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Aetna Aetna
Clinical Policy Bulletin:
Intestinal Transplantation
Number: 0605


Policy

Aetna considers intestinal transplantation medically necessary for persons who have failed total parenteral nutrition (TPN) when the selection criteria below are met.

Parenteral nutrition (see CPB 0061 - Nutritional Support) entails the administration of micronutrients and macronutrients via catheters in central or peripheral veins.  In most cases, the central venous route is used.  For long-term TPN, a central catheter (e.g., Hickman, Broviac, PIC) is placed subcutaneously in the anterior chest.  Indicators of failed TPN are liver failure, thrombosis, frequency of infection, and dehydration as demonstrated in the following clinical situations:

  • Frequent episodes of severe dehydration despite intravenous fluid supplement in addition to TPN.  Under certain medical conditions such as secretory diarrhea and non-constructible gastro-intestinal (GI) tract, the loss of the GI and pancreatobiliary secretions exceeds the maximum intravenous infusion rates that can be tolerated by the cardiopulmonary system.  Frequent episodes of dehydration are detrimental to all body organs, especially the kidney and the central nervous system with the development of multiple kidney stones, renal failure, and permanent brain damage.
  • Frequent line infection and sepsis.  The development of 2 or more episodes of systemic sepsis due 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.
  • Impending or overt liver failure due to TPN-induced liver injury.  The clinical signs include elevated serum bilirubin and/or liver enzymes, splenomegaly, thrombocytopenia, gastro-esophageal varices, coagulopathy, stomal bleeding or hepatic fibrosis/cirrhosis.
  • Other complications leading to loss of vascular access.  TPN failure may due to inadequate TPN access, which is an indication for intestinal transplantation.
  • Thrombosis of the major central venous channels, jugular, subclavian, and femoral veins.  Thrombosis of 2 or more of these vessels is considered a life-threatening complication and failure of TPN therapy.  The consequence of central venous thrombosis is a lack of access for TPN infusion, fatal sepsis as a result of infected thrombi, pulmonary embolism, superior vena cava syndrome, or chronic venous insufficiency.

Selection Criteria: Aetna considers intestinal transplant medically necessary for the indications listed above for persons who meet the transplanting institution's protocol eligibility criteria.  In the absence of a protocol, Aetna considers intestinal transplant medically necessary for the indications listed above when all of the following selection criteria are met:

  1. Absence of acute or chronic active infections that are not effectively treated; and
  2. Adequate cardiovascular function (ejection fraction greater than or equal to 40 %); and
  3. Adequate liver and kidney function, defined as a bilirubin of less than 2.5 mg/dL and a creatinine clearance of greater than 50 ml/min/kg; and
  4. No active alcohol or chemical dependency that interferes with compliance to a strict treatment regimen.  Persons with a history of drug or alcohol abuse must be abstinent for at least 3 months before being considered a transplant candidate eligible for coverage; and
  5. No uncontrolled and/or untreated psychiatric disorders that interfere with compliance to a strict treatment regimen; and
  6. Absence of inadequately controlled HIV/AIDS, defined as:
  • CD4 count greater than 200 cells/mm3 for more than 6 months; and
  • HIV-1 RNA (viral load) undetectable; and
  • No other complications from AIDS, such as opportunistic infections (e.g., aspergillus, tuberculosis, Pneumocystis carinii pneumonia, toxoplasmosis encephalitis, cryptococcal meningitis, disseminated coccidioidomycosis, other resistant fungal infections) or neoplasms (Kaposi's sarcoma, non-Hodgkin's lymphoma); and
  • On stable anti-viral therapy for more than 3 months.

A combined intestinal and liver transplant is considered medically necessary for persons with advanced liver disease necessitating liver transplantation (see CPB 0596 - Liver Transplantation) who meet the medical necessity criteria above (other than the requirement for adequate liver function).  Note: In candidates for a combined transplant, adequacy of renal function should be assessed with a measured glomerular filtration rate (GFR), as a calculated GFR is inaccurate in advanced liver disease.

Contraindications: Intestinal transplant is considered not medically necessary for persons with the following contraindications:

  • Advanced neurological disorders (e.g., neuroaxonal dystrophy, Tay-Sachs disease, Niemann-Pick disease and variants, neuronal ceroid lipofuscinosis, and Huntington disease);
  • Congestive heart failure with refractory symptoms and ejection fraction less than 40 %;
  • Malignancy, other than non-melanomatous skin cancer, that is not effectively treated such that there is a substantial risk of recurrence;
  • Multi-organ failure;
  • Presence of other GI diseases (e.g., bleeding peptic ulcer, diverticulitis, chronic hepatitis);
  • Sepsis.

Aetna considers multi-visceral transplants from deceased donors medically necessary for adults and children who meet criteria for the combined small bowel/liver transplant and require 1 or more abdominal visceral organs to be transplanted due to concomitant organ failure or anatomical abnormalities that preclude a small bowel/liver transplant.

Aetna considers multi-visceral transplants experimental and investigational for individuals with neuroendocrine pancreatic tumors.

Aetna considers measurement of fecal calprotectin experimental and investigational as a test for intestinal allograft rejection because its clinical value has not been established.

See also CPB 0342 - Intestinal Rehabilitation Programs.



Background

Intestinal transplantation has become the treatment of choice for patients with chronic intestinal failure whose illness can not be maintained on total parenteral nutrition (TPN).  The term "intestinal failure" refers to gastro-intestinal (GI) function insufficient to meet body fluid and nutrient requirements; it includes short bowel syndrome (SBS) and severe motility disorders (e.g., chronic intestinal pseudo-obstruction syndrome in children and congenital intractable intestinal mucosa disorders).  Short bowel (also known as short gut) syndrome is a condition in which the absorbing surface of the small intestine is inadequate as a result of extensive disease or surgical removal of a large segment of the small intestine.  Patients with SBS are unable to obtain adequate nutrition from enteral feeding.

In infants, SBS is generally due to congenital anomalies.  Common causes of a SBS in infants and children include microvillus atrophy, intestinal atresia, midgut volvulus, complicated gastroschisis, aganglion syndrome, and necrotizing enterocolitis.  In adults, severe SBS usually occurs following a massive small bowel resection, which results in rapid intestinal transit and loss of absorptive function.  Common causes of SBS in adults include Crohn's disease, desmoid tumors (familial polyposis with Gardner’s syndrome), radiation enteritis, iatrogenic jejunal-ileal bypass (for morbid obesity), mesenteric venous thrombosis, superior mesenteric artery thrombosis, and traumatic mesenteric transection (blunt abdominal trauma).

Parenteral nutrition and home parenteral nutrition are the mainstay of therapy for children with SBS and other causes of intestinal failure.  Most infants with SBS eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for an extended period of time.  However, a subgroup of patients with intestinal failure who remain dependent on parenteral nutrition will develop life-threatening complications as a consequence of standard therapy.  The literature indicates that intestinal transplantation is recommended for this select group.  The majority of intestinal transplantation recipients are children, especially those under the age of 5.

Indications for intestinal transplantation include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access.  The literature suggests 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 to 4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins.

In children, the 1- and 3-year graft survival rates for isolated small bowel and combined small bowel and liver transplantations range from 40 to 50 %, while the 1- and 3-year patient survival rates range from 80 to 100 %, depending on the age range of the patient.  Successful transplant recipients resume unrestricted oral diets.  Despite the use of potent immunosuppressive agents, rejection rates are still 50 % or higher.  Sepsis rates are also higher for patients who have had intestinal transplantation than for those who have received other organs because of bacterial translocation from the gut secondary to preservation injury and graft rejection.  Graft and patient survival rates after intestinal transplantation are comparable to rates after lung transplantation.

In addition to rejection and infection (bacterial, fungal, and viral), other complications of intestinal transplantation are graft-versus-host disease, cytomegalovirus infection as well as post-transplant lymphoproliferative disease associated with aggressive immunosuppression and Epstein-Barr virus.

Sudan et al (2007) stated that protocol endoscopy with biopsy is currently the gold standard of small bowel transplantation (SBTx) monitoring, however it is invasive, costly, needs skilled operator, may require anesthesia and may cause complications.  These researchers investigated fecal calprotectin level (FCL) as a candidate non-invasive marker for monitoring patients after SBTx.  Ileostomy effluents were collected at various post-operative days before endoscopy and biopsy.  Fecal calprotectin levels were measured by enzyme-linked immunosorbent assay and a cut-off level of 100 ng/mg was considered positive.  Results were retrospectively evaluated in combination with clinical, endoscopic, and histopathological findings.  Fecal calprotectin levels were presented as median ng/mg.  Fecal calprotectin levels were measured in 122 samples that were obtained from 29 patients after SBTx.  Only 1 of 69 positive FCL did not accompany abnormal findings.  Retrospective evaluation showed that 11 samples from 6 patients (FCL: 217) coincided with rejection episodes, 6 samples from 3 patients (FCL: 125) coincided with viral enteritis, 51 samples from 21 patients (FCL: 207) coincided with non-specific inflammation, 11 samples from 2 patients (FCL: 998) coincided with chronic intestinal ulceration, and finally 50 samples from 19 patients (FCL: 43) coincided with normal findings.  No significant FCL difference was found between rejection, infection, and inflammation.  Evolution in FCL in transplant recipients showed that FCL can predict rejection days before histopathological diagnosis.  The authors concluded that FCL is a promising clinical screening test for intestinal allograft rejection.  The major drawback of this study was that it was a retrospective study of selected patient samples with known diagnosis.  If the clinical utility of FCL is confirmed by prospective validation studies, its use may avoid unnecessary protocol endoscopy with biopsy.

Multi-visceral transplantation entails the simultaneous transplantation of multiple abdominal viscera including the stomach, duodenum, pancreas, and small intestine, with (multi-visceral transplant [MVT]) or without the liver (modified MVT, [MMVT]).

Abu-Elmgagd et al (2009) evaluated the evolution of visceral transplantation in the milieu of surgical technical modifications, new immunosuppressive protocols, and other management strategies.  Divided into 3 eras, a total of 453 patients received 500 visceral transplants.  The primary used immunosuppression was tacrolimus-steroid-only during Era I (5/90 to 5/94), adjunct induction with multiple drug therapy during Era II (1/95 to 6/01), and recipient pre-treatment with tacrolimus monotherapy during Era III (7/01 to 11/08).  During era II/III, donor bone marrow was given (n = 79), intestine was ex-vivo irradiated (n = 44), and Epstein-Barr-Virus (EBV)/cytomegalovirus (CMV) loads were monitored.  Actuarial patient survival was 85 % at 1-year, 61 % at 5-years, 42 % at 10-years, and 35 % at 15-years with respective graft survival of 80 %, 50 %, 33 %, and 29 %.  With a 10 % re-transplantation rate, second/third graft survival was 69 % at 1-year and 47 % at 5-years.  The best outcome was with intestine-liver allografts.  Era III rabbit anti-thymocyte globulin or alemtuzumab pre-treatment-based strategy was associated with significant (p < 0.0001) improvement in outcome with 1- and 5-year patient survival of 92 % and 70 %.  The authors concluded that survival has greatly improved over time as management strategies evolved.  The current results justified elevating the procedure level to that of other abdominal organs with the privilege to permanently reside in a respected place in the surgical armamentarium.  Meanwhile, innovative tactics are still required to conquer long-term hazards of chronic rejection of liver-free allografts and infection of multi-visceral recipients

Vianna et al (2012) evaluated the clinical outcomes of MVT in the setting of diffuse thrombosis of the porto-mesenteric venous system.  A database of intestinal transplant patients was maintained with prospective analysis of outcomes.  The diagnosis of diffuse porto-mesenteric thrombosis (PMT) was established with dual-phase abdominal computed tomography or magnetic resonance imaging with venous reconstruction.  A total of 25 patients with grade IV PMT received 25 MVT.  Eleven patients underwent simultaneous cadaveric kidney transplantation.  Biopsy-proven acute cellular rejection was noted in 5 recipients, which was treated successfully.  With a median follow-up of 2.8 years, patient and graft survival were 80 %, 72 %, and 72 % at 1, 3, and 5 years, respectively.  To date, all survivors have good graft function without any signs of residual/recurrent features of portal hypertension.  The authors concluded that MVT can be considered as an option for the treatment of patients with diffuse PMT.  They stated that MVT is the only procedure that completely reverses portal hypertension and addresses the primary disease while achieving superior survival results in comparison to the alternative options.

Trevizol et al (2013) stated that intestinal transplantation (IT)/MVT is the gold standard treatment for patients with intestinal failure and complications related to TPN, gastro-intestinal inoperable indolent tumors, or diffuse portal thrombosis.  Currently, the reported 1-year patient survival rate is around 80 %, similar to other solid organ abdominal transplantations.  Unfortunately, the patient survival decreases after the first year with the 5-year rate not close to 70 % yet.  Acute cellular rejection (ACR) is the main cause of graft loss.  Its early diagnosis may make it possible to improve survival of re-transplantations.  These investigators analyzed the reported results published in the last 5 years by leading transplant centers to evaluate IT/MVT re-transplantation results.  They performed a literature review using PubMed focusing on multi-visceral and intestinal re-transplantation in articles published between 2006 and 2012.  In relation to the first transplantation, these researchers analyzed demographics, immunosuppression, rejection, infection as well as graft and patient survival rates.  Two centers reported results on intestinal and multi-visceral re-transplantations.  Mazariegos et al reported their experience with 15 intestinal re-transplantations in 14 pediatric recipients.  Four patients died from post-transplant lympho-proliferative disease, severe ACR, fungal sepsis, or bleeding from a pseudo-aneurysm at a mean time of 5.7 months post-transplantation.  Total parenteral nutrition was weaned at a median time of 32 days.  Abu-Elmaged et al reported 47 cases with a 5-year survival of 47 % for all re-transplant modalities.  Re-transplantation with liver-contained visceral allograft achieved a 5-year survival rate of 61 % compared with 16 % for liver-free visceral grafts.  The authors concluded that despite those huge improvements, some transplanted patients develop severe ACR, culminating in graft loss and re-transplantation.  Reports on multi-visceral and intestinal re-transplantation outcomes suggested that it is a viable procedure with appropriate patient survival after primary graft loss.

Mangus et al (2013) reviewed the changing indications and outcomes for this procedure over a 7-year period.  This study was a retrospective case review of MVTs performed between 2004 and 2010 at a single center.  All cases were either MVT or MMVT and included a simultaneous kidney transplant, if indicated.  Graft failure was defined as loss of the graft or complete loss of function.  Graft function was monitored by clinical function, laboratory values, and serial endoscopy with biopsy.  During the study period, 95 patients received 100 transplants including 84 MVT and 16 MMVT.  There were 19 patients who received a simultaneous kidney graft.  There were 24 pediatric and 76 adult recipients (age range of 7 months to 66 years).  Indications included intestinal failure alone, intestinal failure with cirrhosis, complete PMT, slow-growing central abdominal tumors, intestinal pseudo-obstruction, and frozen abdomen.  All patients received antibody-based induction immunosuppression with calcineurin inhibitor-based maintenance immunosuppression.  At a median mortality adjusted follow-up of 25 months, 1- and 3-year patient survival rates were 72 % and 57 %, respectively.  There was a learning curve with this complex procedure resulting in a 48 % patient survival during the period from 2004 to 2007, followed by a 70 % patient survival during the period from 2008 to 2010.  Post-transplant complications included rejection (50 % MMVT and 17 % MVT), infection (greater than 90 % first year), graft-versus-host disease (13 %), and post-transplant lymphoproliferative disorder (5 %).  The authors concluded that indications for MVT and MMVT have broadened to include patients with terminal conditions not amenable to other medical therapies such as slow-growing tumors of the mesenteric root, complete PMT, and abdominal catastrophes/frozen abdomen.  Outcomes have improved over time with many patients returning to full functional status and enjoying long-term survival.

Varkey et al (2013) stated that the current treatment of choice for patients with intestinal failure is parenteral nutrition, whereas medical therapy or resection is preferred for patients with neuroendocrine pancreatic tumors (NEPT) along with liver metastasis.  As the survival of patients undergoing IT and MVT is improving, the discussion for expansion of treatment options has become a subject of debate.  These researchers investigated the outcome for patients referred for IT and MVT and determined which patient group are the ones most likely to benefit the most from transplantation.  The authors included all patients evaluated for IT and MVT at the Sahlgrenska University Hospital and The Queen Silvia Children's Hospital center between February 1998 and November 2009.  Patients were classified according to proposed treatment strategy, and the outcome was evaluated.  A total of 43 adults and 19 children with either intestinal failure or NEPT with liver metastases were evaluated for transplantation.  Of these patients, 15 adults and 5 children were transplanted.  Transplantation was life-saving for most children -- all the children survived after transplantation, but 70 % (4/6) died while awaiting transplantation.  Among the adult patients with intestinal failure, the survival rate for patients considered to be stable on parenteral nutrition was higher than the transplanted adult patients.  The survival rate of patients with NEPT was similar to the results seen among patients transplanted for intestinal failure.  The authors concluded that the results confirmed the poor prognosis of patients with intestinal failure awaiting transplantation and indicated that different transplantation criteria may be applied for adults and children, especially when early transplantation is the preferred treatment.  Moreover, they stated that the role of MVT in patients with NEPT remains uncertain.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
CPT codes covered if selection criteria are met:
44132
44133
44135
44136
44137
44715
44720
44721
CPT codes not covered for indications listed in the CPB:
47136
83993
Other CPT codes related to the CPB:
36555 - 36597
47135
47143
47144
47145
47146
47147
99601 - 99602
HCPCS codes covered if selection criteria are met:
S2053 Transplantation of small intestine, and liver allografts
S2054 Transplantation of multivisceral organs
S2055 Harvesting of donor multivisceral organs, with preparation and maintenance of allografts; from cadaver donor
Other HCPCS codes related to the CPB:
B4164 - B5200 Parenteral nutrition solutions and supplies
B9004, B9006 Parenteral nutrition infusion pump, portable or stationary
S9364 - S9368 Home infusion therapy, total parenteral nutrition (TPN)
ICD-9 codes NOT covered for indications listed in the CPB:
209.25 Malignant carcinoid tumor of the foregut NOS [neuroendocrine pancreatic tumor] [not covered for multi-visceral transplants]
209.65 Benign carcinoid tumor of the foregut NOS [neuroendrocrine pancreatic tumor] [not covered for multi-visceral transplants]
Other ICD-9 codes related to the CPB:
014.8 Tuberculosis of intestines (large) (small)
038.0 - 038.9 Septicemia
042 Human immunodeficiency virus [HIV] disease
070.22, 070.23, 070.32, 070.33, 070.54 Viral hepatitis B, C, or delta, chronic
140.0 - 209.30 Malignant neoplasm
209.50 - 209.56 Benign carcinoid tumors of the appendix and large intestine
211.3 Benign neoplasm of colon
238.1 Neoplasm of uncertain behavior of connective and other soft tissue
238.77 Post-transplant lymphoproliferative disorder (PTLD)
272.7 Lipidoses
276.5 Volume depletion
279.00 - 279.9 Disorders involving the immune mechanism
286.7, 286.9 Acquired coagulation factor deficiency or other and unspecified coagulation defects
287.3 - 287.5 Thrombocytopenia
330.1 Cerebral lipidoses
333.4 Huntington's chorea
428.0 - 428.9 Heart failure
453.8 Other venous embolism and thrombosis of other specified veins
456.0 - 456.21 Esophageal varices
533.00 - 533.91 Peptic ulcer, site unspecified
555.0 - 555.9 Regional enteritis
557.0 Acute vascular insufficiency of intestine
558.1 Gastroenteritis and colitis due to radiation
560.2 Volvulus
560.8 - 560.9 Other and unspecified intestinal obstruction
562.00 - 562.13 Diverticula of intestine
564.89 Other functional disorders of intestine
569.89 Other specified disorder of intestine
570 - 573.9 Acute and subacute necrosis of liver, chronic liver disease and cirrhosis, liver abscess and sequelae of chronic liver disease, and other disorders of liver
579.3 Other and unspecified postsurgical nonabsorption
584.9 - 586 Acute renal failure, unspecified, chronic kidney disease (CKD), and renal failure, unspecified
751.0 - 751.5 Other congenital anomalies of digestive system
756.79 Other congenital anomalies of abdominal wall (e.g., exomphalos, gastroschisis, omphalocele)
777.5 Necrotizing enterocolitis in fetus or newborn
902.20 - 902.29 Injury to celiac and mesenteric arteries
996.62 Infection and inflammatory reaction due to other vascular device, implant , and graft
996.87 Complications of transplanted organ, intestines
999.2 Other vascular complications [loss of vascular access]
V42.84 Organ or tissue replaced by transplant, intestines
V45.3 Intestinal bypass or anastamosis status


The above policy is based on the following references:
  1. United Network for Organ Sharing (UNOS). United Network for Organ Sharing Online [website]. Richmond, VA: UNOS; 2002. Available at: http://www.unos.org. Accessed April 17, 2002.
  2. Kaufman SS, Atkinson JB, Bianchi A, et al. Indications for pediatric intestinal transplantation: A position paper of the American Society of Transplantation. Pediatr Transplant. 2001;5(2):80-87.
  3. Ghanekar A, Grant D. Small bowel transplantation. Curr Opin Crit Care. 2001;7(2):133-137.
  4. Reyes J. Intestinal transplantation for children with short bowel syndrome. Semin Pediatr Surg. 2001;10(2):99-104.
  5. Madariaga JR, Reyes J, Mazariegos G. The long-term efficacy of multivisceral transplantation. Transplant Proc. 2000;32(6):1219-1220.
  6. Goulet O, Lacaille F, Jan D, et al. Intestinal transplantation: Indications, results and strategy. Curr Opin Clin Nutr Metab Care. 2000;3(5):329-338.
  7. Silver HJ, Castellanos VH. Nutritional complications and management of intestinal transplant. J Am Diet Assoc. 2000;100(6):680-468, 687-689.
  8. Grant D. Intestinal transplantation: 1997 report of the international registry. Intestinal Transplant Registry. Transplantation. 1999;67(7):1061-1064.
  9. Niv Y, Mor E, Tzakis AG. Small bowel transplantation -- a clinical review. Am J Gastroenterol. 1999;94(11):3126-3130.
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  11. Goulet O. Intestinal transplantation. Curr Opin Clin Nutr Metab Care. 1999;2(4):315-321.
  12. Goulet O. Complications after intestinal transplantation: Traditional and new. Pediatr Transplant. 1999;3(2):89-91.
  13. Jan D, Michel JL, Goulet O, et al. Up-to-date evolution of small bowel transplantation in children with intestinal failure. J Pediatr Surg. 1999;34(5):841-843; discussion 843-844.
  14. Rovera GM, DiMartini A, Schoen RE, et al. Quality of life of patients after intestinal transplantation. Transplantation. 1998;66(9):1141-1145.
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  16. Asfar S, Atkison P, Ghent C, et al. Small bowel transplantation. A life-saving option for selected patients with intestinal failure. Dig Dis Sci. 1996;41(5):875-883.
  17. Langnas AN, Shaw BW Jr, Antonson DL, et al. Preliminary experience with intestinal transplantation in infants and children. Pediatrics. 1996;97(4):443-448.
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  19. Grant D. Current results of intestinal transplantation. The International Intestinal Transplant Registry. Lancet. 1996;347(9018):1801-1803.
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  22. Nightingale JM, Lennard-Jones JE. The short bowel syndrome: What's new and old? Dig Dis. 1993;11(1):12-31.
  23. Ingham Clark CL, Lear PA, Wood S, et al. Potential candidates for small bowel transplantation. Br J Surg. 1992;79(7):676-679.
  24. Buchman AL, Scolapio J, Fryer J. AGA technical review on short bowel syndrome and intestinal transplantation. Gastroenterology. 2003;124(4):1111-1134.
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  26. Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat. Small bowel transplant. Health Technology Scientific Literature Review. Toronto, ON: Ontario Ministry of Health and Long-Term Care; April 2003. Available at:http://www.health.gov.on.ca/english/providers/program/mas/archive.html. Accessed August 4, 2004.
  27. Fishbein TM. The current state of intestinal transplantation. Transplantation. 2004;78(2):175-178.
  28. Fryer JP. Intestinal transplantation: An update. Curr Opin Gastroenterol. 2005;21(2):162-168.
  29. Fishbein TM, Matsumoto CS. Intestinal replacement therapy: Timing and indications for referral of patients to an intestinal rehabilitation and transplant program. Gastroenterology. 2006;130(2 Suppl 1):S147-S151. 
  30. Selvaggi G, Tzakis AG. Intestinal and multivisceral transplantation: Future perspectives. Front Biosci. 2007;12:4742-4754.
  31. DeLegge M, Alsolaiman MM, Barbour E, et al. Short bowel syndrome: Parenteral nutrition versus intestinal transplantation. Where are we today? Dig Dis Sci. 2007;52(4):876-892. 
  32. Selvaggi G, Weppler D, Tzakis A. Liver and gastrointestinal transplantation at the University of Miami. Clin Transpl. 2003;:255-266.
  33. Renz JF, McDiarmid SV, Edelstein S, et al. Application of combined liver-intestinal transplantation as a staged procedure. Transplant Proc. 2004;36(2):314-315.
  34. Herlenius G, Friman S, Bäckman L, et al. Initial experience with multivisceral, cluster, and combined liver and small bowel transplantation in Sweden. Transplant Proc. 2002;34(3):865.
  35. Muiesan P, Dhawan A, Novelli M, et al. Isolated liver transplant and sequential small bowel transplantation for intestinal failure and related liver disease in children. Transplantation. 2000;69(11):2323-2326.
  36. Farmer DG, McDiarmid SV, Smith C, et al. Experience with combined liver-small intestine transplantation at the University of California, Los Angeles. Transplant Proc. 1998;30(6):2533-2534.
  37. Lacaille F, Jobert-Giraud A, Colomb V, et al. Preliminary experience with combined liver and small bowel transplantation in children. Transplant Proc. 1998;30(6):2526-2527.
  38. Sudan D, Vargas L, Sun Y, et al. Calprotectin: A novel noninvasive marker for intestinal allograft monitoring. Ann Surg. 2007;246(2):311-315.
  39. Fryer JP. The current status of intestinal transplantation. Curr Opin Organ Transplant. 2008;13(3):266-272.
  40. Vianna RM, Mangus RS, Tector AJ. Current status of small bowel and multivisceral transplantation. Adv Surg. 2008;42:129-150.
  41. Millar AJ, Gupte G, Sharif K. Intestinal transplantation for motility disorders. Semin Pediatr Surg. 2009;18(4):258-262.
  42. Fishbein TM. Intestinal transplantation. N Engl J Med. 2009;361(10):998-1008.
  43. Weimann A, Ebener Ch, Holland-Cunz S, et al; Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine. Surgery and transplantation - Guidelines on Parenteral Nutrition, Chapter 18. Ger Med Sci. 2009;7:Doc10.
  44. Sudan D. Long-term outcomes and quality of life after intestine transplantation. Curr Opin Organ Transplant. 2010;15(3):357-360.
  45. Roskott AM, Nieuwenhuijs VB, Dijkstra G, et al. Small bowel preservation for intestinal transplantation: A review. Transpl Int. 2011;24(2):107-131.
  46. Pironi L, Joly F, Forbes A, et al; Home Artificial Nutrition & Chronic Intestinal Failure Working Group of the European Society for Clinical Nutrition and Metabolism (ESPEN). Long-term follow-up of patients on home parenteral nutrition in Europe: Implications for intestinal transplantation. Gut. 2011;60(1):17-25.
  47. Venick RS, Wozniak LJ, Colangelo J, et al. Long-term nutrition and predictors of growth and weight gain following pediatric intestinal transplantation. Transplantation. 2011;92(9):1058-1062.
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  49. Vianna RM, Mangus RS, Kubal C, et al. Multivisceral transplantation for diffuse portomesenteric thrombosis. Ann Surg. 2012;255(6):1144-1150.
  50. Trevizol AP, David AI, Yamashita ET, et al. Intestinal and multivisceral retransplantation results: Literature review. Transplant Proc. 2013;45(3):1133-1136.
  51. Mangus RS, Tector AJ, Kubal CA, et al. Multivisceral transplantation: Expanding indications and improving outcomes. J Gastrointest Surg. 2013;17(1):179-186; discussion p.186-187.
  52. Varkey J, Simren M, Bosaeus I, et al. Survival of patients evaluated for intestinal and multivisceral transplantation - the Scandinavian experience. Scand J Gastroenterol. 2013;48(6):702-711.


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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna 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 Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
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