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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_927_Библиотеки_им_академика_М_И_Перельмана.pdf
SMALL INTSESTINE 371
Adults with SBS and PN/IVF dependence
(*Refer to exclusion criteria)
Refer back to RD for gut
rehabilitation
Exclusion Criteria:
• Suspected or active malignancy
• History of malignancy within past 5 years
• Ultra short bowel syndrome (duodenostomy)
• Current alcohol or drug addiction; uncontrolled
psychiatric illness
• Obstructive disease (pSBO, SBO, strictures)—
Ongoing radiation enteritis, celiac disease,
tropical sprue, pseudo-obstruction
• If moderate or severe renal impairment, reduce
the dose by 50%
• Active IBD that requires chronic systemic
immunosuppressant
therapy that has been changed or introduced
in the past 3 months
• Compromised immune system (e.g., AIDS)
• Pregnancy or lactation
• Medically unstable
Additional Exclusion Criteria fo HGH:
• DM
• Carpal tunnel syndrome
Maximized gut rehabilitation interventions:
No Yes
Diet and medications
No Yes
Stabilize PN/IVF
regimen
Are they on a stable
PN/IVF regimen?
Intestinotrophic
hormone
FIGURE 72-2 Protocol for usage of human growth hormone (HGH) and glucagon-like peptide 2. AIDS, Acquired immunodeficiency syndrome;
DM, diabetes mellitus; IBD, inflammatory bowel disease; IVF, intravenous fluid; ORS, oral rehydration solution; PN, parenteral nutrition; pSBO, partial
small bowel obstruction; R D, registered dietitian; SBO, small bowel obstruction; SBS, short bowel syndrome.
O’Keefe SJ, Buchman AL, Fishbein TM, et al. Short bowel syndrome and
BOX 72-1: Common Antibiotic Treatment for Small
Intestine Bacterial Overgrowth
Metronidazole, 250 mg, 3×/day for 7-14 days/month
Tetracycline, 250 mg 4×/day for 7-14 days/month
Rifaximin, 550 mg 2×/day for 7-14 days/month
Amoxicillin clavulanate, 500 mg 3×/day for 7-14 days/month
Ciprooxacin, 500 mg 2×/day for 7-14 days/month
Neomycin, 500 mg 4×/day for 7-14 days/month
Noroxacin, 800 mg/day for 7-14 days/month
intestinal failure: consensus denitions and overview. Clin Gastroenterol
Hepatol. 2006;4(1):6–10.
Parekh N, Steiger E. Short bowel syndrome. Curr Treat Options Gastroenterol.
2007;10:10–23.
Peterson C. D-Lactic acidosis. Nutr Clin Pract. 2005;20(6):634–645.
Shatnawei A, Parekh N, Rhoda K, etal. Intestinal failure management at the
Cleveland Clinic. Arch Surg. 2010;145(6):521–527.
ompson JS, Rochling FA, Weseman RA, etal. Current management of short
bowel syndrome. Curr Prob Surg. 2012;49(2):52–115.
Ziegler TR, Cole CR. Small bowel bacterial overgrowth in adults: a potential
contributor to intestinal failure. Curr Gastroenterol Rep. 2007;9:463–467.
S u g g e S t e d R e a d i n g
Ladefoged K, Christensen KC, Hegnjoj J, etal. Eect of a long acting soma-
tostatin analogue SMS 201–995 on jejunostomy euents in patients with
severe short bowel syndrome. Gut. 1989;30:943–949.
Matarese L. Nutrition and uid optimization for patients with short bowel
syndrome. J Parenter Enteral Nutr. 2013;37:161–170.
Messing B, Crenn P, Beau P, etal. Long-term survival and parenteral nutrition
dependence in adult patients with the short bowel syndrome. Gastroenter-
ology. 1999;117:1043–1050.
S G F:
A-R
A-T
Kareem Abu-Elmagd, Ajai Khanna, Masato Fujiki, Koji Hashimoto, Galal El-Gazzaz,
Abdullah Shatnawei, and Guilherme Costa
INTRODUCTION
e successful clinical introduction of intestinal and multivisceral
transplantation in the 1990s fueled a great interest in the management of patients with short gut syndrome (SGS) and gastrointestinal
failure. With the early restricted utilization of transplantation as a
rescue therapy, the concept of gut rehabilitation was introduced as
a new therapeutic dimension to restore the nutritional autonomy of
the native digestive system. ese nontransplant rehabilitative measures include advanced nutritional care, new biologic therapy, and
novel surgical techniques including autologous gut reconstruction
and bowel lengthening. Adopting a multidisciplinary team approach,
these therapeutic modalities have been successful in restoring nutritional autonomy in properly selected groups of patients without the
need for visceral transplantation. Creative eorts have also been
made to treat certain gastrointestinal malignancies with ex-vivo
tumor resection and gut autotransplantation.
When attempts to restore nutritional autonomy fail, intestinal
and multivisceral transplantation should be promptly considered,
particularly for patients who can no longer be maintained on total
parenteral nutrition (TPN). e procedure also oers a valid therapeutic option for patients with complex abdominal disease that is
not amenable to conventional medical and surgical treatment. With
the continual improvement in survival, intestinal and multivisceral
transplantation has become the standard of care for gut failure in both
children and adults. In 2000, Medicare and other commercial health
insurances approved the procedure, particularly for patients who no
longer can be maintained on TPN. Similar waves of clinical interest
were witnessed across North America and Europe with an increase
in the worldwide clinical practicality of the procedure, which is currently available in all continents but Africa. Such an achievement has
been the result of surgical innovations, novel immunosuppressive
protocols, and better postoperative management.
is chapter is designed to address the comprehensive strategic management of gut failure, including medical therapy, surgical
rehabilitation, and intestinal transplantation. e newly introduced
treatment algorithm is discussed in the setting of recent therapeutic advances with special reference to innovative surgical techniques.
In addition, the current status of intestinal and multivisceral transplantation, including survival, gra function, and quality of life, are
highlighted, with new insights to further improve the long-term therapeutic ecacy of the transplant procedures.
GUT ADAPTATION
Soon aer each small bowel resection, the natural process of gut adaptation is initiated in both adults and children and continues for at least
the next 2 years. e dynamic process includes structural and functional changes in the residual visceral organs with enhanced nutrient and uid absorption. e extent of gut adaptation is commonly
372
inuenced by the site and extent of bowel resection, the presence of
active intrinsic gastrointestinal disorders such as Crohn disease, early
initiation of enteral feeding, growth of benecial intestinal microbiota, and stimulation of the endogenous enterotropic factors, including glucagon-like peptide 2 (GLP-2). e dierent phases of such a
natural phenomenon and its triggering mechanisms, including the
potent stimulatory eect of luminal nutrients with upregulation of
the colonic peptide transporter Pep T1, are discussed elsewhere. It
is also our speculation that changes in the gut-brain neural circuit
activities with altered gut neuropeptides may play an important role,
with enhancement of intestinal gluconeogenesis and gut homeostasis.
MEDICAL MANAGEMENT
Prompt comprehensive medical management and optimal nutritional care are the foundations of successful restoration of nutritional
autonomy. In addition to TPN, treatment includes dietary modication, antidiarrheal medication, and oral hydration with vitamin, mineral, and trace element replacement. Since its inception in the 1960s,
TPN has undergone several modications to reduce associated lifethreatening complications. For example, antibiotic-impregnated central indwelling catheters and ethanol-lock therapy were introduced
to reduce risk of line infection, and more recently, a short-chain lipid
formulation has been prescribed to reduce risk of hepatic injury.
Since its clinical introduction in 2005, omega-3 lipid formulation
replaced the standard omega-6 storage-based lipids for children in
many intestinal failure programs across both Europe and Canada.
However, despite a reported signicant reduction in serum bilirubin,
there has been no noticeable eect on the degree of hepatic brosis,
and the formulation has yet to become the standard of care in the
United States. Eorts to optimize TPN are crucial to the interval and
long-term management of patients with gut failure, particularly those
who are not candidates for transplantation.
Pharmacologic manipulation of the gut adaptation process has
been used increasingly in recent years. In addition to growth hormone, teduglutide (Gattex), a recombinant analog of human GLP2, has recently been approved in the United States for the treatment
of adult patients with intestinal failure due to SGS, including those
with quiescent Crohn disease. Approval for the pediatric population
is pending the results of a recently initiated clinical trial. e synthetic protease-resistance analogue, with a longer half-life, has been
shown to promote changes in intestinal structure with increased villous height and crypt depth and a subsequent increase in the intestinal absorptive capacity. In addition, GLP-2 inhibits gastric emptying,
increases intestinal transit time, suppresses gastric acid secretion,
improves bone mineral density, protects intestinal barrier function,
and increases intestinal blood ow. Nonetheless, there is a current
need to establish standard criteria and practical guidelines to optimize the utilization and cost-eectiveness of such an expensive medical therapy.
SMALL INTESTINE 373
Gallbladder
Ventral
pancreatic
bud
SURGICAL REHABILITATION
Strategy
Along with visceral transplantation, other innovative surgical modalities have been introduced to treat patients with intestinal failure due
to SGS and complex abdominal pathology. Other innovative operations have been comprehensively addressed in one of our recent
review articles. Such surgical rehabilitative eorts have been fueled
by the limited indications and potential complications of transplantation. Two of the most commonly used rehabilitative surgical techniques are autologous gut reconstruction and bowel lengthening.
e therapeutic benets of these multidisciplinary rehabilitative
measures are largely determined by the ability to control the primary
disease, restore continuity, slow transit time, prevent intraluminal
bacterial overgrowth, and enhance overall gut absorptive capacity.
Failure to restore nutritional autonomy should prompt early consideration for transplantation.
Autologous Reconstruction
Preoperative planning with in-depth understanding of the underlying
surgical disease and the residual gut anatomy is essential to achieve
a successful outcome and minimize risk of postoperative complications. Each operation is an organ salvage procedure with conservative
techniques guided by the embryonic development of the alimentary
canal (Fig. 73-1). Of crucial importance is complete awareness of
any abnormal vascular and structural anatomy that may dictate the
need for technical modications to avoid injury of the residual native
organs, particularly in patients with prior multiple abdominal operations and complex anatomy.
All surgical procedures should be performed with an open
approach with placement of bilateral external ureteric stents in
patients with frozen abdomens to avoid incidental ureteric injury.
Sharp tissue dissection with use of thermal hemostatic tools is advisable. Excision of all scar and granulation tissues is essential to identify the residual organs with careful preservation of the segmental
blood supply and any aberrant vasculature, particularly of the liver.
All anastomoses must be tension-free and hand sewn in two layers
using ne surgical techniques. Pyloroplasty is required with foregut reconstruction for drainage of a denervated stomach. Complete
removal of any abdominal wall surgical mesh is necessary to avoid
postoperative abdominal infection and recurrent enterocutaneous
stulae. Safe abdominal wall closure can be performed simply in a
single layer using nonabsorbable material, particularly in patients
with an infected abdomen.
Autologous reconstruction has frequently been used for patients
with complex enterocutaneous and genitourinary stulae, recurrent
strictures, and loss of gut continuity (Fig. 73-2). Most of these patients
have hostile abdomens with loss of the main domain. Common operative ndings in these patients with complex disease include a recalcitrant gut disorder, technically awed surgery, and infected abdominal
wall synthetic mesh. Foregut reconstruction is commonly indicated
for patients with bariatric surgery–associated gut failure and other
patients with complicated gastric surgery (Fig. 73-3). With residual
gastric segments, primary gastrogastric reconstruction is performed at
levels dictated by the size and integrity of the segmental blood supply
of the retained gastric portion(s). Proximal gastrogastric anastomosis
(Fig. 73-3, A) is commonly performed with esophagogastric reconstruction (Fig. 73-3, B), which is oen needed in patients with a small
brotic gastric fundus and those with a disrupted esophagogastric
junction. Complete salvage of residual portions of the stomach oen
requires two-level anastomoses, particularly in patients with combined high and low gastric disruption (Fig. 73-3, C). With proximal
and mid gastric reconstruction, takedown of the short gastric vessels
is oen necessary, and a pyloroplasty is required for drainage. In addition, all eorts should be made to avoid disruption of the angle of His.
In patients with massive gastric necrosis and a prior gastrectomy,
maintenance of the normal alimentary ow is crucial to restore full
nutritional autonomy, particularly in patients with SGS. erefore,
innovative surgical techniques should be used to create a neostomach
with a visceral conduit (Fig. 73-4) to avoid exclusion of the duodenal
from the alimentary ow and the accelerated exposure of the intestine to undigested nutrients. Interposition of a vascularized jejunal
segment (Fig. 73-4, A) or colonic segment (Fig. 73-4, B) between the
abdominal esophagus and gastric antrum or duodenum (Fig. 73-4,
C) is eective in restoring gut continuity and optimizing absorptive
capacity with achievement of full nutritional autonomy in patients
with sucient residual intestine. A pyloroplasty should be performed
in patients with a retained antrum.
Liver
Cecal bud
FIGURE 73-1 Embryonic development of the gas-
trointestinal solid and visceral organs along with the
axial blood supply. (Reprinted with permission, Cleveland
Clinic Center for Medical Art & Photography. Copyright
Esophagus
Stomach
Celiac artery
Dorsal
pancreatic
bud
Superior
mesenteric
artery
Inferior
mesenteric
artery
Foregut
Midgut
Hindgut
2009-2016. All Rights Reserved.)
Surgery for gut failure: auto-reconStruction and allo-tranSplantation374
AB
Midgut reconstruction has been the most common rehabilitative procedure, particularly in patients with mesenteric ischemia,
Crohn disease, and adhesive disorders (Fig. 73-5, A). All efforts
should be made to restore continuity of the hindgut, particularly
in patients with residual large bowel and a spared anorectum
(Fig. 73-5, B). When extensive hindgut resection is indicated—
particularly in patients with Crohn disease, dysmotility,
FIGURE 73-2 A hostile abdomen
with multiple enterocutaneous fistulae before (A) and after (B) successful autologous reconstruction
with full restoration of nutritional
autonomy.
A B
familial adenomatous polyposis, and colonic ischemia—it is our
recommendation that the anal sphincters be preserved for a future
pull-though operation using the donor colon at the time of transplantation. These genuine and technically challenging autologous reconstructive procedures have evolved as a result of our
cumulative surgical experience in the field of abdominal visceral
transplantation.
FIGURE 73-3 Major foregut reconstruction: proximal gastrogastric (A), esophagogastric (B), and combined esophagogastric and distal gastrogastric
(C). Note preservation of the segmental branches of left gastric artery. A pyloroplasty was required with all types of reconstruction for drainage of
the denervated stomach. (Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography. Copyright 2009-2016. All Rights Reserved.)
C
SMALL INTESTINE 375
AB C
FIGURE 73-4 A neostomach with an interposition alimentary conduit to restore normal alimentary flow in patients with prior gastrectomy
and unreconstructable stomach; jejunal interposition (A), colonic interposition with (B) and without retained gastric antrum (C). Pyloroplasty is
required for patients with a retrained antrum. (Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography. Copyright 2009-2016. All
Rights Reserved.)
FIGURE 73-5 Midgut (A) and
hindgut (B) reconstruction. Note
multiple enteroenteric anastomoses with different alignments
guided by the diameter of the
proximal and distal intestinal segment. Hindgut reconstruction is
commonly performed with one
or two left colon and rectal anastomoses, including taking down of
the previous colostomy. (Reprinted
with permission, Cleveland Clinic
Center for Medical Art & Photography. Copyright 2009-2016. All Rights
Reserved.)
AB
Surgery for gut failure: auto-reconStruction and allo-tranSplantation376
A
C
B
FIGURE 73-6 Longitudinal (Bianchi) bowel lengthening for patients with short bowel syndrome. Longitudinal stapler resection of a dilated bowel
loop between the anterior and posterior mesenteric leaves (A) resulting in two hemiloops (B), with each having its own blood supply. The two loops
are anastomosed sequentially (C), doubling the length and halving the diameter of the loop operated upon. (Reprinted with permission, Cleveland Clinic
Center for Medical Art & Photography. Copyright 2009-2016. All Rights Reserved.)
A
FIGURE 73-7 Intestinal lengthening with serial transverse enteroplasty. A, Alternating mesenteric and antimesenteric cuts using a GIA stapler, cre-
ating a zigzag-like channel that reduces diameter and increases length. B, Operative photo with enforcement of the staple lines with interrupted seromuscular sutures (arrows). (A, Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography. Copyright 2009-2016. All Rights Reserved.)
Intestinal Lengthening
Bowel lengthening increasingly has been used for patients with SGS
who have normal structural and vascular anatomy of the residual
gut. Figure 73-6 illustrates the technical steps of both the longitudinal (Bianchi; Fig. 73-6) and serial transverse enteroplasty (Fig.
73-7) procedures, with full details described elsewhere. Both opera-
tions can be successfully performed in patients with dilated bowel
loops to enhance gut absorption by reducing transit time and eliminating the risk of bacterial overgrowth. With nutritional and pharmacologic support, nutritional autonomy is achievable in properly
selected patients within the rst few months of surgery, particularly
in those with residual small and large bowel. e procedure could
also be repeated at a later time, particularly in patients who continue
to require TPN with redilated intestinal loops.
B
INTESTINAL AND MULTIVISCERAL TRANSPLANTATION
Types
e main “icons” of abdominal visceral transplantation are intestine alone (Fig. 73-5, A), combined liver-intestine (Fig. 73-5, B),
and multivisceral with (Fig. 73-5, C) and without (Fig. 73-5, D)
inclusion of the liver. e combined liver-intestinal gra commonly
includes the pancreas to maintain continuity of the axial blood supply and the biliopancreatic system. e multivisceral gra includes
the stomach, duodenum, pancreas, and intestine with (full) and
without (modied) the liver. Inclusion of the donor colon is recommended for a selected group of patients, in particular those who are
SMALL INTESTINE 377
AB CD
Portal vein
Interposition vein graft
Ligated middle
colic artery
Simple
loop
ileostomy
Marginal arterial arcades
Transplanted
organs
FIGURE 73-8 The different types of visceral transplantation. A, Isolated intestine. B, Combined liver-intestine, and multivisceral that includes the
stomach, duodenum, pancreas, and intestine with (C) and without (D) the liver. (Reprinted with permission, Cleveland Clinic Center for Medical Art &
Photography. Copyright 2009-2016. All Rights Reserved.)
Transplanted
organs
Transplanted
organs
Transplanted
organs
suitable candidates for a pull-through operation (Fig. 73-9) or other
innovative reconstructive procedures. In patients with concomitant failure of other organs, the needed organ such as the kidney
or pancreas is either added en bloc to the visceral allogra or rarely
implanted separately.
When native hepatic functions are preserved, patients with irreversible intestinal failure undergo isolated intestinal transplantation. A pancreas or kidney is simultaneously transplanted for those
with insulin-dependent diabetes and renal failure, respectively, and
a composite liver-intestinal allogra is given to patients with combined liver and intestinal failure. Full multivisceral transplantation is
indicated for patients with liver failure and diuse end-stage gastrointestinal disorders. e procedure is also applied for patients with
a hostile abdomen and complex surgical disease, particularly those
Infrarenal
aortic graft
who require retransplantation with more complex visceral allogras.
Modied multivisceral transplantation is commonly used for patients
with combined foregut and midgut organ loss or failure with preserved hepatic function. With the recent broadening of indications
for transplantation and the diversity of the underlying gastrointestinal disorders, various innovative surgical techniques have recently
been introduced to the originally described donor and recipient
operations.
Indications
Small bowel and multivisceral transplantation is currently indicated for
patients with irreversible intestinal failure who experience signicant
complications of TPN. It is also required for patients with complex
abdominal pathology who failed conventional surgical intervention.
Internal, external
anal sphincters
FIGURE 73-9 Pull-through reconstruction with en bloc colon and
intestinal transplantation in a patient with intact anal sphincters. (Modified with permission from Eid KR , Costa G, Bond GJ, et al. An innovative
sphincter preserving pull-through technique with en bloc colon and small
bowel transplantation. Am J Transplant. 2010;10:1940-1946.)
SGS is the most common cause of intestinal failure and the leading indication for transplantation in both children and adults. e main causes
in adults are mesenteric vascular occlusion, recalcitrant Crohn disease,
dysmotility syndromes, neoplastic disorders, adhesive disease, and
impaired enterocyte functions. Mesenteric vascular thrombosis is most
commonly precipitated by a prothrombotic state including protein C,
S, and antithrombin III deciencies, factors V/II and Jake-2 mutations,
myeloproliferative disorders, essential thrombocytosis, lupus anticoagulant, and anticardiolipin antibodies. Crohn disease is the second most
common indication, and candidates are those either with type 3 intestinal failure or type 2 with failure of surgical rehabilitation. In children,
the precipitating causes of SGS are commonly gastroschisis, volvulus,
Time after transplantation (year)
Primary graft survival (%)
100
intestinal atresia, and necrotizing enterocolitis.
Dysmotility and neoplastic syndromes are common indications for
transplantation among both children and adults. e spectrum of the
gastrointestinal motility disorders include enteric dysmotility, hollow
visceral myopathy and neuropathy, total intestinal aganglionosis, and
secondary syndromes due to viral illnesses, autoimmune diseases, and
other unknown causes. e main hereditary neoplastic disorder is familial adenomatous polyposis, although other, rarer dysplastic conditions
also exist. End stage deciencies of enterocyte absorptive capacity are
commonly seen in children with microvillus inclusion disease and in
adults with irradiation enteritis, autoimmune enteropathy, lymphangiectasia, and inammatory bowel disease. e extent and severity of the
disease process commonly dictate the necessity for spontaneous en-bloc
replacement of more than one of the abdominal visceral organs.
Of the recently emergent indications for transplantation are gut
failure aer bariatric surgery and diuse portomesenteric venous
hrombosis inpatients with liver failure. e catastrophic loss of the
gastrointestinal organs aer the weight reduction procedures (type 1)
and the unsuccessful surgical rehabilitation of type 2 (chronic technical complication) and type 3 (functional disorders) commonly dictate the need for intestinal and multivisceral transplantation. In the
presence of diuse thrombosis of the portomesenteric venous system, replacement of a failing liver can only be successfully achieved
in most patients with full multivisceral transplantation.
Despite continual improvement in survival aer transplantation,
failure of TPN has continued to be a prerequisite for intestinal and
multivisceral transplantation. In our formal request for national coverage in 2000, TPN failure was dened as “signicant biochemical
or histologic evidence of hepatic injury, loss of central venous access
with occlusion of at least two central veins, frequent line sepsis or
single episode of fungal infection, and recurrent episodes of severe
dehydration despite intravenous uid supplementation.” In addition,
ultra-SGS and end stage gastrointestinal disorders that are not amenable to medical and surgical rehabilitative measures are legitimate
indications for visceral transplantation.
Retransplantation with an intestinal or multivisceral gra is indicated as a life-saving procedure in about 10% of the patients. With
intestine-alone allogras, a two-stage surgical strategy with a time
interval between allogra enterectomy and retransplantation may
achieve a better outcome. Despite a satisfactory outcome, novel strategies are required to reduce the risk of recurrent intractable rejection,
particularly of a liver-free allogra. Recipient pretreatment with lymphoid-depleting agents, anti–B cell therapy, better human leukocyte
antigen (HLA) match, and simultaneous replacement of the native
liver utilizing the domino procedure are such novel approaches that
could potentially improve outcome aer retransplantation.
Contraindications
Signicant cardiopulmonary insuciency, incurable malignancy, persistent life-threatening intra-abdominal or systemic infections, and
severe immune deciency syndromes are absolute contraindications to
an intestinal transplant. e coexistence of acquired immune deciencies dictates the need for a stem cell transplantation rst to avoid the
inevitable risk of gra-versus-host disease aer visceral transplantation.
Recently, poor psychosocial support has been identied as a
major risk factor for compromising a long-term successful outcome,
and thus the lack of adequate social support should be considered
a relative contraindication for transplantation. Meanwhile, all multidisciplinary eorts should be made to improve the psychosocial support of these unfortunate patients, particularly children. However,
the presence of long-standing neuropsychiatric disorders should not
preclude transplantation because successful rehabilitation aer transplantation has recently been documented.
A history of gastrointestinal malignancy, loss of central venous
access, and older age should not exclude candidacy for transplantation.
Surgery for gut failure: auto-reconStruction and allo-tranSplantation378
90
80
70
60
50
40
30
20
Isolated intestine (n = 198)
10
0
0 246810121416
FIGURE 73-10 Graft survival according to duration of total parenter-
al nutrition (TPN) before transplant. Early transplantation is associated
with a better outcome. (Modified with permission from Abu-Elmagd K,
Costa G, Bond GJ, et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances and new challenges. Ann Surg.
2009;250:567-581.)
1 year (n = 63)≤TPN
TPN >1 year (n = 135)
P = .1
Chemical dependency, psychosomatic disorders, active abdominal
infection, and the presence of locally advanced desmoids or stroma
cell tumors should be addressed before the patients are considered
unsuitable for transplantation.
Early Referral
Early consideration for transplantation before the development of
TPN failure or progression of complex abdominal disease is not yet
the standard of care. However, recently published data favor early
transplantation with increased candidacy and survival (Fig. 73-10)
and better quality of life. e native liver can be saved with reduction
or elimination of the potential prohibitive risk of dying while patients
are on the United Network for Organ Sharing (UNOS) waiting list
for an allogra that contains a liver. An additional advantage is the
ability to perform allogra enterectomy to rescue the intestine-alone
recipients with reinstitution of TPN.
It is important to realize that current survival aer transplantation
is comparable with that of patients with TPN-dependent intestinal
failure despite the use of the procedure as a rescue therapy. Equally
important is the achievement of nutritional autonomy with better
quality of life and improved value of health care.
Transplantation Surgery
e standard donor and recipient surgical techniques, including major
vascular and gastrointestinal reconstructions, are described elsewhere.
In brief, restoration of the arterial inow is established with an arterial conduit anastomosed to the native infra-renal or supra-celiac (with
multivisceral) aorta. e venous return of the isolated intestinal and
modied multivisceral gra is established by an interposition vein gra
anastomosed to the native portal vein or inferior vena cava. ese free
donor arterial and venous conduits are placed in the recipient before
bringing the visceral allogra to the operative eld to facilitate a safe
vascular reconstruction. Meanwhile, the Carrel patch reconstructive
technique, which is used to establish a single arterial conduit for the
superior mesenteric artery and celiac trunk of the composite visceral
gra, has remained the Achilles heel of the back table donor procedure.
With combined liver-intestinal transplantation, a native portocaval
SMALL INTESTINE 379
AB
FIGURE 73-11 Modified multivisceral transplantation that includes the stomach, duodenum, pancreas, and intestine (blue). Note preservation of the
native spleen (brown) with (A) and without (B) the duodenopancreatic complex.
shunt is created to drain the retained le upper quadrant organs. e
venous outow of the composite visceral allogras, including the combined liver-intestinal and full multivisceral gra, is via the standard
contains a segment of the donor colon (Fig. 73-9). Accordingly, it is our
recommendation that the anal sphincters be preserved in all patients
who are in need of a proctocolectomy for benign disease.
piggyback caval reconstruction (Fig. 73-8, B and C).
Reconstruction of the gastrointestinal tract includes proximal
anastomosis with native esophagus or residual gastric cu in recipients of a full or modied multivisceral allogra (Fig. 73-8, C and D).
With isolated intestinal and combined liver-intestinal transplantation, the anastomosis is performed between the native duodenum or
jejunum and the allogra jejunum (Fig. 73-8, A and B). In patients
with residual hindgut, distal continuity is restored by anastomosing
the allogra ileum to the native colon or rectum. A temporary chimney or simple loop ileostomy is performed in all patients for surveillance ileoscopy and random mucosal biopsies.
In patients with gut dysmotility, the native pancreaticoduodenal
complex, including the spleen (Fig. 73-11, A), is commonly preserved. e primary objectives are to reduce risk of posttransplant
lymphoproliferative disorder (PTLD), maintain the portosplenic circulation during allogra implantation, eliminate the need for biliary
reconstruction, and augment the islet cell mass by retaining the native
pancreas. In these patients, a piggyback duodenoduodenal anastomosis is performed. It is also our practice in these patients to preserve
a short segment of the native rectosigmoid and establish continuity
of the hindgut with the ileal allogra. In patients with familial adenomatous polyposis, total pancreaticoduodenectomy with possible
preservation of the spleen is sometimes achievable, with duct to duct
or Roux-en-Y biliary reconstruction (Fig. 73-11, B).
In recipients with ultra-SGS and a prior duodenocolonic anastomosis
close to the duodenal papilla, a segment of the native colon can be used
as a visceral conduit between the native duodenum and proximal end of
the allogra jejunum (Fig. 73-12). e allogra terminal ileum is then
anastomosed to the distal end of the remaining native colon. In patients
with prior total proctocolectomy and preserved anal sphincters, a pullthrough operation is commonly performed using a visceral allogra that
Postoperative Management
Immunosuppressive therapy, early diagnosis of allogra rejection,
infectious prophylaxis, and nutritional care are crucial to posttransplant management. Introduction of novel immunosuppressive and
immune modulatory strategies has been one of the seminal contributions that improved the therapeutic ecacy of visceral transplantation. With new insights into the mechanism of allogra acceptance
and transplant tolerance, recipient preconditioning with lymphoiddepleting agents combined with posttransplant minimal immunosuppression was introduced with improved survival and reduced
incidence of intractable rejection, PTLD, and fatal infections. Recent
data have also suggested the possible therapeutic benets of mammalian target of rapamycin (mTOR) inhibitors (sirolimus) as a maintenance therapy. With better understanding of the mechanisms of
allogra tolerance and the introduction of new scientic discoveries,
we hope that establishment of long-term drug-free allogra acceptance will be achievable in the very near future.
With no biochemical or biological markers currently available,
surveillance endoscopy with multiple mucosal biopsies is the only
tool to diagnose intestinal rejection. e diagnostic criteria of rejection are fever, diarrhea or high stoma output, abdominal distension,
leukocytosis, thrombocytopenia, gastrointestinal bleeding, endoscopic ndings of mucosal erythema or ulceration, and histologic
evidence of allogra injury including crypt damage, apoptosis, and
sloughing of the intestinal mucosa. With chronic rejection, recipients
present with weight loss, severe malnutrition, gastrointestinal bleeding, bowel obstruction, and enterocutaneous stulae with full-thickness histopathologic evidence of cryptopenia obliterative arteriopathy
Surgery for gut failure: auto-reconStruction and allo-tranSplantation380
Patient survival (%)
Time after transplantation (years)
–1995)
100
mesenteric scleorsis and lymphnode depletion. Augmented immunosuppression with steroids and antilymphoid preparations is required
for treatment of acute rejection, and advanced chronic rejection is
treated with allogra enterectomy and/or retransplantation.
As part of the two-way immune interaction, the incidence of
gra-versus-host disease is reported to be less than 10%. is clinically suspected disease that commonly involves the recipient’s skin
and gastrointestinal tract is conrmed with histopathologic examination of the aected organ(s) and detection of circulating donor
cells in the peripheral blood of the recipient. It happens at a relatively
higher rate in composite visceral allogra recipients, particularly
children with immunodeciency, and in those who had splenectomy
or were pretreated with antilymphocyte-depleting agents.
Management of infectious complications has gradually been
enhanced as the result of cumulative clinical experience, advances in
molecular diagnostic techniques, and availability of new antimicrobial
drugs. e clinical availability of the quantitative competitive polymerase chain reaction assay triggered serial monitoring of Epstein-Barr
virus and cytomegalovirus (CMV) load in peripheral blood. Treatment strategies include prophylactic antibiotics, preemptive therapy of
Epstein-Barr virus and CMV viremia, and active treatment of bacterial
and fungal infections. ese management protocols, along with minimization of posttransplant immunosuppression, have signicantly
reduced risk and mortality of PTLD, CMV, and microbial infections.
When transplantation is successful, most recipients tolerate oral
feeding within the rst 2 weeks of surgery. Within 4 weeks, TPN is commonly discontinued with achievement of full nutritional autonomy.
Serial measurement of body weight, uid and electrolyte balance, and
micronutrient serum levels are valuable tools to monitor the absorptive
functions of the intestinal allogra. e development of allogra dysfunction as a result of dierent infectious and immunologic complications commonly dictates the need for reinstitution of TPN.
Long-term follow-up, including close monitoring of the cardiovascular system, glucose homeostasis, skeletal health, and renal
function, along with the standard tumor surveillance protocols, is
strongly recommended. Successful interventions have been eective
in minimizing the unwanted impact of long-term morbidities on the
health status and quality of life of these unique survivors.
De novo nonlymphoid malignancy has also been a potential threat
to long-term intestinal and multivisceral transplant survivors. Such a
life-threatening morbidity is due to prolonged exposure to dierent
environmental and nonenvironmental carcinogens with the foreseeable
acquired impaired immune surveillance. Regular follow-ups with universal and specic tumor surveillance protocols have been eective in
the early diagnosis with prompt intervention and satisfactory outcome.
Current Global Activities
As of June 2015, more than 3000 transplants had been performed
at 78 centers in all continents but Africa, with increased transplant
activities in Europe, South America, and Asia. is activity reects
the growing worldwide interest in the eld with cumulative improvement in surgical experience, postoperative care, and overall survival.
However, the total yearly global activity has decreased during the past
few years, particularly among the pediatric population, because of the
growing interest in medical and surgical gut rehabilitation. In addition, there has been a gradual decline in the number of adult livercontained visceral transplants in the United States because of changes
in the UNOS/Organ Procurement and Transplantation Network
(OPTN) policy with limited access to the national donor pool. It is
our expectation that the continual evolution of gut rehabilitation and
TPN therapy may oset the expected increase in transplant activity as
a result of recent broadening of the indications as previously outlined.
FIGURE 73-12 Native colonic conduit in a patient with ultra-short
gut syndrome who required isolated intestinal transplant. A segment
of the native colon (arrow) that was previously anastomosed to the
second part of the duodenum was retained at the time of transplant
and anastomosed to the jejunal end of the allograft. (Reprinted with
permission, Cleveland Clinic Center for Medical Art & Photography. Copyright
2009-2016. All Rights Reserved.)
Long-Term Survival
e cumulative largest single center (Fig. 73-13) and worldwide (Fig.
73-14) clinical experience has shown steady improvement in 1- and
90
80
70
60
50
40
30
20
10
0
0 2 4 6 8 10 12 14 16 18 20
FIGURE 73-13 Continual improvement in survival after intestinal and
multivisceral transplantation. (Modified with permission from Abu-Elmagd
K, Costa G, Bond GJ, et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances and new challenges. Ann Surg.
2009;250:567-581.)
P = 0.000
Era III (2001–2009
n = 285
)
Era II (1996–2000)
n = 106
Era I (1990
n = 62