1. Small Bowel Transplantation

2. Intestinal Transplantation
Indications include:
Short-bowel syndrome with complications associated with parenteral nutrition
Irreversible intestinal failure
End-stage liver disease for combined liver and small-intestine transplantation
Congenital mucosal disorders
Chronic pseudo-obstruction of intestine
Locally invasive tumors at the base
Transplant options include:
Isolated intestinal (cadaveric or living-related)
Multivisceral transplantation (combined liver and multivisceral)
4/21/2017
Dr .yekehfallah-phd of nursing-2015

3. Contraindications of Small Bowel Transplant
Presence of Active Infection
Aggressive Malignancy
Multi-System Organ Failure
Cerebral Edema
AIDS
4/21/2017
Dr .yekehfallah-phd of nursing-2015

4. History of the Procedure
Lillehei et al reported the first case of human bowel transplantation in October 1967
Alexis Carrel was the first one to perform it in an animal model
Before 1970, 8 clinical cases of small-intestine transplantation were reportedly performed worldwide
maximum graft survival time was 79 days
All patients died of technical complications, sepsis, or rejection
4/21/2017
Dr .yekehfallah-phd of nursing-2015

5. Intestinal Transplantation - Etiology
Worldwide, the leading cause of intestinal failure is short-bowel syndrome caused by surgical removal
~10-20cm of small bowel needed with an ileocecal valve
40cm without a ileocecal valve
Conditions leading to short-bowel syndrome include
Midgut volvulus
Gastroschisis
Trauma
Necrotizing enterocolitis (NEC)
Ischemia
Crohn’s disease
4/21/2017
Dr .yekehfallah-phd of nursing-2015

6. Dr .yekehfallah-phd of nursing-2015
Short Bowel Syndrome
In patients with short bowel syndrome, absorption of nutrients is significantly altered, leading to electrolyte and mineral imbalances and inadequate delivery of calories (severe dehydration and malnourishment)
Symptoms are common: persistent diarrhea, muscle wasting, poor growth, frequent infections, weight loss, fatigue, and dehydration
4/21/2017
Dr .yekehfallah-phd of nursing-2015

7. Preoperative evaluation and selection
Preoperative evaluation requires a complete multidisciplinary assessment to clearly define the cause of isolated intestinal or intestinal/hepatic failure
Evaluation of comorbidities and organ dysfunction
Optimization of preoperative morbid conditions (infection, malnutrition) can significantly affect outcome
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Dr .yekehfallah-phd of nursing-2015

8. Preoperative evaluation and selection
Referring patients before the onset of hepatic dysfunction is important
Progression of liver injury, as manifested by jaundice, significantly influences life expectancy
Bilirubin concentrations >3 mg/dL have 1- and 2-year survival rates of 42% and 20%
Bilirubin <3 mg/dL have a survival rate of 80%
pT >15 and pTT >40 also associated with poorer outcomes
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Dr .yekehfallah-phd of nursing-2015

9. Isolated Intestinal Transplantation
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Dr .yekehfallah-phd of nursing-2015

10. Multivisceral transplantation
Pts with permanent intestinal dysfunction, those with TPN dependency with complications, and those with a systemic motility disorder (e.g., chronic pseudo-obstruction, traumatic loss of the stomach or duodenum)
Can receive a stomach, duodenum, pancreas, and small intestine, with or without the liver
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Dr .yekehfallah-phd of nursing-2015

11. Dr .yekehfallah-phd of nursing-2015
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Dr .yekehfallah-phd of nursing-2015

12. Dr .yekehfallah-phd of nursing-2015
An isolated intestine being prepared on the back table prior to implantation
4/21/2017
Dr .yekehfallah-phd of nursing-2015

13. Transplantation – Intra-operative Details
Transplantation surgical therapy
Carefully preservation of the vascular pedicle comprising the ileocolic artery & vein with end-to-side anastomoses to the recipient's infrarenal aorta & vena cava
For cadaveric intestinal grafting, arteries are anastomosed directly to the infrarenal aorta with a Carrel patch
Venous drainage through an anastomosis or patch to the recipient's IVC (combined)
Isolated cadaveric intestinal grafting -> preferred venous drainage =portal vein
In addition, a gastrostomy or jejunostomy is usually performed for continuous enteral feeding
Graft ileostomy permits frequent endoscopic and histologic postoperative monitoring
4/21/2017
Dr .yekehfallah-phd of nursing-2015

14. Dr .yekehfallah-phd of nursing-2015
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Dr .yekehfallah-phd of nursing-2015

15. Dr .yekehfallah-phd of nursing-2015
4/21/2017
Dr .yekehfallah-phd of nursing-2015

16. Intestinal Transplantation – Follow-up care
At regular intervals, perform
CMV antigenemia
Quantitative EBV polymerase chain reaction (PCR) surveillance
Routine cultures
Transplant ileostomal endoscopy & biopsy (as often as twice weekly)
Additionally, monitor fluid status, stool losses, and serum electrolytes
4/21/2017
Dr .yekehfallah-phd of nursing-2015

17. Major Post Operative Complications
Bleeding
Thrombosis
Anastomatic Leaks
Sepsis from bacterial translocation of Graft
GVHD
Acute Rejection
4/21/2017
Dr .yekehfallah-phd of nursing-2015

18. Intestinal Transplantation - Complications
Infectious complications account for ~60% of intestinal graft losses
Bacterial and fungal infections in intestinal transplantation are similar to those found in other solid-organ transplantations
Rejection and technical errors accounting for a further 36%
An autopsy series found 94% had a coexisting infection, even in cases in which sepsis was not the immediate cause of death
Post-transplant lymphoproliferative disease and graft rejection can lead to breakdown of the mucosal barrier, resulting in bacteremia or fungemia
4/21/2017
Dr .yekehfallah-phd of nursing-2015

19. Intestinal Transplantation - Complications
CMV infection
Immunosuppression is maintained to avoid breakthrough rejection but is decreased if the patient's condition worsens.
~ 15-30% of patients (most often involves an allograft intestine)
One of the most serious infections that can occur, because it can lead to loss of the transplanted organ and even death
Incidence is highest in CMV-negative recipients who receive CMV-positive grafts (thus avoided)
Infection is diagnosed by measuring CMV antigenemia and by findings on endoscopic examination
Endoscopy shows superficial ulcers, and histopathology confirms CMV inclusion bodies
4/21/2017
Dr .yekehfallah-phd of nursing-2015

20. Intestinal Transplantation - Complications
CMV infection
Treatment consists of IV ganciclovir in combination with CMV immune globulin (CytoGam) and valganciclovir (Valcyte) tablets
Valganciclovir is the oral prodrug of ganciclovir (ester prodrug converted by intestinal & hepatic esterases)
Valganciclovir delivers the same active drug ingredient with up to 10 times more bioavailability
Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV
4/21/2017
Dr .yekehfallah-phd of nursing-2015

21. Intestinal Transplantation - Complications
EBV-associated lymphoproliferative disease
Posttransplantation lymphoproliferative disease occurs more often in children > adults (29% vs. 11%)
Occurs more commonly within 24 months after multivisceral transplantation than after isolated intestinal transplantation
Linked to EBV infection in association with the use of anti-CD3 monoclonal antibody (OKT3) and steroids
The high incidence in small-intestine recipients is presumably caused by the large amount of immunosuppression necessary to prevent transplant rejection
EBV may lead to a wide spectrum of clinical disease, ranging from a benign mononucleosis syndrome to a polyclonal proliferative tumor or monoclonal type lymphoma.
Present with fever, abdominal pain, & either lymphadenopathy or masses on abdominal imaging
In addition, low-grade EBV infections often precede posttransplantation lymphoproliferative disease
4/21/2017
Dr .yekehfallah-phd of nursing-2015

22. Intestinal Transplantation - Complications
EBV-associated lymphoproliferative disease
Treatment of posttransplantation lymphoproliferative disease involves
Reduction of immunosuppression
Administration of ganciclovir (10 mg/kg/d)
Mortality has decreased with improved early diagnosis
In situ hybridization staining for EBV
Early ribonucleic acid (RNA) and EBV PCR surveillance
Combined with early intervention
4/21/2017
Dr .yekehfallah-phd of nursing-2015

23. Intestinal Transplantation - Complications
Acute allograft rejection
Rejection is diagnosed by endoscopic intestinal biopsy
Diagnosis can be difficult because of the patchy nature of rejection and the presence of bleeding & perforation complications
Histologic evidence -> mucosal necrosis and loss of villous architecture with transmural cellular infiltrate
Histopathology -> crypt cell apoptosis, cryptitis or crypt loss, necrosis, and endotheliitis
Treatment ->
IV bolus of methylprednisolone (10 mg/kg), followed by steroid recycle and optimization of the tacrolimus level
OKT3 therapy may be used to treat steroid-resistant rejection
Some centers report that combined liver-intestine transplantation provides a greater protective benefit (i.e., lower incidence and severity of acute rejection) than intestinal transplantation.
OKT3 ( also called muromonab) is an immunosuppressant drug given to reduce acute rejection in transplant patients. A major milestone in the prevention of acute allograft rejection was achieved with the development of the mAb OKT3, the first mAb to be approved for clinical use in humans. OKT3 is a murine monoclonal IgG2a antibody that specifically reacts with the T cell receptor-CD3 complex on the surface of circulating human T cells.[13] The T cell has 2 molecules on its surface which function primarily in antigen recognition. These antigen recognition structures are associated with 3 polypeptide chains (the CD-3 complex). The CD-3 complex transduces the signal for the T cell to react to the foreign antigen, proliferate, and attack the foreign matter. OKT3 is a monoclonal antibody that specifically reacts with the T-3 complex by blocking the function of T cells
4/21/2017
Dr .yekehfallah-phd of nursing-2015

24. Intestinal Transplantation - Complications
Chronic allograft rejection
With improvements in immunosuppressive drugs, chronic rejection has become an increasingly important cause of late allograft dysfunction
Little is known of the clinical and pathophysiologic course of chronic intestinal rejection
In 1990, Goulet reported muscular fibrosis & chronic infiltrate with intact mucosal and epithelial structures in a small-intestine transplant removed from a 17-month-old infant
Obliterative arteritis, atrophic Peyer patches and mesenteric lymph nodes
Possibly caused by injury to the vascular endothelium, with a complex inflammatory cascade occurring in the vessel wall
Therefore, prevention and treatment of chronic intestinal rejection are difficult
4/21/2017
Dr .yekehfallah-phd of nursing-2015

25. Intestinal Transplantation - Complications
Graft versus host disease
Small intestine = immunocompetent organ
Population of lymphoid cells can mount an immunologic response to the host—a GVHD reaction
Although animal models have shown that GVHD is a common occurrence and GVHD has not been a significant clinical problem
Acute GVHD presents 1-8 weeks post-transplantation with
Fever
Leukopenia
Diarrhea
Rash
Other symptoms may include malaise, anorexia, arthralgia, and abdominal pain.
Confirm diagnosis by biopsy
Treatment -> high-dose steroids & antithrombocyte globulin or with OKT3
4/21/2017
Dr .yekehfallah-phd of nursing-2015

26. Intestinal Transplantation - Complications
Technical errors (up to 50%)
More common in children than in adults
May cause graft loss
The errors include
Anastomotic leaks
Hepatic artery thrombosis
Biliary anastomosis leaks or stricture
Intra-abdominal hemorrhage
Intra-abdominal abscess
Chylous ascites
4/21/2017
Dr .yekehfallah-phd of nursing-2015

27. Intestinal Transplantation - Outcome and Prognosis
In 1999, Mazariegos reported a 55% patient survival rate and 52% graft survival rate at 5 years following intestinal transplantation
Matched group of patients (no transplantation) demonstrated 30% 1-year and 22% 2-year survival rates
Isolated intestinal grafts reportedly provide better patient and graft survival rates than multivisceral grafts
Graft and patient survival rates are improving as centers gain experience (51 worldwide centers)
Main centers – U of Pittsburgh, U of Nebraska, U of Miami, Hopital Necker-Enfants-Malades, & London Health Sciences Center
4/21/2017
Dr .yekehfallah-phd of nursing-2015

28. Intestinal Transplantation - Outcome and Prognosis
Small-intestine transplantation has higher incidences of rejection, sepsis, and post-transplantation lymphoproliferative disease than other organ transplantations
These outcomes may be secondary to bacterial translocation
Overall, 78% of intestinal transplant patients can be expected to be free of TPN and to tolerate oral nutrition following surgery
4/21/2017
Dr .yekehfallah-phd of nursing-2015

29. Intestinal Transplantation – Outcome and Prognosis
The introduction of tacrolimus immunosuppression, in combination with decontamination protocols, antibiotic regimens, and antiviral measures against CMV and EBV, has improved patient and graft survival rates
Survival rates at 1 year as high as 90% have been achieved for patients receiving isolated intestinal grafts
3 year survival > 70%
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Dr .yekehfallah-phd of nursing-2015

30. Dr .yekehfallah-phd of nursing-2015?
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Dr .yekehfallah-phd of nursing-2015