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Intestinal Transplantation

Deborah A. Andersen, RN, BSN, CCTC. Pediatric Clinical Transplant Coordinator University of Nebraska Medical Center

Alexis Carrell - 1900's Richard Lillehei - dogs 1950's 30 years of failure Thomas Starzl: 1987 > First Intestinal Tx > 3 ½ child with mid-gut volvulus > Survived for >6 months > Died from PTLD David Grant: 1988 > First Liver/Intestine Tx > 41 y/o adult > Anti-thrombin 3 deficiency which caused superior mesenteric artery thrombosis > survived for 4+ 1990s Pittsburgh, Miami and Omaha programs

The Top 10 Reasons that it takes Guts to do Intestinal Transplantation

#1 #2 #3 #4 #5 Massive gut lymphocyte content and bacterial load Intestine supported by relatively small blood vessels It a very technically demanding surgery Inpatient stays on average 30-40 days Patients require higher levels of immunosuppression

#6

There are numerous post-operative infectious complications #7 Must coordinate a lot of services upon discharge #8 Outpatient care and follow-up is intense and immediate #9 PTLD occurs more frequently in pediatric intestinal transplant patients #10 There are NUMEROUS social issues surrounding parents

International Intestinal Transplant Registry: April 1985-May 2007

69 intestinal transplant centers world wide 1720 intestinal transplants done

> 746 Intestine > 594 Liver and Intestine > 380 multi-visceral

909 survivors Current rate of transplant 200-250 / year The top five programs responsible for 2/3 of transplant volume

International Intestinal Transplant Registry: 2007

One year survival 80%

> Largest volume centers have best outcomes

Five year survival is still 50% world wide Longest survivor out 18 years, France

Candidates Waiting 235 Transplants Performed To Date 1530

> 1 year survival: > 3 year survival: > 5 year survival:

75% 57.3% 49.5%

UNOS Regional Distribution of Intestinal Transplant

Region 1: Northeast

> 11: Boston

Region 7: North-central

> 90: U of Minnesota

Region 2: PA,WV,MD,NJ

> 534: U Pitts, Children's

Region 8: Midwest

> 277: U of Nebraska

Region 3: Southeast

> 289: Jackson, Miami

Region 9: NY,VT

> 99: Mt. Sinaii

Region 4: Texas, OK

> 14

Region 10: IN, MI, OH

> 83 Riley, Clarion

Region 5: Southwest

> 120: UCLA, Stanford

Region 11: East-central

> 12

Region 6: Northwest

> 3

Intestinal Failure

Gut which is unable to digest or absorb adequate nutrition to support life

Is Intestinal Failure Permanent?

Length of gut:

> Adults

<65 cm intestine with colon <120 cm intestine without colon

> Infants <30cm of intestine with colon <15cm of intestine with ileocecal valve Feeding intolerance/Inability to digest nutrients

Bowel rehabilitation

Intestinal reconstructive surgery

>

Tapering, bianchi, STEP, reconnection

Parenteral + Enteral Nutrition Registry

> SBS: 1 + 4 year survival 94% + 80% > motility disorder: 1 and 4 year survival 87% + 70%

UCLA, Omaha, Denver, Paris

What are the causes of Intestinal Failure??

Massive Resection

> Necrotizing enterocolitis > Gastroschisis > Mid-gut volvulus > Congenital intestinal atresias > Massive abdominal trauma > Omphalocele > Mesenteric thrombosis > Desmoid tumor

Short Bowel Syndrome

A disorder in which mal-absorption occurs as a result of massive resection of the small intestine, abnormal gut motility, or mucosal disorders which prevent absorption or digestion.

Dysmotility Syndromes

> Pseudo-obstruction > Hirschbrung's Disease/Aganglionosis

Congenital Enteropathy

> Microvillus inclusion disease > Secretory diarrhea

Indications for Evaluation for Intestinal Transplantation

No hope of discontinuation of parenteral nutrition Complication of parenteral nutrition > One or more episodes of life threatening sepsis > Limited vascular access > Elevation in liver function tests > Extremely short gut with no enteral feedings > MID

Evaluation for Intestinal Transplantation

Referral Obtain medical information regarding patient Review medical information with physician

Evaluation for Intestinal Transplantation

Laboratory Studies

> Nutritional labs > Cytotoxic antibodies (PRA)

Radiology Studies

> Upper gi and SBS > Barium enema > ECHO > Vascular studies > Abd Ultrasound

Indications for Intestinal Transplantation

No hope for discontinuation of parenteral nutrition One or more episodes of life threatening sepsis Limited vascular access Elevation of liver function tests

Liver Failure and TPN

Multiple situations work together to create liver disease

> TPN itself: toxicity of ingredients > Bile remaining in liver damages hepatocytes > Immature liver > Multiple central line infections and sepsis > Decreased immunogenicity of liver

Indications for Liver and Intestinal Transplant

No hope for discontinuation of parenteral nutrition Biopsy-proven liver cirrhosis or extensive bridging fibrosis

Indications for Isolated Liver Transplantation

Biopsy-proven liver cirrhosis or extensive bridging fibrosis Enough functioning bowel to discontinue parenteral nutrition

Contraindications for Transplantation

Psychosocial instability that would interfere with compliance Severe psychiatric impairment which would interfere with ability to understand informed consent and compliance with therapeutic regimen Severe neurological impairment Active systemic infection Active cancer Sever cardiovascular disease Active alcohol, narcotic abuse or illicit drug use Absence of funding for the transplant procedure and/or medications post-transplant Pregnancy

Listing for Liver and Intestinal Transplantation

PELD score plus increased risk of mortality on wait list: calculated score

+ 23 points

UNOS: Implementation of Change to Policy 3.6.4.7 (Combined LiverIntestine Candidates).

Require rescore at specfic intervals or can elect to rescore anytime: need to have all labs from same day

Listing for Intestinal Transplantation

Patients are listed for intestinal transplantation according to

> Blood type > Body size > Medical necessity Status #1 Status #2

Listing and Waiting Times

Waiting Times Waiting time varies between organ types Blood types Size of recipient

ABO compatible, < 50 yr Smaller/same body size as recipient Hemodynamically stable, minimal pressors, no down time Normal intestinal function Negative cross-match - center specific CMV and EBV compatible

Gut decontamination ­ oral antibiotics IV antibiotics Donor induction immunosuppression (center specific) Surgical discussion of vessel sharing in multi-organ donor, particularly pancreas

Small Bowel Transplant

Liver, small bowel, pancreas transplant

Multi-Visceral Transplant

Surgical Complications

Hepatic artery thrombosis Portal vein thrombosis Bleeding Perforation of bowel Wound infection Wound dehiscence Leaking from anastomosis Primary graft non-function

Immediate Post-Op Period Days 0-7

The Honeymoon Period

Intermediate Post-Operative Phase (Day 7-discharge)

Shift in emphasis to:

> Immunosuppression > Monitoring for rejection > Monitoring for infection > Nutritional status > Fluid and electrolyte replacement > Psychosocial issues

Immunosuppression

Tacrolimus

> > > >

level level level level

initially 12-15 at 3 months 8-10 at 6 months 5-8 > one year 5

Prednisone

> 1mg/kg IV x 7 days > 0.5mg/kg po x 1 year > At 1 year QOD x 3 months and then dc

Rejection

Protocol tissue biopsies Signs and symptoms of rejection

Increased stool outputs

Treated with pulse IV steroids and increased levels of tacrolimus May require enteral rest Set patient up for increased infections

Monitoring for Infection

Culture...culture....culture Everyone gets a central line infection Bacterial infections occur first, then viral infections....fungal infections occur any time Monitoring CMV and EBV DNA levels monthly and with symptoms Stool studies done frequently

> norwalk, adenovirus, rotovirus, viral studies, bacterial studies, c.diff

(Stool infections last forever)

Infections con'd

CMV: Donor/recipient matching, gancyclovir IV + Cytogam prophylaxis. Routine CMV screening EBV: Routine EBV screening. Early aggressive treatment. PTLD: Major cause of morbidity and mortality Bacterial: Bacterial translocation. Gut decontamination

Nutritional Support

Small Bowel Transplantation

> Discontinuation of parenteral nutrition is slow process Increase by 10ml enterally, decrease by 5ml on TPN until up to full feeds > Conversion to full enteral feeding > Oral feedings > Oral aversion

Fluids and Electrolyte Balance

Allowable stool outputs are 50cc/kg/day Must provide replacement fluids for outputs > this to prevent dehydration Tacrolimus affects kidney's absorption of of electrolytes

> KCl, Na, Bicarbonate, Mg

Psychosocial Considerations

Parents may have never had children out of hospital after birth Parents may have been told that their child is going to die multiple times Parents have never delt with loss of the dream Understand diagnosis at different levels and different intervals Have overwhelming at home considerations

Home Care Considerations

Care partner Nutrition

> Enteral feedings > Fluid and electrolyte balance

Oral medication Wound care Physical and occupational therapy Feeding team

Home Care Considerations

Educational Development Biopsies Clinic visits PRN clinic visits for any change in status

Considerations for long-term follow-up

Small bowel rejection

> Increased stool outputs > Amount > Fever with increased outputs > > > >

Feeling great otherwise Change in color, watery Time since transplantation Duration of increased outputs

Considerations for long-term follow-up

Have other medical problems just like everybody else. Not everything is related to their transplant Need close PTLD surveillance

> Swollen lymph nodes, tonsillitis, malaise. fever

Must remain on immunosuppressive drug tacrolimus for life Must maintain close contact with transplant team Continue to need close surviellence for years after transplantation

UNMC 15 year Experience

Grp1 (n=87) Rejection free < 90 days Moderate/Severe rejection at any time GVHD Viral (CMV/adenovirus) PTLD Days for initial hospitalization (ave) 3 mo patient survival after primary IT 1 yr patient survival after primary IT 3 yr patient survival after primary IT

*p<0.05 vs Grp1 and Grp2, ** p<0.05 vs. Grp1

Grp2 (n=34) 79.5% 14.7% 2.9% 5.8% 11.17% 63.1 85.3% 61.8% 50.0%

Grp3 (n=61) 93.4%* 9.8%** 3.2% 6.5% 13.1% 58.5 93.2% 84.0%* 80.5%*

33.3% 36.7% 1.1% 9.1% 13.7% 81.9 85.1% 64.4% 50.6%

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