Staff Publication

Epidermal growth factor receptor copy number gain (EGFR CNG) and response to gefitinib in esophageal cancer (EC): Results of a biomarker analysis of a phase III trial of gefitinib versus placebo (TRANS-COG) (2014)

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Type of publication:
Conference abstract

Author(s):
Petty R.D., Dahle-Smith A., Miedzybrodzka Z., Dutton S.J., Murray G.I., Stevenson D., *Massie D., Osbourne A., Clark C., Mansoor W., Thompson J., Harrison M., Chatterjee A., Falk S., Elyan S., Garcia-Alonso A., Fyfe D.W., Chau I., Collinson D., Ferry D.

Citation:
Journal of Clinical Oncology, May 2014, vol./is. 32/15 SUPPL. 1, 0732-183X (20 May 2014)

Abstract:
Background: The Cancer Oesophagus Gefitinib (COG) trial randomised (1:1) 450 patients(pts) with advanced EC who had progressed after 1-2 lines of chemotherapy to gefitinib (G) or placebo (P). Improved disease control rates- DCR= RECIST CR+PR+SD at 8 weeks (P 15.6%, G 24.1%, p = 0.016), improved patient reported outcomes, and progression free survival (HR = 0.80, 95%CI 0.66, 0.96, p = 0.020) were seen with G-indicative of rapid and durable responses that were observed in a subset. We hypothesised that EGFR CNG in ECs would identify a subgroup responsive to G. Methods: EGFR CNG was determined by FISH on FFPE tumour specimens(all subject to central pathology review) and performed blind to treatment allocation and outcome. Disomy, low and high trisomy and low polysomy were classified as negative (No CNG) and high polysomy and amplification as positive(CNG). Primary endpoint was OS for G versus P in EGFR CNG and no CNG groups. Secondary endpoints were PFS, DCR and HRQL and outcomes in EGFR amplified patients only. Results: EGFR FISH results were available for 295 patients. Clinical features were not different from the COG trial . EGFR CNG was found in 46/295 (15.6%). There was no significant correlation with EGFR CNG and any clinical features which were also balanced in G and P groups. In EGFR CNG Pts OS was improved with G compared to P (HR=0.53 95%CI 0.28, 0.98 p=0.042), with survival for G vs P 71 vs 64% ,38 vs 14% , 25 vs 5% and 13 vs 0% at 3 ,6, 9, and 12 months respectively. There was no difference in OS for G vs P in EGFR No CNG pts (HR=0.892 95%CI 0.69, 1.16 p=0.395). For PFS EGFR CNG pts, HR=0.58, 95%CI 0.30, 1.07 p=0.080 for G vs P and HR=0.83 95% CI 0.64, 1.07,p=0.144 for EGFR No CNG pts. DCR was improved for G in EGFR CNG pts(42 vs 13%, p=0.035), and less so for EGFR No CNG (24 vs 14 %, p=0.053). EGFR amplification(6%) pts gained greatest benefit from G ( OS, HR=0.19 95%CI 0.05, 0.65 p=0.007). Conclusions: EGFR CNG identified a subgroup of EC who benefit from Gefitinib as a second line treatment and is a useful predictive biomarker for the first stratified treatment approach in this setting and also a subgroup that may be responsive to other anti-EGFR therapies.

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A prospective observational study of real-world treatment patterns and treatment outcomes in patients with advanced or metastatic renal cell carcinoma (mRCC) receiving pazopanib (2014)

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Type of publication:
Conference abstract

Author(s):
Bamias A., Bono P., Procopio G., Herrmann E., Vazquez-Estevez S., Rodriguez Sanchez A., *Srihari N., Schrijvers D.L., Hawkins R.E., Vogelzang N.J., Sapunar F.J., Kothari D., Khan S., Mehmud F., Jonasch E., Schmidinger M.

Citation:
Journal of Clinical Oncology, May 2014, vol./is. 32/15 SUPPL. 1, 0732-183X (20 May 2014)

Abstract:
Background: Pazopanib is an oral, selective, multikinase inhibitor of VEGF receptors 1/2/3, PDGF receptors alpha/s, and stem cell factor receptor (c-Kit) that is approved for first-line treatment of patients with advanced renal cell carcinoma (RCC) and for patients who received prior cytokine therapy. The COMPARZ study of pazopanib versus sunitinib as first-line treatment demonstrated noninferiority of pazopanib for progression-free survival (PFS) in the intention-to-treat population, and pazopanib statistically favored health-related quality of life (HRQoL) in 11 of the 14 domains measured (NEJM 2013;369:722-31). The PISCES patient preference study demonstrated that significantly more patients preferred pazopanib over sunitinib due to overall better HRQoL and less fatigue (JCO 2012;30 suppl 15:CRA4502). The purpose of the PRINCIPAL study is to evaluate the real-world effectiveness and safety of pazopanib in patients with advanced or mRCC. Methods: This is a global, multicenter, prospective, observational study (VEG115232, NCT01649778 ) designed to enrol up to 700 patients. Primary endpoints include PFS, overall response rate, overall survival, relative dose intensity data, HRQoL data, and safety data. Additional treatment strategies for RCC will be obtained post-progression. Key inclusion criteria include a clinical decision to initiate treatment with pazopanib (before enrolment in the study), no prior systemic therapy for advanced or mRCC, and no participation in an interventional trial. The study has enroled 339 patients to date and is currently recruiting in 15 countries, including Europe, Asia, Latin America, and the United States. This study will determine patient outcomes with pazopanib in a real-world setting in terms of efficacy, safety, and patient compliance outside the normal parameters of a controlled trial. PRINCIPAL will also provide further data in patient groups that were under-represented in the controlled clinical trials to date, such as the elderly and patients with co-morbidities.

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The spectrum of dermal hyperneury. Report of six cases (2014)

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Type of publication:
Conference abstract

Author(s):
Ieremia E., *Mudaliar V., *Kelly S., Grech B., Rodriguez P., Martin B., Calonje E.

Citation:
British Journal of Dermatology, July 2014, vol./is. 171/(90), 0007-0963 (July 2014)

Abstract:
Dermal hyperneury is defined as the presence of increased and hypertrophic myelinated and nonmyelinated nerve fibres in the dermis. Cutaneous nerve hyperplasia is rare and can be seen in lesional skin in multifocal or localized forms. When multifocal, it can be present in a pure cutaneous or mucocutaneous form or it may have syndromic associations. It is fascinating that it is present in the normal skin of patients with multiple endocrine neoplasia type 2b (MEN2b) and Cowden syndrome, but also in the lesional skin of those patients, as well as in neurofibromatosis (type 2), attenuated forms of MEN2b and in medullary thyroid carcinoma with macular amyloidosis. Localized, it may be encountered in areas of trauma, nodular prurigo, notalgia paraesthetica, neurocristic hamartoma and rarely in cases of chronic rubbing/scratching (Schaffer JV, Kamino H, Witkiewitcz A et al. Mucocutaneous neuromas. An underrecognised manifestation of PTEN hamartoma- tumor syndrome. Arch Dermatol 2006; 142: 625-32; Winkelmann RK, Carney JA. Cutaneous neuropathology in multiple endocrine neoplasia, type 2b. J Invest Dermatol 1982; 79: 307-12). We present six cases spanning through the spectrum of conditions described. We describe four patients with multiple cutaneous papules, variably symptomatic. Extensive investigations did not reveal any syndromic associations. Furthermore, we include two localized forms: one case of notalgia paraesthetica and one case of trauma. It is interesting to note that PTEN and RET mutations seen in Cowden and MEN2b syndromes, respectively, are implicated in common pathways of the growth and development of neural-crestderived and nerve tissue. We would like to propose dermal hyperneury as a distinct rare entity specifically in those cases presenting with multiple lesions confined to the skin and no syndromic stigmata, and therefore, no associated risk of malignancy.

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A novel sampling device for collecting mucocellular material from the unprepared rectum (2014)

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Type of publication:
Conference abstract

Author(s):
Booth J., *Lacy-Colson J., Norwood M., Murray C.

Citation:
Gut, June 2014, vol./is. 63/(A124-A125), 0017-5749 (June 2014) (also published in European Journal of Cancer, July 2014, vol./is. 50/(S240), 0959-8049 (July 2014))

Abstract:
Background: In vitro diagnostic tests are being developed to evaluate informative protein or DNA biomarkers in stool or blood samples. Stool samples are inconvenient to collect and handle, and may suffer from contamination that interferes with molecular assays. Blood samples may not be as informative early in the disease process. Studies have shown that significant numbers of exfoliated cells and their products are retained in a muco-cellular layer overlaying the colonic mucosa, but distinct from the stool, and that this material flows toward the rectum, where it can be captured for analysis. Materials and Methods: Origin Sciences (OS) has developed a novel sampling device that incorporates an inflatable nitrile membrane. Following insertion into the unprepared rectum via a standard proctoscope, the membrane is inflated to make contact with the rectal mucosa for 10 seconds. The membrane is then deflated and retracted into the device prior to removal from the patient. Upon retraction the sampled material is retained on the inverted membrane, which acts as a receptacle for the addition of buffer preserving the material for subsequent analysis. Results: The sampler has now been tested in over 2000 patients and healthy volunteers, and has shown excellent acceptability. Tests and in vitro experiments with monolayers of cultured human cells indicate that the membrane captures intact cells, which are easily washed off the membrane for further investigation. Detailed evaluation of the mucous-associated material captured by the device, in both normal and diseased states, shows it to be rich in protein and nucleic acids. Levels of soluble protein present in standard 3 mL capture buffer varied between 90 and 3000 mug/mL, with a mean of 710 mg/muL. OS has detected informative auto-antibodies of isotypes IgA, IgG, and IgM by ELISA in the protein component of these preparations. These preparations are also rich in nucleic acids; DNA was found at levels ranging from 0.5 to 21.9 mg/muL. This DNA appears to retain a high degree of integrity, since a number of informative genes have been detected by quantitative PCR. Conclusions: The sampling device represents a novel and minimally invasive tool for capturing biomarker-rich material from the unprepared rectum. With minimal contamination by stool, the material collected is readily analysable. In principle this device lends itself to point-of-care testing for a range of indications, including infectious and inflammatory diseases of the GI tract, in addition to malignancy.

Link to more details or full-text:
http://gut.bmj.com/content/63/Suppl_1/A124.2

Demonstrating the impact of laboratory medicine on clinical outcomes (2014)

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Type of publication:
Conference abstract

Author(s):
*Hallworth M.

Citation:
Clinical Chemistry and Laboratory Medicine, July 2014, vol./is. 52/(S34), 1434-6621 (July 2014)

Abstract:
Clinical laboratory workers believe that the work they perform in providing laboratory tests is valuable. However, data to validate this has been limited, and evidence of the contribution of laboratory medicine to the overall process of diagnosis and management is not easy to obtain. This session will describe the work of the IFCC Task Force on the Impact of Laboratory Medicine on Clinical Management and Outcomes (TF-ICO). It will examine existing evidence, review the gaps in our understanding and deficiencies in the way laboratory medicine is used, and indicate how these can be remedied. Many articles and presentations seeking to promote the value of laboratory medicine have made use of what has become known as the ”70% claim”. This is presented in various forms, most commonly that ”Laboratory Medicine influences 70% of clinical decisions”, or minor variations around this figure. However, the data on which this estimate was based represents unpublished studies and anecdotal observations, and cannot now be objectively verified. The IFCC TF-ICO was established in 2012 to evaluate the available evidence supporting the impact of laboratory medicine in healthcare, and to develop the study design for new studies to generate evidence of the contribution made by laboratory medicine. This presentation will examine existing evidence, review the gaps in our understanding and deficiencies in the way laboratory medicine is currently used, indicate how these might be remedied and offer a vision of a future state in which laboratory medicine is used effectively to support patient care and enhance patient safety. An approach to measuring value will be proposed in which the net value of a testing process is defined as delivered benefits minus delivered harm (undesirable effects of testing). Value is maximized by increasing the benefits and reducing harm. Much of the evidence relating to the value of laboratory medicine is poorly structured and does not relate to clinical outcomes. A more rigorous approach is required. Laboratory medicine has much to offer, but can cause adverse outcomes if not properly used. Laboratorians need to refocus their attention onto improving outcomes.

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Top 15 research priorities for preterm birth with clinicians and service users' involvement-outcomes from a james lind alliance priority setting partnership (2014)

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Type of publication:
Conference abstract

Author(s):
Uhm S., Alderdice F., Chambers B., Gyte G., Gale C., Duley L., James C.P., David A.L., McNeill J., Turner M.A., Shennan A., *Deshpande S., Crowe S., Chivers Z., Brady I., Oliver S.

Citation:
Archives of Disease in Childhood: Fetal and Neonatal Edition, June 2014, vol./is. 99/(A158), 1359-2998 (June 2014)

Abstract:
Background Preterm birth is the single most important determinant of adverse infant outcomes in terms of survival, quality of life, psychosocial and emotional impact on the family, and health care costs. Research agenda in this area has been determined primarily by researchers, and the processes for priority setting in research have often lacked transparency. Objectives To identify 15 most important priorities for future research for practitioners and service users in the area of preterm birth. Methods A priority setting partnership was established by involving clinicians, adults who were born preterm, and parents and families with experience of preterm birth. Research uncertainties were gathered from surveys of service users and clinicians, and analyses of systematic reviews and clinical guidance, and then prioritised in a transparent process, using a methodology advocated by the James Lind Alliance. Results 593 uncertainties were submitted by 386 respondents and 52 were identified from literature reviews. After merging similar questions, a long list of 104 questions were distributed for voting. The 30 most popular items were then prioritised at a workshop. The top 15 research priorities included prevention of preterm birth, management of neonatal infection, necrotising enterocolitis, pain and lung damage, care package at discharge, feeding strategies, pre-eclampsia, emotional and practical support, attachment and bonding, premature rupture of membranes and best time for cord clamping. Conclusions These top research priorities in preterm birth provide guidance for researchers and funding bodies to ensure that future research addresses questions that are important to both clinicians and service users.

Link to more details or full-text: http://fn.bmj.com/content/99/Suppl_1/A158.1.abstract

 

Is it a time to consider introducing simulation training for 'Child Safeguarding'? (2014)

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Type of publication:
Conference abstract

Author(s):
*Saran S., *Brough R., *Ganesh M., *Vadali Y.

Citation:
Archives of Disease in Childhood, April 2014, vol./is. 99/(A64), 0003-9888 (April 2014)

Abstract:
Background Child protection medical examination is an essential competency for any trainee to progress through CCT. Often trainees are apprehensive when asked to perform Child Protection medicals. Inadequate training may lead to poor quality assessments resulting in potential risk to the child, family and possible litigations. Aim To elucidate the learning opportunities which Paediatric trainees get in an average sized district general hospital in England. Methods We have audited notes of children who were referred for the ”Child Protection Medical Examination” to our hospital between 01/05/2012 to 30/09/2013. Results There were 24 ”Child Protection Medical Assessments” performed during 16 months. Both boys and girls were equal in number (12 each). 3 (12%) children were under the age of 12 months, 11 (46%) were between 1 and 5 years and 10 (42%) were older than 5 years. 20 (84%) of these assessments were performed during the weekday and 4 (16%) were done during the weekends. 9 (38%) of the assessments were performed by the ’Community Paediatric Registrars’ who are on call to perform this task in the weekdays during the normal working hours. Equal number 9 (38%) of assessments was performed by the ’Ward Registrars’. On call general paediatric consultants did remaining 6 (24%) assessments. Conclusion Child safeguarding attracts media attention often due to medical inadequacies. We are aware about various serious case reviews in the past and a common recommendation in all of them was to ensure proper training of the front line staff. 24 child protection examinations in 16 months imply an average of 1.5 per month. Just to add to our worry is that on call registrars for child safeguarding have only performed 9 assessments in 16 months, i.e. approximately one assessment every other month. We are seriously concerned about lack of exposure which trainees are getting in this very important component of Paediatric training. We strongly feel to consider other training modalities including introducing simulation technique for ”Child Safeguarding” in the Paediatric curriculum.

Link to more details or full-text: http://adc.bmj.com/content/99/Suppl_1/A64.1

 

Does compliance with the 2 week wait colorectal cancer referral system lead to a higher cancer detection rate? (2014)

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Type of publication:
Conference abstract

Author(s):
*Kaur P., *Cheetham M. , *McCloud J.

Citation:
Colorectal Disease, July 2014, vol./is. 16/(73), 1462-8910 (July 2014)

Abstract:
Background: Current guidelines suggest that patients with a suspected colorectal cancer are seen within 2 weeks of the referral made by general practitioners. Recent data has shown an increase in referrals with a decrease in cancer yield, with up to 25% of all referrals made not meeting referral guidelines. This study aims to determine if there is a higher cancer detection rate in referrals compliant with the referral criteria. Method: A retrospective study of patients referred to a 2-week wait colorectal clinic over a 3-month period was performed. Referral proformas and initial clinic letters were assessed to determine compliancy with the 2 week wait criteria and number of cancers diagnosed. Results: 287 patients were seen in the 3 month period. 38% of referrals were not compliant with the referral criteria. The main reasons for noncompliance were age of the patient (28%) and duration of symptoms (21%). 15 (5.2%) patients were diagnosed with cancer. Compliant referrals had higher cancer detection rate, 13/180 patients (7.2%) when compared with non-compliant referrals, 2/107 patients (1.9%). Conclusion: Compliance with the referral criteria is associated with a higher cancer detection rate. Better education for general practitioners may help to reduce the number of non-compliant referrals reducing work load on strained colorectal units.

 

Laparoscopic ileocaecal resection for Crohn's disease: Initial experience in Shrewsbury (2014)

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Type of publication:
Conference abstract

Author(s):
*Vidyasankar V., *Cheetham M. , *McCloud J

Citation:
Colorectal Disease, July 2014, vol./is. 16/(189), 1462-8910 (July 2014)

Abstract:
Aim: Randomised controlled trials have demonstrated short-term advantages to laparoscopic surgery for ileocaecal Crohn’s disease. Following the introduction of laparoscopic colorectal surgery, we extended our repertoire to include laparoscopic Crohn’s resections. The aim of our study was to assess the safety and outcome following the introduction of laparoscopic resection for ileocaecal Crohn’s. Method: Between January 2008 and November 2012, 30 patients (12 men and 18 women, Median age 30 years), underwent laparoscopic ileocaecal resection for Crohn’s disease. 27 patients had stricturing disease, 2 patients presented with a mass and 1 presented with perforation. Patients were given an intraoperative spinal anaesthetic followed by PCA for 48 hours. All patients were commenced on an enhanced recovery programme. Results: Mean operative time was 90 min. Mean hospital stay was 3 days (range 3-7 days). Two patients (6%) required conversion to open surgery because of a fixed mass (n = 1) and dense adhesions (n = 1). One patient (3%) required reoperation due to haemorrhage. One patient (3%) had prolonged hospital stay due to ileus. One patient (3%) had an anastomotic leak. There were no deaths in this series. Conclusion: Our study demonstrates that laparoscopic resection of ileocaecal Crohn’s disease can be safely performed at a district general hospital with a short length of stay and minimal morbidity.

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