Small Bowel Transplantation

Small Bowel Transplantation
Keith Thatch, M.D. St. Luke’s-Roosevelt Hospital Center May 16th, 2007

Intestinal Transplantation
Small-intestine transplantation continues to evolve as a surgical procedure used in the management of intestinal failure in children and adults Intestinal transplantation offers the hope of increased longevity & improved quality of life to patients with intestinal failure and life-threatening complications of chronic TPN Progress in various aspects of organ preservation, surgical technique, immunosuppression, and postoperative management has improved the outcomes of organ transplantation in children and adults.

Over the last three decades, intestinal transplantation has evolved from experimental to a standard therapeutic option for intestinal failure patients Primarily a pediatric procedure with ~2/3s performed on children Remains less successful to other solid organ transplantation -> presumably due to the preponderance of lymphocytes in the bowel (strong stimulus for rejection) Progress in various aspects of organ preservation, surgical technique, immunosuppression, and postoperative management has improved the outcomes of organ transplantation in children and adults.

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)

Patient survival & graft survival rates have improved with The introduction of tacrolimus (FK506)–based immunosuppression (calcineurin inhibitor) Used in combination with Decontamination protocols Antibiotic regimens Antiviral measures against cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Pre-tacrolimus – pt survival 0-28% and graft survival 0-11% With tacrolimus – pt & graft survival exceed 50% Tacrolimus is chemically known as a macrolide. It reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription.[3] Although this activity is similar to ciclosporin, studies have shown that the incidence of acute rejection is reduced by tacrolimus use over ciclosporin

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

This continued until the early 1980s, with the advent of cyclosporine, immunosuppressive medications (azathioprine), steroids, and antilymphocyte globulin (ALG) However, clinical results with cyclosporine were disappointing (most grafts lost to rejection) Deltz reported the first successful long-term transplantation in Germany year-old woman received a segment of her sister's jejunum and ileum The graft survived until > lost to chronic rejection Goulet reported on 9 patients in 1990 (including a 9-month-old infant who received 2 intestinal transplants) with poor success rates under cyclosporine-based immunosuppression Graft survival time ranged from 10 days to 49 months.

The most significant advance in the development of intestinal transplantation was the introduction of TACROLIMUS (1990) The Starzl group (1998) reported that in 55 children who underwent small-intestine transplantations with tacrolimus 28 girls and 27 boys Median age = 3.2 years of age Patient survival rates were 55% Graft survival rates were 52% Greater understanding of the unique immunologic properties of the intestine has furthered the advancement of small-intestine transplantation

As a result of these advances and a growing appreciation of the phenomenon of chimerism, the number of intestinal transplants has steadily increased More than 100 intestinal transplants being performed each year in the United States Most active programs in North America: Univ of Pittsburgh, Univ of Nebraska, Univ of Miami, and the Toronto Hospital

Intestinal Transplantation Frequency
Difficult to measure the incidence of intestinal failure 2ndary to complications of TPN Studies demonstrate the incidence of irreversible intestinal failure is ~ 2-3 cases per million per year Success of intestine transplantation was first reported Multivisceral transplantation (University of Pittsburgh) Isolated bowel transplantation (University of Kiel, Germany) 1988 – Liver-small bowel transplantation (London Health Sciences Center) 1989 – Total small bowel transplantation (Hopital Necker-Enfants-Malades, Paris)

As of November 2005, the United Network for Organ Sharing (UNOS) database listed 190 patients awaiting intestinal transplantation In 2003, 116 small-intestine transplantations were performed in adult and pediatric patients in the United States

Graft survival rates at 1 and 5 years have been reported to be as high as 84% and 63%, respectively Waiting times were relatively brief (for a suitable small intestine) from , yet the mortality rate was 66% for intestinal failure patients on the waiting list Currently >150 patients waiting, but, unfortunately, very few cadaveric donors are suitable for intestinal transplantation

Intestinal Transplantation - Etiology
TPN = current standard of care for patients unable to maintain adequate nutrition via the intestinal tract alone Patients with poor intestinal function who cannot be maintained on TPN are potential candidates for transplantation

Intestinal failure—defined as the inability to maintain sufficient electrolyte, nutrient, and fluid balance for more than 1 month without TPN and no adaptive potential to meet these needs in the future May result from surgical short-bowel syndrome or intestinal dysfunction in children

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

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

Other causes of intestinal dysfunction are Absorptive disorders Microvillus inclusion Secretory diarrhea Autoimmune enteritis Dysmotiliy disorders Pseudo-obstruction Hirschsprung disease Visceral neuropathy A tumor (desmoid tumor and familial polyposis (eg, Gardner disease))

Leading causes of intestinal failure in children (in order of decreasing frequency) Intestinal atresia Gastroschisis Crohn’s disease Microvillus involution disease NEC Midgut volvulus (leading to infarction) Chronic intestinal pseudo-obstruction Massive resection secondary to tumor Hirschsprung disease Leading causes of intestinal failure in adults Crohn’s disease Superior mesenteric artery thrombosis Superior mesenteric vein thrombosis Trauma Desmoid tumor Volvulus Pseudo-obstruction Massive resection secondary to tumor Radiation enteritis

Intestinal transplantation is reserved for TPN-dependent patients with permanent intestinal insufficiency Pts become intolerant of TPN -> which manifests in potentially fatal complications Recurrent sepsis Thrombosis of access sites Metabolic disorders Cholestasis Hepatic dysfunction

Isolated intestinal grafting Poor venous access or moderate hepatic dysfunction and for those who develop severe fluid and electrolyte abnormalities that cannot be managed with TPN Combined small-intestine and liver transplantation Intestinal insufficiency & irreversible hepatic failure or coagulopathy Multivisceral transplants (ie, combined stomach, duodenum, pancreas, small intestine) Following extensive surgical resection of abdominal organs for aggressive tumor or severe abdominal trauma

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

Sixth International Small Bowel Transplant Symposium – referral criteria: Intestinal failure with impending life-threatening complications (i.e. end-stage liver disease) Recurrent sepsis (bacterial translocation 2ndary chronic TPN) Impending loss of central venous access Locally invasive tumors of the abdomen (desmoid) Rescue therapy for visceral vascular thrombosis, primary intestinal graft loss, and poor quality of life secondary to intestinal failure

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

Isolated intestinal transplantation
Transplantation may not be indicated for patients who have complications of their disease but maintain a borderline length of intestine May respond to intensive medical management Medical management may involve Modified administration of TPN Selective gut decontamination Optimized enteral feedings ( at least 20-30% caloric needs)

Isolated intestinal transplantation
Must evaluate liver function Suspected progression of liver dysfunction requires prompt evaluation for intestinal transplantation and a liver biopsy to determine whether a combined liver and small-intestine transplantation is needed

Isolated Intestinal Transplantation

Combined liver and small-intestine transplantation
Patients with end-stage liver disease (often TPN-related liver disease) & intestinal failure The highest mortality rate of all patients on the waiting lists for organ transplantations Chronic TPN -> cholestatic liver disease (esp. children) Very few size-match quality organs are available, and these patients are competing for organs with patients on longer waiting lists who are waiting for an isolated liver transplantation Represent only 2% of the patients on the liver waiting list Do not rank well in the MELD (model for end-stage liver disease) and PELD (pediatric end-stage liver disease) scoring system

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

Intestinal Transplantation Contraindications
Absolute contraindications Congenital immunodeficiency syndromes, systemic malignancy, metastatic disease, AIDs, cardiopulmonary insufficiency & overwhelming sepsis Because of the risk of unrestrained graft versus host disease (GVHD) Relative contraindications are evolving, but concern about transplantation from CMV- or EBV-positive donors to CMV- or EBV-negative recipients, weight (<5kg) and elderly pts High morbidity & mortality rates associated with the development of CMV or lymphoproliferative disease in pediatric intestinal transplants Although critically ill patients should be excluded, a history of multiple abdominal surgeries is not a contraindication for transplantation No clear lower age limit for pediatric patients (better results >2yrs of age)

Intestinal Transplantation Pediatric Recommendations
Hakim (1999) recommended cadaveric tranplantations from a donor with a beating heart 20% smaller than the recipient Designed to ensure that the pediatric recipient (who is likely to have a contracted peritoneal cavity) can accommodate the graft The shortage of potential donors because of size constraints is prompting development of novel harvesting and grafting techniques

Intestinal Transplantation - Workup
Preoperative workup: All potential transplant recipients require a review of Comorbidities Relevant laboratory Imaging studies

Laboratory studies include the following: CBC Chem-20 Prothrombin time (PT) Activated partial thromboplastin time (aPTT) Blood group and screen Serologic testing for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), CMV, EBV, syphilis, blood group system (ABO), and human leukocyte antigen (HLA) status When indicated, a hypercoagulable workup (i.e., protein C, protein S, antithrombin III, factor V mutation)

Imaging Studies: Perform angiography and or additional Duplex studies Assess the vascular supply for potential isolated living-related intestine donors Angiography helps evaluate the SMA to ensure a normal vascular intestinal distribution Duplex and Doppler studies help asses for possible inflow/outflow stenosis Adequate assessment & preservation of the descending branch of the right colic artery are important to provide adequate blood supply to the areas of the terminal ileum and ileocecal valve

Diagnostic Procedures: Dysmotility disorders require assessment of the stomach to exclude functional abnormalities Manometry of the stomach, esophagus, and rectum may be required to exclude sphincter achalasia and gastroparesis Pediatric pseudo-obstruction pts require urologic assessment Up to 1/3 may have a dysfunctional urinary tract NEC -> full neurologic and pulmonary workup Exclude the possibility of associated intraventricular hemorrhage & bronchopulmonary dysplasia Liver biopsy in patients with intestinal failure and hepatic insufficiency

Transplantation – Preoperative Details
Cadaveric small-intestine procurement Choose smaller donors than the intended recipient Preferentially direct CMV– donors to CMV– recipients Perform selective gut decontamination with antibiotic and antifungal preparations administered via a NGT along with standard IV antibiotic prophylaxis Use University of Wisconsin Universal Organ Preservation (UW) solution for both in situ flushing and cold storage Polyethylene glycol electrolyte solution Obtain wide exposure to the abdominal cavity, and encircle the abdominal aorta distally for subsequent insertion of the infusion cannula and proximally above the celiac axis for cross-clamping

Cadaveric small-intestine procurement Perform dissection, in situ cooling of abdominal organs, and exsanguination before removing the organs to the back table for preparation. Mobilize and devascularize the cecum and ascending colon with care to preserve the ileal branches of the ileocolic artery. Divide and close the ileum with the GIA stapler near the ileocecal valve Devascularize the colon by ligating and dividing the middle colic, left colic, and inferior mesenteric arteries near their origin After transection of the gastrocolic ligament and transection of the stapled sigmoid colon, remove the large bowel and greater omentum

Cadaveric small-intestine procurement Free the small-bowel mesentery from its retroperitoneal attachments Expose the mesenteric root, abdominal aorta, and infrahepatic vena cava (including renal veins entry) Divide the highest jejunal vascular arcades Preserve the vascular supply to the fourth part of the duodenum and the proximal part of the jejunum. Transect the proximal jejunum after mobilizing and dividing the ligament of Treitz and the IMV Suture the jejunal end of the intestine to help orient the allograft At this stage, the intestine is attached to the donor only by the superior mesenteric pedicle (SMA & SMV) Divide the mesenteric root distal to the level of the ligated middle colic vessel

Transplantation – Intra-operative Details
In situ organ cooling and removal Transaortic cooling requires perfusion with UW solution, mL/kg, for pediatric donors Remove the small-intestine graft by dissection of the SMA & SMV below the origin of the inferior pancreaticoduodenal artery Excise a large Carrel patch from the anterior aortic wall containing the celiac axis and superior mesenteric artery. Procure iliac and carotid arteries and veins as potential vascular grafts

Back-table preparation of organs Small-intestine grafts require little revision If the pedicle of the superior mesenteric artery is too short, it may be lengthened with free vascular grafts The anastomoses are made to the recipient aorta and portal vein or vena cava

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

Transplantation surgical therapy Isolated living-related intestinal grafting requires as much as cm of distal jejunum and ileum to ensure that the recipient has a sufficient amount of small bowel to be completely free of TPN

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

Transplantation – Postoperative Details
Require ICU monitoring postoperatively Induction therapy with tacrolimus and steroids is typically begun most often in conjunction with an interleukin-2 (IL-2) receptor antibody Maintain high levels of immunosuppression early in the postoperative period (risk of rejection is greatest) Then follow with a lower dose for maintenance therapy Consider the variable absorption and bioavailability of whichever immunosuppression regimen is used (ie, tacrolimus, cyclosporine microemulsion) Because the bioavailability of these drugs depends on intestinal surface area and transit time, the function of the grafts directly affects drug availability In addition, multiple immunosuppressive agents are used (as in other organ transplants) to minimize toxicity and to maximize therapeutic efficacy

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

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

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

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

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

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

Acute allograft rejection Early diagnosis of allograft rejection, a major contributor to both the high morbidity and the high mortality associated with small-intestine transplantation, is essential Allograft rejection incidence rates as high as 87% have been reported Manifests clinically Fever abdominal pain increased output from the ostomy abdominal distention Acidosis Malabsorption and electrolyte abnormalities occur in some patients Bacterial & fungal sepsis can be life threatening because of the intestine's loss of barrier function, making early diagnosis and effective treatment of the rejection vital

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

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

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

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

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

Author Transplant type Graft 1 Yr % Patient 1 Yr % Graft 5 Yr % Patient 5 Yr % Lagnas(Neb) Liver & S.I. 61 76 Reyes (Pitt) All 63 73 Grant S.I. 55 69 66 Multivisceral Mazariegos 52 Control 30 Madariaga 54 42 Farmer 77 90

Intestinal Transplantation - Outcome and Prognosis University of Miami experience
Type of Graft 8/94 – 6/95 7/95-12/97 1/98-9/99 Isolated small bowel 0% 50% 80% Liver-small bowel 40% 30% 48% Multivisceral 27%

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

One study demonstrates 50% normal growth in pediatric patients who receive intestinal transplants Sudan et al (2000) reported 11% of patients maintained pre-transplant growth at less than the 10th percentile 15% demonstrated catch-up growth 84% of these children were able to return to day care, preschool, or school at the appropriate level for their development

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%

Intestinal Transplantation – Future and Controversies
Outcomes may improve with further work to overcome the lack of suitable organ donors through living-related intestinal transplantation, improved immunosuppression, and infection surveillance Promising procedures, although still unproven, include new immunosuppressive drugs and regimens, as well as unmodified donor bone marrow infusions to induce chimerism and to promote graft acceptance

Intestinal Transplantation – Future and Controversies
Cost analyses of continued medical management versus early liver-intestine and intestinal transplantation requires further study to help guide policy According to Dr. Abu-Elmagd of the Univ of Pittsburgh “the data …(has)… shown that the total cost is unequivocally cost-effective. It pays for itself in the following two years — exactly the same as in kidney transplantation."

Future and Controversies
Current Research led by Dr. Marshall Schwartz at St. Christopher’s Pediatric Hospital Center Can Parenteral Nutrition Induced Liver Injury Be Prevented in Children with Short Bowel Syndrome? Investigating the potential role of growth factors on enhancing the function of the residual small intestine in SBS and thereby preventing liver injury Esp. Hepatocyte Growth Factor (believed to be the most potent) The use of novel quantum dot technology in the early detection of graft rejection and the role of a growth factor on amelioration of bowel injury following small bowel transplantation Inorganic fluorophores use to detect surface molecular attachment and epidermal receptor function – minimally invasive evaluation for possible acute rejection

Thomas E. Starzl Transplant Institute – 13 year survival data
Abu-Elmagd et al reported on the status 96 children who received 102 allografts (29 intestine, 60 liver & intestine, & 13 multivisceral) Since 1990, 54% still alive with an overall 5 yr survival rate of 58% & 5yr graft survival of 50% Quality of life is also greatly improved with re-institution of enteral feeding

Intestinal Transplant Patients
Transplant: MB has a small bowel transplant for Near Total Hirschsprung's Disease Requires 24-hours a day Performed at Children's Hospital of Pittsburgh Continues to receive continual medical testing and care

SR was only 5 months old when she received a bowel-liver-stomach-pancreas transplant (1997) London Health Sciences Center Here she is at the age of 4

AC small bowel transplant 2ndary to obstructive tumor (gardiner’s syndrome), s/p previous colectomy Dr. Fishbein and the Georgetown Univ Transplant team AC became to eat again after a few post-operative weeks

AG received a liver and small bowel transplant when he was just three years old and has also undergone two heart operations in Scotland Currently 10 years, he enjoys many of the same activities as his peers

References Abu-Elmagd K, Fung J, Bueno J: Logistics and technique for procurement of intestinal, pancreatic, and hepatic grafts from the same donor. Ann Surg 2000 Nov; 232(5): 680-7[Medline]. Beath SV, Protheroe SP, Brook GA: Early experience of paediatric intestinal transplantation in the United Kingdom, 1993 to Transplant Proc 2000 Sep; 32(6): 1225[Medline]. Benedetti E, Baum C, Raofi V: Living related small bowel transplantation: progressive functional adaptation of the graft. Transplant Proc 2000 Sep; 32(6): 1209[Medline]. Bueno J, Ohwada S, Kocoshis S: Factors impacting the survival of children with intestinal failure referred for intestinal transplantation. J Pediatr Surg 1999 Jan; 34(1): 27-32; discussion 32-3[Medline]. Carrel A: La technique des anastomese vasculaires et la transplantation des visceres. Lyon Med 1902; 98: 859. Cicalese L, Sileri P, Green M: Bacterial translocation in clinical intestinal transplantation. Transplant Proc 2000 Sep; 32(6): 1210[Medline]. Deltz E, Schroeder P, Gebhardt H: [First successful clinical small intestine transplantation. Tactics and surgical technic]. Chirurg 1989 Apr; 60(4): 235-9[Medline]. Farmer DG, McDiarmid SV, Yersiz H: Improved outcome after intestinal transplantation: an 8-year, single-center experience. Transplant Proc 2000 Sep; 32(6): [Medline]. Filston HC, Colombani PM: Preliminary experience with intestinal transplantation in infants and children. Pediatrics 1996 Apr; 97(4): 583-4[Medline]. Finn L, Reyes J, Bueno J: Epstein-Barr virus infections in children after transplantation of the small intestine. Am J Surg Pathol 1998 Mar; 22(3): [Medline]. Frezza EE, Tzakis A, Fung JJ: Small bowel transplantation: current progress and clinical application. Hepatogastroenterology 1996 Mar-Apr; 43(8): [Medline]. Giraldo M, Martin D, Colangelo J: Intestinal transplantation for patients with short gut syndrome and hypercoagulable states. Transplant Proc 2000 Sep; 32(6): [Medline].

References Goulet O, Revillon Y, Jan D: Small-bowel transplantation in children. Transplant Proc 1990 Dec; 22(6): [Medline]. Grant D: Intestinal transplantation: 1997 report of the international registry. Intestinal Transplant Registry. Transplantation 1999 Apr 15; 67(7): [Medline]. Grebe SC, Streilein JW: Graft-versus-Host reactions: a review. Adv Immunol 1976; 22: [Medline]. Gruessner RW, Sharp HL: Living-related intestinal transplantation: first report of a standardized surgical technique. Transplantation 1997 Dec 15; 64(11): [Medline]. Hakim NS, Papalois VE: Small bowel transplantation. Int Surg 1999 Oct-Dec; 84(4): 313-7[Medline]. Kahan BD: Cyclosporine. N Engl J Med 1989 Dec 21; 321(25): [Medline]. Kato T, Berho M, Weppler D: Is severe rejection an indication for retransplantation? Transplant Proc 2000 Sep; 32(6): 1201[Medline]. Kocoshis SA: Small bowel transplantation in infants and children. Gastroenterol Clin North Am 1994 Dec; 23(4): [Medline]. Langnas AN, Shaw BW Jr, Antonson DL: Preliminary experience with intestinal transplantation in infants and children. Pediatrics 1996 Apr; 97(4): 443-8[Medline]. Langrehr JM, Banner B, Lee KK: Clinical course, morphology, and treatment of chronically rejecting small bowel allografts. Transplantation 1993 Feb; 55(2): [Medline]. Lee C et al: Pharmacokinetics of tacrolimus (FK506) prior to kidney transplantation. Clin Pharmacol Ther 1993; 62: 2. Lillehei RC, Idezuki Y, Feemster JA: Transplantation of stomach, intestine, and pancreas: experimental and clinical observations. Surgery 1967 Oct; 62(4): [Medline]. Madariaga JR, Reyes J, Mazariegos G: The long-term efficacy of multivisceral transplantation. Transplant Proc 2000 Sep; 32(6): [Medline].

References Margreiter R: The history of intestinal transplantation. Transplant Rev 1977; 11: 9. Mazariegos GV, Reyes J: What's new in pediatric organ transplantation. Pediatr Rev 1999 Nov; 20(11): [Medline]. Mazariegos GV, Kocoshis S: Patient selection for intestinal transplantation. Curr Opin Organ Transplant 1998; 3: Nalesnik M, Jaffe R, Reyes J: Posttransplant lymphoproliferative disorders in small bowel allograft recipients. Transplant Proc 2000 Sep; 32(6): 1213[Medline]. Reyes J, Bueno J, Kocoshis S: Current status of intestinal transplantation in children. J Pediatr Surg 1998 Feb; 33(2): [Medline]. Reyes J: Liver and intestine transplantation. Immunol Allergy Clin North Am 1996; 16(2): Roberts CA, Radio SJ, Markin RS: Histopathologic evaluation of primary intestinal transplant recipients at autopsy: a single-center experience. Transplant Proc 2000 Sep; 32(6): [Medline]. Sudan DL, Kaufman S, Horslen S: Incidence, timing, and histologic grade of acute rejection in small bowel transplant recipients. Transplant Proc 2000 Sep; 32(6): 1199[Medline]. Sudan DL, Iverson A, Weseman RA: Assessment of function, growth and development, and long-term quality of life after small bowel transplantation. Transplant Proc 2000 Sep; 32(6): [Medline]. Thompson JS: Intestinal transplantation. Experience in the United States. Eur J Pediatr Surg 1999 Aug; 9(4): 271-3[Medline]. Todo S, Tzakis A, Abu-Elmagd K: Current status of intestinal transplantation. Adv Surg 1994; 27: [Medline].

Small Bowel Transplantation

Similar presentations

Presentation on theme: "Small Bowel Transplantation"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Small Bowel Transplantation

Similar presentations

Presentation on theme: "Small Bowel Transplantation"— Presentation transcript:

Similar presentations

About project

Feedback