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304 P. Gionchetti, C. Morselli, F. Rizzello, R. Tambasco, G. Poggioli, S. Laureti, F. Ugolini, F. Pierangeli, M. Campieri
the treatment of pouchitis compared with oral
metronidazole. This study showed that budesonide
enemas (2 mg/100 ml at bedtime) have a similar effi-
cacy as oral metronidazole (0.5 g bid) in terms of dis-
ease activity, clinical and endoscopic findings (58
and 50% of patients, respectively, improved with a
decrease in PDAI score 艌3), but less side-effects (25
vs. 57%) and better tolerability, representing conse-
quently a valid therapeutic alternative for active pou-
chitis [37].
While no data have been published on the efficacy
of oral 5-ASA, uncontrolled studies have suggested the
efficacy of topical 5-ASA either as suppositories or ene-
mas in treatment of acute pouchitis [38]. As concerns
immunosuppressive agents, cyclosporine enemas have
been reported to be successful in chronic pouchitis in a
pilot study [39] and other small studies have suggested
that oral azathioprine may also be useful.
The observation reported in some studies [40], but
not all [41], that the faecal concentration of SCFAs is
lower in patients with pouchitis, led to the hypothe-
sis that the topical administration of nutrients, such
as SCFAs or butyrate or glutamine, may produce
clinical benefit. Poor clinical results were obtained in
uncontrolled trials using SCFAs enemas [42-43]. In a
3-week double-blind trial, glutamine and butyrate
suppositories were compared in a group of 19
patients with chronic pouchitis with recurrent symp-
toms; the end-point was clinical remission. As the
relapse rate was 40% for the glutamine group and
67% for the butyrate group and no placebo group
was included, it was almost impossible to state if the
two treatments were both ineffective and similarly
effective [44]. In consideration of all these studies,
nutritional therapy thus far should not be considered
beneficial for pouchitis.
Bismuth, effective in UC and traveller’s diarrhoea
because of its anti-microbial and anti-diarrhoeal
effects, was also investigated. One open-label long-
term study evaluated the efficacy and safety of bis-
muth-citrate carbomer enemas in achieving and
maintaining remission in a group of patients with
chronic treatment-resistant pouchitis. After 45 days
of nightly treatment, 83% of patients went into
remission with a significant decrease of the mean
total PDAI score from 12 to 6. Moreover, these
patients entered a maintenance phase with enemas
administered every third night for 12 months (60%)
were able to maintain remission for 12 months [45].
On the other hand, a double-blind randomised trial
in patients with active chronic pouchitis did not find
a difference between bismuth enemas and placebo
[46]. More recently, a 4-week treatment open trial
showed patients benefited from bismuth subsalicy-
late tablets administered for chronic antibiotic-
resistant pouchitis [47].
Allopurinol, a scavenger of oxygen-derived free
radicals through inhibition of xanthine oxidase, was
evaluated as post-operative prophylactic treatment
(100 mg twice daily) against pouchitis in a ran-
domised placebo-controlled double-blind study con-
ducted at 12 centres in Sweden; however, it was not
proven to be able to reduce the risk of a first attack of
pouchitis [48].
Treatment of Chronic Pouchitis
Medical treatment of patients with chronic refracto-
ry pouchitis is particularly difficult and disappoint-
ing. The usual therapeutic strategy for these patients,
who fail to respond to antibiotics or relapse once
antibiotic therapy is stopped, includes: (1) a pro-
longed course of an antimicrobial agent, (2) a main-
tenance therapy with the most effective antibiotic at
the lowest clinically effective dose, (3) cycles of mul-
tiple antibiotics at 1-week intervals. A possible thera-
peutic alternative for chronic refractory pouchitis is
the use of a combined antibiotic treatment. We car-
ried out a pilot trial to evaluate the efficacy of the
association of two antibiotics in chronic active treat-
ment-resistant pouchitis. Eighteen patients who were
not responders to the standard therapy (metronida-
zole or ciprofloxacin or amoxycillin/clavulanic acid)
for 4 weeks, were treated orally with rifaximin
2 g/day (non-absorbable, wide spectrum antibiotic)
plus ciprofloxacin 1 g/day for 15 days; symptoms
assessment, endoscopic and histologic evaluations
were performed at screening and after 15 days using
the PDAI. Sixteen out of 18 patients (88.8%) either
improved (n=10) or went into remission (n=6); the
median PDAI scores before and after therapy were 11
and 4 respectively (p<0.002) [49]. Unfortunately all
patients relapsed within 2 months.
More recently, 44 patients with refractory pouchi-
tis received metronidazole 800 mg – 1 g/day and
ciprofloxacin 1 g/day for 28 days. Symptomatic,
endoscopic and histological evaluations were under-
taken before and after the antibiotic therapy, accord-
ing to the PDAI score, and the related quality of life
was assessed with the inflammatory bowel disease
questionnaire (IBDQ). Thirty-six patients (82%)
went into remission; the median PDAI scores before
and after therapy were 12 and 3 respectively
(p<0.0001). Patients’ quality of life significantly
improved with the treatment and median IBDQ
strongly correlated with the disease activity and gen-
eral satisfaction (from 96.5 to 175). Even in the eight
patients who did not go into remission, the median
PDAI score significantly improved from 14.5 to 9.5 as
well as the median IBDQ score from 96 to 127 [50].
Oral-controlled release budesonide can be useful
Management of Pouchitis 305
for certain patients. In a small open trial, 16 patients
with chronic pouchitis refractory to a 1-month
antibiotic therapy (ciprofloxacin 1 g/day and
metronidazole 1 g/day) were treated with budesonide
CIR 9 mg/day for 8 weeks; the dose was gradually
tapered (3 mg every month) and remission was
defined as a clinical PDAI score 艋2 and an endo-
scopic PDAI 艋1. Twelve patients (72%) went into
remission and the total PDAI score significantly
decreased from 13 (range 8–16) to 3 (range 2-9)
(p<0.001). Budesonide treatment increased the IBDQ
score from 102 (range 77–176) to 182 (range 84–225)
(p<0.001) [51].
In a subsequent study, 12 patients with active pou-
chitis refractory to ciprofloxacin and metronidazole
for 1 month and oral budesonide for 8 weeks, were
treated with three infusions of infliximab at a dosage
of 5 mg/kg at week 0, 2 and 6. Ten patients (83.3%)
achieved remission; the total PDAI score decreased
from 13 (range 8–18) to
2 (range 0–9) (p<0.001). The
IBDQ score strongly increased from 96 (range
74–184) to 196 (range 92–230; p<0.001) [52].
Probiotics
The term “probiotic” refers to “living organisms,
which upon ingestion in certain numbers, exert
health benefits beyond inherent basic nutrition” [53].
Recent observations have suggested a potential ther-
apeutic role for probiotics in inflammatory bowel
diseases (IBD), based on convincing evidence impli-
cating intestinal bacteria in their pathogenesis [54].
On the basis of this information, we carried out a
double-blind study comparing the efficacy of a high-
ly concentrated probiotic preparation, VSL#3 (450
billion bacteria of eight different strains; VHS Phar-
ma, USA) vs. placebo in maintenance treatment of
chronic relapsing pouchitis. In our study, 40 patients
who obtained clinical and endoscopic remission after
one month of combined antibiotic treatment (rifax-
imin 2 g/day plus ciprofloxacin 1 g/day), were ran-
domised to receive either VSL#3, 6 g/day (1 800 bil-
lion bacteria per day), or an identical-appearing
placebo for 9 months. Relapse was defined as an
increase of at least 2 points in the clinical portion of
PDAI, which should be confirmed by endoscopy and
histology. All the 20 patients who received the place-
bo relapsed; in contrast 17 of the 20 patients (85%)
treated with VSL#3 were still in remission at the end
of the study. All the 17 patients had a relapse within
4 months after suspension of the treatment. The
results of this study suggested that oral administra-
tion of this highly concentrated probiotic preparation
is effective in preventing relapse of chronic pouchitis,
enhancing the concentration of protective bacteria
and their metabolic activities in the ileal pouch [55].
These results have been recently confirmed by a
study evaluating the efficacy of a single, daily dose of
VSL#3 in maintaining antibiotic-induced remission
(obtained after a 1 month treatment with metronida-
zole 800 mg/day plus ciprofloxacin 1 g/day) for 1 year
in patients with refractory or recurrent pouchitis: 20
patients received VSL#3 at 1 800 billion bacteria once
a day for 1 year and 16 patients received a placebo
during the same period. Clinical, endoscopic and his-
tological evaluations were made before 2 and
12 months after the randomisation. A parallel assess-
ment of quality of life (QoL) was obtained with IBDQ.
This study has substantially confirmed the observa-
tions made previously, with a maintenance remission
rate of 85% at 1 year in the VSL#3 group and 6% in
the placebo group. A high rating in the QoL score was
obtained by the group treated with VSL#3
[56].
The same probiotic preparation was also more
recently shown to be significantly superior to place-
bo in the prevention of pouchitis onset within the
first year after surgery in a randomised double-blind
placebo-controlled study. Forty consecutive patients
who underwent IPAA for UC were randomised with-
in a week after ileostomy closure, and received VSL#3
at a dosage of 3 g per day or an identical placebo for
12 months. They were assessed clinically, endoscopi-
cally, histologically at 1, 3, 6, 9 and 12 months,
according to PDAI; QoL was also assessed at baseline
at the end of the study. Patients treated with VSL#3
had a significantly lower incidence of acute pouchitis
(10%) compared with those treated with placebo
(40%) (p<0.05), and they experienced a significant
improvement in quality of life, whereas this did not
happen in the placebo group, indicating the effective-
ness of a highly concentrated probiotic preparation
in preventing pouchitis onset during the first year
after surgery [57].
Preliminary data of a pilot study to evaluate the
efficacy of high dosage of VSL#3 (6 g b.i.d. equivalent
to 3 600 billion bacteria per day) administered for
1 month as treatment for mildly active pouchitis
(PDAI score 7–12), have shown its potential useful-
ness in improving active pouch inflammation and
health related quality of life [58].
Management
In a proposed algorithm for treatment of pouchitis,
once diagnosis is confirmed by endoscopy and his-
tology, and other causes of inflammation or pouch
dysfunction have been excluded, the main treatment
consists of metronidazole 250 mg three times/day or
ciprofloxacin 500 mg b.i.d. for at least 2 weeks. In
case of a subsequent prompt relapse, the patients can
306 P. Gionchetti, C. Morselli, F. Rizzello, R. Tambasco, G. Poggioli, S. Laureti, F. Ugolini, F. Pierangeli, M. Campieri
be treated with a prolonged course of the same
antibiotic or with a combined antibiotic treatment; in
case of positive response we suggest starting mainte-
nance treatment with highly concentrated probiotics.
In refractory pouchitis, patients should be treated
with other antibiotics or prolonged combined antibi-
otic treatment. Again, in case of response, mainte-
nance probiotic treatment after the stopping of anti-
microbial agents is suggested. When no positive
response is obtained one should try other types of
treatment such as topical corticosteroids, immuno-
suppressive agents, or topical bismuth. Patients who
are refractory to all forms of medical treatment
should be referred to a surgeon for a pouch recon-
struction or pouch excision (Fig. 1).
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Fig. 1. Proposal for a treat-
ment algorithm
treatment
Probiotics maintenance
Response
or combined antibiotic
MTZ or Cipro
prompt relapse no relapse
Response
Pouch excision
or
reconstruction
No response
5-ASA, AZA/6MP
GCS,Budesonide, Infliximab
No response
Probiotics maintenance
treatment
Response
other antibiotics or
combined antibiotic
treatment
Exclude CD
stenosis, cuffitis
CMV infection
No response
Metronidazole/Ciprofloxacin
Pouchitis
Prompt relapse No relapse
O
Management of Pouchitis 307
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Introduction
Bowel transplantation has become a valuable option
for patients with intestinal failure or short-bowel
syndrome who do not tolerate total parenteral nutri-
tion or have no vascular access for TPN. Up until
March 31, 2005, a total of 1292 intestinal transplants
(in altogether 1210 patients) have been reported to
the international registry. Of these 1292 transplants,
570 of them were isolated small-bowel transplants,
490 combined small-bowel/liver transplants, and 232
were multivisceral transplants. Additionally, 772
transplants were performed in 721 pediatric recipi-
ents and 520 transplants in 489 adult patients [1].
It goes without saying that no bowel transplanta-
tion was done for inflammatory bowel diseases in the
pediatric group, but 68 transplants were performed
in adults for this indication. In total, we have experi-
ence with 16 isolated small-bowel transplants and ten
multivisceral transplants, and four of the isolated
intestinal transplants in three patients were per-
formed for Crohn’s disease.
Presently, appropriate indications, the timing of
referral and the outcome of bowel transplantation
are not well recognized among physicians caring for
patients who may be candidates for this therapeutic
option. Definitions of terms such as “intestinal fail-
ure” and “failure of parenteral nutrition” are not
standardized and there is no accepted algorithm that
integrates parenteral nutrition, intestinal rehabilita-
tion and transplantation for patients with intestinal
failure.
Herein, with special emphasis on inflammatory
bowel diseases, we review the various aspects of
bowel transplantation such as the indications for it,
the current state of medical practice in intestinal
transplantation, and its outcome.
History
Intestinal transplantation techniques were developed
in animal models in 1959 and first attempted in
humans in 1964 [2]. In those days, immunosuppres-
sion consisted of steroids and azathioprine after
induction with an antilymphocyteglobulin. Under
this type of rejection prophylaxis, altogether eight
isolated intestinal transplants were performed. The
first two transplants performed in Boston in 1964,
however, have never been officially reported as files
remain untraceable. The first well-documented case
was reported from Minneapolis in 1967 [3]. Under
unconventional immunosuppression, all but one
graft failed within a few days. The last graft in this
series was from a HLA identical sister and survived
for 79 days. The recipient was able to be fed orally
from day 23 until day 60 [4].
The first bowel transplant in the Cyclosporine era
was performed in 1985 in Toronto [5]. Patient No. 8
in this series received 60 cm of jejunoileum from her
sister in 1988 and became the first long-term sur-
vivor. It has to be said, however, that oral food intake
was never sufficient and had to be supplemented by
parenteral infusions. The patient experienced several
episodes of rejection, developed end-stage renal dis-
ease and died a few years later [6].
On March 19, 1989, a 5-month old girl received
80 cm of jejunoileum from a neonate. This patient
transplanted in Paris is still alive and well with a nor-
mally functioning graft [7]. Already in 1960, Starzl
reported on a series of multivisceral transplants in
dogs [8]. The same author performed the first human
multivisceral transplant in 1983 in a 6-year-old girl in
Pittsburgh. The girl, however, died only a few hours
after surgery from exsanguination. The same hap-
pened to a 1-year-old male who underwent trans-
plantation in 1986 in Chicago. In 1987, Starzl per-
formed another transplantation in a 3.5-year-old girl
and Williams in Chicago did the same in the follow-
ing year in a 0.7-year-old neonate. Both children died
192 and 109 days, respectively, after transplantation
from lymphoma. The type of IS consisted of OKT3
induction followed by cyclosporin and steroids. Both
children were never discharged from the hospital [9, 10].
On December 26, 1989, a multivisceral transplant was
carried out for the first time in an adult recipient
Bowel Transplantation for Inflammatory Bowel Disease
Raimund Margreiter
310 R. Margreiter
48 years of age in Innsbruck. This patient lived on
oral food intake for 9 months when he died from
tumor recurrence [11].
On November 13, 1988, Grant performed the first
combined small-bowel/liver transplantation in Lon-
don/Ontario in a 41-year-old woman with short-gut
syndrome with a hypercoagulable state associated
with low antithrombin III levels. The patient survived
for several years [12].
Indications
It is now generally accepted that small-bowel trans-
plantation is indicated in patients suffering from
irreversible small-intestinal failure coexisting with
failure of parenteral nutrition. The main causes of
parenteral nutrition failure are recurrent line related
sepsis, loss of venous access due to thrombosis and
PN-related liver disease. Medicare and Medicaid Ser-
vices in the US have established indications that
include impending or overt liver failure due to TPN-
induced liver injury, thrombosis of two or more cen-
tral veins, the development of two or more episodes
of systemic sepsis secondary to line infection per year
that require hospitalization, a single episode of line-
related fungemia, septic shock and/or acute respira-
tory distress, and frequent episodes of severe dehy-
dration despite intravenous fluid supplementation in
addition to TPN [13].
These criteria should help to avoid late referrals. A
timely referral for pretransplant assessment is essen-
tial for allowing the optimization of physical and psy-
chological factors and should be at a stage when the
central venous access is adequate for surgery and
management of postoperative complications which
may include renal replacement therapy. Unfortu-
nately, it is our experience, that most patients are not
referred, but rather come on their own initiative.
Diseases Causing Intestinal Failure
Diseases leading to intestinal failure include loss of
bowel length, loss of bowel function, or convention-
ally unresectable tumors involving the bowel or its
feeding vessels. Short-bowel syndrome, the loss of
intestinal length and absorptive surface areas due to
surgical resection, are the most common cause of
intestinal failure leading to bowel transplantation.
The loss of mucosal absorptive surface area is associ-
ated with malabsorption and rapid transit through
the jejunoileum leading to malnutrition, recurrent
dehydration, and electrolyte abnormalities. Short-
bowel syndrome can be caused by a variety of condi-
tions and diseases in adults such as thrombosis or
embolism to the superior mesenteric vessels, inflam-
matory bowel disease, volvulus, radiation enteritis,
trauma or other causes of infarction.
In pediatric patients, most frequent causes of
short-bowel syndrome are malrotation, volvulus,
necrotizing enterocolitis, jejunoileal artresias, gas-
troschisis, and omphalocele among other congenital
disorders. Transplant candidacy has to be considered
in the context of alternatives to transplantation
including the potential for rehabilitation or success-
ful lifelong parenteral nutrition. In a large series,
about 20% of adult patients with less than 100 cm of
residual intestine could be weaned from TPN. In chil-
dren, less than 30 cm of jejunoileum, lack of entero-
colonic continuity, and lack of feeding tolerance
early after birth correlate to failure of weaning from
parenteral nutrition [14].
Functional Disorders
Functional disorders of the small bowel that may lead
to intestinal failure include disorders of motility and
disorders of enterocyte function. The most common
motility disorders are chronic pseudo-obstruction,
visceral myopathy, visceral neuropathy, total intes-
tinal aganglionosis, and some forms of mitochondri-
al respiratory chain disorders that affect gastroin-
testinal motor function.
Epithelial disorders causing intractable secretory
diarrhea or failure of absorption are more common
in children and include microvillus inclusion disease,
tufting enteropathy and autoimmune enteritis.
Tumors
Tumors involving the root of the mesentery are often
benign but locally invasive and therefore lethal. The
most common of these lesions are desmoid tumors in
patients with familial adenomatous polyposis. Only
complete resection of the tumor and sacrifice of the
intestines can provide a cure. The most common of
these lesions are desmoid tumors in patients with
Gardeners’ syndrome. This tumor often involves the
mesenteric vessels and requires exenteration of the
small bowel for complete resection. Since these
tumors may involve other foregut organs such as the
pancreas, stomach, duodenum or spleen, a multivis-
ceral transplant is required in these patients. Patients
with Gardeners’ syndrome usually do not have intes-
tinal failure and are therefore not dependent on par-
enteral nutrition prior to transplantation.
Bowel Transplantation for Inflammatory Bowel Disease 311
Types of Transplants
Intestinal transplantation may be performed as an
isolated bowel transplant together with the liver as a
combined small-bowel–intestinal transplant or as a
multivisceral transplant procedure. The common
element of these procedures is transplantation of the
jejunoileum, with or without other organs. Soon after
transplantation, most surgeons create an ileostomy
to allow easy endoscopic surveillance of the graft for
abnormalities. We prefer a technique where the dis-
tal end of the graft is brought out as a stoma wherev-
er it is best situated; the ileum, however, is anasto-
mosed with the remaining colon some 10–20 cm
before its entrance into the abdominal wall. Gas-
trointestinal continuity is restored simply by stapling
and transecting this chimney just distally to the anas-
tomosis, which can then be used as a sentinel grafted
tissue. We call this the “Innsbruck stoma.”
Isolated Bowel Transplantation
Isolated intestinal transplantation may be performed
with portal or systemic drainage. If the venous out-
flow is drained into the portal system via the superi-
or mesenteric vein or directly into the portal vein, the
transplant is called orthotopic. If, for technical rea-
sons, portal drainage cannot be achieved, the superi-
or mesenteric vein of the graft is anastomosed to the
inferior vena cava; therefore, this type of transplant
called heterotopic.
The graft artery is virtually in all cases anasto-
mosed to the infrarenal aorta. In case of a segmental
jejunoileum graft from a live donor, recipient iliac
vessels are preferentially used for revascularization.
The proximal end of the gut is attached to the first
loop of native jejunum or to the third portion of duo-
denum. Isolated bowel transplant is carried out in
patients with intestinal failure but no damage to the
liver or other organs.
Combined Liver–Bowel Transplantation
Presently, most centers would transplant a liver and
bowel that has an intact mesenteric–portal circulato-
ry system en bloc. Therefore, the entire duodenum
with a rim of pancreas is left with the graft. Because
all the other upper abdominal organs such as the
stomach, pancreas, spleen and duodenum are left in
place, a portocaval shunt has to be created in order to
provide venous drainage for these organs. This tech-
nique makes reconstruction of the biliary system
unnecessary. Both grafts, however, can be transplant-
ed simultaneously but not as a composite graft.
Combined liver-intestinal transplantation is per-
formed in patients with intestinal failure together
with liver damage (considered irreversible), usually
due to parenteral nutrition. Severe fibrosis on histol-
ogy with bilirubin of more than 10 mg/dl may indi-
cate a point of no recovery for liver function.
Multivisceral Transplantation
Multivisceral transplantation refers to en-bloc trans-
plantation of the liver, stomach, pancreaticoduode-
nal complex as well as the small bowel, sometimes
also including a kidney. Some authors, however, call
it a multivisceral transplant if the stomach, pancreas
and intestine are transplanted together without the
liver. Exenteration of all native viscera which must
precede the multivisceral transplants can be techni-
cally demanding in patients with portal hypertension
due to diffuse splanchnic thrombosis or with severe
adhesions after multiple laparotomies. Multivisceral
transplantation is performed in patients with either
diffuse thrombosis of all splanchnic veins usually
associated with coagulation abnormalities, desmoid
tumors involving the vascular supply of the liver,
pancreas and intestines, or severe motility disorders.
Postoperative Management
Immunosuppression
The enormous amount of lymphatic tissue trans-
planted together with the bowel, be it in the form of
mesenteric lymph nodes or mucosa-associated lym-
phatic tissue, is responsible for the heightened
immunogenicity of an intestinal graft over other
solid organs. This is the reason why recipients of a
bowel transplant require more immunosuppression
as compared to recipients of a kidney or heart trans-
plant.
Following induction with lymphocyte depleting
antibodies such as antithymocite globulin, Campath
1H (Genzyme, MA, USA), OKT3 (Ortho Biotech, NJ,
USA) or with monoclonal anti-interleukin 2 (IL-2)
receptor antibodies. Maintenance immunosuppres-
sion is usually based on the calcineurin inhibitor
tacrolimus together with other anti-proliferative
agents such as mycophenolate mofetil and steroids.
There is a trend to minimize the use of the latter. The
combination of tacrolimus and sirolimus seems not
to have additional benefit over tacrolimus alone.
Antibody preconditioning seems to allow less potent
subsequent maintenance immunosuppression. Anti-
bodies, however, are occasionally associated with
312 R. Margreiter
severe adverse reactions caused by cytokine release
[14, 15].
Infection Prophylaxis
Decontamination of bacterial and fungal organisms
of the intestinal allograft is attempted before pro-
curement by administering enteric antibiotics to the
donor. Mechanical cleansing has turned out to be
impractical in deceased donors. Since the graft is cer-
tainly not sterile, broad-spectrum antibiotics togeth-
er with antifungal agents are given to the recipient
during transplantation. Because of the powerful
immunosuppression, patients are particularly at high
risk for developing viral infections. The matching of
allografts for cytomegalovirus is difficult to put into
routine practice. Patients are given an antiviral agent
(usually ganciclovir) prophylactically. Some centers
add to this therapy CMV specific hyperimmunoglob-
ulin in recipients of CMV positive grafts. Early diag-
nosis of CMV infection by a variety of means permits
pre-emptive treatment of asymptomatic viremia
[14].
Lymphoproliferative disorders related to Epstein-
Barr virus mediated B-cell proliferation still repre-
sent a major problem after intestinal transplantation.
In recent years, it occurs less frequently after a gen-
eral reduction of immunosuppression, but it still
occurs more often than after most solid organ trans-
plantations. This complication is more common in
the pediatric population with de novo EBV infection.
Quantification of the viral load using quantitative
polymerase chain reaction allow for the early imple-
mentation of therapeutic strategies including
changes in the immunosuppression and medication
of antiviral therapy. The use of rituximab, a human-
ized monoclonal antibody, directed against the CD20
molecule expressed on most B-cell lines and most
PTLD clones, has led to a significant improvement in
outcome [14].
Graft Monitoring
The enormous antigen load makes an intestinal
transplant more prone to rejection than other solid
organs. In addition, rejection may impair the absorp-
tive capacity of the graft leading to further under-
immunosuppression and aggravation of the rejection
process. Therefore, timely diagnosis of any patholo-
gy of the graft is essential. For graft monitoring, rou-
tine endoscopies and biopsies are performed fre-
quently in the early phase after transplantation.
Starting at three times a week immediately following
surgery, the frequency is continuously reduced over
the following weeks. After restoration of the gas-
trointestinal continuity, biopsies can be obtained
from above with the help of an endoscope and from
below via a colonoscopic approach. It has to be
emphasized, however, that these patients require life-
long monitoring and attention. Therefore, a close
relationship between the physician following the
patient, the patient himself and the transplant center
is essential. Although most rejection episodes are
observed during the first year, they may occur any
time after transplantation. Rejection is clinically rec-
ognized by the development of diarrhea, but other
gastrointestinal symptoms such as ileus, emesis, or
general malaise may also occur. These symptoms
should always prompt endoscopic evaluation of the
graft which usually looks grossly normal unless rejec-
tion is severe. Therefore, multiple random biopsies
should be taken and evaluated by a pathologist expe-
rienced with intestinal transplants. It should be rec-
ognized that no serum marker accurately diagnoses
bowel rejection at present. Even concomitantly
transplanted organs such as the liver or a pancreas
are not reliable indicators for rejection of the intes-
tinal component of the graft.
Results
Up until March 31, 2005, a total of 1292 intestinal
transplants in 1210 patients have been reported at 65
centers to the International Intestinal Registry: 570
were isolated small-bowel transplants, 490 combined
liver–small-bowel transplants and 232 were multivis-
ceral transplants. Of the 1292, 772 intestinal trans-
plants were performed in 721 pediatric recipients.
For transplants carried out between 2003 and 2005,
graft survival at 1 year was calculated to be around
80% with a patient survival percentage that was
somewhat higher. Center experience, patient status
prior to transplantation and induction therapy and
the type of calcineurin inhibitor had a significant
impact on outcome. Sepsis was the leading cause of
death. Most survivors have full graft function with no
requirement for parenteral nutrition (Figs. 1–4;
Table 1) [1].
We have performed altogether 4 small bowel
transplants in three patients suffering from end stage
Crohn’s disease. Patient characteristics are summa-
rized in Table 1.
Patient #1 was a 35-year-old male who had a com-
pletely uneventful postoperative course and is alive
and well with good graft function 64 months after
transplantation.
Patient #2 was a 37-year-old female who lost the
first graft 2 years after transplantation for chronic
rejection and underwent re-transplantation in June
Bowel Transplantation for Inflammatory Bowel Disease 313
2002. 42 months later she has a well function bowel
allograft, but requires intermittent hemodialysis for
chronic renal failure.
Patient #3 was a 60-year-old female suffering from
endstage intestinal and renal failure due to chronic
pyelonephritis und underwent combined small
bowel-kidney transplantation on July 7, 2003. She
developed early after transplantation a T-cell lym-
phoma of the intestinal graft requiring resection of
the graft. 29 months later she is alive with good renal
allograft function.
Recurrence of Crohn’s Disease
Crohn’s disease is considered to be an autoimmune
disorder. Therefore, the possibility of recurrence
within the graft is an important issue. So far, only two
well-documented cases of recurrent disease have
been reported. The first case was a 33-year-old
female, who underwent small-bowel transplantation
in December 1994. After induction with donor bone
marrow infusion and with OKT3, immunosuppres-
sion consisted of tacrolimus and methylpred-
nisolone. Only 7 months post-transplant did the
Fig. 1. 2003–2005 patient survival according to transplant
type. MVT, multivisceral transplantation; SB/Liver com-
bined small bowel-liver transplantation; SBT, small bowel
transplantation alone
Fig. 3. Graft survival according to pretransplantation status
of the recipients. Home, patients awaiting transplantations
at home; hospitalized, patients awaiting transplantation at
the hospital
Fig. 4. Graft survival according to centre size: >
100
, number
of transplants more than hundred;
11
–
100
, number of
transplants between 11 and 100;
1
–
10
, transplants per cen-
tre
Fig. 2. 2003–2005 graft survival according to D-transplant
type. MVT, multivisceral transplantation; SB/Liver, com-
bined small bowel-liver transplantation; SBT, small bowel
transplantation alone
p=0.531
p=0.544
p=0.000
p=0.014
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