Background

Small 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 the small intestine. In adults, etiologies of short bowel syndrome include ischemia, trauma, volvulus, and tumors. In children, gastroschisis, volvulus, necrotizing enterocolitis, and congenital atresia are predominant causes.

Treatment

The small intestine, particularly the ileum, can adapt to some functions of the diseased or removed portion over a period of one to two years. Prognosis for recovery depends on the degree and location of small intestine damage. Therapy focuses on achieving adequate macro- and micronutrient 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. Patients with complications from total parenteral nutrition may be considered candidates for a small bowel transplant. Complications include catheter-related mechanical problems, infections, hepatobiliary disease, and metabolic bone disease. While cadaveric intestinal transplant is the most commonly performed transplant, there has been a recent interest in using living donors.

Intestinal transplants (including multivisceral and bowel/liver) represent a small minority of all solid organ transplants. In 2016, 147 intestinal transplants were performed in the U. S.; all were from cadaver donors.^1,

Regulatory Status

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

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation Title 21, parts 1270 and 1271. Small bowel transplants are included in these regulations..

Related Policies

• Small Bowel/Liver and Multivisceral Transplant (Policy #096 in the Surgery Section)

A. member has intestinal failure characterized by loss of absorption and the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance;
B. member has an established long-term dependence on total parenteral nutrition (TPN); and
C. member is developing or has developed severe complications due to total parenteral nutrition (TPN).

For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

Policy Guidelines: (Information to guide medical necessity determination based on the criteria contained within the policy statements above.)

General Criteria
Potential contraindications for solid organ transplant are subject to the judgment of the transplant center include the following:

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

Patients who are developing or have developed severe complications due to total parenteral nutrition (TPN) include, but are not limited to, the following: multiple and prolonged hospitalizations to treat TPN-related complications (especially repeated episodes of catheter-related sepsis) or the development of progressive 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. In those receiving TPN, liver disease with jaundice (total bilirubin >3 mg/dL) is often associated with development of irreversible, progressive liver disease. The inability to maintain venous access is another reason to consider small bowel transplant in those who are dependent on TPN.


[RATIONALE: The policy was created in 2009 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through June 10, 2019.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Small Bowel Transplantation

Clinical Context and Test Purpose

The purpose of a small bowel transplant in patients who have an intestinal failure is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does a small bowel transplant improve the net health outcome in individuals with intestinal failure?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals with intestinal failure.

Interventions

The therapy being considered is a small bowel transplant. Small bowel transplantation is provided in a hospital setting by specialized staff who are equipped to perform the surgical procedure and manage postsurgical intensive care.

Comparators

The following practices are currently being used to make decisions about intestinal failure: medical management and parenteral nutrition.

Outcomes

The general outcomes of interest are overall survival (OS) and treatment-related adverse events (e.g., immunosuppression, graft failure, surgical complications, infections). See the Adverse Events section for a detailed discussion. Short-term follow-up ranges from immediately postsurgery to 30 days posttransplantation; lifelong follow-up (out to at 10 years or more given current survival data) is necessary due to ongoing immunosuppression drugs and risk of graft failure.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

a. To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
b. In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
c. To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
d. Studies with duplicative or overlapping populations were excluded.

This policy has been informed by 2 TEC Assessments conducted in the 1990s. The first TEC Assessment (1995) concluded that, in children, small bowel transplant was associated with improved survival rates compared with total parenteral nutrition (TPN) because the associated adverse events for small bowel transplant were offset by severe TPN-related complications.^2,The second TEC Assessment (1999) reevaluated the data on adults and concluded that, because it is not possible to predict which patients would survive longer on TPN vs small bowel transplant, transplantation may be considered a reasonable option in select adults.^3,

Case Series

Most of the published literature consists of case series, mainly reported by single-centers in the U. S., Japan, and Europe. Tables 1 and 2 summarize the characteristics and results of these case series, respectively. Many case series have included small bowel/liver transplantations and multivisceral transplantations (which are the focus of the separate policy on 'Small Bowel/Liver and Multivisceral Transplant' (Policy #096 in the Surgery Section).

Reasons for transplantations were mainly short bowel syndrome. Other reasons included 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 rates were reported by type of transplant, isolated transplantations had higher survival rates than multivisceral transplants (see Table 2).

Several investigators have reported higher survival rates in transplantations conducted more recently than those conducted earlier.^4,5, Reasons for improved survival rates in more recent years have been attributed to the development of more effective immunosuppressive drugs and the learning curve for the complex procedure.

Sudan (2010) published a review of the current literature on long-term outcomes after intestinal transplantation.^6, Sudan (2010) noted that intestinal transplantation had become standard therapy for patients with life-threatening complications from parenteral nutrition therapy. Data from current single-center series have indicated 1-year patient survival rates between 78% and 85% and 5-year or more survival rates between 56% and 61%. Concerning pediatric intestinal transplant patients, most achieve normal growth velocity at two years posttransplant. However, oral aversion is common; tube feedings are necessary for 45% of children. Sudan (2010) also reported on parental surveys of quality of life for pediatric transplant patients in which intestinal transplant patients appear to have modestly improved quality of life compared with those remaining on TPN and slightly worse than matched school-age controls without intestinal disease.

Authors of these series, as well as related 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. A separate discussion of adverse events follows the evidence tables.

Table 1. Summary of Key Case Series Characteristics for Transplantations

Study	Location	N	Median Age (Range), y	Interventions		Follow-Up (Range), mo
				Treatment	n
Lacaille et al (2017)7,	France	110	5.3 (0.4-19)	•Isolated IT • Combined liver IT • Multivisceral graft	60 45 5	Of 55 alive: •17 at <5 y •17 at 5-10 y •21 at ≥10 y
Garcia Aroz et al (2017)[8a]	U.S.	10	1.5 (0.7-13)	•Isolated IT • Combined liver IT	7 3	6/7 alive at follow-up ≥10 y
Dore et al (2016)8,	U.S.	30	0.2 (0.1-18)	•Isolated IT • Combined liver IT • Multivisceral graft	6 6 18	28 (4-175)
Rutter et al (2016)9,	U.K.	60	1.8 (0-8)	•Isolated IT • Multivisceral graft • Modified multivisceral	16 35 9	21.3 (0-95)
Lauro et al (2014)10,	Italy	46	34 (NR)	•Isolated IT • Combined liver IT • Multivisceral graft	34 6 6	51.3
Ueno et al (2014)[4b]	Japan	24	0-2 y: 6c 3-6 y: 6 7-18 y: 8 ≥19 y: 4	•Isolated IT • Combined liver IT	23 1	NR
Benedetti et al (2006)5,,a	U.S.	11	27 (1.5-50)	•Isolated IT	11	NR

IT: intestinal transplantation; NR: not reported.

^a All living donors.

^b Twelve living donors and 12 cadaveric donors.

^c Reported as age range and n.

Study	Interventions		Survival		Off Total Parenteral Nutrition
	Treatment	n	Years	%	Measure	%
Lacaille et al (2017)7,	•Isolated IT • Combined liver • Multivisceral graft	60 45 5	10 18 10 NR	59 54 48 NR	All combined at last FU	73
Garcia Aroz et al (2017)11,,a	•Isolated IT •Combined liver IT	7 3	All combined:	70	All combined at last FU	100
Dore et al (2016)8,	•Isolated IT • Combined liver IT • Multivisceral graft	6 6 18	9 10 2.5	83 33 67	All combined: • in 31 days • at last FU	71 62
Rutter et al (2016)9,	•Isolated IT • Multivisceral graft • Modified multivisceral	16 35 9	1 5 1 5 1 5	92 37 71 33 85 65		NR
Lauro et al (2014)10,	•Isolated IT • Combined liver IT • Multivisceral graft	34 6 6	All combined: 1 3 5 10	77 58 53 37		NR
Ueno et al (2014)[4b]	•Isolated IT •Combined liver IT	23 1	All combined: 1 5	86 68		80
Benedetti et al (2006)5,,a	•Isolated IT	11	1 3	82 82		100

^a All living donors.

^b Twelve living donors and 12 cadaveric donors.

Systematic Reviews

One issue discussed in intestinal transplantation literature is an earlier referral to avoid combined liver and intestine transplantation.^12, It has been suggested that removing the restriction on intestinal transplantation to patients who have severe complications from TPN and recommending earlier transplantation may improve survival. However, in a review of the status of intestinal transplantation, Vianna et al (2008) identified no randomized trials that compared intestinal transplantation with long-term TPN; therefore, optimal timing for earlier transplantation has not been established.^13,

Case Series

Wu et al (2016) investigated the incidence and risk factors of acute antibody-mediated rejection (ABMR) among patients undergoing intestinal transplantation (n=175).^14, Patients were 25 years of age. Acute ABMR was diagnosed by clinical evidence; histologic evidence of tissue damage; focal or diffuse linear C4d deposition; and circulating anti-human leukocyte antigen antibodies. Of the 175 intestinal transplants, 58% were liver-free small intestine grafts, 36% included a liver graft, and 6.3% were retransplantations. Eighteen cases of acute ABMR were identified, 14 (14%) among the patients undergoing first liver-free transplantation, 2 (3%) among patients undergoing liver/small bowel transplantations, and 2 (18%) among the patients undergoing retransplantation. Graft failure occurred in 67% of patients with acute ABMR. The presence of a donor-specific antibody and a liver-free graft were associated with the development of acute ABMR.

Florescu et al (2012) have published several retrospective reviews of complications in a cohort of 98 pediatric patients. Twenty-one (21.4%) of these children had an isolated small bowel transplant; the remainder had combined transplants. Their 2012 study reported that 68 (69%) of the 98 patients developed at least 1 episode of bloodstream infection.^15, Among patients with an isolated small bowel transplant, the median time to infection for those who developed one was 4.5 months (95% confidence interval, 2.4 to 6.7 months). Also in 2012, these researchers reported that 7 (7%) of 98 patients developed cytomegalovirus disease; only 1 had an isolated small bowel transplant.^16, Florescu et al (2010) previously reported that, in 25 (25.5%) of 98 cases reviewed who developed at least 1 episode of fungal infection, Candida infection was most common.^17, Mortality rates did not differ significantly between patients who did (32.3%) and did not develop a fungal infection (29.8%; p=0.46).

Several other series have reported on renal failure after intestinal transplantation. For example, Calvo Pulido et al (2014) reported on 21 adults who underwent intestinal transplantation; 17 were isolated small bowel transplants.^18, Thirteen (62%) patients experienced renal failure; the etiology included high ileostomy output, immunosuppression, and medical treatment. Boyer et al (2013) reported that 7 of 12 children who had an isolated small bowel transplant developed renal function complications at some point after surgery.^19, Before treatment, all patients had normal renal functioning.

Living Donor Transplants

Cadaveric intestines are most commonly used, but recently there has been an interest in using a portion of intestine harvested from a living, related donor. Potential advantages of a living donor include the ability to plan the transplantation electively and better antigen matching, leading to improved management of rejection. Case reports from the 1990s have reported on 1 or 2 patients with different lengths of the ileum or jejunum.^20,21,22,23, While there appear to be few complications to the donors, of the six cases reported, five recipients remain on TPN for at least part of their caloric intake. One patient was weaned off TPN.

Tables 1 and 2 provide details on case series that used living donors (Garcia Aroz et al [2017],^11, Ueno et al [2014],^4, Benedetti et al [2006]^5,). 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.

Human Immunodeficiency Virus-Positive Transplant Recipients

The 2013 HIV Organ Policy Equity Act in the U. S. permitted scientists to research organ donations from a person with HIV to another HIV-infected person.^24, In 2015, the Organ Procurement and Transplant Network updated its policies to be consistent with the HIV Organ Policy Equity Act.^25, The Organ Procurement and Transplant Network and United Network for Organ Sharing policies specify that organs from HIV-positive patients be used only for HIV-positive transplant recipients.

Current Organ Procurement and Transplantation policy permits HIV-positive transplant candidates.^26,

The British HIV Association and the British Transplantation Society (2017) updated their guidelines on kidney transplantation in patients with HIV disease.^27, These criteria may be extrapolated to other organs:

• Adherent with treatment, particularly antiretroviral therapy
• Cluster of differentiation 4 count greater than 100 cells/mL (ideally >200 cells/mL) for at least 3 months
• Undetectable HIV viremia (<50 HIV-1 RNA copies/mL) for at least 6 months
• No opportunistic infections for at least six months
• No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.

Small bowel transplant is infrequently performed, and only relatively small case series, generally single-center, are available. 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 TPN dependence. In addition, early small bowel transplant may obviate the need for a later combined liver/small bowel transplant. Guidelines and U.S. federal policy no longer view HIV infection as an absolute contraindication for solid organ transplantation.

Small Bowel Retransplantation

Clinical Context and Test Purpose

The purpose of small bowel retransplants in patients who have failed small bowel transplant and do not have contraindication(s) for retransplant is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does small bowel retransplant improve the net health outcome in individuals whose small bowel transplant has failed?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals who have failed small bowel transplant and do not have contraindication(s) for retransplant.

Interventions

The therapy being considered is a small bowel retransplant. Small bowel transplantation is provided in a hospital setting by specialized staff who are equipped to perform the surgical procedure and manage postsurgical intensive care.

Comparators

The following practices are currently being used to make decisions about the intestinal failure of an initial small bowel transplant: medical management and parenteral nutrition.

The general outcomes of interest are OS and treatment-related adverse events (e.g., immunosuppression, graft failure, surgical complications, infections). See the Adverse Events section for initial transplants for detailed discussion. Short-term follow-up ranges from immediately postsurgery to 30 days posttransplantation; lifelong follow-up (out to at 10 years or more given current survival data) is necessary due to ongoing immunosuppression drugs and risk of graft failure.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

a. To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
b. In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
c. To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
d. Studies with duplicative or overlapping populations were excluded.

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 failed primary small bowel transplant. Case series characteristics and results are detailed in Tables 3 and 4, respectively.

Desai et al (2012) have published the most comprehensive reporting of outcomes after repeat small bowel transplant in the U. S.^28, They evaluated data for patients in the United Network for Organ Sharing database who underwent small bowel transplants in the U. S. between 1987 and 2009.

Table 3. Summary of Key Case Series Characteristics for Retransplantations

Study	Location	N	Median Age (Range), y	Interventions		Follow-Up (Range), mo
				Treatment	n
Lacaille et al (2017)7,	France	10	13 (5-16)	•Isolated IT • Combined liver IT	3 7	4
Desai et al (2012)28,	U.S.	72 adults 77 children	NR	Adults: •Isolated IT • Combined liver IT Children: • Isolated IT • Combined liver IT	41 31 28 49	NR
Abu-Elmagd et al(2009)29,	U.S.	47	NR	•Isolated IT • Combined liver IT • Multivisceral graft	31 7 9	NR

IT: intestinal transplantation; NR: not reported.

Table 4. Summary of Key Case Series Results for Retransplantations

Study	Interventions		Survival		Off TPN
	Treatment	n	Years	%
Lacaille et al (2017)7,	•Isolated IT • Combined liver IT	3 7	All combined at last follow-up:	30	NR
Desai et al (2012)28,	Adults: •Isolated IT • Combined liver IT Children: • Isolated IT • Combined liver IT	41 31 28 49	Adults: 1/3/5 1/3/5 Children: 1/3/5 1/3/5	80/47/29 63/56/47 81/74/57 42/42/42	NR
Abu-Elmagd et al (2009)29,	•Isolated IT • Combined liver IT • Multivisceral graft	31 7 9	All combined: 1 5	69 47	NR

IT: intestinal transplantation; NR: not reported; TPN: total parenteral nutrition.

Section Summary: Small Bowel Retransplantation

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

Summary of Evidence

For individuals who have intestinal failure who receive a small bowel transplant, the evidence includes case series. The relevant outcomes are OS, morbid events, and treatment-related mortality and morbidity. Small bowel transplant is infrequently performed, and only relatively small case series, generally single-center, are available. 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 dependence. In addition, early small bowel transplant may obviate the need for a later combined liver/small bowel transplant. Transplantation is contraindicated in patients in whom the procedure is expected to be futile due to comorbid disease or in whom posttransplantation care is expected to worsen comorbid conditions significantly. Guidelines and U.S. federal policy no longer view HIV infection as an absolute contraindication for solid organ transplantation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have failed small bowel transplant without contraindication(s) for retransplant who receive a small bowel retransplant, the evidence includes case series. The relevant outcomes are OS, morbid events, and treatment-related mortality and morbidity. Data from a small number of patients undergoing retransplantation are available. Although limited in quantity, the available data have suggested a reasonably high survival rate after small bowel retransplantation in patients who continue to meet criteria for transplantation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

SUPPLEMENTAL INFORMATION

Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 2 physician specialty societies and 2 academic medical centers while this policy was under review in 2009. The consensus of those providing input was that small bowel transplant should be performed in patients who are developing severe total parenteral nutrition-related complications and that small bowel transplant from living donors may be considered when cadaveric intestinal transplants are not available.

Practice Guidelines and Position Statements

American Gastroenterological Association

The American Gastroenterological Association (2003) produced a medical position statement on short bowel syndrome and intestinal transplantation.^30, It recommended dietary, medical, and surgical solutions. Indications for intestinal transplantation mirrored those of the Centers for Medicare & Medicaid Services. 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."

The American Society of Transplantation (2001) issued a position paper on indications for pediatric intestinal transplantation.^31,The Society listed the following disorders in children as potentially treatable by intestinal transplantation: short bowel syndrome, defective intestinal motility, and impaired enterocyte absorptive capacity. Contraindications for intestinal transplant to treat pediatric patients with intestinal failure are similar to those of other solid organ transplants: profound neurologic disabilities, life-threatening comorbidities, severe immunologic deficiencies, nonresectable malignancies, autoimmune diseases, and insufficient vascular patency.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in June 2019 did not identify any ongoing or unpublished trials that would likely influence this review.]
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Isolated Small Bowel Transplant
Small Bowel Transplant, Isolated

References:
1. U. S. Department of Health and Human Services (DHHS). Organ Procurement and Transplantation Network National Data. 2018; https://optn.transplant.hrsa.gov/data/. Accessed August 29, 2019.

2. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Small bowel transplant. TEC Assessments. 1995;Volume 10:Tab 27.

3. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Small bowel transplants in adults and multivisceral transplants. TEC Assessments. 1999;Volume 14:Tab 9.

4. Ueno T, Wada M, Hoshino K, et al. Impact of intestinal transplantation for intestinal failure in Japan. Transplant Proc. Jul-Aug 2014;46(6):2122-2124. PMID 25131121.

5. Benedetti E, Holterman M, Asolati M, et al. Living related segmental bowel transplantation: from experimental to standardized procedure. Ann Surg. Nov 2006;244(5):694-699. PMID 17060761.

6. Sudan D. Long-term outcomes and quality of life after intestine transplantation. Curr Opin Organ Transplant. Jun 2010;15(3):357-360. PMID 20445450.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. Matarese LE, Costa G, Bond G, et al. Therapeutic efficacy of intestinal and multivisceral transplantation: survival and nutrition outcome. Nutr Clin Pract. Oct 2007;22(5):474-481. PMID 17906271.

13. Vianna RM, Mangus RS, Tector AJ. Current status of small bowel and multivisceral transplantation. Adv Surg. Oct 2008;42:129-150. PMID 18953814.

14. 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.

15. Florescu DF, Qiu 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.

16. 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.

17. 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.

18. Calvo Pulido J, Jimenez Romero C, Morales Ruiz E, et al. Renal failure associated with intestinal transplantation: our experience in Spain. Transplant Proc. Jul-Aug 2014;46(6):2140-2142. PMID 25131125.

19. 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.

20. Fujimoto Y, Uemoto S, Inomata Y, et al. Living-related small bowel transplant: management of rejection and infection. Transplant Proc. Feb 1998;30(1):149. PMID 9474986.

21. Gruessner RW, Sharp HL. Living-related intestinal transplantation: first report of a standardized surgical technique. Transplantation. Dec 15 1997;64(11):1605-1607. PMID 9415566.

22. Jaffe BM, Beck R, Flint L, et al. Living-related small bowel transplantation in adults: a report of two patients. Transplant Proc. May 1997;29(3):1851-1852. PMID 9142299.

23. Tesi R, Beck R, Lambiase L, et al. Living-related small-bowel transplantation: donor evaluation and outcome. Transplant Proc. Feb-Mar 1997;29(1-2):686-687. PMID 9123480.

24. Colfax G. HIV Organ Policy Equity (HOPE) Act Is Now Law. 2013; https://obamawhitehouse.archives.gov/blog/2013/11/21/hiv-organ-policy-equity-hope-act-now-law. Accessed August 29, 2019.

25. United Network for Organ Sharing (UNOS). OPTN policies, procedures implemented to support HOPE Act. 2015; http://www.unos.org/optn-policies-procedures-implemented-to-support-hope-act/. Accessed August 29, 2019.

26. Organ Procurement and Transplantation Network (OPTN). Organ Procurement and Transplantation Network Policies. 2018; https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf. Accessed August 29, 2019.

27. Working Party of the British Transplantation Society. Kidney and Pancreas Transplantation in Patients with HIV. Second Edition (Revised). British Transplantation Society Guidelines Macclesfield, UK: British Transplantation Society; 2017.

28. Desai CS, Khan KM, Gruessner AC, et al. Intestinal retransplantation: analysis of Organ Procurement and Transplantation Network database. Transplantation. Jan 15 2012;93(1):120-125. PMID 22113492.

29. 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):567-581. PMID 19730240.

30. American Gastroenterological Association. American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation. Gastroenterology. Apr 2003;124(4):1105-1110. PMID 12671903.

31. Kaufman SS, Atkinson JB, Bianchi A, et al. Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation. Pediatr Transplant. Apr 2001;5(2):80-87. PMID 11328544.

32. Centers for Medicare and Medicaid Services. National Coverage Determination for Intestinal and Multi-visceral Transplantation (260.5). 2006; https://www.cms.gov/medicare-coverage-database/details/ncd- details.aspx?NCDId=280&ncdver=2&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=All&KeyW ord=intestinal+transplantation&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAACAAAAAAAA%3d %3d&. Accessed August 29, 2019.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

44132
44133
44135
44136
44715
44720
44721