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Desmoid Tumours in Familial Adenomatous Polyposis 369
noted that this favourable response to chemotherapy
of DTs defies the dogma in oncology that low-grade
tumours without metastatic potential do not respond
to chemotherapy [113].
Mesenteric Desmoid and Surgery
The presence of mesenteric DT can be incidentally dis-
covered at the time of total colectomy and can preclude
the scheduled procedure on account of technical rea-
sons. In the experience of the Saint-Antoine Hospital
of Paris, the presence of mesenteric DT ruled out con-
struction of IPAA (three patients), conversion of an
ileo-rectal anastomosis into an IPAA (three patients),
removal of the rectum for carcinoma (two patients),
construction of a continent ileostomy (two patients)
and duodenal-pancreatic resection (two patients) [13].
According to Hartley et al. [113], this situation was dis-
covered in 3% of the patients submitted to a first
laparotomy and in 30% of those submitted to a second
laparotomy, and also influenced the scheduled surgical
procedure, generally IPAA. Similarly, Cohen observed
significant mesenteric desmoid disease at the time of
the attempted IPAA in seven patients and a definitive
ileostomy was necessary [114].
The presence of a fibrous mesenteric mass or a
mesenteric fibromatosis may preclude the construc-
tion of an IPAA for two reasons: (1) the shortness of
the mesentery, (2) the impossibility of folding the
ileal loops. In these cases we were able to perform a
straight ileo-anal anastomosis since the terminal
ileum must not be folded and can be carried down to
the anal canal more easily than to the pouch, allow-
ing the ileo-anal anastomosis to be performed with-
out tension. However, the straight ileo-anal anasto-
mosis has been abandoned on account of the
unfavourable functional results. In our experience,
multiple longitudinal myotomies of the last 15 cm of
ileum provide a satisfactory functional result [115].
Surgical Treatment
For several authors, surgical intervention is the treat-
ment of choice for DTs. A complete excision is rec-
ommended because partial excision may trigger a
prompt recurrence. However, considering that DTs
are basically benign, the advantage of surgery may be
weighed with its consequences.
A different approach must be considered for
abdominal wall or mesenteric DTs. Common opinion
is that abdominal wall DTs can be removed, since the
surgical procedure is relatively easy and the possibili-
ty of a radical removal is high even in presence of a
huge mass. In order to obtain clear margins on histo-
logical examination excision in the muscular tissue is
recommended, often with the sacrifice of most
abdominal wall muscles. It is therefore important to
treat DTs when they are small, otherwise a large mus-
culoaponeurotic defect of the abdominal wall requires
reconstruction with synthetic devices or myocuta-
neous flaps. However, some authors [16, 26, 114]
maintain that surgery is not advisable even for DTs of
the abdominal wall. In fact, the recurrence rate varies
from 25 to 100% of cases, even when the DT has been
radically resected [13, 15, 87] and the iterative opera-
tion can provoke the development of DT within the
mesentery [18, 21–31]. Against imperative surgery, it
must be considered that DTs can cease to grow [27] or
even regress spontaneously [14, 33]. We are in favour
of surgery for this type of DT, but believe it necessary
to adopt a chemoprevention of the recurrence just
after surgery. We treated 15 abdominal-wall DTs with
radical surgery and employed SERMs as adjuvant
therapy in the postoperative period. Recurrence was
observed in two patients.
Conversely, mesenteric DTs can be removed only
when small and relatively distant from the root of the
small-bowel mesentery; since there is no plane of
cleavage around the mass, enucleation is impossible
and a concomitant resection of the surrounding
intestinal tract is frequently needed. Otherwise, the
risk is to remove a large part or the whole of the small
bowel. Treatment of intra-abdominal DTs is usually
reserved to cases in which complications occur such
as small-bowel obstruction, bowel perforation, intes-
tinal bleeding, hydronephrosis or deterioration of
the functional results after IPAA. When surgery is
chosen with curative intent, radical resection is
achieved in about 20% of cases [14–16] with a mor-
tality rate ranging from 2 to 10% [14, 19, 21]. In the
other 80% of cases, partial resection or biopsy alone
with or without intestinal bypass were performed.
Severe complications are reported in up to 60% of
cases [14]. Short-bowel syndrome, following wide or
multiple bowel resections, is reported in 4.7–20% of
cases [19, 21, 34]. Long-term parenteral nutrition and
small-bowel transplantation can be necessary in
some of these patients. The recurrence rate is around
70–80% (Table 3). The personal attitude was to avoid
surgery and treat the lesions medically with SERMs
or, in rare cases of refractory response, cytotoxic
drugs. In the majority of cases we could arrest the
growth of DTs and observe regression of symptoms
and mass.
Conclusions
Abdominal wall and mesenteric DTs are a common
manifestation in patients with FAP. The natural his-
370 F. Tonelli, L. Picariello, G. Nesi, A. Franchi, R. Valanzano, C.R. Asteria, M.L. Brandi
tory is extremely variable and largely depends on the
site of DT and its growth rate. Previous abdominal
surgery, family history of DTs, APC germline muta-
tion distal to codon 1444 and the female gender sig-
nificantly increase the susceptibility of developing
DTs. Prophylactic colectomy may be delayed in
women with an attenuated FAP and in patients
belonging to a family with evidence of DTs in more
than 50% of the members. It seems probable that an
attenuated form of mesenteric fibrosis represents the
precursor of infiltrating fibromatosis and large mass.
Even if the majority of DTs grow slowly and are
asymptomatic, a minority of DTs may present a fast
increase causing serious compression of intra-
abdominal structures and life-threatening complica-
tions. In recent years, research has clarified the
mechanism of actions of NSAIDs or SERMs and the
rationale for their use in DTs. Considering the low
toxicity of these drugs, they must be considered
either as a first-line treatment when a DT or a mesen-
teric fibromatosis is diagnosed or as a preventive
measure when DPLs are discovered at surgery. A
close surveillance of the lesions by regular clinical
and imaging assessment is mandatory. Progression
of the tumour or occurrence of symptoms despite
this treatment should promptly indicate cytotoxic
chemotherapy. The medical treatment must be pur-
sued for a long time, since shrinkage of DTs can be
delayed by months or even years. However, regres-
sion can continue after discontinuation of the thera-
py. Surgical therapy is indicated when its conse-
quences are not detrimental. Therefore, only extra-
abdominal DTs or small mesenteric DTs that are
located far from the mesenteric vessels and do not
require a large intestinal resection, are susceptible of
surgical resection. Postoperative therapy for preven-
tion of recurrence is indicated.
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Introduction
To have a better understanding of the role of
endoscopy in familial adenomatous polyposis, it is
necessary to clarify some concepts in colon cancer
development. Colon cancer (CRC) arises from a dys-
plastic precursor lesion called adenomatous polyp
(or adenoma). Approximately 30–40% of people over
50 years of age will develop an adenoma, but not all
adenomas will progress to CRC. In the general popu-
lation some individuals tend to develop one or only a
few adenomas and endoscopic polypectomy is often
sufficient for removing them, thereby markedly
reducing the subsequent development to CRC. Ade-
nomas arise when both copies of the APC gene are
lost. Indeed, the APC gene is considered the “gate-
keeper” of the colon, protecting against the develop-
ment of adenomas. The loss of APC gene function
permits adenoma formation and sets the stage for
subsequent molecular alterations of genes such as k-
ras and p53, which promote further progression to
CRC (Fig. 1). Some people develop multiple polyps of
the colon at a younger age due to inheritance of a
germline mutation of a gene that predisposes to CRC.
Since these patients are at increased risk of CRC (and
other types of cancer), it is important to recognize
these syndromes earlier (Table 1). Therefore, endo-
scopic procedures play a crucial role in the diagnosis,
staging and follow-up of these conditions.
Familial Adenomatous Polyposis
In these patients, the disease begins at the age of
8–10 years with a small number of colonic polyps,
increasing progressively until the colon becomes
studded with adenomas. Endoscopy mainly plays a
diagnostic role (Fig. 2) since colorectal cancer should
be considered an inevitable consequence in the natu-
ral history of FAP, appearing approximately 15 years
after the onset of the polyps. For this reason prophy-
lactic proctocolectomy is the procedure of choice for
this condition. After the proctocolectomy, the ileal
pouch could develop polyps even if the risk of pouch
cancer in FAP is unclear. Therefore, long-term endo-
scopic surveillance (pouchoscopy) is recommended
[1].
It is known that FAP patients frequently develop
The Endoscopic Procedures in Familial Adenomatous
Polyposis (FAP): a Critical Review
Walter Piubello, Fabrizio Bonfante, Morena Tebaldi
Normal
mucosa
Early
adenoma
Intermediate
adenoma
Late
adenoma
Carcinoma
APC
K-ras
DCC/18q
genes
P53
Fig. 1. Steps of colon carcinogenesis
376 W. Piubello, F. Bonfante, M. Tebaldi
tumours (either benign or malignant) in other
organs besides the colon, mainly in the upper GI tract
(stomach, small intestine). Gastric polyps occur in
30–100%, but adenomas are uncommon, occurring
in approximately 5% of FAP patients usually in the
gastric antrum (Fig. 3). The development of gastric
carcinoma in FAP patients is only very high in Japan
where the gastric cancer rate in the general popula-
tion is higher. In other populations it occurs in less
than 5% of the population. Proximal small-bowel
cancer is one of the two leading causes of death in
FAP patients with previous colectomy [2, 3]. It develops
Table 1. Features of adenomatous polyposis syndromes
Syndrome Type of Location of Other manifestations Germline gene
polyps polyps mutation
FAP (autosomal Adenomas Colon, Benign: desmoid APC
dominant) (100s-1000s) duodenum, tumours, osteomas,
jejunum, ileum, epidermoid cysts,
stomach, (fundic CHRPE
a
gland polyps) Malignant:
medulloblastoma,
hepatoblastoma, thyroid
cancer, adrenal cancer
Attenuated FAP Adenomas Colon, Osteomas APC (5’ and 3’)
(autosomal (5–100) duodenum, (mandible) APC E1317Q
dominant) stomach
MYH polyposis Adenomas Colon, Osteomas, CHRPE
a
MYH
b
(autosomal (5–100) duodenum,
recessive) stomach
a
CHRPE, congenital hypertrophy of the retinal pigment epithelium;
b
MYH, is a gene that repairs DNA damage (if defecting, the resulting
loss of APC function causes an increase in multiple adenomas)
Fig. 2. Diffuse polyposis of the colon
The Endoscopic Procedures in Familial Adenomatous Polyposis (FAP): a Critical Review 377
from pre-existing adenomas which are present in
approximately 100% of these patients in the duode-
num (Fig. 4). Duodenal adenomas can be classified
through macroscopic and histologic criteria in five
stages (0–IV) following the Spigelman’s classification
(Table 2) [4, 5].
In all FAP patients submitted to proctocolectomy,
screening and surveillance for duodenal and small-
bowel polyps are mandatory. Duodenoscopy (side
vision) should be performed, taking several biopsies
from the duodenal papilla and from all the polyps,
Fig. 3. Gastric polyps in FAP
Fig. 4. Duodenal adenoma in FAP
Table 2. Spigelman’s score and classification (modified)
Score No. of duodenal polyps Size (mm) Histology Dysplasia
1 point 1–41–4 Tubulous Low grade
2 points 5–20 5–10 Tubulous-villous –
3 points > 20 >10 Villous High grade
Classification Stage 0 Point – (no polyps)
I 1–4
II 5–6
III 7–8
IV 9–12
378 W. Piubello, F. Bonfante, M. Tebaldi
also by means of chromoendoscopy (Fig. 5). At the
first duodenoscopy, the prevalence of duodenal
adenomatosis is 58–74% in the major series, and
only about 10% of adenomas are diagnosed histo-
logically.
The risk of duodenal carcinoma is related to the
Spigelman stage (about 7% in stage IV, 0.7% in stage
0–III) [6]. In Spigelman stage III–IV, endoscopic
ultrasonography is recommended to ensure that
invasive growth has not occurred. The regular endo-
scopic surveillance of the duodenum should be
offered to all FAP patients (Table 3) [7]. The first
upper endoscopy should be carried out at the age of
30 years and include multiple random biopsies taken
from the duodenal mucosa in patients without visible
polyps. Endoscopic surveillance (included ultra-
sonography) is recommended at intervals of
3 months in patients who are not suitable for or
refuse surgery.
Screening or surveillance for small-bowel polyps
is difficult with current technologies. By means of
traditional push enteroscopy (PE), up to only 30% of
the small-bowel length can be visualized. A new
promising endoscopic method for allowing complete
visualisation, biopsies and treatment in the small
bowel is the double balloon enteroscopy (DBE; push
and pull; Fig. 6), but the use of this technique in FAP
patients is not yet routine [8].
Capsule endoscopy (CE) is another recent tech-
nology that allows a non-invasive endoscopic assess-
ment of the entire small bowel (Fig. 7) [9]. Published
clinical trials have shown that CE carries a high diag-
nostic yield in patients suffering from obscure gas-
trointestinal bleeding [10–13]. Beyond this role, the
value of CE in other small bowel disorders has to be
evaluated. CE may also be used to search for
tumours or tumour-like lesions in patients that
present with a known increased risk of small bowel
carcinomas such as familial adenomatous polyposis,
Peutz-Jeghers syndrome and familial juvenile poly-
posis. The comparison between CE and DBE in
detecting small bowel tumours is shown in Table 4
[12–16].
In FAP patients, preliminary results [17] suggest
that capsule endoscopy can only be used additional-
ly to identify patients with significant distal jejunal
polyposis. However, this is suggested to be a rather
infrequent situation. The correlation between the
findings of capsule endoscopy and conventional
endoscopy is reported in Table 5. Active control of
the capsule endoscopy, the precise assessment of
polyps size and the opportunity to obtain biopsies
are important long-term future requirements for
extending the indication to FAP patients.
In the first study that compares the value of CE
and DBE in the diagnosis of small intestinal polypo-
sis [18], the diagnostic yield of DBE was superior in
comparison to CE in almost the same area explored.
Even Yamamoto et al. [19] have shown that with this
method, total enteroscopy can be achieved by com-
bining antegrade and retrograde examinations, how-
ever, DBE in comparison with CE is an inconvenient
and invasive procedure that requires specialized
equipment, sedation of the patients, fluoroscopy and
Fig. 5. Duodenal chromoendoscopy (methylene blue)
Table 3. Programme for surveillance and treatment of duo-
denal adenomatosis
Spigelman’s stage Frequency of endoscopy
05years
a
I 5 years
b
II 3 years
b
III 1–2 years
b
IV Endoscopic ultrasonography
Consider pancreas sparing and
pylorus sparing duodenectomy
a
Including multiple random biopsies from the mucosal fold in
patients without visible polyps;
b
Including multiple biopsies from
polyps
Fig. 6. Double balloon enteroscopy
The Endoscopic Procedures in Familial Adenomatous Polyposis (FAP): a Critical Review 379
a prolonged examination time.
At the end of this report, the role of endoscopic
procedures in FAP patients can be summarized as
follows (Table 6):
– Conventional colonoscopy should be performed
with multiple biopsies and polypectomy, starting
at the age of 8–10, considering prophylactic proc-
tocolectomy when the number of polyps are
increasing and the risk of carcinoma is very high
(10–15 years from the onset of polyps).
– Pouchoscopy, after proctocolectomy, should be per-
formed because the ileal pouch could develop
polyps even if the real risk of pouch cancer is
unclear.
– Gastric endoscopy to show fundic gland polyps
(frequent) and adenomas (rare).
– Duodenoscopy with side view to remove all the
polyps, particularly near the papilla, and to per-
form several random biopsies by using chromoen-
doscopy with methylene blue.
– Endoscopic ultrasonography in patients with
Spigelman stages III–IV.
Fig. 7. Ileal polyp at capsule endoscopy
Table 4. Comparison between capsule endoscopy (CE) and push enteroscopy (PE) in detecting small-bowel tumours
Author Year No. of patients No. of tumours (%)
Total PE CE
Cosentino et al. [14] 2003 33 4 (10.7) 42
Delvaux et al. [15] 2002 57 1 (1.8) 01
Ell et al. [12] 2002 32 2 (6.3) 22
Mylonaky et al. [16] 2002 38 2 (5.3) 22
Pennazio et al. [11] 2002 50 3 (6) 22
Table 6. Endoscopic procedures in FAP
GI site Endoscope Findings Time and follow-up
Stomach Conventional Fundic gland polyps At first diagnosis
(adenoma)
Duodenum Side vision Adenomas Spigelman stage (endoscope
(±chromoendoscopy) ultrasonography stages III–IV)
Small bowel Capsule endoscopy, Polyps At first diagnosis?
double balloon Surveillance?
enteroscopy
Colon Conventional Adenomas (100s–1000s) -
Ileal pouch Conventional Polyps ?
Table 5. Correlation of Spigelman’s score (modified) meas-
ured by capsule endoscopy and conventional endoscopy
Capsule endoscopy Conventional endoscopy
(score) (score)
No. of patients
0 1
–
2 3
–
4 5
–
6
0
51 --
1
–
2
1 - 1 -
3
–
4
1 ± 7 -
5
–
6
-- - 7
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