Download Small Bowel Transplantation

Small Bowel
Transplantation
Intestinal Transplantation
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Indications include:
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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:
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Isolated intestinal (cadaveric or living-related)
Multivisceral transplantation (combined liver and
multivisceral)
Dr .yekehfallah-phd of nursing-2015
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Contraindications of Small Bowel
Transplant
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Presence of Active Infection
Aggressive Malignancy
Multi-System Organ Failure
Cerebral Edema
AIDS
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History of the Procedure
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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
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Intestinal Transplantation - Etiology
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Worldwide, the leading cause of intestinal failure is
short-bowel syndrome caused by surgical removal
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~10-20cm of small bowel needed with an ileocecal valve
40cm without a ileocecal valve
Conditions leading to short-bowel syndrome include
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Midgut volvulus
Gastroschisis
Trauma
Necrotizing enterocolitis (NEC)
Ischemia
Crohn’s disease
Dr .yekehfallah-phd of nursing-2015
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Short Bowel
Syndrome
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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
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Preoperative evaluation and selection
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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
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Optimization of preoperative morbid conditions
(infection, malnutrition) can significantly affect
outcome
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Preoperative evaluation and selection
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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 2year 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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Isolated Intestinal Transplantation
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Multivisceral transplantation
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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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An isolated intestine being prepared on the back table
prior to implantation
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Transplantation – Intra-operative
Details
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Transplantation surgical therapy
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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
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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
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Intestinal Transplantation –
Follow-up care
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At regular intervals, perform
CMV antigenemia
 Quantitative EBV polymerase chain reaction (PCR)
surveillance
 Routine cultures
 Transplant ileostomal endoscopy & biopsy (as often
as twice weekly)
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Additionally, monitor fluid status, stool losses,
and serum electrolytes
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Major Post Operative Complications
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Bleeding
Thrombosis
Anastomatic Leaks
Sepsis from bacterial translocation of Graft
GVHD
Acute Rejection
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Intestinal Transplantation Complications
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Infectious complications account for ~60% of
intestinal graft losses
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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
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Dr .yekehfallah-phd of nursing-2015
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Intestinal Transplantation Complications
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CMV infection
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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
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Endoscopy shows superficial ulcers, and histopathology confirms
CMV inclusion bodies
Dr .yekehfallah-phd of nursing-2015
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Intestinal Transplantation Complications
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CMV infection
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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
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Ganciclovir is a synthetic analogue of 2'deoxyguanosine, which inhibits replication of human
CMV
Dr .yekehfallah-phd of nursing-2015
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Intestinal Transplantation Complications
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EBV-associated lymphoproliferative disease
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Posttransplantation lymphoproliferative disease occurs more
often in children > adults (29% vs. 11%)
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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.
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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
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
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Intestinal Transplantation Complications
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EBV-associated lymphoproliferative disease
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Treatment of posttransplantation
lymphoproliferative disease involves
Reduction of immunosuppression
 Administration of ganciclovir (10 mg/kg/d)
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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
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Dr .yekehfallah-phd of nursing-2015
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Intestinal Transplantation Complications
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Acute allograft rejection
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Rejection is diagnosed by endoscopic intestinal biopsy
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Histologic evidence -> mucosal necrosis and loss of villous
architecture with transmural cellular infiltrate
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Histopathology -> crypt cell apoptosis, cryptitis or crypt loss,
necrosis, and endotheliitis
Treatment ->
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Diagnosis can be difficult because of the patchy nature of rejection
and the presence of bleeding & perforation complications
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
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Intestinal Transplantation Complications
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Chronic allograft rejection
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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
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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
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Possibly caused by injury to the vascular endothelium, with a complex
inflammatory cascade occurring in the vessel wall
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Obliterative arteritis, atrophic Peyer patches and mesenteric lymph
nodes
Therefore, prevention and treatment of chronic intestinal rejection are
difficult
Dr .yekehfallah-phd of nursing-2015
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Intestinal Transplantation Complications
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Graft versus host disease
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Small intestine = immunocompetent organ
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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
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Population of lymphoid cells can mount an immunologic response to the
host—a GVHD reaction
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
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Intestinal Transplantation Complications
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Technical errors (up to 50%)
More common in children than in adults
 May cause graft loss
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Anastomotic leaks
 Hepatic artery thrombosis
 Biliary anastomosis leaks or stricture
 Intra-abdominal hemorrhage
 Intra-abdominal abscess
 Chylous ascites
Dr .yekehfallah-phd of nursing-2015
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Intestinal Transplantation Outcome and Prognosis
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In 1999, Mazariegos reported a 55% patient survival
rate and 52% graft survival rate at 5 years following
intestinal transplantation
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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)
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Main centers – U of Pittsburgh, U of Nebraska, U of Miami,
Hopital Necker-Enfants-Malades, & London Health Sciences
Center
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Intestinal Transplantation Outcome and Prognosis
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Small-intestine transplantation has higher
incidences of rejection, sepsis, and posttransplantation lymphoproliferative disease than
other organ transplantations
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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
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Intestinal Transplantation –
Outcome and Prognosis
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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
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3 year survival > 70%
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?
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