Medical Policies - Surgery


Small Bowel/Liver and Multivisceral Transplant

Number:SUR703.009

Effective Date:10-15-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

A small bowel/liver transplant or multivisceral transplant may be considered medically necessary for pediatric and adult patients with intestinal failure (characterized by loss of absorption and the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance) who have been managed with long-term total parenteral nutrition (TPN) and who have developed evidence of impending end-stage liver failure.

A small bowel/liver retransplant or multivisceral retransplant may be considered medically necessary after a failed primary small bowel/liver transplant or multivisceral transplant.

A small bowel/liver transplant or multivisceral transplant is considered experimental, investigational and/or unproven in all other situations.

NOTE: Refer to SUR703.001, Organ and Tissue Transplantation for general donor and recipient information.

Description:

Small bowel/liver transplantation is transplantation of an intestinal allograft in combination with a liver allograft, either alone or in combination with one or more of the following organs: stomach, duodenum, jejunum, ileum, pancreas, or colon.

Background

Small bowel transplants are typically performed in patients with short bowel syndrome (SBS), defined as an inadequate absorbing surface of the small intestine due to extensive disease or surgical removal of a large portion of small intestine. In some instances, SBS is associated with liver failure, often due to the long-term complications of total parenteral nutrition (TPN). These patients may be candidates for a small bowel/liver transplant or a multivisceral transplant, which includes the small bowel and liver with 1 or more of the following organs: stomach, duodenum, jejunum, ileum, pancreas, and/or colon. A multivisceral transplant is indicated when anatomic or other medical problems preclude a small bowel/liver transplant.

Intestinal transplants (including multivisceral and bowel/liver) represent a small minority of all solid organ transplants. (1)

General Considerations for Small Bowel/Liver and Multivisceral Transplantation

Potential Contraindications Subject to the Judgment of the Transplant Center:

1. Known current malignancy, including metastatic cancer;

2. Recent malignancy with high risk of recurrence;

3. History of cancer with a moderate risk of recurrence;

4. Systemic disease that could be exacerbated by immunosuppression;

5. Untreated systemic infection making immunosuppression unsafe, including chronic infection;

6. Other irreversible end-stage disease not attributed to intestinal failure;

7. Psychosocial conditions or chemical dependency affecting ability to adhere to therapy.

Small Bowel/Liver Specific Concerns

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. SBS is an example of intestinal failure.

Additionally, candidates should meet the following criteria:

Adequate cardiopulmonary status.

Documentation of patient compliance with medical management.

Evidence of intolerance of TPN includes, but is not limited to, multiple and prolonged hospitalizations to treat TPN-related complications, or the development of progressive but reversible liver failure. In the setting of progressive liver failure, small bowel transplant may be considered a technique to avoid end-stage liver failure related to chronic TPN, thus avoiding the necessity of a multivisceral transplant.

Regulatory Status

Small bowel/liver and multivisceral transplantation is a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration.

Rationale:

The policy was originally created in 1996 and updated with searches of the MedLine database. The most recent literature search was conducted through March 2017.

Transplantation of Small Bowel/Liver or Multivisceral Organs

A 1999 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment focused on multivisceral transplantation and offered the following conclusions: “Multivisceral transplantation in patients with small bowel syndrome, liver failure, and/or other gastrointestinal problems such as pancreatic failure, thromboses of the celiac axis and the superior mesenteric artery, or pseudo-obstruction affecting the entire gastrointestinal tract is associated with poor patient and graft survival. Pediatric and adult patients have a similar 2- and 5-year survival of 33% to 50%. However, without this procedure, it is expected that these patients would face 100% mortality.” (2)

The published literature consists of case series, mainly reported by single centers. Authors of these series, as well as reviews, have observed that while outcomes have improved over time, recurrent and chronic rejection and complications of immunosuppression continue to be obstacles to long-term survival.

Among recent publications is a 2016 report by Rutter et al. from the United Kingdom. (3) Between January 2007 and June 2015, 60 transplant procedures were performed in 54 patients. Of these, 35 were multivisceral transplants, 9 were modified multivisceral transplants, and 16 were small bowel transplants. Recipients’ median age was 47 years (range, 18-61 years). Median length of follow-up was 21.3 months (range, 0-95 months). One- and 5-year patient survival rates were 77% and 62%, respectively. One-year survival by type of procedure was 71% for multivisceral transplant, 85% for modified multivisceral transplant, and 92% for small bowel transplant. Five-year survival rates in these groups were 33%, 65% and 83%, respectively. Most deaths occurred in the first year after transplant.

A 2014 single-center Italian case series reported on 45 patients who received either intestinal transplants alone or a combined transplant procedure. (4) Twelve patients had small bowel/multivisceral transplants. Five of them had the procedure due to short-bowel syndrome (SBS), 2 due to chronic intestinal pseudo-obstruction, and 5 due to Gardner syndrome. Survival rates for the entire patient population were 77% at 1 year, 58% at 3 years, 53% at 5 years, and 37% at 10 years.

A 2013 single-center study in Sweden included 30 patients accepted for intestinal and multivisceral transplantation. (5) One- and 3-year survival rates were 68% and 61%, respectively. Among patients awaiting transplantation after being accepted as candidates, there was a 34% survival rate.

Also in 2013, Mangus et al. reported on 95 patients who underwent multivisceral transplantation with or without liver transplantation at a single U.S. center. (6) One-year patient survival rate was 72% and 3-year survival was 57%. Authors noted a learning curve, with a 48% survival rate for transplants performed between 2004 and 2007 and a 70% survival rate for operations between 2008 and 2010.

Complications

Several case series have focused on complications after small bowel and multivisceral transplantation. For example, in 2016 Nagai et al. reported on cytomegalovirus (CMV) infection after intestinal or multivisceral transplantation at a single center in the United States. (7) A total of 210 patients had an intestinal transplant, multivisceral transplant, or modified multivisceral transplant between January 2003 and June 2014. Median length of follow-up was 2.1 years. Thirty-four (16%) patients developed CMV infection a median of 347 days after transplantation. Nineteen patients had tissue invasive CMV disease. In a report from another U.S. center, 16 (19%) of 85 patients undergoing intestinal or multivisceral transplantation developed CMV infection a mean of 139 days (range, 14-243 days) postoperatively. (8)

In 2011 Wu et al. reported on 241 patients who underwent intestinal transplantation. (9) Of these, 147 (61%) had multivisceral transplants, 65 (27%) had small bowel transplants, and 29 (12%) had small bowel/liver transplants. There were 151 (63%) children and 90 (37%) adults. Twenty-two (9%) patients developed graft-versus-host disease (GVHD). Children younger than 5 years old were more likely to develop this condition; the incidence in this age group was 16 (13.2%) of 121 compared with 2 (6.7%) of 30 in children between 5 and 18 years and 9 (4.4%) of 90 in adults older than 18 years. In a 2016 series by Cromvik et al., 5 (19%) of 26 patients were diagnosed with GVHD after intestinal or multivisceral transplantation. (10) Risk factors for GVHD were malignancy as a cause of transplantation and neoadjuvant chemotherapy or brachytherapy before transplantation.

A 2012 study retrospectively reported on bloodstream infections among 98 children (>18 years) with small bowel/combined organ transplants. (11) Seventy-seven (79%) underwent small bowel transplant in combination with a liver, kidney or kidney and pancreas, and 21 had an isolated small bowel transplant. After a median follow-up of 52 months, 58 (59%) patients had survived. The 1-year survival rate was similar in patients with combined small bowel transplant (75%) and those with isolated small bowel transplant (81%). In the first year after transplantation, 68 (69.4%) patients experienced at least 1 episode of bloodstream infection. The 1-year survival rate for patients with bloodstream infections was 72% compared with 87% in patients without bloodstream infections (p=0.056 for difference in survival in patients with and without bloodstream infections).

HIV-Positive Transplant Recipients

No studies reporting on outcomes in HIV-positive (+) patients who received small bowel/liver or multivisceral transplants were identified in literature reviews.

In 2001, the American Society of Transplantation proposed that the presence of HIV or AIDS could be considered a contraindication to kidney transplant unless the following criteria were present. (12) These criteria may be extrapolated to other organs, such as multivisceral transplantation:

CD4 count greater than 200 cells/mm3 for more than 6 months;

HIV-1 RNA undetectable;

On stable antiretroviral therapy for more than 3 months;

No other complications from AIDS (e.g., opportunistic infection, including aspergillus, tuberculosis, coccidioidomycosis, resistant fungal infections, Kaposi’s sarcoma, or other neoplasm);

Meeting all other criteria for transplantation.

In 2006, the British HIV Association and the British Transplantation Society published guidelines for kidney transplantation in patients with HIV disease. (13) As noted, these criteria may be extrapolated to other organs. The guidelines recommended that any patient with end-stage organ disease with a life expectancy of at least 5 years is considered appropriate for transplantation under the following conditions:

• CD4 greater than 200 cells/mL for at least 6 months;

Undetectable HIV viremia (<50 HIV-1 RNA copies/mL) for at least 6 months;

Demonstrable adherence and a stable highly active antiretroviral therapy (HAART) regimen for at least 6 months;

Absence of AIDS-defining illness following successful immune reconstitution after HAART.

In 2013 the HIV Organ Policy Equity (HOPE) Act in the U.S. permitted scientists to research organ donations from a person with HIV to another HIV-infected person. (14) In 2015, the Organ Procurement and Transplant Network (OPTN) updated its policies to be consistent with the HOPE Act. (15) OPTN and United Network for Organ Sharing policies specify that organs from HIV-positive patients be used only for HIV-positive transplant recipients.

Section Summary: Transplantation of Small Bowel/Liver or Multivisceral Organs

These transplantation procedures are infrequently performed and only relatively small case series, generally single-center, are available. These series have shown a reasonably high posttransplant survival rates. Guidelines and U.S. federal policy no longer view HIV infection as an absolute contraindication for solid organ transplantation.

Retransplantation of Small Bowel/Liver or Multivisceral Organs

In 2013, Trevizol et al. reviewed literature on intestinal and multivisceral retransplantation. (16) They found articles from 2 centers. Mazariegos et al. reported on 15 retransplantations in 14 pediatric patients. (17) By the end of follow-up, 4 patients had died and 10 patients had a normal graft function. Total parenteral nutrition (TPN) was weaned at a mean of 32 days after retransplantation. A 2009 study by Abu-Elmagd et al. reported on 47 retransplants after 500 intestinal and multivisceral transplantations in adults and children. (18) Included were 31 intestinal retransplants, 9 multivisceral retransplants, and 7 intestinal/liver retransplants. For all types of retransplants combined, there is a 5-year survival rate of 47%.

Desai et al. reported intestinal retransplantation data from the Organ Procurement and Transplant Network (OPTN) database. (19) Between 1987 and 2009, there were 31 cases of small bowel/liver retransplants in adults and 49 in children. Among adults, 1-, 3-, and 5-year survival rates after retransplantation were 63.1%, 56.1%, and 46.8%, respectively. This compares with survival rates after primary small bowel/liver transplants of 67%, 53.3%, and 46% at 1, 3, and 5 years. Among children, there was a consistent 42.1% survival rate at 1, 3, and 5 years after retransplantation. Survival rates after primary small bowel/liver transplantation were 67.6%, 56.1%, and 51.4%, respectively.

Section Summary: Retransplantation of Small Bowel/Liver or Multivisceral Organs

Data from only a small number of patients undergoing retransplantation are available. Although limited in quantity, the available data after retransplantation have suggested reasonably high survival rates after small bowel/liver and multivisceral retransplantation in patients who continue to meet criteria for transplantation.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in March 2017 did not identify any ongoing or unpublished trials that would likely influence this review.

Practice Guidelines and Position Statements

American Gastroenterological Association (AGA)

In 2003, the AGA published a position statement on short bowel syndrome and intestinal transplantation. (20) It recommended dietary, medical, and surgical solutions. The statement additionally noted that only patients with life-threatening complications due to intestinal failure or long-term total parenteral nutrition have undergone intestinal transplantation. Indications for intestinal transplantation mirror those of the Centers for Medicare and Medicaid Services (CMS). The guidelines acknowledged the limitations of transplant for these patients. The statement recommended the following Medicare-approved indications, pending availability of additional data:

1. “Impending or overt liver failure.…

2. Thrombosis of major central venous channels….

3. Frequent central line-related sepsis….

4. Frequent severe dehydration.”

Medicare National Coverage

“Effective for services performed on or after April 1, 2001, this procedure [intestinal and multivisceral transplantation] is covered only when performed for patients who have failed total parenteral nutrition (TPN) and only when performed in centers that meet approval criteria.

1. Failed TPN – The TPN delivers nutrients intravenously, avoiding the need for absorption through the small bowel. TPN failure includes the following:

Impending or overt liver failure due to TPN induced liver injury. The clinical manifestations include elevated serum bilirubin and/or liver enzymes, splenomegaly, thrombocytopenia, gastroesophageal varices, coagulopathy, stomal bleeding or hepatic fibrosis/cirrhosis.

Thrombosis of the major central venous channels; jugular, subclavian, and femoral veins. Thrombosis of two or more of these vessels is considered a life-threatening complication and failure of TPN therapy. The sequelae of central venous thrombosis are lack of access for TPN infusion, fatal sepsis due to infected thrombi, pulmonary embolism, Superior Vena Cava syndrome, or chronic venous insufficiency.

Frequent line infection and sepsis. The development of two or more episodes of systemic sepsis secondary to line infection per year that requires hospitalization indicates failure of TPN therapy. A single episode of line-related fungemia, septic shock and/or acute respiratory distress syndrome are considered indicators of TPN failure.

Frequent episodes of severe dehydration despite intravenous fluid supplement in addition to TPN. Under certain medical conditions such as secretory diarrhea and non-constructible gastrointestinal tract, the loss of the gastrointestinal and pancreatobiliary secretions exceeds the maximum intravenous infusion rates that can be tolerated by the cardiopulmonary system.

Frequent episodes of dehydration are deleterious to all body organs particularly kidneys and the central nervous system with the development of multiple kidney stones, renal failure, and permanent brain damage.

2. Approved Transplant Facilities – Intestinal transplantation is covered by Medicare if performed in an approved facility. The criteria for approval of centers will be based on a volume of 10 intestinal transplants per year with a 1-year actuarial survival of 65 percent using the Kaplan-Meier technique.” (21)

Summary of Evidence

For individuals who have intestinal failure and evidence of impending end-stage liver failure who receive a small bowel and liver transplant alone or multivisceral transplant, the evidence includes case series. Relevant outcomes are overall survival, morbid events, and treatment-related mortality and morbidity. These procedures are infrequently performed and only relatively small case series, generally single-center, are available. These series have shown reasonably high postprocedural survival rates. Given exceedingly poor survival rates without transplantation of patients who have exhausted other treatments, evidence of postoperative survival from uncontrolled studies is sufficient to demonstrate that small bowel/liver and multivisceral transplantation provides a survival benefit in appropriately selected patients. Transplantation is contraindicated for patients in whom the procedure is expected to be futile due to comorbid disease or in whom posttransplantation care is expected to significantly worsen comorbid conditions. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have a failed small bowel and liver or multivisceral transplant without contraindications for retransplant who receive a small bowel and liver retransplant alone or multivisceral retransplant, the evidence includes case series. Relevant outcomes are overall survival, morbid events, and treatment-related mortality and morbidity. Although limited in quantity, the available post retransplantation data has suggested reasonably high survival rates. Given exceedingly poor survival rates without retransplantation of patients who have exhausted other treatments, evidence of postoperative survival from uncontrolled studies is sufficient to demonstrate that retransplantation provides a survival benefit in appropriately selected patients. Retransplantation is contraindicated for patients in whom the procedure is expected to be futile due to comorbid disease or in whom posttransplantation care is expected to significantly worsen comorbid conditions. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

44120, 44121, 44132, 44133, 44135, 44136, 44137, 44715, 44720, 44721, 44799, 47133, 47135, 47140, 47141, 47142, 47143, 47144, 47145, 47146, 47147, 47399

HCPCS Codes

S2053, S2054, S2055, S2152

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. OPTN – Allocation of Intestines (March 1, 2017). Organ Procurement and Transplantation Network. Available at: <http://optn.transplant.hrsa.gov> (accessed March 22, 2017).

2. Small Bowel Transplants in Adults and Multivisceral Transplants. Chicago, Illinois: Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). TEC Assessments (1999) Volume 14, Tab 9.

3. 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):468-72. PMID 27109980

4. Lauro A, Sanfi C, Dassi A, et al. Disease-related intestinal transplant in adults: results from a single center. Transpl Proc. Jan-Feb 2014; 46(1):245-8. PMID 24507060

5. Varkey J, Simren M, Bosaeus I, et al. Survival of patients evaluated for intestinal and multivisceral transplantation - the Scandinavian experience. Scand J Gastroenterol. Apr 2 2013; 48(6):702-11. PMID 23544434

6. Mangus RS, Tector AJ, Kubal CA, et al. Multivisceral transplantation: expanding indications and improving outcomes. J Gastrointest Surg. Jan 2013; 17(1):179-86; discussion p 86-7. PMID 23070622

7. 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):451-60. PMID 26247555

8. Timpone JG, Yimen M, Cox S, et al. Resistant cytomegalovirus in intestinal and multivisceral transplant recipients. Transpl Infect Dis. Apr 2016; 18(2):202-9. PMID 26853894

9. Wu G, Selvaggi G, Nishida S, et al. Graft-versus-host disease after intestinal and multivisceral transplantation. Transplantation. Jan 27 2011; 91(2):219-24. PMID 21076376

10. Cromvik J, Varkey J, Herlenius G, et al. Graft-versus-host disease after intestinal or multivisceral transplantation: a Scandinavian single-center experience. Transpl Proc. Jan-Feb 2016; 48(1):185-90. PMID 26915866

11. Florescu DF, Qiu F, Langnas AN, et al. Bloodstream Infections during the First Year after Pediatric Small Bowel Transplantation. Pediatr Infect Dis J. Mar 29 2012; 31(7): 700-4. PMID 22466325

12. Steinman TI, Becker BN, Frost AE et al. Guidelines for the referral and management of patients eligible for solid organ transplantation. Transplantation. May 15 2001; 71(9):1189-204. PMID 11397947

13. Bhagani S, Sweny P, Brook G. Guidelines for kidney transplantation in patients with HIV disease. HIV Med. Apr 2006; 7(3):133-9. PMID 16494626

14. Colfax G. HIV Organ Policy Equity (HOPE) Act is Now Law (November 21, 2013). Available at: <https://www.obamawhitehouse.gov> (accessed March 22, 2017).

15. OPTN – Policies Management (March 1, 2017). Organ Procurement and Transplantation Network. Available at: <http://optn.transplant.hrsa.gov> (accessed March 22, 2017).

16. Trevizol AP, David AI, Yamashita ET, et al. Intestinal and multivisceral retransplantation results: literature review. Transplant Proc. Apr 2013; 45(3):1133-6. PMID 23622645

17. Mazariegos GV, Soltys K, Bond G, et al. Pediatric intestinal retransplantation: techniques, management, and outcomes. Transplantation. Dec 27 2008; 86(12):1777-82. PMID 19104421

18. Abu-Elmagd KM, Costa G, Bond GJ, et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg. Oct 2009; 250(4):567-81. PMID 19730240

19. Desai CS, Khan KM, Gruessner AC, et al. Intestinal retransplantation: analysis of Organ Procurement and Transplantation Network database. Transplantation. Jan 15 2012; 93(1):120-5. PMID 22113492

20. American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation. Gastroenterology. Apr 2003; 124(4):1105-10. PMID 12671903

21. CMS – National Coverage Determination for Intestinal and Multi-Visceral Transplantation (260.5) (2006). National Centers for Medicare and Medicaid Services. Available at: <http://www.cms.gov> (accessed March 22, 2017).

22. Small Bowel/Liver and Multivisceral Transplant. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (December 2016) Surgery: 7.03.05.

Policy History:

Date Reason
10/15/2018 Reviewed. No changes.
6/1/2017 Document updated with literature review. Coverage unchanged.
11/1/2016 Reviewed. No changes.
2/1/2016 Document updated with literature review. The following was added: A small bowel/liver transplant or multivisceral transplant is considered experimental, investigational and/or unproven in all other situations.
2/1/2014 Document updated with literature review. The following changes were made to coverage: 1) “short bowel syndrome” changed to “intestinal failure”. 2) Intestinal failure defined. 3) A small bowel/liver retransplant or multivisceral retransplant may be considered medically necessary after a failed primary small bowel/liver transplant or multivisceral transplant. Title changed from: Liver, Small Bowel, and Multivisceral Transplants. CPT/HCPCS codes updated.
7/1/2004 Document updated
3/1/2000 Document updated
5/1/1996 Document updated
4/1/1996 New medical document

Archived Document(s):

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