SlideShare a Scribd company logo
1 of 3
Download to read offline
Making internal biopsies redundant
                                     Associate Professor Rupert Leong is using laser light to probe the intestinal lining, a pioneering
                                     technique which can provide both structural and functional details of gastrointestinal diseases
  associate professor rupert leong




                                                                                           for patients. Some patients need minimal               barrier. The microscope allows us to visualise
                                                                                           medication to reconstitute the barrier function,       living tissue of the bowel and we can then
                                                                                           but others require the ‘big-guns’ of treatment         evaluate the endoscopy in the standard fashion,
                                                                                           called biological agents. This concept of              plus obtain functional information on the bowel
                                                                                           personalised medicine works well using confocal        wall lining. We have already obtained good
                                                                                           endomicroscopy and proteomics.                         evidence that drugs used to treat inflammatory
                                                                                                                                                  bowel disease can all reverse the barrier
                                                                                           Have you been able to explore certain features         dysfunction. In particular, biological agents are
                                                                                           of inflammatory bowel diseases that other              the best drugs to repair the barrier breakdown of
                                                                                           procedures are unable to identify?                     the bowel lining.

                                                                                           Yes, the functional effect of the bowel lining –       The technology is constantly improving and we
                                                                                           the barrier function. This is the barrier that stops   have moved on to looking at other diseases that
                                                                                           bacteria and other organisms from entering the         include detecting Barrett’s mucosa pre-cancerous
                                                                                           bloodstream. At present, the concept behind            changes of the oesophagus and gastric intestinal
                                                                                           inflammatory bowel disease is that this barrier        metaplasia, which may also be pre-cancerous
                                                                                           may be broken and leak bacterial products              changes of the stomach.
                                                                                           into the intestinal wall, resulting in chronic
                                     To begin, could you provide a broad outline           inflammation in the bowel. Taking conventional         And lastly, what have been your proudest
                                     of your recent project and your reasons for           forceps biopsies kills the cells and they no           achievements during your work so far?
                                     venturing into this area of research?                 longer function so you cannot evaluate the
                                                                                           barrier function.                                      My research has attracted a level two (the
                                     Confocal endomicroscopy allows endoscopists                                                                  highest) clinical Career Development Fellowship
                                     to view the cell structure of the lining of the       When an intravenous contrast is introduced             from the National Health and Medical Research
                                     bowel. The main function of the bowel is to           at the time of the confocal endomicroscopy             Council of Australia because the research
                                     protect the rest of the body from the bacteria        procedure, the contrast leaks out of the bowel         materials are novel and the topic is high in
                                     inside the bowel ‘lumen’ – the cavity where the       into the gut. This is significantly more common        impact. Only five of these fellowships were
                                     faeces reside. Using confocal endomicroscopy,         in inflammatory bowel diseases than in age-            awarded nationally at this level for clinical
                                     we are now validating the characteristics of the      matched controls, ie. people who do not have           research when I applied. In addition, I
                                     bowel wall barrier. This is really exciting because   inflammatory bowel diseases. What we are               enjoy seeing my previous trainees
                                     this has never been seen before. With confocal        noticing may be the reason why patients have           and fellows doing well in their
                                     endomicroscopy technology, we can see things          inflammation in their bowels – the gut lining          careers, and some have even
                                     that conventional microscopy misses because           may no longer block the entry of foreign matter        followed my footsteps
                                     we are viewing living tissue. For instance, the       into the bowel wall. This could then trigger the       into gastroenterology
                                     functional effect of the bowel lining is not seen     inflammation cascade that results in ulcers            research. 
                                     when taking forceps biopsies, because removing        forming in the inner lining of the gut. In severe
                                     the cells from the bowel wall kills the cells and     cases, the intravenous contrast floods through
                                     they are no longer functional. In vivo in situ        into the bowel very rapidly and in multiple
                                     visualisation of the intestinal lining cells gives    areas. This way we can measure the severity of
                                     us not only the information of their structure        the leakage.
                                     and architecture, but their adequacy of barrier
                                     function as well.                                     What advantages have you gained by fitting
                                                                                           the flexible endoscope with a confocal laser
                                     Further to this, how are you integrating              microscope, and where do you go next
                                     your dual research directions of confocal             with the research?
                                     endomicroscopy and proteomics?
                                                                                           Our ongoing research seeks
                                     In combination, proteomics and confocal               to objectively measure
                                     endomicroscopy allows us to evaluate both the         the dysfunction of the
                                     structure and the barrier function of the bowel,      gastrointestinal
                                     and this is a new way of assessing the disease        tract and to see if
                                     process. Confocal endomicroscopy can visualise        medications can
                                     and measure the severity of the breakdown in the      reverse this
                                     barrier of the bowel lining. Plasma proteomics        breakdown
                                     then measures the bacteria products that escape       in the
                                     into the bloodstream to quantitate the aftermath
                                     of the breakdown.

                                     In addition to the diagnosis and assessment of
                                     the severity of bowel inflammation, I also
                                     hope to be able to individualise treatment

	64	International innovation
associate professor rupert leong




                                                                 Illuminating
                                                                inflammatory
                                                                bowel disease
                                 A new imaging technique pioneered in Australia is
                               revolutionising our understanding of bowel diseases
                               by bringing together laboratory and clinical research
                                     to analyse the microscopic structure of the gut

    Endoscopy is a medical technique                           disease – a genetically determined wheat
    in widespread use for the diagnosis and                    allergy disease – can be diagnosed immediately. 
    treatment of bowel complaints. It consists
    of a camera mounted on the end of a                        Typically, analysis of the cellular architecture
    flexible tube to allow direct visualisation                (histology) requires biopsies to be taken by
    of the internal gastrointestinal lining (the               forceps from the wall of the gastrointestinal
    mucosa). A new technique called confocal                   tract. However, the forceps often disrupt the
    endomicroscopy (CEM) is a revolutionary                    structure of the sample as well as removing
    improvement in endoscopic imaging as it                    the tissue from its living environment, resulting
    incorporates a confocal laser microscope into              in artefacts that may lead to misdiagnosis.
    the tip of the endoscope.                                  Furthermore, biopsies may result in false
                                                               negative results from non-representative
    Associate Professor Rupert Leong from The                  specimens or failure to orientate tissue samples.
    University of New South Wales is pioneering                In addition, using forceps biopsies carries the
    this technique. His research focuses on the                rare risk of bleeding and bowel perforation.
    microscopic cellular architecture of the                   The advantage of CEM is that it allows for the
    bowel wall which is invisible to conventional              analysis of the gastrointestinal mucosa in its
    endoscopes. CEM          instantly diagnoses               natural living environment.
    neoplastic growth in the gastrointestinal
    tract through the irregular arrangement, size
                                                               Pioneering research
    and shape of cells. The microscopic hair-like
    projections of the small bowel (called villi) can          In Australia, Leong has been the top contributing
    be instantly recognised using CEM and coeliac              research gastroenterologist for two consecutive
                                                               years at their annual national society
                                                               conference and has achieved the highest level
                                                               clinical Career Development Fellowship from
                                                               the Australian National Health and Medical
                                                               Research Council – only five such fellowships
                                                               were awarded nationally in the year of Leong’s
                                                               application. This reflects both the novelty and
                                                               impact of his research.

                                                               As an Associate Professor at The University
                                                               of New South Wales, and as Head of the
                                                               Inflammatory Bowel Diseases Services at
                                                               Concord and Bankstown Hospitals, Sydney,
                                                               Australia, Leong is ideally positioned to bring
                                                               together laboratory and clinical research.
                                                               Previously, he has shown CEM to be as least
     Image of confocal endomicroscopy of the bowel
     showing leakage of intravenous contrast into the lumen.
                                                               as accurate as forceps biopsies in the diagnosis
                                                               of coeliac disease, and has reviewed the safety
	www.researchmedia.eu	
                    65
Intelligence                                  of the intravenous contrast agent fluorescein          bowel disease patients, Leong noticed that the
                                                        that can be used to stain cellular structures          fluorescein contrast agent given intravenously
          Proteomics and confocal                       for visualisation during CEM. Recently, Leong          was leaking through the gut lining and into
          endomicroscopy in the                         has turned his expert eye towards CEM in the           the lumen of the intestine. One of the most
          evaluation of inflammatory                    diagnosis and evaluation of inflammatory               important functions of the mucosa is as a barrier
          bowel diseases                                bowel diseases.                                        to separate the contents of the lumen, including
          OBJECTIVES                                                                                           digestive enzymes, bacteria and faecal waste,
                                                                                                               from the rest of the body. Therefore, a ‘leaky’
          To measure the integrity of the
                                                        Inflammatory bowel diseases
                                                                                                               lining, seen to a significantly higher degree in
          intestinal mucosal barrier. Confocal          Currently, little is known of the causes of            inflammatory bowel disease patients relative to
          laser endomicroscopy visualises leakage       inflammatory bowel diseases, which include             age-matched controls, represents a loss of this
          across the intestinal lining. Evaluation of   Crohn’s disease and ulcerative colitis. Both           barrier function.
          intestinal microorganisms contaminating       genetic and environmental factors have been
          the bloodsteam is performed with a            recognised. With no known causes, it follows           With this discovery, Leong is focusing his
          sensitive tool called proteomics. Together,   that there are no known cures for these diseases;      research on using CEM to study the integrity
          they support the theory that the bowel        current medication focuses on controlling the          of the intestinal mucosa in the pathogenesis
          wall barrier is broken in inflammatory        symptoms and disease progression.                      of inflammatory bowel disease: “We are now
          bowel diseases.                                                                                      validating the features of a ‘leaky gut’ – this is
                                                        A major symptom is the development of ulcers           really exciting because it has never been seen
          KEY PARTNERS                                  in the gastrointestinal tract. Ulcers are typically    before”. He theorises that invasion of the gut
                                                        the cause of bleeding from the bowel, severe           wall by foreign matter from the intestinal lumen
          Bankstown-Lidcombe Hospital                   abdominal pain, weight loss and diarrhoea.             may trigger the inflammatory cascade, resulting
          Concord Repatriation General Hospital         In addition, patients often become iron-               in ulceration of the mucosa.
                                                        deficient and hence anaemic, afflicting them
          NSW Health                                    with additional symptoms such as fatigue. In
                                                                                                               Proteomics
                                                        extreme cases, patients may develop cancer
          University of New South Wales
                                                        or require extensive surgery to remove whole           To explore the effects of the leaky gut, Leong
          FUNDING                                       sections of the bowel. Up to three in 1,000            is searching for the presence of bacterial
                                                        people suffer from inflammatory bowel                  proteins in the blood of inflammatory bowel
          National Health and Medical Research          diseases. Unfortunately, many patients are             disease patients. And in order to do this, he is
          Council of Australia                          in the formative years of their lives and the          using proteomics – the identification of the
          CONTACT                                       debilitating impact of Crohn’s or ulcerative           constituent proteins of a system from protein
                                                        colitis can be highly inconvenient.                    fragments known as peptides. Peptides, or
          Associate Professor Rupert Leong                                                                     combinations of peptides, are unique to
          MBBS, MD, FRACP, AGAF                         Normally, inflammatory bowel diseases                  their parent proteins. As different organisms
          Director of Endoscopy, Concord and            are diagnosed by a colonoscopy to look for             (and indeed different cells) are composed of
          Bankstown Hospitals                           inflammation and ulcers, followed by biopsies          different sets of proteins, proteomics can be
          Conjoint Associate Professor of Medicine      for further study by pathologists. Leong instead       used to detect the presence of foreign bodies.
                                                        has been using CEM not only to diagnose and            If the leaky mucosa of inflammatory bowel
          Bankstown Hospital                            evaluate inflammatory bowel diseases at                disease patients is indeed allowing gut bacteria
          Eldridge Road                                 Bankstown Hospital – his instrument is the only        and other foreign matter to cross the gut wall,
          Bankstown                                     one in the state of New South Wales – but now          then there will be higher concentrations of
          NSW 2200                                      to also assess the barrier function of the bowel       gut bacterial proteins in the blood of these
          Australia                                     lining. From these clinical investigations, he         patients relative to healthy individuals.
                                                        has shown that CEM is superior to biopsies and
          T +61 2 9767 6111                             has furthermore revealed that the lining of the        Leong hopes to use the presence of these
          F +61 2 9767 6767                             gastrointestinal tract of inflammatory bowel           proteins as a measure of leakiness and to help
          E rupertleong@unsw.edu.au                     disease patients becomes ‘leaky’.                      confirm the findings of the impaired barrier
                                                                                                               function of the bowel. By combining CEM and
          RUPERT LEONG is a consultant Senior                                                                  proteomics, both the structure and function of
                                                        Discovering a ‘leaky’ lining
          Staff Specialist gastroenterologist at                                                               the mucosa can be evaluated, and the result of
          Bankstown, Concord and Macquarie              CEM has allowed Leong to view the function             the loss of bowel integrity can be measured.
          University Hospitals, and Associate           as well as the structure of the gut lining.            Reversal of the abnormal changes and
          Professor of Medicine at the University       Biopsies disrupt the natural environment of            normalising the protein constitutent of the
          of New South Wales and Macquarie              and kill the extracted cells, resulting in a loss of   blood may be an end point of treatment. He
          University, Sydney, Australia. His            function. Therefore, biopsies can only provide         has already extended this combined approach
          expertise includes interventional             information on the structure of tissue. In             to other diseases such as pre-cancerous
          endoscopy and management of                   contrast, CEM visualises living tissue, providing      changes of Barrett’s oesophagus, gastric
          inflammatory bowel diseases. Leong is         information on both structure and function.            intestinal metaplasia and pre-cancerous
          committed to individualised, high-quality     When examining the mucosa of inflammatory              changes of the stomach.
          management, and fostering
          novel research.


                                                           By combining confocal endomicroscopy and proteomics, both the
                                                         structure and function of the mucosa can be evaluated, giving a more
                                                         in-depth analysis of the pathogenesis of inflammatory bowel disease


	   66	   International innovation

More Related Content

Viewers also liked (15)

Evaluation
EvaluationEvaluation
Evaluation
 
Evaluation
EvaluationEvaluation
Evaluation
 
Presentation1
Presentation1Presentation1
Presentation1
 
Greco luciana (2)
Greco luciana (2)Greco luciana (2)
Greco luciana (2)
 
fourseasonsapthomes
fourseasonsapthomesfourseasonsapthomes
fourseasonsapthomes
 
Risk assessment
Risk assessmentRisk assessment
Risk assessment
 
Corso Joomla - Joomla!® 1.5.x - Introduzione al CMS
Corso Joomla - Joomla!® 1.5.x - Introduzione al CMSCorso Joomla - Joomla!® 1.5.x - Introduzione al CMS
Corso Joomla - Joomla!® 1.5.x - Introduzione al CMS
 
Full set of Townhouse plans
Full set of Townhouse plansFull set of Townhouse plans
Full set of Townhouse plans
 
Role of Advertisement in Recession
Role of Advertisement in RecessionRole of Advertisement in Recession
Role of Advertisement in Recession
 
Analysis – Album 3
Analysis – Album 3Analysis – Album 3
Analysis – Album 3
 
Photo shoot for my music magazine
Photo shoot for my music magazinePhoto shoot for my music magazine
Photo shoot for my music magazine
 
Andrew goodwin's theory
Andrew goodwin's theoryAndrew goodwin's theory
Andrew goodwin's theory
 
Evaluation
EvaluationEvaluation
Evaluation
 
Aspen Pines Powerpoint
Aspen Pines PowerpointAspen Pines Powerpoint
Aspen Pines Powerpoint
 
Poweka
PowekaPoweka
Poweka
 

Recently uploaded

In Kuwait Abortion pills (+918133066128)@Safe abortion pills in Kuwait City
In Kuwait Abortion pills (+918133066128)@Safe abortion pills in Kuwait CityIn Kuwait Abortion pills (+918133066128)@Safe abortion pills in Kuwait City
In Kuwait Abortion pills (+918133066128)@Safe abortion pills in Kuwait City
Abortion pills in Kuwait Cytotec pills in Kuwait
 
Connective Tissue II - Dr Muhammad Ali Rabbani - Medicose Academics
Connective Tissue II - Dr Muhammad Ali Rabbani - Medicose AcademicsConnective Tissue II - Dr Muhammad Ali Rabbani - Medicose Academics
Connective Tissue II - Dr Muhammad Ali Rabbani - Medicose Academics
MedicoseAcademics
 
Failure to thrive in neonates and infants + pediatric case.pptx
Failure to thrive in neonates and infants  + pediatric case.pptxFailure to thrive in neonates and infants  + pediatric case.pptx
Failure to thrive in neonates and infants + pediatric case.pptx
claviclebrown44
 

Recently uploaded (20)

Report Back from SGO: What’s the Latest in Ovarian Cancer?
Report Back from SGO: What’s the Latest in Ovarian Cancer?Report Back from SGO: What’s the Latest in Ovarian Cancer?
Report Back from SGO: What’s the Latest in Ovarian Cancer?
 
In Kuwait Abortion pills (+918133066128)@Safe abortion pills in Kuwait City
In Kuwait Abortion pills (+918133066128)@Safe abortion pills in Kuwait CityIn Kuwait Abortion pills (+918133066128)@Safe abortion pills in Kuwait City
In Kuwait Abortion pills (+918133066128)@Safe abortion pills in Kuwait City
 
Connective Tissue II - Dr Muhammad Ali Rabbani - Medicose Academics
Connective Tissue II - Dr Muhammad Ali Rabbani - Medicose AcademicsConnective Tissue II - Dr Muhammad Ali Rabbani - Medicose Academics
Connective Tissue II - Dr Muhammad Ali Rabbani - Medicose Academics
 
Gait deviations in Transtibial prosthesis users
Gait deviations in Transtibial prosthesis usersGait deviations in Transtibial prosthesis users
Gait deviations in Transtibial prosthesis users
 
Get the best psychology treatment in Indore at Gokuldas Hospital
Get the best psychology treatment in Indore at Gokuldas HospitalGet the best psychology treatment in Indore at Gokuldas Hospital
Get the best psychology treatment in Indore at Gokuldas Hospital
 
ESC HF 2024 Spotlights Day-2.pptx heart failure
ESC HF 2024 Spotlights Day-2.pptx heart failureESC HF 2024 Spotlights Day-2.pptx heart failure
ESC HF 2024 Spotlights Day-2.pptx heart failure
 
^In Pietermaritzburg Hager Werken Embalming +27789155305 Compound Powder in ...
^In Pietermaritzburg  Hager Werken Embalming +27789155305 Compound Powder in ...^In Pietermaritzburg  Hager Werken Embalming +27789155305 Compound Powder in ...
^In Pietermaritzburg Hager Werken Embalming +27789155305 Compound Powder in ...
 
SEMESTER-V CHILD HEALTH NURSING-UNIT-1-INTRODUCTION.pdf
SEMESTER-V CHILD HEALTH NURSING-UNIT-1-INTRODUCTION.pdfSEMESTER-V CHILD HEALTH NURSING-UNIT-1-INTRODUCTION.pdf
SEMESTER-V CHILD HEALTH NURSING-UNIT-1-INTRODUCTION.pdf
 
ANAPHYLAXIS BY DR.SOHAN BISWAS,MBBS,DNB(INTERNAL MEDICINE) RESIDENT.pptx
ANAPHYLAXIS BY DR.SOHAN BISWAS,MBBS,DNB(INTERNAL MEDICINE) RESIDENT.pptxANAPHYLAXIS BY DR.SOHAN BISWAS,MBBS,DNB(INTERNAL MEDICINE) RESIDENT.pptx
ANAPHYLAXIS BY DR.SOHAN BISWAS,MBBS,DNB(INTERNAL MEDICINE) RESIDENT.pptx
 
TEST BANK for The Nursing Assistant Acute, Subacute, and Long-Term Care, 6th ...
TEST BANK for The Nursing Assistant Acute, Subacute, and Long-Term Care, 6th ...TEST BANK for The Nursing Assistant Acute, Subacute, and Long-Term Care, 6th ...
TEST BANK for The Nursing Assistant Acute, Subacute, and Long-Term Care, 6th ...
 
CONGENITAL HYPERTROPHIC PYLORIC STENOSIS by Dr M.KARTHIK EMMANUEL
CONGENITAL HYPERTROPHIC PYLORIC STENOSIS  by Dr M.KARTHIK EMMANUELCONGENITAL HYPERTROPHIC PYLORIC STENOSIS  by Dr M.KARTHIK EMMANUEL
CONGENITAL HYPERTROPHIC PYLORIC STENOSIS by Dr M.KARTHIK EMMANUEL
 
Sell 5cladba adbb JWH-018 5FADB in stock
Sell 5cladba adbb JWH-018 5FADB in stockSell 5cladba adbb JWH-018 5FADB in stock
Sell 5cladba adbb JWH-018 5FADB in stock
 
ROSE CASE SPINAL SBRT BY DR KANHU CHARAN PATRO
ROSE  CASE SPINAL SBRT BY DR KANHU CHARAN PATROROSE  CASE SPINAL SBRT BY DR KANHU CHARAN PATRO
ROSE CASE SPINAL SBRT BY DR KANHU CHARAN PATRO
 
The Clean Living Project Episode 24 - Subconscious
The Clean Living Project Episode 24 - SubconsciousThe Clean Living Project Episode 24 - Subconscious
The Clean Living Project Episode 24 - Subconscious
 
Failure to thrive in neonates and infants + pediatric case.pptx
Failure to thrive in neonates and infants  + pediatric case.pptxFailure to thrive in neonates and infants  + pediatric case.pptx
Failure to thrive in neonates and infants + pediatric case.pptx
 
Post-Cycle Therapy (PCT) in bodybuilding docx.pdf
Post-Cycle Therapy (PCT) in bodybuilding  docx.pdfPost-Cycle Therapy (PCT) in bodybuilding  docx.pdf
Post-Cycle Therapy (PCT) in bodybuilding docx.pdf
 
Renal Replacement Therapy in Acute Kidney Injury -time modality -Dr Ayman Se...
Renal Replacement Therapy in Acute Kidney Injury -time  modality -Dr Ayman Se...Renal Replacement Therapy in Acute Kidney Injury -time  modality -Dr Ayman Se...
Renal Replacement Therapy in Acute Kidney Injury -time modality -Dr Ayman Se...
 
Capillary Blood Collection Tubes: The Complete Guidebook
Capillary Blood Collection Tubes: The Complete GuidebookCapillary Blood Collection Tubes: The Complete Guidebook
Capillary Blood Collection Tubes: The Complete Guidebook
 
Tips to Choose the Best Psychiatrists in Indore
Tips to Choose the Best Psychiatrists in IndoreTips to Choose the Best Psychiatrists in Indore
Tips to Choose the Best Psychiatrists in Indore
 
Unveiling Alcohol Withdrawal Syndrome: exploring it's hidden depths
Unveiling Alcohol Withdrawal Syndrome: exploring it's hidden depthsUnveiling Alcohol Withdrawal Syndrome: exploring it's hidden depths
Unveiling Alcohol Withdrawal Syndrome: exploring it's hidden depths
 

2012 International Innovation www.researchmedia.eu

  • 1. Making internal biopsies redundant Associate Professor Rupert Leong is using laser light to probe the intestinal lining, a pioneering technique which can provide both structural and functional details of gastrointestinal diseases associate professor rupert leong for patients. Some patients need minimal barrier. The microscope allows us to visualise medication to reconstitute the barrier function, living tissue of the bowel and we can then but others require the ‘big-guns’ of treatment evaluate the endoscopy in the standard fashion, called biological agents. This concept of plus obtain functional information on the bowel personalised medicine works well using confocal wall lining. We have already obtained good endomicroscopy and proteomics. evidence that drugs used to treat inflammatory bowel disease can all reverse the barrier Have you been able to explore certain features dysfunction. In particular, biological agents are of inflammatory bowel diseases that other the best drugs to repair the barrier breakdown of procedures are unable to identify? the bowel lining. Yes, the functional effect of the bowel lining – The technology is constantly improving and we the barrier function. This is the barrier that stops have moved on to looking at other diseases that bacteria and other organisms from entering the include detecting Barrett’s mucosa pre-cancerous bloodstream. At present, the concept behind changes of the oesophagus and gastric intestinal inflammatory bowel disease is that this barrier metaplasia, which may also be pre-cancerous may be broken and leak bacterial products changes of the stomach. into the intestinal wall, resulting in chronic To begin, could you provide a broad outline inflammation in the bowel. Taking conventional And lastly, what have been your proudest of your recent project and your reasons for forceps biopsies kills the cells and they no achievements during your work so far? venturing into this area of research? longer function so you cannot evaluate the barrier function.  My research has attracted a level two (the Confocal endomicroscopy allows endoscopists highest) clinical Career Development Fellowship to view the cell structure of the lining of the When an intravenous contrast is introduced from the National Health and Medical Research bowel. The main function of the bowel is to at the time of the confocal endomicroscopy Council of Australia because the research protect the rest of the body from the bacteria procedure, the contrast leaks out of the bowel materials are novel and the topic is high in inside the bowel ‘lumen’ – the cavity where the into the gut. This is significantly more common impact. Only five of these fellowships were faeces reside. Using confocal endomicroscopy, in inflammatory bowel diseases than in age- awarded nationally at this level for clinical we are now validating the characteristics of the matched controls, ie. people who do not have research when I applied. In addition, I bowel wall barrier. This is really exciting because inflammatory bowel diseases. What we are enjoy seeing my previous trainees this has never been seen before. With confocal noticing may be the reason why patients have and fellows doing well in their endomicroscopy technology, we can see things inflammation in their bowels – the gut lining careers, and some have even that conventional microscopy misses because may no longer block the entry of foreign matter followed my footsteps we are viewing living tissue. For instance, the into the bowel wall. This could then trigger the into gastroenterology functional effect of the bowel lining is not seen inflammation cascade that results in ulcers research.  when taking forceps biopsies, because removing forming in the inner lining of the gut. In severe the cells from the bowel wall kills the cells and cases, the intravenous contrast floods through they are no longer functional. In vivo in situ into the bowel very rapidly and in multiple visualisation of the intestinal lining cells gives areas. This way we can measure the severity of us not only the information of their structure the leakage. and architecture, but their adequacy of barrier function as well. What advantages have you gained by fitting the flexible endoscope with a confocal laser Further to this, how are you integrating microscope, and where do you go next your dual research directions of confocal with the research? endomicroscopy and proteomics? Our ongoing research seeks In combination, proteomics and confocal to objectively measure endomicroscopy allows us to evaluate both the the dysfunction of the structure and the barrier function of the bowel, gastrointestinal and this is a new way of assessing the disease tract and to see if process. Confocal endomicroscopy can visualise medications can and measure the severity of the breakdown in the reverse this barrier of the bowel lining. Plasma proteomics breakdown then measures the bacteria products that escape in the into the bloodstream to quantitate the aftermath of the breakdown. In addition to the diagnosis and assessment of the severity of bowel inflammation, I also hope to be able to individualise treatment 64 International innovation
  • 2. associate professor rupert leong Illuminating inflammatory bowel disease A new imaging technique pioneered in Australia is revolutionising our understanding of bowel diseases by bringing together laboratory and clinical research to analyse the microscopic structure of the gut Endoscopy is a medical technique disease – a genetically determined wheat in widespread use for the diagnosis and allergy disease – can be diagnosed immediately.  treatment of bowel complaints. It consists of a camera mounted on the end of a Typically, analysis of the cellular architecture flexible tube to allow direct visualisation (histology) requires biopsies to be taken by of the internal gastrointestinal lining (the forceps from the wall of the gastrointestinal mucosa). A new technique called confocal tract. However, the forceps often disrupt the endomicroscopy (CEM) is a revolutionary structure of the sample as well as removing improvement in endoscopic imaging as it the tissue from its living environment, resulting incorporates a confocal laser microscope into in artefacts that may lead to misdiagnosis. the tip of the endoscope. Furthermore, biopsies may result in false negative results from non-representative Associate Professor Rupert Leong from The specimens or failure to orientate tissue samples. University of New South Wales is pioneering In addition, using forceps biopsies carries the this technique. His research focuses on the rare risk of bleeding and bowel perforation. microscopic cellular architecture of the The advantage of CEM is that it allows for the bowel wall which is invisible to conventional analysis of the gastrointestinal mucosa in its endoscopes. CEM instantly diagnoses natural living environment. neoplastic growth in the gastrointestinal tract through the irregular arrangement, size Pioneering research and shape of cells. The microscopic hair-like projections of the small bowel (called villi) can In Australia, Leong has been the top contributing be instantly recognised using CEM and coeliac research gastroenterologist for two consecutive years at their annual national society conference and has achieved the highest level clinical Career Development Fellowship from the Australian National Health and Medical Research Council – only five such fellowships were awarded nationally in the year of Leong’s application. This reflects both the novelty and impact of his research. As an Associate Professor at The University of New South Wales, and as Head of the Inflammatory Bowel Diseases Services at Concord and Bankstown Hospitals, Sydney, Australia, Leong is ideally positioned to bring together laboratory and clinical research. Previously, he has shown CEM to be as least Image of confocal endomicroscopy of the bowel showing leakage of intravenous contrast into the lumen. as accurate as forceps biopsies in the diagnosis of coeliac disease, and has reviewed the safety www.researchmedia.eu 65
  • 3. Intelligence of the intravenous contrast agent fluorescein bowel disease patients, Leong noticed that the that can be used to stain cellular structures fluorescein contrast agent given intravenously Proteomics and confocal for visualisation during CEM. Recently, Leong was leaking through the gut lining and into endomicroscopy in the has turned his expert eye towards CEM in the the lumen of the intestine. One of the most evaluation of inflammatory diagnosis and evaluation of inflammatory important functions of the mucosa is as a barrier bowel diseases bowel diseases. to separate the contents of the lumen, including OBJECTIVES digestive enzymes, bacteria and faecal waste, from the rest of the body. Therefore, a ‘leaky’ To measure the integrity of the Inflammatory bowel diseases lining, seen to a significantly higher degree in intestinal mucosal barrier. Confocal Currently, little is known of the causes of inflammatory bowel disease patients relative to laser endomicroscopy visualises leakage inflammatory bowel diseases, which include age-matched controls, represents a loss of this across the intestinal lining. Evaluation of Crohn’s disease and ulcerative colitis. Both barrier function. intestinal microorganisms contaminating genetic and environmental factors have been the bloodsteam is performed with a recognised. With no known causes, it follows With this discovery, Leong is focusing his sensitive tool called proteomics. Together, that there are no known cures for these diseases; research on using CEM to study the integrity they support the theory that the bowel current medication focuses on controlling the of the intestinal mucosa in the pathogenesis wall barrier is broken in inflammatory symptoms and disease progression. of inflammatory bowel disease: “We are now bowel diseases. validating the features of a ‘leaky gut’ – this is A major symptom is the development of ulcers really exciting because it has never been seen KEY PARTNERS in the gastrointestinal tract. Ulcers are typically before”. He theorises that invasion of the gut the cause of bleeding from the bowel, severe wall by foreign matter from the intestinal lumen Bankstown-Lidcombe Hospital abdominal pain, weight loss and diarrhoea. may trigger the inflammatory cascade, resulting Concord Repatriation General Hospital In addition, patients often become iron- in ulceration of the mucosa. deficient and hence anaemic, afflicting them NSW Health with additional symptoms such as fatigue. In Proteomics extreme cases, patients may develop cancer University of New South Wales or require extensive surgery to remove whole To explore the effects of the leaky gut, Leong FUNDING sections of the bowel. Up to three in 1,000 is searching for the presence of bacterial people suffer from inflammatory bowel proteins in the blood of inflammatory bowel National Health and Medical Research diseases. Unfortunately, many patients are disease patients. And in order to do this, he is Council of Australia in the formative years of their lives and the using proteomics – the identification of the CONTACT debilitating impact of Crohn’s or ulcerative constituent proteins of a system from protein colitis can be highly inconvenient. fragments known as peptides. Peptides, or Associate Professor Rupert Leong combinations of peptides, are unique to MBBS, MD, FRACP, AGAF Normally, inflammatory bowel diseases their parent proteins. As different organisms Director of Endoscopy, Concord and are diagnosed by a colonoscopy to look for (and indeed different cells) are composed of Bankstown Hospitals inflammation and ulcers, followed by biopsies different sets of proteins, proteomics can be Conjoint Associate Professor of Medicine for further study by pathologists. Leong instead used to detect the presence of foreign bodies. has been using CEM not only to diagnose and If the leaky mucosa of inflammatory bowel Bankstown Hospital evaluate inflammatory bowel diseases at disease patients is indeed allowing gut bacteria Eldridge Road Bankstown Hospital – his instrument is the only and other foreign matter to cross the gut wall, Bankstown one in the state of New South Wales – but now then there will be higher concentrations of NSW 2200 to also assess the barrier function of the bowel gut bacterial proteins in the blood of these Australia lining. From these clinical investigations, he patients relative to healthy individuals. has shown that CEM is superior to biopsies and T +61 2 9767 6111 has furthermore revealed that the lining of the Leong hopes to use the presence of these F +61 2 9767 6767 gastrointestinal tract of inflammatory bowel proteins as a measure of leakiness and to help E rupertleong@unsw.edu.au disease patients becomes ‘leaky’. confirm the findings of the impaired barrier function of the bowel. By combining CEM and RUPERT LEONG is a consultant Senior proteomics, both the structure and function of Discovering a ‘leaky’ lining Staff Specialist gastroenterologist at the mucosa can be evaluated, and the result of Bankstown, Concord and Macquarie CEM has allowed Leong to view the function the loss of bowel integrity can be measured. University Hospitals, and Associate as well as the structure of the gut lining. Reversal of the abnormal changes and Professor of Medicine at the University Biopsies disrupt the natural environment of normalising the protein constitutent of the of New South Wales and Macquarie and kill the extracted cells, resulting in a loss of blood may be an end point of treatment. He University, Sydney, Australia. His function. Therefore, biopsies can only provide has already extended this combined approach expertise includes interventional information on the structure of tissue. In to other diseases such as pre-cancerous endoscopy and management of contrast, CEM visualises living tissue, providing changes of Barrett’s oesophagus, gastric inflammatory bowel diseases. Leong is information on both structure and function. intestinal metaplasia and pre-cancerous committed to individualised, high-quality When examining the mucosa of inflammatory changes of the stomach. management, and fostering novel research. By combining confocal endomicroscopy and proteomics, both the structure and function of the mucosa can be evaluated, giving a more in-depth analysis of the pathogenesis of inflammatory bowel disease 66 International innovation