Kawasaki Disease presenting with intussusception: a case report

A 3 yr old boy presented with abdominal pain, fever and red jelly stools. Intussusception was diagnosed and effectively reduced with air insufflation. However, despite an improvement in his clinical condition, the child remained febrile and miserable; 5 days later he developed characteristic signs of Kawasaki disease and was treated with intravenous immunoglobulin and high dose aspirin with good results. Intussusception prior to the typical features of Kawasaki disease has not been described previously in the English literature. This case illustrates a novel presentation of Kawasaki disease

Presumed bilateral branch retinal vein occlusions secondary to antiepileptic agents

A 61-year-old man presented to the ophthalmology department having developed bilateral branch retinal vein occlusions. Baseline blood tests revealed no abnormality; however, subsequent investigations showed a raised plasma homocysteine (HC) level. The patient has been treated for refractory epilepsy for a number of years. Although antiepileptic medications have been shown to reduce folate levels and result in a raised HC level, this has not previously been shown to be to a level causing a retinal vascular event

Radiation Biology of Uveal Melanoma

Uveal melanoma (UM) is a rare cancer with an annual incidence of approximately 5-8/million, but is the most common primary intraocular malignancy in adults. Treatment of this condition is generally successful with local primary tumour control being at 90-95%; localised radiotherapy in the form of plaque brachytherapy or proton beam radiotherapy are the most utilised in the UK, with primary enucleation still contributing to around a third of cases. Although the response to radiation treatment tends to be excellent, the basic mechanisms of radiation response, DNA repair and tissue reactions have not been well documented or established. The aim of this thesis was to investigate the DNA repair mechanisms in response to exogenous radiation sources (both x-rays and protons) in UM cell lines to determine the basic radiation sensitivity of these cells as well as the pathways involved in DNA repair; such pathways have been utilised in multiple other malignancies as targets for treatment strategies. Chapter 2 investigates this in detail and describes the differences in the radiosensitivities of different UM cell lines, which can be correlated with an upregulation in the ATM-checkpoint pathway involved in DNA repair in more radioresistant lines (OMM2.5 and Mel 270). The use of ATM inhibitors demonstrates this further with a disruption in both x-ray and proton-exposed cell culture analysis regarding both clonogenic assays for cell viability and comet assays for DNA repair response efficiency. Furthermore, tumour responses to radiation, although previously described, have not been correlated to these specific pathways. Chapter 3 describes the cellular and tissue responses in UM after radiotherapy (i.e. following both ruthenium-106 and proton exposure) with a time-independent marked inflammatory and necrotic reaction. The immunohistochemistry of these tissues with ATM demonstrated no significant differences in sample types, but may have been underpowered to do so, and should be investigated in future studies with fresh tissues. The thesis also aims to address the dilemmas in managing patients with UM with regards to reliability of prognostic genetic analysis of tumour biopsies following radiation, as well as the structural and subsequent visual sequelae following exposure to these forms of radiation. Chapter 4 shows the reliability of DNA-based prognostic analyses with regards to estimation of patient mortality from metastatic disease following radiotherapy. However, the reliability of these tests is time-limited with those samples taken many months after radiation treatments demonstrating anomalous results. The recommendation is therefore to aim for UM sample analysis for prognostication within 4 weeks of treatment. Structural radiation effects on local tissues has also been addressed in Chapter 5 with OCT assessment of retinal tissues following both ruthenium-106 and proton beam exposure. Brachytherapy leads to a rapid atrophic response with outer retinal layer disruption and destruction evident within 6 months in the majority of cases; proton beam exposure however shows a significantly different reaction and timeline with minimal outer retinal layer changes in the first 2 years. Visual outcomes following radiation exposure of essential structures for central vision, such as the fovea, therefore demonstrate rapid deterioration following plaque brachytherapy but much less pronounced over a longer time period in proton beam treated patients. This determines the form of treatment utilised for these patients in the medium and long term. In conclusion, this thesis has described the basic radiosensitivity linked with the DNA repair response and time efficiencies of UM cell lines, the UM tissue responses in response to radiation exposure, the structural changes in the tissues surrounding treatments and demonstrated the genetic reliability of post irradiation biopsies. Although answering many questions, it has formed the basis for future work, which may be carried on into more advanced models such as 3D spheroids, and into tissues examining a shorter term response to radiation exposure

Conjunctival Melanoma: A Clinical Review and Update.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global incidence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked, leading to vision loss either from the destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised the treatment of cutaneous melanomas, which share some similarities to Co-M. Importantly, a better understanding of Co-M and its precursor lesions is urgently needed to lead to the development of novel targeted and immunotherapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge regarding Co-M, its epidemiology, pathogenesis, presentation, diagnosis and recent changes in the classification of its precursor lesions, management, and recent advances in novel biological therapies for personalised treatment of this disease

Smokeless tobacco initiation, use and cessation in south Asia: A qualitative assessment

Introduction: Smokeless tobacco (ST) is a significant South Asian public health problem. This paper reports a qualitative study of a sample of South Asian ST users.Methods: Interviews, using a piloted topic guide, with 33 consenting, urban dwelling adult ST users explored their ST initiation, continued use and cessation attempts. Framework data analysis was used to analyse country specific data before a thematic cross-country synthesis was completed.Results: Participants reported long term ST use and high dependency. All reported strong cessation motivation and multiple failed attempts because of ease of purchasing ST, tobacco dependency and lack of institutional support.Conclusions: Interventions to support cessation attempts amongst consumers of South Asian ST products should address the multiple challenges of developing an integrated ST policy, including cessation services.Implications: This study provides detailed understanding of the barriers and drivers to ST initiation, use and cessation for users in Bangladesh, India and Pakistan. It is the first study to directly compare these three countries. The insight was then used to adapt an existing behavioural support intervention for ST cessation for testing in these countries

Prediction of all-cause mortality from 24 month trajectories in patient-reported psychological, clinical and quality of life outcomes in uveal melanoma patients

AbstractA number of patient-reported outcomes (PROs) predict increased mortality after primary cancer treatment. Studies, though, are sometimes affected by methodological limitations. They often use control variables that poorly predict life expectancy, examine only one or two PROs thus not controlling potential confounding by unmeasured PROs, and observe PROs at only a single point in time. To predict all-cause mortality, this study used control variables affording good estimates of life expectancy, conducted multivariate analyses of multiple PROs to identify independent predictors, and monitored PROs two years after diagnosis. We recruited a consecutive sample of 824 patients with uveal melanoma between April 2008 and December 2014. PROs were variables shown to predict mortality in previous studies; anxiety, depression, visual and ocular symptoms, visual function impairment, worry about cancer recurrence, and physical, emotional, social and functional quality of life (QoL), measured 6, 12 and 24 months after diagnosis. We conducted Cox regression analyses with a census date of December 2018. Covariates were age, gender, marital and employment status, self-reported co-morbidities, tumor diameter and thickness, treatment modality and chromosome 3 mutation status, the latter a genetic mutation strongly associated with mortality. Single predictor analyses (with covariates), showed 6-month depression and poorer functional QoL predicting mortality, as did 6–12 month increases in anxiety and 6–12 month decreases in physical and functional QoL. Multivariate analyses using all PROs showed independent prediction by 6-month depression and decreasing QoL over 6–12 months and 12–24 months. Elevated depression scores six months post-diagnosis constituted an increased mortality risk. Early intervention for depressive symptoms may reduce mortality.</jats:p

Prevalence, temporal course and risk factors for phantom eye symptoms in uveal melanoma

BACKGROUND: Phantom eye symptoms (PES), particularly phantom visual sensations (PVS) and phantom eye pain (PEP), are common in enucleated patients and can lead to psychological distress. Current cross-sectional studies cannot examine the temporal course of symptoms, nor can they identify dynamic risk factors or consequences of PES.METHODS: Cohort study of 105 enucleated uveal melanoma patients returning self-report questionnaires, within 4 weeks of diagnosis and 6-, 12- and 24-months post-treatment. Questionnaires measuring PVS and PEP symptoms in the week prior to completion, pain severity, Hospital Anxiety and Depression Scale scores and the Functional Assessment of Cancer Therapy scale (FACT-G) measuring quality of life.RESULTS: PVS and PEP emerged after 6 months, were relatively stable over the study and did not remit. PVS showed 6-, 12- and 24-month prevalence rates of 44.6%, 48.2% and 30.2%, and PEP 16.1%, 18.4% and 17.5% respectively. PVS were generally elementary, with only 10–15% of the total cohort experiencing complex sensations. PEP was generally neither prolonged nor intense, except in a small proportion. PVS and PEP were showed moderate associations but did not predict each other prospectively. Anxiety within 4 weeks of diagnosis was a risk factor for the initiation of PEP. Neither PVS nor PEP prospectively predicted anxiety, depression or quality of life.CONCLUSIONS: PES were prevalent and non-remitting, beginning within 6 months of enucleation. PVS and PEP may not represent symptoms of a coherent syndrome. We discuss fndings with reference to theories of phantom sensations, and directions for clinical practise and research

Associations between empirically proportionate and disproportionate fears of cancer recurrence and anxiety and depression in uveal melanoma survivors: Five-year prospective study.

ObjectiveFear of cancer recurrence (FCR) may develop into elevated anxiety or depression symptoms, but few risk factors for this development are known. Objective recurrence risk estimation is possible in some cancers. Using theories of risk communication and phobias, we examined whether the proportionality of FCR to known objective recurrence risk influences the development of anxiety and depression symptoms.MethodUveal melanoma (UM) patients can opt for reliable prognostic testing. Patients experience either a 'good' or 'poor' prognostic outcome, whereby 10-year mortality due to metastatic disease is, respectively, low or high. In a five-year prospective study of a consecutive sample of 589 UM survivors, we used random intercept cross lagged panel analyses to examine whether proportionality differentially influences whether FCR progresses to anxiety and depression.ResultsPositive cross paths predicting anxiety from FCR were stronger in the poor prognosis group than the good prognosis and not tested groups. Prognostic group differences were not evident for depression.ConclusionsFCR was more likely to progress to elevated anxiety symptoms when proportionate to the known objective recurrence risk. Objective evidence may play a prominent role in the development and structure of fear because it assumes a high epistemic weight that activates a wide range of emotional and cognitive responses. Interventions that assist survivors to tolerate FCR in the presence of higher recurrence risks may be important in reducing anxiety symptoms