INTESTINAL FAILURE, REHABILITATION & TRANSPLANTATION ... · DEFINITIONS Intestinal Failure...
Transcript of INTESTINAL FAILURE, REHABILITATION & TRANSPLANTATION ... · DEFINITIONS Intestinal Failure...
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INTESTINAL FAILURE, REHABILITATION& TRANSPLANTATION:
Indications, Techniques and Outcomes
Douglas G. Farmer, MD.Professor of Surgery
Director, Intestinal Transplant ProgramDumont-UCLA Transplant Center
Los Angeles, CA
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Short Bowel/Gut Syndrome
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Short Bowel/Gut Syndrome
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DEFINITIONS
Intestinal FailureCondition resulting “from obstruction, dysmotility,surgical resection, congenital defect, or diseaseassociated loss of absorption and is characterized by theinability to maintain protein-energy, fluid, electrolyte ormicronutrient balance”.
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Intestinal FailureFunctional Causes
• Chronic Intestinal Pseudo-obstruction• Adhesions• Fistulae
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Intestinal FailureMucosal Causes
• Microvillous inclusion disease• Tufting enteropathy• Congenital neuroendocrinopathy
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Intestinal FailureSurgical Causes (ADULT)
• IBD• Trauma• Volvulus• Mesenteric venous thrombosis• Mesenteric arterial thrombosis• Embolic phenomenon• XRT• Adhesions• Fistulae• Tumor (GIST, Desmoid; FAP)
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Intestinal FailureSurgical Causes (CHILDREN)
• In utero volvulus• JI atresia• Gastroschisis• Omphalocele• Meconium ileus• Hirschsprungs
Disease
• NEC• Post-Natal volvulus• Pseudoobstruction
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The Journey
IntestinalFailure
EnteralAutonomy
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The Journey
IntestinalFailure
EnteralAutonomy
ParenteralNutritionSupport
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The Journey
IntestinalFailure
EnteralAutonomy
ParenteralNutritionSupport
EnteralFeedingRegimen
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The Journey
IntestinalFailure
EnteralAutonomy
ParenteralNutritionSupport
EnteralFeedingRegimen
MedicalTherapy
GlutamineGH/GLP
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The Journey
IntestinalFailure
EnteralAutonomy
ParenteralNutritionSupport
EnteralFeedingRegimen
TPNAlterations
(Lipids)
MedicalTherapy
GlutamineGH/GLP
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The Journey
IntestinalFailure
EnteralAutonomy
ParenteralNutritionSupport
EnteralFeedingRegimen
TPNAlterations
(Lipids)
Autologous Reconstructive
Surgery
MedicalTherapy
GlutamineGH/GLP
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The Journey
IntestinalFailure
EnteralAutonomy
ParenteralNutritionSupport
EnteralFeedingRegimen
TPNAlterations
(Lipids)
Autologous Reconstructive
Surgery
MedicalTherapy
GlutamineGH/GLP
Fistula ManagementStricture/adhesion ManagementOstomy ManagementLengthening Procedure (S.T.E.P)
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The Journey
IntestinalFailure
EnteralAutonomy
ParenteralNutritionSupport
EnteralFeedingRegimen
TPNAlterations
(Lipids)
Autologous Reconstructive
Surgery
Intestinal Transplantation
MedicalTherapy
GlutamineGH/GLP
Fistula ManagementStricture/adhesion ManagementOstomy ManagementLengthening Procedure (S.T.E.P)
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Parenteral Nutrition Support
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OUTCOME PREDICTORSSURVIVAL
• SMALL BOWELLENGTH
• ILEOCECAL VALVE• COLONIC RESECTION• ENTEROSTOMA• PN COMPLICATIONS• PN LIVER DISEASE
ADAPTATION• SMALL BOWEL
LENGTH• ILEOCECAL VALVE• COLONIC RESECTION• ENTEROSTOMA• CHOLECYSTECTOMY• #INFECTIONS• TIME ON TPN
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TPN ComplicationsCatheter Sepsis
Catheter OcclusionVascular thrombosis
CholelithiasisLiver DiseaseBone DiseaseNephrolithiasisRenal Function
Death
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Survival on TPN
Aliment Pharmacol Ther 2006
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TPN Alterations to MinimizeComplications
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Minimization of TPN Complications
• Optimize enteral feeding• Eliminate sepsis• Line care
– Vanco and ampho Locks– Ethanol locks
• Identify coagulation disorders• TPN formulation alterations
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Fish Oil EmulsionsOmegaven®
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Prospective, Case Controlled Trial of 24weeks of Intravenous Fish Oil in Children with
Intestinal Failure Associated Liver Disease
Kara Calkins*1, Stephen Shew2, JamesDunn2, Douglas Farmer2, and Robert
Venick1,2
*SupportedbyNIHgrantT32GM75776‐6
1DepartmentofPediatrics,2DepartmentofSurgeryUniversityofCalifornia,LosAngeles
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RETROSPECTIVE SO COHORT
Satisfies Inclusion Criteria
SOIntralipid™ 0.5 – 4 gm/kg/d
x 24 weeks or untildeath/transplant
PROSPECTIVE FO COHORT
Satisfies Inclusion Criteria
FO Omegaven™ 1 gm/kg/d IV
X 24 weeks or until death/transplant
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BILIRUBIN
**p-value<0.0001
FOSO
Weeks
Geo
met
ric M
ean
Tota
l Bili
rubi
n
(
mg/
dL)
-20246810121416
5 10 15 20 25
** ** ** **
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Medical Therapies foradaptation
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Glutamine and Growth Hormone
“In the last decade, most IF research hasbeen focused on exploring the potential ofthese substances as supportive IF treatment.However, clinical trials so far have notdemonstrated reproducible or meaningfulclinical benefits with the use of glutamine orgrowth hormone.”
C. Tee, K. Wallis, S. Gabe, Clin Exp Gastro 2011
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Glucagon-like Peptide 2 (GLP2)
• Gattex ® (teduglutide)• FDA approved• 24 week phase 3 trial• 63% vs 30% achieved a 20% reduction in
tpn at 24 weeks
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Surgical Therapies foradaptation
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STEP
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STEP
Kim et al., JPS 2003
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STEP
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International STEP RegistryData
HB Kim, MDBoston Children’s Hospital
Pediatric Intestinal Failure and RehabilitationSymposium (PIFRS)
Chicago, IL 2010
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STEP Registry
• 111 patients• 9/2004 – 1/2010• 50 worldwide centers
HB Kim, MD
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111 Patients
97 STEP
9 Death 4 SBT 8 TPN 14 TPN+EN 45 100%EN
14 Lost
3 Poor data
14 Repeat STEP (3rd STEP=2)
2 Death 1 SBT 4 TPN+EN 3 100% EN
48/94=51%
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Transplantation
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Intestinal TransplantationIndications
Irreversible Intestinal Failure associated with oneor more life-threatening complications:
• Liver Disease• Loss Vascular Access
• Recurrent Catheter Sepsis• Complex fluid and electrolyte management
• Non-reconstructible GI Tract
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Intestinal TransplantationGraft Options
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IsolatedIntestine
Implantation
WJS 2002
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Miami Ped Transpl 1999
COMBINED LIVER-INTESTINALIMPLANTATION
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Multivisceral Implantation
WJS 2002
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ModifiedMultivisceralImplantation
Ann Surg 2001
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The liver, spleen and preformed antibodies areimportant predictors of survival after intestinal
transplantation:Analysis of a single center, 20 year experience
Douglas G Farmer, Robert S Venick, Laura Wozniak, YvonneE Esmailian, Hasan Yersiz, Kanela Artavia, Laurie Reyen,
Susan Ponthieux, Erin Core, Villy Hwang, Anna Zafar, GalenCortina, Sue V McDiarmid, Ronald W Busuttil
Intestinal Transplant ProgramDumont UCLA Transplant Center
XIth International Small Bowel Transplant SymposiumWashington, DC, September 2011
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Introduction
• Short term survival after intestinaltransplantation has markedly improved– 80-90% 1-year survival has been reported
• Medium term survival (1-5 yr) still lags– UNOS 5-yr survival 40-45%– ITR 2009 5-yr survival 50%
• Long term outcomes (>5 yr) are rarelyreported
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Results
• 97 recipients– 59% male– 74% children– 12.1 ± 13.9 yrs old– Actual MELD/PELD 13.7 ± 11.3– Adjusted MELD/PELD 34.4 ±11.0– 45% hospitalized (25% ICU)– cGFR 109 ± 56 ml/min/1.73m2
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Results• 115 ITx
– 6 kidney inclusive– 6 colon inclusive– 0 stomach inclusive
23%
62%
11%
4%
iITx
OLT-ITX
MVTx
mMVTx
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Results
INDUCTION IMMUNOTHERAPY
10%
60%
30%
NONE
IL2RA
ANTIBODY
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Results
• Acute Rejection– 43% without ACR– Median 1 ACR/graft
• Chronic Rejection: 8 pt (7%)– 3.5 ± 2.4 yrs post-ITx
• GVHD: 3 pt (2.6%)• Tissue invasive CMV Dz: 6 pt (5%)• PTLD: 9 pt (8%)• Infectious Enteritis: 70 pt (61%)
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Post-Transplant Survival
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0S
urv
ival
0 12 24 36 48 60
Time Post-Transplant (months)
Survival Plot
Patient
Graft*(*actual)
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0 = No risk factors1 = DSA+ OR non-Liver graft2 – DSA+ AND non-liver graft
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0 = No risk factors1 = DSA+ OR splenectomy2 – DSA+ AND splenectomy
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CONCLUSIONS
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CONCLUSION 1
• TPN therapy required for all• Long-term TPN management appropriate
in some case• Emphasize PN weaning• Minimize PN associated complications
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CONCLUSION 2
• Fish oil based lipid formulations appear tobe safer in short-term for infants andchildren with early IFALD
• No long-term data• Other emulsions in development
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CONCLUSION 3
• Medical consideration should be given tothe use of GLP2 analog in scientific study
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CONCLUSION 4
• Surgical options should be considered inall
• STEP best applied to patients with– dilated small bowel segments– Dependent on PN for 25-75% of calories– Absence of advanced hepatic
fibrosis/cirrhosis
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CONCLUSION 5
• Reserve transplantation for patients who– Fail with adaptation– Develop 1 or more life-threatening TPN
complications– Careful patient selection, operative planning– Choose the correct organs!
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Thank You!