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.
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4. Novak A, Dedhar S. Signaling through β-catenin and Lef/Tcf. Cellular and
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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
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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.
Clinical Cancer Research. 2011;17(9):2693-2701.
21. Correa P, et al. A model for gastric cancer epidemiology. Lancet. 1975;2
(7924):58-59.
22. Machado JC, et al. E-cadherin gene mutations provide a genetic basis for
the phenotypic divergence of mixed gastric carcinomas. Laboratory
Investigation. 1999;79(4):459-465.
23. Schrader KA, et al. Hereditary diffuse gastric cancer: Association with
lobular breast cancer. Familial Cancer. 2008;7(1):73-82.
24. Guilford P, Humar B, Blair V. Hereditary diffuse gastric cancer:
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25. Guilford PJ, et al. E-cadherin germline mutations define an inherited
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26. Tamura G, et al. E-cadherin gene promoter hypermethylation in primary
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27. Lee TL, et al. Detection of gene promoter hypermethylation in the tumor
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28. Maxwell KN, Domchek SM. Familial Breast Cancer Risk. Current Breast
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30. Pharoah PDP, et al. Polygenic susceptibility to breast cancer and
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31. Brzozowska A, et al. Evaluation of prognostic parameters of E-cadherin
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32. Liu T, et al. Dysregulated expression of Slug, vimentin, and E-cadherin
correlates with poor clinical outcome in patients with basal-like breast
cancer. Journal of Surgical Oncology. 2013;107(2):188-194.
33. Lu L, et al. 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
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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
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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
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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.
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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.
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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.
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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