Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1515_Библиотеки_им_академика_М_И_Перельмана
.pdf
380 W. Piubello, F. Bonfante, M. Tebaldi
– Capsule endoscopy to better explore the small
bowel.
– DBE to eventually remove the intestinal polyps
found at CE examination.
References
1. Groves CJ, Beveridge G, Swain DJ et al (2005) Preva-
lence and morphology of pouch and ileal adenomas in
familial adenomatous polyposis. Dis Colon Rectum
48:816–823
2. Arvanitis ML, Jagelman DG, Fazio VW et al (1990)
Mortality in patients with familial adenomatous poly-
posis. Dis Colon Rectum 33:639–642
3. Nugent KP, Spigelman AD, Phillips RK (1993) Life
expectancy after colectomy and ileorectal anastomosis
for familial adenomatous polyposis. Dis Colon Rec-
tum 36:1059–1062
4. Spigelman AD, Williams CB, Talbot IC (1989) Upper
gastrointestinal cancer in patients with familial adeno-
matous polyposis. Lancet 2:783–785
5. Spigelman AD (2004) Extracolonic polyposis in famil-
ial adenomatous polyposis: so near and yet so far. Gut
53:322–327
6.Bülow S, Bjiörk J, Christensen IJ et al ( 2004) Duodenal
adenomatosis in familial adenomatous polyposis. Gut
53:381–386
7. Saurin JC, Gutknecht C, Napoleon B et al (2004) Sur-
veillance of duodenal adenomas in familial adenoma-
tous polyposis reveals high cumulative risk of advance
disease. J Clin Oncol 22:493–498
8. May A, Nachbar L, Ell C (2005) Double–balloon
enteroscopy (push and pull enteroscopy) of the small
bowel: feasibility and diagnostic and therapeutic yield
in patients with suspected small bowel disease. Gas-
trointest Endosc 62:62–70
9. De Franchis R, Rondonotti E, Abbiati C et al (2004)
Small bowel malignancy. Gastrointest Endosc Clin N
Am 14:139–148
10. Lewis BS, Swain P (2002) Capsule endoscopy in the
evaluation of patients with suspected small intestinal
bleeding: results of a pilot study. Gastrointest Endosc
56:349–353
11. Pennazio M, Santucci R, Rondonotti E et al (2002
)
Capsule endoscopy: diagnostic yield and comparison
with push enteroscopy in patients with obscure gas-
trointestinal bleeding: the Italian multicentre experi-
ence. Endoscopy 34 (suppl II):A91
12. Ell C, Remke S, May A et al (2002) The first prospective
controlled trial comparing wireless capsule endoscopy
with push enteroscopy in chronic gastrointestinal
bleeding. Endoscopy 34:685–689
13. Piubello W, Bonfante F, Tebaldi M et al (2005) Pillcam
videocapsule endoscopy and obscure gastrointestinal
bleeding: our experience. Dig Liver Dis 37(suppl 1):160
14. Cosentino F, Morandi E, Rubis-Passoni G et al (2003)
Wireless capsule endoscopy: limits and complications.
Abstracts of the 2003 Meeting of the Italian Federation
for Digestive Disease, Italian Federation for Digestive
Disease, Florence, p 41
15. Delvaux M, Saurin JC, Gaudin JC et al (2002) Compar-
ison of wireless endoscopic capsule and push-
enteroscopy in patients with obscure occult/overt
digestive bleeding: results of a prospective, blinded,
multicentre trial. Gastrointest Endosc 55:AB88
16. Mylonaky M, Fritscher-Ravens A, Swain PC (2002)
Clinical results of wireless capsule endoscopy. Gas-
trointest Endosc 55:AB146
17. Schulmann K, Schmiegel W (2004) Capsule endoscopy
for small bowel surveillance in hereditary intestinal
polyposis and non-polyposis syndromes. Gastrointest
Endosc Clin N Am 14:149–158
18. Matsumoto T, Esaki M. Horiyama T et al (2005) Com-
parison of capsule endoscopy and enteroscopy with
the double-balloon method in patients with obscure
bleeding and polyposis. Endoscopy 37:827–832
19. Yamamoto H, Kita H, Sugano K et al (2004) Clinical
outcomes of double-balloon endoscopy for the diag-
nosis and treatment of small intestinal diseases. Clin
Gastroenterol Hepatol 2:1010–1016
This is the story of Rosa Gallo, a young and bright
student of medicine, who died of Gardner’s syn-
drome at 21 years of age; this story allows us to more
easily explain the history of the disease, the various
aspects of which (aetiology, clinical history, diagnos-
tic and therapeutical approach) are extensively cov-
ered in several chapters of this book.
Rosa Gallo was born on 6 August 1982, second
born of the Gallo family, 4 years younger than the
first born, Carmine. She was a happy child and soon
stood out among her friends of the same age, for her
lively wit. Fondly loved by mom and dad, the two
children grew up happy and carefree. In 1990, Rosa’s
paternal aunt, who moved from Altavilla Salentina to
Milan, underwent coloscopy due to lower gastroin-
testinal (GI) bleeding. The result of the examination
would upset the life of the whole Gallo family: the
diagnosis was familial adenomatous polyposis coli
(FAP). All first degree relatives underwent coloscopy,
and Rosa’s father, Rosario, was found to be bearer of
this disease. Now the high presence of rectal cancer
in the Gallo family could be explained (Fig. 1).
FAP coli is a well-described autosomal syndrome
characterised by diffused polyposis of the colon. The
first description of intestinal polyposis dates back to
1721 with Menzelio [1]. In 1882, Cripps [2] described
the inhered predisposition (brother and sister, both
affected by FAP) while Smith [3] found the progress
of the disease from an adenoma to a cancer that was
then histologically described, in 1890 by Handford
[4]. This disease is the most diffused heritable cause
FAP History Through a Patient’s Story
Gian Gaetano Delaini, Gianluca Colucci, Filippo Nifosì
Fig. 1. Gallo family genetic
tree
382 G.G. Delaini, G. Colucci, F. Nifosì
of colorectal cancer (CRC), second only to the Lynch
syndrome. FAP stems from mutation of the APC
gene localised on 5q21. The APC gene plays several
important roles in cells, influencing cell adhesion,
cytoskeleton and cell cycle [5, 6.] Since the first
description in 1986 [7], much progress has been
accomplished in determining the mutations causing
this disease, thanks to the cloning technique, and
over 1,000 mutations have been found [8], which
have been inserted into an international reference
database (http://perso.curie.fr/tsoussi). Now it seems
certain that there is a correlation between genotype
and phenotypic manifestation of the disease, as
mutation in different areas of the APC leads to dif-
ferent manifestations of the disease [9]
Clinically, FAP is characterised by the presence of
a high number (>100) of adenomatous polyps of the
colon and rectum [10]. These polyps are charac-
terised by a neoplastic degeneration, and these
patients with them, if they do not undergo prophy-
lactic colectomy, will develop colon cancer and will
be doomed because of this neoplasty. Sometimes the
disease has a slower course and a lower number of
polyps, probably because of a milder form of the dis-
ease called attenuated adenomatous polyposis coli
AAPC [11]. Usually in AAPC, polyps are right-sided
and the rectum is spared. The disease develops over
time. Bulow [12], in a now historic review, deter-
mined that the onset of polyps usually begins at 16
years of age (range: 5–38), at 29 years of age (range
12–73) the first symptoms begin (generally lower GI
bleeding) and at 36 years of age (range: 17–63) rec-
tal/colonic cancer appears.
Besides in the colon–rectum, the disease is charac-
terised by the high incidence (from 28% to 68%)
[13–15] of polyps in the stomach and duodenum.
With the diffusion of the prophylactic colectomy, this
associated pathology grew increasingly important, as
extension of the average duration of life in these
patients brought to light the risk of neoplastic degen-
eration. It also evidenced the need to perform a suit-
able follow-up with gastroscopy [16] and stratifica-
tion of patients using Spigelman’s classification [17]
to determine which patients may be treated with
endoscopic polypectomy only and which must
undergo surgery, usually consisting of a pancreatico-
duodenectomy.
Rosa’s father and aunt were operated in London
by Prof. Nicholls and underwent total colectomy with
ileorectal anastomosis because preoperative exami-
nations revealed the absence of polyps at rectum
level.
The surgical therapy chosen to treat FAP was
restorative proctocolectomy with ileal pouch anal
anastomosis [18–20] due to the high risk of neoplas-
tic degeneration in the residual rectal stump even
though ileal rectal anastomosis might be a surgical
option acceptable by patients with rectal sparing and
a good compliance to follow-up [21, 22].
The years went by peacefully. Rosario’s and his
sister’s follow-ups showed an absence of residual dis-
ease. The risk of this disease hung over Rosario’s
children, too. At 18 years of age, Carmine underwent
the first colonoscopy and the diagnosis, for him, too,
was FAP. He was then hospitalised at the Verona
Surgery Clinic and underwent restorative procto-
colectomy with ileal pouch anal anastomosis (RP-
IPAA). The postoperative course went without com-
plications, and after about 45 days, the loop ileosto-
my was closed.
Rosa, who by the time was a happy-go-lucky
teenager, attended high school with very good
results. She was always happy; she supported her
family with her happiness and maturity during the
Fig. 2a, b. Preoperative computed tomography (CT) scan. D, desmoid tumour
a b
FAP History Through a Patient’s Story 383
hard times, well aware of the risk that she could suf-
fer from the disease, too. In May 1998, when she was
17 years old, Rosa began to complain about a pain
localised in the left side, which grew increasingly
annoying. Her parents decided to subject the girl to a
series of examinations. Rosa underwent colonoscopy,
which revealed many polyps in the colon and rectum.
Moreover, she underwent a computed tomography
(CT) scan (Fig. 2) and magnetic resonance imaging
(MRI) (Fig. 3), which revealed a voluminous mass
filling the left hemiabdomen and infiltrating the
spleen, pancreas, kidney and left ureter. The diag-
nostic procedure included, moreover, an ophthal-
mology exam, which revealed congenital hypertro-
phy of the retinal pigment epithelium. The cranial
radiography did not reveal supernumerary teeth or
osteomas. The diagnosis was then clear: Gardner’s
syndrome.
FAP may be associated with the presence of many
extraintestinal manifestations characterising various
syndromes, such as Gardner’s syndrome [23] and
Turcot’s syndrome [24]. Table 1 summarises the
main features of these syndromes.
The Voluminous Mass was a Desmoid Tumour
Desmoid (from the Greek desmos, which means ten-
don like) tumours are begnin tumours arising from
the muscle-aponeurotic structures [25]. They are
usually well differentiated but with an aggressive
behaviour. Even if they have no metastatic potential,
they can locally infiltrate the adjacent structures,
leading to morbility/mortality because of the defor-
mity resulting from the pressure or obstruction of
vital structures/organs [26–28]. They represent
0.03% of all neoplasies [29] but this incidence
increases up to 13% in patients with FAP [30], affect-
ing mostly women (female:male ratio 2:1). Generally,
desmoid tumours are localised in the abdominal wall
or in the shoulder girdle, but in Gardner’s syndrome,
they mostly develop in the retroperitoneal space [31].
Many of these tumours are revealed after RP-IPAA
[32, 33] or may be revealed, despite the preoperative
staging, only during laparotomy and presenting
small-sized masses, making deciding upon the kind
of treatment difficult and controversial [34]. In order
to determine approach to these tumours and assess
their response to therapy, a method of staging intra-
abdominal desmoid tumours was recently formulat-
ed [35].
In the effort to reduce the abdominal mass, before
performing surgical resection, Rosa was treated with
tamoxifen and sulindac, which she had to stop after 3
months due to the appearance of side effects
(abdominal and limb cramps).
Despite anecdotes about the spontaneous reduc-
tion of the mass of desmoid tumours, the latter, as
already stated above, tend to grow, sometimes fast,
showing signs connected with infiltration of the sur-
rounding structures or of space filling. As we will
later see, the surgical approach proved to be at once
subject to a high rate of relapses and to a high rate of
complications [36], leading us to explore the possi-
bility of using pharmacologic therapy as a primary
choice.
Schematically, we can say that the drugs used
may be divided into 5 groups: hormonal modula-
tors, that is non-steroidal anti-inflammatory agents
(NSAIDs); cAMP modulators, that is, cytotoxic
a
b
Fig. 3a, b. Preoperative magnetic resonance imaging (MRI)
scan. D, desmoid tumour
384 G.G. Delaini, G. Colucci, F. Nifosì
chemotherapeutic agents and other various agents
(interferon gamma and, recently, imatinib mesy-
late). Cytotoxic drugs did not prove to be particu-
larly effective in treating desmoid tumours, and
their use was reserved to a few patients who did not
respond to the other agents. Various therapeutic
patterns were used, all including doxorubicin in
association with other agents, also associated in
some cases with radiotherapy [37–40] The action
pattern of the NSAIDs is not yet clear, but it seems
to be connected with a decreased prostaglandin
synthesis due to cyclooxygenase reduction. The
results obtained show a regression (either partial or
complete) of the mass ranging from 0% [36] to 45%
[41]. The side effects, though, are high, with a GI
bleeding (in 29% of cases), gastric ulcer, nausea or
vomiting [41].
The use of antiestrogens has its rationale in the
proof, in many cases, of the presence of receptors for
progesterone on desmoid tumour cells. By blocking
these receptors, as in other neoplasties, activation of
some genes is negatively inhibited (such as ornithine
decarboxylase), influencing cell growth [42]. More-
over, there is an action pattern that is independent
from the presence of receptors and is connected with
stimulation of the secretion of the growth factor-b,
which in turn inhibits the growth of abnormal fibrob-
last present in the desmoid tumour. Results in the lit-
erature are extremely various, with a success rate
(either complete or partial response) ranging from
25% to 100% [41, 43, 44]. This treatment, though, due
to the lower side effects, may be considered a first-
line therapy and tried in most patients, even if it
seems (the studies include a decreasing number of
patients) to have better results if progesterone is
expressed [43].
The introduction of imatinib mesylate (which
proved extremely effective to treat another class of
solid tumours, that is, GI stromal tumour), seems to
offer some hope, considering the remarkable results
described in a report [45], even if its usage seems to
be limited to cases expressing the CD117 surface
receptor.
A new abdomen CT showed growth of the abdom-
inal mass, compelling us to choose surgery as an
option.
Table 1. Physical characteristics associated with Gardner’s and Turcot’s syndromes
Gardner syndrome
Skin Epidermal cyst
Sebaceous cyst
Craniofacial Osteomas Supernumerary teeth
Dental abnormalities Missing teeth
Root abnormalities
Gastrointestinal Multiple gastric polyps
Multiple duodenal polyps
Multiple colonic polyps (FAP)
Desmoid tumours (abdominal or/and thoracic
wall; mesenteric)
Endocrine Cushing syndrome
Multiple endocrine neoplasia
Turcot syndrome
Skin Café au lait spots
Multiple lipomas
Gastrointestinal Basal cell carcinoma of scalp
Multiple colonic polyps (FAP)
Hepatic nodular hyperplasia
Gastric carcinoma
Central nervous system Glioma
Glioblastoma multiforme
Astrocytoma
FAP, familial adenomatous polyposis coli
FAP History Through a Patient’s Story 385
Fig. 4a-d. Operative specimen. Gross appearance. a En bloc
resectioned specimen. b Details of spleen included by the
desmoid tumor. c Adenomatous polyps. d Macroscopic
appearance of desmoid tumour
a
c
d
b
386 G.G. Delaini, G. Colucci, F. Nifosì
a
c
e
b
d
f
Fig. 5. Operative specimen: histologic involvement of colon (a); spleen (b); pancreas (c); kidney (d); surrenalic gland (e);
ureter (f)
FAP History Through a Patient’s Story 387
Resective therapy is considered the only alterna-
tive to pharmacological therapy if the latter fails, but
it must be carefully considered due to the high rate of
recurrence and the need to perform extended inci-
sions to resect the tumours [46–48].
On 8 October 1998, Rosa underwent an en bloc
resection of a large desmoid tumour (including pan-
creatic tail, spleen, left kidney, ureter and surrenal
gland) (Figs. 4a–c and 5a–f), total colectomy with ter-
minal ileostomy and closure of the rectal stump. The
postoperative course was very good, and the MRI
revealed complete resection of the tumorous mass
(Fig. 6). Rosa was then dismissed. Rosa’s recovery
was unbelievable. She resumed school after a short
while and managed to lead an ordinary life despite
the stoma, which she managed autonomously with-
out any limitation to her daily living.
In June 1999, at the end of school year, Rosa was
hospitalised again to close the ileostomy. Preopera-
tive exams, particularly the MRI did not reveal the
presence of a desmoid tumour. On 25 June, Rosa was
then subjected to surgery. At laparotomy, many nod-
ules were revealed (likely recurrence of desmoid
tumour) in the mesentery. Some nodules were resect-
ed, but it was not possible to remove them all without
performing too wide a resection on the small bowel.
The ileostomy was resected and, after mobilisation of
the ileum, a side-to-end ileorectal anastomosis was
made. Also in this case, there were no important
complications during the postoperative course, and
Rosa was dismissed after 2 weeks.
After just 8 months, during follow-up, an MRI
revealed a new abdominal mass of about 10 cm in
diameter. Moreover, a fast-growing mass in the
abdominal–thoracic area was found. Rosa again
underwent surgery. At laparotomy, a voluminous
desmoid tumour was found (12–14 cm) growing
from the mesentery and involving the origin of the
mesenteric artery. Resection of such a mass was
impossible without resecting over 80% of the small
intestine. Some small desmoid tumours were then
removed along the abdominal incision, and the
abdominal–thoracic mass (a new desmoid tumour).
Postoperative hospitalisation lasted 10 days only,
and Rosa was dismissed. In the meantime, proving to
be very brave, Rosa moved to Verona by herself and
to attend the faculty of medicine at the university.
The next 2 years went by rather peacefully. Rosa,
always smiling and in a good mood, often walked
down the hospital aisles, alternating her role of a
bright student of medicine with the role of the patient
undergoing periodical follow-ups. The big abdomi-
nal desmoid tumour seemed to have stopped grow-
ing, apparently responding well to the new therapy
with raloxifene.
At the beginning of January 2003, Rosa began to
report recurring abdominal pains, nausea and intes-
tinal subocclusion. The situation slowly progressed;
her appetite diminished and she consequently lost
weight [actual body mass index (BMI): 17.5]. Consid-
ering the symptomatology, oral intake was stopped
and was positioned at the central line. The abdominal
radiograph showed a pattern of intestinal subocclu-
sion. The MRI revealed persistence of the previously
described mass and the appearance of new nodules in
the abdomen and abdominal wall. After 2 days, the
physicians decided, considering the persistence of
the symptoms, to perform surgery again. Laparoto-
my revealed a situation of diffused adherences and
two new desmoid masses. Some jejunal loops were
dilated and strictly connected to the bigger desmoid
tumour. A jejunal–ileal bypass was created. The post-
operative course was difficult, with slow reactivation
of intestinal movements.
Rosa, at this point, seeing there were no further
alternatives, was sent to the surgical clinic in Inns-
bruck managed by Prof. Margreiter to be evaluated
for an intestinal transplant. After careful clinical
Fig. 6. Postoperative magnetic resonance imaging (MRI)
scan
388 G.G. Delaini, G. Colucci, F. Nifosì
evaluation and a thorough explanation of the surgery
to be performed (Fig. 7) and short- and long-term
risks, Prof. Margreiter proposed that Rosa undergo
intestinal or multiorgan transplant. With her usual
bravery, Rosa accepted and was placed on the waiting
list.
The multiorgan transplant is a very complicated
procedure, especially due to postoperative manage-
ment of rejection. Even if the experiences in major
centres are limited, the multiorgan transplant, in the
case of large desmoid tumours, is becoming a reality
[49–53]. However, besides the risks connected with
the procedure, there is the possibility of recurrence of
the desmoid tumour, with the risk of having to per-
form new resective operations [54].
During the following months, Rosa resumed an
ordinary life. Despite the fact that her parents want-
ed and encouraged her to go home, she returned to
live in Verona with her mates and resumed studying,
taking exams and getting the best grades. Follow-ups
revealed a stationary situation, with a discreet nutri-
tional status. In November 2003, things began to get
worse. Rosa began to report the return of abdominal
pains and fever. She was then treated at the outpa-
tient clinic but on 25 November 25 2003 had to be
hospitalised due to the reappearance of sepsis white
blood cell count (WBC): 20,000, fever 40.5°C). A
broad-spectrum antibiotic therapy was then started
and a abdomen CT was performed. The latter
revealed the presence of an abdominal purulent con-
centration. Rosa was then subjected to a new laparo-
tomy and drainage of the purulent concentration,
which was probably due to a fistula between a jejunal
loop and the bigger desmoid tumour. Because of the
abdominal situation, only drainage of this abdominal
abscess was done. Her case was then declared urgent,
and she was placed on the top of the transplant list.
The postoperative course was extremely difficult.
After an initial period of relative well-being, bacteri-
al and fungal infections occurred, becoming increas-
ingly difficult to control with therapy. A new abdom-
inal abscess close to the abdominal wall was drained
percutaneously. After more than 2 months of hospi-
talisation, on 15 February 2004, Rosa received the
long-awaited call: a donor was found. Rosa was
moved to Innsbruck at once. While going into the
operating theatre, she said goodbye to Prof. Delaini
with a smile on her face; he had been following her
since the beginning of the disease and saw her as far
as Innsbruck: “Professor, these surgeons will try to
kill me anyway. Please, oversee the operation”, she
said. Surgery was extremely complicated. In the
demolitive stage, all desmoid abdominal tumours
were abscessed, resecting the aorta vena cava. The
desmoid tumours of the abdominal and thoracic wall
were then abscessed, demolishing a large portion.
Rosa was then subjected to a multivisceral trans-
plant: liver, pancreas, stomach (with gastric anasto-
mosis), duodenum, jejunum and ileum. A terminal
ileostomy was made. The abdominal wall was recon-
structed by a large abdominal Gore-Tex patch. The
final stage of the operation was characterised by dif-
ficulty controlling bleeding and the need to perform
an abdominal patching. After 4 days, the abdominal
patches were removed. On 5 March, Rosa underwent
a new surgery to drain an infected retrogastric
haematoma [positive for methicillin-resistant
Staphylococcus aureus (MRSA)]. The remaining
operative course was without complications. Rosa
began a by-mouth feeding even though prudentially
a Port-a-Cath was inserted.
Antirejection therapy, after some initial adjust-
ments and the need to undergo a unique dialysis ses-
sion due to worsening of kidney function following a
temporary high haematic concentration of FK-506,
Fig. 7. Picture drawn by Prof. Margreiter during the
informed consent process
FAP History Through a Patient’s Story 389
had a very good range and response. The duodenal
biopsies through ileostomy did not reveal the
appearance of any sign of acute or chronic rejection.
Moreover, echo-colour Doppler revealed very good
hepatic perfusion. On 13 May 2004, Rosa was dis-
missed, and follow-ups at the outpatient clinic were
scheduled. The first 2 months went by satisfactorily
despite the need to undergo 2 cycles of high-dosage
corticosteroids to avoid rejection. During this period,
Rosa could even leave her apartment near Innsbruck,
where she lived with her parents, and travel to
Altavilla Salentina.
On 11 July 2004, Rosa was hospitalised due to
upper GI bleeding that, at gastroscopy, revealed two
duodenal ulcers that only required the transfusion of
3 units of blood. This event, which apparently was
not so serious, was the initial cause of a miserable
course. Rosa began to have a series of bacterial infec-
tions, which required broad-spectrum antibiotic
therapy and removal of the Port-a-Cath (16 July).
Subsequently, a state of sepsis began to appear (on 27
July), with an increase of lactates and worsening of
the cardiocirculatory condition. To support circula-
tion, it was necessary to begin the administration of
pressor amines. On 4 August a massive left pleuritic
effusion was surgically drained, which on 6 August
required a review due to bleeding with haematoma.
Moreover, following the development of respiratory
insufficiency, Rosa was intubated, and respiratory
function was mechanically supported.
Following the bacterial infections came fungal
infections and the development of coagulative defi-
ciencies. On 20 August, a surgical tracheostomy was
performed. After a few hours, Rosa’s circulatory sta-
tus worsened and despite all efforts, she died at 21.04
on 21 August 2004. The autopsy was performed 1 day
later, but it only confirmed the damage caused by the
septic shock.
Rosa Gallo was an extraordinary young woman
who, despite her short life, deeply changed all who
knew her. With her wonderful smile and her incredi-
ble stamina, she faced her disease and trouble serene-
ly. This book is the first step towards the realisation
of a dream that led her to attend the faculty of medi-
cine: to help all people suffering with FAP. Thank
you, Rosa.
References
1. Menzelio D (1721) De excrescentis verrucoso cristosis
copiose in intestinis crassis dysenteriam passi obser-
vatis. Acta Medicorum Berolinensium IX:68–71
2. Cripps WH (1882) Two cases of disseminated polypus
of the lower bowel occurring in one family. Trans Path
Soc London 33:165–168
3. Smith T (1887) Three cases of multiple polypi of the
lower bowel occurring in one family. St. Bartholomew’s
Hosp Rep 23:225–229
4. Handford H (1890) Disseminated polypi of the large
intestine becoming malignant; strictures (malignant
adenoma) of the rectum and of splenic flexure of the
colon; secondary growths in the liver. Trans Path Soc
London 133–137
5. Kita K, Wittmann T, Nathke IS, Waterman-Storer CM
(2006) APC on microtubule plus ends in cell exten-
sions can promote microtubule net growth with or
without EB1. Mol Biol Cell [Epub ahead of print]
6. Gayther SA, Wells D, Sen-Gupta SB et al (1994)
Regionally clustered APC mutations are associated
with a severe phenotype and occur at a high frequency
in new mutation cases of adenomatous polyposis coli.
Hum Mol Genet 3:53–56
7. Herrera L, Kakati S, Gibas L et al (1986) Gardner syn-
drome in a man with an interstitial deletion of 5q. Am
J Med Genet 25:473–476
8. Laurent-Puig P, Beroud C, Soussi T (1998) APC gene:
database of germline and somatic mutations in human
tumors and cell lines. Nucleic Acids Res 26:269–270
9. Fearnhead NS, Britton MP, Bodmer WF (2001) The
ABC of APC. Hum Mol Genet 10:721–733
10. Bussey HJR (1975) Familial polyposis coli. John Hop-
kins University Press, Baltimore
11. Soravia C, Berk T, Madlensky L et al (1998) Genotype-
phenotype correlations in attenuated adenomatous
polyposis coli. Am J Hum Genet 62:1290
–1301
12. Bulow S (1987) Familial polyposis coli. Dan Med Bull
34:1–15
13. Bulow S, Bjork J, Christensen IJ et al (2004) Duodenal
adenomatosis in familial adenomatous polyposis. Gut
53:381–386
14. Church JM, McGannon E, Hull-Boiner S et al (1992)
Gastroduodenal polyps in patients with familial ade-
nomatous polyposis. Dis Colon Rectum 35:1170–1173
15. Bjork J, Akerbrant H, Iselius L et al (2001) Peri-
ampullary adenomas and adenocarcinomas in familial
adenomatous polyposis: cumulative risks and APC
gene mutations. Gastroenterology 121:1127–1135
16. Groves CJ, Saunders BP, Spigelman AD, Phillips RK
(2002) Duodenal cancer in patients with familial ade-
nomatous polyposis (FAP): results of a 10 year
prospective study. Gut 50:636–641
17. Spigelman AD, Williams CB, Talbot IC et al (1989)
Upper gastrointestinal cancer in patients with familial
adenomatous polyposis. Lancet 2:783–785
18. Krausz MM, Duek SD (2005) Restorative proctocolec-
tomy with ileal pouch-anal anastomosis for ulcerative
colitis and familial adenomatous polyposis: twenty
years follow-up in 174 patients. Isr Med Assoc J
7:23–27
19. Penna C, Tiret E, Kartheuser A et al (1993) Function of
ileal J pouch-anal anastomosis in patients with famil-
ial adenomatous polyposis. Br J Surg 80:765–767
20. Ziv Y, Church JM, Oakley JR et al (1996) Results after
restorative proctocolectomy and ileal pouch-anal
anastomosis in patients with familial adenomatous
polyposis and coexisting colorectal cancer. Br J Surg
83:1578–1580
21. Soravia C, Klein L, Berk T et al (1999) Comparison of
ileal pouch-anal anastomosis and ileorectal anastomo-
Соседние файлы в папке Библиотека им академика М.И. Перельмана