohistochemistry (IHC) for confirmation. We present the experience of a tertiary-care hospital serving rural western Kenya, which developed and validated an IHC laboratory in support of a growing cancer care service. OBJECTIVES METHODS AND OUTCOMES: Over the past decade, in an academic North-South collaboration, cancer services were developed for the catchment area of Moi Teaching and Referral Hospital in western Kenya. A major hurdle to treatment of cancer in a resource-limited setting has been the lack of adequate diagnostic services. Building upon the foundations of a histology laboratory, strategic investment and training were used to develop IHC services. Key elements of success in this endeavour included: translation of resource-rich practices to a resource-limited setting, such as using manual, small-batch IHC instead of disposable- and maintenance-intensive automated machinery, engagement of outside expertise to develop reagent-efficient protocols and supporting all levels of staff to meet the requirements of an external quality assurance programme. CONCLUSION: Development of low- and middle-income country models of services, such as the IHC laboratory presented in this paper, is critical for the infrastructure in resource-limited settings to address the growing cancer burden. We provide a low-cost model that effectively develops these necessary services in a challenging laboratory environment.

17.
Afr. j. lab. med. (Online) ; 5(1): 1-7, 2016. tab
Artigo em Inglês | AIM (África) | ID: biblio-1257308

RESUMO

Background: Cancer is becoming a major cause of mortality in low- and middle-income countries. Unlike infectious disease; malignancy and other chronic conditions require significant supportive infrastructure for diagnostics; staging and treatment. In addition to morphologic diagnosis; diagnostic pathways in oncology frequently require immunohistochemistry (IHC) for confirmation. We present the experience of a tertiary-care hospital serving rural western Kenya; which developed and validated an IHC laboratory in support of a growing cancer care service. Objectives; methods and outcomes: Over the past decade; in an academic North-South collaboration; cancer services were developed for the catchment area of Moi Teaching and Referral Hospital in western Kenya. A major hurdle to treatment of cancer in a resource-limited setting has been the lack of adequate diagnostic services. Building upon the foundations of a histology laboratory; strategic investment and training were used to develop IHC services. Key elements of success in this endeavour included: translation of resource-rich practices to are source-limited setting; such as using manual; small-batch IHC instead of disposable- and maintenance-intensive automated machinery; engagement of outside expertise to develop reagent-efficient protocols and supporting all levels of staff to meet the requirements of an external quality assurance programme. Conclusion: Development of low- and middle-income country models of services; such as the IHC laboratory presented in this paper; is critical for the infrastructure in resource-limited settings to address the growing cancer burden. We provide a low-cost model that effectively develops these necessary services in a challenging laboratory environment


Assuntos
Institutos de Câncer , Quênia , Neoplasias/química , Neoplasias/imunologia
18.
PLoS Pathog ; 11(10): e1005158, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26468873

RESUMO

Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.


Assuntos
Linfoma de Burkitt/genética , Linfoma de Burkitt/virologia , Infecções por Vírus Epstein-Barr/virologia , Citomegalovirus/isolamento & purificação , Análise Mutacional de DNA , Doenças Endêmicas , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase , RNA Viral/análise , RNA Viral/genética , Uganda
19.
Pediatr Blood Cancer ; 62(2): 252-256, 2015 02.
Artigo em Inglês | MEDLINE | ID: mdl-25382257

RESUMO

BACKGROUND: Survival from Wilms tumor (WT) in sub-Saharan Africa remains dismal as a result of on-therapy mortality and treatment abandonment. Review of patients diagnosed from 2008 to 2011 in our Kenyan Wilms Tumor Registry showed a loss to follow up (LTFU) rate approaching 50%. The purpose of this study was to trace those LTFU, estimate the survival rate, and identify risk factors for treatment abandonment. PROCEDURE: We administered a comprehensive survey to parents of patients with WT at the two largest referral hospitals in Kenya to identify barriers to care. We also telephoned families who had abandoned care to determine vital status and identify risk factors for treatment abandonment. RESULTS: Of 136 registered patients, 77 were confirmed dead (56.7%), 38 remained alive (27.9%), and the vital status of 21 patients remains unknown (15.4%). After contacting 33 of the patients who either abandoned curative treatment (n = 34) or did not attend off-therapy visits (n = 20), the best estimate of 2-year overall survival of patients with WT in Kenya approaches 36%. Sixty-three percent of parents misunderstood treatment plans and 55% encountered financial barriers. When asked how to increase comfort with the child's treatment, 27% of parents volunteered improving inefficient services and 26% volunteered reducing drug-unavailability. CONCLUSIONS: Treatment abandonment remains a significant problem contributing to increased mortality from WT in developing countries. This multi-center survey identified the barriers to treatment completion from the parental perspective to be lack of education about WT and treatment, financial constraints, need for quality improvement, and drug-unavailability. Pediatr Blood Cancer 2015;62:252-256. © 2014 Wiley Periodicals, Inc.


Assuntos
Efeitos Psicossociais da Doença , Tumor de Wilms/mortalidade , Tumor de Wilms/terapia , Suspensão de Tratamento/estatística & dados numéricos , Humanos , Quênia , Inquéritos e Questionários , Taxa de Sobrevida
20.
J Pediatr Surg ; 48(6): 1254-62, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23845615

RESUMO

PURPOSE: Survival from Wilms Tumor (WT) exceeds 90% at 5 years in developed nations, whereas at last report, 2-year event-free survival (EFS) in Kenya reached only 35%. To clarify factors linked to these poor outcomes in Kenya, we established a comprehensive web-based WT registry, comprised of patients from the four primary hospitals treating childhood cancers. MATERIALS AND METHODS: WT patients diagnosed between January 2008 and January 2012 were identified. Files were abstracted for demographic characteristics, treatment regimens, and enrollment in the Kenyan National Hospital Insurance Fund (NHIF). Children under 15 years of age having both a primary kidney tumor on imaging and concordant histology consistent with WT were included. RESULTS: Two-year event-free survival (EFS) was 52.7% for all patients (n=133), although loss to follow up (LTFU) was 50%. For the 33 patients who completed all scheduled standard therapy, 2-year EFS was 94%. Patients enrolled in NHIF tended to complete more standard therapy and had a lower hazard of death (Cox 0.192, p < 0.001). CONCLUSION: Survival of Kenyan WT patients has increased slightly since last report. Notably, WT patients completing all phases of standard therapy experienced 2-year survival approaching the benchmarks of developed nations. Efforts in Kenya should be made to enhance compliance with WT treatment through NHIF enrollment.


Assuntos
Neoplasias Renais/mortalidade , Sistema de Registros , Tumor de Wilms/mortalidade , Adolescente , Adrenalectomia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Internet , Quênia/epidemiologia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Tumor de Wilms/patologia , Tumor de Wilms/terapia
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