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1.
Br J Cancer ; 128(5): 760-765, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36517550

RESUMEN

BACKGROUND: Although suggestive of dysregulated metabolism, the relationship between serum LDH level, phenotypic/aetiologic diagnostic Global Leadership Initiative on Malnutrition (GLIM) criteria and survival in patients with advanced cancer has yet to examined. METHODS: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011-2016, was retrospectively analysed. LDH values were grouped as <250/250-500/>500 Units/L. Relationships were examined using χ2 test for linear-by-linear association and binary logistics regression analysis. RESULTS: A total of 436 patients met the inclusion criteria. 46% (n = 200) were male and 59% (n = 259) were ≥65 years of age. The median serum LDH was 394 Units/L and 33.5% (n = 146) had an LDH > 500 Units/L. LDH was significantly associated with ECOG-PS (p < 0.001), NLR (p < 0.05), mGPS (p < 0.05) and 3-month survival (p < 0.001). LDH was significantly associated with 3-month survival independent of weight loss (p < 0.01), BMI (p < 0.05), skeletal muscle mass (p < 0.01), metastatic disease (p < 0.05), NLR (p < 0.05) and mGPS (p < 0.01). DISCUSSION: LDH was associated with performance status, systemic inflammation and survival in patients with advanced cancer. LDH measurement may be considered as an aetiologic criteria and become a potential therapeutic target in the treatment of cancer cachexia.


Asunto(s)
Desnutrición , Neoplasias , Humanos , Masculino , Femenino , Caquexia , Estudios Retrospectivos , L-Lactato Deshidrogenasa , Liderazgo , Neoplasias/patología , Desnutrición/diagnóstico , Evaluación Nutricional , Estado Nutricional
2.
Value Health ; 26(3): 402-410, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36368626

RESUMEN

OBJECTIVES: This study aimed to assess the cost-effectiveness of pembrolizumab monotherapy in the first-line treatment of advanced non-small cell lung cancer (NSCLC) in adults whose tumors expressed programmed death-ligand 1 (PD-L1) with a tumor proportion score (TPS) ≥ 50% in the Irish healthcare setting. METHODS: Effectiveness inputs were derived from the 5-year analysis of KEYNOTE-024 phase III clinical trial. The intervention was pembrolizumab monotherapy; the comparator was a weighted average of the 5 chemotherapy regimens from the trial. The population included those with previously untreated advanced PD-L1 TPS ≥ 50% NSCLC. A de novo partitioned survival model was developed. Survival modeling was done using Bayesian model averaging on fitted parametric functions. Costs included drug acquisition, treatment initiation, administration and monitoring, adverse events, subsequent treatments, and terminal care. Costs and health state utilities were sourced from the literature and Irish sources. The model had a 20-year time horizon. The perspective taken was the Health Service Executive. A 4% discount rate was applied. Outcomes were expressed as an incremental cost-effectiveness ratio (ICER), measured in terms of incremental costs per quality-adjusted life-year (QALY). Probabilistic sensitivity analysis and 1-way sensitivity analyses were conducted. RESULTS: The model estimated a base case ICER of €54 237 per QALY. The probabilistic sensitivity analysis estimated an average ICER of €54 568 per QALY and a 11% probability of cost-effectiveness at the Irish cost-effectiveness threshold of €45 000 per QALY. CONCLUSION: At the current list price, first-line pembrolizumab monotherapy is not considered cost-effective for the treatment of advanced PD-L1 TPS ≥ 50% NSCLC in the Irish healthcare setting.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Antígeno B7-H1 , Neoplasias Pulmonares/tratamiento farmacológico , Análisis Costo-Beneficio , Teorema de Bayes , Atención a la Salud , Años de Vida Ajustados por Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
3.
J Vis ; 23(11): 22, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37733556

RESUMEN

The non-human primate (NHP) is the gold standard animal model for preclinical development of gene and cell based therapies for vision restoration. However, the ocular immune response to these interventions remains poorly understood. We conducted a proof of concept study using offset aperture adaptive optics scanning light ophthalmoscopy (AOSLO) to visualize cellular-scale changes in the primate retina following photoreceptor (PR) ablation. Ultrafast 730nm laser exposure at 26.6 - 32.5 J/cm2 was used to create six lesions in four NHPs. Offset aperture images focused on retinal vascular layers were collected with an offset distance of ~10 Airy Disk Diameters from 15 minutes up to three hours after PR ablation. We observed putative immune cells in and around vessels supplying the lesioned areas. Consistent with previous findings in murine models, cells within vessels adhered to the inner wall, exhibited crawling behavior, and had a diameter ranging from ~9.3 - 11.5 µm. Additionally, we observed the emergence of cellular-scale structures above the PR layer that originated in the center of the lesion 15 minutes post-insult and gradually radiated outward. Vascular perfusion was maintained in these regions. Our data suggest that offset aperture imaging offers cellular-scale, label free, in vivo assessment of the retinal response to insult in NHPs and could be employed to advance our understanding of the ocular immune response provoked by disease and therapeutic interventions.


Asunto(s)
Diagnóstico por Imagen , Retina , Animales , Ratones , Retina/diagnóstico por imagen , Cara , Modelos Animales , Primates
4.
Omega (Westport) ; : 302228231196620, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37670454

RESUMEN

The COVID-19 pandemic compounded isolation for patients through social distancing measures and staff shortages. We were concerned about the impact of COVID-19 on the quality of care provided at end-of-life in 2021 in a national cancer centre, and instigated the first ever review of the care of the dying. Quality of care was assessed retrospectively using a validated instrument developed by the United Kingdom's National Quality Board. Sixty-six patient deaths occurred in our cancer centre in 2021. The 'risk of dying' was documented in 65.2% of records. Palliative care services were involved in 77%, and pastoral care in 10.6%. What was important to the patient was documented in 24.2%. The 'quality-of-death' score was satisfactory for most but poor in 21.2%. Our study prompted change, including appointment of an end-of-life coordinator, development of a checklist to ensure comprehensive communication, expansion of the end-of-life committee to include junior doctors, and regular audit.

5.
Oncologist ; 26(4): e603-e607, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33252154

RESUMEN

INTRODUCTION: "Transgender" and "gender diverse" are umbrella terms encompassing those whose gender identities or expressions differ from those typically associated with the sex they were assigned at birth. There is scant global information on cancer incidence, outcome, and mortality for this cohort. This group may present with advanced cancer, have mistrust in health care services and report anxiety and depression at higher frequencies, a finding often seen in marginalized groups because of minority stress. MATERIALS AND METHODS: Medical oncologists were contacted by secure email to identify patients who self-identify as transgender and gender diverse in three Irish hospitals. Five patients were identified. A retrospective chart review was conducted and a pseudonymized patient survey was distributed. RESULTS: All patients included in our chart review (n = 5) were diagnosed with advanced disease on initial diagnosis. Two patients identified as men, two as women, and one as a transwoman. Two of five patients' health record charts reflected a name or gender change. Three patients had gender transitioning treatment postponed. Assessing comorbidities, it was seen that four patients required psychiatry input. Predominant issues noted in our patient survey by the two respondents (n = 2) were "mis-gendering," lack of a gender-neutral hospital environment, lack of inclusion in cancer groups, and barriers in changing name and/or sex on hospital records. CONCLUSION: Components of care requiring revision include patient accessible pathways to change names and gender on health records, earlier access to psychological support and targeted screening and support groups. Resources for hospital staff to improve awareness of correct terminology and to provide gender neutral facilities are worthwhile. IMPLICATIONS FOR PRACTICE: The implications for practice on an international level include patient-friendly pathways for changing hospital name and gender so that patients may feel comfortable using wristbands. The need for international screening guidelines for transgender patients and national transgender cancer support groups is highlighted. On a day-to-day level for providers, the correct use of pronouns makes a big difference to patients. Asking about preferred pronoun on first visit and noting on patient's file is worthwhile. It is important for providers to know that increased psychological support should be offered early on first clinic visit and engaged with as necessary when patient has a history of anxiety or depression. Providers should discuss openly that some gender transitioning treatment will be postponed because of cancer care and refer to both the physical and psychological sequelae of this. Asking transgender patients which room or bathroom they would prefer when rooms are gendered is essential.


Asunto(s)
Neoplasias , Personas Transgénero , Femenino , Identidad de Género , Humanos , Recién Nacido , Irlanda/epidemiología , Masculino , Neoplasias/epidemiología , Neoplasias/terapia , Investigación Cualitativa , Estudios Retrospectivos
6.
Cancer ; 126(12): 2872-2882, 2020 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-32267548

RESUMEN

BACKGROUND: Optimizing quality of life (QoL) remains the central tenet of care in patients with incurable cancer; however, determinants of QoL are not clear. The objective of the current study was to examine which factors influence QoL in patients with incurable cancer. METHODS: A multicenter study of adult patients with advanced cancer was conducted in Ireland and the United Kingdom between 2011 and 2016. Data were collected from patients at study entry and included patient demographics, Eastern Cooperative Oncology Group performance status (ECOG-PS), nutritional parameters (the percentage weight loss [%WL]), muscle parameters assessed using computed tomography images (skeletal muscle index and skeletal muscle attenuation), inflammatory markers (modified Glasgow Prognostic score [mGPS]), and QoL data (the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30). The relation between clinical, nutritional, and inflammatory parameters with QoL was assessed using the Spearman rank correlation coefficient and multivariate binary logistic regression. Components of the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30 (physical function, fatigue, and appetite loss) and summary QoL scores were mean-dichotomized for the logistic regression analyses. RESULTS: Data were available for 1027 patients (51% men; median age, 66 years). Gastrointestinal cancer was most prevalent (40%), followed by lung cancer (26%) and breast cancer (9%). Distant metastatic disease was present in 87% of patients. The %WL, ECOG-PS, and mGPS were significantly correlated with deteriorating QoL functional and symptom scales (all P < .001). On multivariate regression analysis, >10% WL (odds ratio [OR], 2.69; 95% CI, 1.63-4.42), an ECOG-PS of 3 or 4 (OR, 14.33; 95% CI, 6.76-30.37), and an mGPS of 2 (OR, 1.58; 95% CI, 1.09-2.29) were independently associated with poorer summary QoL scores. These parameters were also independently associated with poorer physical function, fatigue, and appetite loss (all P < .05). Low skeletal muscle attenuation was independently associated with poorer physical functioning (OR, 1.67; 95% CI, 1.09-2.56), but muscle parameters were not independently associated with fatigue, appetite loss, or QoL summary scores. CONCLUSIONS: The current findings indicate that QoL is determined (at least in part) by WL, ECOG-PS, and the systemic inflammatory response in patients with advanced cancer. Identifying early predictors of poor QoL may allow the identification of patients who may benefit from early referral to palliative and supportive care, which has been shown to improve QoL.


Asunto(s)
Neoplasias/etiología , Calidad de Vida , Anciano , Anciano de 80 o más Años , Composición Corporal , Fatiga/etiología , Femenino , Humanos , Inflamación/etiología , Irlanda , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/terapia , Estado Nutricional , Reino Unido
8.
J Cutan Pathol ; 46(2): 117-122, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30430609

RESUMEN

BACKGROUND: Techniques for the accurate identification of activating mutations of BRAF in metastatic melanoma are of great clinical importance, due to the availability of targeted therapies for these tumors. There is uncertainty regarding the frequency with which BRAF status differs between primary and metastatic sites. METHODS: Between 2011 and 2016, 219 melanoma cases underwent BRAF testing in our institution. In 53 of these cases, paired primary and metastatic specimens were available for polymerase chain reaction (PCR) and immunohistochemical evaluation. RESULTS: Fifty-two out of 53 cases (98%) showed concordant BRAF status between primary and metastatic site by immunohistochemistry (IHC). In one case, a metastasis and its matched primary were positive by IHC, but the metastasis was negative on PCR. On further investigation, PCR was positive in the primary, and repeat PCR in the metastasis was positive, following macrodissection. CONCLUSIONS: Our results suggest that discordance of BRAF mutational status between primaries and metastases is a rare occurrence. In one case, IHC provided strong evidence that initial PCR testing had provided a false-negative result due to low tumor volume. Thus, in cases where tissue is difficult to obtain from a metastasis or unavailable, the primary tumor can be used with confidence.


Asunto(s)
Melanoma , Mutación , Proteínas Proto-Oncogénicas B-raf , Neoplasias Cutáneas , Adulto , Anciano , Femenino , Humanos , Inmunohistoquímica , Masculino , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Metástasis de la Neoplasia , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología
9.
J Clin Nurs ; 28(23-24): 4424-4433, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31410895

RESUMEN

AIMS AND OBJECTIVES: To measure cancer-related fatigue (CRF), self-care agency (SCA) and fatigue self-care strategies, and to explore the relationship between CRF and SCA. BACKGROUND: Cancer-related fatigue has been consistently rated as the most elusive, common and severe of symptoms that patients with cancer undergoing chemotherapy experience. Despite its frequency and severity, CRF is poorly managed. A renewed focus on supporting self-care among patients with cancer has been found to reduce symptom burden, empower patients and improve patient satisfaction. Understanding the link between self-care agency (i.e. capability and willingness to self-care) and CRF levels will help practitioners to better support individuals on the cancer journey. DESIGN: A descriptive, correlational survey design was employed. METHODS: Patients (n = 362) undergoing chemotherapy with a primary diagnosis of breast, colorectal, Hodgkin's and non-Hodgkin's lymphoma cancers were recruited from four oncology centres in one city in the South of Ireland. Participants completed the Piper Fatigue Scale-Revised, Appraisal of Self-care Agency Scale and a researcher-developed Fatigue Self-Care Survey. Multivariate logistic regression was used to examine the relationship between CRF and self-care agency using a dichotomous dependent variable score of four as the cut-off between those deemed to be fatigued (≥4) and those not fatigued (<4). As recommended by the EQUATOR Network, the STROBE checklist of items for cross-sectional studies is used to report the study. RESULTS: The incidence of CRF was high with 75% of participants scoring clinically relevant CRF. Higher SCA (OR = 0.96, 95% CI = 0.93-0.99, p = .011) was associated with decreased odds of developing CRF. Having non-Hodgkin's lymphoma (OR = 3.02, 95% CI = 1.29-7.07, p = .011) was associated with increased odds of developing CRF. CONCLUSIONS: Patient's undergoing chemotherapy experience significant fatigue. Higher capability for self-care is associated with lower fatigue. The promotion of SCA and self-care strategies can impact on CRF. RELEVANCE TO CLINICAL PRACTICE: Understanding the link between self-care abilities and fatigue can lead to more individualised and tailored approaches to CRF.


Asunto(s)
Antineoplásicos/efectos adversos , Fatiga/etiología , Neoplasias/tratamiento farmacológico , Autocuidado/psicología , Adulto , Anciano , Estudios Transversales , Fatiga/psicología , Femenino , Humanos , Irlanda , Modelos Logísticos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
10.
Biochim Biophys Acta ; 1866(1): 87-105, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27373814

RESUMEN

Increased glycolysis is the main source of energy supply in cancer cells that use this metabolic pathway for ATP generation. Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the "hallmarks of cancer". The immune system can prevent tumour growth by eliminating cancer cells but this editing process ultimately results in poorly immunogenic cells remaining allowing for unchallenged tumour growth. In this review we look at the glycolysis pathway as a target for cancer treatments. We also examine the interplay between the glycolysis modulation and the immune response as an anti-cancer therapy.


Asunto(s)
Glucólisis/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Metabolismo Energético/efectos de los fármacos , Humanos , Redes y Vías Metabólicas/efectos de los fármacos , Terapia Molecular Dirigida , Neoplasias/metabolismo , Neoplasias/patología
11.
Br J Cancer ; 116(3): 310-317, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-28072766

RESUMEN

BACKGROUND: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established. METHODS: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0). RESULTS: Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR=5.34, 95% CI: 1.15-24.88, P=0.033; OR=5.23, 95% CI: 1.41-19.30, P=0.013, respectively), and low MA was associated with high-grade irAEs (OR=3.57, 95% CI: 1.09-11.77, P=0.036). Longitudinal analysis (n=59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P=0.030). Mean reduction in SMA was 3.3%/100 days (95% CI: -4.48 to -1.79%, P<0.001). A loss of SMA ⩾7.5%/100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02-4.56, P=0.046). CONCLUSIONS: Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Composición Corporal/fisiología , Melanoma/tratamiento farmacológico , Melanoma/mortalidad , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Composición Corporal/efectos de los fármacos , Femenino , Humanos , Ipilimumab , Masculino , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Retrospectivos , Sarcopenia/mortalidad , Neoplasias Cutáneas/patología , Análisis de Supervivencia , Adulto Joven
12.
J Biol Chem ; 290(45): 27297-27310, 2015 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-26378236

RESUMEN

Our functional genomic RNAi screens have identified the protein components of the FACT (facilitates chromatin transcription) complex, SUPT16H and SSRP1, as top host factors that negatively regulate HIV-1 replication. FACT interacts specifically with histones H2A/H2B to affect assembly and disassembly of nucleosomes, as well as transcription elongation. We further investigated the suppressive role of FACT proteins in HIV-1 transcription. First, depletion of SUPT16H or SSRP1 protein enhances Tat-mediated HIV-1 LTR (long terminal repeat) promoter activity. Second, HIV-1 Tat interacts with SUPT16H but not SSRP1 protein. However, both SUPT16H and SSRP1 are recruited to LTR promoter. Third, the presence of SUPT16H interferes with the association of Cyclin T1 (CCNT1), a subunit of P-TEFb, with the Tat-LTR axis. Removing inhibitory mechanisms to permit HIV-1 transcription is an initial and key regulatory step to reverse post-integrated latent HIV-1 proviruses for purging of reservoir cells. We therefore evaluated the role of FACT proteins in HIV-1 latency and reactivation. Depletion of SUPT16H or SSRP1 protein affects both HIV-1 transcriptional initiation and elongation and spontaneously reverses latent HIV-1 in U1/HIV and J-LAT cells. Similar effects were observed with a primary CD4+ T cell model of HIV-1 latency. FACT proteins also interfere with HTLV-1 Tax-LTR-mediated transcription and viral latency, indicating that they may act as general transcriptional suppressors for retroviruses. We conclude that FACT proteins SUPT16H and SSRP1 play a key role in suppressing HIV-1 transcription and promoting viral latency, which may serve as promising gene targets for developing novel HIV-1 latency-reversing agents.


Asunto(s)
Proteínas de Ciclo Celular/fisiología , Proteínas de Unión al ADN/fisiología , VIH-1/fisiología , Proteínas del Grupo de Alta Movilidad/fisiología , Virus Linfotrópico T Tipo 1 Humano/fisiología , Factores de Transcripción/fisiología , Factores de Elongación Transcripcional/fisiología , Latencia del Virus/fisiología , Linfocitos T CD4-Positivos/fisiología , Linfocitos T CD4-Positivos/virología , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Línea Celular , Ciclina T/fisiología , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/genética , Células HEK293 , Duplicado del Terminal Largo de VIH , VIH-1/genética , Proteínas del Grupo de Alta Movilidad/antagonistas & inhibidores , Proteínas del Grupo de Alta Movilidad/genética , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/fisiología , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Modelos Biológicos , Factor B de Elongación Transcripcional Positiva/fisiología , Regiones Promotoras Genéticas , Interferencia de ARN , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Factores de Elongación Transcripcional/antagonistas & inhibidores , Factores de Elongación Transcripcional/genética , Latencia del Virus/genética
13.
Biochim Biophys Acta ; 1846(2): 510-23, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25286319

RESUMEN

The relationship between cancer and the immune system is a complex one. The immune system can prevent tumour growth by eliminating cancer cells but this editing process ultimately results in poorly immunogenic cells remaining allowing for unchallenged tumour growth. In light of this, the focus of cancer treatment should be to maximise cancer elimination and the prevention of escape mechanisms. In this review we will examine current and emerging ablative treatment modalities that induce Immunogenic Cell Death (ICD), a special type of cell death that allows for immune cell involvement and the generation of an anti-tumour specific immune response. When paired with immune modulating agents, capable of potentiating the immune response and reversing the immune-suppressive environment created by tumours, we may be looking at the future of anti-cancer therapy.


Asunto(s)
Neoplasias/inmunología , Neoplasias/terapia , Animales , Apoptosis , Proteína HMGB1/fisiología , Proteínas de Choque Térmico/fisiología , Humanos , Neoplasias/patología , Fotoquimioterapia , Escape del Tumor
14.
Oncologist ; 20(4): 372-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25746344

RESUMEN

BACKGROUND: Knowledge of cancer risk factors is unknown in Ireland. An understanding of risk factors could help inform cancer prevention programs. AIMS AND METHODS: A 48-question online survey was designed to gather data to assess levels of public knowledge about cancer risk factors. RESULTS: There were 748 participants (648 women, 100 men). Mean age was 37 years (range: 18-74 years). For the public, 81% were concerned about developing cancer; however, 20% believed that cancer is unavoidable if a family history exists, 27% believed that >50% of cancers are inherited, and 54% believed that 10%-20% of cancers are inherited; 20% were unaware that risk increases with age. The top five risk factors listed by respondents were smoking (87%), diet (76%), genetics (47%), alcohol (42%), and obesity (33%). Only 32% of the public were aware that obesity is a risk factor, and 33% did not think the location of fat was important. Moreover, 29% and 48% believed that risk could be increased by wearing a tight bra and by a blow to the breast, respectively. In addition, 85% and 86% believed that stress and that mobile phones, respectively, "strongly" increase risk; 12% believed that luck is important in avoiding cancer; 35% thought that "detox" diets could reduce risk; and 61% believed that organic food reduces risk. The majority were aware that physical activity of 30 minutes per day can reduce risk. CONCLUSION: A sizable portion of the population is misinformed about cancer risk. Most participants were aware of classic risk factors (e.g., smoking, diet); however, many overestimated risk attributable to genetics, environment, and stress and underestimated age, obesity, and sunlight. One in seven participants believed that lifetime risk of cancer is not modifiable.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Encuestas Epidemiológicas , Neoplasias/etiología , Neoplasias/prevención & control , Adolescente , Adulto , Anciano , Teléfono Celular , Dieta , Femenino , Alimentos Orgánicos , Predisposición Genética a la Enfermedad , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Actividad Motora , Obesidad/complicaciones , Factores de Riesgo , Fumar/efectos adversos , Adulto Joven
15.
Ann Surg Oncol ; 21(2): 479-86, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24154839

RESUMEN

PURPOSE: Systemic bevacizumab (Bev) was added to hepatic arterial infusion (HAI) floxuridine (FUDR)-based chemotherapy in three studies in an attempt to improve outcomes. A specific review of biliary toxicity was carried out. METHODS: This analysis included 203 patients from three prospective studies. The first (study A) was an adjuvant study after liver resection of colorectal metastases in which patients received HAI and systemic chemotherapy (Sys) with or without Bev. Study B comprised unresectable colorectal patients who received HAI and Sys plus Bev. Study C included patients with unresectable cholangiocarcinoma or hepatocellular carcinoma who received HAI plus systematic Bev. The outcome and toxicity of patients in studies B and C were compared with historical controls. RESULTS: In all three studies, the incidence of hyperbilirubinemia and biliary stent placement within 1 year of treatment was increased with the addition of Bev. In the no-Bev versus Bev groups, the placement of biliary stents was as follows: study A, 0 of 38 versus 4 of 35 patients (p = 0.05); study B, 0 of 49 versus 3 of 24 (p = 0.06); and study C, 0 of 34 versus 3 of 22 (p = 0.15). Elevation in bilirubin was noted in the no-Bev versus Bev groups: study A, 0 of 38 versus 5 of 35 patients (p = 0.02); study B, 1 of 49 versus 7 of 24 (p = 0.005); and study C, 2 of 34 versus 5 of 22 (p = 0.10). The addition of Bev did not seem to be associated with improved progression-free or overall survival. CONCLUSIONS: The addition of Bev to HAI FUDR resulted in increased biliary toxicity in three separate studies. Although the sample sizes were small, there was no evidence of improved PFS or OS with the addition of Bev. Bev should not be combined with HAI FUDR.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares Intrahepáticos/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Colangiocarcinoma/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Arteria Hepática , Hiperbilirrubinemia/inducido químicamente , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/patología , Colangiocarcinoma/patología , Ensayos Clínicos Fase II como Asunto , Neoplasias Colorrectales/patología , Femenino , Floxuridina/administración & dosificación , Estudios de Seguimiento , Humanos , Hiperbilirrubinemia/diagnóstico , Infusiones Intraarteriales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
Rep Pract Oncol Radiother ; 19(1): 62-4, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24936321

RESUMEN

BACKGROUND: Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non-small cell lung cancer. There is no consensus regarding optimal management for this disease. CASE REPORT: We present a case of MEC of the lung in a 75 year-old female with a history of superficial urothelial carcinoma of the bladder. The patient was found to have an asymptomatic lung mass. Initial biopsy suggested metastatic recurrence of urothelial carcinoma and therefore, cisplatin and gemcitabine chemotherapy was administered prior to surgical resection. Pathological analysis of the resected specimen confirmed a diagnosis of stage IIIA MEC with focal high-grade features including transitional cell-like areas. Adjuvant radiotherapy was administered due to a positive microscopic resection margin. No chemotherapy was given due to lack of supporting data. The patient developed widespread metastatic disease 3 months following completion of radiotherapy and died 1 month later. CONCLUSION: This case demonstrates the possibility of dual pathology in cases where metastatic disease is suspected. The use of small tissue samples may complicate diagnosis due to the heterogeneity of malignant tumours.

18.
bioRxiv ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38854151

RESUMEN

In response to central nervous system (CNS) injury, tissue resident immune cells such as microglia and circulating systemic neutrophils are often first responders. The degree to which these cells interact in response to CNS damage is poorly understood, and even less so, in the neural retina which poses a challenge for high resolution imaging in vivo. In this study, we deploy fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) to study fluorescent microglia and neutrophils in mice. We simultaneously track immune cell dynamics using label-free phase-contrast AOSLO at micron-level resolution. Retinal lesions were induced with 488 nm light focused onto photoreceptor (PR) outer segments. These lesions focally ablated PRs, with minimal collateral damage to cells above and below the plane of focus. We used in vivo (AOSLO, SLO and OCT) imaging to reveal the natural history of the microglial and neutrophil response from minutes-to-months after injury. While microglia showed dynamic and progressive immune response with cells migrating into the injury locus within 1-day after injury, neutrophils were not recruited despite close proximity to vessels carrying neutrophils only microns away. Post-mortem confocal microscopy confirmed in vivo findings. This work illustrates that microglial activation does not recruit neutrophils in response to acute, focal loss of photoreceptors, a condition encountered in many retinal diseases.

19.
Ir J Med Sci ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806877

RESUMEN

BACKGROUND: Expanded access programs (EAPs) allow cancer patients with unmet clinical need to obtain access to pre-authorisation treatments. There is no standardised process for implementing these programs nationally, and real-world data on their impact is lacking. AIMS: This study aimed to evaluate the prevalence of such EAPs and their impact in a cancer centre. METHODS: Data relating to adult cancer patients treated via EAPs from 2011 to 2021 in three Cork university hospitals was collated. Descriptive statistics were employed to get an overview of the impact these programs currently have on cancer care provision. RESULTS: We identified 193 patients who accessed EAPs during the study period, availing of 33 separate drugs for a total of 50 different cancer indications. The prevalence of EAP usage was shown to have been trending upwards in recent years with a total of 189 programs being accessed throughout the period. Drugs provided were from a number of different anti-cancer drug classes, particularly targeted therapies (n = 18) and immune checkpoint inhibitors (n = 17). Cancers from a wide range of both solid and liquid tumour types were treated with EAP drugs, and patients treated were from across a broad spectrum of ages (26-82, SD 11.99). CONCLUSIONS: EAPs have an increasing role in accessing novel cancer therapies in our community and by extension nationally. Equity of EAP access would be facilitated by a national registry of available agents which we have established. Assessment of their benefits and toxicities would be enhanced by the requirement for a real-world database as a condition of EAP approval.

20.
Onkologie ; 36(12): 760-2, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24356568

RESUMEN

BACKGROUND: Treatment of germ cell tumours with cisplatin-based chemotherapy results in cure for the majority of patients. There is, however, a small but significant mortality rate, reported to be higher in patients with multiple co-morbidities. CASE REPORT: We report our management of a renal transplant patient with spina bifida, who was diagnosed with stage IIIC, poor-risk, non-seminomatous germ cell carcinoma. A marker-negative partial response, which has been maintained more than 2 years following completion of treatment, was seen following chemotherapy with cisplatin and etoposide. Performance status has been preserved at pre-treatment levels. CONCLUSION: Administration of cisplatin-based chemotherapy is feasible for treatment of renal transplant patients with advanced non-seminomatous germ cell tumours. Treatment strategies require careful planning and monitoring. Dose modifications may be required. This case highlights a favourable outcome in spite of multiple obstacles to ideal management.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/secundario , Adulto , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/patología , Disrafia Espinal/complicaciones , Resultado del Tratamiento
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