Neurogastroenterology and Motility Section
& Surgical Joint Symposium
Thursday 17th March 2005
BSG, Birmingham
Part One - Hall 5
Chair – Professor Q Aziz and Mr K Wedgewood
09.0 - 09.30
Overview of Oesophageal Dysmotility
Associated medical conditions & management
Andreas Smout, Utrecht, Holland
9.30 – 10.00
Investigation of oesophageal dysmotility and Gastro-oesophageal reflux
– Novel approaches
Daniel Sifrim, Leuven, Belgium
09.55 – 10.30
Neurophysiological assessment of the oesophagus – How can it help
the clinician?
Cortical Evoked Potentials/Magnetoencephalograpy/transcranial magnetic
stimulation
Anthony Hobson, Manchester, UK
10.30 – 11.00
Coffee
11.00 – 11.30
Achalasia
Medical vs Surgical management
Professor Giovanni Zaninotto, University Dept of Surgery, Padua, Italy
11.30 – 12.00
Gastroparesis – aetiology, diagnosis and management
Jan Tack, Leuven, Belgium
12.05 – 12.45
Keynote Speech
Autonomic Neuropathy & GI Dismotility
Prof CJ Mathias, institute of neurology, London.
2
Neurogastroenterology and Motility Section
& Surgical Joint Symposium
Thursday 17th March 2005
BSG, Birmingham
Part Two - Hall 1
Chair – Professor RC Spiller & Mr GM Fullerton
2.00 – 2.30
Chronic Intestinal Pseudo-obstruction
Greger Lindberg – Huddinge University – Sweden
2.30 – 3.00
Colonic Inertia
Devinder Kumar, St Georges, London
3.00 – 3.30
Adult Hirschsprung / Megacolon: novel insights in aetiology and
management
Mr Charlie Knowles, Royal London Hospital, London
3.30 – 3.45
Coffee
3.45 – 4.15
ACE Procedure
Graham Duthie, Castle Hill Hospital, East Yorkshire
4.15 – 4.45
Incontinence & Neosphincter Formation
Medical Vs Surgical Management
Prof Norman Williams, Royal London Hospital, UK
4.45 – 5.15
Key Note Speech
Current and evolving treatments for motor disorders of the GI tract
Vincenzo Stanghellini – Bologna, Italy
3
André Smout
André J.P.M. Smout was born in 1950 in Amsterdam, the Netherlands. He studied medicine at the
University of Amsterdam and subsequently specialized in internal medicine and gastroenterology in
Rotterdam and Utrecht. After his registration as a gastroenterologist in 1984 he became staff
member of the Department of Gastroenterology of the University Medical Centre in Utrecht. In this
position he is involved in patient care, teaching and research.
Since 1976 André Smout's research activities have been devoted to gastrointestinal motility and
perception in health and disease. The subject of his doctoral thesis (1980) was the myoelectrical
activity of the stomach. Over the years, he was involved in studies into the pathophysiology,
diagnosis and treatment of functional bowel disorders and abnormal gastrointestinal motility,
including gastro-oesophageal reflux disease. In 1989 and 1992 he worked for short periods of time
in the departments of Dr. Don Castell (Winston-Salem, NC, USA) and Dr. Michael Horowitz
(Adelaide, South-Australia).
Since 1994 André Smout is holder of the Chair of "Gastrointestinal motility disorders" at the
University of Utrecht. He is author of about 200 peer-reviewed scientific publications, several books
and many book chapters on gastrointestinal motility and functional bowel disorders.
Abstract - Overview of oesophageal dysmotility
Disordered oesophageal motor function may give rise to a limited spectrum of symptoms among
which dysphagia and chest pain are the most prominent. Oesophageal dysmotility may be confined
to the tubular oesophagus or the lower oesophageal sphincter (LOS) or the function of both
structures may be abnormal. Manometry remains to constitute the cornerstone of the diagnosis of
oesophageal dysmotility. Assessment of oesophageal transit, either by means of radiography or by
means of radioscintigraphy may provide useful additional information.
Recently, a new classification of oesophageal motor disorders was proposed. As was the case with
previous classification systems, the new system is based on findings made during a manometric
study of the oesophagus. In the new classification of oesophageal motor disorders, the diagnosis
“ineffective oesophageal motility” (IOM) was introduced. It largely replaces the term “non-specific
oesophageal motility disorders” that was used in previous classifications. IOM appears to be the
most frequent abnormality observed in patients undergoing oesophageal manometry. The disorder
can be associated with a number of systemic conditions, such as diabetes mellitus, scleroderma,
reflux disease and chronic idiopathic intestinal pseudoobstruction, but it may also occur without any
association with other disorders.
Achalasia and diffuse spasm appear to be related disorders caused by degenerative changes in the
neurons involved in the regulation of oesophageal motor function. In both disorders substantial
thickening of the muscular layers of the oesophagus can be found. In the treatment of these
disorders, smooth muscle relaxing drugs, forceful dilatation, surgical myotomy and injection of
botuline toxin have a place. However, the side-effects of smooth muscle relaxants severely limit their
usefulness. The pathogenesis of the manometric disorder known as nutcracker oesophagus,
characterized by high-amplitude oesophageal contractions, is much less clear and its association
with symptoms is poorly understood. The therapeutic options in IOM are disappointing; there is a
complete lack of oesophagus-specific prokinetic drugs.
Some recent studies suggest that sustained oesophageal shortening caused by longitudinal muscle
contraction may cause chest pain. This abnormality cannot be detected by conventional techniques
including manometry.
References:
1.
Spechler SJ, Castell DO. Classification of oesophageal motor abnormalities. Gut
2001;49:145-151.
2.
Dent J, Holloway RH. Esophageal motility and reflux testing. State-of-the art and clinical role
in the twenty-first century. Gastroenterol Clin North Am 1996;25:51-73.
3.
Mittal RK, Bhalla V. Oesophageal motor functions and its disorders. Gut 2004;53:1536-1542.
4
Daniel Sifrim, MD, PhD
Daniel Sifrim, born 23rd of April 1955, is Professor of Medicine at the University of Leuven, Belgium
and member of the Center for Gastroenterological Research K.U.Leuven. He graduated as MD in
1979 at the University of Buenos Aires, Argentina and did his Internal Medicine and
Gastroenterology training at the Posadas General Hospital, in Buenos Aires where he also served
as Chief Medical Resident. Dr. Sifrim started his research career in 1990 at the Center for
Gastroenterological Research of the University of Leuven founded by Prof. Dr. G. Vantrappen and
currently directed by Prof. Dr. J. Janssens. He obtained his PhD degree at the University of Leuven
in 1994.
Dr. Sifrim has been actively involved in clinical and basic research related to esophageal motility
disorders and gastroesophageal reflux disease.
Abstract - Investigation of esophageal dysmotility and gastro-esophageal
reflux - Novel approaches
Esophageal motility has several components: in the esophageal body there are circular peristaltic
contractions, contractions of the longitudinal muscle layer inducing esophageal shortening, and
continuous tone. The lower esophageal sphincter offers a barrier to reflux by generating a high
pressure zone that relaxes with swallowing, belching and vomiting. Several techniques are available
to study esophageal motility. Some of them are used routinely in the clinic, like fluoroscopy and
stationary manometry. However, new techniques allow a better understanding of the
pathophysiology of esophageal motor disorders.
With topographic evaluation of esophageal manometry the number of recording sites is increased
such that accurate axial data interpolation becomes feasible. Four discrete pressure segments have
been identified consistently from the proximal esophagus through the LES that are separated by
three pressure troughs. The first segment presumably represents the skeletal muscle component of
the esophageal body. The smooth muscle segment of the esophageal body is then identified by the
second and third peristaltic segments that are separated by a second trough. Available data suggest
that these two segments are under different neuromuscular control and can react separately. The
proximal segment is more responsive to cho-linergic stimulation, whereas the distal segment
probably is more reflective of noncholinergic control mechanisms in that region.
Evaluation of bolus transit without radiation became available using multichannel intraluminal
impedance (MII)(7,8). This technique uses differences in resistance to alternating current between
air, bolus and esophageal wall to determine intraesophageal bolus transit. Simultaneous
multichannel intraluminal impedance and fluoroscopy validated bolus transit timings identified by
MII. Esophageal motor disorders can now be re-classified according to bolus transit abnormalities.
Assessment of the degree of stretch of a hollow viscus in vivo is now possible using impedance
planimetry. Impedance planimetry measures cross-sectional area (CSA) and intraluminal pressure
simultaneously and facilitates calculation of some of the biomechanical properties of the esophageal
wall (11). This technique allows evaluation of the sensory, motor, and viscoelastic properties of the
esophagus. Studies on esophageal motility have mainly focussed on phasic peristaltic contractions
and lower esophageal sphincter (LES) function. However, recent studies in cats and human using a
modified barostat technique demonstrated the presence of a low resting tone in the esophageal
body. The pathophysiological relevance of esophageal tone is not clear. Changes in esophageal
5
tone might modulate the oral progression of a bolus or the proximal extent of gastroesophageal
reflux. Finally, like in the stomach or colon, esophageal tone might modulate the sensitivity to
distension or chemical stimulation. High-frequency intraluminal ultrasonography (HFIUS) measures
changes in muscle thickness as an index of muscle contraction. Continuous high-frequency
intraluminal ultrasonography was used to characterize basal esophageal wall thickness in patients
with primary motor disorders and changes in thickness at the time of spontaneous and provoked
chest pain. Spontaneous chest pain episodes could be preceded by a sustained esophageal
contraction (SEC) detected on ultrasonography.
Gastroesophageal reflux disease (GERD) arises from an increased exposure and/or sensitivity of
the esophageal mucosa to gastric contents. Up until now, most concepts about the frequency of
gastroesophageal reflux episodes and the efficiency of the antireflux barrier have been based on
inferences derived from measurement of esophageal pH. However, pH monitoring does not detect
all gastroesophageal reflux events even when special pH analysis criteria are used, particularly
when little or no acid is present in the refluxate. This is the case in both adults and infants after
eating, before the gastric contents have become acidified and it also applies to reflux in patients
undergoing antisecretory therapy. Not only the acidity, but also the air-liquid composition of the
refluxate could be relevant in the pathogenesis of GERD.
The total rate of reflux episodes is an important indicator of the competence of the antireflux barrier
and is therefore relevant when evaluating the effect of therapies directed at improving the antireflux
barrier function. Furthermore, esophageal or extraesophageal symptoms of GERD may be related to
less acidic or gas reflux that is not detected by pH-metry.
Other methodologies have evolved to complement ambulatory pH monitoring for detection and
characterisation of gastroesophageal reflux. Intraluminal electrical impedance offers the potential to
detect and monitor liquid or air movement within the esophageal lumen and Bilitec, a
spectrophotometric method, can detect the presence of bilirubin in the refluxate . These new
techniques have enabled more precise evaluation of GERD and they offer the opportunity to
conceive gastroesophageal reflux more broadly, both in terms of frequency and characteristics of
the refluxate.
6
Dr Anthony R. Hobson, PhD
Dr Hobson is a Clinical Scientist / Research Fellow in GI Science at the University of Manchester.
Over the past ten years his research has focussed on understanding the extrinsic control of GI
sensory and motor functions. In particular he has an interest in mechanisms of visceral
hypersensitivity in patients with functional gastrointestinal disorders which formed the basis of his
PhD. This research has required training in the use of several neurophysiological techniques and
functional brain imaging and their novel application in neurogastroenterology.
Abstract - Neurophysiological assessment of the oesophagus – How can it
help the clinician?
The ability to dissociate specific neurophysiological mechanisms of aberrant gastrointestinal (GI)
sensorimotor processing in patients with a wide range of clinical disorders has been the aspiration of
an increasing number of GI clinicians / researchers. Improved access to state of the art
neuroscience tools such as transcranial magnetic stimulation and cortical evoked potentials,
previously the reserve of specialist neurology centres, has vastly increased our understanding of the
central and peripheral processing of GI sensorimotor function in health. The solid foundation based
on this understanding of normal physiology has recently allowed us to investigate, for example,
factors such as the mechanisms of recovery in dysphagic patients following stroke.
The challenge now for researchers in this field is to translate this wealth of information to the clinical
setting in order to have an impact on the diagnosis and treatment of GI sensorimotor disorders. The
aim of this presentation is to provide a concise overview of the current literature pertaining to
neurophysiological assessment of the oesophagus, covering disorders such as dysphagia, chest
pain, gastro-oesophageal reflux and oesophageal motility disorders. Whilst these data have been
acquired from studies of the oesophagus, such approaches can also be utilised to study abnormal
function throughout the GI tract.
From a clinical perspective, the advantage of this approach is that the acquisition of objective,
neurophysiological data from the GI tract will enable future treatment and management strategies to
be targeted to specific aberrant mechanisms. The aim of this is to increase both patient well being
and the efficiency of health service utilisation.
7
Professor Giovanni Zaninotto, MD
Giovanni Zaninotto, born in 1951, graduated in Padua 1976, married in 1981, two daughters and two
dogs. Trained in general surgery. Research fellow in Thoracic Surgery at Creighton University
(Omaha, Ne U.S.A.) from 1986 to 1987. Present position: associated professor of surgery (Dept of
General Surgery and Organ Transplantation – University of Padova). Main interests: esophageal
surgery; Mini-invasive surgery. At present, acts as general secretary of the European Society of
Esophagology and as vice-president of the Italian Society of Endo Laparoscopic Surgery. He
published 73 articles in peer-reviewed journals.
Abstract - Achalasia
Oesophageal achalasia (OA) is an idiopathic disorder of oesophageal motility that results from the
destruction of post-inhibitory neurons in Auerbach’s plexus; this leads to impaired lower
oesophageal sphincter relaxation and aperistalsis. The aetiology of OA is unknown and, though no
definitive therapy is currently available, there are numerous palliative treatments aiming to reduce
the Lower Oesophageal Sphincter (LOS) pressure and enable the passage of the bolus into the
stomach by gravity. Nitrates, calcium blockers, botulinum toxin, pneumatic dilation and
(laparoscopic) Heller myotomy all have a place in the armamentarium against this disease. These
options vary in efficacy and durability, and carry different risks and costs. OA is a relatively
uncommon disease (incidence: 0.03 to 1.1 per 100,000 population) and randomised controlled trials
on adequate numbers to compare these treatments “head to head” are scarce, so the choice of
treatment is often based on “environmental” factors (availability of local expertise) or the personal
preference of the physician or patient. Pharmacological therapy: calcium channel blockers and
long-acting nitrates are the two most often used medications. They both reduce LOS pressure and
the patient’s symptoms, but side effects (headache, hypotension, pedal oedema) and a short-lived
action limit their use to “bridging” therapy or patients unsuitable for more effective treatments.
Botulinum toxin: of the seven botulinum toxins existing in nature, only Botulinum toxin type A is
commercially available. BoTox is delivered by endoscopic injection in the cardia: the procedure is
virtually without morbidity or mortality. BoTox blocks the release of acetylcholine from nerve
endings, thereby inducing a persistent LOS pressure reduction. The therapy is effective in 80-90%
of cases in the short term, but the success rate drops to 30% after 2 years. When this treatment was
compared with pneumatic dilation and laparoscopic myotomy, BoTox proved the least effective in all
the trials. Pneumatic dilation (PD): forceful dilation of the cardia was introduced in the Twenties
using mechanical dilators (whereas low-compliance pneumatic dilators are used nowadays). There
is no agreement among endoscopists as to the number (frequency), calibre, duration and pressure
needed in PD to treat achalasia. Overall, a 60-80% five-year success rate is reported, but recent
studies have shown a much lower (30%) long-term success rate (at 10 years). Oesophageal
perforation is the most common complication of PD: the risk is estimated at 2-5%. Myotomy of the
cardia (MC): introduced by Heller at the beginning of the last century, this operation is currently
performed via a laparoscopic approach, thus reducing post-operative pain and hospital stay. No
randomised trials comparing open and laparoscopic myotomy have been performed, but the results
of laparoscopic MC seem very similar to those of open surgery. An antireflux partial fundoplication
(anterior, i.e. Dor, or posterior, Toupet) is usually added and a recent trial has shown that this
effectively prevents reflux. The success rate of MC is estimated at between 85 and 95%. Data on
long-term (10-year) outcome show that dysphagia palliation persists in 80% of operated patients.
Mortality is only occasionally reported and the morbidity rate is around 10-15%. While prior
8
endoscopic dilations do not affect the result of myotomy, it is not clear whether the same can be said
of BoTox injections. So far, only one randomised controlled trial on PD and CM has been performed
(now 30 years old), which showed better results for CM, but this study was widely criticised because
of the patient selection methods and certain technical details concerning the PD. An economic
analysis showed that PD was the more effective procedure (at least in the mid-term). From an
exclusively economic point of view, the treatment for achalasia should be based on dilation(s),
reserving surgery for patients who relapse. None of the economic studies consider the outcome over
a longer period of observation, however. A European multicenter randomised trial comparing PD
and CM is currently underway, the results of which are eagerly awaited to settle the nearly hundredyear-old conundrum as to which is the best treatment for achalasia.
9
Professor Jan Tack
Professor Jan Tack, born 25th of June 1962, is currently Head of Clinic in the Department of
Gastroenterology, and Professor in Internal Medicine at the University of Leuven, Belgium. He is in
charge of the laboratory for Gastrointestinal Motility in the Center for Gastroenterological Research
at the University of Leuven. He graduated summa cum laude in 1987 at the University of Leuven
and specialized in Internal Medicine and Gastroenterology at the same institution. He was a
research fellow at the Department of Physiology at the Ohio State University, Columbus, Ohio,
U.S.A. with Dr. J. D. Wood from 1989 to 1990 and at the Center for Gastroenterological Research at
the University of Leuven with Dr. G. Vantrappen and Dr. J. Janssens since 1990. Prof. Tack is
married and has four children aged between 6 and 11 years old. His research lies in the field of
Neurogastroenterology and Motility, and includes diverse topics such as the physiology and the
pharmacology of the enteric nervous system, gastrointestinal hormones, intestinal inflammation, and
the pathophysiology of functional dyspepsia, of gastro-esophageal reflux disease and of the irritable
bowel syndrome. He published more than 140 articles and more than 30 book chapters on various
aspects of scientific and clinical gastroenterology. Prof Tack won several research awards including
the G. Brohee prize for Gastroenterological Research, the Baron Simonart prize for Clinical
Pharmacology, the Paternoster-Vantrappen prize for neurogastroenterology, the AstraZeneca prize
for Gastroenterological Research and the international Janssen Award for Basic and Clinical
Research in Gastrointestinal Science. Prof. Tack has served as associate editor of “Gut” and
“Digestion”, and as member of the editorial board of “Gastroenterology” and “Bailliere’s Clinical
Gastroenterology”.
Abstract - Gastroparesis
Delayed gastric emptying in the absence of mechanical obstruction is called gastroparesis. Delayed
gastric emptying may be caused by a variety of mechanical and non-mechanical causes.
Gastroparesis is the end result of neuromuscular failure or excessive inhibitory influence, or both, on
the components of the gastric emptying process. The most important pathophysiological
abnormalities, described in subgroups of patients, include fundal hypomotility, antral hypomotility,
gastric arrhythmia and lack of antropyloroduodenal coordination. In addition, excessive negative
feedback mechanisms may also delay gastric emptying rate.
The prevalence of (idiopathic) gastroparesis in the population has not really been studied. The most
important causes of gastroparesis are idiopathic (33%), diabetes mellitus (24%) and post-surgical
(19%). Gastroparesis is also occurring in association with less frequent disorders such as anorexia
nervosa, renal failure, Parkinson’s disease and chronic intestinal pseudo-obstruction. Delayed
gastric emptying is often occurring in anorexia nervosa, probably rather as a consequence of
malnutrition and muscular atrophy. The presence of gastroparesis has usually been studied in the
context of dyspeptic symptoms. In large series, up to 30% of patients have delayed gastric
emptying, but the correlation with symptoms is rather poor. Recent data in patients with idiopathic
gastroparesis suggest that symptom pattern and severity are determined by proximal stomach
dysfunction rather than severity of delayed emptying.
Radionuclide gastric emptying measurement is considered the standard method to assess gastric
emptying rate. Solid and liquid emptying can be assessed separately or simultaneously. Breath tests
can also be used to measure gastric emptying rates. Interference by drugs that delay gastric
emptying should be considered. A suspected diagnosis of gastroparesis warrants ruling out of
mechanical causes and serum electrolyte imbalances, followed by empirical treatment with a
gastroprokinetic like domperidone or metoclopramide. Several studies have reported on successful
use of cisapride in gastroparesis. However, because of an enhanced risk of QT prolongation with
cardiac arrhythmia’s, the availability of cisapride has been suspended. Short term studies in diabetic
and postsurgical gastroparesis have reported beneficial effects of treatment with erythromycin. This
macrolide antibiotic acts as a motilin receptor agonist and has prokinetic properties. Attempts to
develop macrolide prokinetics devoid of antibiotic properties have been disappointing. Tegaserod, a
new prokinetic 5-HT4 agonist, Mitemcinal, a macrolide prokinetic, and Itopride, a mixed dopamine
10
antagonist and cholinesterase inhibitor, are currently under evaluation. Recent studies have
reported that gastric electrical stimulation may relieve symptoms among patients with intractable
nausea and vomiting and gastroparesis. Only one controlled trial of this treatment approach over a
short term period is available and, this is not fully convincing
11
Professor Christopher J Mathias, DPhil, DSc, FRCP, FMedSci
Abstract - Autonomic failure and gastrointestinal dysmotility
Motility of the gastrointestinal tract is affected in many autonomic disorders, both localised and
generalised. This review will provide a non-gastroenterological perspective into the neurological and
medical causes of gastrointestinal dysmotility associated with autonomic failure. Disorders affecting
the autonomic nervous system will be classified. These include acute autonomic neuropathies, pure
autonomic failure, multiple system atrophy and idiopathic Parkinson’s disease. Secondary disorders
will also be described, with an emphasis on common disorders such as diabetes mellitus and spinal
cord injuries. The role of gastrointestinal dysfunction in common causes of intermittent autonomic
dysfunction, such as neurally-mediated syncope, will be covered.
The lecture will provide an outline of clinical features of the major disorders that are of relevance to
the general physician and gastroenterologist, together with key management approaches.
References
1.
2.
3.
Mathias CJ. Autonomic diseases – clinical features and laboratory evaluation. Journal of Neurology,
Neurosurgery & Psychiatry 2003, 74; 31-41
Mathias CJ. Autonomic diseases – Management. Journal of Neurology, Neurosurgery & Psychiatry 2003, 74;
42-47
Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s Disease. In: Parkinson’s Disease. Eds. Ebadi M &
Pfeiffer RF. CRC Press LLC, New York 2005, 259-274.
12
Greger Lindberg, MD, PhD
Greger Lindberg is Associate Professor of Medicine at Karolinska Institutet, Stockholm, Sweden. He
is consultant gastroenterologist at Karolinska University Hospital and head of the Gastrointestinal
Physiology Laboratory. His research interest mainly concerns gastrointestinal motility disorders. His
scientific production includes 64 original papers, 21 books and book chapters, and 12 other scientific
communications.
Abstract - Chronic Intestinal Pseudo-Obstruction
Chronic intestinal pseudo-obstruction (CIP) is a severe form of gut dysfunction that may arise from
congenital or acquired damage to enteric nerves or muscle cells. Previously, the diagnosis of CIP
rested upon roentgenologic evidence of dilated bowel and absence of a mechanical obstruction. The
increased availability of GI physiology studies and in particular small bowel manometry has led to
many more cases of gut dysmotility now being diagnosed on the basis of symptoms and small bowel
motility patterns. However, the diagnosis of CIP requires not only evidence of abnormal motor
activity but also the presence of clinical signs mimicking those of a mechanical obstruction. The
latter has been defined as sub-occlusive events with air-fluid levels on plain abdominal radiograph
and/or dilated bowel loops (1). A new diagnostic entity, enteric dysmotility (ED), has been put
forward for patients with abnormal small bowel motor activity but no signs of pseudo-obstruction,
whereas normal or inconclusive small bowel manometry places the patient in the group of functional
bowel disorders. We compared symptoms, manometry findings and findings from full-thickness
biopsies of the jejunum in 67 patients (55 females) with CIP and 36 patients (31 females) with ED.
Patients with CIP more often reported distension (79% vs. 47%) but no difference was found for
other symptoms such as heartburn, nausea, vomiting, abdominal pain, constipation, or diarrhea.
Small bowel manometry exhibited similar abnormalities in the two groups regarding Phase-III
propagation and configuration, and burst activity. Patients with CIP more often had sustained
periods of uncoordinated phasic activity, abnormal response to food intake, and severe hypomotility
(Table 1).
Table 1. Manometry findings in patients with CIP and ED.
ED (n=36)
Abn. P-III Abn.
P-III
BUPA
propagation configuration
SPUPA
Abn.
fed Severe
activity
hypomotility
45%
25%
0%
30%
72%
0%
CIP (n=66) 37%
47%
74%
45%*
25% **
11% *
Abn. = Abnormal; P-III = Phase III; BUPA = bursts of uncoordinated phasic activity; SPUPA =
sustained periods of uncoordinated phasic activity
Histomorphological findings differed substantially between CIP and ED. The most common finding in
patients with ED was inflammatory neuropathy, whereas CIP often was due to visceral myopathies
and combined neuro-myopathies (Table 2).
Table 2. Histopathology findings in patients with CIP and ED.
Myopathy
Inflammatory
neuropathy
Degenerative
neuropathy
Combined
myopathy
neuro-
13
ED (n=34) 6%
76%
CIP
(n=64)
33%
25% *
***
18%
0%
22%
19%
**
Problems with nutrition and abdominal pain dominate the clinical management of patients with CIP
and ED. There are few controlled clinical trials of drug therapy in either of the two conditions.
Prokinetic drugs including neostigmine, erythromycin, cisapride, and octreotide have been reported
to be beneficial in selected cases. Pain treatment in severe motility disorders is particularly difficult,
since opiates tend to worsen already impaired peristalsis.
1. Wingate D, Hongo M, Kellow J, Lindberg G, Smout A. Disorders of gastrointestinal motility:
towards a new classification. J Gastroenterol Hepatol 2002;17 Suppl:S1-14.
14
Mr Charles H Knowles, PhD, FRCS
Charles Knowles is a Specialist Registrar in Surgery (sub-specialty interest: coloproctology) in North
East Thames (London) as well as Clinical Lecturer in Academic Surgery at Queen Mary's School of
Medicine & Dentistry. In 2000, he was awarded the degree of PhD at the University of London for a
body of work on the subject of slow-transit constipation. This and subsequent research have
focussed on physiological and neuropathological aspects of several gastrointestinal motility
disorders including those characterised by inflammation and visceral pain.
Abstract - Adult Hirschsprung / Megacolon: Novel Insights In Aetiology And Management
Severe constipation in adulthood encompasses a wide range of underlying pathophysiologies. The
majority of these are associated with no overt macrostructural abnormality but may still have a
demonstrable disorder of motor or sensory function e.g. slow-transit constipation. Others e.g. IBS
have neither an easily measurable functional disturbance nor structural abnormality. In contrast, a
small proportion of patients with intractable constipation who fail to respond to non-surgical
intervention have persistent dilatation of the bowel and are described as having megacolon /
megarectum or both: megabowel. A quick view of any coloproctological tome will provide the reader
with a list of causes of megabowel e.g. pseudo-obstruction, Chagas’ disease, adult Hirschsprung’s
disease. However in practice in the developed world, the disorder usually has no obvious cause and
such patients are thus described as idiopathic. This condition, whilst very uncommon compared with
other defaecatory disorders, causes considerable physical and social disability to the sufferer and
similarly presents a challenge to the attending physician / surgeon faced with its management. The
session will focus on:
Part I: An overview of the causes of megabowel (acute and chronic)
Part II: Idiopathic megabowel
Definition (diagnosis) based on radiological measurement (Preston et al., 1985) especially in the
context of distinguishing it from other conditions with a similar presentation and overlapping
pathophysiology.
Epidemiology (uncommon).
Evidence for possible aetiologies.
Clinical presentation and routine investigations.
Pathophysiology. The physiological findings based on specialist testing (polymodal sensory findings,
tone, compliance, contractile activity and transit) and histopathological findings (routine and
immunohistochemical) will be discussed (Gattuso et al., 1997).
Medical management.
Surgical management. Using data from an up to date systematic review (Gladman et al., 2004), the
outcomes from conventional and some novel surgical approaches will be presented.
Part III Adult Hirschsprung’s disease
Definition and brief resume of the contempory understanding of Hirschsprung’s disease (HSCR)
including genetics.
Epidemiology (very rare).
Distinguishing adult HSCR from idiopathic megabowel based on clinical and pathophysiological
findings.
Principles of surgical management and outcome.
15
Possible future treatments of HSCR including colonisation with enteric nervous system progenitor
cells (EPCs) (Bondurand et al., 2003).
References
1.
2.
3.
4.
Bondurand N, Natarajan D, Thapar N, Atkins C, Pachnis V. Neuron and glia generating progenitors of the
mammalian enteric nervous system isolated from foetal and postnatal gut cultures. Development 2003; 130:
6387-6400.
Gattuso JM, Kamm MA, Talbot. Pathology of idiopathic megarectum and megacolon. Gut 1997; 41: 252-7.
Gladman MA, Scott SM, Lunniss PJ, Williams NS. Systematic review of surgical options for idiopathic
megarectum and megacolon. Ann Surg 2004 (in press).
Preston DM, Lennard-Jones JE, Thomas BM. Towards a radiologic definition of idiopathic megacolon.
Gastrointest Radiol 1985; 10: 167-9.
16
Graeme S Duthie,
Was appointed as a consultant, and reader in surgery in 1994 at the University of Hull and Castle
Hill Hospital. Prior to this was a senior registrar on the Lothian rotation. His research experience and
involvement with functional bowel disorders started as a research fellow with David Bartolo in Bristol
and subsequently in Edinburgh.
With the appointment in Hull, came the opportunity to build a new physiology unit and practice in the
region. The unit now undertakes in excess of 1000 patient assessments annually of which 30% are
tertiary referrals. Medically and surgically the unit offers all the options for both constipation and
incontinence, and a multidisciplinary approach is used with regular interdisciplinary meetings.
Abstract – ACE Procedure
In 1990 Malone described the ACE procedure in children, a procedure designed to allow access to
the caecum so the colon and rectum could be flushed through, thus emptying the bowel. Initially
described for incontinence it was also subsequently used in constipation. Success in the paediatric
population led to extrapolation of the procedure into adult practice, mainly for use in chronic
constipation, but also for some with incontinence.
The procedure as initially described used the Mitrofanoff principle. The appendix was detached from
the caecum, then inverted and reinserted through the caecal wall to form a basic antireflux valve.
This conduit was brought out through the RIF skin to allow catheter access to thecolon. The colon
was then lavaged to clean on a regular basis to aid bowel emptying / or to control incontinent
episodes.
In the absence of the appendix a medially based colonic tube could be constructed, or an ileal spout
could be used.
Since the original description, most surgeons have stopped inverting the appendix as there is a
possibility of vascular compromise and necrosis. In addition a simple appendostomy is attractive as
a minimally invasive procedure with the laparoscope.
Post-operatively the conduit remains catheterised for 6 weeks to allow healing and minimise
stenosis. It is flushed with 20-30 mls water daily for 3 days and then full lavage is implemented. The
usual starting regime is100-200ml of diluted phosphate enema syringed down the catheter followed
by 500mls of water with 2 teaspoons of salt dissolved in it. This is carried out with the patient on the
toilet. The whole procedure takes about 45 mins.
This is usually done daily or every second day, but the frequency is determined by the patients
desired outcome.
Results have been mixed in the adult population. Part of this may be because of expectations.
Patients with incontinence may still have leaks, and may leak mucus between lavages. Patients
should be warned, achieving a balance of lavage and bowel function may take as long as a year.
In the first 20 undertaken here (97-01), 14 were done laparoscopically, and 3 needed a conduit
constructed from a caecal flap. 3 required antibiotics for minor wound infections, all of which settled.
Subsequent to catheter removal, 2 required revision of the Ace due to stenosis, and difficuilty with
intubation has meant that at various times 9 have left the catheter insitu, and 4 have had a PEG
button fitted for this reason or due to the fact they continued to leak lavage fluid or mucus. In a
recent assessment, 7 had ceased to use there Ace, one that has had a successful graciloplasty, 2
required reversal for persistant leakage, and 4 had healed due to disuse. This is perhaps the most
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interesting group, all were done for constipation, and all are now reporting normal bowel function
without laxatives.
For a quality of life assessment both the physical and mental components of the score have
improved.
Other groups are reporting similar experience, with up to 30% stomal stenosis, and the resolution of
constipation is also confirmed by other studies. In our continuing experience, use of an Ace for outlet
obstruction has given universally poor results.
In summary, an Ace procedure can be a useful first surgical procedure when medical management
of incontinence and constipation fails. Patients need to appreciate they may have to experiment with
a variety of regimes to get the best results, and that in some cases function may not improve
significantly.
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Professor Norman S. Williams
Norman Williams is the Professor and Director of the Centre for Academic Surgery at Barts and The
London, Queen Mary's School of Medicine and Dentistry, from where he originally qualified. His
early surgical training was in London and Bristol, before moving to Leeds General Infirmary as a
Research Fellow, and subsequently Lecturer and Senior Lecturer. His principal interest is in
coloproctology, and particularly reconstructive surgery. During his Lecturer years, he went as a
Fullbright Scholar to the University of California, Los Angeles (UCLA), and gained particular
expertise in gastrointestinal motility. He has won the Patey Prize of the Surgical Research Society,
the Moynihan Fellowship of the Association of Surgeons and the BUPA Society of Authors' Prize
(Jointly) for the textbook "Surgery of the Anus, Rectum and Colon". He was awarded the Nessim
Habif Prize for Surgery in 1995 and the Galen Medal in Therapeutics in recognition of the advances
made in colorectal surgery in 2002. He was elected as a Fellow of the Academy of Medical
Sciences in 2004. He has been President of European Digestive Surgery, Vice-Chairman of the
Editorial Board of the British Journal of Surgery, Chairman of the UKCCCR Committee on Colorectal
Cancer, and a member of the National Cancer Research Network Steering Group. He is President
of the Ileostomy and Internal Pouch Support Group of Great Britain. He has been the Sir Alan Parks
Visiting Professor 2002, the John Goligher Lecturer, Tripartite Meeting, Melbourne 2002, the
Zachary-Cope Lecturer for the Royal College of Surgeons 2003 and most recently GB Ong Visiting
Professor in Hong Kong in 2004.
Abstract - Incontinence and neosphincter formation
Conservative treatment for severe faecal incontinence often fails. More active treatment involves
direct sphincter repair when there is a defined defect in the external anal sphincter. More recently
sacral nerve stimulation has been shown to be effective for some patients with moderate symptoms
in whom an intact sphincter is present. However, in patients where the sphincter is severely
damaged or absent, the only alternative to a permanent stoma is some form of neosphincter. Such
a neosphincter can be developed either by using synthetic material or autologous tissue. An artificial
sphincter derived from that used for urinary incontinence and consisting of an inflatable silastic cuff
has been used as a neoanal sphincter in recent years. However, despite optimistic initial reports
there is a significant failure rate as a result of erosion and sepsis, so much so that its future use
must be in doubt. We have concentrated on developing a neoanal sphincter from autologous tissue
and have utilised the gracilis muscle for this purpose. This muscle has in fact been used since the
1950’s. Pickrell et al (1953) first wrapped the muscle around a deficient anal sphincter in children
with faecal incontinence due to a variety of causes. Although this proved successful in some, it was
disappointing in many and especially when adapted for use in adults. The gracilis is a fast twitch
muscle that fatigues rapidly when contracted and cannot fulfil the requirements of an anal sphincter
which is a slow twitch muscle, composed of Type 1 muscle fibres, enabling it to contract
continuously without fatigue. However, based on the work of Salmon et al (1980) it is possible to
stimulate fast twitch muscle electrically and transform it into slow twitch muscle and thus convert the
gracilis muscle into a neoanal sphincter.
Between 1988-1997 we developed a neoanal sphincter from the gracilis muscle by attaching an
electrode to the main nerve of the muscle which in turn was connected to an implanted stimulator.
Biochemical, physiological and clinical studies demonstrated that it was possible to convert the
muscle from fast to slow twitch, and useful continence could be achieved. However, morbidity was
high. Subsequently, funding from the Department of Health via NSCAG enabled a specialist unit to
be established, The Colorectal Development Unit (CDU), which allowed us to concentrate on the
further development of the procedure.
The (CDU) was established to treat patients with end stage faecal incontinence with the electrically
stimulated gracilis neoanal sphincter (ESGN). From March 1997 to March 2003, 53 patients
underwent ESGN formation. The results were compared with 65 patients undergoing ESGN surgery
prior to the establishment of the Unit (Pre-CDU) between 1988 and 1997, who were similar with
regard to age, sex, aetiology and follow-up. Thirty-three CDU patients (70%) had a good functional
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outcome defined as continence to solid and liquid stool, a significant improvement when compared
to the Pre-CDU group, successful in 29 (45%) (P=0.01). Episodes of technical complications leading
to stimulator replacement were significantly reduced, from 25 to 3 over time (P<0.001). Severe
septic episodes were significantly reduced from 21 to 4 (P=0.003) but there was no significant
change in the incidence of postoperative evacuatory dysfunction. The conclusion from this study
was that since the setting up of the CDU, a successful outcome had been achieved in 33 of 47
patients (70%) undergoing ESGN surgery, which represented a significant improvement over time.
This was most likely related to improved patient assessment and selection, more reliable equipment
and increased operative and perioperative experience that came with a multidisciplinary team
approach.
We have further developed the technique to treat patients in whom the whole of the anorectal
mechanism is congenitally absent or has been excised as part of an abdominoperineal resection.
Such a procedure is referred to as Total Anorectal Reconstruction and is far more demanding than
just replacing the anal sphincter. Such patients have lost motor, sensory and reservoir function. In
these patients it is necessary to combine the ESGN with some form of conduit to aid evacuation.
50% of such patients have reasonable function, and this remains a viable option for highly motivated
individuals who wish to avoid a permanent stoma. Nevertheless, this technique can only be
considered as a developmental procedure which hopefully will be refined.
Another technique has also been developed in those patients with severe urge incontinence.
Physiological studies have demonstrated that such individuals have reduced rectal volumes, low
compliance and generate high pressure propulsive rectal waves which tend to coincide with the
episodes of incontinence. In selected patients with this problem we have augmented the rectum
using an isolated loop of ileum which has been stapled on to the anterior rectal wall to create a
recto-ileal pouch. Such a rectal augmentation has been done with and without an ESGN. Postoperative studies confirm that neorectal compliance, volume and motility can be restored to normal
using this technique and it has been successful in 10 of 12 patients after one year.
20
Professor Vincenzo Stanghellini
Prof. Vincenzo Stanghellini graduated from Bologna Medical School in 1978. At the University of
Bologna he also became a specialist in Internal Medicine and in Gastroenterology. During his early
days after graduation he moved to United States where he worked as a Research Fellow at the
Gastrointestinal Unit of the Mayo Clinic, Rochester, Minnesota for two years. Thereafter he
continued his scientific collaboration with the same institution as a Visiting Professor for further three
years, while establishing his own research program at the University of Bologna where he was
appointed Assistant Professor in 1986. In 1994 he obtained a position of Chairman of
Gastroenterology at the University of Pavia and, in 1997, he returned to the University of Bologna
where he is Associate Professor of Internal Medicine at the Department of Internal Medicine and
Gastroenterology and Chief of the Functional Digestive Disorders Laboratory of the University
Hospital.
He is currently leading a successful group of investigators of international reputation. Over the years
he has established fruitful research collaborations with research centres worldwide including: Mayo
Clinic, Rochester Minnesota (Michael Camilleri, Giarrico Farruggia), UCLA, Los Angeles California
(Catia Sternini), McMaster University, Hamilton Ontario (Stephen Collins), University of Sheffield,
Sheffield UK (David Grundy), Technical University of Munich, Munich Germany (Michael
Schemann), Hospital Val d’Hebron, Barcelona Spain (Juan Malagelada, Fernando Azpiroz),
University of Pavia, Pavia Italy (Marcello Tonini), University of Florence (Pierangelo Geppetti).
He is the author of 140 scientific publications on peer review journals (see PubMed for details). He is
member of the following Scientific Associations: United European Gastroenterological Federation
(UEGF), where he also serves as a member of the Educational Committee; European Society of
Neurogastroenterology and Motility, where he also serves as member of the Steering Committee;
American Gastroenterological Association (AGA); British Society of Gastroenterology (BSG); Italian
Society of Gastroenterology (SIGE); Italian Group for the Study of Gastrointestinal Motility
(GISMAD) (past-President); European Digestive Motility Centre (EDMC), where he also serves as a
member of the Scientific Committee. He is also Associate Editor of American Journal of
Gastroenterology, member of the Editorial Board of Alimentary Pharmacology and Therapeutics,
Neurogastroenterology and Motility, Digestive and Liver Disease, World Journal of
Gastroenterology. He is President of the Italian Group of Intestinal Pseudo-obstruction (GIPSI).
His main research interests are represented by the pathophysiology of the GI tract (with specific
emphasis on GI motility and gastric secretion), as well as treatment of functional digestive
syndromes.
Abstract - Current and evolving treatments for motor disorders of the GI tract
The ill-defined, multifactorial pathogenesis of symptoms in functional digestive syndromes is
hampering efforts to develop effective treatments. Several digestive symptoms are suggestive of an
underlying gastrointestinal motor disturbance and indeed such abnormalities can be demonstrated
in a substantial proportion of patients by different techniques. Postprandial fullness and vomiting
have been found to be associated with delayed gastric emptying of solids, while early satiety and
weight loss to postcibal impaired accommodation of the gastric fundus. Traditional prokinetics have
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been repeatedly shown to exert beneficial effects, at least in some dyspeptics, provided that they do
not induce an increase in fundic tone, which might in turn even worsen symptoms. On the contrary,
drugs capable of enhancing postprandial fundic relaxation have been reported to improve dyspeptic
symptoms, although conflicting results have also been published. Some patients also present an
overdistended antrum, but neither its potential pathogenetic role, nor the effects on drugs on this
motor abnormality have been formally investigated. Abnormal motor functions have been shown
also in IBS. Diarrhea is assocted with accelerated small and/or large bowel transit, while delayed
transit has been reported in constipation predominant IBS. Crampy pain episodes are temporally
associated to high pressure contractions in the terminal ileum, but these observations have not been
confirmed. Hypercontractlity of the sigmoid colon, particularly in the postprandial periods, also
characterise IBS patients. Inability of the small bowel to normally handle gas and variations of rectal
and sigmoid colon have also been recently reported. The diversity of these motor abnormalities
accounts for the failure of any drug to treat them all. Visceral hypersensitivity has been
demonstrated at different levels of the alimentary canal in patients with functional GI syndromes and
has become the target for therapeutic intervention. Chemo- and mechanoreceptors can trigger
hyperalgesic responses. To which extent abnormal smooth muscle function is involved in activating
the latter receptors has not been fully elucidated. Psychosocial abnormalities have been consistently
found in functional digestive syndromes and antidepressants have been shown to be clinically useful
in patients with the irritable bowel syndrome
Although associations between specific symptoms and underlying pathophysiological mechanisms
are increasingly recognised, this new understanding has not resulted as yet into a better
management of affected individuals, but it is likely that, in the near future, drugs will receive
marketing authorisation with specific indication for different subpopulations of patients with functional
dyspepsia. New agents that are potentially useful for the treatment of the syndrome are being
developed, but a major gap often exists between basic and clinical evidence. Research is being
extensively directed towards serotoninergic receptors, since serotonin is implicated in the control of
both motor and sensory events. 5-HT4 receptor agonists exert a prokinetic effect and might also
affect visceral sensitivity, although the latter effect is still controversial. Unlike motilides, 5-HT4
receptor agonists do not appear to increase the gastric fundus tone and this may contribute to
improve dyspeptic symptoms and ultimately favour a clinical application of these compounds. 5-HT3
receptor antagonists have been investigated mainly in the irritable bowel syndrome and the few
studies carried out in functional dyspepsia have provided conflicting results. -opioid receptor
agonists might also be useful for functional digestive syndromes because of their antinociceptive
effects. Other receptors with a potential to become targets for novel drugs include: purinoceptors
(especially the P2X2/3 receptors), NMDA receptors (especially the NR2B subtype), proteaseactivated receptors-2, the vanilloid receptor 1, tachykinin receptors (especially NK1/NK2 receptors)
and CCK1 receptors.