Guidelines for the surveilance and management of familial adenomatous polyposis (FAP):a
world survey among 41 registries
(By: Vasen HFA, Bülow S, and The Leeds Castle Polyposis Group, Colorectal Disease 199; 1,
214-221)
Summary
Background: Familial adenomatous polyposis (FAP) is an autosomal dominant disease
characterized by numerous adenomas in the colorectum. The majority of patients
also develop adenomas in the duodenum. The purpose of the study was to evaluate
the management and screening protocols implemented in FAP families at various
polyposis registries in the world.
Methods: A questionnaire was mailed to the members of the Leeds Castle Polyposis
Group requesting information on: diagnostic evaluation of polyposis, recommendations
for screening and surgical management of the colon, surveillance of the upper
gastrointestinal tract and the management of duodenal polyposis
Findings: Almost all members agreed that a newly-diagnosed patient should be
referred to a polyposis registry and to a clinical genetic centre for genetic
counselling and DNA-testing. If the mutation has been detected in the family,
DNA-testing should be offered to first-degree relatives of patients from age
10-12 onwards. The surveillance protocol generally advised includes sigmoidoscopy
from age 10-12 at two-year-intervals until age 40. There was no agreement on
the preferred surgical treatment of colonic polyposis. Almost all members advised
follow-up after colonic surgery. Surveillance of the duodenum was recommended
by most members; this would start from age 30. There was no agreement on the
preferred surgical treatment of duodenal polyposis, or on the indication for
operation.
Interpretation: This survey provides insight into the guidelines used at various
polyposis registries for the surveillance and management of FAP patients, and
this insight may contribute to the appropriate management of these patients.
Introduction
Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease
caused by inactivating mutations at the APC-gene on chromosome 5.1,2,3 The disease
affects about 30 persons per million. Most polyposis patients develop hundreds
of colorectal adenomas during their second and third decade of life. Without
timely surgical intervention, the patients almost inevitably develop colorectal
carcinoma by the age of 40-50 years. A small proportion of the families (<10%)
have an attenuated or atypical form of polyposis, which is characterised by
the development of a smaller number of polyps and the development of colorectal
cancer at a more advanced age.4 The majority of the patients also develop polyps
in the upper-GI tract, i.e., fundic gland polyposis (40%), gastric adenomas
(5-10%) or adenomas in the duodenum (90%). Other extracolonic lesions observed
in FAP are desmoid tumors (10-15%), epidermoid cysts (in 50%), congenital hypertrophy
of the retinal pigment epithelium (CHRPE) (75-80%), dental anomalies (17%),
and osteomas (75-90%). FAP patients also have an increased risk of developing
brain tumours, hepatoblastoma and papillary carcinoma of the thyroid.1.2.3
The management of some aspects of FAP is controversial and lacks a strong scientific
basis or the available evidence is contradictory. The aim of the present study
was to evaluate the guidelines for the surveillance and management of polyposis
patients currently used in centres specialised in the care of such patients.
Methods
In June 1997, a meeting of the Leeds Castle Polyposis Group was held in Noordwijk
in the Netherlands. This international group includes specialists with a particular
interest in familial adenomatous polyposis. The members, mainly surgeons,
gastroenterologists and geneticists, are involved in the care of such families
at clinical departments, polyposis registries or clinical genetic centres.
In mid-1997, a questionnaire was mailed to the members of the collaborative
group requesting information on the guidelines used in their respective registries
for surveillance and management. The questionnaire addressed the following
issues:(1) diagnostic evaluation of FAP, (2) the surgical management of colonic
polyposis, (3) follow-up after colonic surgery, (4) surveillance protocol
in polyposis of the upper GI tract, (5) the management of duodenal adenomatosis,
and (6) the management of desmoid tumours.
The questionnaire comprised specific statements formulated by the authors
on each subject; participants were asked whether or not they agreed with these
statements, and whether they had specific comments on them.
Results:
Completed questionnaires were received from 41 centres in 16 countries: Australia, Canada, Denmark, Finland, Germany, Hong Kong, Italy, Japan, Korea, Norway, Portugal, Switzerland, Singapore, the Netherlands, the United Kingdom, and the USA.
(1) Diagnostic evaluation of FAP:
Statement: A newly-diagnosed polyposis patient and his/her family should be
referred to a polyposis registry and to a clinical genetic centre for genealogic
study, genetic counselling and DNA-testing in order to identify all the at-risk
individuals in the family and to ensure lifelong follow-up.
Reply: 93% of the clinicians agreed with this statement. One specialist suggested
replacing “registry and genetic centre" with "registry or
genetic centre".
Statement: Children and siblings of FAP-affected individuals should be offered
presymptomatic DNA-testing from age 10-12, if the mutation in the family has
been detected or linkage analysis has given high lodscores.
Reply: 88% of the respondents agreed with the statement. Two specialists would
not accept the results of linkage analysis. One specialist suggested that
sigmoidoscopy should start at age 10-12, and that DNA mutation analysis be
postponed until age 16. One specialist suggested that the result of a DNA
test should be confirmed by a second test. Another specialist emphasised that
DNA-testing should be performed after appropriate genetic counselling.
Statement: At the very minimum, clinical examination should include a search
for skin lesions, which occur mainly on the head, trunk and arms; it may also
include retinal examination (by an ophthalmologist), and orthopantomographic
X-ray for jaw and dental abnormalities.
Reply: 71% agreed with this statement. Ten respondents considered X-ray of
the jaws and/or retinal examination to be unnecessary, because neither has
any clinical implications. Two of these respondents claimed that these examinations
would be useful only in the event of an inconclusive DNA-test. One specialist
emphasised that if retinal examination is performed, it should be done by
a experienced ophthalmologist.
Statement: If the result of DNA-testing is inconclusive (i.e., mutation is
not identified in the family, or there are low or negative lodscores, as in
about 30% of the families), it is recommended that regular sigmoidoscopy (preferably
by a flexible scope) should start from age 10-12, and continue at two-year-intervals
until at least age 40. In families in which the disease tends to manifest
late, surveillance should continue to a later age.
Reply: 78% agreed; three centres recommended starting from age 14 or 15. Three
centres advised a one-year interval instead of a two-year interval. Four specialists
recommended that examinations be continued until age 55-60.
Statement: Total colonoscopy should be considered in families with an atypical
form of polyposis, as adenomas may only be located in the right colon. In
such families the endoscopic examinations may be started at a later age, e.g.
from age 18-20, because adenomas often develop at a late age.
Reply: 78% agreed. Two respondents suggested that periodic examinations should
start 10 years before the age at diagnosis of the index case.
Statement: If DNA-testing proves the carrier status of the at-risk family
member, the endoscopic programme should be continued as described above. If
the test reveals that the person does not carry the mutation, the periodic
examinations can be discontinued.
Reply: 73% agreed. Five clinicians did not fully trust negative results of
the DNA-test (in a family with a known APC-mutation), and therefore continued
endoscopic examinations at longer intervals. Two specialists would perform
endoscopic examinations every year in gene carriers.
(2) The surgical management of colonic polyposis:
Statement: Colectomy should be performed soon in an adult family member with
a newly-diagnosed FAP. The timing of prophylactic colectomy in a child who
has been identified during a family surveillance depends on the number, size
and degree of dysplasia of the adenomas. In addition, individual social and
educational factors concerning the patient may be taken into account. Most
patients are operated on between age 15 and 25.
Reply: 97% agreed. There were no specific comments.
Statement: There are two main techniques of reconstruction following colectomy
and proctocolectomy:
(1) Colectomy and ileorectal anastomosis (IRA) at about 12 cm from the anal
verge. Compared to a restorative proctocolectomy with an ileo-anal pouch (RPC),
this has three advantages: it is a one-stage procedure, has a low complication
rate, and leads to total continence. The disadvantages are a high cumulative
risk of secondary proctectomy (30% after 15 years of follow up), and a 10-15%
cumulative 25-year risk of rectal cancer, despite regular follow-up.
(2) Restorative proctocolectomy with an ileo-anal pouch (RPC). The advantages
of this compared to IRA are that it involves a more radical removal of rectal
mucosa, and thereby a very low risk of rectal cancer. The disadvantages are
that it is usually a two-stage procedure, has a higher complication rate,
involves a 5-10% risk of suboptimal continence, and that there is a 5% risk
of pouch removal due to complications or malfunction. Two techniques are currently
used: (1) a double-stapled anastomosis, i.e., a stapled anastomosis between
the pouch and the anal canal at the level of the anorectal junction, and (2)
a hand-sewn anastomosis, i.e., mucosectomy with a hand-sewn ileo-anal anastomosis
at the dentate line. Most surgeons perform a mucosectomy with a hand-sewn
pouch-anal anastomosis, but some prefer a double-stapled anastomosis. The
former ensures a radical mucosal removal, but may be followed by a longer
acclimatisation period before total continence and a final functional result
is achieved. The latter involves a risk of leaving 1-2 cm mucosa, but leads
to very good functional results shortly after the operation.
Both IRA and RPC result in an average of 3-6 daily bowel movements without
urge, and a good quality of life. However, RPC requires a high level of expertise
and experience, and should therefore be carried out by a surgeon who is used
to performing it. The technique of mucosectomy and hand-sewn pouch-anal anastomosis
is recommended.
Reply: 76% of the respondents agreed with the pros and cons of the surgical
procedures specified above. Two clinicians did not agree on the level of risk
of cancer developing after ileorectal anastomosis. One specialist mentioned
impotence and proctalgia as consequences of the surgical procedures. One responded
that an additional disadvantage of IRA is that it cannot be converted to RPC
if mesenterial fibrosis develops after the operation. One respondent emphasised
the possibility of a permanent ileostomy as a disadvantage of an RPC. A possible
disadvantage of a mucosectomy and handsewn anastomosis is that mucosa might
be left behind extraluminally and, consequently, that adenomas cannot be detected
by endoscopy.
Of the respondents who had a clear opinion on the technique of anastomosis,
67% preferred mucosectomy with a hand-sewn anastomosis, and 32% preferred
a double-stapled anastomosis procedure.
Statement: The choice of procedure remains controversial among surgeons, and
the pros and cons of the two alternatives should be discussed with the patient.
Most surgeons agree on the following general guidelines:
IRA is recommended in the following patients: those with few (less than approx.
20) rectal adenomas of less than 5 mm; those from families with attenuated
FAP; those with desmoid tumours; and those with a metastatic cancer of the
upper rectum or colon.
RPC is preferred in patients with a large number of rectal adenomas, in patients
with a non-metastatic cancer of the upper rectum or colon, and in patients
in whom a life-long follow-up cannot be assured.
Reply: 67% of the clinicians agreed that the presence of few adenomas is an
indication for IRA, whereas 32% also preferred an RPC in such patients. 73%
were in favour of an IRA in patients with an attenuated form of FAP, against
27% of the specialists who preferred an RPC. 58% preferred an IRA in patients
with a desmoid tumour, against 42% who were in favour of a RPC in such patients.
89% were in favour of IRA for patients with metastatic disease. 100% regarded
a large number of adenomas in the rectum and 94% noncompliance as an indication
for RPC. Nonmetastatic rectal and colon cancer are regarded as an indication
for RPC by 97% and 94% of the respondents, respectively. One specialist stated
that a low age might also be considered as an indication for IRA, and another
specialist mentioned poor sphincter function (i.e., poor control) as an additional
indication for IRA.
(3) Follow-up after colonic surgery.
Statement: After IRA, an endoscopic follow-up of the rectum is indicated at
intervals of 3-12 months, the intervals depending on the number, size and
degree of dysplasia of new adenomas. While adenomas > 5 mm should be removed
at each endoscopy, it is not necessary to remove every adenoma, irrespective
of its size, since such a practice may lead to scarring of the rectum, which
makes subsequent assessment difficult.
Reply: 87% agreed with the statement. Two specialists preferred one-year intervals
between examinations. Another respondent suggested a four-month interval in
patients older than age 50.
Statement: After RPC, an annual follow up by digital examination and rectoscopy
is indicated to identify adenomas at the site of the ileo-anal anastomosis
and in the pouch.
Reply: 78% agreed that annual follow up is indicated, both after the double-stapled
procedure and after hand-sewn anastomosis. 17% were of the opinion that follow-up
is indicated only after the use of the double-stapled technique. 94% recommended
both digital examination and rectoscopy.
Statement: Treatment of a patient with rectal adenomas after IRA with NSAID
(e.g. Sulindac) should only take place in the setting of a prospective study.
The follow-up should continue even after the adenomas have disappeared.
Reply: 76% agreed with this statement. 24% thought that treatment with NSAID
might also be justified outside the setting of a prospective study if the
follow-up were appropriate.
(4) The surveillance protocol of polyposis of the upper GI tract,
Statement: Although the value of the screening of the upper GI is unknown,
the option of regular gastroduodenoscopy should be discussed with the patient:
the pros are early detection, and the surgical treatment of severe duodenal
adenomatosis or early carcinoma. The cons are the low risk (probably <
5%) of duodenal cancer; the absence of definite proof of the benefit of prophylactic
examinations, the increased risk of carcinophobia, the morbidity associated
with periodic endoscopies; and the risk of morbidity and even mortality associated
with major surgery, which in this case is carried out for a condition that
is most often non-malignant.
Reply: All respondents recommended surveillance of the upper GI tract. 95%
agreed with the pros and cons of surveillance specified above.
Statement: If the patient agrees, one should start regular gastroduodenoscopy
at the age of 30 years, continuing this at intervals of 1-3 years, depending
on the stage of the duodenal adenomatosis. The Spigelman classification 5 should
be used, and examinations should preferably be carried out in the setting of
a prospective study.
Reply: 79% of the respondents agreed with the proposed protocol. Among the
other respondents, five recommended that surveillance should start at an earlier
age, e.g., at the age at diagnosis of FAP, or an age between 20-25. Two participants
reported problems with defining the interval of the examinations on the basis
of the Spigelman classification, because a small adenoma with high degree
of dysplasia together with a low Spigelman score is also an indication for
shortening the interval.
Statement: A pancreas-sparing duodenectomy or a partial pancreatico-duodenectomy
should be considered in patients older than 35-40 years with a continued finding
of duodenal adenomatosis Spigelman stage IV after one year.
Reply: 65% agreed with this statement, while 24% did not, and 11% did not
know what would be the best policy. Among the 24% who did not agree, three
were of the opinion that Whipple’s operation should be reserved for
patients with malignant disease. Three other respondents would prefer a less
radical operation. One participant stressed that ‘we really don’t
know what would be the best approach.’
The various surgical procedures were recommended as follows: pancreas sparing
duodenectomy (11 respondents), partial pancreaticoduodenectomy (12 respondents),
duodenectomy with mucosectomy (4 respondents), and ampullectomy (2 respondents).
(5) The management of desmoid tumours
Statement: Examination should include evaluation by CT-scanning and, if possible,
MRI.
Reply: 82% agreed. There were no specific comments.
Statement: Surgical treatment is indicated in extra-abdominal and abdominal
wall desmoids. Surgical treatment of intra-abdominal desmoids may be considered,
as a palliative treatment, only in severely symptomatic cases.
Reply: 85% agreed. Two respondents stressed that intestinal by-pass is the
sole intervention indicated in severe cases of intra-abdominal desmoids.
Statement: Medical treatment with Sulindac and Tamoxifen (or Toremifene) may
be of benefit, and chemotherapy with Doxorubicin and Dacarbazine may be considered
in severe cases for which there are no other therapeutic options. Treatment
of desmoids should preferably take place in the setting of an international
study.
Reply: 97% agreed. One respondent would prefer radiotherapy to chemotherapy.
Discussion
FAP is a rare dominantly inherited disorder with a high penetrance but a variable expression. In order to improve the care of affected patients, its management is often centralised or co-ordinated by a polyposis registry.1,2,3 To enhance research in FAP, an international collaborative group of specialists and scientists – The Leeds Castle Polyposis Group – was established more than a decade ago.6 The data presented in this manuscript are the result of a survey conducted among the members of this group. The aim of the survey was to outline current ideas on the management of FAP at the various polyposis registries.
Diagnostic evaluation
All respondents agreed that a newly-identified polyposis family should be
referred both to a polyposis registry and to a clinical genetic centre. The
original aims of polyposis registries are to promote the identification of
relatives at risk, and to ensure their lifelong participation in the surveillance
programme. The clinical genetic centres that became interested in FAP after
the identification of the polyposis gene are specialised in genetic counselling
and the DNA-testing of families. The tasks of both types of institute might
therefore be considered to be complementary.
A recent study in the USA7 revealed that few of the individuals who had been
tested for mutations in the APC-gene had received appropriate genetic counselling.
The fact that all respondents in the present survey considered the involvement
of a genetic centre to be mandatory, indicates that all polyposis families
will receive the appropriate counselling.
The study showed that specialists involved in the care of polyposis families
have more trust in the outcome of the results of the DNA-test than they had
a number of years ago. Very few specialists would continue periodic examinations
after a negative test in the case of a known mutation in the family. If mutation
analysis did not lead to the identification of the mutation, it might be useful
to use linkage analysis, especially in large families. Two respondents reported
that they would not use the results of linkage analysis for the detection
of carriers of FAP. Although mutation analysis is the method of choice because
of its absolute reliability, the linkage approach becomes almost as reliable
as mutation analysis in families with sufficient support for linkage between
the disease and the APC locus (lodscore > 0.9).8
It should be emphasised that genetic testing led to identification of the
mutation in only 67-82% of the families.9,10 In the remaining families it
is possible to estimate the risk of being a carrier on the basis of age of
the last negative (i.e., polyp-free) sigmoidoscopy, or of the absence or presence
of retinal lesions and osteomas. The most important indications for retina
examination and orthopantographic examination of the jaws are in families
where DNA-testing did not lead to the identification of the mutation.
Most respondents agreed that the surveillance programme (sigmoidoscopy at
two-year intervals from age 10-12) is appropriate, both for at-risk relatives
and for proven gene carriers.
Surgical management of colonic polyposis
Experience has shown that most polyposis patients identified through family
screening have colonic surgery at an age between 15 and 25. There was general
agreement that the exact timing of the operation depends both on the severity
of the polyposis and on personal social factors.
The well-known disadvantages of IRA are the high cumulative risk of secondary
proctectomy and the risk of developing rectal cancer.11 The disadvantages
of RPC are the higher complication rate, and the less satisfactory functional
outcome. One respondent indicated that an additional disadvantage of IRA is
that the development of an intra-abdominal desmoid tumor after the operation
can make a secondary proctectomy impossible.
There was no agreement about the preferred surgical procedure. Although the
majority of the respondents considered both the finding of a few polyps in
the rectum and an attenuated form of polyposis to be appropriate indications
for an IRA, a substantial proportion of the respondents (one third) would
also perform an RPC for these indications. For some respondents, the presence
of an intra-abdominal desmoid is a reason to perform an IRA; however, for
an equal number of respondents, it is an indication for a RPC. The most important
argument for choosing an RPC as the preferred primary option is the fact that
conversion into RPC might be impossible in the event of the further growth
of the desmoid. On the other hand, it might be argued that the most extensive
surgical procedure that may lead to growth of the desmoid (i.e., RPC) should
be avoided. One respondent suggested that a poor sphincter is a contraindication
for IRA. In the opinion of the authors, this would represent a relative contraindication
for both procedures. There was no doubt among the respondents about the indications
for RPC, i.e., patients with a large number of polyps in the rectum, and patients
who do not wish to comply with the follow-up examinations. Most members agreed
that patients with a mild form of polyposis are good candidates for an IRA.
A recent study revealed that patients with mutations known to be associated
with a less aggressive form of polyposis had a lower risk of a secondary proctectomy
due to uncontrollable polyps, than patients with mutations known to be associated
with an aggressive form of polyposis.12 If larger studies confirm these findings,
the result of mutation analysis in combination with the clinical phenotype
of a specific family might be helpful in the surgical decision-making.
One respondent suggested that IRA should be performed in young patients, and
RPC in those whose age was more advanced. The background for this suggestion
lay in the results of a St Mark’s study13 that showed that the risk
of rectal cancer increases sharply between age 50 and 60. On the basis of
these findings it was proposed to convert an IRA into an RPC in patients reaching
this high-risk age. If a patient had already reached an advanced age, it might
be argued that RPC should be performed as the primary procedure in order to
avoid a second operation a little later. However, there are as yet no published
results of such a policy, and the potential reduction of the incidence of
metachronous rectal cancer must be outweighed by the morbidity of the conversion
procedure. More studies are needed to find out whether the reported increase
of risk between age 50-60 applies to all patients.
There was no agreement pertaining to the technique for performing the anastomosis.
Two techniques are currently used: i.e., a stapled anastomosis between the
pouch and the anal canal at the level of the anorectal junction (double-stapled
anastomosis), or a mucosectomy with a conventional ileoanal anastomsis at
the dentate line (hand-sewn anastomosis). Two thirds of the respondents preferred
a hand-sewn anastomosis, while one third advised a double-stapled anastomosis
in polyposis patients. A well-known disadvantage of the double-stapled anastomosis
is the fact that it may leave 1-2 cm mucosa which is at risk for adenoma/carcinoma
development. A disadvantage of the hand-sewn anastomosis is that there might
be a risk of leaving mucosa extraluminally, which might make early detection
by endoscopy impossible. The few studies that are available suggest that functional
outcome is better after a double-stapled technique than after the hand-sewn
technique.14
Most respondents recommend follow-up after IRA (at a three to twelve-month
interval), and after RPC, regardless of the technique that has been used (i.e.,
follow-up annually both by digital examination and endoscopy).
Surveillance of the upper GI tract
Several reports indicated that at least two thirds of polyposis patients have
duodenal polyposis. There is ample evidence that the duodenal adenoma also
follow the adenoma-carcinoma sequence observed in the colorectum.15 A recent
retrospective registry-based study suggested that the lifetime risk of developing
duodenal cancer is less than 5%.16 The present study showed that, despite
the fact that the effectiveness of surveillance is unknown, all participants
discussed the possibility of surveillance with their patients. There was also
general agreement about the surveillance programme, i.e., gastroduodenoscopy
at 1-3 year intervals starting from age 30.
In contrast, there was no agreement about the indication for and the timing
of surgery. Criteria regarding size, rapid growth, polyp induration, or consistently
severe dysplasia or villous change suggest that intervention is necessary.
In view of the morbidity of major pancreatic surgery, some respondents would
consider surgery only in patients with histologically proven carcinoma. Hopefully,
ongoing studies17,18 on the natural history of duodenal polyposis will lead
to the identification of patients at high risk of developing cancer. Treatment
could be more focused if it were possible to predict the natural history of
the disease, such that those individuals destined to develop duodenal cancer
would be treated in a premalignant stage. Five respondents recommended a duodenoscopy
at an earlier age, e.g., at the time of colonic surgery. Although this might
be appropriate, especially to reassure relatives of patients with duodenal
disease, it not strictly necessary, as the natural history of the disease
indicates that duodenal cancer is extremely rare before age 30.
There was no consensus on the preferred surgical procedure. However, as recent
studies indicate that mortality due to pancreatic surgery is significantly
higher in hospitals with limited experience (i.e., those carrying out fewer
than five procedures per year), we would therefore like to emphasise that
such procedures should be performed at highly specialised centres.
The management of desmoids
Desmoids are benign fibromatous lesions that arise most often in the abdominal wall and mesentery, but also occasionally in the extremities and trunk.19 These lesions are observed in 7-11% of polyposis patients. The mean age at diagnosis is 30 years. Complications from desmoids have been reported to be second only to metastatic cancer as a cause of death in FAP patients. The cause of desmoids is unclear. In FAP patients, desmoid development has been associated with abdominal surgery, pregnancy and exposure to oral contraceptives. The family history of desmoids may also be an important risk factor. A recent study20 showed that the desmoid risk in FAP family members of a desmoid patient was 25% in first degree relatives. The treatment of desmoids is controversial, and is based largely on anecdotal reports and on studies of small series of patients. The extremely variable natural history of desmoids hampers the evaluation of a specific treatment. The present survey indicated that there is agreement that surgery should be avoided for mesenteric desmoids because of the risk of accelerated growth and the high risk of recurrence. The problem with radiotherapy suggested by one of the respondents is that its use is limited by the radiosensitivity of the surrounding intra-abdominal structures. Most respondents recommended Sulindac as the initial treatment. If growth continues, Tamoxifen or Toremifene is added. If the desmoid is still growing or is giving rise to significant symptoms, Doxorubicin and Dacarbazine chemotherapy is considered. As emphasized by several respondents, operation on intra-abdominal desmoids may be needed to bypass bowel obstruction or to relieve ureteric obstruction.
Conclusion
The survey demonstrates agreement on most parts of the protocol, but also conspicuous differences of opinion on some other parts. It should be emphasised that not all these recommendations have a strong scientific basis. Careful education and counselling of patients and their relatives about all details of the disease are therefore essential. Ideally, the outcome of the protocols should be collected in a uniform manner at a polyposis registry. Hopefully, this information will help to extend effective care to all carriers of the disease.
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