• Use of the PTW Starcheck Maxi MR for commissioning a 1.5 Tesla MR Lina.

      Berresford, Joe; Agnew, James Paul; Budgell, Geoff J; The Christie NHS Foundation Trust, CMPE, Manchester (2018)
    • Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial.

      Slotman, B J; van Tinteren, H; Praag, J O; Knegjens, J L; El Sharouni, S Y; Hatton, M; Keijser, A; Faivre-Finn, Corinne; Senan, S; Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands (2015-01-03)
      Most patients with extensive stage small-cell lung cancer (ES-SCLC) who undergo chemotherapy, and prophylactic cranial irradiation, have persistent intrathoracic disease. We assessed thoracic radiotherapy for treatment of this patient group.
    • The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index.

      Jostel, Andreas; Ryder, W David J; Shalet, Stephen M; Christie Hospital, Department of Endocrinology, Manchester, United Kingdom. (2009-02-18)
      SUMMARY Background: TSH secretion in hypopituitary patients may be decreased due to TSH deficiency, but it remains also under feedback inhibition by fT4. We propose a TSH Index (TSHI) as 'fT4-adjusted TSH', that corrects for any physiological TSH suppression, in order to provide a true estimate of pituitary thyrotrope function and any pathological pituitary suppression. Methods: 9519 TFTs (Bayer Immuno-1(R)) in 4064 patients of our institution were examined, including 444 patients investigated for hypopituitarism. Based on the physiological log-linear relationship between fT4 and TSH, we estimated the amount of feedback-induced change in logTSH per change in fT4, which allowed the extrapolation of logTSH to a fixed fT4 of 0, defining the TSH Index. TSH Indices were compared with other measures of pituitary function. Results: Feedback inhibition was estimated to cause a 0.1345 decrease in logTSH[mU/L] per 1pmol/L increase in fT4 concentration, i.e. TSHI=logTSH+0.1345xfT4. Patients with lower peak stimulated GH and cortisol concentrations had significantly lower TSHI (p<0.0001). TSH Indices measured before pituitary stimulation tests predicted highly significantly the risk of test failure (p=0.0002). 21.9% of all potential fT4-TSH combinations within the current reference ranges were identified as abnormal on the basis of the TSHI. Conclusion: The TSH Index provides an accurate estimate of the severity of pituitary dysfunction in hypopituitary patients based on simple TFTs. It predicts the probability of pituitary stimulation test failure, and extends the diagnosis of TSH deficiency into areas of the normal TFT reference ranges.
    • Use of whole genome sequencing to resolve a surgical ward cluster of meticillin-resistant Staphylococcus aureus.

      Chadwick, Paul; Peel, Alex; Thirkell, Gary; Pichon, B; The Christie NHS FT, Manchester (2019)
      Introduction: Whole genome sequencing (WGS) has been proposed to replace spa typing and pulsed field gel electrophoresis (PFGE) for the investigation of Staphylococcus aureus clusters, but its place has yet to be established for routine outbreak analyses. A cluster of meticillin-resistant Staphylococcus aureus (MRSA) isolates provided an opportunity to compare typing methods for resolving suspected linked cases. Methods: A cluster of MRSA colonisations occurred over six weeks on a surgical ward. It was established that isolates from seven patients were linked in both time and place, with all patients staying in one of two bays. There were no common links in terms of theatres, procedures or theatre staff. Six isolates were typed using spa typing and PFGE by the National Infection Service. In addition, isolates were genome sequenced and their genetic relatedness was assessed using SnapperDB, a single nucleotide polymorphisms (SNP) based typing method. Results: Spa typing, PFGE and genome clustering provided concordant results and linked six isolates to two independent events of transmission of the EMRSA15 strain. However, while SNP addresses showed that all isolates belonged to a single monophyletic clade (within 25 SNP distance), isolates formed two distinct sub-clades of triplets, each clustered within 5 SNP distance. Comparison with genome sequences of local EMRSA15 isolates suggested the presence of an endemic strain, probably introduced several years ago. Conclusion: WGS provided valuable support to the ascertainment of a cluster in a hospital setting. Routine WGS testing of S. aureus would provide strong evidence for effective management of incidents.
    • The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval.

      Darzy, Ken H; Aimaretti, G; Wieringa, Gilbert E; Gattamaneni, Rao; Ghigo, E; Shalet, Stephen M; Department of Endocrinology, Christie Hospital, Manchester, United Kingdom M20 4BX. (2003-01)
      The diagnostic usefulness of the insulin tolerance test (ITT) in patients with radiation-induced GH deficiency (GHD) is well established, whereas that of the combined GHRH plus arginine stimulation test (AST) is unproven. Both tests were undertaken in 49 adult survivors (aged 16-53.7 yr), who were previously irradiated for non-pituitary brain tumors or leukemia, and 33 age-, gender-, and BMI-matched controls. The aims of the study were to examine the impact of the time interval after irradiation on the pattern of GH responsiveness to the two provocative tests and to establish the role of the GHRH + AST in the diagnosis of radiation-induced GHD. The median (range) peak GH responses to either test were significantly lower (P < 0.0001) in the patients [GHRH + AST, 19.9 (range, 2.7-103.5) microg/liter; ITT, 5 (0.2-34.8) microg/liter] than in normals [GHRH + AST, 55 (5.7-173.5) microg/liter; ITT, 23.8 (4.2-80) microg/liter]. In patients and normal controls, the median peak GH response to the GHRH + AST was significantly greater (P < 0.0001) than the response to the ITT. However, the ratio of the peak GH response to the GHRH + AST over that achieved with the ITT (discordancy ratio) was significantly higher (P = 0.007) in the patients (median, 3.45; range, 0.8-53.5) compared with normals (median, 2; range, 0.34-18.6), consistent with dominant hypothalamic damage and relatively preserved somatotroph responsiveness. The peak GH response to the ITT fell significantly within 5 yr of irradiation with little further change over the subsequent 10 yr. In contrast, the peak GH response to the GHRH + AST barely changed within 5 yr of irradiation but subsequently declined significantly over the next 10 yr. Thus, the evolution of change in GH responsiveness to the two different stimuli over time was markedly different, resulting in a significantly raised discordancy ratio of 6 within the first 5 postirradiation years, which then normalized over the next 10 yr. The peak GH responses to the GHRH + AST and the discordancy ratio were negatively correlated with the time interval after irradiation (r = -0.40, P = 0.0037; and r = -0.4, P = 0.0046, respectively). On a practical clinical level, the discordancy between the GH test results was important; 50% of those classified as severely GHD patients by the ITT were judged normal or only GH insufficient by the GHRH + AST. In conclusion, these findings suggest that hypothalamic dysfunction occurs early and somatotroph dysfunction occurs late, following radiation damage to the hypothalamic-pituitary axis. This time dependency of somatotroph dysfunction may reflect either secondary somatotroph atrophy due to hypothalamic GHRH deficiency or delayed direct radiation-induced damage to the pituitary gland. The high false negative diagnosis rate for severe GHD makes the GHRH + AST an unreliable test in clinical practice when GH status is explored in the early years after cranial irradiation with the intention to treat.
    • Using a training needs analysis framework in career development.

      Pennington, Hazel; Christie NHS Foundation Trust, Manchester. (2011-05)
      This is the second of two articles looking at the use of training needs analysis frameworks to streamline the provision of continuing professional development (CPD) in healthcare settings. The first article described the process and academic strategy used to design the framework. Part two describes how one department has used the tool to identify and address staff training and CPD needs, and how this has helped meet individual, departmental and organisational objectives.
    • Using electronic patient records as an effective tool to screen and improve recruitment to a Phase 1 trial in non-small cell lung cancer.

      Haslett, Kate; Ashcroft, Linda; Bramley, Rhidian; Wilson, Ben; Livsey, Jacqueline E; Asselin, M; Bayman, Neil A; Burt, Paul A; Chan, Clara; Coote, Joanna H; et al. (2016)
    • Using information and communication technologies to improve the management of pain from advanced cancer in the community: Qualitative study of the experience of implementation for patients and health professionals in a trial

      Hackett, J; Allsop, MJ; Taylor, Sally; Bennett, MI; Bewick, BM; University of Leeds, UK (2020)
      In cancer care, there are emerging information and communication technology systems being developed, enabling real-time information sharing between patients and health professionals. This study explored health professionals' and patients' perceptions of their engagement with an information and communication technology system for pain management to understand the mechanisms that could support implementation into routine palliative care practice. This was a qualitative study, embedded within a randomised control trial, using semi-structured face-to-face interviews. Data were analysed using thematic analysis. The role of health professionals was a key component to patient engagement with the information and communication technology system. Where patients engaged with the information and communication technology system, both patients and health professionals reported benefits to system use in addition to usual care. Implementation issues were identified that can be used to guide future system development to support pain management in the context of routine clinical care in palliative care services. Where interventions are dependent on multiple providers, collaborative working and consideration of the context within which they are set are needed.
    • Using Local Lexicalized Rules to Identify Heart Disease Risk Factors in Clinical Notes.

      Karystianis, George; Dehghan, A; Kovacevic, A; Keane, J; Nenadic, G; School of Computer Science, University of Manchester, Manchester, UK (2015-06-29)
      Heart disease is the leading cause of death globally and a significant part of the human population lives with it. A number of risk factors have been recognised as contributing to the disease, including obesity, coronary artery disease (CAD), hypertension, hyperlipidemia, diabetes, smoking, and family history of premature CAD. This paper describes and evaluates a methodology to extract mentions of such risk factors from diabetic clinical notes, which was a task of the i2b2/UTHealth 2014 Challenge in Natural Language Processing for Clinical Data. The methodology is knowledge-driven and the system implements local lexicalised rules (based on syntactical patterns observed in notes) combined with manually constructed dictionaries that characterize the domain. A part of the task was also to detect the time interval in which the risk factors were present in a patient. The system was applied to an evaluation set of 514 unseen notes and achieved a micro-average F-score of 88% (with 86% precision and 90% recall). While the identification of CAD family history, medication and some of the related disease factors (e.g. hypertension, diabetes, hyperlipidemia) showed quite good results, the identification of CAD-specific indicators proved to be more challenging (F-score of 74%). Overall, the results are encouraging and suggested that automated text mining methods can be used to process clinical notes to identify risk factors and monitor progression of heart disease on a large-scale, providing necessary data for clinical and epidemiological studies.
    • Using sedation without the consent of the terminally ill.

      Raftery, Anne-Marie; Willard, Carole; The Christie Foundation NHS Trust, Manchester, University of Derby, UK. peter.mackereth@christie.nhs.uk (2009)
    • Using the Malthus programme to predict the recruitment of patients to MR-linac research trials in prostate and lung cancer.

      McWilliam, Alan; Jena, R; Mee, Thomas; Faivre-Finn, Corinne; Sanderson, Benjamin; Kirkby, Norman; Choudhury, Ananya; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, UK (2016-12-07)
      In this study, we used evidence-based mathematical modelling to predict the patient cohort for MR-linac to assess its feasibility in a time of austerity. We discuss our results and the implications of evidence-based radiotherapy demand modelling tools such as Malthus on the implementation of new technology and value-based healthcare.
    • Using whole exome sequencing to identify genetic markers for carboplatin and gemcitabine-induced toxicities.

      Green, H; Hasmats, J; Kupershmidt, I; Edsgard, D; de Petris, L; Lewensohn, R; Blackhall, Fiona H; Vikingsson, S; Besse, B; Lindgren, A; et al. (2015-09-16)
      Chemotherapies are associated with significant inter-individual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients are basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression.
    • Uterine manipulators in laparoscopic or robotic procedures and their role in endometrial cancer recurrence.

      Iavazzo, Christos; Gkegkes, I; Gynaecological Oncology, The Christie NHS Foundation Trust, Manchester (2015)
    • Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry.

      Reyes, C; Karamurzin, Y; Frizzell, N; Garg, K; Nonaka, Daisuke; Chen, Y; Soslow, R; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. (2014-07)
      Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutaneous and uterine leiomyomas and aggressive renal cell carcinomas. Altered fumarate hydratase leads to fumarate accumulation in affected cells with formation of S-(2-succino)-cysteine, which can be detected with the polyclonal antibody. High levels of these modified cysteine residues are found characteristically in fumarate hydratase-deficient cells but not in normal tissues or tumors unassociated with hereditary leiomyomatosis and renal cell carcinoma syndrome. We hypothesized that S-(2-succino)-cysteine-positive leiomyomas, indicating fumarate hydratase aberration, have morphologic features that differ from those without S-(2-succino)-cysteine positivity. Hematoxylin and eosin-stained slides of uterine smooth-muscle tumors were prospectively analyzed for features suggesting hereditary leiomyomatosis and renal cell carcinoma syndrome, such as prominent eosinophilic macronucleoli with perinucleolar halos, yielding nine cases. Germline genetic testing for fumarate hydratase mutations was performed in three cases. A detailed morphological analysis was undertaken, and S-(2-succino)-cysteine immunohistochemical analysis was performed with controls from a tissue microarray (leiomyomas (19), leiomyosarcomas (29), and endometrial stromal tumors (15)). Of the nine study cases, four had multiple uterine smooth muscle tumors. All cases had increased cellularity, staghorn vasculature, and fibrillary cytoplasm with pink globules. All cases had inclusion-like nucleoli with perinuclear halos (7 diffuse, 1 focal). All showed diffuse granular cytoplasmic labeling with the S-(2-succino)-cysteine antibody. Two of three tested patients had germline fumarate hydratase mutations. Only one leiomyoma from the tissue microarray controls was immunohistochemically positive, and it showed features similar to other immunohistochemically positive cases. Smooth-muscle tumors with fumarate hydratase aberration demonstrate morphological reproducibility across cases and S-(2-succino)-cysteine immuno-positivity. Although the features described are not specific for the germline fumarate hydratase mutation or the hereditary leiomyomatosis and renal cell carcinoma syndrome, their presence should suggest fumarate hydratase aberration. Identifying these cases is an important step in the diagnostic workup of patients with possible hereditary leiomyomatosis and renal cell carcinoma.
    • Utility of 18-fluorodeoxyglucose positron emission/computed tomography in the management of recurrent colorectal cancer.

      Liong, Sue Y; Kochhar, Rohit; Renehan, Andrew G; Manoharan, Prakash; Department of Clinical Radiology, The Christie, Manchester, UK. (2012-10)
      This study aimed to evaluate the utility of 18-fluorodeoxyglucose positron emission/computed tomography (PET/CT) in the management of colorectal cancer (CRC) patients with suspected recurrence.
    • Utility of 18F-FDG-PET/CT in lymphoblastic lymphoma

      Fox, T. A.; Carpenter, B.; Taj, M.; Perisoglou, M.; Nicholson, E.; Castleton, Anna; Elliot, Johnathan; Uttenthal, B.; Wright, C.; Halsey, R.; et al. (2020)
    • Utility of bladder-sparing therapy vs radical cystectomy for muscle-invasive bladder cancer

      Efstathiou, JA; Choudhury, Ananya; Kiltie, AE; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston (2018)
    • Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study

      Rothwell, Dominic G; Ayub, Mahmood; Cook, Natalie; Thistlethwaite, Fiona C; Carter, Louise; Dean, Emma J; Smith, Nigel K; Villa, Shaun; Dransfield, Joanne; Clipson, Alexandra; et al. (2019)
      Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. When a 2.5% variant allele frequency (VAF) threshold was applied, actionable mutations were identified in 41 of 100 patients, and 11 of these patients received a matched therapy. These data support the application of ctDNA in this early phase trial setting where broad genomic profiling of contemporaneous tumor material enhances patient stratification to novel therapies and provides a practical template for bringing routinely applied blood-based analyses to the clinic.
    • Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients.

      Westwood, Thomas D; Hogan, C; Julyan, Peter J; Coutts, Glyn; Bonington, Suzanne C; Carrington, Bernadette M; Taylor, Benjamin; Khoo, S; Bonington, A; Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, United Kingdom. Electronic address: tdwestwood@googlemail.com. (2013-04-08)
      BACKGROUND AND PURPOSE: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. METHODS: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. RESULTS: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. CONCLUSION: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.
    • Utility of prognostic markers in second-line treatment of metastatic urothelial cancer.

      Raby, Sophie; Conroy, Ruth; Lyons, Jeanette; Weaver, Jamie M; Elliott, Tony; Choudhury, Ananya; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK (2017-08-19)