The document discusses intestinal transplantation, including: 1. Intestinal transplantation was first performed in animals in the 1960s and in humans in the 1960s-1980s but had poor outcomes until immunosuppression with tacrolimus in the 1990s improved survival rates. 2. Intestinal transplantation treats intestinal failure but carries high risks of rejection due to the intestinal epithelium's immunogenicity and infections due to intestinal bacteria. 3. With improved patient management, surgical techniques, immunosuppression, and graft surveillance, one-year patient survival after intestinal transplant is now over 90% at major transplant centers.

1. Hsin-Lin Tsai, MD, PhD, FACS
臺北榮總
Department of Surgery,
Taipei Veterans General Hospital

2.  Part of the digestive system, one of the largest
organ systems in the body
 Moves food
 Absorbs fluids, nutrients and minerals
 Also an essential endocrine organ
 produces hormones that influence hunger, satiety, and
electrolyte homeostasis.
 Symptoms of intestinal failure include:
 persistent diarrhea, dehydration, muscle wasting, poor
growth, frequent infections, weight loss, and fatigue,
eventually leading to death

3.  Based on data of safety
and efficacy:
 HPN, primary treatment
of IF
 Recent advances in HPN
 Lower rate and later
onset of complications
 The number of
transplants/year
declined
• 15~20% of HPN patients
are potential candidate for
SBT

4.  Inability of the GI-tract to maintain an adequate
nutritional status and a fluid/electrolyte balance
 Pathophysiology of IF
 Short bowel syndrome
 Motility disorder
 Extensive parenchymal disease
 Intestinal fistula
 Intestinal rehabilitation programs
 Medical treatment
 Non-transplant surgery
 Home parenteral nutrition (HPN)

5.  Alexis Carrel (1912, Nobel Prize winner) was the first one to perform
it in an animal model
 his description of a method of performing vascular anastomosis
 Lillehei et al reported
 The first canine model, 1959
 The first case of human bowel transplantation, 1967
 Deterling in Boston in 1964 (unpublished data), the first human
intestinal transplant
 Between 1970 to1980
 Poor outcome
 All patients died of technical complications, sepsis, or rejection
 The most significant advance in the development of intestinal
transplantation was the introduction of TACROLIMUS (1990)
 The Starzl group (1998)
 55 children
 Patient survival rates were 55%, Graft survival rates were 52%

6.  High immunogenicity
 Intestinal epithelium: large absorptive surface
expresses donor HLA and non-HLA antigens
 Large number of white cells
 High risk of infection
 Large number of bacteria

7. • Intestinal failure + life-threatening
complications
• Failure of HPN
• IFALD: 5-year risk of death Relative Risk (RR)/
3.2
• CVC-related thrombosis/sepsis: RR/1.1-2.1
 Underlying disease
 Desmoid tumor: RR/7.1
 High morbidity and very poor quality of life

10.  The busiest programs: USA
 North America: 76% of the world
activity
 Asian centers perform 34% of
their transplants using live donor
grafts vs. 1% worldwide
 Centers in South America and
Asia
 more transplants in sicker patients
(63% vs. 79% of patients were called
from home; p<0.001)
 fewer grafts with liver component
(14% vs. 58%; p<0.001)

11.  Small intestine transplant: intestine without the
liver or stomach;
 Liver and small intestine transplant: intestine
with the liver but no stomach;
 Modified multivisceral transplant: stomach and
intestine without a liver graft;
 Multivisceral transplant: intestine plus liver and
stomach
 The pancreas is included in the composite graft usually for
technical reasons and less frequently for medical indications

13. Liver and intestine
Pancreas included
Multivisceral
Isolated Intestine
Type of grafts
Modified MVT

16. Improvements
 Improved patient
management
 Advances in surgical
technique
 Immunosuppression
 Graft surveillance
For patients transplanted at centres of excellence the actuarial overall patient
survival rate now is 93% at 1 year, 70% at 5 years and 50% at 10 years

17.  History and physical (including mother history,
prematurity, previous surgeries)
 Psychosocial evaluation
 Laboratory analysis
 Radiological studies
 Tissue biopsy: liver, suspected lesion…etc
 Cardiac and pulmonary status
 Serology and tissue typing

18.  Anesthetic induction and maintenance
 Preenterectomy stage
 Blood loss, core temperature
 Enterectomy stage
 Compromising venous return, toxin released from
abdominal infections
 Neointestinal stage
 Reperfusion effects, hypothermia

19.  Improved patient management
 Advances in surgical technique
 Immunosuppression
 Graft surveillance

20. • Technical
modifications:
– Spleen, native
spared/donor graft
origin; donor
lymphocyte filter,
associated with GVHD
– Gastro-gastric
anastomosis; GE Reflux
– Donor colon, presently
30% inclusion rate;
fluid/electrolyte balance

21.  Primary abdominal closure is sometimes impossible
 Failure to close exposes the patient to serious
complications

22.  Transplantation
of the abd. Wall
 Artificial mesh
 Fascia of rectus
muscle implant

23.  Improved patient management
 Advances in surgical technique
 Immunosuppression
 Graft surveillance

24.  Induction therapy
 IL-2 blocker: basiliximab (Simulect), daclizumab
(Zenapax)
 Depleting agent: thymoglobulin, alemtuzumab
(Campath)
 Maintenance
 Tacrolimus, turning point to success
 Sirolimus (rapamycin), emerging alternative option

26.  Improved patient management
 Advances in surgical technique
 Immunosuppression
 Graft surveillance

27.  Serum citrulline
 Fecal calprotectin
 Cylex Immune Cell Function Assay
 Donor specific antibodies (DSA)
 Noninvasive biobarkers
 Low specificity between rejection and infection

28.  Endoscopic biopsy
 Rejection
 Preservation injury
 Infection
 Appropriate ISP
without delay

29.  Signs and symptoms
 Abdominal pain
 Fever, nausea, vomiting
 Increased stomal output
 Septic shock if severe
 Endoscopic findings
 Edema, hyperemia
 Granularity
 Loss of fine mucosal vascular pattern
 Mucosal ulceration
 Differential Diagnosis
 Nonspecific infectious enteritis
 Viral infections: CMV, adenovirus, HSV…
 PTLD
 Chronic rejection
 Sclerosing peritonitis

30. The most common symptom of rejection is:
No symptoms

32. • Twice/week endoscopy in the first 4 weeks after
transplant, once weekly for 3 months, then
monthly
• Daily or every other day when rejection diagnosed
until resolution of clinical and histological signs

33. Height
Erythema

34. Moderate ACR  Treatment  30 days later

35.  Indeterminate
 Up to 6 apoptotic bodies per 10 crypts
 Mild
 >6 apoptotic bodies per 10 crypts
 Moderate
 Confluent apoptosis
 Increased inflammation
 Epithelial injury
 Severe /Exfoliative
 Features of moderate rejection plus mucosal ulceration
 May have arteritis
 Must be distinguished from CMV ulcers
 Poor prognosis

41. GF GF

42. Plasma cell
depletion

43. Complement
inhibition

44. • Rejection
• Infection
• PTLD
• GVHD

45. • The leading cause of death and graft loss after SBT
• Nearly all patients (>95%) develop one or more
episodes of documented infections after transplant
• Average number of infection episodes: 5 per patient
• More common early after transplant: 50% 1-3 months,
25% 3-12 months, 25% > 12 months
• Causative agents:
– Bacterial
– Fungal
– Viral
– Many episodes of mixed infections (viral/bacterial
or bacterial/fungal)

46. EBV-infected cells Polyclonal
proliferation
Monoclonal
proliferation
Malignant
lymphoma
PTLD
POST-TRANSPLANT
LYMPHOPROLIFERATIVE DISORDERS

48. 1. Infection with EBV
2. Seronegativity for EBV at the time of transplant
(post-transplant EBV infection)
3. Type of transplanted organ
• Intestinal transplant (28%), Heart/lung (10%), Liver
(2.2%)
4. Strength and length of immunosuppression
 T-cell depletion agents (ATG, OKT-3), higher risk
 High targeted level of tacrolimus, higher risk
5. Associated with CMV infection episodes

49.  Reduction of immunosuppression (even at risk of
rejection)
 Antiviral medications (Gancyclovir, Acyclovir),
hyper immune immunoglobulins (Cytogam)
 Surgical resection/local irradiation
 Anti- CD20 antibody therapy (Rituximab)
 Interferon alpha
 Conventional chemotherapy

51. Incidence:
BMT: 30-50%
SBT: 5-6%
Liver: 1%

54.  From IF to SBT: careful decision on a case-by
case basis
 Current graft survival rates are comparable with
the results of other solid organ transplants
 How to manage the complications, i.e. rejection,
infection, and PTLD is the challenge