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2.
Cancers (Basel) ; 16(8)2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38672688

RESUMEN

BACKGROUND: We estimated metastatic-death risk when the treatment of small choroidal melanomas is deferred until growth is observed. METHODS: In 24 patients with choroidal melanoma (median diameter 5.85 mm), the exponential growth rate estimated by a mixed-effects model was 4.3% per year. Using the Liverpool Uveal Melanoma Prognosticator Online v.3 (LUMPO3), we measured changes in 15-year metastatic and non-metastatic death risks according to whether the tumor is treated immediately or after observing growth 4 or 12 months later, considering age, sex, and metastasis predictors. RESULTS: In 40-year-old females with 10 mm, disomy 3 and monosomy 3 choroidal melanomas (prevalence 16%), the 15-year absolute risks of metastatic death are 4.2% and 76.6%, respectively, increasing after a 4-month delay by 0.0% and 0.2% and by 3.0% and 2.3% with tumor growth rates of 5.0% and 20.0%, respectively. With 12-month delays, these risks increase by 0.0% and 0.5% and by 1.0% and 7.1%, respectively. Increases in metastatic-death risk are less with smaller tumors and with a higher risk of non-metastatic death. CONCLUSIONS: Deferring treatment of choroidal melanomas until documentation of growth may delay iatrogenic visual loss by months or years and is associated with minimal increase in metastatic mortality, at least with small tumors with usual growth rates of up to 40% per year.

3.
J Orthop Sci ; 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38262799

RESUMEN

BACKGROUND: This study evaluated a patellar tendon shortening (PTS) surgical procedure that uses an overlapping repair combined with an additional Tycron non-absorbable suture to support the shortening in children with Cerebral Palsy (CP). This study aimed to outline this surgical technique and to evaluate its effectiveness in restoring the knee extensor mechanism. METHODS: The sagittal plane lower limb kinematics, peak knee extensor moment, gait deviation index (GDI), localised movement deviation profile (MDP), temporospatial parameters, passive knee extension ROM, quadriceps lag, and knee extensor strength were calculated pre- and postoperatively. To determine significant differences a robust linear regression model with high breakdown point and high efficiency was fitted to the data. RESULTS: In this retrospective cohort study, a total of 41 patients with CP who were treated with unilateral or bilateral PTS in isolation or as part of single event multilevel surgery (SEMLS), with a mean age of 11.1 years were included. The knee extension angle improved at initial contact (p < 0.0001), and during stance phase (p < 0.0001). The peak internal knee extensor moment decreased during early (p = 0.0014) and late stance phase (p < 0.0001). The quadriceps lag decreased (p < 0.0001) and knee extensor strength increased (p < 0.0001). The GDI improved (p < 0.0001), as well as the localised MDP for sagittal angles (p < 0.0001) and moments (p = 0.0001). Walking speed (p = 1.0) remained unchanged, but the cadence decreased (p = 0.024) and step length increased (p = 0.0001). CONCLUSIONS: The knee extension angle and moment during stance phase improved significantly. The children with CP in this study showed improvements in knee extensor strength and quadriceps lag. Thereby it can be concluded that the PTS procedure was able to restore the knee extensor mechanism effectively.

5.
Cancers (Basel) ; 15(9)2023 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-37174076

RESUMEN

Uveal melanoma (UM) metastasises in ~50% of patients, most frequently to the liver. Surveillance imaging can provide early detection of hepatic metastases; however, guidance regarding UM patient risk stratification for surveillance is unclear. This study compared sensitivity and specificity of four current prognostic systems, when used for risk stratification for surveillance, on patients treated at the Liverpool Ocular Oncology Centre (LOOC) between 2007-2016 (n = 1047). It found that the Liverpool Uveal Melanoma Prognosticator Online III (LUMPOIII) or Liverpool Parsimonious Model (LPM) offered greater specificity at equal levels of sensitivity than the American Joint Committee on Cancer (AJCC) system or monosomy 3 alone, and suggests guidance to achieve 95% sensitivity and 51% specificity (i.e., how to detect the same number of patients with metastases, while reducing the number of negative scans). For example, 180 scans could be safely avoided over 5 years in 200 patients using the most specific approach. LUMPOIII also offered high sensitivity and improved specificity over the AJCC in the absence of genetic information, making the result relevant to centres that do not perform genetic testing, or where such testing is inappropriate or fails. This study provides valuable information for clinical guidelines for risk stratification for surveillance in UM.

6.
Cancers (Basel) ; 14(9)2022 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-35565316

RESUMEN

PURPOSE: To determine liver screening frequency and modality in UM patients following primary treatment, and the characteristics of detected metastases. METHODS: A 10-year retrospective study of 615 UM patients undergoing liver surveillance in Liverpool. Information was collected from liver scan reports of these patients. RESULTS: Of 615 UM patients analyzed, there were 337 men (55%) and 278 women (45%). Median age at primary treatment was 61 years (range, 22-94). At study end, median follow-up was 5.1 years, with 375 patients (61%) alive and 240 deceased (39%). Of the deceased patients, 187 (78%) died due to metastatic UM; 24 (10%) deaths were due to other causes; and 29 (12%) patients died of unknown conditions. In total, 3854 liver scans were performed in the 615 UM patients, with a median of 6.2 scans per patient (range, 1-40). Liver MRI was most frequently performed (62.8%). In total, 229 (37%) UM patients developed metastases during the study period: 150 were detected via liver surveillance and 79 were observed post-mortem. CONCLUSIONS: Metastatic UM onset is related to the size and genetic profiles of the primary UM, and can be predicted using the model LUMPO3. Regular liver surveillance allowed for timely detection of metastases, and through metastasectomy can lead to prolongation of life in some patients.

7.
Cancers (Basel) ; 13(9)2021 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-34066842

RESUMEN

Our aim was to determine whether size impacts on the difference in metastatic mortality of genetically high-risk (monosomy 3) uveal melanomas (UM). We undertook a retrospective analysis of data from a patient cohort with genetically characterized UM. All patients treated for UM in the Liverpool Ocular Oncology Centre between 2007 and 2014, who had a prognostic genetic tumor analysis. Patients were subdivided into those with small (≤2.5 mm thickness) and large (>2.5 mm thickness) tumors. Survival analyses were performed using Gray rank statistics to calculate absolute probabilities of dying as a result of metastatic UM. The 5-year absolute risk of metastatic mortality of those with small monosomy 3 UM was significantly lower (23%) compared to the larger tumor group (50%) (p = 0.003). Small disomy 3 UM also had a lower absolute risk of metastatic mortality (0.8%) than large disomy 3 UM (6.4%) (p = 0.007). Hazard rates showed similar differences even with lead time bias correction estimates. We therefore conclude that earlier treatment of all small UM, particularly monosomy 3 UM, reduces the risk of metastatic disease and death. Our results would support molecular studies of even small UM, rather than 'watch-and-wait strategies'.

8.
Eur J Cancer Care (Engl) ; 30(5): e13463, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34028120

RESUMEN

OBJECTIVES: To assess the association between risk factors, including socioeconomic deprivation, and mortality, recurrence and chemo- or radiation toxicity in cervical cancer patients. METHODS: Retrospective study of cervical cancer patients diagnosed between January 2007 and July 2018. Patient characteristics and mortality data, including recurrence, were assessed, together with socioeconomic deprivation measures evaluated using the English Indices of Multiple Deprivation. Markov multi-state models were used to model mortality and recurrence, and logistic regression models were used to model chemo- or radiation toxicity. RESULTS: Included were 243 women with a median age of 49 years. A total of 57 patients died (23%), of which 41 due to cervical cancer, and 21 (9%) had recurrent disease. Hazard ratios (HR) showed no evidence of association between socioeconomic deprivation and cancer-specific hazard of mortality from diagnosis or recurrence, hazard of mortality due to other causes or hazard of cancer recurrence. Furthermore, there was no evidence of association between socioeconomic deprivation and chemo- or radiation toxicity (bowel, bladder or vaginal stenosis). CONCLUSIONS: No associations were found between socioeconomic deprivation and cancer mortality or recurrence in cervical cancer patients in the population of Cornwall. In addition, no association was found between socioeconomic deprivation and chemo- or radiation toxicity.


Asunto(s)
Neoplasias del Cuello Uterino , Constricción Patológica , Inglaterra , Femenino , Humanos , Recién Nacido , Estudios Retrospectivos , Factores Socioeconómicos , Vagina
9.
Comput Biol Med ; 130: 104221, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33516960

RESUMEN

This paper outlines a method for cost-utility analysis of liver screening for metastases in patients with posterior uveal melanoma (UM). A semiparametric model of the cumulative incidence of onset of liver metastases was fitted to a retrospective data set of 615 subjects with clinical follow-up with respect to liver surveillance imaging and outcome. The model was internally validated via bootstrap resampling in terms of its discrimination and calibration performance. Receiver operating characteristics (ROC) were derived at different time points. The discrimination performances are consistent across time. The area under the ROC curve at 5 years post treatment was 0.85 [95% CI: 0.81-0.88]. A goodness-of-fit test gives χ2(10)=5.3,p=0.9 demonstrating no evidence against the null hypothesis of zero difference between observed and expected onset of metastatic events. Results showed that at 80% sensitivity, 87% of UM patients will avoid unnecessary radiological scans. This provides potential cost savings of between £46,000 and £97,000 per year to the National Health Service assuming 600 new cases per year.


Asunto(s)
Neoplasias Hepáticas , Neoplasias de la Úvea , Análisis Costo-Beneficio , Humanos , Hígado , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/epidemiología , Melanoma , Estudios Retrospectivos , Medicina Estatal , Neoplasias de la Úvea/diagnóstico por imagen , Neoplasias de la Úvea/epidemiología
10.
Invest Ophthalmol Vis Sci ; 61(4): 35, 2020 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-32334433

RESUMEN

Purpose: To develop parsimonious models for estimating metastasis mortality in patients with choroidal melanoma for situations where use of the Liverpool Uveal Melanoma Prognosticator Online (LUMPO) or Tumor, Node, Metastasis (TNM) staging system is not possible. Methods: A backward-selection algorithm identified largest basal tumor diameter (LBTD) and chromosome 3 status (C3S) as the most informative predictors of metastatic death. We defined two prognostic models, based on LBTD with or without known C3S, that took into account competing risks of death from other causes by using the Aalen estimator. The bootstrap procedure was used to estimate discrimination accuracy, expressed by the C-index. Results: The cohort was comprised of 8348 patients with choroidal melanoma, 4174 of whom had known chromosome 3 status; of the 1553 deaths that occurred among these patients, 956 were attributed to metastasis. For LBTD with or without known C3S, the metastatic-death-specific C-indices at 2, 5, and 10 years were 0.85, 0.85, and 0.84 and 0.79, 0.77, and 0.74, respectively, as compared with 0.81, 0.79, and 0.76 for Kaplan-Meier prognostication using the 8th edition of the TNM staging system. Conclusions: We have developed parsimonious models for predicting the absolute risks of metastatic death from choroidal melanoma that take into account competing causes of death and which compare favorably with the current version of the TNM staging system. There is a need for further studies to validate the use of these models in situations where use of the TNM or LUMPO is not possible.


Asunto(s)
Causas de Muerte , Neoplasias de la Coroides/mortalidad , Neoplasias de la Coroides/patología , Melanoma/mortalidad , Melanoma/patología , Adulto , Factores de Edad , Anciano , Neoplasias de la Coroides/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/genética , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Factores Sexuales , Análisis de Supervivencia
11.
Cancers (Basel) ; 12(2)2020 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-32085617

RESUMEN

Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3's performance using discrimination and calibration methods. LUMPO3's ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers.

12.
Br J Ophthalmol ; 104(10): 1462-1466, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32024655

RESUMEN

BACKGROUND/AIMS: Proton beam radiotherapy and plaque brachytherapy are commonly applied in primary uveal melanoma (UM); however, their effect on chromosome 3 classification of UM by microsatellite analysis (MSA) for prognostication purposes is unknown, where the tumour is sampled post-irradiation. This study examined the prognostic accuracy of genotyping UM biopsied before or after administration of radiotherapy, by MSA. METHODS: 407 UM patients treated at the Liverpool Ocular Oncology Centre between January 2011 to December 2017, were genotyped for chromosome 3 by MSA; 172 and 176 primary UM were sampled prior to and post irradiation, respectively. RESULTS: Genotyping by MSA was successful in 396/407 (97%) of UM samples (196 males, 211 females; median age of 61 years (range 12 to 93) at primary treatment). There was no demonstrable association between a failure of MSA to produce a chromosome 3 classification and whether radiation was performed pre-biopsy or post-biopsy with an OR of 0.96 (95% CI 0.30 to 3.00, p=0.94). There was no evidence of association (measured as HRs) between risk of metastatic death and sampling of a primary UM before administration of radiotherapy (HR 1.1 (0.49 to 2.50), p=0.81). Monosomy 3 (HR 12.0 (4.1 to 35.0), p<0.001) was significantly associated with increased risk of metastatic death. CONCLUSIONS AND RELEVANCE: This study revealed that successful genotyping of UM using MSA is possible, irrespective of irradiation status. Moreover, we found no evidence that biopsy prior to radiotherapy increases metastatic mortality.


Asunto(s)
Braquiterapia , Cromosomas Humanos Par 3/genética , Melanoma/radioterapia , Repeticiones de Microsatélite/genética , Terapia de Protones , Neoplasias de la Úvea/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Niño , ADN de Neoplasias/genética , Femenino , Estudios de Seguimiento , Genotipo , Técnicas de Genotipaje , Humanos , Masculino , Melanoma/genética , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias de la Úvea/genética
13.
Psychooncology ; 28(1): 48-53, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30286263

RESUMEN

OBJECTIVES: To investigate the association between body mass index (BMI) and sexual functioning in gynaecologic cancer patients. To determine the association between socio-economic deprivation and sexual functioning. METHODS: This is a prospective cohort study on women undergoing surgery for suspected or proven gynaecological cancer between September 2014 and February 2016 in the Royal Cornwall Hospital Trust. Patients were invited to participate by completing the Female Sexual Function Index (FSFI) at three time points: preoperative, 3 months postoperative, and 1 year postoperative. A semiparametric model of the FSFI score was used to establish the association between BMI and sexual functioning. RESULTS: A total of 257 patients were approached of which 166 patients were included. Fifty-two patients (33.8%) were overweight (BMI, 25-29.9 kg/m2 ), 44 (28.6%) were obese (BMI, 30-39.9 kg/m2 ), and a further 20 (13.0%) morbidly obese (BMI ≥ 40 kg/m2 ). Overweight and obese women reported improved sexual functioning compared with normal-weight women in endometrial, ovarian, and vulvar cancers. Among cervical cancer, worse sexual functioning was seen in women with an increased BMI; however, this was not significant. Younger age was associated with improved sexual function, and sexual functioning was better postoperatively for all patients compared with preoperatively. There was no evidence of relationship between deprivation and sexual functioning in gynaecological cancer patients. CONCLUSION: Higher BMI is associated with improved sexual functioning in endometrial, ovarian, and vulvar cancer; however, this was not seen in cervical cancer patients. There is no evidence of correlation between deprivation and sexual functioning.


Asunto(s)
Imagen Corporal/psicología , Supervivientes de Cáncer/psicología , Neoplasias de los Genitales Femeninos/psicología , Conducta Sexual/psicología , Adulto , Índice de Masa Corporal , Femenino , Neoplasias de los Genitales Femeninos/terapia , Humanos , Persona de Mediana Edad , Obesidad/psicología , Satisfacción Personal , Estudios Prospectivos
14.
Comput Biol Med ; 102: 151-156, 2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30278339

RESUMEN

BACKGROUND/AIMS: Uveal melanoma is fatal in almost 50% of patients. We previously developed a prognostic model to predict all-cause mortality. The aim of this study was to improve our model by predicting metastatic death as a cause-specific event distinct from other causes of death. METHODS: Patients treated in Liverpool were included if they resided in England, Scotland or Wales and if their uveal melanoma involved the choroid. They were flagged at the National Health Service Cancer Registry, which automatically informed us of the date and cause of death of any deceased patients. A semiparametric Markov multi-state model was fitted. Two different baseline hazard rates were assumed, with state transition-specific covariates. For both failure types, age at treatment and sex were used. For the metastatic death case, these factors were added: anterior margin position, largest basal tumour diameter, tumour thickness, extra-ocular extension, presence of epithelioid melanoma cells, presence of closed connective tissue loops, increased mitotic count, chromosome 3 loss, and chromosome 8q gain. Missing data required a multiple-imputation procedure. RESULTS: The cohort comprised 4161 patients, 893 of whom died of metastastic disease with another 772 dying of other causes. The optimism-corrected, bootstrapped C-index for metastatic death prediction was 0.86, denoting very good discriminative performance. Bootstrapped calibration curves at two and five years also showed very good performance. CONCLUSIONS: Our improved model provides reliable, personalised metastatic death prognostication using clinical, histological and genetic information, and it can be used as a decision support tool to individualize patient care in a clinical environment.


Asunto(s)
Informática Médica/métodos , Melanoma/diagnóstico , Melanoma/mortalidad , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Algoritmos , Calibración , Neoplasias de la Coroides/diagnóstico , Neoplasias de la Coroides/mortalidad , Estudios de Cohortes , Sistemas de Apoyo a Decisiones Clínicas , Femenino , Humanos , Incidencia , Masculino , Cadenas de Markov , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
15.
Diabetologia ; 60(11): 2174-2182, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28840258

RESUMEN

AIMS/HYPOTHESIS: Individualised variable-interval risk-based screening offers better targeting and improved cost-effectiveness in screening for diabetic retinopathy. We developed a generalisable risk calculation engine (RCE) to assign personalised intervals linked to local population characteristics, and explored differences in assignment compared with current practice. METHODS: Data from 5 years of photographic screening and primary care for people with diabetes, screen negative at the first of > 1 episode, were combined in a purpose-built near-real-time warehouse. Covariates were selected from a dataset created using mixed qualitative/quantitative methods. Markov modelling predicted progression to screen-positive (referable diabetic retinopathy) against the local cohort history. Retinopathy grade informed baseline risk and multiple imputation dealt with missing data. Acceptable intervals (6, 12, 24 months) and risk threshold (2.5%) were established with patients and professional end users. RESULTS: Data were from 11,806 people with diabetes (46,525 episodes, 388 screen-positive). Covariates with sufficient predictive value were: duration of known disease, HbA1c, age, systolic BP and total cholesterol. Corrected AUC (95% CIs) were: 6 months 0.88 (0.83, 0.93), 12 months 0.90 (0.87, 0.93) and 24 months 0.91 (0.87, 0.94). Sensitivities/specificities for a 2.5% risk were: 6 months 0.61, 0.93, 12 months 0.67, 0.90 and 24 months 0.82, 0.81. Implementing individualised RCE-based intervals would reduce the proportion of people becoming screen-positive before the allocated screening date by > 50% and the number of episodes by 30%. CONCLUSIONS/INTERPRETATION: The Liverpool RCE shows sufficient performance for a local introduction into practice before wider implementation, subject to external validation. This approach offers potential enhancements of screening in improved local applicability, targeting and cost-effectiveness.


Asunto(s)
Retinopatía Diabética/diagnóstico , Tamizaje Masivo/métodos , Presión Sanguínea/fisiología , Progresión de la Enfermedad , Hemoglobina Glucada/metabolismo , Humanos , Factores de Riesgo , Factores de Tiempo
16.
Doc Ophthalmol ; 135(2): 97-106, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28795295

RESUMEN

PURPOSE: As part of a long-term, prospective study of prenatal and clinical risk factors for optic nerve hypoplasia (ONH) at Children's Hospital Los Angeles, pattern ERGs (PERGs) were evaluated for prognostic value using an automated objective and robust analytical method. METHODS: Participants were 33 children with ophthalmoscopically diagnosed ONH [disc diameter-to-disc macula ratio (DD/DM) less than 0.35 in one or both eyes on fundus photographs]. Using cycloplegia and chloral hydrate sedation in one session before 26 months of age, we recorded PERGs to checkerboard reversal using five check sizes. Participants were followed with clinical and psychometric testing until 5 years of age. PERGs were analysed using automated robust statistics based on magnitude-squared coherence and bootstrapping optimized to objectively quantify PERG recovery in the challenging recordings encountered in young patients. PERG measures in the fixating or better-seeing eyes were compared with visual outcome data. RESULTS: PERG recording was complete to at least three check sizes in all eyes and to all five sizes in 79%. Probability of recording a PERG that is significantly different from noise varied with check size from 73% for the largest checks to 30% for the smallest checks (p = 0.002); smaller waveforms were associated with earlier implicit times. The presence of significant PERGs in infancy is associated with better visual outcomes; the strongest association with visual outcome was for the threshold check size with a significant N95 component (ρ = 0.398, p = 0.02). CONCLUSIONS: Automated statistically robust signal-processing techniques reliably and objectively detect PERGs in young children with ONH and show that congenital deficits of retinal ganglion cells are associated with diminished or non-detectable PERGs. The later negativity, N95, was the best indicator of visual prognosis and was most useful to identify those with good visual outcomes (≤0.4 LogMAR). Although PERGs reflect function of the inner layers of the central retina, they lack the specificity required to determine prognosis reliably in individual cases.


Asunto(s)
Anomalías del Ojo/fisiopatología , Nervio Óptico/anomalías , Retina/fisiología , Células Ganglionares de la Retina/fisiología , Niño , Preescolar , Electrorretinografía/métodos , Femenino , Humanos , Lactante , Masculino , Oftalmoscopía , Nervio Óptico/fisiopatología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador , Agudeza Visual/fisiología
17.
Invest Ophthalmol Vis Sci ; 57(14): 6116-6122, 2016 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-27835710

RESUMEN

PURPOSE: To validate the Liverpool Uveal Melanoma Prognosticator Online (LUMPO) in a cohort of patients treated at the University of California-San Francisco (UCSF). METHODS: A retrospective chart review was performed of 390 patients treated between 2002 and 2007 for choroidal melanoma at UCSF. Similar patients (n = 1175) treated at the Liverpool Ocular Oncology Centre (LOOC) were included in the study. The data were analyzed using the model previously developed for LUMPO, an online prognostication tool combining multiple prognostic factors. Main outcome measures included all-cause mortality and melanoma-specific mortality. Reliability of the survival estimates in each group of patients was indicated by the C-indices of discrimination and Hosmer-Lemeshow test. RESULTS: Patients treated at UCSF tended to be younger with thicker tumors, and were more likely to receive proton beam radiotherapy as primary treatment compared to patients at LOOC. There were no significance differences with respect to ciliary body involvement, melanoma cytomorphology, and mitotic counts between the two groups. Death occurred in 140/390 (35%) patients from UCSF and 409/1175 (34%) patients from LOOC, with no difference in overall mortality by Kaplan-Meier analysis (log rank test, P = 0.503). For all-cause mortality and melanoma-specific mortality, the C-index of discrimination and Hosmer-Lemeshow test at 5 years after treatment indicated good discrimination performance of the model, with no statistically significant difference between observed and predicted survival. CONCLUSIONS: Despite differences between the two cohorts, external validation in patients treated at UCSF indicates that LUMPO estimated the all-cause and melanoma-specific mortality well.


Asunto(s)
Predicción , Internet , Melanoma/mortalidad , Estadificación de Neoplasias , Neoplasias de la Úvea/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte/tendencias , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Estados Unidos , Neoplasias de la Úvea/diagnóstico , Adulto Joven
18.
Mol Vis ; 21: 1-11, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25684974

RESUMEN

PURPOSE: To determine underlying correlations in multiplex ligation-dependent probe amplification (MLPA) data and their significance regarding survival following treatment of choroidal melanoma (CM). METHODS: MLPA data were available for 31 loci across four chromosomes (1p, 3, 6, and 8) in tumor material obtained from 602 patients with CM treated at the Liverpool Ocular Oncology Center (LOOC) between 1993 and 2012. Data representing chromosomes 3 and 8q were analyzed in depth since their association with CM patient survival is well-known. Unsupervised k-means cluster analysis was performed to detect latent structure in the data set. Principal component analysis (PCA) was also performed to determine the intrinsic dimensionality of the data. Survival analyses of the identified clusters were performed using Kaplan-Meier (KM) and log-rank statistical tests. Correlation with largest basal tumor diameter (LTD) was investigated. RESULTS: Chromosome 3: A two-cluster (bimodal) solution was found in chromosome 3, characterized by centroids at unilaterally normal probe values and unilateral deletion. There was a large, significant difference in the survival characteristics of the two clusters (log-rank, p<0.001; 5-year survival: 80% versus 40%). Both clusters had a broad distribution in LTD, although larger tumors were characteristically in the poorer outcome group (Mann-Whitney, p<0.001). Threshold values of 0.85 for deletion and 1.15 for gain optimized the classification of the clusters. PCA showed that the first principal component (PC1) contained more than 80% of the data set variance and all of the bimodality, with uniform coefficients (0.28±0.03). Chromosome 8q: No clusters were found in chromosome 8q. Using a conventional threshold-based definition of 8q gain, and in conjunction with the chromosome 3 clusters, three prognostic groups were identified: chromosomes 3 and 8q both normal, either chromosome 3 or 8q abnormal, and both chromosomes 3 and 8q abnormal. KM analysis showed 5-year survival figures of approximately 97%, 80%, and 30% for these prognostic groups, respectively (log-rank, p<0.001). All MLPA probes within both chromosomes were significantly correlated with each other (Spearman, p<0.001). CONCLUSIONS: Within chromosome 3, the strong correlation between the MLPA variables and the uniform coefficients from the PCA indicates a lack of evidence for a signature gene that might account for the bimodality we observed. We hypothesize that the two clusters we found correspond to binary underlying states of complete monosomy or disomy 3 and that these states are sampled by the complete ensemble of probes. Consequently, we would expect a similar pattern to emerge in higher-resolution MLPA data sets. LTD may be a significant confounding factor. Considering chromosome 8q, we found that chromosome 3 cluster membership and 8q gain as traditionally defined have an indistinguishable impact on patient outcome.


Asunto(s)
Secuencia de Bases , Neoplasias de la Coroides/genética , Cromosomas Humanos Par 3/química , Cromosomas Humanos Par 8/química , Melanoma/genética , Eliminación de Secuencia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Coroides/mortalidad , Neoplasias de la Coroides/patología , Análisis por Conglomerados , Femenino , Sitios Genéticos , Humanos , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Datos de Secuencia Molecular , Técnicas de Amplificación de Ácido Nucleico , Análisis de Componente Principal , Estudios Retrospectivos , Análisis de Supervivencia , Carga Tumoral
19.
J Vet Med Educ ; 41(3): 233-42, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25000879

RESUMEN

Veterinary surgeons working on farms and food-processing establishments play a fundamental role in safeguarding both public health and the welfare of animals under their care. An essential part of veterinary public health (VPH) undergraduate training in the UK involves students undertaking placements within abattoirs, a practice that remains vital to the educational experience of future veterinary professionals. However, several issues have adversely affected the ability of students to gain such extramural placements. For this reason, the Virtual Slaughterhouse Simulator (VSS) was developed to strengthen and enhance undergraduate VPH teaching at the Royal (Dick) School of Veterinary Studies, enabling students to explore a realistic abattoir work environment with embedded educational activities. The aim of this research project was to evaluate the VSS as a teaching and learning tool for training and educating veterinary students. Ninety-eight final-year veterinary students engaged with the prototype VSS, followed by assessment of their knowledge and behavior when faced with a "real-life" abattoir situation. Further evaluation of their experiences with the VSS was carried out using questionnaires and focus groups. The results of this investigation show that there is the potential for the VSS to enhance the student learning experience in basic abattoir procedures. This innovative tool provides a visually based learning resource that can support traditional lectures and practical classes and can also be used to stimulate interactive problem-solving activities embedded in the relevant context.


Asunto(s)
Mataderos , Simulación por Computador , Educación en Veterinaria/métodos , Estudiantes/psicología , Estudiantes del Área de la Salud
20.
Graefes Arch Clin Exp Ophthalmol ; 250(5): 645-52, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22138760

RESUMEN

BACKGROUND: Silicone oil (SO) is an established tamponade in treating complex vitreoretinal diseases. Although SO is intended to be removed after several weeks to months, permanent SO might be unavoidable in a small subgroup of patients with an extremely complicated clinical course. The aim of this study is to describe the long-term effects of intraocular SO tamponade. METHODS: This retrospective study included 50 patients with intraocular SO (Oxane 5700 Bausch & Lomb, Kingston-upon-Thames, UK) for at least 12 months. The most common reasons for long-term SO tamponade were: retinal re-detachment (re-RD), proliferative diabetic retinopathy (PDR), ocular trauma, and persistent hypotony. RESULTS: Mean age was 59.2 ± 18.4 years, and mean duration of silicone oil in the eye was 54.5 ± 58.6 months (median, 30 months). The average number of previous surgeries were 2.2 ± 1.5. Anatomic success was achieved in 37/50 (74%) of patients. Visual acuities (logMAR) were 1.8 ± 0.6, 1.6 ± 0.6, 2 ± 0.7 and intraocular pressures (mmHg) were 15.6 ± 7, 15.7 ± 5.5, 16.5 ± 7.1 at 3 months, 1 year and at last follow-up respectively. The main long-term silicone-oil-related complications observed were: band keratopathy (8%), corneal decompensation (12%), iris rubeosis (14%), and optic neuropathy (28%). Forty percent of patients achieved ambulatory vision in the SO-filled eye at final follow-up. CONCLUSION: Long-term silicone oil can be a last-resort option in selected patients with severe vitreoretinal disease. Anterior and posterior segment complications did occur at significant rates. Forty percent of our patients maintained ambulatory vision. The actual number of patients that achieved satisfactory stereopsis and benefited functionally from long-term SO was much less [7/50 (14%)].


Asunto(s)
Endotaponamiento , Enfermedades de la Retina/cirugía , Aceites de Silicona/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/fisiopatología , Estudios Retrospectivos , Factores de Tiempo , Agudeza Visual/fisiología , Vitrectomía
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