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422 M. Pescatori
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Introduction
Inflammatory bowel diseases (IBD), which appear
mainly in the form of ulcerative colitis (UC) and
Crohn’s disease (CD), represent complex disorders
as documented by the wide variations found in clini-
cal practice. IBD has an impressive impact on
patients and society because the presentation of the
disease occurs in the majority of cases at a young age
and, depending on its chronic evolution, has the
potential of causing lifelong ill health.
Patients suffering from this disease present symp-
toms and clinical situations often embarrassing and
having deep impact on their quality of life. Consider-
ing the young age of this patient population and the
long duration of the disease, the problem of adequate
medical management has crucial relevance. Conse-
quently, we realised an interdisciplinary IBD Unit in
our hospital with the aim of improving our clinical
results and developing closer and stronger contact
with the patients.
The medical strategy should always take in
account some critical points such as the type of the
disease, the severity and extent, the clinical response
and tolerance of drugs and the follow-up in terms of
monitoring the quality of life and preventing possible
complications.
Diagnosis of IBD
This is often not a simple issue. The classical clinical
pattern is well known, but the symptoms are not so
clear and the differential diagnosis includes infective
diarrhoeas, drugs intolerance, haematological dis-
eases and neoplasia. Once the diagnosis of IBD is
clear, we have to remember, before starting with
therapy, that 50% of relapses are associated with
pathogens. Moreover, the radiologist, the endo-
scopist and the pathologist should have detailed
information about the clinical situation, so that they
can make every effort to get the right diagnosis. That
means that special attention and training in this dis-
ease is required for any specialist involved in the
diagnostic process.
Ulcerative Colitis
Proctitis affects approximately 30% of patients at
presentation and later spreading to a more proximal
extent is possible in about 40% of cases. The main-
stay of treatment is topical administration of
mesalazine or steroids. The topical or oral route is
sometimes insufficient with the frustrating problem
of a proctitis unresponsive to medical therapy. In the
non-responders, rectal bismuth preparations [1] and
arsenical suppositories [2] seem to be effective and
safe, but about 5% of the cases need total colectomy
because of impaired quality of life [3].
Left-sided and pan-colitis are usually well man-
aged with the standard regimens of steroids and
mesalazine, but attention has to be paid to the
patients who develop resistance or dependence of
steroids. The gastroenterologist and the surgeon
should very carefully consider the possible options,
particularly in cases of severe, unresponsive or ful-
minant colitis in which the lack of clinical improve-
ment within the first week of medical therapy repre-
sents an indication for colectomy. This observation is
even stronger in patients with toxic dilation of the
colon-in this case colectomy is mandatory in the
absence of response within 24 h [4].
In all these situations we should always bear in
mind a comprehensive view of the life of our patients
in terms of severity of symptoms, safety of the cur-
rent therapy, drug toxicity, safety of surgical proce-
dure and quality of life expectancy. As David Sachar
said some years ago “we too readily accept as a crite-
rion of success the ability to keep patients out of sur-
gery. Somehow the internists tend to view surgery as
a last resort or as indication of failure of medical
therapy. In adopting such an attitude we render our
patients a terrible disservice.”
Interdisciplinary Management of Inflammatory Bowel
Diseases
Michele Comberlato, Federico Martin
424 M. Comberlato, F. Martin
Crohn’s Disease
Given the complexity and heterogeneity of the dis-
ease and the different options for combining therapy,
it is unlikely that sufficient controlled trials will ever
be conducted to provide evidence for the best treat-
ment for every clinical scenario. In many patients,
several therapeutic options may represent valid alter-
natives. In this field, as in many others, patient pref-
erence should be an important factor in determining
the choice of therapy. All physicians need to be aware
that smoking is the most important risk factor statis-
tically associated with Crohn’s disease, with higher
relapse rates following surgical resections and a
greater risk of perforating disease [5, 6]. In a patient
with a classical clinical ileal/colonic manifestation,
there are many valid options including antibiotics,
steroids, immunosuppressives, enteral nutrition and
surgery.
A typical ileitis with poor response to medical
therapy, and consequently poor quality of life for the
patient, is a clear and unquestionable indication for
surgery. On the other hand, a patient with multiple
ileal localisations of the disease has to be conserva-
tively managed for as long as possible.
In any severe situation, we should consider the
great impact of the quality of nutrition on the state of
the intestinal wall. Enteral nutrition employed as the
only source of feeding is an effective therapy for
Crohn’s disease and its mechanism of action,
although poorly understood, consists of an
immunomodulatory procedure on the bowel
mucosa, which consequently effects the bacterial
flora. An elemental or polymeric diet is equally effec-
tive [7, 8].
Perineal disease occurs in up to one third of
patients with Crohn’s disease, impacting differently
according to the different clinical phenotypes: ileal
CD 12%, ileo-cecal CD 15%, colonic CD 41%, col-
orectal CD 92% [9]. The medical management of per-
ineal disease has been absolutely unsatisfactory with
poor results in the short as well as in the long term.
The availability of infliximab made it possible to
greatly improve our results, which were even better
when infliximab was associated with local non-inva-
sive surgery such as drainage of fluid collection, fis-
tulotomy or application of setons [10].
Topics on IBD
Fecundity and Pregnancy
Women with UC and CD are known to have fecundi-
ty and pregnancy equal to that of the general popula-
tion [11, 12], but they are worried about the risks to
the newborn in terms of damage by drugs or by the
illness itself. The medical staff plays a very crucial
role in informing and encouraging women with IBD,
explaining the safety of the drugs employed and the
general risks regarding pregnancy for healthy
women.
In comparison with the general population,
women in remission under azatioprine have no
impairment, either in fecundity or in the capability of
having a regular pregnancy without particular risks.
In women who underwent restorative proctocolecto-
my with ileo pouch-anal anastomosis (IPAA), partu-
rition is normal and IPAA function is not damaged
[13]. However, there are reports in the literature that
give advice about the critical risk of infertility after
IPAA including a decrease of potential fertility up to
80% [14, 15]. Our female patients should be correctly
and tactfully informed about this possible complica-
tion, due in most cases to a tubal occlusion from
adhesive disease. Would a more diffuse laparoscopic
approach ameliorate this data?
Pouchitis
Pouchitis seldom occurs after IPAA and is usually
easily resolved with topical therapy and antibiotics,
but doubts should arise in case of poor response and
a tendency to chronicity. IPAA fails in 8% of patients
with evident differences in the different groups:
6.5–19% in indeterminate colitis, 15–43% in CD and
1.4–8% in UC [16–18]. Only close collaboration
between the gastroenterologist and the surgeon dur-
ing the follow-up of pouchitis can evaluate the results
of conservative therapy and decide the right time for
revision of the pouch, which shows good clinical out-
come in up to two thirds of patients [19, 20].
Surveillance for Dysplasia and Cancer
The clinical heterogeneity of IBD is reflected in the
heterogeneity in the macro and microscopic feature
and makes cancer surveillance in this population
much more challenging than in the general popula-
tion. IBD associated risk factors for colorectal cancer
are well known and this is the reason why any patient
with a history of extensive disease, whether UC or
CD, of more than 10 years must undergo a complete
colonoscopy with multiple biopsies every 2 years.
Any dubious situation should be carefully discussed
by the gastroenterologist, the surgeon and the
pathologist and the maximal alert in case of dysplasia
or cancer on flat inflamed mucosa should be given.
In the past, the more crucial issue was the signifi-
Interdisciplinary Management of Inflammatory Bowel Diseases 425
cance of dysplasia in endoscopically visible lesions
(Dysplasia Associated Lesion or Mass) with high rates
of carcinoma when these patients underwent colecto-
my. In more recent data, about 10 surveillance pro-
grams reported findings of carcinoma in 17 out of 40
(43%) colectomies performed with an indication of
DALM [21]. However, not all polypoid lesions with
dysplasia carry the same significance for IBD patients.
Some polyps can be snared like adenomas unrelated
to colitis, particularly if they arise in a segment of the
colon not involved in inflammation, and can be man-
aged like polyps in the general population [22].
The dysplasia encountered in an adenoma or in
chronic inflammation is quite identical and so we
have no reliable means of differentiating between
them in regards to our decision. A well-conducted
study tried to answer this question and concluded
that no adverse outcomes resulted after endoscopic
removal of 70 polyps (three with high-grade non-
invasive dysplasia) from 48 IBD patients in a mean
follow-up time of 4.1 years [23].
The best way to manage dysplasia and colorectal
cancer is via a surveillance program; however, in this
case the patients have to be correctly and clearly
informed that dysplasia and cancer can still arise
despite the program of close observation and the
skilfulness of the medical staff [24]. In our opinion,
the development of dysplasia itself in a surveillance
program is not enough in itself to advise patients to
undergo colectomy. Situations are different and, as
mentioned before, even a severe dysplasia in an ade-
nomatous polyp not related to inflammatory disease,
could be optimally managed with a radical polypec-
tomy. As always in this context, such a decision of
course requires that the gastroenterologist, surgeon
and pathologist develop a decision-making protocol
through which information about the patient, specific
literature data, personal experience and skills are
clearly shared and accepted.
Intestinal Strictures
Intestinal fibrostenosis is a debilitating complication;
even in this era of potent biologic therapies, the
mechanisms promoting the underlying fibrosis in
IBD are still misunderstood. From a conservative
point of view, the target of therapy in this field is
TGFb and its intracellular mediators (SMAD pro-
teins) and, theoretically, interleukin 10 could be the
ideal cytokine to be used in IBD, since it has been
proven to be a potent anti-inflammatory and anti-
fibrogenic agent. Nevertheless, clinical data about IL-
10, antibodies against TGFb and SMAD proteins, Ca
2+
blocking and cyclic nucleotides to modulate collagen
production gave no results.
Drugs are useful in reducing the inflammatory
component of the stricture, but once the fibrosis has
scared the lumen, there are only two options: endo-
scopic balloon dilation or surgical intervention,
which means either strictureplasty or resection.
Endoscopic balloon dilation has been proven to be
very effective, safe and repeatable when used in short
and anastomotic strictures. A recent trial on endo-
scopic management of CD upper and lower strictures
in association with local steroid injection had very
good results: technical success (ability of the scope to
pass the stenosis) of 29 dilations on 17 patients was
96.5%, the long-term success (mean follow-up
18.8 months, 5–50) was 70% if the dilation
was<15 mm and 68.4% for dilations >15 mm. The
recurrence rate in the group with steroid injection
was 10 and 31.3% in patients who only received dila-
tion. The long-term success rate was 76.5% with a
10% complication rate, with no mortality [25].
As in other critical situations, the decision of what
to do should be shared with the patient; repeat endo-
scopic dilation is of course a valid and safe option
and the length of the symptom-free interval will be
the main parameter used to decide between conser-
vative management and surgery.
Prevention of Post-Operative Relapse
The 5-aminosalicylates remain the most controver-
sial agents in the maintenance of remission of
Crohn’s disease. Several studies and a recent meta-
analysis have shown no significant benefit in com-
parison to placebo, but the meta-analysis suggested a
potential role in patients with surgically induced
remission, where mesalazine lowered the risk of
relapse by 13% [26]. These general data were better
clarified in a randomised study in which 5-ASA
gained a significant reduction in relapse rate in post-
operative prophylaxis in a subgroup of patients with
limited ileal disease [27]. Therefore, while waiting for
confirmation data, our team routinely treats resected
patients for ileal CD.
The Patient’s Point of View
The patient’s point of view is a very crucial issue in
regard to patients who suffer from IBD. The majority
of newly diagnosed cases are between 18 and 35 years
of age and, considering the peculiar characteristics of
the disease, it is fundamental that any doctors
involved in the management of the patient establish,
maintain and improve on a long-term doctor–patient
relationship.
The diagnosis of IBD has a profound impact on the
426 M. Comberlato, F. Martin
lives of patients, so any physician notifying the
patient should be aware of this impact, be able to han-
dle a variety of reactions of the patient, and be sure to
leave the patient with a sense that they are not going
to have to go through the challenges of IBD alone [28].
The characteristics of the disease must be
explained as well as the medical options and even the
chance of possible surgery. A recent UK study out-
lined the key issues that concern IBD patients:
– Fear of incontinence when using public transport,
shopping, vacationing and when at work.
– Fear of hospitals and treatment.
– Fear of cancer.
– Effects on employment including limitations in
regards to types of jobs and promotion prospects
– Effects on holiday medical and life insurance.
– Guilt because of the effects of the above problems
on the family.
– Anxiety and sense of isolation.
Regarding these considerations, the multidiscipli-
narity organisation of the management program
should be made clear to the patient. Previously
healthy young patients who seldom saw a physician
find themselves in a situation where they are sur-
rounded by many doctors and, therefore, they
absolutely need a primary care figure who can medi-
ate with others, discuss and explain any proposal
offered by different specialists and coordinate the
work of the entire group.
IBD group support services are very helpful for
patients with severe disease in providing practical
information, sharing concerns and personal fears
and acquiring, step by step, the balance necessary to
enjoy a good life in spite of IBD.
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Introduction
Colorectal carcinoma (CRC) represents a clinical and
epidemiological relevant illness due to problems of
acquiring an early diagnosis and the fact that it is a
major cause of mortality worldwide and accounts for
nearly 4% of all deaths in Western countries [1, 2].
Nearly 90% of CRC is the final result of a step-by-step
progression from the normal mucosa to adenoma-
tous polyps and finally to dysplasia and adenocarci-
noma. The biological evolution takes many years and
should allow enough time for early diagnosis and
therapy, as it is widely accepted that endoscopic/sur-
gical polypectomy prevents the otherwise natural
progression to carcinoma.
The two major forms of hereditary CRC, which are
quite different, include the hereditary non-polyposis
colorectal cancer (HNPCC) and the familial adeno-
matous polyposis (FAP), which represents 5–10% of
the total number of cases of CRC. Familial adenoma-
tous polyposis is a troublesome autosomal dominant
disease that evolves quietly until clinical manifesta-
tions appear, which means that the development of
innumerable adenomatous polyps start to develop at
puberty and gradually increase their growth to
involve the whole colon at adulthood. The manage-
ment of FAP represents a challenge for gastroen-
terologists and surgeons in terms of history of the
disease, evaluation of the clinical pattern, therapeutic
options, follow up and chemoprevention of relapses.
History of the Disease
As mentioned before, FAP is a hereditary autosomal
dominant disease and the responsible gene is the
APC gene, a quite large gene located on chromosome
5q21, of which there are more than 1400 described
mutations [3, 4]. The APC mutation is inherited as a
germline mutation from the affected parent, but ade-
nomas start their uncontrolled growth only when the
second allele has mutated or is inactivated. The
coded APC protein plays a critical role in the difficult
balance between healthy and diseased cells, since it is
responsible for tumour suppression, cellular prolif-
eration, regular differentiation, migration and apop-
tosis [5].
This multifactorial regulation produces many
extremely different clinical features and the main dif-
ficulty lies in relating a peculiar disease to a multifac-
torial genetic disease. Most likely, before the APC
gene was identified, many syndromes were known:
Turcot’s syndrome (FAP, neoplasia of central nerv-
ous system); Gardner’s syndrome (intestinal polyps,
multiple osteomata, cysts, desmoid tumours, gastro-
duodenal polyps, mesenteric fibromatosis, lymphoid
hyperplasia of the distal ileum, ileal adenomas and
dental abnormalities); Cronkite-Canada syndrome
(gastrointestinal polyps, skin hyperpigmentation,
nail dystrophy and alopecia) and attenuated FAP
(<100 intestinal polyps, primarily located in the right
colon) [6, 7], which now simply reflect different loca-
tions of mutations along the gene.
A recent study in the UK examined 614 families
recorded in six regional registries regarding polypo-
sis and identified 111 family clusters as having nei-
ther the dominant transmission nor evidence of APC
mutation. Molecular genetic tests showed the pres-
ence of a biallelic mutation in the MYH gene [8] in 25
families.
The MYH gene is responsible for base excision
repair mechanisms and its mutations have been
shown to produce an autosomal recessive trait
expressed by multiple colorectal adenomas and relat-
ed high risk of colorectal cancer [9,10]. Now we know
that FAP can be transmitted not only as an autosomal
dominant disease but also as an autosomal recessive
trait, a situation that requires a change in how the
physicians regard FAP, in genetic counselling, testing
and surveillance.
Clinical Features
The core of the clinical and diagnostic problem is the
nature of APC gene itself. The APC gene is a germline
Interdisciplinary Management of Familial Adenomatous
Polyposis
Michele Comberlato, Federico Martin
430 M. Comberlato, F. Martin
mutation, which means there is a wide possibility
that the mutation will find expression not only in
intestinal but also in extra-intestinal sites including
the thyroid, pancreas and duodenum, adrenal glands
and liver. Such variability in clinical manifestation of
the same genetic disorder represents real problems
for physicians in terms of the right initial diagnosis,
therapeutic options, follow-up and need for accurate
clinical surveillance of the relatives.
The classical intestinal syndrome has a specific
and more or less severe pattern including intestinal
bleeding, abdominal pain, diarrhoea, mucous dis-
charge. A patient reporting these symptoms usually
refers to the family doctor and then will be sent to a
gastrointestinal unit for a visit or colonoscopy. What
a surprise for the endoscopist and for the patient as
well in discovering hundreds of polyps along the
colon.
The presence of a hypercatabolic balance with
weight loss, anaemia and intestinal obstruction
makes the development of a neoplasia suspicious and
approximately 25% of patients present colorectal
cancer at first diagnosis [11]. Moreover, the risk of
developing a CRC is directly related to the number of
polyps [12]. The first point at this time is to be aware
of the peculiar genetic pathology and of the wide dis-
play of clinical features and to create a task force
involving all the needed specialists–the pathologist,
the gastroenterologist, the surgeon, the radiologist
and the geneticist–in the management of the patient.
While waiting for molecular genetic tests, which
need months to be completed, the patient should
undergo a full diagnostic program to detect or
exclude other clinical relevant diseases, due to the
wide clinical expression of the genetic alteration.
Genetic testing is the sole and most efficient proce-
dure for discovering gene carriers in a suspected FAP
patient and in the relatives. Once a distinct mutation
is recognised in a subject, the linkage analysis on
chromosome 5 has an accuracy of 70–90% [13].
Screening colonoscopy in patients known as carri-
ers of an APC mutation should start at the age of
10–12 years and in the risk population of 15 years of
age, with colonoscopic follow up every year between
15–26 years of age, every second year from
26–35 years of age and then every 3 years [14]. In
spite of the lack of a clear, validated diagnostic pro-
tocol, all patients should undergo an upper tract
endoscopy with forward- and side-viewing instru-
ments.
Duodenal polyps are found in the majority of
polyposis patients and may lead to carcinoma devel-
opment. An endoscopic and histological classifica-
tion for the evaluation of the severity of duodenal
adenomatosis was published in 1998 and has become
the gold standard in several subsequent studies [15].
As in the colon, duodenal and ampullary polyps have
to be resected, either endoscopically or surgically,
and then regular scheduled follow-ups have to start,
based on the histology of the removed polyps. Carci-
noma of the duodenum, ampulla of Vater or pan-
creas have been strongly associated with Gardner’s
syndrome and a research at St. Mark’s Hospital doc-
umented a 12% incidence of periampullary cancer in
a series of patients 5 years after colonoscopy [16].
That means that every patient should undergo fre-
quent upper gastrointestinal endoscopies yearly, a
full clinical examination and many other examina-
tions because of the risk of developing diseases in
extra-colonic sites.
Mesenteric fibrosis and desmoid tumours are
often severe complications of FAP with a reported
incidence of 3.5–5.7% between 1 and 3 years after
colectomy [17]. Desmoid tumours usually arise in the
abdominal cavity, in the retroperitoneum or in the
abdominal incision; extensive small bowel and uri-
nary resections are often needed to resolve complica-
tions usually secondary to intestinal or vascular
occlusion [18, 19]. Epidermal cysts are common
benign findings, but seldom appear before puberty,
so an early diagnosis could represent a warning for
the physician to proceed with further evaluations for
gastrointestinal polyps [20].
Sites for osteomas are typically found in the
mandibula and skull and may be the only extra-
colonic manifestation of the disease [21, 22]. Annual
examinations should screen the thyroid and liver
because of the risk of neoplasia. Lastly, the presence of
ocular alteration as asymptomatic pigmented fundic
lesions are reported in more than 90% of FAP and
Gardner’s patients. The congenital hypertrophy of the
retinal pigmented epithelium, when present in the rel-
atives, is almost 100% predictive of FAP (Table 1)
[6, 7].
So the familial adenomatous polyposis is much
more than a disease of the bowel and a very close
cooperation between different physicians is neces-
sary to ensure that our patients receive the best
chances for an early and correct diagnosis, the best
possible management and an optimal follow-up.
Management
Up to now, surgery is the only effective therapy for
removing all the polyps and preventing the inevitable
progression to cancer. The general recommendation
is that prophylactic colectomy is advisable by the late
teens in patients with a sure diagnosis of FAP [5].
There are currently three surgical options including:
(1) restorative proctocolectomy with ileal pouch anal
anastomosis (RPC/IPAA) with mucosectomy, (2)
Interdisciplinary Management of Familial Adenomatous Polyposis 431
RPC/IPAA using the double staple technique and (3)
colectomy with ileo-rectal anastomosis (IRA). A
fourth option, a proctocolectomy with permanent
ileostomy, can only be considered in the few cases in
which an RPC/IPAA or an IRA is contraindicated.
An RPC/IPAA with mucosectomy has the advan-
tage of removing the entire colon, that means all the
polyps, and taking away the anal mucosa with mini-
mal remaining risk of developing colorectal cancer.
In spite of the obvious technical problems, restora-
tive proctocolectomy with IPAA and mucosectomy
has been the preferred approach at the Mayo Clinic
with a low reported post-operative complication rate
and satisfactory functional results [23, 24].
As a critical comment on these results, some
authors argue that islands of rectal mucosa might be
retained even with mucosectomy, in other words the
risk of developing new polyps is reduced, but not
eliminated [25, 26]. The alterative double-stapling
technique performed at the Cleveland Clinic offers a
better functional outcome, but also presents a 28%
increase in the development of adenomas in the tran-
sitional zone [27].
A total colectomy with ileo-rectal anastomosis
could offer better compliance, but needs a very care-
ful surveillance program. It is usually offered to
young patients with partial rectal sparing and less
than 20 rectal polyps. As in other critical patient
populations, like the IBD patients, surgical manage-
ment should be tailored to the different patients.
A review at Mount Sinai Medical Center docu-
mented the rise of rectal cancer at a mean follow-up of
13 years in 25% of patients with ileo-rectal anastomo-
sis. They concluded that proctocolectomy with ileo-
anal pouch should be the preferred surgical option,
which is in agreement with other authors [28, 29].
Medical Management
Prophylactic resection of target organs is usually per-
formed as treatment for familial tumours. However,
it should be preferable in preventing the develop-
ment of tumours thereby ensuring a better function-
al result for the patient and a better quality of life.
Although cancer prevention has been a matter of
debate for many years, an effective and safe strategy
has not yet been established. Since the first report by
Kudo about the ability of indomethacin in preventing
chemically induced colon cancer in rats [30], many
authors reported the low incidence of CRC in people
taking aspirin for a long time [31, 32]. In 1983, Wad-
dell and Loughry observed a significant reduction in
rectal polyps in four patients with FAP who took
NSAIDs on a regular basis for pain relief [33].
Successive studies reported that sulindac decreas-
es polyps in FAP and that cyclooxygenase 2 (COX-2),
which is not expressed in normal mucosa, is largely
expressed in colonic adenomas and cancerous tissue
[34, 35] with a large amount of proneoplastic effects
such as resistance to apoptosis via an increased level
of the Bcl-2 protein [36], increased cell migration and
invasion due to an over-expression of metallopro-
teinases [37] and increased levels of angiogenic fac-
tors [38].
This data promoted a lot of interest about the ther-
apeutic use of the new generation of the COX-2
inhibitors, which are more effective and clinically
safer in comparison with other NSAIDS. Recent stud-
ies have noted the role of the COX-2 inhibitors pre-
senting evidence of its abilities in reducing the
amount and size of polyps, preventing the occur-
rence/recurrence of colorectal adenomas and cancer
and counter-regulating angiogenesis in CRC liver
metastases [39-41]. Therefore, once the efficacy of the
COX-2 inhibitors is verified, what then should be the
role of medical therapy in this complex disease?
There is no doubt about the supremacy of surgery
as the only effective option for treating patients with
FAP in a radical way. However, considering the risk
of tumour should the relatives be diagnosed as carri-
ers of a high-risk mutation, and the risk of new ade-
nomas in the rectum should an ileo-rectal anasto-
moses be performed, anti-COX-2 drugs represent a
good therapeutic option, but clinical data do not
authorise their wide use outside of clinical trials.
Table 1. FAP: associated benign and malign lesions (modified from [5])
Neoplastic lesions Non-neoplastic lesions
Duodenal polyps/tumour (5–11%) Osteomas
Pancreatic tumour (2%) Desmoid tumours
Thyroid cancer (2%) Duodenal, jejunal, ileal polyps
Brain, medulloblastoma (<1%) Gastric adenomas
Hepatoblastoma (0.7% of children <5 years) Ocular fundic lesions
Epidermoid cysts
Radiopaque jaw lesions
432 M. Comberlato, F. Martin
In spite of all that, the efficacy shown in previous
studies using sulindac was not confirmed and the
National Cancer Institute in the United States is cur-
rently enrolling patients with FAP for a new clinical
study of a combination therapy with celecoxib,
eflorinithine (an ornithine decarboxylase inhibitor)
or a placebo [42].
Surveillance Protocol
As far as the post-surgical surveillance program is
concerned, there are no approved guide lines, so the
following considerations are based on data taken
from the literature.
Ileo-Rectal Anastomosis
In patients not protected by prophylactic therapy or
by a surveillance program, the incidence of cancer is
7% and 23–37% after 10 and 20 years respectively,
with a risk of secondary proctectomy at 70% 40 years
after initial surgery [43]. An endoscopy should be
performed 6 months after surgery and then every
year, and every single polyp should be resected or
destroyed with laser or APC coagulation.
Ileo-Anal Anastomosis
Data from literature report a 13 and 50% persistence
of residual rectal mucosa in manual and mechanical
anastomosis, respectively [44], with an ongoing risk
for new adenomas and cancer also in the pouch
where polyps can arise in 30–60% of patients, in rela-
tion to the endoscopic technique with or without
staining [45]. As in other fields, the literature in this
field also lacks validated data and in our opinion we
confirm the above recommendations about ileo-rec-
tal anastomosis.
Upper Digestive Tract and Small Bowel
As mentioned before, adenomas can also develop in
the upper digestive tract and the general risk of an
adenocarcinoma developing in these sites is 300
times higher than in the general population. Surveil-
lance should start very early in life at 20 years, and
full endoscopic examination has to be performed at
an interval of 6 months to 1 year, depending on the
amount of polyposis. Exams should be performed
with forward and side-view instruments in an
attempt to enhance the diagnostic power, and with a
liberal use of endoscopic staining.
The Spiegelman’s classification has defined four
stages according to the number of polyps, size, histo-
logical pattern (tubular or villous) and degree of dys-
plasia [15]. The presence of multiple small adenomas
is not an indication for therapy, but the development
of invasive cancer in the submucosa indicates a clear
need for surgical resection. Because of the variety of
clinical patterns of the disease, which causes over
500 000 deaths annually all over the world, looking at
FAP is like looking in a kaleidoscope. The key to the
problem is to better understand the complex mecha-
nisms that promote colon carcinogenesis so that we
can better target the diagnostic and therapeutic pro-
tocols.
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