CHAMPIONING STUDENT RESEARCH Volume 1 Issue 1 | SPRING 2014 JMSG THE JOURNAL OF MEDICAL STUDENTS, GALWAY Breast Cancer The role of microRNAs Measuring excision performance Case report: CDH1 splice-site mutation carriage The 14thof July Making the transition from final med to Intern Messages from the top From the desks of Professor O’Brien & Dr. Dinneen Cover image: Oblique mammogram showing breast arterial calcification in a 70-year-old female lady. This incidental finding has no link to breast cancer yet several studies suggest a potential link to increased cardiovascular risk. Image courtesy of Donegal Clinical Research Academy. Nahid S, Amir RR, Ali R, et al. Breast arterial calcification and risk of carotid atherosclerosis: Focusing on the preferentially affected layer of the vessel wall. European Journal of Radiology. 2011;79(2):250–256. Schnatz PFI, Marakovits KA, O'Sullivan DM. The association of breast arterial calcification and coronary heart disease. Obstet Gynecol. 2011;117(2 Pt 1):233-41. Copyright © 2014 Journal of Medical Students, Galway School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway, Ireland ISSN (Print): 2009-728X ISSN (Online): 2009-7298 Printed and bound in Co. Galway, Ireland by PrintThat. The content published in this journal is entirely the responsibility of a student organisation, supervised by the faculty of medicine at the Clinical Sciences Institute, and operates independently from the National University of Ireland, Galway (NUIG). The opinions expressed do not necessarily reflect those of the University or University Hospital Galway. NUIG shall not be held liable for any damages resulting directly or indirectly from the use or misuse of the published content. volume 1 issue 1 | 2014 JMSG | CONTENTS 4 Foreword from the Chairman 5 Message from the Founders & Message from the Committee Editorial Committee Abstract 6 Abnormalities in hippocampal morphology in patients with euthymic bipolar affective disorder 7 Stigma of mental illness and help-seeking intention in university students 8 A spatial analysis of antibiotic prescribing and resistance in urinary tract infections in the community 9 Medical student attire: Does it influence patient or medical student attitudes? 10 Characterising airway inflammation in cystic fibrosis 11 Factors associated with the C-reactive protein level in patients with inflammatory bowel disease 12 Managing type 1 diabetes and preventing ketoacidosis during acute illness in children and young adults: Identifying the population for a targeted intervention 13 The role of -defensin 3 in psoriasis 14 The effect of local injury factors on the therapeutic potential for mesenchymal stem cells in treating acute lung injury 15 Uptake of atherogenic lipoproteins is increased in a novel subset of circulating monocytes`in humans 16 Investigating the role of microRNAs as potential circulating biomarkers of breast cancer 17 Exosome-mediated active and selective secretion of microRNAs by breast cancer cells in vitro 18 New emergency surgery course — an exciting development? 19 The use of ultrasound as a histologic predictor of testicular cancer subtypes 20 A biomaterials approach to the treatment of interstitial cystitis: understanding the mechanism of hyaluronan 21 The centricity score; A surgeon’s technical performance in tumour excision during conservative breast surgery Case Report Fatigue and abdominal pain in childhood 24 Refractory anastomotic strictures after oesophagectomy 26 Post hysterectomy and bilateral oophorectomy recurrence of endometrial cancer in the vaginal vault 28 Lobular breast cancer in a CDH1 splice-site mutation carrier Review Article 32 Bibliotherapy in paediatric medicine 34 Making sense of the mesh: A review of pelvic organ prolapse (POP) and the literature surrounding the use of mesh materials in the surgical treatment of PO Opinion Piece Transitioning from medical student to intern 38 Mentorship is a privilege for the mentor 39 Medical students in a changing world Elective Experience 40 A breath of fresh air 42 Sponsors 43 Anatomy Competition volume 1 issue 1 | 2014 Director Yasir Loai Deputy Director Alan Jacobsen Editorial Board Yii Chun Khiew Aoife Murray Ashley Nadeau Ryan Sugrue Faculty Review Board Dr Zuhair Ali Ms Gloria Avalos Dr Diarmuid O’Donovan Public Relations Tariq Esmail Layout Michelle Choynowski Anne-Marie Sweeney Publication Fiona Nolan 22 37 Founders Yasir Loai Alan Jacobsen 2 Webmaster Christopher Wong Staff Advisors Professor Peter McCarthy Dr Zuhair Ali Ms Gloria Avalos Dr Diarmuid O’Donovan JMSG | FOREWORD Dear Colleagues, It is my great pleasure to write the foreword for the inaugural issue of the Journal of Medical Students, Galway (JMSG). This excellent initiative, which has come from the student body, has been supported by a start-up grant from EXPLORE, an NUI Galway based facility for innovative and collaborative research projects between students and staff. The genesis of this project arose due to the very active undergraduate research programme present in this University, which has been going now since 1997. From 12 papers proffered for the inaugural meeting, it has flourished with over 90 papers presented at each of the past two meetings. The strength and quality of the research has increased astonishingly during that time. Having overseen the expansion of the programme as Chairman of the Undergraduate Research Committee over the past several years, it is clear that student input into the Research Committee has been essential for this endeavour to flourish. In this respect, I would like to pay particular tribute to Yasir Loai, currently a final medical student, and Alan Jacobsen, a fourth year medical student, as well as other hard working Committee members in the student body, who have collaborated to ensure that this project has come to fruition with this publication. JMSG is intended to offer a conduit for student research to be published in hardcopy and on-line. All students who present at the annual Research Meeting in October will have the opportunity to have their abstracts considered for publication in the journal. Those of you as long in the tooth as I, will remember the Galway Medical Annual, a paper journal published from 1969 until the early 1980s. In a similar fashion, JMSG strives to afford a facility for undergraduate publications with a newsletter type approach. To my knowledge this is the first attempt at a student journal from the School of Medicine in Galway, and it is to be strongly encouraged. I hope you will give it full support, and I look forward to its continued publication for many years to come. Yours sincerely, Professor Peter McCarthy Chairman of the Undergraduate Research Committee, NUI Galway 3 volume 1 issue 1 | 2014 JMSG | WELCOME Message from the Founders Research is our compass to evidence-based practice and the delivery of optimal patient care. As healthcare professionals and medical scholars, we have the privilege to exercise our intellectual freedom and contribute to scientific discoveries in disease prevention and health promotion. We hope that JMSG, a peerreviewed and open-access student medical journal, paves the path for students to explore the breadths of medical research. support from the EXPLORE initiative. We would like to thank everyone who submitted, and welcome your future contributions or any feedback to facilitate the growth and development of JMSG. In this first issue, we present a selection of breast cancer related articles, mental health focused abstracts, and a particularly thought -provoking paediatric case. Personal messages from the newly appointed Dean and Head of School of Medicine are also featured. Yasir Loai Founder and Director JMSG 2013-2014 This publication would not have been possible without the hard work from the JMSG committee and staff advisors, as well as Alan Jacobsen Founder and Deputy Director JMSG 2013-2014 JMSG Committee “Wednesday evening at 6.00. This meeting will only take 30 minutes.” This was the reminder sent out to each member every week from January to April 2014. We had finished exams in December and began a completely different course, “Co-operation and Journal Production.” “Coming together is a beginning; keeping together is progress; working together is success.” Henry Ford We, having no experience in how to set up a medical journal, were navigating through uncharted territory. Discussing ideas, researching precedents, and debating deadlines, meetings seldom ended on time; but with patience and some guidance from the staff members we began to manage. This is the very first publication of the JMSG. It will not be perfect, and it is not supposed to be perfect. It is a foundation and just the beginning. Whether it is submitting an abstract or reviewing and editing on the other side, JMSG provides a platform for students and staff of the School of Medicine to collaborate. (back) Aoife Murray, Tariq Esmail, Alan Jacobsen, Yasir Loai, Ryan Sugrue, Anne-Marie Sweeney (front) Michelle Choynowski, Mary Khiew, Fiona Nolan absent: Ashley Nadeau, Christopher Wong Please email comments and/or questions to contact@jmsgalway.com, visit our website at www.jmsgalway.com and join our Facebook page. Please submit to submit@jmsgalway.com volume 1 issue 1 | 2014 4 JMSG | ABSTRACT Abnormalities in hippocampal morphology in patients with euthymic bipolar affective disorder Murray Michael1, Scanlon Cathy2, Kilmartin Liam3, Emsell Louise2, Langan Camilla2, McDermott Emma2, Ridge Jason2, Kenney Joanne2, Cannon Dara M4, McDonald Colm2 1 School of Medicine, NUI Galway Clinical Neuroimaging Laboratory, Department of Psychiatry, UHG 3 Department of Electrical/Electronic Engineering, NUI Galway 4 Department of Anatomy, NUI Galway 2 Introduction Impairment in declarative memory has frequently been observed in bipolar affective disorder (BD). Since declarative memory is believed to be primarily formed in the hippocampus, many neuroimaging studies for BD examine hippocampal structure. While overall volume has been investigated in the majority of studies, shape analysis, particularly regional differences in hippocampal structure, provides a means of further examining hippocampal changes in BD. the right hippocampal tail medially (pFDR < 0.05) and contraction in the anterior head and medial border of the left hippocampus (pFDR < 0.05) relative to the control group. The changes in shape detected were not correlated to lithium use, duration of use or duration of illness. Aims To identify the presence of structural abnormalities in hippocampal morphology in patients with euthymic bipolar affective disorder. Methods T1-weighted MR images were acquired for 60 euthymic BD type-1 patients and 60 healthy controls individually matched for age and gender. The hippocampus was manually segmented according to a strict anatomical protocol (intrarater-reliability, ICC=0.92; inter-rater-reliability, ICC=0.88). Hippocampus shape was modelled using SPHARM-mat and normalized to remove the effect of overall volume. Independent t-tests were used to determine group differences across the hippocampal surface and False Discovery Rate (FDR) multiple comparison correction used. Results BD was associated with regions of expansion in Figure 1. Image portrays hippocampal shape changes and are visual representations of statistical analysis. Conclusions Current studies reveal areas of regional shape difference in BD independent of volume change1. The specific reduction in structure in the left hippocampus agrees with those seen in other studies2 but the expansion in the right tail appears to be a novel finding. In summary, we detected a change in the shape of the hippocampus in BD however; the contributing factors and consequences of such changes remain unknown. References 1. Emsell et al.,2010.ISMRM. 2. Bearden et al. J Am Acad Child Adolesc Psychiatry. 2008;47:515-25. 5 volume 1 issue 1 | 2014 JMSG | ABSTRACT Stigma of mental illness and help-seeking intention in university students Quigley Sara1, Lally John2, O’Conghaile Aengus3, Bainbridge Emma3, McDonald Colm3 1 School of Medicine, NUI Galway Institute of Psychiatry, King’s College London 3 Department of Psychiatry, UHG 2 Introduction Personal stigma is each individual’s prejudices and negative attitudes towards those with mental illness. Perceived public stigma is the extent to which an individual perceives the public to negatively stereotype and discriminate against those with mental illnesses Aims To ascertain the levels of personal and perceived public mental health stigma and the association between the respective levels of stigma and help seeking intention. Methods This cross-sectional study was conducted at the NUI Galway primary care student health clinic using a self-administered questionnaire containing an adaptation of the Discrimination-Devaluation scale. All attendees at the clinic over a two week period were invited to participate. A 77% response rate was obtained. Results 735 students participated in the study. Within this cohort, 12% (n=88) reported a personal history of mental illness with 57% (n=417) having personal contact with a person with a mental illness. 15% (n=109) had received treatment for a mental health problem in the previous 12 months. However, 48% (n=356) reported a perceived need for help in the same time period. On the personal stigma scale, 92% (n=675) of respondents would not think less of someone for having received mental health treatment. Interestingly, mean perceived stigma levels were higher than personal stigma levels, indicating that students have an inflated view of public stigma. Personal stigma was significantly associated with a decreased likelihood of future help seeking intention (OR=1.44, p-value=0.048), though perceived stigma was not similarly associated (OR=0.871, p-value=0.768). Having had personal contact with an individual with a history of mental illness was significantly associated with non-help-seeking intention (OR=1.868, pvalue=0.005). Conclusions This study, with a large representative sample, indicates that personal stigma, distinct from perceived stigma, is a significant barrier to mental health utilization for a student population. The discrepancy between those reporting a history of mental illness and those receiving treatment for a mental health problem highlights that not everyone associates receiving treatment for a mental health problem with having a mental illness. The marked discrepancy between the number of students who received treatment and those who felt that they needed help indicates that the majority of students had not engaged in seeking clinical help. Personal stigmatizing attitudes in students suffering from a mental health problem pose an important barrier to help seeking. Stigma reduction campaigns should focus on reducing personal stigma, potentially leading to increased help seeking intention and behaviour. References 1. Thornicroft G, Brohan E, Rose D, Sartorius N, Leese M. Global pattern of experienced and anticipated discrimination against people with schizophrenia: a cross-sectional survey. Lancet. 2009;373:408-15. 2. Mittal D, Sullivan G, Chekuri L, Allee E, Corrigan PW. Empirical studies of self-stigma reduction strategies: a critical review of the literature. Psychiatr Serv. 2012; 63: 974-81 3. Corrigan P. How stigma interferes with mental health care. Am Psychol. 2004;59:614-25 volume 1 issue 1 | 2014 6 JMSG | ABSTRACT A spatial analysis of antibiotic prescribing and resistance in urinary tract infections in the community Bergin Niall1, Hennessy Ronan2, Galvin Sandra2, Vellinga Akke2 1 2 School of Medicine, NUI Galway Departments of Bacteriology and General Practice, NUI Galway Introduction Antibiotic use has been increasing steadily over the past six decades, bringing with it an increase in resistant bacterial strains. Antibiotic resistance is associated with the level of antibiotic use in the population. Urinary tract infections (UTIs) are routinely diagnosed in general practice and reflect antibiotic resistance in the community. Understanding geographical patterns of resistance allows for optimal prescribing in common infections, such as UTI, in primary care. Aims This study aimed to provide a geographical visualisation of data on antibiotic prescribing and resistance in UTIs and to investigate whether spatial maps can be used to demonstrate resistance at the community level. Methods Resistance patterns were examined using geographical information systems and antimicrobial resistance in the form of zone diameters was mapped against patient addresses using ArcGIS software. Patients included in the study presented to one of 22 general practices over a nine month period with both clinical signs of UTI and a urine culture positive for E. coli. Patients were enrolled by means of an opt-out methodology. Resistance to the antimicrobials, ciprofloxacin and trimethoprim, was mapped for all patients (n=752). Data on the prescribing patterns of the twenty-two practices involved was also geo-mapped. A series of maps detailing antibiotic prescribing and resistance patterns in a sample population in the West of Ireland were generated. Results The spatial data demonstrated a trend toward higher resistance in urban centres (Figures 1 and 7 Figures 1 & 2. Maps of the West of Ireland, displaying resistance to trimethoprim (1) or ciprofloxacin (2). The degree of resistance from high to low is represented by a colour gradient, ranging from red to yellow. Locations of GP practices and nursing homes involved in the study are also included. 2. Some rural areas also displayed this trend and these correlated with the presence of nursing homes. Conclusions Our study is a novel example of the spatial analysis of community antibiotic resistance in E. coli from UTIs. Greater application of geomapping in the community and presentation of resistance data in this format could be used to improve prescribing. volume 1 issue 1 | 2014 JMSG | ABSTRACT Medical student attire: Does it influence patient or medical student attitudes? Lyons-Mehl Louise (1)1, Renssen Catherine (1)1, Healy Nuala2, Kearney David2, Malone Carmel2, Kerin Michael J2 1 2 School of Medicine, NUI Galway Department of Surgery, University Hospital Galway Introduction Whilst the white coat has long been a symbol of the medical profession, it is being abandoned as it may provide a barrier to communication and for hygiene purposes. Aims To determine patients’ and medical student views of medical student attire in a variety of clinical scenarios and whether the choice of attire has an impact on patient and student attitudes regarding key student clinical and personal attributes. Methods A prospective cross-sectional descriptive study was conducted from January to March 2012. Study respondents included patients and visitors in the waiting room of outpatient clinics in University College Hospital Galway and medical students attending National University of Ireland Galway. A questionnaire was devised. This included photographs of male and female medical students in three different attires: professional look, scrubs or a casual look (Figure 1). The survey contained questions on respondents baseline demographics and their preference of medical students’ attire for different clinical scenarios e.g. during an emergency or discussing psychological problems. Results 308 patients and 273 students completed the survey. 55% of patients would prefer to have a physical exam performed by students wearing the professional attire. Patients felt that such students, wearing professional attire, were more confident (46%), authoritative (54.6%), responsible (53.7%) and more knowledgeable and competent (55.6%) than medical students dressed in scrubs or casual attire. Both patients (56.9%) and students (85.7%) felt scrubs were most suitable in an emergency setting. Patients and students felt that casual dress was more suitable for discussing sexual (patients 43.1%, students 63.2%) or psychological problems (patients 45%, students 70%). 39% of students admitted that they washed their coat at most once a month. Conclusions Patients would prefer to see medical students dressed in professional attire in a variety of clinical scenarios, including physical examination, as such students appear more trustworthy, knowledgeable, competent, responsible and in control. These results should be taken into consideration when devising guidelines regarding medical student attire. Figure 1. Medical students in professional attire, scrubs and casual attire volume 1 issue 1 | 2014 8 JMSG | ABSTRACT Characterising airway inflammation in cystic fibrosis Rooney Sean1, Murphy Stephen2, Flaus A2, O’Mahony Michael3 1 School of Medicine, NUI Galway Department of Biochemistry, NUI Galway 3 Department of Respiratory Medicine, UHG 2 Introduction Cystic fibrosis (CF) is the most common lifeshortening autosomal recessive disease among Caucasian populations. It is a multisystem condition affecting the sweat glands and the GI, reproductive and endocrine systems. However, progressive lung disease is the major cause of complications and mortality. Currently, there are no reported biomarkers used to characterise pulmonary exacerbations and determine disease stability, with reliance essentially upon FEV1 values. Mean ∆FEV1% from day 1 to day 14 was an increase of 7.33% [(-2)-19)] (p-value=0.07). There was an inverse relationship between change in NE concentration and change in FEV1%; R2 = -0.94, a very strong inverse correlation. The clinical scores used showed significant (p-value < 0.05) discrimination between those with stable disease and exacerbation. Aims The aims were threefold; to develop a biobank of expectorated sputum, serum and clinical information from both exacerbated and stable CF patients, to correlate these results with validated clinical scores1 and pulmonary function tests and to assess neutrophil elastase (NE) as a potential biomarker in airway inflammation in CF. Methods Five stable CF patients were recruited into the project from the CF clinic in UHG. Six patients with an exacerbation of their CF were recruited on admission to hospital; clinical data, sputum and serum samples were collected on admission and again after 14 days of IV antibiotic treatment. Sputum samples were homogenised with ice cold saline and stored with and without protease inhibitors. NE ELISA assays were performed on the processed samples. Results NE levels were standardised based on total protein concentration of the sputum samples. No relationship between the clinical state of the patient and the absolute NE level was found. As a result we looked at how NE changed with FEV1%. Figure 1. Sputum cytology - CF sputum cytospin stained with Hema Gurr, showing abundant neutrophils Conclusions NE can be detected in sputum produced by CF patients using ELISA assay. Change in NE levels in sputum show an inverse relationship with FEV1. Characterising the role of NE in respiratory inflammatory processes has great potential for developing further disease progression indicators, future therapeutics and better understanding of CF and other inflammatory respiratory conditions such as COPD and asthma. References 1. Kanga J, Kuhn R, Craigmyle L, et al. Cystic fibrosis clinical score: a new scoring system to evaluate acute pulmonary exacerbation. Clin Ther. 1999;21:1343-56 9 volume 1 issue 1 | 2014 JMSG | ABSTRACT Factors associated with the C-reactive protein level in patients with inflammatory bowel disease Finnegan Rebecca1, Hong You Ying2, Griffin Damien2, Egan Laurence2 1 2 School of Medicine, NUI Galway Department of Gastroenterology, UHG Introduction C-reactive protein (CRP) is a useful biological marker for underlying inflammation or infection processes. It is widely used for the evaluation of patients with inflammatory bowel disease (IBD). Previous studies have shown that CRP is associated with clinical disease activity, type of IBD and severity of endoscopic findings1. However, some patients with IBD have elevated CRP but remain asymptomatic without evidence of inflammation while others have a normal CRP in the presence of symptoms and active inflammation2. duration of diagnosis of 10.7 years. There was no association between the duration of UC diagnosis, gender, co-morbidities or type of IBD medications with CRP level. There were a total of 140 patients with Crohn’s disease (CD) (81 female; 59 male), with a mean duration of diagnosis of 10.5 years. There was no correlation between CD and the above mentioned factors in relation to CRP level. Interestingly, CRP level was strongly associated with the type of IBD; patients with CD had a higher mean CRP level when compared to patients with UC (8.7 mg/L vs. 4.3 mg/L, p-value=0.005). Aims To investigate associations between the duration of disease, gender, type of IBD, use of IBD medications and co-morbidities and the level of CRP among IBD patients. Methods Data was collected retrospectively from clinic letters and laboratory information systems for all IBD patients attending the outpatient department from January 2011 to May 2012. Patients who attended clinics of non-gastroenterology specialties, or who lacked a record for CRP level were excluded. Data was analysed using Stata statistical package, where a p-value < 0.05 is considered statistically significant. Linear regression analysis was performed to evaluate factors associated with the CRP level in IBD patients. Results Out of the 124 patients with ulcerative colitis (UC) (59 female; 65 male), there was a mean Figure 1. Histological features of inflammatory bowel disease Conclusions CRP level was strongly associated with CD. However, no associations or correlations were found between CRP level and gender, comorbidities, type of IBD medications or the time since diagnosis of UC or CD. Therefore, the utility of routine CRP measurement in patients with IBD may be questionable, however its role in acute exacerbations is well-documented2. References 1. Tsampalieros A, Griffiths AM, Barrowman N, Mack DR. Use of C-reactive protein in children with newly diagnosed inflammatory bowel disease. Journal of Paediatrics. 2011;159(2):340-2. 2. Vermeire S, Van Assche G, Rutgeerts P. C-reactive protein as a marker for Inflammatory Bowel Disease. Inflammatory Bowel Disease. 2004;10(5):661-5. 3. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature, 2007;448:427-434. volume 1 issue 1 | 2014 10 JMSG | ABSTRACT Managing type 1 diabetes and preventing ketoacidosis during acute illness in children and young adults: Identifying the population for a targeted intervention Card Casey1, Weyman Kate2, Michaud Camille2, Sikes Kristen2, Palau-Collazo Miladys2, Tamborlane William2, Weinzimer Stuart2 1 2 School of Medicine, NUI Galway Department of Paediatric Endocrinology, Yale University Introduction Home management of type 1 diabetes (T1D) during acute illness is complex. Supplemental blood glucose and urine ketone testing plus alterations in insulin administration are often necessary to prevent clinical deterioration and development of diabetic ketoacidosis (DKA)1. Despite continuing patient education in clinic, the rate of admissions for diabetes-related emergencies remains unacceptably high. Aims To identify patients who could benefit most from an educational intervention for handling sick days in an attempt to decrease emergency department (ED) admissions. Methods A short (12 question) questionnaire for patients with T1D (if age ≥13 years) or their parents (if age ≤13 years) was developed to assess baseline understanding of DKA (knowledge), the management of diabetes during acute illness (skills), and self-reported comfort and perceived knowledge and skills. Questionnaires and demographic information were collected from 246 subjects (115 female and 131 male, age 13.9±4.4 years, diabetes duration 5.6(0.04, 21.8) years, most recent HbA1c 8.2±1.6%). Results 35% of patients with a HbA1c ≥10% reported having been admitted to the ED in the last twelve months compared with 15% of those with a HbA1c between 8-9.9% and a mere 9% of the 67.9% group. A negative correlation (r-value=0.22, p-value=0.0009) was found between self-reported comfort in managing diabetes during acute illness and HbA1c, with a marked decrease in comfort found in those with a HbA1c of 12% or higher. There was no significant difference between the mean combined knowledge and skill scores of patients who had been to the hospital (+ED) and those who had not (-ED) (+ED: 52.3%, -ED: 53.8%, p=0.6). There was, however, a discrepancy between the parent scores in these two groups (+ED: 50.0%, -ED: 61.9%, p=0.004). In addition, there was decreased parent presence in the +ED group (+ED: 27 patients & 20 parents, -ED: 121 patients & 140 parents). Conclusions Our results indicate that our intervention should target specific groups; patients requiring hospital visits for diabetes-related illness, those uncomfortable managing sick days, patients with high HbA1c levels, those who attend clinic without parents and the parents of T1D patients. We will assess the intervention’s efficacy 3 months post-participation, seeing if questionnaire scores and reported comfort improve and if reported ED visits decrease. References 1. Brink S, Laffel L, Likitmaskul S, Liu L, Maguire A, Olsen B, et al. Sick day management in children and adolescents with diabetes. Pediatric Diabetes. 2007;8(6):401-407. 11 volume 1 issue 1 | 2014 JMSG | ABSTRACT The role of β-defensin 3 in psoriasis Nicholson Laura1, Sweeney Cheryl2, Kirby Brian3 1 School of Medicine, NUI Galway Education and Research Centre, St. Vincent’s University Hospital, Dublin 3 Department of Dermatology, St. Vincent’s University Hospital, Dublin 2 Introduction Psoriasis is a chronic immune-mediated skin disease, characterised by hyperproliferation of keratinocytes and infiltration of inflammatory cells. It is a non-contagious, recurring disease, affecting 1-2% of the European population1. Its aetiology is a complex interaction between genetic, immunological and environmental factors, though not fully understood. The role of innate immunity is suggested by the presence of innate immune cells and their products, such as inflammatory cytokines, IL-23 and IL-1b, in psoriatic skin plaques2. Moreover, the expression of -defensin-3, a small antimicrobial peptide, is enhanced in psoriasis skin. As control rather than cure is currently the aim of psoriasis management, a clear understanding of the role of individual components of the innate immune system in psoriasis is essential to fully comprehend its pathogenesis. This, in turn, is vital to identify potential targets for new therapies. Aims As the relationship between IL-23 and -defensin -3 in psoriasis is unclear, this study examined the expression of IL-23 and -defensin-3 by immune cells in psoriasis patients and healthy controls. Methods Peripheral blood mononuclear cells (PBMC) were activated with the toll-like receptor (TLR) ligands, LPS and zymosan, with or without vitamin D, and the production of inflammatory cytokines was examined by ELISA. Messenger ribonucleic acid (mRNA) was isolated from PBMC and the expression of -defensin-3 was determined by quantitative polymerase chain reaction. Results TLR-4 and TLR-2 activation by LPS or zymosan induced the expression of the inflammatory cytokines IL-23 and IL-1b, as well as the antiinflammatory cytokine IL-10 by PBMC from healthy controls. Moreover, the psoriasis therapy Vitamin D tended to suppress the production of IL-23 by PBMC but did not affect IL-1b or IL-10. Zymosan enhanced the expression of -defensin3 by PBMC. Finally, the expression of -defensin3 was increased in the serum of psoriasis patients versus healthy controls. Conclusions These results demonstrate that TLR activation promotes the expression of both IL-23 and defensin-3 by PBMC. -defensin-3 has been shown to signal through TLR-2 and since this study shows that -defensin-3 is enhanced in psoriasis, targeting TLR-2 may be beneficial in therapies for psoriasis. References 1. Gelfand JM, Weinstein R, Porter SB, et al. Prevalence and treatment of psoriasis in the United Kingdom: a populationbased study. Arch Dermatol. 2005;141:1537-41 2. Sweeney CM, Tobin AM, Kirby B. Innate immunity in the pathogenesis of psoriasis. Archives of Dermatological Research. 2011;303:691-705 volume 1 issue 1 | 2014 12 JMSG | ABSTRACT The effect of local injury factors on the therapeutic potential for mesenchymal stem cells in treating acute lung injury Palmer Conor1, Scully Michael2 1 2 School of Medicine, NUI Galway Department of Anaesthesia, UHG Introduction Acute Lung Injury and Acute Respiratory Distress Syndrome (ALI/ARDS) are devastating disease processes, characterised by life-threatening respiratory and multiple organ failure. There remains no specific therapy for ALI/ARDS. A Cochrane review of 22 studies of 14 different drugs concluded that: "Effective pharmacotherapy for ALI and ARDS is extremely limited, with insufficient evidence to support any specific intervention2.” Mesenchymal stem cells (MSCs) have shown promise in treating lung injury3. Aims To investigate the potential use for MSCs derived from human bone marrow in treating ALI/ALRDS through a series of tissue culture experiments. Methods A549 lung epithelial cells were cultured for use in the series of experiments. Samples of human MSC secretory fluid were prepared for use as conditioned medium (CM). The A549 cells were seeded into 96-well plates at 30,000 cells per plate and divided into three equal groups of 15 wells each. Each was incubated with one of the following: MSC-CM, Minimum Essential Medium (MEM) or Lung Fibroblast Conditioned Medium (FCM). Following incubation, each group of 15 was further divided into three sub-groups of five wells each. One sub-group was challenged with IL-1, one with TNF-α and one with Phosphate Buffer Solution. IL-8 ELISA immunoassay performed on the samples determined inflammatory response. Results were tested for normality and compared for significance using ANOVA with a p-value < 0.05 deemed significant. Results A549 epithelial lung cells incubated in MSC-CM showed significantly reduced production of IL-8 under cellular stress conditions produced by IL-1 challenge compared to MEM (f-value=12.706; pvalue=0.027). There was also a significant decrease in the inflammatory response in MSCCM treated cells challenged with TNF-α (fvalue=14.765; p-value=0.001). In comparison, no significant changes to IL-8 concentration were seen in the FCM incubated cells similarly challenged (f-value=0.989, p-value=0.796). Conclusions This study has shown that MSCs exhibit antiinflammatory effects in lung epithelial cells. This property may lead to the development of useful therapies in treating ALI/ARDS. References 1. Sheridan M, Donnelly M, Bailie R, et al. Acute lung injury and the acute respiratory distress syndrome in Ireland: a prospective audit of epidemiology and management. Critical Care. 2008;12(1):30. 2. Adhikari N, Burns K, Meade M, Others. Pharmacologic therapies for adults with acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev. 2004;4(4). 3. Hare J, Traverse J, Henry T, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. Journal of the American College of Cardiology. 2009;54(24):2277-2286. 13 volume 1 issue 1 | 2014 JMSG | ABSTRACT Uptake of atherogenic lipoproteins is increased in a novel subset of circulating monocytes in humans Mozo Mico1, Dennedy Michael2, Connaughton Eanna2, O’Brien Timothy2, Griffin Matthew2 1 2 School of Medicine, NUI Galway Regenerative Medicine Institute (REMEDI), Galway Introduction Scavenger receptor mediated uptake of modified lipoproteins by monocytes produces foam cells which drive atherosclerosis in humans1. Scavenger receptor expression and uptake of modified lipoproteins in a novel subpopulation of human monocytes have been investigated. These are expanded in obesity and type 2 diabetes mellitus (T2DM) and associated with a poor clinical cardiovascular profile. Expanded CD14++/CD16+/HLADRmid (intermediate) monocytes were previously described in obesity and T2DM. and scavenger receptor A (SRA) was investigated by flow cytometry. Uptake of LDL and pathogenic forms, acetylated (ac)LDL and oxidized (ox)LDL, was investigated using fluorescent boron-dipyrromethene conjugates of each lipoprotein. Aims This study aims to identify whether intermediate monocytes have a possible role in the pathogenesis of atherosclerosis. Results Uptake of both modified forms of lipoprotein, namely acLDL and oxLDL was increased on the novel intermediate subpopulation of monocytes when compared to all other monocyte subpopulations (p-value < 0.01). Surface expression for each scavenger receptor, CD36 and SRA was higher on intermediate monocytes (p-value < 0.01) and this expression was upregulated following modified lipoprotein exposure. Methods Human monocytes were isolated from peripheral blood and subclassified according to CD14, CD16 and HLA-DR expression using flow cytometry3. Surface expression of native lipoprotein receptors, lipoprotein related protein 1 (LRP-1), low density lipoprotein (LDL) receptor, lipoprotein scavenger receptors, CD36 Conclusions This data demonstrates preferential uptake of lipoproteins in a novel subpopulation of human monocytes. These are expanded in obesity and T2DM and associated with cardiovascular risk. In addition they may represent specific precursors to foam cells, prominent in the pathogenesis of atherosclerosis. References 1. Moore KJ, Tabas IA. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145:341-355 2. Wong KL, Tai JJY, Wong WC, et al. Gene expression profiling reveals the defining features of the classical, intermediate and nonclassical human monocyte subsets. Blood. 2011. 3. Wang L, Gaigalas AK, Marti G, Abbasi F, Hoffman RA. Toward quantitative fluorescence measurements with multicolor flow cytometry. Cytometry Part B: Clinical Cytometry. 2008;73A:279-288 volume 1 issue 1 | 2014 14 JMSG | ABSTRACT Investigating the role of microRNAs as potential circulating biomarkers of breast cancer Suresh Malavika1, Dwyer Roisin M2, Brougham Cathy2, Kerin Michael J2 1 2 School of Medicine, NUI Galway Discipline of Surgery, NUI Galway Introduction Despite improvements in detection and treatment, over 600 people die annually from Breast Cancer in Ireland. The stage at diagnosis is intrinsically linked to patient prognosis, highlighting the need for novel, sensitive and specific biomarkers to detect breast cancer. MicroRNAs (miRNAs) are small non-coding RNA molecules approximately 19-25 nucleotides in length. They are detectable in blood and have been shown to be dysregulated in many diseases including breast cancer, highlighting their immense potential as non-invasive biomarkers of disease. Preliminary studies in this laboratory suggested a potential role for miR-296 and miR-146a in breast cancer. Aims This study aimed to investigate the potential of miR-296 and miR-146a as circulating biomarkers of breast cancer. Any correlation with patient clinicopathological details was also investigated. Methods Following informed patient consent, preoperative whole blood samples were harvested from breast cancer patients (n=27) and healthy 15 controls (n=31). RNA was extracted from 1 ml of whole blood and samples were analysed using real-time quantitative PCR targeting miR-146a and miR-296. U6 was employed as an endogenous control. Results miR-296 and miR-146a were detected in the circulation of all breast cancer patients and healthy controls in the study (n=58). miR-296 was significantly down-regulated in breast cancer patients (n=27, Mean ± SEM; 1.26 ± 0.79 log10Relative Quantity (RQ)) compared to healthy controls (n=31, 2.02 ± 0.79 log10RQ, pvalue < 0.01). In contrast, miR-146a was not significantly altered in the circulation of patients with breast cancer (1.38 ± 0.83 log10RQ) compared to controls (1.71±0.7 log10RQ, pvalue=0.069). Neither miR-296 nor miR-146a displayed any significant correlation with patient clinicopathological characteristics. Conclusions This study highlights potential for miR-296 as a novel circulating biomarker for breast cancer. Further analysis of miR-296 expression and function in breast cancer is warranted. volume 1 issue 1 | 2014 JMSG | ABSTRACT Exosome-mediated active and selective secretion of microRNAs by breast cancer cells in vitro Rahmani Lua S1, Glynn Claire L2, Kerin Michael J2, Dwyer Roisin M2 1 2 School of Medicine, NUI Galway Discipline of Surgery, NUI Galway Introduction MicroRNAs are small non-coding RNA molecules that modulate gene expression posttranscriptionally1. MicroRNA dysregulation has been implicated in a whole variety of diseases, including breast cancer. Recent findings suggest that functional microRNAs may be packaged into microvesicles known as exosomes, and transferred between cells2. Aims This study aimed to determine if microRNAs are actively and selectively packaged into exosomes by breast cancer cells and secreted in vitro. Methods Three breast cancer cell lines, each representing a different epithelial subtype of breast cancer, were employed. T-47D (luminal A), SK-BR-3 (HER 2/neu) and BT-20 (basal) cells were cultured in exosome-depleted media for 48 hours. The cell-conditioned media, containing all factors secreted by the cells, was harvested. Exosomes were isolated from cell-conditioned media by differential centrifugation, filtration and ultracentrifugation. Cells were also harvested. MicroRNAs were extracted from exosomes, cellconditioned media and cells using the mirVana™ miRNA Isolation Kit, and real-time quantitative PCR (RQ-PCR) performed targeting three microRNAs of interest, previously implicated in the breast cancer setting: miR-16, miR-138 and miR-379. Results Exosomes which contained nucleic acids were secreted by breast cancer cells and successfully isolated. The presence of a selection of microRNAs was demonstrated in all fractions using RQ-PCR. Each cell line expressed detectable levels of all microRNAs analysed. miR -16 was detected in all cell populations, and additionally secreted in conditioned media and exosome fractions. miR-138, while detectable in all cells, was not present in exosomes or cellconditioned media secreted by T-47D or SK-BR3 cells. However, miR-138 was selectively packaged into exosomes and secreted in cellconditioned media by BT-20 cells, which also expressed higher miR-138 levels than T-47D or SK-BR-3 cells. miR-379 was secreted from all cells, detected in cell-conditioned media, and also selectively packaged into exosomes. In both the SK-BR-3 and BT-20 cell lines, miR-379 expression was greater in the exosome fraction than in the cell-conditioned media which contains all secreted factors, again suggesting selective packaging. Conclusions This novel data demonstrates that microRNAs are actively secreted in exosomes by breast cancer cells. Secretion was shown to be selective, with a distinct panel of microRNAs detected in exosomes. These exosomeencapsulated microRNAs may play an important role in intercellular communication within the breast tumour microenvironment. References 1. Chen X, Liang H, Zhang J, Zen K, Zhang CY. Secreted microRNAs: a new form of intercellular communication. Trends in cell biology. 2012;22:125-32. 2. Hannafon BN, Ding WQ. Intercellular Communication by Exosome-Derived microRNAs in Cancer. International journal of molecular sciences. 2013;14:14240-69. volume 1 issue 1 | 2014 16 JMSG | ABSTRACT New emergency surgery course — an exciting development? Regan Paul1,2, Couse Neville3, Sugrue Michael3 1 School of Medicine, NUI Galway Donegal Clinical Research Academy, Letterkenny General Hospital 3 Department of Surgery, Letterkenny General Hospital 2 Introduction Emergency Surgery counts for 15 to 25% of all hospital admissions. Wide variations in delivery of care and outcomes are reported in emergency surgery. Optimising training in key emergency presentations may improve delivery of care. Aims To report on a new Emergency Surgery Course developed and organised by the Donegal Clinical Research Academy (DCRA) at Letterkenny General Hospital. Methods Common presentations in emergency general surgery were identified and a curriculum based on short lectures, recent guidelines and literature review was established. Each session was followed by an interactive case discussion including video of presentation, examination imaging and surgery. The course was first run in 2012 and modified in 2013. The course was delivered by a faculty of 14. International Faculty members representative of the European Society of Trauma and Emergency Surgery, the American College of Surgeons, MOSES course from Australia and the Association of Surgeons of Great Britain and Ireland were present. 17 The 50 participants ranged from basic surgery trainees to consultant surgeons, mainly from Ireland. All 50 participants who attended in Dublin in July 2013 were asked to complete an evaluation form assessing case discussions, talks and the overall rating of the course on a scale from 1-10, with 10 being excellent and 1 being poor. Results 39/50 completed the evaluation forms. The mean overall rating was 8.5 ± 0.9. Case discussions were rated more highly at 8.7 ± 0.2, compared to talks at 8.3 ± 0.5. 37 of the 39 rated the course as ‘better than any they had previously attended’ in their surgical training. Comments were universally favourable. Conclusions The Emergency Surgery Course was an outstanding success, setting a potential platform for optimising the delivery of surgical education and enhancing Emergency Surgery knowledge. The evaluation completed by the participants provided largely positive feedback which will allow the DRCA to build and improve the course in years to come. volume 1 issue 1 | 2014 JMSG | ABSTRACT The use of ultrasound as a histologic predictor of testicular cancer subtypes O’Donnell Killian1, Butt Muhammad2, Zuhair Ali2, McCarthy Peter2 1 2 School of Medicine, NUI Galway Department of Radiology, UHG Introduction Testicular tumour subtypes have very different treatment plans post orchidectomy; seminomas may be amenable to radiotherapy while nonseminomatous germ cell tumours are typically treated with highly invasive retroperitoneal lymph node dissection. Direct testicular biopsy is not undertaken due to the risk of tumour seeding. Histopathology is determined after orchidectomy. Aims This study was performed to investigate the use of ultrasonography to differentiate between seminomas and non-seminomas. Methods A cohort of patients (n=81) with histologically confirmed testicular tumours, that had been in contact with the surgery/pathology department of Galway University Hospital in the period of 2005 to 2013, had their initial ultrasound scans reviewed retrospectively for ultrasonic features which may allow histologic distinction between seminomas and non-seminomas. Characteristics of testicular tumours such as tumour echogenicity, borders, multiplicity, microlithiasis and vascularity were reviewed in reference to ultrasonic appearances and histology. Patient age of diagnosis ranged from 14 to 71. The mean age was 35 and the median 34. Results Of the 81 patients, 42 patients had seminomas (1 bilateral) and 39 had non-seminomas. Of the 39 in the non-seminoma group, there were 25 nonseminomatous germ cell tumours, six sex cord stromal tumours, four mixed tumours and four tumours not of a testicular origin. Some characteristics did have differences in proportions between the groups but not mounting statistically significant differences. Well defined borders were more common in the seminoma group with an odds ratio of 3.2 (pvalue=0.013, 95% CI 1.3-8.3). A reduced echotexture was also more common in the seminoma group at 85.7% versus 23.1% of nonseminomas (p-value ≤ 0.0001), giving an odds ratio of 20 (95% CI 6.4-62.6). A heterogenous echotexture with cystic components was not seen in the seminoma group whatsoever as opposed to almost a quarter of non-seminomas The seminoma group gave an odds ratio of 17.7 (p-value < 0.001, 95% CI 3.4-57.7) for reduced echotexture, after using a logistic regression model to correct for the next biggest predictor, tumour borders. Figure 1. An intra-testicular mass with well defined borders and reduced echotexture. This is a pathologically confirmed seminoma with characteristics that are statistically significant predictors for an ultrasound diagnosis of seminoma Conclusions Analysis of the basic ultrasound appearances of testicular tumours, such as tumour borders, echogenicity and presence of cystic components can help predict the likelihood of histological subtypes. Ultrasound may be well placed to aid in preliminary diagnoses and early clinical management. References 1. Middleton WD, Teefey SA, Santillan CS. Testicular microlithiasis: prospective analysis of prevalence and associated tumor. Radiology. 2002;224(2):425-8. volume 1 issue 1 | 2014 18 JMSG | ABSTRACT A biomaterials approach to the treatment of interstitial cystitis: understanding the mechanism of hyaluronan Harney Orla1, Rooney Peadar2, Pandit Abhay2, Quinlan Leo3 1 School of Medicine, NUI Galway Network of Excellence for Functional Biomaterials, NUI Galway 3 Department of Physiology, NUI Galway 2 Introduction Interstitial Cystitis (IC) is a chronic debilitating disorder of unknown aetiology. It is characterised by symptoms of increased urinary frequency and urgency, dysuria and dyspareunia. Symptoms are currently attributed to defects in the urothelial glycosaminoglycan layer, which facilitate diffusion of harmful urinary metabolites into underlying bladder tissue where they precipitate chronic inflammation. Subsequent sensory and motor nerve activation within the bladder wall results in pain and increased detrusor muscle contractions. There is not yet a definitive treatment for IC, but standard therapy currently includes intravesical instillation of hyaluronan. Hyaluronan is thought to work by replenishing the glycosaminoglycan layer, however little is known about its potential anti-inflammatory effect1. Aims To analyse the effect of hyaluronan on glycosaminoglycan concentration and proinflammatory interleukin-8 (IL-8) levels in order to evaluate its use in the treatment of IC. Methods In vitro study: Cultured urothelial cells were treated with (a) phosphobuffered saline (control); (b) protamine sulphate (to remove the glycosaminoglycan layer); (c) hyaluronan; or (d) protamine sulphate and hyaluronan. Hyaluronan was added to groups (c) and (d) after six hours of incubation. Cells were incubated at 37°C. At specific time intervals, culture media was removed and stored. ELISA was carried out to measure IL-8 levels in each treatment group. In vivo study: Sections of rat urothelium previously treated with phosphobuffered saline, cyclophosphamide (to induce IC) or Cystistat™ (hyaluronan) were stained with Haematoxylin & Eosin, Safranin-O or Alcian Blue. Slides were examined for glycosaminoglycan concentration and cellular influx by light microscopy. Results In vitro study: At 24 hours of incubation, two-way ANOVA demonstrated a statistically significant reduction in IL-8 levels in group (d) when compared with the control (p-value < 0.05). In vivo study: Microscopic analysis revealed decreased glycosaminoglycan concentration and increased cellular influx in cyclophosphamide treated sections. Increased glycosaminoglycan concentration and decreased cellular influx was observed in Cystistat™ treated sections. Conclusions Both components of this study support the use of hyaluronan as a treatment option for IC. By reducing cytokine secretion and replenishing the glycosaminoglycan layer, hyaluronan may be used to treat both the symptoms of IC, and the cause of these symptoms. Further studies are required to establish the therapeutic potential of hyaluronan. References 1. Parsons CL. Interstitial cystitis: Epidemiology and clinical presentation. Clin Obstet Gynecol. 2002;45:242-9. 19 volume 1 issue 1 | 2014 JMSG | ABSTRACT The Centricity Score: A surgeon’s technical performance in tumour excision during conservative breast surgery Noor Aslam1, Sugrue Ryan1, McNamara Cillian1, Sugrue Michael2, McGowan Katherine2 1 2 School of Medicine, NUI Galway Department of Breast Surgery and Radiology, Donegal Clinical Research Academy, Letterkenny General Hospital Introduction Primary breast surgery should ideally achieve a balance between a clear margin in wide local excision (WLE) and excellent cosmesis. A clear margin reduces the need for re-excision and thus contributes to better oncological outcomes. There are no current scoring systems to aid in complete tumour excision or assess the surgeon’s performance in accurately excising the tumour. Positive margin rates and need for reexcision can vary widely, an issue which the Centricity Score addresses. Aim Using the centricity score, this study aims to assess a single surgeon’s ability to centrally locate and excise cancerous breast tissue in conservative surgery. Methods The scoring system involves the determination of both specimen and tumour centre points within the specimen. This was calculated using intraoperative digital specimen imaging and the Agfa IMPAX 6.4 radiological imaging system in 50 patients who underwent WLE. The Centricity Score is defined as 100 – (ICD/SD x 100), where ICD is the inter-centric distance between the specimen centre and tumour centre and SD is the Specimen Diameter. A score of 100 indicates the tumour was in the dead-centre of the excised specimen. Patients with primary ductal carcinoma in situ were not included. Results 50 patients with a mean age of 63 years (range 38-88) and a mean tumour and specimen diameter of 21.5 ± 8.4 mm and 67.7 ± 14.7 mm respectively were included in the study. Five patients had positive margins and four underwent re-excision. The mean Centricity Score was 87.1 ± 7.6. Figure 1. Radiological analysis of breast specimen Conclusions This follow-up study, which uses a larger cohort than the pilot study, describes a radiological spatial scoring system for patients undergoing WLE which incorporates both the size of the specimen and the excised tumour. This study found that most tumours were well centred in the specimen with an overall high Centricity Score of 87. It is not suitable for mammographically occult lesions. The Centricity Score is used to determine accuracy in the location and excision of cancerous breast tissue. It may also be used as a teaching tool for breast surgical and radiological trainees with the aim of reducing the large variability in margin positivity rates seen in breast cancer surgery. References 1. Kim S, Cornacchi S, Heller B, et al. An evaluation of intraoperative digital specimen mammography versus conventional specimen radiography for the excision of nonpalpable breast lesions. Am J Surg. 2013;6:703-710. 2. Agresti R, Trecate G, Ferraris C, et al. Ex vivo MRI evaluation of breast tumors: a novel tool for verifying resection of nonpalpable only MRI detected lesions. Breast J. 2013;19(6):659–63. 3. Camp MS, Valero MG, Opara N, et al. Intraoperative digital specimen mammography: a significant improvement in operative efficiency. Am J Surg. 2013;206(4):526–9. volume 1 issue 1 | 2014 20 JMSG | CASE REPORT Fatigue and abdominal pain in childhood Conor Fahy School of Medicine, NUI Galway Introduction Neuroblastoma, a malignancy originating from embryonic neural crest cells of the peripheral sympathetic nervous system, is the most common extracranial solid tumour of childhood, responsible for 15% of cancer-related deaths in children1. The cell of origin is believed to be an incompletely committed precursor cell derived from neural crest tissues2. The majority of cases are sporadic; however, a subset of cases show autosomal dominant inheritance and an association has been made between neuroblastoma and other neural crest cell disorders, such as Hirschsprung’s disease1.3. The clinical presentation is highly variable. Around 40% of patients present with signs and symptoms owing to localised disease4. The most common presentations include abdominal mass, with or without concomitant gastrointestinal symptoms of anorexia, abdominal pain, vomiting, and constipation4,5. Localised masses in other anatomical sites may lead to symptoms such as a head/neck mass, dyspnoea or back pain4. Many patients present with nonspecific constitutional symptoms4. For example, neuroblastoma has an unexplained tendency to metastasize to the bony orbit causing periorbital bruising (‘‘raccoon eyes’’) and proptosis4. History This is a case of a five-year-old boy, who presented to the Emergency Department, complaining of a two-week history of exhaustion and abdominal pain. He had been feeling unwell and exhausted for two weeks prior to presentation, and his parents noted that he seemed lethargic and pale. Recently, he was becoming short of breath and fatigue quickly when playing football at school. He had been sleeping during the day for the past week, and he had missed several days of school due to exhaustion. He had pain in the centre of his abdomen, which came on two days after he started to feel exhausted. It was a dull, grumbling pain that did not radiate or change location at any stage. The pain was constant and was not relieved or exacerbated by position, movement or analgesia. He had never had a pain like this before. His appetite had been decreased over the past two weeks. His mum noted that he had lost some 21 weight in recent weeks and his clothes seemed a bit loose. He felt nauseous, but did not vomit at any stage. He had not passed stool for three days prior to presentation, although his bowel motions had previously been normal. His most recent bowel motion was pale, although the passage of any dark urine was denied. Mum had also noticed that his face seemed “puffy” for the last few days, especially around his eyes. Prior to his most recent complaint, PM was a healthy boy, developing and growing normally with no past medical or surgical history. Physical Examination He was febrile, tachycardic (120 bpm, regular rhythm) and pale with mild bilateral periorbital oedema. He had reduced chest expansion on the right side with dullness to percussion, reduced air entry and crackles at the right base. Abdominal examination revealed right upper quadrant tenderness on deep palpation and hepatomegaly of 4 cm. Differentials included malignancy, infectious mononucleosis, viral or autoimmune hepatitis, and pneumonia. Investigations and Diagnosis Immediate investigations included a full blood count, urea and electrolytes, liver function, coagulation screen, ABG, C-RP, urine dipstick, urinalysis. FBC revealed hypochromic microcytic anaemia, with a low haemoglobin of 8.4 g/dL and a low mean corpuscular volume of 69.9 fL. Anaemia or other cytopenias, or haematopoietic failure, may be indicative of bone marrow involvement in patients with neuroblastoma5. His low platelet count of 101 lends further evidence to the hypothesis that there may be bone marrow involvement. Notably, his ferritin and lactate dehydrogenase were both elevated; a finding which is consistent with malignant disease. Ferritin is known to be elevated in patients with active neuroblastoma, and a return of ferritin to a normal level may coincide with remission9. LDH may be elevated in neuroblastoma, germ cell tumours and lymphomas10. PM’s iron studies further supports an underlying malignancy. High ferritin and LDH levels are correlated with a poorer outcome when elevated1. Liver function tests were elevated nonspecifically, with AST 102 U/L and -GT 112 U/L. volume 1 issue 1 | 2014 Imaging Ultrasonography is the initial modality of choice for a suspected abdominal or pelvic mass5,8,9. This patient’s USS revealed a large mass in the right upper quadrant, mild splenomegaly, and a poorly visualised liver margin and right adrenal gland, suggestive of both neuroblastoma and hepatoblastoma. However, α-fetoprotein and -HCG, which are commonly elevated in hepatoblastoma, were normal in this patient. CT has long played an essential role in the evaluation of a patient with suspected neuroblastoma6. Neuroblastoma has a number of characteristic CT features, and extent of spread can be assessed5,8,9. PH’s CT scans revealed a heterogeneous mass posterior to the right lobe of the liver, with internal low density, consistent with necrosis; bilateral mildly enlarged axillary adenopathy; periportal, para-aortic and inguinal (0.8 cm right axillary node); and diffuse nodules in the right lung, consistent with pulmonary metastases. Findings were highly suggestive of neuroblastoma. Further Management Urinary catecholamines, often elevated in patients with neuroblastoma, were ordered neuroblastoma7. However, PM was transferred to a paediatric hospital for further management. Once neuroblastoma has been confirmed, evidence of bone marrow metastases should be sought4,10 via MIBG (metaiodobenzylguanidine) scan and bone marrow aspirate4,14 MIBG scan involves use of a radioisotope which is selectively taken up by catecholamine-secreting neuroblastoma cells5. Treatment Therapeutic options for neuroblastoma include surgical resection, chemotherapy and radiotherapy; the treatment regimen chosen is highly dependant on the stage/extent of spread of the malignancy11. For fortunate patients with low-risk localised disease, surgery may be the only treatment that is required2. Current treatment for high -risk neuroblastomas can be divided into three distinct phases: induction of remission, consolidation, and finally a maintenance phase focused on eradication of residual disease2. Myeloablative chemotherapy has been shown to produce an improvement in survival, administered after induction therapy and followed by rescue with autologous hematopoietic stem cell rescue2. Clinical stage remains the most statistically significant and clinically important determinant of prognosis12. The INSS staging system is the most commonly used; however, the newer INRG guidelines may be superior12. Discussion Paediatric oncology remains one of the most emotive areas of medicine today. The diagnosis and treatment of cancer is associated with profound psychological and social changes in the lives of patients and their parents13. Medical professionals must have an intimate understanding of these issues and look on the patient and family first and foremost as human beings, rather than as medical cases to be managed. In recent decades, the field of paediatric oncology has undergone a paradigm shift, from a focus on “cure at any cost” to a more holistic model emphasising longterm, complication-free survival14. The severity and extent of spread of disease must be taken into account when deciding treatment regimen. In children with life-limiting disease, paediatric palliative care is a growing field whose importance must not be underestimated15. Parents suffer enormous distress and anxiety over their children’s diagnoses; they not only have to cope with this distress, but must also fulfil their responsibilities as their child’s main source of physical, emotional and psychosocial support13. An awareness of these stresses, and the provision of necessary support, are key responsibilities for healthcare workers dealing with childhood malignancy. It is difficult not to be distressed by witnessing the suffering of someone facing a life-threatening illness; the fact that a child is the one affected in this case makes it all the more emotive and saddening. This case reinforces the crucial importance of dealing with challenging cases in a sensitive and empathetic manner, and understanding what the patient and his family are going through. Sometimes, even when best efforts fail and medical treatments are ineffective, sympathy, understanding and kindness may make a huge difference to patients and their families, and it is important not to forget this. References 1. Goldsby RE, Matthay KK. Neuroblastoma: evolving therapies for a disease with many faces. Paediatric drugs. 2004;6(2):107-22. 2. Maris JM. Recent advances in neuroblastoma. The New England journal of medicine. 2010;362(23):2202-11. 3. Knudson AG, Strong LC. Mutation and cancer: neuroblastoma and pheochromocytoma. American journal of human genetics. 1972;24(5):51432. 4. Chu CM, Rasalkar DD, Hu YJ, Cheng FW, Li CK, Chu WC. Clinical presentations and imaging findings of neuroblastoma beyond abdominal mass and a review of imaging algorithm. The British journal of radiology. 2011;84(997):81-91. 5. Hallett A, Traunecker H. A review and update on neuroblastoma. Paediatrics and Child Health. 2012;22(3):103-7. 6. Kushner BH. Neuroblastoma: a disease requiring a multitude of imaging studies. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2004;45(7):1172-88. 7. Strenger V, Kerbl R, Dornbusch HJ, Ladenstein R, Ambros PF, Ambros IM, et al. Diagnostic and prognostic impact of urinary catecholamines in neuroblastoma patients. Pediatric blood & cancer. 2007;48(5):504-9. 8. Mehta K, Haller JO, Legasto AC. Imaging neuroblastoma in children. Critical reviews in computed tomography. 2003l;44(1):47-61. 9. Hugosson C, Nyman R, Jorulf H, McDonald P, Rifai A, Kofide A, et al. Imaging of abdominal neuroblastoma in children. Acta radiologica (Stockholm, Sweden : 1987). 1999;40(5):534-42. 10. Lissauer T, Clayden G. Illustrated Textbook of Paediatrics: With STUDENT CONSULT Online Access: Elsevier Health Sciences; 2007. 11. Park JR, Eggert A, Caron H. Neuroblastoma: biology, prognosis, and treatment. Pediatric clinics of North America. 2008;55(1):97-120, x. 12. Brisse HJ, McCarville MB, Granata C, Krug KB, Wootton-Gorges SL, Kanegawa K, et al. Guidelines for imaging and staging of neuroblastic tumors: consensus report from the International Neuroblastoma Risk Group Project. Radiology. 2011;261(1):243-57. 13. Suzuki LK, Kato PM. Psychosocial support for patients in pediatric oncology: the influences of parents, schools, peers, and technology. Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses. 2003;20(4):159-74. 14. Masera G, Chesler M, Zebrack B, D'Angio GJ. Cure is not enough: one slogan, two paradigms for pediatric oncology. Pediatric blood & cancer. 2013;60(7):1069-70. 15. Bergstraesser E. Pediatric palliative care-when quality of life becomes the main focus of treatment. European journal of pediatrics. 2013;172(2):13950. volume 1 issue 1 | 2014 22 JMSG | CASE REPORT Refractory anastomotic strictures after oesophagectomy Alireza Esfandiari School of Medicine, NUI Galway Introduction Oesophageal squamous cell carcinoma is the predominant histological type of oesophageal cancer worldwide, and has a strong association with smoking and alcohol use. Locally advanced disease is usually treated with curative intent with a multidisciplinary approach that includes surgery. However, up to 40% of oesophagectomies are complicated by benign strictures, requiring further treatment and follow-up1. Case Report This is a case of PF, a 62 year old female who presented to the emergency department in the early hours of the morning, after having one episode of severe vomiting. She has a significant past surgical history of oesphagectomy due to oesophageal squamous cell carcinoma. She was awoken from her sleep with vomiting, and had vomited 12 cupfuls of clear fluid containing no blood or bile. Following the event, she had severe dysphagia to the extent that she was not able to swallow saliva, although this had now resolved. She was also suffering from mild, burning, non-radiating epigastric pain which had no exacerbating or relieving factors. PF had no change in bowel habit, nausea, bleeding per rectum or recent weight loss, and review of systems was unremarkable. Of note, she is an exsmoker of two years, with a 45 pack-year history, and has not drunk alcohol since her youth. In 2010, PF underwent a transhiatal oesophagectomy with gastric pull-up and neoadjuvant chemoradiotherapy following a diagnosis of squamous cell oesophageal cancer. Post-operative management was complicated by a transient ischaemic attack, and more significantly, the development of anastomotic strictures which is currently managed by balloon dilations every 2 months. Additionally, since the operation, she has lost over 30kg in weight and suffers from severe gastro-oesophageal reflux and occasional dysphagia. Despite sleeping at a 45 degree angle, she is woken at least once every night with regurgitation and an unpalatable taste in her mouth. She has sometimes restricted her diet to 23 liquid. Thus far, there is no evidence of recurrence of oesophageal carcinoma. Pre-existing medical conditions include hypothyroidism (diagnosed in 1970), depression (2009), and a transient ischaemic attack postoesophagectomy. Her current medications consist of Lansoprazole 30mg OD, Levothyroxine 100µg OD, Mirtazapine 45mg OD, Citalopram 60mg OD, Clonazepam 0.25mg BD, Aspirin 75mg OD, Atorvastatin 40mg OD. On examination, PF appeared well with stable vital signs. She has a well-healed midline laparotomy scar and a 5cm transverse scar on the left side of her neck. Full systems examination was unremarkable. In summary, PF is a 62 year old woman who presented with 1 episode of severe vomiting, dysphagia, and epigastric pain on a background of post-oesophagectomy strictures from surgery for oesophageal carcinoma. 2 days post-admission she has no abdominal distension or tenderness, and is clinically well. Differentials include narrowing of the stricture, peptic ulcer disease in light of aspirin use, recurrence of neoplasia, gastritis, bowel obstruction caused by adhesions or herniation through the diaphragm, and adverse drug reactions from citalopram or levothyroxine. Whilst patients like PF often present with recurrent symptoms, their aetiology should never be assumed; a thorough history and examination should be carried out regardless to prevent misdiagnoses. Management The patient was stabilised and given intravenous fluids to rehydrate. Morphine sulphate was administered for analgesia, and blood was drawn for a full blood count, urea and electrolytes, thyroid and liver function tests. PF was admitted to the surgical ward and booked for semi-elective balloon dilation. Informed consent was obtained from PF, who was familiar with balloon dilations of the oesophagus. Common and major complications volume 1 issue 1 | 2014 such as haemorrhage, infection, anastomotic breakdown, oesophageal rupture, injury to the tract, and failure of the procedure were explained. Alternative management techniques were described, as well as risks to the patient if no intervention was undertaken. Two days following admission, with the patient fasting and under conscious sedation, the oesophagus was dilated to 15mm under endoscopic guidance. Aspirin was continued and no antibiotic cover was deemed necessary. Follow-up PF was discharged the following day with a follow up clinic appointment scheduled in 3 weeks time. She is currently taking lanzoprazole at 30mg OD, the maximum dose recommended for gastrooesophageal reflux disease, although higher doses have been used in Zollinger-Ellison syndrome and other hypersecretory conditions. Given her unrelenting reflux symptoms, it may be prudent to increase this dose should they persist. years).10 However, she should be warned of red flag symptoms (e.g. dysphagia, early satiety, weight loss), and told to seek medical attention sooner if any occur. At follow-up, a full history and examination should be taken, and a plasma carcinoembryonic antigen ± computed tomography of the thorax should be ordered. Finally, a formal assessment of PF’s mood should be made to assess the need for a psychiatric referral. Student’s Learning Points  Due to its invasive nature, surgery is often accompanied by complications. Awareness of these complications and vigilance in their detection will allow for prompt treatment to ensure the best outcome for patients.  Aetiology should never be assumed. A thorough history and examination should always be carried out to prevent misdiagnoses.  When one treatment modality fails, alternatives should be Alternative management should be considered as long-term dilation of a stricture is usually achieved with a median of 3 sessions of balloon dilation.2 Other options include bougie dilation, which has been shown to have fewer symptoms and achieves a larger oesophageal diameter.3 Intralesional steroid injections have also shown to significantly reduce the need for repeat dilation (13 vs 60 %) one year after the procedure.4 Temporary placement of a self-expanding plastic stent has debatable efficacy,5-8 whilst metal stents should not be used.9 considered. In this case it may be wise to discuss other treatment options with the patient.  Patients’ comorbidities should be fully investigated as they may be affecting other systems. For example, could this patient’s depression be influencing her gastrointestinal symptoms? Following this, PF will only need to be seen on an annual basis given her low risk of cancer recurrence (<10% occur after 2 References 1. Van Heijl M, Gooszen JA, Fockens P, et al. Risk factors for development of benign cervical strictures after esophagectomy. Ann Sueg. 2010;251:10649. 2. Honkoop P, Siersema P, Tilanus H, Stassen L, Hop W, Van Blankenstein M. Benign anastomotic strictures after transhiatal esophagectomy and cervical esophagogastrostomy: risk factors and management. The Journal of thoracic and cardiovascular surgery. 1996;111(6):1141. 3. Cox J, Winter R, Maslin S, Jones R, Buckton G, Hoare R, et al. Balloon or bougie for dilatation of benign oesophageal stricture? An interim report of a randomised controlled trial. Gut. 1988;29(12):1741-7. 4. Ramage JI, Rumalla A, Baron TH, Pochron NL, Zinsmeister AR, Murray JA, et al. A prospective, randomized, double-blind, placebo-controlled trial of endoscopic steroid injection therapy for recalcitrant esophageal peptic strictures. The American journal of gastroenterology. 2005;100(11):241925. 5. Dua KS, Vleggaar FP, Santharam R, Siersema PD. Removable selfexpanding plastic esophageal stent as a continuous, non-permanent dilator in treating refractory benign esophageal strictures: a prospective twocenter study. The American journal of gastroenterology. 2008;103 (12):2988-94. volume 1 issue 1 | 2014 6. Evrard S, Le Moine O, Lazaraki G, Dormann A, El Nakadi I, Devière J. Selfexpanding plastic stents for benign esophageal lesions. Gastrointestinal endoscopy. 2004;60(6):894. 7. Holm AN, de la Mora Levy JG, Gostout CJ, Topazian MD, Baron TH. Selfexpanding plastic stents in treatment of benign esophageal conditions. Gastrointestinal endoscopy. 2008;67(1):20-5. 8. Repici A, Conio M, De Angelis C, Battaglia E, Musso A, Pellicano R, et al. Temporary placement of an expandable polyester silicone-covered stent for treatment of refractory benign esophageal strictures. Gastrointestinal endoscopy. 2004;60(4):513-9. 9. Sandha G, Marcon N. Expandable metal stents for benign esophageal obstruction. Gastrointestinal endoscopy clinics of North America. 1999;9 (3):437. 10. Toh Y, Oki E, Minami K, Okamura T. Follow-up and recurrence after a curative esophagectomy for patients with esophageal cancer: the first indicators for recurrence and their prognostic values. Esophagus. 2010;7 (1):37-43. 24 JMSG | CASE REPORT Post hysterectomy and bilateral oophorectomy recurrence of endometrial cancer in the vaginal vault Yvonne Lillis School of Medicine, NUI Galway Introduction Post-menopausal bleeding is a common presentation of endometrial cancer. This case is centred on the recurrence of endometrial cancer in the vaginal vault, which presented with postmenopausal bleeding in a hysterectomised patient. History RH presented to the Gynaecological Clinic with a three month history of painless per vaginal bleeding and brown discharge with mucous. Fresh, bright red blood and clots were also noted. There were no changes in appetite or weight. These symptoms have significantly impacted her social life, restricting her independence and limiting her social interaction in recent months. Of note, RH had a deep vein thrombosis (DVT) one week prior and was commenced on warfarin. One year prior, RH was diagnosed with endometrial cancer FIGO stage 1B (intermediate risk) and underwent a transabdominal hysterectomy, bilateral salpingooophorectomy, and lymph node dissection with radiotherapy and brachytherapy. Physical Examination The patient appeared well and was sitting comfortably, with no obvious signs of distress. She was apyrexic, normotensive (112/83), and mildly tachycardic with a heart rate of 101 beats/minute. She was pale with pallor of the conjunctiva consistent with anaemia. Abdominal examination revealed a 10 cm incisional hernia containing bowel in the left middle quadrant. Investigations Bloods were taken for a full blood count, coagulation screen, and group and hold. Prior to further investigations, RH was changed from warfarin to therapeutic tinzaparin. Colposcopy revealed focal bleeding from the left lower vagina wall. Given the patient’s previous history of endometrial cancer, a CT abdomen and pelvis was performed. Imaging showed probable left iliac and femoral vein thrombus, secondary to necrotic lymph nodes. Based on her history and CT results, a working diagnosis of recurrent endometrial carcinoma in the vaginal vault was made. Subsequent investigations – EUA (examination 25 under anaesthetic), cystoscopy, vaginal biopsy and punch biopsy – were supportive of the working diagnosis. Discussion Continuity of Care - Following initial diagnosis and treatment of endometrial cancer, most recurrence occurs in the first three years. Unfortunately, there is often a breakdown in quality of care despite routine follow up1. Ideally, review should be conducted every three months for the first three years after treatment, every six months after four years, and every 12 months after the fifth year2. However, due to patient waiting lists and economic constraints, there is a significant disparity between ideal quality of care and what happens in real practice.3 Consequently, women are not often given specific follow-up plans posttreatment. One study investigating follow up care of endometrial cancer survivors revealed that only 62% of women were aware of the health risks and long term effects following treatment4. As suggested by a recent Institute of Medicine Report, there is a clear need for a more structured and planned transition from specialists in post treatment care6. Shared specialist and GP care plans which include information of diagnosis, treatment plan, follow up care, as well as monitoring strategies, have been most effective7,8. Integrated care also enables patients to have the knowledge and understanding to self-manage their condition9. The ambiguity in the defined roles of an oncologist, gynaecologists and general practitioners leads to deficiencies in care10.11. Patient Education - Despite evidence that continuity of care improves survival rates and decreases psychological stress, few women are aware of the symptoms of recurrence to look out for4,5. Likewise, only 58% of women understood the management of health risks post treatment, and only 45% of women were aware of the significant chance of recurrence4. This is evident in the case of RH. Though follow up was maintained every four months, RH was unaware of the significance of recurrent symptoms, and thus did not seek urgent medical attention. As a result, lack of volume 1 issue 1 | 2014 patient knowledge and post-treatment care plan contributed to RH’s poor outcome. Treatment Options - Treatment recommendations for locoregional recurrence of endometrial cancer after surgery are poorly defined. Current evidence-based management includes tumour directed radiation therapy, and/or chemotherapy, and/or surgical resection 13. The choice treatment of women presenting with locoregional recurrence or metastasis depends on prior treatment received. The PORTEC trial showed a lower incidence of recurrence when adjuvant radiation was given at initial presentation12. For patients who did not receive adjuvant therapy previously, radiation therapy (RT) was used with excellent survival outcomes12,14. In the PORTEC trial 87% of women had a complete response12. However, despite receiving adjuvant radiation therapy with surgery during initial treatment, RH still had vaginal recurrence. This is uncommon and is associated with a poor prognosis. In the PORTEC trial, only seven out of 354 women treated with both surgery and RT had vaginal vault recurrences12 warranting surgical resection of the tumour. However, this is restricted to highly motivated, young and otherwise healthy women with no further regional spread, and where resection of the disease is technically feasible15. Pelvic radiation is not an option for women with vaginal vault recurrence due to the risk of local invasion and metastasis to normal surrounding tissue. However, tailored treatment regimens, which require a significant expertise, may allow for re-treatment16,17. Though re-treatment was initially considered, radiological review concluded that RH was not eligible for further radiotherapy, and she was ultimately deemed unsuitable for further surgery. Adjuvant chemotherapy was also a potential treatment option. A 2012 meta-analysis examined chemotherapy regimens in the treatment of metastatic and recurrent endometrial cancer19. Unfortunately, it did not include carboplatin and paclitaxel (first line agents in the treatment for recurrent metastatic cancer), providing no further insight to best practice management18,20. RH’s CT abdomen and pelvis showed “probable left iliac and femoral vein thrombus secondary to necrotic lymph nodes in the obturator fossa and retroperitoneal and mesenteric nodes.” A haematology consult postulated that the thrombus suggests an aggressive cancer, and RH would require a minimum of six months anticoagulation. The thrombotic risk is also further increased by chemotherapy. Currently, chemotherapy is being considered by a multidisciplinary team. Further follow-up is warranted to determine the multidisciplinary approach in devising a plan of care for RH. Conclusion Although there are multiple options available, the management of recurrent endometrial cancer remains unclear. Further stratification based on site, prior RT, prior chemotherapy, and disease is required to clarify best practice for further management. Randomised controlled trials are also necessary to look at locoregional recurrence and the impact of initial therapy. Future studies examining aggressive initial treatment can help determine its impact on disease recurrence and survival. This case highlights the need for follow up care to address recurrence and detection, specific late and long-term effects of treatment, as well as emphasize the value of self-management and patient education. References 1. Faul LA, Shibata D, Townsend I, et al. Improving survivorship care planning for patients with colorectal cancer. Cancer Control. 2010;17(1):35–43 2. Baekelandt M, Castiglione M. Endometrial carcinoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Annals of Oncology Department of Gynecological Oncology, The Norwegian Radium Hospital, Oslo, Norway. 2009;20(4):iv29–iv31. 3. Erikson C, Saisber E, Forte G et al. Future supply and demand for oncologists: challenges to assuring access to oncology services. J of Oncol Pract. 2007;3(2):79–86 4. Jones JM, Ferguson S, Elizabeth E, et al. Experiences of care delivery: Endometrial cancer survivors at end of treatment. Gynecologic Oncology. 2012;124(3)458–464. 5. Stiegelis HE, Hagedoorn M, Sanderman R, et al.The impact of an informational self-management intervention on the association between control and illness uncertainty before and psychological distress after radiotherapy. Psychooncology. 2004;13(4):248–59 6. Institute of Medicine. From cancer patient to cancer survivor: lost in transition. Washington DC: The National Academies Press, 2005. 7. Institute of Medicine. Implementing Cancer Survivorship Care Planning: Workshop Summary. Washington DC: The National Academies Press, 2007. 8. Earle C. Failing to plan is planning to fail: improving the quality of care with survivorship care plans. J Clin Oncol. 2006;24(32):5112-6. 9. Hasman A, Coulter A, Askham J. Education for partnership: developments in medical education. Picker Institute Europe, Oxford. 2006. 10. Cheung WY, Neville BA, Cameron DB, et al. Comparisons of patient and physician expectations for cancer survivorship care. J Clin Oncol. 2009;27 (15):2489–95. 11. Miedema B, MacDonald I, Tatemichi S. Cancer follow-up care. Patients' perspectives. Can Fam Physician. 2003;49:890–895. 12. Creutzberg CL, van Putten WL, Koper PC, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003;89(2):201-9 13. Benedt JL, Bender H, Jones H, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO committee on gynecologic oncology. Int J Gynae Obset. 2000;70:209–262. 14. Lin LL, Grigsby PW, Powell MA, Mutch DG. Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer. Int J Radiat Oncol Biol Phys. 2005;63(2):500-4. 15. Barakat RR, Goldman NA, Patel DA, et al. Pelvic exenteration for recurrent endometrial cancer. Gynecol Oncol. 1999;75(1):99-102. 16. Viswanathan AN, Cormack R, Holloway CL, et al. Magnetic resonanceguided interstitial therapy for vaginal recurrence of endometrial cancer. Int J Radiat Oncol Biol Phys. 2006;66(1):91-9. 17. Abusaris H, Hoogeman M, Nuyttens JJ. Re-Irradiation: Outcome, Cumulative Dose and Toxicity in Patients Retreated with Stereotactic Radiotherapy in the Abdominal or Pelvic Region. Technol Cancer Res Treat. 2012;11(6):591-7. 18. Miller DS, Filiaci V, Fleming G, et al. Randomized Phase III Noninferiority Trial of First Line Chemotherapy for Metastatic or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study. Gynecologic Oncology. 2012;125(3):771. 19. Vale CL, Tierney J, Bull SJ, Symonds PR. Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma. Cochrane Database Syst Rev. 2012;8:CD003915. 20. Moxley KM, McMeekin DS. Endometrial Carcinoma: A Review of Chemotherapy, Drug Resistance, and the Search for New Agents. The Oncologist. 2010;15(10):1026-33 volume 1 issue 1 | 2014 26 JMSG | CASE REPORT Lobular breast cancer in a CDH1 splice-site mutation carrier Choi Paul Joon Koo1, McVeigh Terri2, Miller Nicola2, Green Andrew3, Kerin Michael J2 1 School of Medicine, NUI Galway Discipline of Surgery, NUI Galway 3 National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Crumlin 2 Case Introduction A 49-year-old female, MON, presented with a four-week history of ill-defined nodularity of her right breast. She underwent triple assessment. Clinical exam confirmed the presence of an indeterminate lesion, for which she underwent mammography, ultrasound, and image-directed biopsy. Histological examination revealed an invasive lobular carcinoma. Subsequently, a wide local excision and sentinel lymph node biopsy was performed. Final histology showed a 51 mm, grade 3, invasive lobular cancer with characteristic down-regulation of E-cadherin. The tumour was strongly positive for the Estrogen Receptor (ER, score 7/8), and Progesterone receptor (PR, score 6/8), but negative for the Her2/Neu receptor. Final histological TNM stage was pT3 N0 (0/6) M0. In 2003, MON underwent a prophylactic total gastrectomy with confirmed splice-site 49-2A>G mutation in the CDH1 gene. She was a heterozygous carrier of the H63D mutation and an obligate carrier of a CFTR gene mutation. Her daughter had cystic fibrosis manifesting with significant hepatic and pancreatic disease with portal hypertension, portal hypertensive gastropathy, and liver cirrhosis. She was found to be a compound heterozygote, with ΔF508 and R117H gene mutations. She had a strong family history (Figure 1) of gastric cancer; two maternal aunts, an uncle, and one first cousin all had gastric cancer. The patient’s mother developed lobular breast cancer at 74, 29 mm in maximal diameter, Luminal A molecular subtype, and node negative and developed nodular basal cell carcinoma of the forehead at 78. Via such a genetically interesting history, we aim to outline the role of CDH1 in breast cancer and investigate the current guidelines in managing and screening the mutation carriers. CDH1 Gene and E-Cadherin The CDH1 gene is a tumour suppressor on chromosome 16q22.11, which encodes Ecadherin, a calcium-dependent adhesion molecule. The Epithelial (E) cadherin protein is expressed in the early human development, causes cellular adhesion, and interacts with the actin cytoskeleton to regulate cell polarity, differentiation, growth, and migration2. Ecadherin binds to various catenins (e.g. β-catenin or plakoglobin) to stabilize the cell adhesion complex within the cytoplasm and maintain Ecadherin interaction with actin filament3. Cadherin-catenin interaction and subsequent impact on the WNT signalling pathway may function in tumour suppression4. Loss of E-cadherin is associated with epithelialmesenchymal transition (EMT), in which epithelial cells lose apical-basal polarity and cellular adhesion and become capable of migration, and in the case of tumour cells, invasion, properties Figure 1. Family Pedigree 27 volume 1 issue 1 | 2014 characteristic of mesenchymal cells5. During embryonic development, and also in tumour metastasis, mesenchymal cells express markers such as N-cadherin, Vimentin, and repressors of E-cadherin such as SNAIL and SLUG6. EMT is critical in several processes of embryogenesis and is essential in facilitating cancer progression and metastasis7-10, as well as in the development of resistance to systemic therapy11. Conversely, mesenchymalepithelial transition (MET) occurs following the development of distant metastases, when tumour cells settle in favourable microenvironments in which mesenchymal cells transform into polarized epithelial cells, up-regulate E-cadherin expression, and regain tight junctions and cell adhesion11. The loss of E-cadherin and the associated changes in epithelial cell adhesion and motility have been noted in several cancers, including gastric12-14 and breast1-8. The region on chromosome 16 that contains CDH1 is often associated with loss of heterozygosity and tumour suppressor function in breast cancer1.17.18. Gastric cancer Gastric cancer is sub-classified into intestinal and diffuse subtypes19.20. In the diffuse subtype, E-cadherin expression is lost with subsequent loss of cellular polarity and adhesion. This facilitates metastatic potential of poorly differentiated tumour cells. In contrast, Intestinal subtypes are well-differentiated with preserved adhesion molecules. The intestinal-type cancers are triggered by Helicobacter Pylori infection that causes gastritis, metaplasia, dysplasia, and then carcinoma21. In tumours with mixed phenotypic morphology, loss of E-cadherin and CDH1 mutations are noted only in the diffuse component22. CDH1 inactivation can occur by germline or somatic mutation, by loss of heterozygosity, or by promoter hypermethylation. Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant syndrome characterized by poorly differentiated, highly invasive adenocarcinoma of the stomach causing linitis plastica. HDGC is highly penetrant and carries a high risk of invasive lobular breast cancer23.24. It does not confer a risk of the intestinal subtype of gastric cancer25. CDH1 promoter hypermethylation is seen in in 30-50% of HDGC and in 40-80% of sporadic cases of diffuse-type gastric cancer23.26,27. Breast cancer Breast cancer is classified as familial in 10-15% of cases28-30. Breast cancer susceptibility genes are sub-classified into three groups based on the penetrance (high, moderate, and low). The high risk group of genes includes BRCA1 and BRCA2, as well as TP53, PTEN, STK11, and CDH128. The lifetime risk of breast cancer in CDH1 gene mutation carriers is in the order of 40-50%23. Ecadherin has been postulated to function as a potent breast tumour suppressor1. E-cadherin down-regulation or loss is associated with poor prognosis in patients with breast cancer across different histological and molecular subtypes31-33. Most invasive lobular breast cancers do not express E-cadherin34-36, and in a smaller proportion show only atypical expression. This subtype often shows loss of heterozygosity of the wild type allele of CDH1, combined with inactivating mutations of the remaining volume 1 issue 1 | 2014 copy. Loss of E-cadherin in the ductal subtype is more heterogeneous and less frequent1. Somatic CDH1 mutations have been implicated in breast cancer38. Lobular breast cancer and HDGC The estimated penetrance of lobular breast cancer in female carriers of CDH1 mutations ranges from 39-54%39.40. The histopathological characteristics of lobular breast cancer and diffuse gastric cancer are similar with their common molecular pathogenesis. They are both characterized by isolated, scattered, motile, and highly infiltrative tumour cells and by mucinous signet ring cells23. Non-sense or frame-shift CDH1 mutations are found in gene in sporadic lobular cancers41,42, compared to in-frame or splice-site mutations found in clusters in sporadic diffuse gastric cancers42. Breast cancer associated mutations are clustered at the 3’ end of CDH123. E-cadherin down-regulation in breast cancers is attributed to loss of heterozygosity or promoter hypermethylation whereas promoter hypermethylation of one allele is combined with mutations in the other allele to achieve bi -allelic silencing in gastric cancer23,43,44. As can be seen, the similar pathogenesis of and the presence of CDH1 gene mutation in the two diseases explain MON’s invasive lobular carcinoma, the splice-site 49-2A>G CDH1 gene mutation responsible for her gastrectomy, and her strong family history of gastric cancer. Gastric cancer surveillance protocols and risk reduction surgery Germline mutations in CDH1 are highly penetrant, with a risk of up 70% of symptomatic diffuse gastric cancer by 7539. However, the age of onset of diffuse gastric cancer in CDH1 mutation carriers is variable from teenage years to eighties40,45. Technical difficulties exist with respect to screening endoscopy, given the diffuse, submucosal nature46. Metastatic dissemination of the disease tends to occur within a short interval of development of symptomatic diffuse gastric cancer47,48 and, therefore, consideration of prophylactic intervention in the asymptomatic CDH1 mutation carrier should be appropriately given 48, acknowledging the associated risks and potential morbidity, and 2% risk of mortality. There are psychological, ethical, and medical influences on the decision to undergo surgery; a normal preoperative screening endoscopy, or living elderly relatives unaffected despite harbouring a CDH1 mutation can serve to dissuade patients from accepting prophylactic intervention 46,49. Multiple foci of microscopic invasive signet ring carcinoma have been identified frequently in specimens from asymptomatic patients47,48,50. Breast cancer surveillance protocols and risk reduction surgery Lobular cancers tend to be radio-occult and difficult to detect on standard screening mammography, although MRI is more sensitive52. Female carriers of CDH1 mutations should at minimum, be offered high-intensity annual surveillance, and may be considered for prophylactic bilateral mastectomy46. 28 were also offered prophylactic intervention56. The same mutation has been identified in a family in Birmingham55 and in another Caucasian family with a high incidence of extra-gastric cancers, including breast57. Other primary cancers in this family included lung, and a rectal tumour in a 30-year-old patient. The splice-site mutation A>C has also been identified at the same locus57, which is also associated with breast cancer59. Oestrogen-directed may also be considered since majority of lobular cancers are oestrogen-receptor positive46. CDH1 mutations in the Irish population Ireland is classified as a low-risk territory in terms of the distribution of CDH1 mutations. To date, 122 germline mutations in CDH1 have been identified53 that range from point mutations, including non-sense, missense, and silent mutations, as well as insertions and deletions of single base pairs; to whole exon deletions. Only 50% of CDH1 mutations are completely inactivating, suggesting down-regulation of E-cadherin may be enough to instigate tumourigenesis51. Phenotypic variations, as well as variability in penetrance, exist between different genotypes, and epigenetic factors may also modify clinical significance of a CDH1 mutation51. Most common mutations in CDH1 in Ireland include whole exon deletions of exons 1 and 2, a splice-site mutation before exon 2 (49-2A>G), an insertion in exon 11 (1682insA), and deletion in exon 15 (2398delC)53. In our patient MON, fluorescent cycle sequence analysis of exon 2 was performed on duplicate samples as part of mutation-specific predictive genetic testing, and revealed a 49-2A>G base change prior to exon 2 of CDH1. The wild type A at this locus is conserved in 100% of mammals54. A splice-site mutation at this locus results in protein truncation55. The patient was elected, on the basis of genetic testing and high prevalence of gastric cancer in her family, for a prophylactic total gastrectomy with retro-colic roux-en-Y anastomosis. All other relatives with the mutation Conclusion Diagnosis of HDGC should be considered in the presence of two or more cases of Diffuse Gastric Cancer (DGC) in the patient’s first or second degree relatives, one of whom must had been diagnosed before the age of 50, or in presence of at least three cases of DGC in first or second degree relatives regardless of age of diagnosis59. Upon identification of asymptomatic mutation carriers, potential prophylactic treatment would be ensued. However, ethical, moral, and psychological factors must also be considered supported by intensive genetic counselling prior to genetic testing. Moreover, the patients must be notified of the nature of incomplete penetrance of these gene mutations, limitations in screening modalities, and the risk and potential benefits of prophylactic surgical interventions. Finally, female patients with CDH1 mutations should be offered, at minimum, annual surveillance with breast MRI. Consideration should also be given towards pharmaceutical prophylaxis with oestrogen-based therapies. References 1. Berx G, van Roy F. The E-cadherin/catenin complex: An important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Research. 2001;3(5):289-293. 2. Buda A, Pignatelli M. E-cadherin and the cytoskeletal network in colorectal cancer development and metastasis. Cell Communication and Adhesion. 2011;18(6):133-143. 3. Pötter E, Bergwitz C, Brabant G. The cadherin-catenin system: Implications for growth and differentiation of endocrine tissues. Endocrine Reviews. 1999;20(2):207-239. 4. Novak A, Dedhar S. Signaling through β-catenin and Lef/Tcf. Cellular and Molecular Life Sciences.1999;56(5-6):523-537. 5. Soncin F, Ward CM. The function of E-cadherin in stem cell pluripotency and self-renewal. Genes. 2011;2(1):229-259. 6. Baum B, Settleman J, Quinlan MP. Transitions between epithelial and mesenchymal states in development and disease. Seminars in Cell and Developmental Biology. 2008;19(3):294-308. 7. Thiery JP. Epithelial-mesenchymal transitions in development and pathologies. Current Opinion in Cell Biology. 2003;15(6):740-746. 8. Vincent-Salomon A, Thiery JP. Epithelia-mesenchymal transition in breast cancer development. Breast Cancer Research. 2003;5(2):101-106. 9. Lee JM, et al. The epithelial-mesenchymal transition: New insights in signaling, development and disease. Journal of Cell Biology. 2006;172(7):973 -981. 10. Ramakrishna R, Rostomily R. Seed, soil, and beyond: The basic biology of brain metastasis. Surg Neurol Int. 2013;4(SUPPL4):S256-64. 11. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits. Nature Reviews Cancer. 2009;9(4):265-273. 12. Corso G, et al. Somatic mutations and deletions of the e-cadherin gene predict poor survival of patients with gastric cancer. Journal of Clinical Oncology. 2013;31(7):868-875. 13. Paredes J, et al. Epithelial E- and P-cadherins: Role and clinical significance in cancer. Biochimica et Biophysica Acta - Reviews on Cancer. 2012;1826 (2):297-311. 14. Yakirevich E, Resnick MB. Pathology of Gastric Cancer and Its Precursor Lesions. Gastroenterology Clinics of North America. 2013;42(2):261-284. 15. Chen X, et al. Loss of E-cadherin promotes the growth, invasion and drug resistance of colorectal cancer cells and is associated with liver metastasis. Molecular Biology Reports. 2012;39(6):6707-14. 16. Lu YJ, et al. The expressions of GM II, E-cadherin and α-catenin in ovarian epithelial tumor tissues and ovarian cancer cells with different abilities of metastasis. Tumor. 2012;32(11):899-906. 17. Caldeira JRF, et al. CDH1 promoter hypermethylation and E-cadherin protein expression in infiltrating breast cancer. BMC Cancer. 2006;6:48. 18. Schubert EL, et al. Whole genome LOH analysis of lobular and ductal breast cancers by Hu-SNP array. Breast Cancer Research and Treatment. 2001;69(3):402-405. 19. Lauren P. The two histological main types of Gastric Carcinoma: Diffuse and so-called Intestinal-type Carcinoma: An attempt at a histo-clinical classification. Acta pathologica et microbiologica Scandinavica. 1965;64:3149. 20. Shah MA, et al. Molecular classification of gastric cancer: A new paradigm. 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Loss of E-Cadherin in multidrug resistant breast cancer cell line MCF-7/Adr: Possible implication in the enhanced invasive ability. European Review for Medical and Pharmacological Sciences. 2012;16(9):1271-1279. 34. Jin X, et al. Expression and significance of E-cadherin and P120 catenin in breast cancer. Chinese Journal of Clinical Oncology. 2013;40(3):144-7. 35. Acs G, et al. Differential Expression of E-Cadherin in Lobular and Ductal Neoplasms of the Breast and Its Biologic and Diagnostic Implications. American Journal of Clinical Pathology. 2001;115(1):85-98. 36. Varga Z, Mallon E. Histology and immunophenotype of invasive lobular breast cancer. Daily practice and pitfalls. Breast Disease. 2008;30:15-19. 37. Lei H, et al. CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk. Int J Cancer. 2002;98(2):199-204. 38. Keller G, Vogelsang H, Becker I, et al. Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. The American journal of pathology. 1999;155(2):33742. 39. Pharoah PD, Guilford P, Caldas C. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology. 2001;121(6):1348-53. 40. Kaurah P, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. Journal of the American Medical Association. 2007;297(21):2360-2372. 41. Berx G, et al. E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO Journal. 1995;14(24):6107-15. 42. Berx G, et al. Mutations of the human E-cadherin (CDH1) gene. Human Mutation. 1998;12(4):226-237. 43. Machado JC, et al. E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene. 2001;20 (12):1525-8. 44. Droufakou S, et al. Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast. International Journal of Cancer. 2001;92(3):404-408. 45. Gayther SA, et al. Identification of germ-line E-cadherin mutations in gastric cancer families of European origin. Cancer Research. 1998;58 (18):4086-4089. 46. Lynch HT, et al. Hereditary Diffuse Gastric Cancer: Prophylactic Surgical Oncology Implications. Surgical Clinics of North America. 2008;88(4):75978. 47. Norton JA, et al. CDH1 truncating mutations in the E-cadherin gene: An indication for total gastrectomy to treat hereditary diffuse gastric cancer. Annals of Surgery. 2007;245(6):873-879. 48. Lewis FR, et al. Prophylactic total gastrectomy for familial gastric cancer. Surgery. 2001;130(4):612-9. 49. Lynch HT, Lynch JF. Hereditary diffuse gastric cancer: Lifesaving total gastrectomy for CDH1 mutation carriers. Journal of Medical Genetics. 2010;47(7):433-435. 50. Rogers WM, et al. Risk-reducing total gastrectomy for germline mutations in E-cadherin (CDH1): Pathologic findings with clinical implications. American Journal of Surgical Pathology. 2008;32(6):799-809. 51. Guilford P, et al. A short guide to hereditary diffuse gastric cancer. Hereditary Cancer in Clinical Practice. 2007;5(4):183-194. 52. Francis A, et al. The diagnosis of invasive lobular breast carcinoma. Does MRI have a role? Breast. 2001;10(1):38-40. 53. Corso G, et al. Frequency of CDH1 germline mutations in gastric carcinoma coming from highand low-risk areas: Metanalysis and systematic review of the literature. BMC Cancer. 2012;12:8. 54. Padgett RA, Grabowski PJ, Konarska MM. Splicing of messenger RNA precursors. Annual Review of Biochemistry. 1986;55:1119-50. 55. Richards FM, et al. Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Human Molecular Genetics. 1999;8(4):607-10. 56. Moran CJ, Joyce M, McAnena OJ. CDH1 associated gastric cancer: A report of a family and review of the literature. European Journal of Surgical Oncology. 2005;31(3):259-64. 57. More H, et al. Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene. Human Mutation. 2007;28(2):203. 58. Salahshor S, et al. Low frequency of E-cadherin alterations in familial breast cancer. Breast Cancer Research. 2001;3(3):199-207. 59. Caldas C, et al. Familial gastric cancer: Overview and guidelines for management. Journal of Medical Genetics. 1999;36(12):873-80. volume 1 issue 1 | 2014 30 JMSG | REVIEW ARTICLE Bibliotherapy in paediatric medicine Kate Niethammer School of Medicine, NUI Galway Bibliotherapy refers to the use of books, fiction and non-fiction, to help patients understand, gain insight into and cope with a medical condition1.2. This is no new concept and can be traced back through many centuries3, however, in the last hundred years its therapeutic value has gained popularity and is now a common form of comanagement in the treatment of disease2. In paediatric medicine, bibliotherapy can have immense therapeutic benefits. It is a way to sensitively introduce children to new and challenging experiences that can be emotionally taxing on both themselves and parents. The overall goals in bibliotherapy are to show the reader that they are not alone, not the first with this specific problem and that there is more than one way to react in a difficult situation; books often portray characters who provide motivation and reassurance to patients who are experiencing a similar struggle. Narratives of endurance, courageous survival and struggles against destiny, are woven throughout human history and are the backbone of myths from all cultures and societies. Using these stories for therapeutic benefit can be dated back to ancient Greece where libraries were the ‘healing place for the soul’4. Aristotle believed emotions aroused through stories could have a therapeutic effect on readers and listeners1. The term “bibliotherapy” was first introduced in 1916, when Samuel Roberts discussed the use of books to enhance the understanding of the impacts and consequences of medical ailments. By the 1930s, librarians began compiling lists of books for therapeutic use by counsellors, doctors and patients. Since then, bibliotherapy has remained an integral part of medicine, and its benefits have become more and more recognised. The connection between reader and character is paramount to the success of bibliotherapy. Literature portrays experiences that are essential to human life and allows readers to relate to characters5. A story’s influence over the reader comes from its commonality with real human experiences. For patients, symbolism in language allows them to relate their own stories to the narrative, helping them to transition from victims into survivors. In essence, stories used in 31 bibliotherapy focus on knowledge to modify thoughts, behaviours and feelings, in order to overcome difficulties and improve well-being2. These changes can renew self-determination and dignity to many patients5. Figure 1. The use of bibliotherapy can reduce a child’s fears and anxieties about doctors and hospitals The goal of children’s books is to entertain, while also introducing new ideas and experiences to aid the psychological development of children1,6. Unbeknownst to children, most stories aim to teach important life lessons including sharing, kindness, respecting others and dealing with hardship6. However, the benefit of reading to children extends beyond teaching life lessons by contributing to overall development6. Reading to a child in a hospital environment opens up the opportunity to sit close or cuddle with a loved one when feeling scared and unsure8. The physical act of bibliotherapy provides children with both physical and emotional support to facilitate emotional growth and healing during an unfamiliar and frightening time2. In order for bibliotherapy to be successful in paediatric medicine, children must be able to identify with a character and become emotionally involved in the story. Ultimately, children recognise themselves in the character’s journey and realise that they too can work through their volume 1 issue 1 | 2014 own problems6. Successful stories are ones in which the characters resemble the patient and their experience7, as well as being entertaining, engaging and offering hope and support to the child2. While reading the book, children begin to identify with the character. With this connection, children realise their experience and feelings are ‘normal,’ which provides relief and inspires them to have an active role in their illness and recovery7. In paediatrics, bibliotherapy is especially useful when the characters have experiences at the doctor or in the hospital. These stories have been shown to diminish children’s fears and anxieties in their own medical experiences2. Popular book series are especially useful, as they capitalise on the pre-existing emotional connection children have with the characters to introduce challenging experiences. For instance, Bernstein Bears Visit the Doctor, Curious George Goes to the Hospital, Winnie the Pooh Plays Doctor, Clifford Visits the Hospital and A Visit to the Sesame Street Hospital8-13, all demonstrate the pain and fear the characters felt before visiting the doctor, and the relief and comfort they felt afterwards. These stories are especially useful in bibliotherapy because they introduce new situations through characters that are already known to the child7. Through these stories, doctors and nurses help children see that they are not alone in their fears, injuries or diseases and that there are many different ways to overcome their problems and the positive future ahead of them3,15. Many facts about diseases are complex and involve a lot of information, which is very challenging for children to understand and discuss. As children may not have the vocabulary to express their fears or concerns, it can be useful to explain issues and demonstrate coping strategies through characters6. This offers potential insight while creating a safe distance between the child and the sensitive issue2. These open discussions are invaluable to children, who before reading a story may have been unsure or afraid to ask questions about their diagnosis. Active participation in discussing a story after it has been read also internalises what was learnt and strengthens the understanding of the information provided2. Through the process of interpreting the story a child brings in their own needs and experiences7. Discussion can clarify misunderstandings and offer reassurance, while offering hope and courage in the struggle ahead by seeing the characters overcome similar dilemmas3,15. Doctors, nurses or parents should select stories that are realistic, feasible and relatable. The story should focus on what the characters are capable of as opposed to their limitations2. A correctly chosen book has been shown to decrease anxiety and depression in children6. However, the use of bibliotherapy must be closely monitored and the reaction to the story must be gauged to see if the child is responding positively before any active discussion should take place16. Not all children enjoy reading, so bibliotherapy may not be as successful in some individuals. This can explain the inconsistent findings on the effectiveness of bibliotherapy16. ‘A book is a tool: a toy becomes a tool because the operator is present, but a book communicates. A child communicates with a Cindy doll, but a book speaks to a child’8. The goal of bibliotherapy in paediatrics is to provide information, insight and alternative solutions in a format that is comforting and easy to understand. Using books that children are already familiar with can decrease anxiety and fear while receiving medical care6. Books that focus on the positives, while explaining in a simplistic way what the child should expect1, have been an invaluable aid to doctors and nurses in paediatrics wards. In the future, bibliotherapy will play a greater role in paediatric medicine with many benefits. References 1. Brewster E. 'Medicine for the Soul' Bibliotherapy and the Public Library. Sheffield: University of Sheffield; 2007. 2. Heath MA, Sheen D, Leavy D, Young E, Money K. Bibliotherapy: A resource to facilitate emotional healing and growth. School Psychology International. 2005;26(5):563-80. 3. Austin C. Bibliotherapy for Children: The use of books to support children needing to process difficult personal events that are painful, confusing and overwhelming. In: Children IRf, editor. Los Angeles: Imaginative Resources for Children. 4. Riordan R, Wilson L. Bibliotherapy: Does it Work? Journal of Counselling and Development. 1989;67(9):506-9. 5. Greenhalgh T, Hurwitz B. Narrative Based Medicine: Dialogue and discourse in clinical practice. London: BMA House; 1998. 6. Tielsch Goddard A. Children's books for use in bibliotherapy. Journal of Pediatric Health Care. 2011;25(1):57-61. 7. Cohen LJ. Discover the healing power of books. American Journal of Nursing. 1993;93(10). 8. Matthews DA, Lonsdale R. Children in hospital: II. Reading therapy and children in hospital. Health libraries review. 1992;9(1):14-26. 9. Rey H, Rey M. Curious George Goes to the Hospital: Houghton Mifflin Harcourt 1966. 10. L Bemelmans. Madeleine: Penguin Young Reader Group; 1940. 11. Bernstein S, Bernstein J. The Bernstein Bears Go to the Doctor: Random House Children's Books; 1981. 12. Bridwell N. Clifford Visits the Hospital: Scholastic Inc; 2000. 13. Zoehfeld K. Winnie the Pooh Plays Doctor: Disney Book Group; 1999. 14. Street S. A Visit to the Sesame Street Hospital: Random House Children's Books; 1985. 15. Davies L. Using Bibliotherapy with Children: Kelly Bear. Available from: http://www.kellybear.com/TeacherArticles/TeacherTip34.html. 16. Amer K. Bibliotherapy: using fiction to help children in two populations discuss feelings. Paediatric nursing. 1999;25(1):91-5. volume 1 issue 1 | 2014 32 JMSG | REVIEW ARTICLE Making sense of the mesh: A review of pelvic organ prolapse (POP) and the literature surrounding the use of mesh materials in the surgical treatment of POP Dómhnall O’Connor School of Medicine, NUI Galway Introduction Pelvic organ prolapse (POP) is a common ailment among the female population. Indeed it is said to affect up to 20% of women1. It is known to be the most common reason for surgical intervention in women who have completed child bearing2 and a condition that has challenged physicians as far back as Hippocrates himself3. Therefore it is reasonable that medical students have a basic understanding of the condition and that gynaecologists are aware of the most recent literature on the options available to them, in the operating theatre, that produce the best results. Figure 1. Female genitourinary anatomy Condition Summary POP most simply put is “downward displacement of pelvic structures”3. This may include the bladder or urethra, uterus, rectum or vaginal vault (seen post hysterectomy)3. There are various theories as to how exactly this occurs but many physicians believe that prolapse comes about as a result of weakening in the support structures of the pelvic organs, which logically leads to their succumbing to the effects of gravity and becoming “downwardly displaced” as mentioned above2,3. Despite the lack of a consensus on the exact pathogenesis of this condition the contribution of factors such as; parity, large infant size, chronic increase in abdominal pressure, increasing age and smoking is generally accepted as fact1-5. Available Treatment Options Treatment options range on a spectrum from the least invasive, conservative management to 33 surgical intervention. The mainstay of treatment in early asymptomatic prolapse is the use of pelvic floor exercises to halt prolapse progression2. In cases where the above has failed or the patient is unfit for surgery, the primary intervention is the placement of a pessary. This intervention is centuries old and has well withstood the trial of time3,5. Finally surgical intervention is implicated once the above methods have failed and in patients with high morbidity1,3. Surgical Management The objectives of whichever surgical intervention is used are to: 1. Restore the normal anatomy of the pelvis 2. Restore normal functioning 3. Ensure that recurrence is prevented1 (may be as high as 50-60%2) One should also consider a vaginal approach which has lower morbidity and better functionality than the abdominal approach and mesh augmentation, which some suggest is key to reduced recurrence and better outcomes, when compared to the traditional suture repair of the defect. Suggestion in favour of mesh augmentation is balanced however by a caution regarding its potential cost and complication burden5. This author would argue that in light of POP being such a common condition, with a high recurrence rate, it already has major cost implications to health services3 and any new therapy to reduce recurrences may be financially viable in the long-term. Possibly the most important consideration is the acknowledgement that “most symptoms relate to quality of life (QoL) issues”3. This author believes that this concept is fundamental to all interventions, be they medical or surgical. There volume 1 issue 1 | 2014 case these results lacked significance12 and in others increased reporting of post operative stress urinary incontinence and the necessity for mesh removal was observed13,14. Figure 2. Diagrammatic depiction of mesh placement is little point in restoring the anatomy of the pelvis if the patient still subjectively perceives a deficit in their QoL. This concept is key in the appraisal of the literature surrounding the use of mesh materials in pelvic organ prolapse repair. Use of Meshes in Surgery The oxford dictionary defines a hernia as “a condition in which part of an organ is displaced and protrudes through the wall of the cavity containing it”6. It may be argued, by way of this definition, that POP is a hernia. Take for example a cystocoele; the bladder is the organ that is displaced and is protruding through the anterior vaginal wall into the vagina. There are similarities and some go so far as to label prolapse as a hernia of some description due to shared aetiologies3. If we are to entertain this idea that hernias and prolapse are related in aspects of aetiology then it is logical to consider the potential for shared techniques in their surgical management. It is well evidenced that hernia repair greatly benefits from the use of mesh materials, as evidenced by Scott in his review of the literature7. Unfortunately the use of mesh in the repair of POP is far more controversial8 and available evidence conflicts as to whether or not POP benefits from mesh augmentation. Regardless, 2008-2010 Results continued to trend towards reduced rates of recurrence in mesh repairs, although as seen previously not always with significant results15,16 and in numerous cases the issues regarding QoL and symptomatology conflicted with one another. Publications from this time period are found to be in stark contrast with one another on areas of subjective symptoms and in particular dyspareunia which was reported as significantly increased, decreased and equivocal in those who underwent a mesh repair compared to traditional techniques, in separate studies15-19. A Cochrane review published towards the end of this period critiqued some of the evidence reproduced here and concluded the following: 1. Evidence suggests better anatomical cure 2. Concerns exist regarding post operative sexual functioning, mesh erosions, damage to surrounding structures and infection. 3. Better anatomical cure is not adequate reasoning to implement mesh repair routinely due to the high rate of complications. 4. The use of meshes in POP surgery is only acceptable in the clinical trial setting. 5. There is a general poverty of evidence in areas of cost, impact of surgery on QoL and subjective symptoms.20 Another review from this time period postulated that mesh repair may indeed become standard of care in the future given the inverse relationship between advancing mesh technology and complication rates21. 2011-2013 The evidence of the past triennium has been resoundingly clear on the issue of anatomical cure. In the majority of cases, whether mesh repair has been studied in isolation22-25 or in comparison to traditional repair26-30 it results in a better anatomical cure in the short to intermediate term. Two studies that looked at 2 and 3 year follow up respectively also found anatomical cure equal or superior in the mesh versus non mesh cohorts31,32. Figure 3. The Lichtenstein “mesh” repair for inguinal hernia is the standard of care in general surgery the topic provokes ongoing interest and further research into the area9-11 and for this reason this author believes it is a topic worthy of review. What the Evidence Says Relevant publications within the past 10 years were identified by way of a Medline and PubMed search for mesh repair or augmentation and pelvic organ prolapse and review carried out. 2005-2007 Initial publications from this time period showed a reduced recurrence in those who underwent mesh repair. However in one volume 1 issue 1 | 2014 Despite the clarity of evidence regarding mesh repair and its superiority at anatomical cure the issues surrounding QoL, subjective symptomatology and complications remain uncertain. While some publications show minimal complication rates in mesh repairs23,25 others demonstrated an increase in haemorrhage and viscus perforation28. Similar discrepancies are seen in the reporting of QoL outcomes. A number of studies reported findings of an improvement in QoL and symptoms22-24,29,31 however the majority of these were designed without a cohort undergoing traditional repair for comparison22,23,29,31. Studies that reported on mesh and traditional repair found increased urinary incontinence28 and de novo dyspareunia27 as well 34 as a decrease in sexual function30 in the mesh group when compared to traditional repair. possible that the centres reporting fewer complications simply have better surgeons. Discussion Earlier in this article the first goal of surgical management was said to be “To restore the normal anatomy of the pelvis”. While this is true this author believes that for all interventions the first goal must be “Primum non nocere” or “to do no harm”. The reviewed literature demonstrates that while mesh augmentation produces the best anatomical result, it may also be associated with complications of varying magnitude and morbidity. In the book “Complications” by Atul Gawande, he speaks of the Shouldice clinic and how their less common repair of inguinal hernias, is done under local anaesthesia, in record time, with few recurrences or complications. He labels the Shouldice Clinic a “focused factory”33. Perhaps there is an argument for a similar approach in mesh repair of POP i.e. a small number of surgeons, proficient in the use of mesh repairs, who would spend their day doing only that very specific operation. Perhaps we would see mesh repair of POP, which is not standard practice become superior to standard practice in that specialised institution (As is the case with the Shouldice clinic). A question one may ask is “why did that patient develop a complication?” or “how can one centre report a high rate of complications and another none?” The solution may be multi factorial but at its core must be the skill of the surgeon. It is Until such a time as that may be considered viable, the obvious conclusion is that mesh use in the repair of POP is without the evidence to develop it into a standard practice. Perhaps De References 1. Rosevear SK. Handbook of gynaecological management. Oxford: Blackwell science ltd; 2002. 2. Einarsson JI. Pelvic relaxation, urinary incontinence and urinary tract infection. In: Reece EA, Barbieri RL, editors. Obstetrics and gynaecology: The essentials of clinical care. Stuttgart, Germany. Thieme. 2010:331-332. 3. Zimmerman CW. Surgical correction of defects in pelvic support. In: Rock JA, Jones HW, editors. Te Linde’s Operative gynaecology. 9th ed. Philadelphia: Lippincott Williams and Wilkins. 2003:327-347. 4. MacLennon AU, Taylor AW, Wilson DH, et al. The prevalence of pelvic floor disorders and their relationship to gender, age, parity and mode of delivery. BJOG. 2000;107(12):1460-70. 5. Kobak WH. Pelvic organ prolapse: diagnosis and treatment. In: Mishell Jr. JR, Goodwin TM, Brenner PF, editors. Management of common problems in obstetrics and gynaecology. 4th ed. Oxford: Blackwell Science ltd; 2002: 300-303. 6. Pearsall J. The concise oxford dictionary. New York: Oxford university press. 1999. 7. Scott NW, Go PM, Graham P, et al. Open mesh versus non-mesh for groin hernia repair. Cochrane Database of Systematic Reviews. 2001, Issue 3. Art. No.: CD002197. DOI: 10.1002/14651858.CD002197. 8. U.S. Food and drug administration. FDA Safety communication: UPDATE on serious complications associated with transvaginal placement of surgical mesh for pelvic organ prolapse. http://www.fda.gov/ MedicalDevices/Safety/AlertsandNotices/ncm262435.htm 9. www.ukctg.nihr.ac.uk/trialdetails/NCT00638235 10. www.ukctg.nihr.ac.uk/trialdetails/ISRCTN60695184 11. Lucot JP, Fritel X, Debodinance P, et al. PROSPERE randomised controlled trial: laparoscopic sacropexy versus vaginal mesh for cystocoele pelvic organ prolapse repair [French]. J Gyenecol Obstet Biol Reprod (Paris). 2013;42(4):334-41. 12. Gandhi S, Goldberg RP, Kwon C, et al. A prospective randomised trial using solvent dehydrated fascia lata for the prevention of recurrent anterior vaginal wall prolapse. Am J Obstet Gynaecol. 2005;192(5):164954. 13. Hittumen R, Nieminem K, Takala T, et al. Low weight polypropylene mesh for anterior vaginal wall prolapse: a randomised controlled trial. Obstet Gynaecol. 2007;110(2 Pt 2):455-62. 14. Mescia M, Pifarotti P, Bernasconi F, et al. Porcine skin collagen implants to prevent anterior vaginal wall prolapse recurrence: a multicenter, randomised study. J urol. 2007;177(1):192-195. 15. Carey M, Higgs P, Gol J, et al. Vaginal repair with mesh versus colporaphy for prolapse: a randomised comtrolled trial. BJOG. 2009;116(10):1380-86. 16. Iglesia CB, Sokol AL, Sokol ER, et al. Vaginal mesh for prolapse: a randomised controlled trial. Obstet Gynaecol. 2010;116(2 Pt 1):293-303. 17. Nguyen JN, Burchette RJ. Outcome after anterior vaginal repair: a randomised controlled trial. Obstet Gynaecol. 2008;111(4):891-898. 18. Nieminem K, Hiltunen R, Heiskanen E, et al. Symptom resolution and sexual function after anterior vaginal wall repair with or without polypropylene mesh. Int Urogynaecol J Pelvic Floor Dysfunct. 2008;19(12): 1611-6. 19. Sivasliogu AA, Unlubilgin E, Dolen I. A randomised comparison of polypropylene mesh surgery with site specific surgery in the treatment of cystocoele. Int Urogynaecol J Pelvic Floor Dysfunct. 2008;19(4):467-71. 20. Maher C, Feiner B, Baessler K, Glazener CMA. Surgical management of pelvic organ prolapse in women. Cochrane database of systematic reviews. 2010, Issue 4. Art. No.: CD004014. 21. De Riddler D. Should we use meshes in the management of vaginal prolapse? Curr Opin Urol. 2008;18(4):377-82. 22. Hefni M, Barry JA, Koukoura O, et al. Longterm quality of life and patient satisfaction following anterior vaginal mesh repair for cystocoele. Arch Gynaecol Obstet. 2013;287(3):441-446. 23. Gad N, Duvvuru A, Burchgart B. Outcome of Prolift mesh repair in treatment of pelvic organ prolapse and its effects on lower urinary tract symptoms. 2013;39(1):243-249. 24. Onol FF, Tosun F, Guzel R, et al. Minimum 1.5 year results of “surgeon tailored” transvaginal mesh repair for female stress urinary incontinence and pelvic organ prolapse. Urology. 2012;80(2):273-279. 25. Mahdy A, Karp D, Davila GW, et al. The outcome of transobturator anterior vaginal wall prolapse repair using porcine dermis graft: intermediate follow up. Int Braz J Urol. 2013;39(4):506-12. 26. Withagen MI, Milani AL, den Boon J, et al. Trocar guided mesh compared with conventional vaginal repair in recurrent prolapse: a randomised controlled trial. Obstet Gynaecol. 2011;117(2 Pt 1):242-250. 27. Vallebregt A, Fischer K, Giethink D, et al. Primary surgical repair of anterior vaginal prolapse: a randomised trial comparing anatomical and functional outcomes between anterior colporaphy and trocar guided transobturator anterior mesh. BJOG. 2011;118(2):1518-1527. 28. Altman D, Vägryuan T, Engl ME, et al. Anterior colporaphy versus transvaginal mesh for pelvic organ prolapse. N Engl J Med. 2011;364 (19):1826-36. 29. El-Nazer HA, Gomoa IA, Ismail Madkone WA, et al. Anterior colporaphy versus repair with mesh for anterior vaginal wall prolapse: a comparative clinical study. Arch Gynaecol Obstet. 2012;286(4):965-972. 30. Long CY, Juan YS, Wu MP, et al. Changes in female sexual function following anterior with and without posterior vaginal mesh surgery for the treatment of pelvic organ prolapse. J Sex Med. 2012;9(8):2167-74. 31. Alperin M, Ellison R, Meyn L, et al. Two-year outcomes after vaginal prolapse reconstruction with mesh pelvic floor repair system. Female Pelvic Med Reconstr Surg. 2013;19(2):72-8. 32. Gutman RE, Nosti PA, Sokol AI, et al. Three year outcomes of vaginal mesh for prolapse: a randomised controlled trial. Obstet Gynaecol. 2013;122(4):770-7. 33. Gawande A. Complications – a surgeon’s notes on an imperfect science. London: Profile Books Ltd; 2002. 35 volume 1 issue 1 | 2014 JMSG | PERSPECTIVE Transitioning from medical student to intern Warn your loved ones to avoid the hospital on the 14th of July – the day medical students become interns. After receiving the longawaited “Dr.” title on graduation day, medical students also begin to face the biggest transition in their career. Within one month, you are expected to apply undergraduate medical knowledge into real life clinical practice, assume clinical responsibility for the first time, and cope with the intense workload of a professional job. As medical students, you are often just observers on clinical rotations with limited hands-on experience in practical skills and patient management. You will finally have a defined role on a clinical team as an intern. In the first few weeks, the learning curve is steep as you scramble to master secretarial tasks that are never taught. From having first preference of seats in the reading room to restarting at the bottom of the medical hierarchy, this transition is exciting, challenging, and nerve wrecking. “Keep motivated, remember the basics, and always ask for help in a difficult situation.” Here are a few reminders for your transition:  Keep motivated, remember the basics, and always ask for help in a difficult situation. Your senior colleagues will be happy to advise you once you provide vital signs, a brief medical history, and have performed necessary first-line blood and imaging investigations.  Keep your ego at bay and respect the ward clerk and nurses, as they will teach you invaluable lessons. They have a wealth of experience in patient management and will guide you when you are panicking.  You will become familiar with prescriptions over time. In the meantime, use your smartphone and the BNF to look up dosages, contraindications, and side effects for medications.  You will become more confident and knowledgeable as you acquire tricks and experience with practical hospital work. Tasks will only become easier and be completed quicker over time.  Intern jobs vary in number of hours, level of responsibility, and administrative tasks. If possible, meet the current interns at the particular job you will have in July. The new intern-shadowing program for final meds should provide a solid foundation. Finally, enjoy your intern year. Celebrate the end to weekends in the reading room. Take advantage of every free evening you have to yourself. Embrace your integral role on a clinical team with confidence, enthusiasm, and an open mind. You have waited a long time to become a doctor. Syed Yaseen Naqvi, Medical Intern, UHG Cliona Small Medical Intern, UHG volume 1 issue 1 | 2014 36 JMSG | PERSPECTIVE Mentorship is a privilege for the mentor The start of the journey I grew up in Cork in a family with no background in medicine. Sport was one of my major hobbies and growing up that was mainly GAA. Unfortunately, I was not as good at it as Prof Kerin! I went to medical school in UCC. At the time, as in all medical schools, the curriculum was not as structured, and was more ‘apprenticeship’-based. My mentor from the earliest stages of my career was Professor DJ O’Sullivan, Professor of Medicine at UCC. He was the best clinician I have ever come across with a bedside manner to be admired; always respectful, courteous, and engaged in a very personal way with patients. We were not taught professionalism formally, but he was the exemplar for me – practice as he did and professionalism would be assured. Consultants should be mindful of the mentorship roles they play and the influence they have on the career choices of junior colleagues. I followed in the subspecialty footsteps of my mentor and chose endocrinology. This was due to my interest in chronic disease management and getting to know patients over a lifetime of their illness. Professor Tim O’Brien, Dean of the College of Medicine, Nursing and Health Sciences, NUI Galway USA “Consultants should be mindful of the mentorship roles they play and the influence they have on the career choices of junior colleagues.” As there were no structured training programmes in Ireland, I moved to the US. Leaving Ireland was difficult, and so I can empathize with the homesickness experienced by many of our overseas students. However, living abroad is an excellent opportunity and experience. I did my residency in internal medicine in the Medical College of Wisconsin in Milwaukee (where I became a Green Bay Packers fan). I then moved to the Mayo Clinic for Endocrinology Fellowship, where I met the 2nd most influential person in my career – Dr Colum Gorman. Colum combined excellent clinical skills and bedside manner with huge curiosity. He was always asking “How do we do things better; how can we enhance the life of patients in the future?” At the end of my fellowship he recruited me onto the Mayo Clinic faculty. Finishing Notes Dealing with anxiety about the challenges of starting life as an intern, moving from theoretical to practical approaches, is difficult. Always engage with senior colleagues. Never be afraid to ask for advice and help. Please remember that the needs of the patient must always come first. Take very careful notes – if it is not documented it did not happen. Remember to enjoy the experience of career development. Galway The Professor of Medicine post in Galway was advertised in 2000. I applied and was fortunate to be offered the position. I returned in July 2001 and was delighted to be moving to Ireland, but really was very sad to be leaving Mayo Clinic. However, I had a very warm welcome when I came to Galway, including an invitation from Mr Padraig Regan to play indoor soccer. When I met a consultant a few days later with a cast on his fractured arm, I decided to decline! JMSG is a great vehicle to promote cohesion and collegiality and I hope it will also foster greater faculty/consultant-student interaction. 37 volume 1 issue 1 | 2014 JMSG | PERSPECTIVE Medical students in a changing world “Medical professionalism is a core element of being a good doctor. Good medical practice is based on a relationship of trust between the profession and society, in which doctors are expected to meet the highest standards of professional practice and behaviour. It involves a partnership between patient and doctor that is based on mutual respect, confidentiality, honesty, responsibility and accountability”. - Medical Council’s Guide to Professional Conduct and Ethics for Registered Medical Practitioners (2009). As clinicians, researchers, medical educators and students we are part of a noble profession that contributes to the health and wellbeing of society, locally and globally. We are witnessing phenomenal technological advances in society, medicine and in education. Societal changes have led to a whole new portfolio of ‘lifestyle’ diseases and ailments such as those associated with stress, bioterrorism and global pandemics. The medical profession and biomedical scientists are responding with new therapies and new ways of organising care delivery, including telemedicine. In the midst of all these advances, however, the kindness and compassion of a caring medical practitioner towards a patient struggling with a life-limiting or disabling condition remains at the heart of what we do. What does this mean for you as medical students? The purpose of medical education is to provide you with the knowledge, skills and attitudes needed to practice as good doctors. As a member of our diverse student body you will have daily face-to-face contact with patients in the clinical years, in one of four Academies affiliated to NUI Galway. You gain exposure to a rich array of cases and become embedded in the realities of (busy) clinical practice. Teaching and learning is ‘on the job’ and less formal or didactic. You need to adapt to this apprenticeship approach and seek out good learning opportunities as selfdirected learners. You can learn much from the many ‘pearls of wisdom’ generously shared by interns or SHOs who, during a teachable moment, highlight something they have learned that has made a difference to their practice. Patients have an invaluable role to play in the education process and the vast majority of them understand and support this. Occasionally, however, individuals decline when asked to give a history or undergo a physical examination: respect for this attitude is really important. It is also vital that students behave in a professional manner on clinical attachments at all time. Patients and relatives may not realise who is the doctor and who is the medical student on the team. From the moment that you step onto a ward, clinic or surgery you are judged by the same high volume 1 issue 1 | 2014 Dr. Sean F. Dinneen, Head of School of Medicine, NUI Galway “What does this mean for you as medical students?” standards that all doctors are judged by. This means that your interaction with fellow students, doctors, nurses, healthcare professionals, administrative staff, the public and especially patients needs to be exemplary. Finally, I would encourage you all to make the most of your time in NUI Galway; this is a very special time in your career. Availing of extra-curricular activities is a good preparation for life in a profession where (sadly) work pressures can sometimes become overwhelming. Looking after one’s own health is something that many doctors are not good at doing. A career in medicine is a wonderful privilege but it needs to be balanced with a set of interests and activities outside of medicine that enable you to switch off and refresh yourself. This can and should start during medical school. 38 JMSG | ELECTIVE EXPERIENCE The Swiss Alps A breath of fresh air Tariq Esmail School of Medicine, NUI Galway Elective Details Lausanne, Switzerland; February 2013, 4 weeks Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois (CHUV) Service de Chirugie Thoracique et Vasculaire/Thoracic and Vascular Surgery Department Supervisor: Prof. Hans-Beat Ris I had just come back to my apartment from my first day on the renowned Swiss Alps slopes outside the city of Lausanne. As I was getting out of the shower I heard an unfamiliar ringtone; it definitely wasn’t mum calling to see if I was alive. Little did I know that answering would be the absolute highlight of my elective. I completed a one month elective in Thoracic and Vascular Surgery at the CHUV, in Lausanne, Switzerland. The hospital was a mini village of smaller hospitals surrounding a main building, which housed 1430 beds. On my first day I received two essential items. My ID card, which was a key to everything: access to the computer system and electronic medical records, a meal card for the doctor/staff only cafeteria, in addition to clean lab coats through the electronic system that dispensed your exact size when prompted. Keeping up with modern technology, Lausanne had replaced the ancient pager with a Nokia mobile phone that was connected to the hospital’s own mobile network. It was associated with a major mobile provider and allowed incoming calls from any outside phone. It was our own personal internal line. I was also introduced to my favourite perk, access to Swiss company Nespresso machines everywhere in the hospital. It was the second week of being in a new country and in a new hospital on a new service when I got that unfamiliar phone call. It was the transplant coordinator. They have a pair of lungs. A PAIR OF LUNGS. 39 volume 1 issue 1 | 2014 Excuse me? Was I just called in to participate in a double lung transplant? Yes I was. I was the student on the list for emergency transplants that night. I couldn’t have felt luckier. Two of the thoracic surgeons had taken a helicopter to retrieve donor lungs that had just become available on the other side of the Swiss mountains. They would be back shortly. Meanwhile, I was in the OR and scrubbed in with the Chief of the service, Prof. Hans-Beat Ris. Within two hours of that initial call, Prof. Ris was making a clamshell incision (bilateral anterior thoracotomy) on the patient to open in preparation for the transplant. I was at the patient’s side learning step by step the remarkable process of such a procedure. The patient’s failing lungs need to be isolated one at a time. The donor lungs arrived and were prepared. After Centre Hospitalier Universitaire Vaudois (CHUV), four hours, it was break time and the new guys stepped in to Lausanne, Switzerland give the gift of new lungs to this patient. The Chief reaches into his lab coat pocket and tosses me a Nespresso capsule – “Voilà, vous allez avoir besoin de ça” - he said. It was 3:15 am and they had only just gotten started. I was able to observe the rest of the procedure and tried to soak it all in. There was nothing better than breathing in the fresh early morning air on my way home to bed, knowing also that our patient will soon be able to do the same. Can you think of a better day? Lake Geneva / Lac Léman, Lausanne Switzerland volume 1 issue 1 | 2014 40 JMSG | SPONSORS BioInnovate Ireland offers a unique medical device innovation training opportunity JMSG | SUPPORTERS NUI Galway Surgical Society NUI Galway Medical Society 41 volume 1 issue 1 | 2014 JMSG | ANATOMY COMPETITION “Vesalius's depiction of the human skull resting on a canine skull, positioned at an angle so that the insides of the eye socket could be seen. I drew this based on an illustration from De Humani Corporis Fabrica (On the Fabric of the Human Body). A subtle juxtaposition of human and animal structures by Vesalius to prove that the lower jaw was only one bone, not two, which Galen had assumed from dissecting dogs.” Stephanie Vincent, 1MB 2014 Winner volume 1 issue 1 | 2014 42