Small Bowel Transplantation. Intestinal Transplantation Indications include: Indications include:...

Small Bowel Small Bowel TransplantationTransplantation

Intestinal Intestinal TransplantationTransplantation

Indications include:Indications include: Short-bowel syndrome with complications Short-bowel syndrome with complications

associated with parenteral nutritionassociated with parenteral nutrition Irreversible intestinal failureIrreversible intestinal failure End-stage liver disease for combined liver and End-stage liver disease for combined liver and

small-intestine transplantationsmall-intestine transplantation Congenital mucosal disordersCongenital mucosal disorders Chronic pseudo-obstruction of intestineChronic pseudo-obstruction of intestine Locally invasive tumors at the base Locally invasive tumors at the base

Transplant options include:Transplant options include: Isolated intestinal (cadaveric or living-related)Isolated intestinal (cadaveric or living-related) Multivisceral transplantation (combined liver Multivisceral transplantation (combined liver

and multivisceral)and multivisceral)

2Dr .yekehfallah-phd of nursing-201504/19/23

Contraindications of Small Contraindications of Small Bowel TransplantBowel Transplant

Presence of Active InfectionPresence of Active Infection Aggressive Malignancy Aggressive Malignancy Multi-System Organ FailureMulti-System Organ Failure Cerebral EdemaCerebral Edema AIDS AIDS


History of the Procedure History of the Procedure

Lillehei et al reported the first case of Lillehei et al reported the first case of human bowel transplantation in human bowel transplantation in October 1967October 1967

Alexis Carrel was the first one to Alexis Carrel was the first one to perform it in an animal modelperform it in an animal model

Before 1970, 8 clinical cases of small-Before 1970, 8 clinical cases of small-intestine transplantation were intestine transplantation were reportedly performed worldwidereportedly performed worldwide maximum graft survival time was 79 daysmaximum graft survival time was 79 days All patients died of technical All patients died of technical

complications, sepsis, or rejectioncomplications, sepsis, or rejection4Dr .yekehfallah-phd of nursing-201504/19/23

Intestinal Transplantation - Intestinal Transplantation - EtiologyEtiology

Worldwide, the leading cause of intestinal failure Worldwide, the leading cause of intestinal failure is short-bowel syndrome caused by surgical is short-bowel syndrome caused by surgical removalremoval ~10-20cm of small bowel needed with an ileocecal ~10-20cm of small bowel needed with an ileocecal

valvevalve 40cm without a ileocecal valve40cm without a ileocecal valve

Conditions leading to short-bowel syndrome Conditions leading to short-bowel syndrome include include Midgut volvulusMidgut volvulus GastroschisisGastroschisis TraumaTrauma Necrotizing enterocolitis (NEC)Necrotizing enterocolitis (NEC) IschemiaIschemia Crohn’s diseaseCrohn’s disease 5Dr .yekehfallah-phd of nursing-201504/19/23

Short Bowel Short Bowel SyndromeSyndrome

In patients with short In patients with short bowel syndrome, bowel syndrome, absorption of nutrients is absorption of nutrients is significantly altered, significantly altered, leading to electrolyte and leading to electrolyte and mineral imbalances and mineral imbalances and inadequate delivery of inadequate delivery of calories (severe calories (severe dehydration and dehydration and malnourishment)malnourishment)

Symptoms are common: Symptoms are common: persistent diarrhea, muscle persistent diarrhea, muscle wasting, poor growth, wasting, poor growth, frequent infections, weight frequent infections, weight loss, fatigue, and loss, fatigue, and dehydration dehydration


Preoperative evaluation and Preoperative evaluation and selection selection

Preoperative evaluation requires a Preoperative evaluation requires a complete multidisciplinary complete multidisciplinary assessmentassessment to clearly define the cause to clearly define the cause of isolated intestinal or of isolated intestinal or intestinal/hepatic failureintestinal/hepatic failure

Evaluation of comorbidities and organ Evaluation of comorbidities and organ dysfunctiondysfunction Optimization of preoperative morbid Optimization of preoperative morbid

conditions (infection, malnutrition) can conditions (infection, malnutrition) can significantly affect outcome significantly affect outcome


Preoperative evaluation and Preoperative evaluation and selection selection

Referring patients before the onset of Referring patients before the onset of hepatic dysfunction is importanthepatic dysfunction is important Progression of liver injury, as manifested by Progression of liver injury, as manifested by

jaundice, significantly influences life jaundice, significantly influences life expectancyexpectancy

Bilirubin concentrations >3 mg/dL have 1- Bilirubin concentrations >3 mg/dL have 1- and 2-year survival rates of 42% and 20% and 2-year survival rates of 42% and 20%

Bilirubin <3 mg/dL have a survival rate of Bilirubin <3 mg/dL have a survival rate of 80% 80%

pT >15 and pTT >40 also associated with pT >15 and pTT >40 also associated with poorer outcomespoorer outcomes


Isolated Intestinal Isolated Intestinal Transplantation Transplantation


Multivisceral Multivisceral transplantation transplantation

Pts with permanent intestinal Pts with permanent intestinal dysfunction, those with TPN dysfunction, those with TPN dependency with complications, and dependency with complications, and those with a systemic motility disorder those with a systemic motility disorder (e.g., chronic pseudo-obstruction, (e.g., chronic pseudo-obstruction, traumatic loss of the stomach or traumatic loss of the stomach or duodenum)duodenum)

Can receive a stomach, duodenum, Can receive a stomach, duodenum, pancreas, and small intestine, with or pancreas, and small intestine, with or without the liver without the liver



An isolated intestine being prepared on An isolated intestine being prepared on the back table prior to implantationthe back table prior to implantation


Transplantation – Intra-Transplantation – Intra-operative Detailsoperative Details

Transplantation surgical therapyTransplantation surgical therapy Carefully preservation of the vascular pedicle Carefully preservation of the vascular pedicle

comprising the ileocolic artery & vein with end-to-comprising the ileocolic artery & vein with end-to-side anastomoses to the recipient's infrarenal side anastomoses to the recipient's infrarenal aorta & vena cava aorta & vena cava

For cadaveric intestinal grafting, arteries are For cadaveric intestinal grafting, arteries are anastomosed directly to the infrarenal aorta with anastomosed directly to the infrarenal aorta with a Carrel patch a Carrel patch

Venous drainage through an anastomosis or patch to the Venous drainage through an anastomosis or patch to the recipient's IVC (combined)recipient's IVC (combined)

Isolated cadaveric intestinal grafting -> preferred Isolated cadaveric intestinal grafting -> preferred venous drainage =portal vein venous drainage =portal vein

In addition, a gastrostomy or jejunostomy is In addition, a gastrostomy or jejunostomy is usually performed for continuous enteral feedingusually performed for continuous enteral feeding

Graft ileostomy permits frequent endoscopic and Graft ileostomy permits frequent endoscopic and histologic postoperative monitoringhistologic postoperative monitoring




Intestinal Intestinal Transplantation – Transplantation –

Follow-up careFollow-up care At regular intervals, perform At regular intervals, perform

CMV antigenemiaCMV antigenemia Quantitative EBV polymerase chain Quantitative EBV polymerase chain

reaction (PCR) surveillancereaction (PCR) surveillance Routine culturesRoutine cultures Transplant ileostomal endoscopy & Transplant ileostomal endoscopy &

biopsy (as often as twice weekly)biopsy (as often as twice weekly) Additionally, monitor fluid status, Additionally, monitor fluid status,

stool losses, and serum electrolytesstool losses, and serum electrolytes


Major Post Operative Major Post Operative Complications Complications

BleedingBleeding Thrombosis Thrombosis Anastomatic LeaksAnastomatic Leaks Sepsis from bacterial translocation Sepsis from bacterial translocation

of Graftof Graft GVHD GVHD Acute Rejection Acute Rejection


Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications

InfectiousInfectious complications account for ~60% of complications account for ~60% of intestinal graft lossesintestinal graft losses Bacterial and fungal infections in intestinal Bacterial and fungal infections in intestinal

transplantation are similar to those found in other transplantation are similar to those found in other solid-organ transplantationssolid-organ transplantations

RejectionRejection and and technical errorstechnical errors accounting for accounting for a further 36%a further 36%

An autopsy series found 94% had a coexisting An autopsy series found 94% had a coexisting infection, even in cases in which sepsis was infection, even in cases in which sepsis was not the immediate cause of deathnot the immediate cause of death

Post-transplant lymphoproliferative diseasePost-transplant lymphoproliferative disease and graft rejection can lead to breakdown of and graft rejection can lead to breakdown of the mucosal barrier, resulting in bacteremia the mucosal barrier, resulting in bacteremia or fungemiaor fungemia



CMV infectionCMV infection Immunosuppression is maintained to avoid Immunosuppression is maintained to avoid

breakthrough rejection but is decreased if the breakthrough rejection but is decreased if the patient's condition worsens. patient's condition worsens.

~ 15-30% of patients~ 15-30% of patients (most often involves an (most often involves an allograft intestine) allograft intestine)

One of the most serious infections that can occur, One of the most serious infections that can occur, because it can lead to loss of the transplanted because it can lead to loss of the transplanted organ and even deathorgan and even death

Incidence is highest in CMV-negative recipients Incidence is highest in CMV-negative recipients who receive CMV-positive grafts (thus avoided)who receive CMV-positive grafts (thus avoided)

Infection is diagnosed by measuring CMV Infection is diagnosed by measuring CMV antigenemia and by findings on endoscopic antigenemia and by findings on endoscopic examinationexamination

Endoscopy shows superficial ulcers, and histopathology Endoscopy shows superficial ulcers, and histopathology confirms CMV inclusion bodiesconfirms CMV inclusion bodies



CMV infectionCMV infection Treatment consists of IV ganciclovir in Treatment consists of IV ganciclovir in

combination with CMV immune globulin combination with CMV immune globulin (CytoGam) and valganciclovir (Valcyte) tablets(CytoGam) and valganciclovir (Valcyte) tablets Valganciclovir is the oral prodrug of ganciclovir Valganciclovir is the oral prodrug of ganciclovir

(ester prodrug converted by intestinal & hepatic (ester prodrug converted by intestinal & hepatic esterases)esterases)

Valganciclovir delivers the same active drug Valganciclovir delivers the same active drug ingredient with up to 10 times more bioavailability ingredient with up to 10 times more bioavailability

Ganciclovir is a synthetic analogue of 2'-Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, which inhibits replication of deoxyguanosine, which inhibits replication of human CMV human CMV



EBV-associated lymphoproliferative diseaseEBV-associated lymphoproliferative disease Posttransplantation lymphoproliferative disease Posttransplantation lymphoproliferative disease

occurs more often in children > adults (29% vs. 11%)occurs more often in children > adults (29% vs. 11%) Occurs more commonly within 24 months after multivisceral Occurs more commonly within 24 months after multivisceral

transplantation than after isolated intestinal transplantationtransplantation than after isolated intestinal transplantation Linked to EBV infection in association with the use of anti-Linked to EBV infection in association with the use of anti-

CD3 monoclonal antibody (OKT3) and steroidsCD3 monoclonal antibody (OKT3) and steroids The high incidence in small-intestine recipients is The high incidence in small-intestine recipients is

presumably caused by the large amount of presumably caused by the large amount of immunosuppression necessary to prevent transplant immunosuppression necessary to prevent transplant rejectionrejection

EBV may lead to a wide spectrum of clinical disease, EBV may lead to a wide spectrum of clinical disease, ranging from a benign mononucleosis syndrome to a ranging from a benign mononucleosis syndrome to a polyclonal proliferative tumor or monoclonal type polyclonal proliferative tumor or monoclonal type lymphoma. lymphoma.

Present with fever, abdominal pain, & either Present with fever, abdominal pain, & either lymphadenopathy or masses on abdominal imaginglymphadenopathy or masses on abdominal imaging

In addition, low-grade EBV infections often precede In addition, low-grade EBV infections often precede posttransplantation lymphoproliferative diseaseposttransplantation lymphoproliferative disease



EBV-associated lymphoproliferative EBV-associated lymphoproliferative diseasedisease Treatment of posttransplantation Treatment of posttransplantation

lymphoproliferative disease involves lymphoproliferative disease involves Reduction of immunosuppressionReduction of immunosuppression Administration of ganciclovir (10 mg/kg/d) Administration of ganciclovir (10 mg/kg/d)

Mortality has decreased with improved Mortality has decreased with improved early diagnosisearly diagnosis In situ hybridization staining for EBV In situ hybridization staining for EBV Early ribonucleic acid (RNA) and EBV PCR Early ribonucleic acid (RNA) and EBV PCR

surveillancesurveillance Combined with early interventionCombined with early intervention



Acute allograft rejectionAcute allograft rejection Rejection is diagnosed by endoscopic intestinal biopsy Rejection is diagnosed by endoscopic intestinal biopsy

Diagnosis can be difficult because of the patchy nature of Diagnosis can be difficult because of the patchy nature of rejection and the presence of bleeding & perforation rejection and the presence of bleeding & perforation complicationscomplications

Histologic evidence -> mucosal necrosis and loss of Histologic evidence -> mucosal necrosis and loss of villous architecture with transmural cellular infiltratevillous architecture with transmural cellular infiltrate

Histopathology -> crypt cell apoptosis, cryptitis or crypt loss, Histopathology -> crypt cell apoptosis, cryptitis or crypt loss, necrosis, and endotheliitis necrosis, and endotheliitis

Treatment -> Treatment -> IV bolus of methylprednisolone (10 mg/kg), followed by IV bolus of methylprednisolone (10 mg/kg), followed by

steroid recycle and optimization of the tacrolimus level steroid recycle and optimization of the tacrolimus level OKT3 therapy may be used to treat steroid-resistant rejection OKT3 therapy may be used to treat steroid-resistant rejection

Some centers report that combined liver-intestine Some centers report that combined liver-intestine transplantation provides a greater protective benefit transplantation provides a greater protective benefit (i.e., lower incidence and severity of acute rejection) (i.e., lower incidence and severity of acute rejection) than intestinal transplantation. than intestinal transplantation.



Chronic allograft rejectionChronic allograft rejection With improvements in immunosuppressive drugs, With improvements in immunosuppressive drugs,

chronic rejection has become an increasingly chronic rejection has become an increasingly important cause of late allograft dysfunctionimportant cause of late allograft dysfunction

Little is known of the clinical and pathophysiologic Little is known of the clinical and pathophysiologic course of chronic intestinal rejectioncourse of chronic intestinal rejection

In 1990, Goulet reported muscular fibrosis & chronic In 1990, Goulet reported muscular fibrosis & chronic infiltrate with intact mucosal and epithelial structures in infiltrate with intact mucosal and epithelial structures in a small-intestine transplant removed from a 17-month-old a small-intestine transplant removed from a 17-month-old infantinfant

Obliterative arteritis, atrophic Peyer patches and mesenteric Obliterative arteritis, atrophic Peyer patches and mesenteric lymph nodes lymph nodes

Possibly caused by injury to the vascular endothelium, Possibly caused by injury to the vascular endothelium, with a complex inflammatory cascade occurring in the with a complex inflammatory cascade occurring in the vessel wallvessel wall

Therefore, prevention and treatment of chronic intestinal Therefore, prevention and treatment of chronic intestinal rejection are difficult rejection are difficult



Graft versus host diseaseGraft versus host disease Small intestine = immunocompetent organ Small intestine = immunocompetent organ

Population of lymphoid cells can mount an immunologic Population of lymphoid cells can mount an immunologic response to the host—a GVHD reaction response to the host—a GVHD reaction

Although animal models have shown that GVHD is a Although animal models have shown that GVHD is a common occurrence and GVHD has not been a significant common occurrence and GVHD has not been a significant clinical problemclinical problem

Acute GVHD presents 1-8 weeks post-transplantation with Acute GVHD presents 1-8 weeks post-transplantation with FeverFever LeukopeniaLeukopenia DiarrheaDiarrhea RashRash Other symptoms may include malaise, anorexia, arthralgia, Other symptoms may include malaise, anorexia, arthralgia,

and abdominal pain. and abdominal pain. Confirm diagnosis by biopsy Confirm diagnosis by biopsy Treatment -> high-dose steroids & antithrombocyte Treatment -> high-dose steroids & antithrombocyte

globulin or with OKT3globulin or with OKT325Dr .yekehfallah-phd of nursing-201504/19/23


Technical errorsTechnical errors (up to 50%) (up to 50%) More common in children than in adults More common in children than in adults May cause graft loss May cause graft loss The errors include The errors include

Anastomotic leaksAnastomotic leaks Hepatic artery thrombosisHepatic artery thrombosis Biliary anastomosis leaks or strictureBiliary anastomosis leaks or stricture Intra-abdominal hemorrhageIntra-abdominal hemorrhage Intra-abdominal abscessIntra-abdominal abscess Chylous ascitesChylous ascites 26Dr .yekehfallah-phd of nursing-201504/19/23

Intestinal Intestinal Transplantation - Transplantation -

Outcome and PrognosisOutcome and Prognosis In 1999, Mazariegos reported a 55% patient In 1999, Mazariegos reported a 55% patient

survival rate and 52% graft survival rate at 5 survival rate and 52% graft survival rate at 5 years following intestinal transplantationyears following intestinal transplantation Matched group of patients (no transplantation) Matched group of patients (no transplantation)

demonstrated 30% 1-year and 22% 2-year survival demonstrated 30% 1-year and 22% 2-year survival ratesrates

Isolated intestinal grafts reportedly provide Isolated intestinal grafts reportedly provide better patient and graft survival rates than better patient and graft survival rates than multivisceral grafts multivisceral grafts

Graft and patient survival rates are improving as Graft and patient survival rates are improving as centers gain experience (51 worldwide centers)centers gain experience (51 worldwide centers) Main centers – U of Pittsburgh, U of Nebraska, U of Main centers – U of Pittsburgh, U of Nebraska, U of

Miami, Hopital Necker-Enfants-Malades, & London Miami, Hopital Necker-Enfants-Malades, & London Health Sciences Center Health Sciences Center


Intestinal Intestinal Transplantation - Transplantation -

Outcome and PrognosisOutcome and Prognosis Small-intestine transplantation has Small-intestine transplantation has

higher incidences of rejection, sepsis, higher incidences of rejection, sepsis, and post-transplantation and post-transplantation lymphoproliferative disease than other lymphoproliferative disease than other organ transplantationsorgan transplantations These outcomes may be secondary to These outcomes may be secondary to

bacterial translocationbacterial translocation Overall, 78% of intestinal transplant Overall, 78% of intestinal transplant

patients can be expected to be free of patients can be expected to be free of TPN and to tolerate oral nutrition TPN and to tolerate oral nutrition following surgeryfollowing surgery 28Dr .yekehfallah-phd of nursing-201504/19/23

Intestinal Intestinal Transplantation – Transplantation –

Outcome and Prognosis Outcome and Prognosis The introduction of tacrolimus The introduction of tacrolimus immunosuppression, in combination immunosuppression, in combination with decontamination protocols, with decontamination protocols, antibiotic regimens, and antiviral antibiotic regimens, and antiviral measures against CMV and EBV, has measures against CMV and EBV, has improved patient and graft survival improved patient and graft survival ratesrates

Survival rates at 1 year as high as 90% Survival rates at 1 year as high as 90% have been achieved for patients have been achieved for patients receiving isolated intestinal grafts receiving isolated intestinal grafts 3 year survival > 70%3 year survival > 70%


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Small Bowel Transplantation. Intestinal Transplantation Indications include: Indications include:...

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