SMJ 2003: 48(2): 43-45
*E.F.Shen, *S. Gladstone, *G. Milne, ^S. Paterson-Brown, *I.D.Penman
*Gastrointestinal
Unit, Western General Hospital, Edinburgh
^Dept
of Surgery, Royal Infirmary Edinburgh
Email:
i.penman@ed.ac.uk
Abstract
Management
of columnar lined oesophagus (CLO; Barretts oesophagus) is controversial. We
prospectively audited surveillance practices in Scotland and prospectively
assessed the impact of introducing local guidelines for Barretts surveillance
in Edinburgh. Most respondents were gastroenterologists. The majority take
random, not four quadrant, biopsies from the CLO. In Edinburgh during 2000, 80
patients underwent surveillance. The guideline protocol was not followed in 30
(37.5%) patients. Follow up of patients without dysplasia generally conformed to
the guidelines. Follow up of patients with low grade dysplasia was highly
variable while management of those with high grade dysplasia followed the
guidelines. Overall we found a wide variability in the management and
surveillance of CLO. Early experience suggests that implementation of guidelines
is helpful but there is still variation in practice.
Key
Words/ Phrases: Barretts oesophagus, specialised intestinal metaplasia,
Columnar lined oesophagus, surveillance
Introduction
In
recent years there has been a marked increase in the incidence of oesophageal
adenocarcinoma in most industrialised countries, but reasons for this are poorly
understood.
1
2; 3
This is especially true in Scotland, with the incidence
increasing in males from 2.2 per 100,000 in 1975 to 3.5 per 100,000 in 1990.
4
Symptomatic patients
diagnosed with oesophageal adenocarcinoma have a poor prognosis, with overall
five-year survival rates less than 15%.
5
Survival is dependent on
stage at diagnosis and detection at an early stage may increase survival.
6; 7
Currently, the only known risk factor for this malignancy is
Barretts oesophagus (columnar lined oesophagus, CLO).
3; 8; 9
CLO is common and found in aproximately 10% of patients
undergoing endoscopy for reflux symptoms.
10; 11
Recent data from Dundee found the incidence of CLO to be 42.7
per 1000 endoscopies performed for any indication.
Since
its initial description the definition of Barretts has evolved over the
years. At endoscopy an obvious change from the normal pale squamous lining of
the oesophagus to a salmon pink columnar mucosa is seen. Biopsies taken from
this area reveal an incomplete, patchy, intestinal metaplasia with goblet cells.
As patients with CLO are at a significantly increased risk of developing
adenocarcinoma, they often undergo surveillance to detect dysplasia or early
changes of malignancy.
Surveillance,
however, can be challenging. Determining the area of CLO can be difficult,
particularly in patients with an irregular squamous-columnar junction, hiatus
hernia or oesophagitis. Biopsies are necessarily random due to the patchy nature
of specialised intestinal metaplasia (SIM) and dysplasia within columnar
segments. In addition the case for endoscopic surveillance is not proven and
many controversial questions remain including whom to survey, frequency of
surveillance, optimum biopsy technique and management of patients with dysplasia.
Guidelines for surveillance have recently been produced in the USA,
6; 12
but to date, no such guidelines exist in the UK.
The
aims of this study were two-fold. Firstly, we conducted a prospective audit of
surveillance practices among Scottish endoscopists. Secondly, we developed,
disseminated and implemented local guidelines for the management of CLO in
Edinburgh in 1999 and audited the impact of this.
Methods
Surveillance
Practice
A
multiple choice questionnaire was designed to ask about specialty and experience
of respondents, their definition of CLO, surveillance practice and surveillance
technique. Hypothetical cases were constructed to question approaches to
management of patients with a) short segment CLO, b) specialised intestinal
metaplasia and no dysplasia, c) low grade dysplasia and d) high grade dysplasia.
The questionnaire was distributed to and completed by members of the
Caledonian Society of Gastroenterology (CSG).
Implementation
of Local Guidelines
A
protocol for surveillance and management of patients with CLO was agreed upon in
Edinburgh in 1999 after careful systematic review of the relevant literature,
and numerous draft protocols had been modified by the Edinburgh
multidisciplinary upper gastrointestinal team. This included gastroenterologists,
upper gastrointestinal surgeons, pathologists and oncologists. The agreed
protocol, with supporting documentation was then sent to all those who perform
endoscopy in Lothian for comment and displayed in each endoscopy suite. If a
patient was suspected of having CLO at index endoscopy they were referred for
further assessment on a dedicated list at either the Western General Hospital or
Royal Infirmary Edinburgh. A number of patients had been referred from open
access lists, having undergone unsedated endoscopy. The lists were supervised by
a consultant with an interest in Barretts oesophagus. Biopsies were taken
from the gastroesophageal junction, the squamous epithelium and a minimum of
four biopsies from the area of CLO. Follow up was as per the local protocol (see
Table 1). Information
collected from the Barretts surveillance lists was entered prospectively into
a database designed for this purpose. The information collected included;
endoscopic features of the CLO: pathological results of biopsies; management
plans of patients after endoscopy; whether
or not the Barretts protocol was followed appropriately.
Results
Surveillance
Practice
A
total of sixty-four questionnaires were distributed and fourty-four (69%) were
returned. Of the respondents, two thirds were consultants and a third were
trainees. The majority of respondents were physician/gastroenterologists (n=39,
86%), the remainder being surgeons. Most (80%) had over 5 years experience, with
45% practicing for over 15 years. There was 80% agreement in the definition of
BO (columnar lined oesophagus containing specialised intestinal metaplasia on
biopsy). Only 50% of the respondents were aware of a Barretts surveillance
protocol in their own hospital.
Seventy-three
percent of respondents currently perform surveillance on patients with CLO. Of
these, ninety-three percent use standard forceps to take biopsies, whereas 7%
use jumbo forceps as recommended in US guidelines. One quarter of respondents
take 4 quadrant biopsies every 1-2cm of CLO as recommended in the USA, while the
rest take multiple random biopsies from the area of CLO.
Management
of the hypothetical case scenarios was at times variable. The first case was of
a 60 year old male with greater than 3 cm of CLO and SIM. Fifty percent of
respondents recommended surveillance every 1-2 years whereas 25% would delay
surveillance for at least 3 years. In contrast fourteen percent stated they
would perform no further surveillance. The second case was of a 45 year old male
with short segment (<3cm) CLO. Attitudes to surveillance in this case were
highly discordant as shown in Figure
1. The final case was of an otherwise fit 67 year old man with high grade
dysplasia. The majority of respondents opted for repeat endoscopy at variable
intervals of 3-12 months, but a fifth of respondents would refer the patient
directly to the surgeons for consideration of an oesophagectomy.
Implementation
of Local Guidelines
The
aim of the second part of our study was to introduce a protocol for surveillance
of CLO in Edinburgh and to monitor its effectiveness. In the year 2000, 80
patients were endoscoped on the Barretts surveillance lists. Forty-six
(57.5%) were male, with an average age of 64 years, all were Caucasian. On
review of adherence to the protocol, we found variance from the biopsy protocol
in 30 (37.5%) patients. Of these, six patients had short segment CLO 3cm and
five patients actually had no evidence of CLO when carefully assessed. Thus,
significant deviation from protocol occurred in 19 patients (23.8%).
Seventy-five
(94%) patients had biopsies taken (See Fig 1). Twenty-eight percent had SIM in
CLO less than 3cm (ie. short segment Barretts) and underwent no further
endoscopy while the rest had SIM in CLO greater than 3cm. Of those with SIM in
CLO >3cm, two thirds had SIM only, 24% had low grade dysplasia, 2 (4%) had
high grade dysplasia and 3 (5%) adenocarcinoma.
Just
over half (54%) of the patients with SIM only were referred for repeat endoscopy
in 3-5 years, but a few (27%) were booked for repeat surveillance in 1-2 years
despite the protocol guidelines. There was obvious confusion about the
management of patients with low grade dysplasia. Follow up plans varied from
repeat endoscopy in 1-3 months, 3-12 months, 1-2 years and 3-5 years. Both
patients with high grade dysplasia had repeat endoscopy within 3 months with
review of histology by a second pathologist and discussion at a
multidisciplinary upper gastrointestinal cancer meeting, as per protocol. Three
patients were found to have adenocarcinoma at index endoscopy when CLO was
discovered. Of these, 2 had symptoms of dysphagia and underwent staging and
referral to the surgeons for consideration of oesophagectomy. The third patient
was unfit for surgery and underwent palliative treatment.
Discussion
This
study shows that there is considerable variability in the management of
Barretts oesophagus in Scotland, although the majority of endoscopists
questioned perform some form of surveillance on patients known to have this
condition. The American College of Gastroenterology states that the optimum
number of biopsies required in a surveillance endoscopy has not been defined.
12
We found that 75% of CSG
members performing surveillance endoscopy take multiple random biopsies from the
area of CLO, while the others attempt to take systematic 4 quadrant biopsies
every 1-2cm as per the widely recommended Seattle protocol practiced in
many countries.
The
hypothetical cases in this study illustrate some of the controversial areas
surrounding management of CLO. A number of respondents stated that they would
not perform surveillance on the first case, a middle-aged male with SIM and CLO
greater than 3cm. Current literature would recommend surveillance, but the
frequency has yet to be determined.
4; 8; 9
The second case was of short segment Barretts oesophagus (SSBO)
with SIM. Current practices range from frequent surveillance every 1-2 years to
none at all, highlighting our current lack of knowledge about the actual cancer
risks in SSBO. Some studies suggest that patients with SSBO do have a relatively
high risk of developing adenocarcinoma, similar to that of patients with longer
columnar segments,
13; 14
while others suggest that the risk is much lower.
15
Further information about
the cancer risk in SSBO is needed before clear guidelines can be developed,
16; 17
especially as SSBO is
common and with limited resources available many centres may be unable to
provide surveillance for these patients.
High
grade dysplasia is the precursor of adenocarcinoma in patients with CLO. In up
to 40% of patients with high grade dysplasia, a focus of adenocarcinoma is also
found when oesophagectomy is performed
12; 18; 19
The American College of Gastroenterology has recommended one
of two approaches to high grade dysplasia, either intensive biopsy until a focus
of adenocarcinoma is detected, or immediate referral for surgical resection.
12
Management by our
respondents echoed these recommendations with the majority performing repeat
endoscopy and biopsy in the near future, and a few referring the patient for
oesophagectomy.
Data
from Edinburgh surveillance lists over a one year period was collected
prospectively. Previous papers have suggested a strong male preponderance to CLO,
4; 19; 20
whereas we found just under half our patients with
Barretts oesophagus to be female, in keeping with other British studies.
10
When
endoscopy was performed by an endoscopist with a special interest in BO,
thirty-two percent of patients were able to be discharged from further
surveillance lists, either because no CLO was found or because the segments were
short (<3cm). The current protocol in Edinburgh does not recommend
surveillance for those with short segments. Those with CLO underwent
histological review. Of these, 20%
had no SIM found, this may be due to the patchy nature of SIM, but almost all of
those with no SIM found had less than 3cm of CLO at endoscopy.
Management
of the patients with CLO generally conformed to the protocol with one major
exception, namely those with low grade dysplasia. The recommended timing of
further surveillance endoscopy ranged between one month and 5 years. Protocol
recommendations (surveillance in 6-12 months) were explicitly stated and reasons
for the wide variation in follow up endoscopy require investigation. The
findings, however, highlight the recognised difficulties in implementing
guidelines and monitoring their effectiveness.
With
regards to the patients with adenocarcinoma, only one patient had the
adenocarcinoma detected purely by surveillance, the other two patients were
symptomatic at first presentation. The symptomatic patients were discussed at
the local multidisciplinary upper gastrointestinal cancer meeting and referred
for surgery. The third patient was elderly and considered unfit for surgery, and
underwent palliation.
In
conclusion, surveillance practice and management of patients with BO in Scotland
varies widely but is similar to that throughout the rest of the UK and the USA.
Surveillance performed by endoscopists with an interest in CLO was able to
prevent a significant number of patients from undergoing further unnecessary
endoscopies. The newly introduced protocol in Edinburgh was followed in
the majority of patients, but long term follow up of these patients will be
necessary. Finally, further
knowledge about the natural history of CLO is needed before definitive protocols
for the management of these patients can be established.
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