Small Bowel Transplant*

 

Medical Policy: 07.03.04 

Original Effective Date: November 2009 

Reviewed: November 2018 

Revised: November 2018 

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

A small bowel (intestinal) transplant may be performed as an isolated procedure.  An isolated small bowel (intestinal)transplant has evolved into an established therapeutic modality in the management of the patient with irreversible intestinal failure. It is performed mainly in patients with short bowel syndrome (SBS) and those who develop severe complications due to total parenteral nutrition (TPN).  The goal of transplantation is to eliminate the need for TPN and to reverse or prevent TPN associated liver disease. 

 

Intestinal failure results from surgical resection, congenital defect or disease-associated loss of absorption and is characterized by the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance. Some conditions are more closely associated with pediatric intestinal failure while others are more common with intestinal failure in adults.

 

The following are pediatric conditions causing intestinal failure:

  • Short bowel syndrome following extensive bowel surgeries (midgut volvulus)
  • Congenital malformations (e.g. intestinal atresia, gastroschisis, aganglionosis)
  • Absorptive impairment (e.g. microvillus involution disease, chronic intestinal pseudo-obstruction)
  • Infections of gastrointestinal tract (e.g. necrotizing enterocolitis)

 

The following are adult conditions causing intestinal failure:

  • Crohn’s disease
  • Tumors of the mesenteric root and retroperitoneum (e.g. desmoid tumor)
  • Short bowel syndrome following extensive surgeries secondary to mesenteric ischemia (following thrombosis, embolism, volvulus or trauma)
  • Chronic intestinal pseudo-obstruction
  • Small bowel tumors such as Gardner’s Syndrome (familial colorectal polyposis) 

 

Short Bowel Syndrome

Short bowel syndrome is a condition in which the absorbing surface of the small intestine is inadequate due to extensive disease or surgical removal of a large portion of small intestine.

 

The small intestine, particularly the ileum, can adapt to some functions of the diseased or removed portion over a period of 1 to 2 years. Prognosis for recovery depends on the degree and location of the small intestine damage. Therapy is focused on achieving adequate macro and micro nutrient uptake in the remaining small bowel. Pharmacologic agents have been studied to increase villous proliferation and slow transit times, and surgical techniques have been advocated to optimize remaining small bowel. However, some patients with short bowel syndrome are unable to obtain adequate nutrition from enteral feeding and become chronically dependent on total parenteral nutrition (TPN). Patients with complications from TPN may be considered candidates for small bowel transplant. 

 

Total parenteral nutrition (TPN) is the current standard of care for patients with intestinal failure. The chronic use of TPN is often associated with life-threatening complications including:

  • Catheter related sepsis
  • Catheter related thrombosis
  • Severe dehydration
  • Parenteral nutrition associated liver disease (PNALD)

 

Small bowel (intestinal) transplant should be recommended in patients with the following conditions:

  1. Failure of parenteral nutrition
    • Impending or overt liver failure
    • Thrombosis of 2 or more central veins
    • Two ore more episodes per year of systemic sepsis secondary to line infections
    • Frequent episodes of dehydration
  2. High risk of death
  3. Severe short bowel syndrome (gastrotomy, duodenostomy, residual small bowel <10 cm in infants and <20 cm in adults)
  4. Frequent hospitalization, narcotic dependency or pseudoobstruction
  5. Unwillingness to accept long-term parenteral nutrition (TPN)

 

Small bowel transplant may be considered a means to avoid end stage liver failure, thus avoiding a multivisceral organ transplant. 

 

Most of the published literature consists of case series, mainly reported by single centers in the United States, Japan and Europe. Many case series have included small bowel/liver transplantation and multivisceral transplantation.

 

Reasons for transplantation were mainly short bowel syndrome. Other reasons include congenital enteropathies and motility disorders. The most common outcomes reported were survival rates and weaning off TPN. Several studies have presented survival rates by type of transplantation, while others have combined all types of transplants when reporting survival rates. When survival rates were reported by type of transplant, isolated small bowel transplantation had higher survival rates than multivisceral transplants.

 

The number of patients who undergo an intestinal transplant is much lower than other forms of organ transplantation, and there are fewer centers that perform it. The outcomes in patients undergoing intestinal transplant has improved significantly compared with early efforts, with improvements in the immunosuppression protocols and early detection and treatment of rejection. Graft survival in adult and pediatric patients is similar.  

 

Living Donor Transplants

Cadaveric intestines are most commonly used, but recently there has been interest in using a portion of intestine harvested from a living related donor. Potential advantages of living donor include the ability to plan transplantation electively and better antigen matching, leading to improved management of rejection.

 

Most of the published literature consists of case series. In general survival rates of recipients with living donors are comparable to rates for recipients of cadaveric donations. Living related donors were reported to have an uneventful recovery. Weight loss and diarrhea were reported among donors, but recovery was without complications.

 

Summary

Small bowel transplant is infrequently performed compared to other forms of organ transplantation. Most of the published literature is case series mainly reported by single centers. Risks after small bowel transplant are high, particularly related to infection, but may be balanced against the need to avoid the long-term complications of total parenteral nutrition (TPN) dependence. In addition, early small bowl transplant may prevent the need for a later combined liver/small bowel transplant. The evidence is sufficient to determine that the technology results in a meaningful improvement in net health outcomes.

 

Retransplantation

A few case series from single institutions and a single analysis of data from the United Network for Organ Sharing database have provided evidence on the use of retransplantation in patients who have failed primary small bowel transplant. The most common causes of graft loss in small bowel transplant are infection, rejection (acute and chronic) and technical or clinical complications. Careful patient selection, post-transplant immunosuppression and patient management are essential for successful long term outcomes.

 

Although the literature is limited in quantity, the available data have suggested reasonably high survival rates after small bowel retransplantation in patients who continue to meet all eligibility criteria for transplantation. The evidence is sufficient to determine that the technology results in a meaningful improvement in net health outcomes. 

 

Practice Guidelines and Position Statements

American Gastroenterological Association

In 2003, the American Gastroenterological Association produced a medical position statement on short bowel syndrome and intestinal transplantation. It recommends dietary, medical and surgical solutions. Indications for intestinal transplant mirror those of Medicare in patients who fail TPN therapy for one of the following reasons:

  • Impending or overt liver failure (increased serum bilirubin and/or liver enzyme levels, splenomegaly, thrombocytopenia, gastroesophageal varicies, coagulopathy, stomal bleeding, hepatic fibrosis or cirrhosis)
  • Thrombosis of central venous channels (2 thromboses in subclavian, jugular or femoral veins)
  • Frequent central line related  sepsis (2 episodes of systemic sepsis secondary to line infection per year, 1 episode of line related fungemia, septic shock, or acute respiratory distress syndrome).
  • Frequent severe dehydration.

 

Until better data become available, these parameters are likely to be widely recognized as the indications for intestinal transplantation.

 

American Society of Transplantation 

In 2001, the American Society of Transplantation issued a position paper on indications for pediatric intestinal transplantation. The position paper included the following:

“Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal transplantation include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Children with liver dysfunction should be considered for isolated intestinal transplantation before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present.”

 

Organ Procurement and Transplantation Network (OPTN)

In 2018, the Organ Procurement and Transplantation Network (OPTN) policy for allocation of intestines includes the following:

Each intestine candidate is assigned a status that reflects the candidate’s medical condition. Candidates may be assigned any of the following:

  • Status 1 
  • Status 2 
  • Inactive status

 

To assign an intestine candidate status 1, the candidate’s transplant program must submit a Status 1 Justification Form to the OPTN Contractor. A candidate may be assigned status 1 if the candidate has any of the following conditions: 

  • Liver function test abnormalities 
  • No vascular access through the subclavian, jugular, or femoral veins for intravenous feeding 
  • Medical indications that warrant intestinal organ transplantation on an urgent basis

 

Any active candidate that does not meet the criteria for status 1 must be registered as status 2.

 

If the candidate is temporarily unsuitable for transplant, then the candidate’s transplant program may classify the candidate as inactive and the candidate will not receive any intestine offers.

 

Prior Approval:

 

Prior approval is required.

 

Policy:

See also medical policy 07.03.05 Small Bowel/Liver and Nultivisceral Transplant

 

Cadaveric Small Bowel Transplant

A small bowel transplant using a cadaveric intestine may be considered medically necessary in adult and pediatric patients when ALL of the following criteria is met:

  • Intestinal failure characterized by loss of absorption and the inability to maintain protein-energy, fluid, electrolyte or micronutrient balance, AND
  • Who have established long-term dependency on total parenteral nutrition (TPN) and are developing or have developed severe complications due to total parenteral nutrition (TPN) to include one or more of the following:
    • Development of progressive liver failure due to TPN induced liver injury and liver disease is felt to be reversible (clinical indications of liver failure include: increased serum bilirubin or liver enzyme levels, splenomegaly, thrombocytopenia, gastroesophageal varices, coagulopathy, stomal bleeding, hepatic fibrosis or cirrhosis) (small bowel transplant may be considered a technique to avoid end-stage liver failure related to chronic TPN, thus avoiding the necessity of a small bowel/liver or multivisceral transplant); OR 
    • Thrombosis of two or more major central venous channels (subclavian, jugular, or femoral veins); OR 
    • Frequent central line related sepsis
      • 2 or more episodes of line-induced systemic sepsis per year
      • 1 episode of line-related fungemia, septic shock, or acute respiratory distress syndrome; OR
    • Frequent episodes of dehydration despite total parenteral nutrition (TPN) and intravenous fluid supplement.

Small bowel transplant would be considered not medically necessary in adult or pediatric patients who do not meet the above criteria and are able to tolerate total parenteral nutrition (TPN).

 

Living Donor Small Bowel Transplant

Small bowel transplant using a living donor intestine may be considered medically necessary only when a cadaveric intestine is not available for transplantation in a patient who meets the above criteria for a cadaveric small bowel transplant. 

 

Small bowel transplant using a living donor is considered not medically necessary in all other situations.

 

Retransplant

Retransplantation in individuals with failed prior small bowel transplant due to non-function of grafted organ, acute rejection requiring enterectomy (surgical removal of a portion of the intestine) or chronic rejection, or return of disease may be considered medically necessary if the individual meets the criteria for small bowel transplantation above.

 

Policy Guidelines

 

Potential contraindications to solid organ transplant are subject to judgement of the transplant center:

  • Known current malignancy, including metastatic cancer
  • Recent malignancy with high risk of recurrence
  • History of cancer with moderate risk of recurrence
  • Untreated systemic infection making immunosuppression unsafe, including chronic infection
  • Other irreversible end stage disease not attributed to intestinal failure
  • Systemic disease that could be exacerbated by immunosuppression
  • Psychosocial conditions or chemical dependency affecting ability to adhere to therapy    

 

Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • 44135 Intestinal allotransplantation; from cadaver donor
  • 44136 Intestinal allotransplantation from living donor

 

Selected References:

  • Steinman TI, Becker BN, Frost AE et al. Guidelines for the referral and management of patients eligible for solid organ transplantation. Transplantation 2001; 71(9):1189-204.
  • O’Keefe SJ, Buchman AL, Fishbein TM et al. Short bowel syndrome and intestinal failure: consensus definitions and overview. Clin Gastroenterol Hepatol 2006; 4(1): 6-10.
  • American Gastroenterological Association. American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation. Gastroenterology. 2003 Apr;124(4):1105-10.
  • Tzvetanov IG, Oberholzer J, Benedetti E. Current status of living donor small bowel transplantation. Curr Opin Organ Transplant. 2010 Jun;15(3):346-8.
  • Gangemi A, Tzvetanov IG, Beatty E et al. Lessons learned in pediatric small bowel and liver transplantation from living-related donors. Transplantation. 2009 Apr 15;87(7):1027-30.
  • Giuliana Testa, M.D., Fabrizio Panaro, M.D., Stefano Schena, M.D., Mark Holterman, M.D., Herand Abcarian, M.D. and Enrico Benedetti, M.D. Annals of Surgery, 2004 November; 240(5); 779-784. Living Related Small Bowel Transplantation. 
  • CMS. National Coverage Determination (NCD) for Intestinal and Multi-Visceral Transplantation (260.5).
  • UpToDate Overview of Intestinal and Multivisceral Transplantation. Farrukh A. Khan, M.D., FACS, Gennaro Selvaggi, M.D. Topic last updated September 16, 2018.
  • Medscape. Intestinal Transplantation. Stuart M. Greenstein, M.D. Updated March 5, 2012.
  • Medscape. Pediatric Intestinal and Multivisceral Transplantation. Seigo Nishida, M.D., PhD. Updated May 30, 2012.
  • UpToDate. Overview of Intestinal and Multivisceral Transplantation. Farrukh A Khan, M.D., FACS, Gennaro Selvaggi, M.D., Topic last updated January 8, 2016.
  • UpToDate. Management of the Short Bowel Syndrome in Children. Danielle A Stamm R.N., MSN, FNP-BC, Christopher Duggan M.D., MPH. Topic last updated July 13, 2018.
  • UpToDate. Management of the Short Bowel Syndrome in Adults. John K. DiBaise M.D. Topic last updated September 24, 2018 
  • Medscape. Stuart M. Greestein, M.D. et. al. Intestinal Transplantation, updated August 17, 2014.
  • Organ Procurement and Transplant Network Allocation of Livers and Liver-Intestines. 
  • Organ Procurement and Transplant Network Intestine, Allocation of Intestines.
  • PubMed. Intestinal and Multivisceral Retransplantation Results: Literature Review. Transplant Proc. 2013 Apr:45(3):1133-6.
  • PubMed. Kaufman SS, Atikinson JB, et. al. Indications for Pediatruc Intestinal Transplantation: A Position Paper of the American Society of Transplantation. Pediatr Transplant 2001 Apr 5(2):80-7
  • Benedetti Enrico, Holterman Mark, et. al. Living Related Segmental Bowel Transplantation from Experimental to Standardized Procedure. Ann Sug. 2006;244(5):694-699
  • PubMed. Sudan D. Long Term Outcomes and Quality of Life after Intestine Transplantation, Curr Opin Organ Transplant 2010 Jun:15(3):357-60
  • PubMed. Desai CS, Khan KM, et. al. Intestinal Retransplantation: Analysis of Organ Procurement and Transplantation Network Database. Transplantation 2012 Jan 15:93(1):120-5
  • Yildix Dogu Baris, Where Are We at With Short Bowel Syndrome and Small Bowel Transplant? World Journal of Transplantation, 2012 December 24;296):95-103
  • Trevizol AP, David AI, Yamashita ET. et.al. Intestinal and Multivisceral Retransplantation Results: Literature Review. Transplant Proc. Apr 2013;45(3):1133-1136
  • O’Keefe SJ, Buchman A, Fishbein TM. et.al. Short Bowel Syndrome and Intestinal Failure: Consensus Definitions and Overview. Clin Gastroenterol Hepatol. Jan 2006;4(1):6-10
  • Benedetti E, Holterman M, Asolati M, et. al. Living related segmental bowel transplantation from experimental to standardized procedure. Ann Surg 2006;244:649-699.
  • Organ Procurement and Transplantation Network Identification of Transmissible Diseases, Policy 15. Effective October 2016.
  • OPTN/SRTR 2012 Annual Data Report: Intestine
  • Organ Procurement and Transplantation Network Data
  • UpToDate. Chronic Intestinal Pseudo Obstruction. Michael Camilleri M.D., Topic last updated July 18, 2016.
  • Blumberg E.A., Rogers C.C., American Society of Transplantation Infectious Diseases Guidelines 3rd Edition, Human Immunodeficiency Virus in Solid Organ Transplantationa. American Journal of Transplantation Volume 13, Issue s4, pages 169-178 
  • Lacaille F, Irtan S, Dupic L, et. al. Twenty-eight years of intestinal transplantation in Paris: experience of the oldest European center. Transpl Int. Feb 2017;30(2):178-186. PMID 27889929
  • Bharadwaj S, Tandon P, Gohel TD, et al. Current status of intestinal and multivisceral transplantation. Gastroenterol Rep (Oxf). Jan 26 2017. PMID 28130374
  • Loo L, Vrakas G, Reddy S, et al. Intestinal transplantation: a review. Curr Opin Gastroenterol. May 2017;33(3):203-211. PMID 28282321
  • Dore M, Junco PT, Andres AM, et al. Surgical rehabilitation techniques in children with poor prognosis short bowel syndrome. Eur J Pediatr Surg. Feb 2016;26(1):112-116. PMID 26535775
  • Rutter CS, Amin I, Russell NK, et al. Adult intestinal and multivisceral transplantation: experience from a single center in the United Kingdom. Transplant Proc. Mar 2016;48(2):468-472. PMID 27109980
  • Garcia Aroz S, Tzvetanov I, Hetterman EA, et al. Long-term outcomes of living-related small intestinal transplantation in children: A single-center experience. Pediatr Transplant. Jun 2017;21(4). PMID 28295952
  • Nagai S, Mangus RS, Anderson E, et al. Cytomegalovirus infection after intestinal/multivisceral transplantation: a single-center experience with 210 cases. Transplantation. Feb 2016;100(2):451-460. PMID 26247555
  • Timpone JG, Yimen M, Cox S, et al. Resistant cytomegalovirus in intestinal and multivisceral transplant recipients. Transpl Infect Dis. Apr 2016;18(2):202-209. PMID 26853894
  • Wu GS, Cruz RJ, Jr., Cai JC. Acute antibody-mediated rejection after intestinal transplantation. World J Transplant. Dec 24 2016;6(4):719-728. PMID 28058223
  • Cromvik J, Varkey J, Herlenius G, et al. Graft-versus-host disease after intestinal or multivisceral transplantation: a Scandinavian single-center experience. Transplant Proc. Jan-Feb 2016;48(1):185-190. PMID 26915866
  • UpToDate. Chronic Intestinal Pseudo-Obstruction. Michael Camileri M.D., Topic last updated July 18, 2016.
  • Ueno T, Wada M, Hoshino K, et. al. Impact of Intestinal Transplantation for Intestinal Failure in Japan. Transplant Proc 2014 Jul-Aug;46(6):2122-4. PMID 25131121
  • Lauro A, Zanfi C, Dazzi A, et. al. Disease related intestinal transplant in adults: results from a single center. Transplant Proc. Jan-Feb 2014:46(1);245-248. PMID 24507060
  • Florescu DF, Qui F, Langnas AN, et. al. Bloodstream infections during the first year after pediatric small bowel transplantation. Pediatr Infect Dis J. Jul 2012;31(7):700-704. PMID 22466325
  • Florescu DF, Langnas AN, Grant W, et. al. Incidence, risk factors and outcomes associated with cytomegalovirus disease in small bowel transplant recipients. Pediatr Transplant. May 2012;16(3):294-301. PMID 22212495
  • Florescu DF, Islam KM, Grant W, et. al. Incidence and outcome of fungal infections in pediatric small bowel transplant recipients. Transpl Infect Dis. Dec 2010;12(6):497-504. PMID 20626710
  • Calvo Pulido J, Jimenz Romero C, Morales Ruiz E. et.al. Renal failure associated with intestinal transplantation: our experience in Spain. Traplant Proc. Jul-aug 2014;46(6):2140-2142. PMID 25131125
  • Boyer O, Noto C, De Serre NP, et. al. Renal function and histology in children after small bowel transplantation. Pediatr Transplant. Feb 2013;17(1):65-72. PMID 22882667    
  • Esker B, Kubal CA, Fridell JA. et. al. Comparable outcomes in intestinal retransplantation: Single-center cohort study. Clin Transplant 2018 Jul;32(7):e13290. PMID 29782661

 

Policy History:

  • November 2018 - Annual Review, Policy Revised
  • November 2017 - Annual Review, Policy Revised
  • November 2016 - Annual Review, Policy Revised
  • November 2015 - Annual Review, Policy Revised
  • December 2014 - Annual Review, Policy Revised
  • February 2014 - Annual Review, Policy Revised
  • March 2013 - Annual Review, Policy Renewed
  • March 2012 - Annual Review, Policy Renewed
  • April 2011 - Annual Review, Policy Revised

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.