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Small Bowel Transplantation

Small Bowel Transplantation. 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

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Small Bowel Transplantation

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  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) 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 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 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 Dr .yekehfallah-phd of nursing-2015

  6. 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 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 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 Dr .yekehfallah-phd of nursing-2015

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

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

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  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 Dr .yekehfallah-phd of nursing-2015

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

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