SMALL INTESTINAL TRANSPLANT OVERVIEW

1. SMALL INTESTINE TRANSPLANT
Moderator: Dr Vivek Gupta
Presenter: Dr. Mahesh. R
SGE, KGMU, LUCKNOW

2. History
• R.Margreiter Transplantation Reviews Volume
11, Issue 1, January 1997, Pages 9-21

3. Type of transplantation
•
IITx L-Itx MVTx
Nickkholgh et al., “Intestinal transplantation: review of operative techniques,” Clinical Transplantation, vol. 27, supplement 25, pp. 56–65, 2013.

4. Indications
• Intestinal failure
Complications of parenteral nutritional therapy
• Liver failure
• Thrombosis of 2 or more central veins
• 2 or more episodes per year of central venous catheter related systemic sepsis requiring hospitalization
• Single episode of catheter related fungemia or septic shock
• Frequent episodes of severe dehydration despite intravenous fluid supplementation in addition to parenteral
nutrition
C S Desai Indian J Gastroenterol (September–October 2012) 31(5):217–222

5. • Intestinal failure is an uncommon condition defined as actual or impending loss of nutritional autonomy due to
intestinal dysfunction.
C S Desai Indian J Gastroenterol (September–October 2012) 31(5):217–222
• Subdivided into two groups:
1.short bowel syndrome
2.functional disorders: impaired motility or absorptive capacity in the presence of sufficient intestinal length and
surface area
• “Short bowel syndrome”, refers to the malabsorptive state that results from an anatomic deficiency of the
small intestine
Khan K; Bannerjee B (ed) Nutritional Management of Digestive Disorders. Boca Ratan: CRC; 2009.p. 233–52

6. Leading Causes of Intestinal Failure in Children and Adults

7. Small bowel transplants alone are offered to patients with
• with irreversible IF and preserved liver function
• Considered only in patients who failed dedicated attempts at intestinal rehabilitation
L. E. Matarese, G. Costa, G. Bond et al., “Therapeutic efficacy of intestinal and multivisceral transplantation: survival and nutrition outcome,” Nutrition in Clinical Practice, vol. 22, no.
5, pp. 474–481, 2007

8. Liver Intestinal Transplant
1.Intestinal failure and advanced, irreversible liver failure due to TPN
2.Intestinal failure due to a hypercoagulable state associated with enzyme deficiencies that can be corrected by a
liver graft
Grant D. Intestinal transplantation: 1997 report of the International Registry. Transplantation. (1999);67:1061–1064
• Currently, there is no clear consensus
• Patients on TPN who develop cirrhosis have essentially a 100% mortality rate at 5 years without transplantation
J. Fryer et al, “Mortality in candidates waiting for combined liver-intestine transplants exceeds that for other candidates waiting for liver transplants,” Liver
Transplantation, vol. 9, no. 7, pp. 748–753, 2003

9. • 2005 UNOS data, 74% in liver transplant list required, before (10%), simultaneously (52%), or after (12%) ITx
L. Buchman, et al., “Parenteral nutrition-associated liver disease and the role for isolated intestine and intestine/liver transplantation,” Hepatology, vol. 43, no. 1, pp. 9–19, 2006
• Prior to 2002, estimated 86% of all deaths occurring in patients listed for ITx were in those waiting for L-ITx
J. Fryer, “Mortality in candidates waiting for combined liver-intestine transplants exceeds that for other candidates waiting for liver transplants,” Liver Transplantation, vol. 9, no. 7, pp. 748–753, 2003.
• 48% of allografts included liver between 2001-2011 vs 61.8% and 53.2% between 1985–1995 and 1995–2001.
ITR, “Bi-annual report,” in Intestinal Transplant Registry, D. Grant, Ed., Toronto, Canada, 2014
Probable reasons
• Better understanding of the physiopathological mechanisms of PNALD
• Improved care of patients on long-term TPN.
• Replacement of the soy-based lipid emulsions by omega-3 rich lipid emulsions
F. Mercer, et al., “Hepatic fibrosis persists and progresses despite biochemical improvement in children treated with intravenous fish oil emulsion,” Journal of Pediatric Gastroenterology and Nutrition, vol. 56, no. 4, pp.
364–369, 2013.

10. • 9 months after transplant, all patients showed regression of liver fibrosis with an improvement of at least one stage
M. I. Fiel et al., “Regression of hepatic fibrosis after intestinal transplantation in total parenteral nutrition liver disease,” Clinical Gastroenterology and Hepatology,
vol. 6, no. 8, pp. 926–933, 2008.
• Early cirrhosis reversal and TPN weaning 17 months after a successful IITx
• Liver biopsy with persistent elevation of the total bilirubin and/or low platelet counts in order to guide the choice of
allograft.
• Transjugular liver biopsy: measurement of portal pressure gradient since in short bowel, wedge pressure may
grossly underestimate actual portal venous pressures.
• M. I. Fiel “Rapid reversal of parenteral-nutrition-associated cirrhosis following isolated intestinal transplantation,” Journal of Gastrointestinal Surgery, vol. 13,
no. 9, pp. 1717–1723, 2009.

11. Multivisceral and Modified Multivisceral Transplantation
• Allografts including stomach and the duodenum
• Refer to the transplantation of all organs dependent on the celiac artery axis and the SMA.
• An alternative definition that has not been widely accepted distinguishes MVTx only by the need for upper
abdominal exenteration and not by the inclusion or exclusion of the stomach.
• “full” (MVTx) if includes liver and “modified” (MMVTx) if it does not
A. Nickkholgh, P. Contin, K. Abu-Elmagd et al., “Intestinal transplantation: review of operative techniques,” Clinical Transplantation, vol. 27, supplement 25, pp. 56–65, 2013.

12. INDICATIONS
• Extensive portomesenteric thrombosis with hepatic decompensation
Other indications
• Familial polyposis syndromes
• Massive abdominal desmoid tumors
• Locally aggressive benign tumors requiring total exenteration .
• Traumatic loss of abdominal viscera, such as can be seen after major motor vehicle accidents
• Diffuse gastrointestinal motility disorders, such as chronic intestinal pseudoobstruction (CIPO), scleroderma, and
hollow visceral myopathy syndrome
L. E. Matarese et al., “Therapeutic efficacy of intestinal and multivisceral transplantation: survival and nutrition outcome,” Nutrition in Clinical Practice, vol. 22, no. 5, pp. 474–481, 2007.

13. Contraindications to intestinal transplantation
• Active systemic infection
• Pre-existence of severe neurologic dysfunction
• Severe Cardiac & Pulmonary dysfunction
• History or presence of systemic aggressive or incurable malignancy
• Patients over 60 years old, or with inactive lifestyle
• Who failed alcohol or drug rehabilitation
Khan K Zakim & Boyer's: Hepatology:A Textbook of Liver Disease. Philadelphia: Elsevier Saunders;2010. p. 986–95

14. Preoperative evaluation
Recipients
• Blood group and HLA typing
• Laboratory tests: CBC, LFT, RFT coagulation profile
• serologic tests: CMV, EBV, HIV, Hepatitis A,B, and C
• Duplex Doppler sonography of intraabdominal vascular system
• Liver biopsy (only for recipient candidates with clinical evidence for TPN-induced liver dysfunction in order to
assess the need for a simultaneous liver transplant)
• Assessment for infectious foci (including dental and ENT)
• Additional organ system-specific investigations as dictated by pathologic results

15. Cadaveric Donor selection and preparation
• ABO identical,
• Hemodynamic stability,
• Compatible size (preferably smaller than the recipient)
• Negative lymphocytotoxic cross-match and cytomegalic virus [CMV]
• Intestinal decontamination: In all donors with amphotericin B, an aminoglycoside, polimyxin, and broad-spectrum
antibiotics before and during procurement.
• In situ perfusion with University of Wisconsin preservation solution.
• The graft is stored in ice for transport. Mean cold ischemia time, the time between organ procurement and
implantation, is approximately 8 hours (range 2.8 - 14.8 hours). A cold ischemia time of less than 10 hours is
recommended to avoid preservation injury.
• Kosmach Park B. Intestinal Transplantation. From Organ Transplantation: Concepts, Issues, Practice and Outcomes. Medscape. Jun 17, 2002.

16. Living Donor Protocol
• ABO compatibility
• If more than one donor was deemed suitable, the one with the best HLA match was chosen.
• Selective angiography of SMA to exclude any vascular abnormality.
• Mechanical preparation of the intestinal graft was performed 1 day prior to surgery.
• 2 doses of 45 mL of phosphosoda were given 4 hours apart on the afternoon before the surgery.
• 3 doses of neomycin 1 g and metronidazole 500 mg were given 18, 17, and 10 hours prior to surgery per os.
• A single preoperative dose of antibiotic prophylaxis with intravenous cefoxitin 2 g IV

17. Operative technique (basic steps)
• Cadaveric transplantation

18. Intestinal transplantation alone
Donor operation
• Kocher & Cattell maneuvers, aorta and inferior vena cava are exposed behind intestinal mesentery up to SMA

19. • Ligament of Treitz broadly mobilized from retroperitoneum & aorta, mobilizing the distal duodenum and proximal
jejunum.
• Abdominal aorta encircled distally for eventual aortic cannulation and flush.
• Gastrocolic omentum is divided, Colon mesentery dissected, exposing right, middle, and left colic vessels.
• Exposure of colic vessels facilitates rapid removal of the colon immediately prior to heparinization and
cannulation.
• If right colon is to be a component , right and transverse colon mesentery must be left intact in order to prevent
internal herniation

20. • Medial visceral rotation mobilizes tail of the pancreas with spleen exposing left side of aorta & origin of
mesenteric vessels
• Pylorus transected with a linear stapler,
• Use of IMV for flush during intestinal procurement is discouraged,as high flow and pressure in the IMV flush may
decrease intestinal outflow through SMV

21. • Prior to administration of systemic anticoagulants, heparinization and aortic cannulation luminal contents are
manually propulsed in antegrade fashion from the pylorus to the ileocecal valve.
• Bowel transected at distal ileum and sigmoid.
• Vascular transection of the colon should be performed last to prevent drainage from an ischemic colon into the
liver

22. • Liver removed first, with transection of PV at level of the coronary vein, and transection of splenic artery.
• Splenic artery always tagged with a fine suture for later identification.
• Pancreas and intestine graft may be removed en bloc, and the pancreas separated from the intestine at the back-
table dissection.
• Division of the base of the small intestine mesentery just below the IPDA performed in situ in a stable donor.
• Jejunum divided 10 cm distal to the ligament
• SMV identified laterally in the mesentery.
• Fine ligation of all lymphatic structures performed.
• If the colon is to be a component middle colic artery and vein should be preserved.

23. Colon
• Paris series: 23/36 children received an allograft including the colon (17 were L-ITx) had no impact on
patient or graft survival
O. Goulet et al., “Intestinal transplantation including the colon in children,” Transplantation Proceedings, vol. 34, no. 5, pp. 1885–1886, 2002.
• Kato et al. reported on 93 ITx that included colon out of 245 ITx . No decreased graft or patient survival
• Colonic inclusion had higher frequency of formed stools after stoma closure (67% vs 48.5%)
T. Kato et al., “Inclusion of donor colon and ileocecal valve in intestinal transplantation,” Transplantation, vol. 86, no. 2, pp. 293–297, 2008.

24. • According to the 2012 ITR report, 30% of the intestinal allografts included the colon in comparison to 4% in 2000
• Improve quality of life after transplantation, being associated with less diarrhea after stoma reversal.
• Increased the likelihood of being free from TPN and iv supplementation by 5% in comparison to those who did
not receive a colonic segment, reflecting the important role of the colon in fluid and free fatty acid absorption.
• Did not increase the risk of rejection
• Does not allow the performance of ITx without a temporary ileostomy. The presence of a temporary ileostomy is
essential for easy access to the allograft for endoscopic monitoring after transplantation.
• Inclusion of the ileocecal valve may increase the difficulty in endoscopically accessing the ileal component of the
graft after ITx and, thus, a temporary ileostomy remains essential
ITR, “Bi-annual report,” in Intestinal Transplant Registry, D. Grant, Ed., Toronto, Canada, 2014

25. Donor operation(L-ITx)
• 10 cm supra celiac aortic segment in continuity with an aortic Carrel-patch bearing the celiac axis and SMA
• Diaphragm must be split.
• GB incised,biliary tract flushed with saline- Division of the CBD
• in situ flush with UW-solution and suprarenal and supradiaphragmatic transection of IVC
• Proximal and distal small bowel transection,
• Bowel-liver graft is procured en bloc,.

26. Multivisceral Transplantation
• Fundamentally same except variable amounts of the stomach or colon
• Renal arteries and veins are not disrupted from their connections to the aorta and vena cava.
• preservation of LGA, gastroepiploic arcade
• Enteric division of GEJ.
• Viscera removed en bloc with vena cava and same Carrel patch or intact aorta as with liver-intestine procurement.

27. With simultaneous pancreas procurement:
• Mesenteric vessels are isolated below the IPD vessels
• Middle colic vessels and first jejunal arcade usually must be ligated.
• Small vascular clamps are placed on SMA and SMV after the flush, and these vessels are transected.
• Pancreatic side is individually oversewn with fine, nonabsorbable suture and the bowel graft is again flushed

28. Recipient operation(IITx)
• Jejunum divided 10–20 cm distal to the ligament of Treitz
• Graft: drained systemically or portally
• Arterial inflow :via graft SMA
• Venous outflow: via graft SMV.
• Vascular conduits(donor EIA, EIV) are universally used.
• Arterial revascularization: infrarenal abdominal aorta
• Donor iliac interposition grafts anastomosed end-to-side fashion
directed caudally
• Graft mesenteric vessels anastomosed to interposition grafts
in and end-to-end fashion.

29. Systemic Vascular Reconstruction
exposure of infrarenal aorta for
anastomosis of the arterial graft IVC & aorta clamped

30. Portal Vs Systemic drainage
Pittsburgh experience: K.M. Abu-Elmagd et al., “500 intestinal and multivisceral transplantations at a single center:
systemic diversion of hepatotrophic factors put to rest with inclusion of the donor pancreas
Miami experience: T. Berney et al., “Portal versus systemic drainage of small bowel allografts, rejection, and bacterial translocation
• No dramatic metabolic consequence with “second pass” effect.
• Hepatotrophic factors: IITx alone, native pancreas is preserved, hepatotrophic factors, released into the
portal directly
• Hepatic encephalopathy: increase in the ratio of aromatic to branched-chain amino acids, was not
observed
• ed mesenteric venous flow to the liver before the transplant but was not altered after systemic drainage
• Liver enzymes and bilirubin initially higher reached levels similar to PD group within 1 month
• synthetic function appeared unaffected by values of albumin and PT/INR at 1 and 3 months
• No major differences in ACR
• increased rate of bacterial infection does not seem to impact on long term results

31. Recipient operation(L-ITx)
• Resection of all native residual bowel and liver with preservation of the IVC
• Suprahepatic caval anastomosis as in piggyback liver transplantation
• Carrel patch or SMA/celiac complex either directly to the aorta or to an interposition conduit of donor thoracic
• End-to-side anastomosis between the PV of recipient and donor
• Intestinal reconstruction anastomosing the first portion of the donor’s jejunal loop to the donor bile duct
followed by anastomosis between the recipient duodenum to the allograft jejunum and completed with a
distal anastomosis
• Biliary drainage: Roux-Y-choledocho-(bowel graft) enterostomy.

32. Recipient operation(MVITx)
• Begins with mobilization of the liver from the retrohepatic vena cava to allow piggyback placement of the allograft.
• Division with a stapling device, preserving the GEJ
• Left colon divided, preserve LCA and IMA
• Vascular clamps can then be placed on the base of the celiac and superior mesenteric arteries
• Hepatic veins clamped and divided.
• Stomach, pancreas, spleen, small bowel, right colon, and liver are removed together, preserving the inferior vena
cava for piggyback allograft implantation.
• The hepatic venous piggyback anastomosis is usually performed first
• Using the native celiac and SMA end-to-end anastomosis with the same donor structures
• Using an iliac bifurcating graft to these vessels from either the supraceliac or infrarenal aorta after ligation of the
native vessels
• Single anastomosis of the infrarenal aorta of the donor allograft end-to-side to the infrarenal aorta of the recipient
via an interposition graft

33. • Preservation of a cuff of native stomach allows for a two layer gastrogastric anastomosis, rather than an
esophagogastric anastomosis
• Pyloroplasty: Gastric emptying (Buchman et al. 2003 ).
• Distal enteral continuity is reestablished with ileostomy construction and colon anastomosis as described above

34. Living donor transplantation
Donor operation
• Length of small bowel measured using 18-inch umbilical tape placed over antimesenteric border from Treitz-ICV.
• 200 or 150 cm of bowel destined to become the graft is measured, starting from 20 cm from the ICV.
• Remainder of the bowel is measured again to assure that at least 60% is left for the donor.
• Segment of ileum to become graft marked to recognize proximal and distal ends on the back table.
• Location of the distal branch of the SMA identified with palpation and transillumination.
• Mesentery scored and terminal branch of SMA dissected free from the take-off of the ileocolic branch distally for
about 2cm.

35. • Mesentery divided in a “V”-shaped fashion with the tip of the V at the vessel take-off and extending
toward the stitches marking the segment of ileum to become the graft.
• Bowel divided using gastrointestinal anastomosis stapler
• Removal of graft performed applying spoon vascular clamps to both vessels 1–2 mm distal to the take-
off of the ileocolic vessels.
• Vascular tissue left on the clamp will allow safe closure of the stumps
• Stumps oversewn with 5–0 polypropylene sutures.
• Back table, the graft is perfused through the artery with University of Wisconsin solution until the
perfusate is clear
• 2 ends of bowel are approximated in side-to-side fashion
• Gruessner R W G, Sharp H L. Living-related intestinal transplantation. Transplantation. (1997);64:1605–1607

36. Recipient operation
• Mobilization of remaining bowel to expose infrarenal aorta and vena cava
Arteriotomy of the anterior wall of aorta made at origins of
IMA and the renal arteries.
• End-to-side (ileocolic artery-to-infrarenal aorta) anastomosis.
• Venous anastomosis: 2-3 cm proximal to arterial anastomosis.
• End-to-side (ileocolic vein to infrarenal cava) anastomosis.
• Proximal end of intestinal graft anastomosed
to remaining recipient duodenum/jejunum.
• Ileostomy fashioned proximal to distal anastamosis
between graft and recipient, allows for surveillance endoscopy
Gruessner R W G, Sharp H L. Living-related intestinal transplantation. Transplantation. (1997);64:1605–1607

37. IMMUNOSUPPRESSION PROTOCOLS
Era I:1990-1994: Tacrolimus-steroid.
Era II: JAN 1995 Donor bone marrow augmentation protocol.
• May 1995:induction therapy added initially cyclophosphamide, then by daclizumab in May 1998.
• April 2000: Low-dose ex-vivo allograft irradiation in adults.
Era III:July 2001: Recipient preconditioning with antilymphoid preparations and minimal immunosuppression.
• Bone marrow augmentation and allograft irradiation continued until August 2003.
• Reduced size allografts, en bloc colon transplant was revisited, and liberal use of CMV-positive donors adopted

38. Based upon type, number of adjunct immunosuppressants, time of therapy initiation
Type I: iv tacrolimus + steroid (bolus plus five-day taper) therapy was begun intraoperatively and gradually
switched to oral doses.
• Azathioprine added.
• High 12-hour target tacrolimus trough (20-30 ng/ml) during the first three months after transplantation.
• Rejection episodes were treated with high-dose steroids and/or OKT3
• The same protocol was used in selected patients during both Eras II and III, but with a 121-hour target tacrolimus
trough level of 15-20 ng/mL and 10-15 ng/mL, respectively.

39. Type II:
Induction therapy was added to the tacrolimus steroid-
• Cyclophosphamide and replaced by daclizumab thereafter.
• Azathioprine, mycophenolate mofetil, and rapamycin were used as a fourth drug.
• The 12-hour tacrolimus trough level was targeted at 15-20 ng/mL during the first 3 postoperative months with
gradual dose reduction .
• rATG was used to treat steroid resistance and severe rejection episodes

40. Type III:
• A single dose of lymphocyte-depleting agent rATG (Thymoglobulin) or alemtuzumab and minimization of post-
transplant immunosuppression were the two principles
• rATG: Single dose 5 mg/kg infused over 4-6 hours and completed before reperfusion of the allograft,
• Alemtuzumab : single dose, 30mg infusion over 2 hours upon induction of anesthesia.
• iv steroids given before and at the end of anti-lymphocyte antibody infusion as a prophylaxis against cytokine
release syndrome.
• Tacrolimus alone was given within the first 24 hours after transplantation, with an initial iv or oral dose to achieve
12-hour drug trough level of 10 to 15 ng/mL by the third postoperative day.
• Same level aimed during first 3 postoperative months, after which levels of 5- 10 ng/mL sought.

41. COMPLICATIONS
1. Surgical
• Thrombosis;
• Pseudo aneurism,Aneurysms of native arteries
• Anastomotic leakage, pancreatic fistula
• loss of domain, hernia
• Chylous ascites
• Gastrointestinal bleeding (rejection being the most common etiology) at anastomotic sites or stomas
2. Rejection
3. Infections
4. Neuropsychiatric disorders:
5. Recurrence of primary disease: Crohn’s disease,desmoids tumors

42. REJECTION
• Onset: Typically between day 5 – 60
• Incidence 36-60%
• Clinical features: Fever, nausea and vomiting, diarrhea, abdominal pain and distension.
• Volume of stomal effluent increases and becomes watery.
• Some cases entail septic shock with metabolic acidosis, hypotesion, and adult respiratory distress syndrome;
• Diagnosis difficult because of patchy nature of rejection

43. Acute allograft rejection
Endoscopic Criteria: Done twice a week for the first month, once a week for the next two months, monthly for the
next three months, and every three to six months or whenever clinically indicated thereafter.
• Mild –moderate: Mucosal Edema,focal or diffuse erythema,hyperemia, congestion, and dusky aspect.
• Severe: Submucosal nodularity, focal or diffuse ulcerations,sloughing of extensive areas with development of
pseudomembranes, bleeding, and no peristalsis
Histologic evidence: Mucosal necrosis and loss of villous architecture with transmural cellular infiltrate.
Radiologic Criteria: Dilatation , edema and thickening of wall, blunting and loss of the mucosal folds, paralytic ileus with
increased transit and emptying times
Adjunct assays: Blood Citrulline levels & fecal calprotectin
• Cytofluorographic analysis of peripheral immune cell populations
• cytokine profiling, and the quantitation of distinct gene set changes .
• Treatment: iv bolus of methylprednisolone 10mg/kg followed by steroid recycle and optimsation of tacrolimus
level
Abu-Elmagd KM et al.long-term outcome with special reference to the liver. Am J Transplant. 2012;12(11):3047-60

44. Chronic Allograft rejection
• Occurs in 15% of cases
• Typically appears 1–5 years following transplantation.
• Clinically: Diarrhoea, nonhealing ulcers, focal loss of mucosal folds, focal ulcers, mural thickening and pruning of
mesenteric artery arcades
Abu-Elmagd KM et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg 2009; 250:567–581
• Diagnosed histologically with identification of an obliterative arteriopathy in medium sized vessels in the serosal
layer with diffuse concentric intimal thickening.
• Immunosuppression may alleviate symptoms, but a retransplant is likely the more durable option .
• Allograft enterectomy is a potential life-saving option for ITx patients who developed severe rejection, and has
similar survival rates with patients who underwent simultaneous enterectomy with retransplantation
Demetris AJ,Murase N, Lee RG, et al. Chronic rejection. A general overview of histopathology and pathophysiology with emphasis on liver, heart and intestinal allografts. Ann
Transplant 1997; 2:27–44

45. • ACR within 90 days: 92% IITx, 66% of MMVITx, 43% MVTx
• ACR after IITx are higher than after L-ITx or MVTx,
• K. M. Abu-Elmagd, G. Costa, G. J. Bond et al., “Five hundred intestinal and multivisceral transplantations at a single center: major advances with new
challenges,” Annals of Surgery, vol. 250, no. 4, pp. 567–581, 2009.
• Liver + intestine promotes tolerance towards the bowel graft by inducing the production of regulatory T-cells and
the deletion of alloreactive T-cells
J. M. Smith, M. A. Skeans, S. P. Horslen et al., “Annual data report: intestine. american journal of transplantation,” Journal of the American Society of Transplantation and the American
Society of Transplant Surgeons, vol. 14, supplement 1, pp. 97–111, 2014.
• Multivisceral allograft might confer even more protection against severe ACR of the intestinal allograft in
comparison to L-ITx
A. G. Tzakis et al., “The Miami experience with almost 100 multivisceral transplants,” Transplantation Proceedings, vol. 38, no. 6, pp. 1681–1682, 2006.
• Risk of ACR might be related to the relative proportion of donor lymphoid tissue transplanted with the allograft
compared to the remaining recipient lymphoid tissue
G. Selvaggi et al., “Analysis of acute cellular rejection episodes in recipients of primary intestinal transplantation: A single center, 11-year experience,” American Journal of Transplantation,
vol. 7, no. 5, pp. 1249–1257, 2007

46. Donor-specific antibodies
• causes of long-term chronic rejection and late allograft failure
• Presence of preformed DSA and/or complement dependent cytotoxicity-panel reactive antibody (PRA) >15%,
correlates with rejection and graft loss
• Besides damaging the graft, increase antigen presentation
• Strategies used to decrease preformed DSAs include plasmapheresis and IVIG.
• Studies in Pittsburgh suggest that if antibody to the donor becomes detectable posttransplant, significant decrease
in survival.
• Liver-free recipients who developed (de novo) DSA, 5-year graft survival was less than 30%, compared to >80% in
recipients who did not develop DSA
M. Bergera et al,Immunologic Challenges in Small Bowel Transplantation

47. GVHD
• Newly transplanted donor cells regard the transplant recipient’s body as foreign and attack it.
• 3 criteria must be met
1.An immuno-competent graft is administered with viable and functional immune cells.
2.Recipient immunologically disparate - histoincompatible.
3.Recipient immuno-compromised therefore cannot destroy or inactivate transplanted cells.
• Within 100 days Acute, after is chronic.
• Monitored by clinical examination (fever, skin rash,septic-like syndrome), standard histology, Immuno staining, and
PCR karyotyping
• Differentiate migrating immunocompetent donor “passenger leukocytes” from recipient cells
• Document immunological injury of recipient tissues by infiltrating donor cells.
• Gradual replacement of donor hematolymphoid cells in recipient
• Treatment: high dose Steroids, ATG

48. Infection
• Sepsis remains the most common cause of death and graft failure, accounting for over 50% of cases
Grant D, Abu-Elmagd K, Mazariegos G, et al. Intestinal transplant registry report: global activity and trends. Am J Transplant 2015; 15:210–219.
• Bacterial infection is common in the immediate phase 2.6 episodes/ patient
Loinaz C, Kato T, Nishida S, et al. Bacterial infections after intestine and multivisceral transplantation. Transplant Proc 2003; 35:1929–1930
• Associated with 15% lower patient survival at 1 year
Sudan D. The current state of intestine transplantation: indications, techniques,outcomes and challenges. Am J Transplant 2014; 14:1976–1984.
• Invasive candidiasis has recently been reported to be the commonest fungal infection
Florescu DF, Sandkovsky U. Fungal infections in intestinal and multivisceral transplant recipients. Curr Opin Organ Transplant 2015; 20:295–302.
• Cytomegalovirus (CMV) and Epstein–Barr Virus (EBV) are common and can be implicated in acute and chronic
rejection as well as PTLD
Timpone JG, Girlanda R, Rudolph L, Fishbein TM. Infections in intestinal and multivisceral transplant recipients. Infect Dis Clin North Am 2013; 27:359–377.

49. CMV INFECTION
• 18.8% incidence in 88 IMVTx recipients from 2003 to 2008
• Recurrences between 50% and 86%. 11-fold increase in mortality.
• Donor and recipient CMV serologic status is an important predictor of posttransplant infection.55
• Highest risk: CMV seronegative recipients of a CMV seropositive donor. However, a seropositive recipient is still at
risk for CMV reactivation regardless of donor status.
• Manifestations: Asymptomatic to viral syndrome including fever, myalgia, leukopenia, and elevated
transaminases, to target-organ involvement.
• Increased ileostomy output or diarrhea and bleeding.
Florescu DF, Langnas AN, Grant W, et al. Incidence, risk factors, and outcomes associated with cytomegalovirus disease in small bowel transplant recipients.Pediatr Transplant
2012;16(3):294–301

50. • Endoscopic findings:vary between mild superficial ulceration and severe mucosal damage with the potential for
bowel perforation, especially following T-cell depletion therapy for acute rejection.
• Histologically: Mucosal injury with crypt and villus loss associated with plasma cell and lymphocyte infiltrate, as
well as the presence of CMV inclusion bodies.
• 48% undetectable in the blood.
• Prophylaxis: iv ganciclovir
• optimal duration: not uniformly established, varies between 3 months to indefinitely.
• Treatment: oral valganciclovir or intravenous ganciclovir
Kotton CN, Kumar D, Caliendo AM, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 2010;89(7):779–95

51. PTLD
• Incidence 5% to 10%
• Undetectable or low viral loads for the first 6 months are unlikely to develop
• Risk factors: EBV infection after transplantation and the net state of immunosuppression.
• CMV infection affects the net state of immunosuppression and is known to be a risk factor for PTLD.
• Prevention: IVIG pre‐emptively to patients with high viral loads (200 genome
copies/100 000 peripheral blood lymphocytes and 15 000 copies/ml of whole blood)
• US – 50 mg IgG/ml
• Europe ‐100 mg IgG/ml.
Allen UD et al., Epstein-Barr virus and posttransplant lymphoproliferative disorder in solid organ transplantation. Am J Transplant 2013; 13: 107–120

52. ALLOGRAFT FUNCTION
• When adjusted for age, race, and diagnosis, post-transplant graft and patient survival data were superior for
intestine-only recipients.
• The differences were more apparent at one year following transplantation, but diminished at subsequent time
intervals.
• Liver-intestine recipients were much sicker, as demonstrated by their higher waiting list mortality and also
because they undergo more extensive surgery then do isolated intestine recipients.
• By five years after transplantation, the gap between the graft and recipients survival curves in both groups may
reflect reduced graft loss due to chronic rejection in the liver intestine recipients.
• 376 patients ( 213 adults) at the Pittsburgh University 149 non-five-year survivors and 227 who survived five years.
Enteric autonomy :54 % of non-five-year, 92 survived beyond five years.
Pomfret EA et al., Liver and intestine transplantation in the United States, 1996-2005. Am J Transpl.2007;7(part 2):1376-89

53. Postoperative course
• All patients started on enteral tube feeds after first confirming recovery of the transplanted small intestine by
endoscopy and biopsy confirmation of normal histology.
• Feeds are initiated with small volumes of non-osmotic formula and gradually once the target volume is achieved
patients are converted to more standard formulas
• Solid food gradually introduced.
• Initially feeding restricted to low fat, low sucrose and low lactose foods to avoid high stoma output amount and then
gradually advanced as tolerated
• Parenteral nutrition is then gradually weaned off during this period.
• Anti-diarrheal medications such as diphenoxylate and atropine or loperamide helpful in reducing stomal losses

54. • Acute cellular rejection is a major concern in the early postoperative period, hence all patients have an ileostomy
from which protocol biopsies are taken.
• In general, 1st month-Twice weekly
• another 3 to 6 months - Once a month
• Gradually used only to evaluate new gastrointestinal symptoms.
• The patients are usually maintained at a high early serum concentration of tacrolimus, around 10-18 ng/dL
• This is generally lowered to 5-8 ng/dL by 6 months after transplantation.
Desai CS et al. Isolated intestinal transplants vs. liver-intestinal transplants in adult patients in the United States: 22 years of OPTN data. Clin Transplant. 2011

56. Outcomes of intestinal transplants
• Intestinal transplants are yet to achieve the same success as that of the other intraabdominal solid organs
transplanted
• Leading cause of death was infection
• Cause of graft failure was rejection (acute and chronic rejection).
• hospitalization before transplant vs admission directly from home was associated with a poor outcome for both
isolated intestine and combined liver and intestine recipients
• Donor age >40 years had negative effect for outcome in combined liver and intestine graft recipients , but not donor
gender.
• Sepsis was predictive of a poor outcome for both isolated intestine transplant and combined liver and intestine graft
recipients

57. • Risks of CMV and PTLD are higher, contributing to the less favorable outcomes .
• Mildly increased risk of graft versus host disease (GVHD) compared to other types of ITx: 14% for MVTx, 10% for
MMVTx, 8% for L-ITx, and 6% for ITx.
M. E. De Vera, et al., “Isolated intestinal versus composite visceral allografts: causes of graft failure,” Transplantation Proceedings, vol. 32, no. 6, pp. 1221–1222, 2000
• In the preinduction era, ACR of the intestinal allograft in the first 30 days after transplantation was reported to be
as high as 88%
J. Reyes et al., “Current status of intestinal transplantation in children,” Journal of Pediatric Surgery, vol. 33, no. 2, pp. 243–254, 1998.
• Cumulative incidence of ACR after ITx is 39% at 12 months and 44% at 24 months
J. M. Smith et al., “Annual data report: intestine. american journal of transplantation,” Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol. 14,
supplement 1, pp. 97–111, 2014.
• From 2001 - 2011, 46.6%-IITx, 26.6%-L-ITx, 21.3%- MVTx, and 5.5%- MMVTx
D. Grant et al., “Intestinal transplant registry report: global activity and trends,” The American Society of Transplantation and the American Society of Transplant Surgeons, vol. 15, pp. 210–219, 2015

58. New candidates added to waiting list
Candidates listed for intestine transplant on December 31
Distribution of candidates waiting for intestine transplant
by waiting time.