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1.
Pediatr Blood Cancer ; : e31020, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38668553

RESUMO

BACKGROUND: The lack of accurate population-based information on childhood cancer stage and survival in low-income countries is a barrier to improving childhood cancer outcomes. METHODS: In this study, data from the Rwanda National Cancer Registry (RNCR) were examined for children aged 0-14 diagnosed in 2013-2017 for the eight most commonly occurring childhood cancers: acute lymphoblastic leukaemia, Hodgkin lymphoma (HL), Burkitt lymphoma (BL), non-Hodgkin lymphoma excluding BL, retinoblastoma, Wilms tumour, osteosarcoma and rhabdomyosarcoma. Utilising the Toronto Childhood Cancer Stage Guidelines Tier 1, the study assigned stage at diagnosis to all, except HL, and conducted active follow-ups to calculate 1-, 3- and 5-year observed and relative survival by cancer type and stage at diagnosis. RESULTS: The cohort comprised 412 children, of whom 49% (n = 202) died within 5 years of diagnosis. Five-year survival ranged from 28% (95% confidence interval [CI]: 12.5%-45.6%) for BL to 68% (CI: 55%-78%) for retinoblastoma. For the cancers for which staging was carried out, it was assigned for 83% patients (n = 301 of 362), with over half (58%) having limited or localised stage at diagnosis. Stage was a strong predictor of survival; for example, 3-year survival was 70% (95% CI: 45.1%-85.3%) and 11.8% (2.0%-31.2%) for limited and advanced non-HL, respectively (p < .001). CONCLUSION: This study is only the second to report on stage distribution and stage-specific survival for childhood cancers in sub-Saharan Africa. It demonstrates the feasibility of the Toronto Stage Guidelines in a low-resource setting, and highlights the value of population-based cancer registries in aiding our understanding of the poor outcomes experienced by this population.

2.
Small ; : e2401264, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634249

RESUMO

Biological photo-responsive ion channels play important roles in the important metabolic processes of living beings. To mimic the unique functions of biological prototypes, the transition metal dichalcogenides, owing to their excellent mechanical, electrical, and optical properties, are already used for artificial intelligent channel constructions. However, there remain challenges to building artificial bio-semiconductor nanochannels with finely tuned band gaps for accurately simulating or regulating ion transport. Here, two well-designed peptides are employed for the WS2 nanosheets functionalization with the sequences of PFPFPFPFC and DFDFDFDFC (PFC and DFC; P: proline, D: aspartate, and F: phenylalanine) through cysteine (Cys, C) linker, and an asymmetric peptide-WS2 membrane (AP-WS2M) could be obtained via self-assembly of peptide-WS2 nanosheets. The AP-WS2M could realize the photo-driven anti-gradient ion transport and vis-light enhanced osmotic energy conversion by well-designed working patterns. The photo-driven ion transport mechanism stems from a built-in photovoltaic motive force with the help of formed type II band alignment between the PFC-WS2 and DFC-WS2. As a result, the ions would be driven across the channels of the membrane for different applications. The proposed system provides an effective solution for building photo-driven biomimetic 2D bio-semiconductor ion channels, which could be extensively applied in the fields of drug delivery, desalination, and energy conversion.

3.
Int J Cancer ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568397

RESUMO

In sub-Saharan Africa, colorectal cancer (CRC) has historically been considered a rare disease, although some previous studies have suggested that the incidence is increasing. We examine time trends in the incidence of CRC using data from 12 population-based cancer registries in 11 countries of sub-Saharan Africa that were able to provide time series data for periods of 12 or more years, or with earlier data with which recent rates may be compared. Age-standardized incidence rates were highest in the higher-income countries, and were increasing in all of the populations studied, and these increases were statistically significant in all but three. Current evidence has suggested a link between the increased adoption of western lifestyle habits with colorectal cancer, and along with increasing urbanization of African populations, there is an increase in body weight, as well as evidence of increasing consumption of meat, sugars, and alcohol.

4.
Int J Cancer ; 154(11): 1911-1919, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339849

RESUMO

Ovarian cancer (OC) is the fourth most common cancer of women in sub-Saharan Africa (SSA), although few data have been published on population-level survival. We estimate ovarian cancer survival in SSA by human development index and histological subtype, using data from seven population-based cancer registries in six countries: Kenya (Nairobi and Eldoret), Mauritius, Uganda (Kampala), Cote d'Ivoire (Abidjan), Ethiopia (Addis Ababa) and South Africa (Eastern Cape). A total of 644 cases diagnosed during 2008-2014 were included, with 77% being of epithelial subtypes (range 47% [Abidjan]-80% [Mauritius]). The overall observed survival in the study cohort was 73.4% (95% CI: 69.8, 77.0) at 1 year, 54.4% (95% CI: 50.4, 58.7) at 3 years and 45.0% (95% CI: 41.0, 49.4) at 5 years. Relative survival at Year 1 ranged from 44.4% in Kampala to 86.3% in Mauritius, with a mean for the seven series of 67.4%. Relative survival was highest in Mauritius at 72.2% and lowest in Kampala, Uganda at 19.5%, with a mean of 47.8%. There was no difference in survival by age at diagnosis. Patients from high and medium HDI countries had significantly better survival than those from low HDI countries. Women with cancers of epithelial cell origin had much lower survival compared to women with other histological subtypes (p = .02). Adjusted for the young age of the African patients with ovarian cancer (44% aged <50) survival is much lower than in USA or Europe, and underlines the need for improvements in the access to diagnosis and treatment of OC in SSA.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Etiópia , Quênia , Côte d'Ivoire , Uganda/epidemiologia , Neoplasias Ovarianas/epidemiologia , Sistema de Registros
5.
J Natl Compr Canc Netw ; 21(9): 924-933.e7, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37673109

RESUMO

BACKGROUND: The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. METHODS: A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients ("traced cohort"). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). RESULTS: Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83-6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07-2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%-76.3%) and 45.3% (95% CI, 38.9%-51.7%), respectively. CONCLUSIONS: Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.


Assuntos
Neoplasias do Colo , Projetos de Pesquisa , Humanos , Masculino , Feminino , Seguimentos , Instalações de Saúde , África Subsaariana/epidemiologia
6.
Pediatr Blood Cancer ; 70(10): e30555, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37432023

RESUMO

BACKGROUND/PURPOSE: Stage at diagnosis is an important metric in treatment and prognosis of cancer, and also in planning and evaluation of cancer control. In sub-Saharan Africa (SSA), for the latter, the only data source is the population-based cancer registry (PBCR). For childhood cancers, the 'Toronto Staging Guidelines' have been developed to facilitate abstraction of stage by cancer registry personnel. Although the feasibility of staging using this system has been shown, there is limited information on the accuracy of staging. METHODS: A panel of case records of six common childhood cancers was established. A total of 51 cancer registrars from 20 SSA countries staged these records, using Tier 1 of the Toronto guidelines. The stage that they assigned was compared with that decided by two expert clinicians. RESULTS: The registrars assigned the correct stage for 53%-83% of cases (71% overall), with the lowest values for acute lymphocytic leukaemia (ALL), retinoblastoma and non-Hodgkin lymphoma (NHL), and the highest for osteosarcoma (81%) and Wilms tumour (83%). For ALL and NHL, many unstageable cases were mis-staged, probably due to confusion over the rules for dealing with missing data; for the cases with adequate information, accuracy was 73%-75%. Some confusion was observed over the precise definition of three stage levels of retinoblastomas. CONCLUSIONS: A single training in staging resulted in an accuracy, for solid tumours, that was not much inferior to what has been observed in high-income settings. Nevertheless, some lessons were learned on how to improve both the guidelines and the training course.


Assuntos
Neoplasias Renais , Linfoma não Hodgkin , Neoplasias , Neoplasias da Retina , Retinoblastoma , Tumor de Wilms , Criança , Humanos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/patologia , Linfoma não Hodgkin/patologia , Retinoblastoma/diagnóstico , Retinoblastoma/epidemiologia , África Subsaariana , Sistema de Registros
7.
Oncologist ; 28(11): e1017-e1030, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37368350

RESUMO

BACKGROUND: Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. METHODS: We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. FINDINGS: Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. INTERPRETATION: This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Adulto , Taxa de Sobrevida , Resultado do Tratamento
8.
Cancer Immunol Res ; 11(6): 720-731, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37058582

RESUMO

The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients' prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the "African Breast Cancer-Disparities in Outcomes (ABC-DO) Study," were analyzed. The immune cell phenotypes, their spatial distribution in the TME, and immune escape mechanisms of breast cancer samples from SSA and Germany (n = 117) were investigated using histomorphology, conventional and multiplex IHC, and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TIL) in the 1,237 SSA breast cancer samples, while the distribution of TILs in different breast cancer IHC subtypes showed regional diversity, particularly when compared with German samples. Higher TIL densities were associated with better survival in the SSA cohort (n = 400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in breast cancer samples from Western SSA. Features of nonimmunogenic breast cancer phenotypes were associated with reduced patient survival (n = 131). We therefore conclude that regional diversity in the distribution of breast cancer subtypes, TME composition, and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies. See related Spotlight by Bergin et al., p. 705.


Assuntos
Neoplasias , Microambiente Tumoral , Prognóstico , Estudos de Coortes , Linfócitos do Interstício Tumoral , Macrófagos , Neoplasias/patologia
9.
Acta Oncol ; 62(4): 335-341, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37102435

RESUMO

BACKGROUND/PURPOSE: Stage at diagnosis is an important metric in treatment and prognosis of cancer, and also in planning and evaluation of cancer control. For the latter purposes, the data source is the population-based cancer registry (PBCR), but, although stage is usually among the variables collected by cancer registries, it is often missing, especially in low-income settings. Essential TNM has been introduced to facilitate abstraction of stage data by cancer registry personnel, but the accuracy with which they can do so is unknown. METHODS: 51 cancer registrars from 20 countries of sub-Saharan Africa (13 anglophone, 7 francophone) were tasked with abstracting stage at diagnosis, using Essential TNM, from scanned extracts of case. The panel comprised 28 records of each of 8 common cancer types, and the participants chose how many to attempt (between 48 and 128). Stage group (I-IV), derived from the eTNM elements that they assigned to each cancer, was compared with a gold standard, as decided by two expert clinicians. RESULTS: The registrars assigned the correct stage (I-IV) in between 60 and 80% of cases, with the lowest values for ovary, and the highest for oesophagus. The weighted kappa statistic suggested a moderate level of agreement between participant and expert (0.41-0.60) for 5 cancers, and substantial agreement (0.61-0.80) for three, with the best for cervix, large bowel, oesophagus and ovary, and the worst (weighted kappa 0.46) for non-Hodgkin lymphoma (NHL). For all except NHL, early stage (I/II) and late stage (III/IV) was correctly identified in 80% or more of the cases. CONCLUSIONS: A single training in staging using Essential TNM resulted in an accuracy that was not much inferior to what has been observed in clinical situations in high income settings. Nevertheless, some lessons were learned on how to improve both the guidelines for staging, and the training course.


Assuntos
Linfoma não Hodgkin , Neoplasias , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/patologia , Sistema de Registros , Prognóstico , África/epidemiologia
10.
Int J Cancer ; 152(7): 1328-1336, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36274630

RESUMO

Ovarian cancer (OC) is one of the commonest cancers of women in sub-Saharan Africa (SSA), although to date no data have been available on time trends in incidence to better understand the disease pattern in the region. We estimate time trends by histological subtype from 12 population-based cancer registries in 11 countries: Kenya (Nairobi), Mauritius, Seychelles, Uganda (Kampala), Congo (Brazzaville), Zimbabwe (Bulawayo and Harare), Cote d'Ivoire (Abidjan), The Gambia, Mali (Bamako), Nigeria (Ibadan) and South Africa (Eastern Cape). The selected registries were those that could provide consistent estimates of the incidence of ovarian cancer and with quality assessment for periods of 10 or more years. A total of 5423 cases of OC were included. Incidence rates have been increasing in all registries except Brazzaville, Congo, where a nonsignificant decline of 1% per year was seen. Statistically significant average annual increases were seen in Mauritius (2.5%), Bamako (5.3%), Ibadan (3.9%) and Eastern Cape (8%). Epithelial ovarian cancer was responsible for the increases observed in all registries. Statistically significant average annual percentage changes (AAPC) for epithelial OC were present in Bamako (AAPC = 5.9%), Ibadan (AAPC = 4.7%) and Eastern Cape (AAPC = 11.0%). Creating awareness among professionals of the growing importance of the disease is surely an important step to improving availability of, and access to, diagnosis and treatment of OC in SSA. Support must be given to the cancer registries to improve the availability of good-quality data on this important cancer.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Incidência , Côte d'Ivoire/epidemiologia , Quênia , Nigéria , Uganda , Zimbábue , Neoplasias Ovarianas/epidemiologia , Carcinoma Epitelial do Ovário/epidemiologia
11.
Biosens Bioelectron ; 218: 114741, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36209531

RESUMO

Light-driven proton directional transport is important in living beings as it could subtly realize the light energy conversion for living uses. In the past years, 2D materials-based nanochannels have shown great potential in active ion transport due to controllable properties, including surface charge distribution, wettability, functionalization, electric structure, and external stimuli responsibility, etc. However, to fuse the inorganic materials into bio-membranes still faces several challenges. Here, we proposed peptide-modified WS2 nanosheets via cysteine linkers to realize tunable band structure and, hence, enable light-driven proton transmembrane transport. The modification was achieved through the thiol chemistry of the -SH groups in the cysteine linker and the S vacancy on the WS2 nanosheets. By tuning the amino residues sequences (lysine-rich peptides, denoted as KFC; and aspartate-rich peptides, denoted as DFC), the ζ-potential, surface charge, and band energy of WS2 nanosheets could be rationally regulated. Janus membranes formed by assembling the peptide-modified WS2 nanosheets could realize the proton transmembrane transport under visible light irradiation, driven by a built-in potential due to a type II band alignment between the KFC-WS2 and DFC-WS2. As a result, the proton would be driven across the formed nanochannels. These results demonstrate a general strategy to build bio-semiconductor materials and provide a new way for embedding inorganic materials into biological systems toward the development of bioelectronic devices.


Assuntos
Técnicas Biossensoriais , Prótons , Cisteína , Ácido Aspártico , Lisina , Transporte de Íons , Semicondutores , Peptídeos
12.
CNS Neurosci Ther ; 28(4): 470-483, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862758

RESUMO

Postoperative neurological disorders, including postoperative delirium (POD), postoperative cognitive dysfunction (POCD), postoperative covert ischemic stroke, and hemorrhagic stroke, are challenging clinical problems in the emerging aged surgical population. These disorders can deteriorate functional outcomes and long-term quality of life after surgery, resulting in a substantial social and financial burden to the family and society. Understanding predisposing and precipitating factors may promote individualized preventive treatment for each disorder, as several risk factors are modifiable. Besides prevention, timely identification and treatment of etiologies and symptoms can contribute to better recovery from postoperative neurological disorders and lower risk of long-term cognitive impairment, disability, and even death. Herein, we summarize the diagnosis, risk factors, prevention, and treatment of these postoperative complications, with emphasis on recent advances and perspectives.


Assuntos
Disfunção Cognitiva , Delírio , Complicações Cognitivas Pós-Operatórias , Idoso , Disfunção Cognitiva/etiologia , Humanos , Complicações Pós-Operatórias , Qualidade de Vida , Fatores de Risco
13.
Int J Syst Evol Microbiol ; 71(12)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34913427

RESUMO

An aerobic Gram-stain-negative, curved rod-shaped and non-spore-forming bacterial strain (NBU2194T) was isolated from seawater collected in an intertidal zone in Ningbo, Zhejiang Province, PR China. It was motile though a single polar flagellum and grew at 20-42 °C (optimum, 30 °C), in 0-2.0 % NaCl (0 %, w/v) and at pH 5.0-9.0 (pH 6.0-7.0). The sole respiratory quinone was ubiquinone-8. The major cellular fatty acids were C16 : 0, C16 : 1 ω7c and/or C16 : 1 ω6c. The polar lipids contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid and two unidentified aminophosphoglycolipids. A phylogenetic analysis based on 16S rRNA gene sequences and 65 genomic core genes showed that strain NBU2194T formed a distinct lineage in the family Alteromonadaceae. The genome of strain NBU2194T was 4 913 533 bp with a DNA G+C content of 43.9 mol% and coded 3895 genes, 12 rRNA genes and 47 tRNA genes. The average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values between strain NBU2194T and related species of Alteromonadaceae were below the threshold limit for prokaryotic species delineation. NBU2194T could be distinguished from other genera in the family Alteromonadaceae based on phenotypic, chemotaxonomic and genomic characteristics. On the basis of the polyphasic taxonomic evidence collected in this study, strain NBU2194T is considered to represent a novel genus and species in the family Alteromonadaceae, for which the name Paraneptunicella aestuarii is proposed. The type strain is NBU2194T (=KCTC 82442T=GDMCC 1.2217T).


Assuntos
Alteromonadaceae , Filogenia , Água do Mar/microbiologia , Alteromonadaceae/classificação , Alteromonadaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
14.
J Natl Compr Canc Netw ; 20(13)2021 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-34965508

RESUMO

BACKGROUND: Breast cancer (BC) is the most common cancer in sub-Saharan Africa (SSA). However, little is known about the actual therapy received by women with BC and their survival outcome at the population level in SSA. This study aims to describe the cancer-directed therapy received by patients with BC at the population level in SSA, compare these results with the NCCN Harmonized Guidelines for SSA (NCCN Harmonized Guidelines), and evaluate the impact on survival. METHODS: Random samples of patients with BC (≥40 patients per registry), diagnosed from 2009 through 2015, were drawn from 11 urban population-based cancer registries from 10 countries (Benin, Congo, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mozambique, Namibia, Uganda, and Zimbabwe). Active methods were used to update the therapy and outcome data of diagnosed patients ("traced patients"). Excess hazards of death by therapy use were modeled in a relative survival context. RESULTS: A total of 809 patients were included. Additional information was traced for 517 patients (63.8%), and this proportion varied by registry. One in 5 traced patients met the minimum diagnostic criteria (cancer stage and hormone receptor status known) for use of the NCCN Harmonized Guidelines. The hormone receptor status was unknown for 72.5% of patients. Of the traced patients with stage I-III BC (n=320), 50.9% received inadequate or no cancer-directed therapy. Access to therapy differed by registry area. Initiation of adequate therapy and early-stage diagnosis were the most important determinants of survival. CONCLUSIONS: Downstaging BC and improving access to diagnostics and care are necessary steps to increase guideline adherence and improve survival for women in SSA. It will also be important to strengthen health systems and facilities for data management in SSA to facilitate patient follow-up and disease surveillance.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Gerenciamento de Dados , África Subsaariana/epidemiologia , Estadiamento de Neoplasias , Sistema de Registros
15.
Cancer Causes Control ; 32(9): 1001-1019, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34244896

RESUMO

OBJECTIVES: To estimate observed and relative survival of prostate cancer patients in sub-Saharan Africa (SSA) and to examine the influence of age, stage at diagnosis and the Human Development Index (HDI). PATIENTS AND METHODS: In this comparative registry study, we selected a random sample of 1752 incident cases of malign prostatic neoplasm from 12 population-based cancer registries from 10 SSA countries, registered between 2005 and 2015. We analyzed the data using Kaplan-Meier and Ederer II methods to obtain outcome estimates and flexible Poisson regression modeling to calculate the excess hazards of death RESULTS: For the 1406 patients included in the survival analyses, 763 deaths occurred during 3614 person-years of observation. Of patients with known stage, 45.2% had stage IV disease, 31.2% stage III and only 23.6% stage I and II. The 1 and 5-year relative survival for the entire cohort was 78.0% (75.4-80.7) and 60.0% (55.7-64.6), while varying between the registries. Late presentation was associated with increased excess hazards and a 0.1 increase in the HDI was associated with a 20% lower excess hazard of death, while for age at diagnosis no association was found. CONCLUSIONS: We found poor survival of SSA prostatic tumor patients, as well as high proportions of late stage presentation, which are associated with inferior outcome. This calls for investment in health-care systems and action regarding projects to raise awareness among the population to achieve earlier diagnosis and improve survival.


Assuntos
Neoplasias da Próstata , África Subsaariana , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Sistema de Registros
16.
J Gastroenterol Hepatol ; 36(12): 3429-3437, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34258777

RESUMO

BACKGROUND AND AIM: Regorafenib is a potent multikinase inhibitor for the second-line targeted therapy against hepatocellular carcinoma (HCC); however, drug resistance is emerging in clinical settings. Although cancer stem cells (CSCs) are considered as key determinate of drug sensitivity, it remains unclear how CSCs may communicate with the differentiated counterparts (non-CSC) to dictate therapeutic efficacy. Therefore, we sought to investigate the regorafenib resistance mechanism of CSCs in HCC. METHODS: We used sphere formation and soft agar colony formation assays to evaluate the stemness capacity of cancer cells. Cell viability assay was performed to detect the sensitivity of cancer cells to regorafenib. Real-time quantitative polymerase chain reaction and western blot were used to analyze gene expression. Mouse xenograft tumor model was performed to assess Regorafenib sensitivity in vivo. RESULTS: Exosomes are highly enriched in CSC supernatant compared with that of non-CSC, and RAB27A mediates exosome secretion from CSCs to maintain stem-like phenotype and regorafenib insensitivity. Moreover, exosomes released by CSCs upregulate the expression of Nanog in non-CSC, while depleting Nanog sensitizes non-CSC to regorafenib in the presence of CSC exosomes. Consistently, analysis of TCGA datasets reveals that RAB27A expression tightly correlates with Nanog in HCC tissues. More importantly, depletion of RAB27A downregulates Nanog expression and sensitizes cancer cells to regorafenib in nude mice. CONCLUSIONS: Our findings suggest that CSCs release exosomes in a RAB27A-dependent manner to induce Nanog expression and regorafenib resistance in differentiated cells, targeting this exosome signaling between distinct cellular subsets may be a potential therapeutic strategy for HCC patients.


Assuntos
Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas , Proteína Homeobox Nanog , Proteínas rab27 de Ligação ao GTP , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/metabolismo , Expressão Gênica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Nus , Proteína Homeobox Nanog/genética , Células-Tronco Neoplásicas/metabolismo , Compostos de Fenilureia/farmacologia , Piridinas/farmacologia , Proteínas rab27 de Ligação ao GTP/genética
17.
Cancer ; 127(22): 4221-4232, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34328216

RESUMO

BACKGROUND: Although prostate cancer (PCa) is the most commonly diagnosed cancer in men of sub-Saharan Africa (SSA), little is known about its management and survival. The objective of the current study was to describe the presentation, patterns of diagnosis, treatment, and survival of patients with PCa in 10 countries of SSA. METHODS: In this observational registry study with data collection from 2010 to 2018, the authors drew a random sample of 738 patients with PCa who were registered in 11 population-based cancer registries. They described proportions of patients receiving recommended care and presented survival estimates. Multivariable Cox regression was used to calculate hazard ratios comparing the survival of patients with and without cancer-directed therapies (CDTs). RESULTS: The study included 693 patients, and tumor characteristics and treatment information were available for 365 patients, 37.3% of whom had metastatic disease. Only 11.2% had a complete diagnostic workup for risk stratification. Among the nonmetastatic patients, 17.5% received curative-intent therapy, and 27.5% received no CDT. Among the metastatic patients, 59.6% received androgen deprivation therapy. The 3- and 5-year age-standardized relative survival for 491 patients with survival time information was 58.8% (95% confidence interval [CI], 48.5%-67.7%) and 56.9% (95% CI, 39.8%-70.9%), respectively. In a multivariable analysis, survival was considerably poorer among patients without CDT versus those with therapy. CONCLUSIONS: This study shows that a large proportion of patients with PCa in SSA are not staged or are insufficiently staged and undertreated, and this results in unfavorable survival. These findings reemphasize the need for improving diagnostic workup and access to care in SSA in order to mitigate the heavy burden of the disease in the region.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , África Subsaariana/epidemiologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Sistema de Registros
18.
Int J Cancer ; 149(8): 1553-1563, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34164808

RESUMO

There are limited population-based survival data for colorectal cancer (CRC) in sub-Saharan Africa. Here, 1707 persons diagnosed with CRC from 2005 to 2015 were randomly selected from 13 population-based cancer registries operating in 11 countries in sub-Saharan Africa. Vital status was ascertained from medical charts or through next of kin. 1-, 3- and 5-year overall and relative survival rates for all registries and for each registry were calculated using the Kaplan-Meier estimator. Multivariable analysis was used to examine the associations of 5-year relative survival with age at diagnosis, stage and country-level Human Development Index (HDI). Observed survival for 1448 patients with CRC across all registries combined was 72.0% (95% CI 69.5-74.4%) at 1 year, 50.4% (95% CI 47.6-53.2%) at 3 years and 43.5% (95% CI 40.6-46.3%) at 5 years. We estimate that relative survival at 5 years in these registry populations is 48.2%. Factors associated with poorer survival included living in a country with lower HDI, late stage at diagnosis and younger or older age at diagnosis (<50 or ≥70 years). For example, the risk of death was 1.6 (95% CI 1.2-2.1) times higher for patients residing in medium-HDI and 2.7 (95% CI 2.2-3.4) times higher for patients residing in low-HDI compared to those residing in high-HDI countries. Survival for CRC remains low in sub-Saharan African countries, though estimates vary considerably by HDI. Strengthening health systems to ensure access to prevention, early diagnosis and appropriate treatment is critical in improving outcomes of CRC in the region.


Assuntos
Neoplasias Colorretais/mortalidade , Sistema de Registros/estatística & dados numéricos , África Subsaariana/epidemiologia , Fatores Etários , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida
19.
Cancer Epidemiol Biomarkers Prev ; 30(5): 867-873, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33619023

RESUMO

BACKGROUND: The cancer registry of Bulawayo (Zimbabwe) operated for 15 years in the preindependence period (1963-77), and was restarted in 2011. This allows comparison of incidence of cancers over a period of almost 50 years. METHODS: Age-standardized rates, with SEs, were calculated for 1963-1972 and 2011-2015. Detailed results are presented for those cancers for which there was a significant (P < 0.05) change in the rates between the two periods. RESULTS: There were declines in the rates of those cancers previously known to be common in East and Southern Africa (esophagus, liver, bladder), and the emergence of cancers associated with "westernization" of lifestyles (breast, prostate, large bowel). Cancers related to infection with HIV-AIDS (Kaposi sarcoma, non-Hodgkin lymphoma, eye cancers) have come to comprise a much larger proportion of the total burden, and cancer of the cervix (also AIDS-related) has shown a large increase in incidence-as elsewhere in sub-Saharan Africa (SSA). More surprising is the decline in cancer of the lung-formerly very high, but by 2011-2015, despite little change in the prevalence of smoking, rates were low-close to the average for SSA. This may relate, in part, to a decline in the numbers of miners, and ex-miners, residing in the city. CONCLUSIONS: The changes in incidence are largely explained by differences in past exposure to environmental risk factors. IMPACT: Few datasets from SSA can document temporal changes in the cancer epidemic on the continent. There are some anticipated observations, as well as unexpected findings meriting further investigation.


Assuntos
Neoplasias/epidemiologia , Distribuição por Idade , Feminino , Humanos , Incidência , Masculino , Vigilância da População , Sistema de Registros , Fatores de Risco , Distribuição por Sexo , Zimbábue/epidemiologia
20.
Oncologist ; 26(5): e807-e816, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33565668

RESUMO

BACKGROUND: Cervical cancer (CC) is the most common female cancer in many countries of sub-Saharan Africa (SSA). We assessed treatment guideline adherence and its association with overall survival (OS). METHODS: Our observational study covered nine population-based cancer registries in eight countries: Benin, Ethiopia, Ivory Coast, Kenya, Mali, Mozambique, Uganda, and Zimbabwe. Random samples of 44-125 patients diagnosed from 2010 to 2016 were selected in each. Cancer-directed therapy (CDT) was evaluated for degree of adherence to National Comprehensive Cancer Network (U.S.) Guidelines. RESULTS: Of 632 patients, 15.8% received CDT with curative potential: 5.2% guideline-adherent, 2.4% with minor deviations, and 8.2% with major deviations. CDT was not documented or was without curative potential in 22%; 15.7% were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease. Adherence was not assessed in 46.9% (no stage or follow-up documented, 11.9%, or records not traced, 35.1%). The largest share of guideline-adherent CDT was observed in Nairobi (49%) and the smallest in Maputo (4%). In patients with FIGO stage I-III disease (n = 190), minor and major guideline deviations were associated with impaired OS (hazard rate ratio [HRR], 1.73; 95% confidence interval [CI], 0.36-8.37; HRR, 1.97; CI, 0.59-6.56, respectively). CDT without curative potential (HRR, 3.88; CI, 1.19-12.71) and no CDT (HRR, 9.43; CI, 3.03-29.33) showed substantially worse survival. CONCLUSION: We found that only one in six patients with cervical cancer in SSA received CDT with curative potential. At least one-fifth and possibly up to two-thirds of women never accessed CDT, despite curable disease, resulting in impaired OS. Investments into more radiotherapy, chemotherapy, and surgical training could change the fatal outcomes of many patients. IMPLICATIONS FOR PRACTICE: Despite evidence-based interventions including guideline-adherent treatment for cervical cancer (CC), there is huge disparity in survival across the globe. This comprehensive multinational population-based registry study aimed to assess the status quo of presentation, treatment guideline adherence, and survival in eight countries. Patients across sub-Saharan Africa present in late stages, and treatment guideline adherence is remarkably low. Both factors were associated with unfavorable survival. This report warns about the inability of most women with cervical cancer in sub-Saharan Africa to access timely and high-quality diagnostic and treatment services, serving as guidance to institutions and policy makers. With regard to clinical practice, there might be cancer-directed treatment options that, although not fully guideline adherent, have relevant survival benefit. Others should perhaps not be chosen even under resource-constrained circumstances.


Assuntos
Neoplasias do Colo do Útero , Estudos de Coortes , Etiópia , Feminino , Fidelidade a Diretrizes , Humanos , Quênia , Gravidez , Uganda , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapia
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