Aetna considers pancreas transplantation alone (PTA) without kidney transplant medically necessary for members who meet the transplanting institution's selection criteria. In the absence of an institution's selection criteria, Aetna considers PTA without kidney transplant medically necessary when all of the following general and disease specific criteria are met:
Absence of ongoing or recurrent active infections that are not effectively treated; and
Absence of uncontrolled HIV/AIDS infection, 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 infection (e.g., aspergillus, coccidioidomycosis, resistant fungal infections, tuberculosis) or neoplasm (e.g., Kaposi's sarcoma, non-Hodgkin's lymphoma); and
On stable anti-viral therapy more than 3 months; and
Documentation of compliance with medical management; and
Member has adequate cardiac status (e.g., no angiographic evidence of significant coronary artery disease, ejection fraction greater than or equal to 40 %, no myocardial infarction in last 6 months, negative stress test); and
Member has satisfactory kidney function (creatinine clearance greater than 40 ml/min); and
No malignancy (except for non-melanomatous skin cancers) or malignancy has been completely resected OR (upon medical review) malignancy has been adequately treated such that the risk of recurrence is small.
Disease Specific Criteria:
Member has a history of labile (brittle) insulin-dependent diabetes mellitus (IDDM); and
Member has recurrent, acute and severe metabolic and potentially life-threatening complications requiring medical attention, as documented by chart notes, frequent emergency room visits and/or hospitalizations. They may include:
Hypoglycemic unawareness associated with high risk of injury; or
Member has consistent failure of exogenous insulin-based management, defined as inability to achieve sufficient glycemic control (HbA1c of greater than 8.0) or recurrent hypoglycemic unawareness, despite aggressive conventional therapy including all of the following:
Adjusting frequencies and amounts of insulin injected; and
Measuring multiple blood glucose levels on a daily basis; and
Modifying diet and exercise; and
Monitoring HgbA1c levels.
Aetna considers pancreas retransplantation after a failed primary pancreas transplant medically necessary when member meets the selection criteria stated above.
Pancreas retransplantation after 2 or more prior failed pancreas transplants may be considered medically necessary upon individual case review.
Contraindications: PTA is considered not medically necessary in members with prohibitive cardiovascular risk because the risks of PTA exceed the benefits. Examples of prohibitive cardiovascular risk include, but are not limited to:
Angiographic evidence of significant non-correctable coronary artery disease; or
Ejection fraction less than 20 %; or
Myocardial infarction within last 6 months; or
Refractory uncontrolled hypertension
Relative Contraindications: Aetna considers pancreas transplant medically necessary for members with the following relative contraindications to pancreas transplant only if the requesting physician documents that these relative contraindications were considered, and has determined that the benefits of pancreas transplant outweigh the risks in these members. Relative contraindications to PTA include the following:
Ejection fraction 20 % to 40 %; or
Severe peripheral vascular disease.
Aetna considers islet cell autotransplantation medically necessary for members undergoing near-total or total pancreatic resection for severe, refractory chronic pancreatitis.
Aetna considers a partial pancreas transplant from a living donor an acceptable alternative to cadaveric transplant for persons who meet medical necessity criteria for pancreas transplant.
Aetna considers any of the following experimental and investigational because their safety and effectiveness have not been established in the peer-reviewed published medical literature.
Islet cell allotransplantation; or
Pancreatic islet xenotransplantation; or
PTA for increased longevity; or
PTA primarily indicated for life-style issues, i.e., a desire to no longer take insulin.
Exogenous insulin is effective therapy for most diabetics. Intensive insulin therapy with multiple daily injections or with a constant infusion pump has been shown to be an effective method of maintaining blood glucose and hemoglobin A1c at near normal levels. Despite maximal medical therapy, a rare (less than 1%) number of non-uremic patients with insulin-dependent diabetes mellitus (IDDM) may experience frequent and unpredictable occurrences of severe hyperglycemia, hypoglycemia, ketoacidosis, and hypoglycemic unawareness, thus labeling them as brittle, labile and unstable. This subgroup tends to have a life that is constantly disrupted by these disabling and life-threatening events, which cause a considerable burden on social and family resources due to multiple emergency room visits and/or hospital admissions. Fortunately, in this small subset of patients, there is sufficient evidence in the medical literature to support performance of pancreas transplantation alone (PTA).
Initially, the reported results of solitary pancreatic transplantation in non-uremic diabetic patients were less favorable than simultaneous pancreas-kidney (SPK) transplantation or pancreas after kidney (PAK) transplantation because of high rates of rejection and difficulties in the diagnosis and treatment of these rejection episodes. Because there was no marker for pancreas rejection with sensitivity similar to serum creatinine for kidney transplant rejection, detection and treatment of PTA rejection was often delayed. Subsequently, outcomes of PTA have substantially improved due to technical refinements of the procedure, the introduction of new immunosuppressive regimens, and better selection of transplant candidates. Unlike SPK and PAK, there is no adequate evidence that PTA can prevent or retard the development and/or progression of the long-term complications of diabetes; nor is there evidence that pancreas transplantation can prolong the life of patients with diabetes mellitus
Pancreas transplantation alone is contraindicated in patients with clinically significant cardiovascular disease. Because of the high prevalence of microvascular disease, especially in the coronary arteries in patients with diabetes, it is especially important to evaluate patients for these risks before PTA surgery. Indeed, one of the most frequent causes of pancreas transplant failure is death from myocardial infarction. Therefore, accepted guidelines state that any substantial coronary artery disease needs to be corrected before transplantation is undertaken.
A history of coronary revascularization is no longer considered an absolute contraindication. Nevertheless, coronary event rates remain greater among pancreas transplant recipients who have undergone coronary revascularization, than among individuals without pre-transplantation coronary artery disease. The literature states that severe peripheral vascular disease is a relative contraindication to PTA since iliac atherosclerosis can complicate the technical procedure. Other relative contraindications to pancreas transplantation include obesity, substance abuse, poorly controlled psychiatric illnesses, noncompliance, and any recent malignancy.
Although segmental grafts (consisting of only the pancreatic body and tail) were once common, the entire pancreas and its associated duodenal segment are now almost always transplanted (unless a living donor is used). This advance provides more insulin-secreting cells. The allograft is positioned laterally in the lower abdomen. Vascular anastomoses in a pancreas transplant are the donor splenic and superior mesenteric artery and portal vein to the recipient iliac artery and vein, respectively. This provides systemic rather than portal delivery of insulin with a resulting baseline fasting hyper-insulinemia. The incidence of post-transplant graft thrombosis has been greatly reduced using this method. Ligation or obliteration of the pancreatic duct was once commonly practiced, but these techniques have also been abandoned. Instead, the pancreatic exocrine secretions are drained internally into either the small intestine or the bladder. In general, immunosuppression is the same as that used for patients with kidney transplants. Induction therapy and rejection treatment usually involves use of ALG or OKT3. All in all, with excellent HLA matching, a graft survival rate of 80 %, comparable with the overall success rate of combined kidney-pancreas transplantation, can be achieved.
The American Diabetes Association (2003) has developed established indications for pancreas transplantation: “In the absence of indications for kidney transplantation, pancreas transplantation should only be considered a therapy in patients who exhibit these 3 criteria: (i) a history of frequent, acute, and severe metabolic complications (hypoglycemia, hyperglycemia, ketoacidosis) requiring medical attention; (ii) clinical and emotional problems with exogenous insulin therapy that are so severe as to be incapacitating; and (iii) consistent failure of insulin-based management to prevent acute complications.”
Autologous islet cell transplantation is an alternative for persons undergoing total pancreatectomy for severe, refractory chronic pancreatitis. Near total or total pancreatic resection can alleviate pain in patients with severe chronic resection. Autologous islet cell transplantation can preserve islet cell function in patients undergoing this procedure. The islet cell transplantation procedure involves the infusion of islet cells into the liver by portal embolization, where the cells function as a free graft. The liver's dual vascular supply allows embolization of isolated pancreatic islets by cannulating the umbilical vein, a tributary of the mesenteric venous system, or by transcutaneous, transhepatic cannulation of the portal vein itself. The terminal portal venule can be occluded without infarcting the transplant site.
Rodriguez Rilo and associates (2003) reported on the results of autologous islet cell transplantation in a consecutive series of patients from one center who received total or near-total pancreatic resection for severe, refractory chronic pancreatitis. From February 2000 to February 2003, a total of 22 patients, whose median age was 38 years, underwent pancreatectomy and autologous islet cell transplantation. Sixty-eight percent of the patients had either a minor or major complication. Major complications included acute respiratory distress syndrome (n = 2), intra-abdominal abscess (n = 1), and pulmonary embolism (n = 1). All patients demonstrated C-peptide and insulin production indicating graft function. Post-operatively, 41 % of subjects were insulin independent, and 27 % required less than 10 units of insulin per day, and the remaining 7 patients require between 15 and 40 units of insulin per day. All patients had pre-operative pain and had been taking opioid analgesics; 82 % no longer required analgesics post-operatively. The investigators concluded that pancreatectomy with autologous islet cell transplantation can alleviate pain for patients with chronic pancreatitis and preserve endocrine function.
Jie et al (2005) reported on outcomes of one center’s experience with 137 patients undergoing autologous islet cell transplantation for pancreatectomy since 1997. Follow-up data was available in 120 patients; 63 % of the patients had complete relief from pain, 22 % experienced partial relief, and 15 % were unchanged. Of patients with complete pancreatectomy since 1995 (n = 73), all but 1 pediatric patient (n = 22) transplanted with less than or equal to 2000 IEQ/kg islets required insulin post-pancreatectomy. Of patients receiving more than 2000 IEQ/kg islets (n = 51), 47 % were completely insulin independent while 25 % were intermittently insulin-treated. The investigators concluded that autologous islet cell transplantation should be considered in patients undergoing primary pancreatic resection for the treatment of refractory pain associated with small duct chronic pancreatitis.
Clayton and colleagues (2003) reported on a single center’s experience with autologous islet cell transplantation for total or partial pancreatectomy from September 1994 to July 2001. Forty patients had been transplanted, with follow-up times range from 6 months to 7 years. At 2 years post transplant, 18 patients had a median hemoglobin A1c of 6.6 % (5.2 to 19.3 %), fasting C-peptide of 0.66 ng/mL (0.26 to 2.65 ng/ml), and required a median of 12 (0 to 45) units of insulin per day. Five patients with 6-year follow-up data had a median hemoglobin A1c of 8 % (6.1 to 11.1 %), fasting C peptide of 1.68 ng/ml (0.9 to 2.78 ng/ml), and required a median of 43 (6 to 86) units of insulin per day. The investigators reported that these data demonstrate that up to 6 years after autologous islet cell transplantation, the grafts continue to function, but that over the time period studied, the level of function appears to be decreasing. The investigators reported that the majority of patients no longer required opiate analgesia.
Allogeneic islet cell transplantation is being investigated as an alternative means of restoring normoglycemia, without the attendant morbidity of the whole-organ procedure, and potentially with significantly less need for immunosuppression than pancreas transplantation. Experience with allogeneic islet cell transplantation has increased and incremental improvements in the islet cell isolation process have been achieved. Islet cell transplantation has several advantages: (i) the cells can be delivered easily into the recipient's portal circulation by umbilical vein cannulation without a major operation, and (ii) allogeneic islets can be cryopreserved. Methods for treating allogeneic islet cells to reduce their immunogenicity are being studied.
Although considerable knowledge regarding allogeneic islet cell transplantation has been accumulated, both in the techniques of islet isolation and in preventing damage to the transplant by rejection or autoimmunity, research has not progressed much beyond experimental models. Until recently, successful human islet transplantation has been exceedingly rare; human islet cell transplantations have been almost uniformly unsuccessful, if success is defined as restoration of normoglycemia with no dependence on exogenous insulin. With continued improvements, allogeneic islet cell transplantation could eventually replace both insulin therapy and whole-pancreas transplantation as the optimal treatment for type 1 diabetes. A number of immunologically privileged transplantation sites have been evaluated, including the anterior chamber of the eye, the brain, the pregnant uterus, the placenta, the testis, and the thymus. Several of these sites have been shown to provide at least partial sanctuary for allogeneic islets while allowing normal physiologic function. However, the technical considerations and potential morbidity of engraftment into these sites discourage their clinical use.
Guidelines from the American Diabetes Association (Robertson et al, 2004) have concluded that “islet cell transplantation is an experimental procedure, also requiring systemic immunosuppression, and should be performed only within the setting of controlled research studies.”
An assessment prepared for the Ontario Ministry of Health and Long-Term Care (2003) concluded that "[t]he current evidence on the use of islet transplantation for non-uremic type 1 diabetic patients is limited since it is based on studies with weak methodological design .… The effect of islet transplantation on restoring hormonal responses to hypoglycemia is inconclusive. Islet transplantation in non-uremic type 1 diabetic patients with hypoglycemia unawareness or uncontrolled diabetes is an evolving procedure with promising preliminary, but inconclusive final results."
An assessment prepared by the Alberta Heritage Foundation for Medical Research (Guo et al, 2003) reached the following conclusions about islet cell transplantation for type 1 diabetes: “Limited evidence suggests that ITA [islet cell transplantation] is effective in controlling labile diabetes and protects against unrecognised hypoglycemia in highly selected patients in the short term. The long-term effects of ITA on metabolic control remain to be proven. Follow-up studies are needed to determine the duration of this metabolic effect in order to assess its potential for preventing or arresting the development of chronic diabetes complications in non-uremic type 1 diabetic patients with severe hypoglycemia. Future research is required to improve measures for islet mass/function in order to appropriately evaluate the effects of the ITA procedure.”
An assessment by the National Institute for Clinical Excellence (2003) states: “Current evidence on the safety and efficacy of pancreatic islet cell transplantation does not appear adequate to support the use of this procedure without special arrangements for consent and for audit or research.” The assessment explained that “the identified studies did not compare blood sugar control or risks of diabetic complications for the treatment options (injected insulin versus pancreatic islet cell transplantation).” The assessment also stated that there was a lack of long-term follow-up data.
An assessment of islet cell transplantation for type 1 diabetes prepared for the Agency for Healthcare Quality and Research (AHRQ) reached the following conclusions: “Evidence on outcomes of islet transplant is limited by small patient numbers, short followup, and lack of standardized reporting. (These issues are being addressed by the NIH funded Collaborative Islet Transplant Registry.) Of 37 patients from 3 centers, 28 (76 %) maintained insulin independence at 1 year (published evidence); similarly, 50 to 90 % of 104 patients from four centers were insulin independent (supplemental evidence). Serious adverse events, including portal vein thrombosis and hemorrhage, occur infrequently. Data are lacking on long-term durability of the procedure, effects on diabetic complications, or long-term consequences of immunosuppression. Evidence is insufficient for comparison with whole-organ pancreas transplant.”
An assessment by the Institute for Health Economics (Guo et al, 2008) of islet cell transplantation for type 1 diabetes concluded that there was insufficient evidence to consider islet cell allotransplantation as standard care in patients with non-uremic type-1 diabetes with severe hypoglycaemia and uncontrolled diabetes. The assessment stated a number of implications for research, including the development of more sensitive methods to predict and detect graft loss, and the need for studies that were larger, prospective and had longer follow-up periods. Studies of single donors with standardized immunosuppressive regimens and studies of patients with and without renal dysfunction were also recommended.
In a pilot study, Mineo and colleagues (2008) attempted to induce recipient chimerism and graft tolerance in islet transplantation by donor CD34+hematopoietic stem cell (HSC) infusion. A total of 6 patients with brittle type 1 diabetes mellitus received a single-donor allogeneic islet transplant (8611 +/- 2113 IEQ/kg) followed by high doses of donor HSC (4.3 +/- 1.9 x 10(6) HSC/kg), at days 5 and 11 post-transplant, without ablative conditioning. An "Edmonton-like" immunosuppression was administered, with a single dose of infliximab added to induction. Immunosuppression was weaned per protocol starting 12 months post-transplant. After transplantation, glucose control significantly improved, with 3 recipients achieving insulin-independence for a short time (24 +/- 23 days). No severe hypoglycemia or protocol-related adverse events occurred. Graft function was maximal at 3 months then declined. Two recipients rejected within 6 months due to low immunosuppressive trough levels, whereas 4 completed 1-year follow-up with functioning grafts. Graft failure occurred within 4 months from weaning (478 +/- 25 days post-transplant). Peripheral chimerism, as donor leukocytes, was maximal at 1-month (5.92 +/- 0.48 %), highly reduced at 1-year (0.20 +/- 0.08 %), and was undetectable at graft failure. CD25+T-lymphocytes significantly decreased at 3 months, but partially recovered thereafter. Combined islet and HSC allotransplantation using an "Edmonton-like" immunosuppression, without ablative conditioning, did not lead to stable chimerism and graft tolerance.
In a review on pancreas retransplants, Humar et al (2000) concluded that pancreas retransplants can be performed with a minimal increase in surgical complications. However, graft survival after retransplants is slightly inferior to that after primary transplants, probably for both immunological and non-immunological reasons. Retransplants can be offered to suitable candidates, but they may require more aggressive monitoring for rejection.
Patients with type 1 diabetes who are appropriate candidates for a pancreas transplantation may be simultaneously evaluated for suitable living segmental pancreas donors (Barr et al, 2006). Potential donors may undergo either segmental pancreas donation alone (for non-uremic or post-uremic recipients) or simultaneous segmental pancreas and unilateral kidney donation (for uremic recipients). Once identified, potential donors will be subject to a thorough medical, metabolic and psychosocial screening. ABO and HLA cross-match compatibility is preferred but not manditory (Barr et al, 2006). A segmental donor pancreatectomy can also be applied for islet isolation and allotransplantation. Donor segmental pancreatectomy (tail) can be done open or laparoscopically.
The largest reported experience with living donor pancreas transplants has been reported from the University of Minnesota (Barr et al, 2006). At the University of Minnesota, there have been 130 live donor pancreas transplants performed between 1977 and 2005. The distribution of these transplants was as follows: 40 % PTA; 25 % pancreas after kidney (PAK); and 35 % simultaneous live donor pancreas and kidney transplants (SPK). There are 20 PTA and PAK live donor grafts functioning between 10 and 30 yeaars following transplantation. There are 3 living donor SPK transplants with function greater than 10 years. There have also been 2 live donor islet cell transplants after kidney transplantation early in the center experience.
Other centers have also reported their experience with living donor pancreas transplantation. At the University of Illinois, Chicago, 9 living-donor simultaneous kidney and segmental pancreas bladder-drained transplants were performed between 1997 and 2004 (Barr et al, 2006). Eight out of 9 pancreas grafts and all the kidney grafts are reported to be working for 1 to 8 years following transplantation. There was no report of a donor death.
As of 2005, there had been 5 live donor segmental pancreatectomies performed in Japan, 1 case of live donor islet cell transplantation in Japan, and 2 live donor segmental pancreatectomies performed in Korea (Barr et al, 2006).
Tan et al (2008) evaluated the safety and effectiveness of simultaneous islet and kidney transplantation in patients with type 1 diabetes and end-stage renal disease using a glucocorticoid-free immunosuppressive regimen with alemtuzumab induction. A total of 7 patients with type 1 diabetes and end-stage renal failure were transplanted with allogenic islets and kidneys procured from brain-dead donors. To prevent organ rejection, patients received alemtuzumab for induction immunosuppression, followed by sirolimus and tacrolimus. No glucocorticoids were given at any time. The median duration of follow-up was 18.3 months (range of 13 to 31). Kidney survival was 100 %. Four patients became insulin independent at 1 year; the other 3 reduced insulin use to less than 25 % of the amount required before transplantation. Serum C-peptide levels were significantly greater post-transplant in all patients, indicating continued islet function. No major procedure-related complications were observed. The authors concluded that these findings demonstrated that a steroid-free immunosuppressive regimen consisting of alemtuzumab, sirolimus, and tacrolimus is feasible for simultaneous islet and kidney transplantation. The question of whether this induction regimen is superior to more standard induction deserves large studies.
Halban et al 92010) stated that beta cell mass and function are decreased to varying degrees in both type 1 and type 2 diabetes. In the future, islet cell replacement or regeneration therapy may thus offer therapeutic benefit to people with diabetes, but there are major challenges to be overcome. These researchers performed a review of published peer-reviewed medical literature on beta-cell development and regeneration. Only publications considered most relevant were selected for citation, with particular attention to the period 2000 to 2009 and the inclusion of earlier landmark studies. Islet cell regenerative therapy could be achieved by in situ regeneration or implantation of cells previously derived in vitro. Both approaches are being explored, and their ultimate success will depend on the ability to recapitulate key events in the normal development of the endocrine pancreas to derive fully differentiated islet cells that are functionally normal. There is also debate as to whether beta-cells alone will assure adequate metabolic control or whether it will be necessary to regenerate islets with their various cell types and unique integrated function. Any approach must account for the potential dangers of regenerative therapy. The authors concluded that islet cell regenerative therapy may one day offer an improved treatment of diabetes and potentially a cure. However, the various approaches are at an early stage of pre-clinical development and should not be offered to patients until shown to be safe as well as more effective than existing therapy.
Marigliano et al (2011) stated that the therapy of type 1 diabetes is an open challenging problem. The restoration of normoglycemia and insulin independence in immunosuppressed type 1 diabetic recipients of islet allotransplantation has shown the potential of a cell-based diabetes therapy. Even if successful, this approach poses a problem of scarce tissue supply. Xenotransplantation can be the answer to this limited donor availability and, among possible candidate tissues for xenotransplantation, porcine islets are the closest to a future clinical application. Xenotransplantation, with pigs as donors, offers the possibility of using healthy, living, and genetically modified islets from pathogen-free animals available in unlimited number of islets. Several studies in the pig to non-human primate model demonstrated the feasibility of successful pre-clinical islet xenotransplantation and have provided insights into the critical events and possible mechanisms of immune recognition and rejection of xenogeneic islet grafts. Particularly promising results in the achievement of prolonged insulin independence were obtained with newly developed, genetically modified pigs islets able to produce immunoregulatory products, using different implantation sites, and new immunotherapeutic strategies. Nonetheless, the authors concluded that further efforts are needed to generate additional safety and efficacy data in non-human primate models to safely translate these findings into the clinic.
CPT Codes / HCPCS Codes / ICD-9 Codes
CPT codes covered if selection criteria are met:
CPT codes not covered for indications listed in the CPB:
Other CPT codes related to the CPB:
HCPCS codes not covered for indications listed in the CPB:
Islet cell tissue transplant from pancreas; allogeneic
ICD-9 codes covered if selection criteria are met:
Personal history of noncompliance with medical treatment
Aortocoronary bypass status
Percutaneous transluminal coronary angioplasty status
The above policy is based on the following references:
Bohman SO, Tyden G, Wilezek A, et al. Prevention of kidney graft diabetic nephropathy by pancreas transplantation in man. Diabetes. 1985;34:306-308.
Najarian JS, Kaufman DB, Fryd DS, et al. Long-term survival following kidney transplantation in 100 type 1 diabetic patients. Transplantation. 1989;1:106-113.
Dubernard JM, Tajra LC, Lefrancois N, et al. Pancreas transplantation: Results and indications. Diabetes Metab. 1998;24:195-199.
Bohman SO, Wilczek H, Jaremko G, et al. Recurrence of diabetic nephropathy in human renal allografts: Preliminary report of a biopsy study. Transplant Proc. 1984;16:649-653.
Kennedy WR, Navarro X, Goetz FC, et al. Effects of pancreatic transplantation on diabetic neuropathy. N Engl J Med. 1990;322:1031-1037.
Van der Vliet JA, Navarro X, Kennedy WR, et al. The effect of pancreas transplantation on diabetic polyneuropathy. Transplantation. 1988;45:368-370.
Ramsay RC, Goetz FC, Sutherland DER, et al. Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus. N Engl J Med. 1988;318:208-214.
Katz H, Homan M, Velosa J, et al. Effects of pancreas transplantation on postprandial glucose metabolism. N Engl J Med. 1991;325:1278-1283.
Sollinger HW, Odorico JS, Knechtle SJ, et al. Experience with 500 simultaneous pancreas-kidney transplants. Ann Surg. 1998;228:284-296.
Sasaki TM, Gray RS, Ratner RE, et al. Successful long-term kidney-pancreas transplants in diabetic patients with high C-peptide levels. Transplantation. 1998;65:1510-1512.
Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) cases reported to the United Network for Organ Sharing (UNOS) and non-US cases reported to the International Pancreas Transplant Registry (IPTR) as of October 2000. Clin Transpl. 2000;45-72.
Sutherland DE, Gruessner RW, Dunn DL, et al. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg. 2001;233(4):463-501.
Odorico JS, Becker YT, Groshek M, et al. Improved solitary pancreas transplant graft survival in the modern immunosuppressive era. Cell Transplant. 2000;9(6):919-927.
Kiberd BA, Larson T. Estimating the benefits of solitary pancreas transplantation in nonuremic patients with type 1 diabetes mellitus: A theoretical analysis. Transplantation. 2000;70(7):1121-1127.
Odorico JS, Leverson GE, Becker YT, et al. Pancreas transplantation at the University of Wisconsin. Clin Transpl. 1999;199-210.
Stratta RJ, Gaber AO, Shokouh-Amiri MH, et al. A prospective comparison of systemic-bladder versus portal-enteric drainage in vascularized pancreas transplantation. Surgery. 2000;127(2):217-226.
Stratta RJ. Review of immunosuppressive usage in pancreas transplantation. Clin Transplant. 1999;13(1 Pt 1):1-12.
Stratta RJ. Immunosuppression in pancreas transplantation: Progress, problems and perspective. Transpl Immunol. 1998;6(2):69-77.
Kuo PC, Johnson LB, Schweitzer EJ, et al. Solitary pancreas allografts. The role of percutaneous biopsy and standardized histologic grading of rejection. Arch Surg. 1997;132(1):52-57.
Robertson RP. Pancreatic islet transplantation for diabetes: Successes, limitations, and challenges for the future. Mol Genet Metab. 2001;74(1-2):200-205.
Atkinson MA, Eisenbarth GS. Type 1 diabetes: New perspectives on disease pathogenesis and treatment. Lancet. 2001;358(9277):221-229.
Shapiro AM, Ryan EA, Lakey JR. Pancreatic islet transplantation in the treatment of diabetes mellitus. Best Pract Res Clin Endocrinol Metab. 2001;15(2):241-264.
Shapiro AM, Lakey JR. Future trends in islet cell transplantation. Diabetes Technol Ther. 2000;2(3):449-452.
Bretzel RG, Brendel M, Eckhard M, et al. Islet transplantation: present clinical situation and future aspects. Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S384-S399.
Federlin KF, Jahr H, Bretzel RG. Islet transplantation as treatment of type 1 diabetes: From experimental beginnings to clinical application. Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S373-S383.
White SA, Kimber R, Veitch PS, et al. Surgical treatment of diabetes mellitus by islet cell and pancreas transplantation. Postgrad Med J. 2001;77(908):383-387.
Benedetti E, Troppmann C, Gruessner AC, et al. Pancreas graft loss caused by intra-abdominal infection. A risk factor for a subsequent pancreas retransplantation. Arch Surg. 1996;131(10):1054-1060.
Stratta RJ, Lowell JA, Sudan D, et al. Retransplantation in the diabetic patient with a pancreas allograft. Am J Surg. 1997;174(6):759-763.
Humar A, Kandaswamy R, Drangstveit MB, et al. Surgical risks and outcome of pancreas retransplants. Surgery. 2000;127(6):634-640.
Reddy KS, Shokouh-Amiri H, Stratta RJ, et al. Successful reuse of portal-enteric technique in pancreas retransplantation. Transplantation. 2000;69(11):2443-2445.
BlueCross BlueShield Association (BCBSA), Technology Evaluation Center (TEC). Pancreas retransplantation. TEC Assessment Program. Chicago IL: BCBSA; April 2002; 16(23). Available at: http://www.bcbs.com/tec/vol16/16_23.html. Accessed April 7, 2004.
Robertson RP, Davis C, Larsen J, et al. Pancreas and islet transplantation for patients with diabetes. Diabetes Care. 2003;26 Suppl:S120.
Guo B, Harstall C, Corabian P. Islet cell transplantation for the treatment of non-uremic type 1 diabetic patients with severe hypoglycemia. Health Technology Assessment. HTA 31. Edmonton, AB: Alberta Heritage Foundation for Medical Research (AHFMR); April 2003.
Institute for Clinical Systems Improvement (ICSI). Pancreas transplant for insulin-dependent diabetes. ICSI Technology Assessment Report No. 4. Bloomington, MN: ICSI; updated October 2003. Available at:http://www.icsi.org/knowledge/detail.asp?catID=107&itemID=603. Accessed January 6, 2004.
Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat. Islet transplantation. Health Technology Scientific Literature Review. Toronto, ON: Ontario Ministry of Health and Long-Term Care; October 2003.
Ruggles JA, Kelemen D, Baron A. Emerging therapies: Controlling glucose homeostasis, immunotherapy, islet transplantation, gene therapy, and islet cell neogenesis and regeneration. Endocrinol Metab Clin North Am. 2004;33(1):239-252, xii.
Stock PG, Bluestone JA. Beta-cell replacement for type I diabetes. Annu Rev Med. 2004;55:133-156.
Hering BJ, Kandaswamy R, Ansite JD, et al. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA. 2005;293(7):830-835.
Korsgren O, Nilsson B, Berne C, et al. Current status of clinical islet transplantation. Transplantation. 2005;79(10):1289-1293.
National Institute for Clinical Excellence (NICE). Pancreatic islet cell transplantation. Interventional Procedure Guidance 13. London, UK: NICE; October 2003.
Robertson P, Davis C, Larsen J, et al. Pancreas transplantation in type 1 diabetes. Diabetes Care. 2004;27(Suppl 1):S105.
Piper M, Seidenfeld J, Aronson N. Islet transplantation in patients with type 1 diabetes mellitus. Evidence Report/Technology Assessment No. 98. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No. 290-02-0026). AHRQ Publication 04-E017-2. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); August 2004. Available at: http://www.ahcpr.gov/clinic/epcsums/isletsum.htm. Accessed September 16, 2005.
Rodriguez Rilo HL, Ahmad SA, D'Alessio D, et al. Total pancreatectomy and autologous islet cell transplantation as a means to treat severe chronic pancreatitis. J Gastrointest Surg. 2003;7;978-989.
Jie T, Hering BJ, Ansite JD, et al. Pancreatectomy and auto-islet transplant in patients with chronic pancreatitis [abstract]. Surgical Forum, Alimentary Tract Category. #2005-466. American College of Surgeons 91st Annual Clinical Congress, San Francisco, CA, October 16-20, 2005.
Clayton HA, Davies JE, Pollard CA, et al. Pancreatectomy with islet autotransplantation for the treatment of severe chronic pancreatitis: The first 40 patients at the Leicester General Hospital. Transplantation. 2003;76(1):92-98.
Ryan EA, Bigam D, Shapiro AM. Current indications for pancreas or islet transplant. Diabetes Obes Metab. 2006;8(1):1-7.
Balamurugan AN, Bottino R, Giannoukakis N, Smetanka C. Prospective and challenges of islet transplantation for the therapy of autoimmune diabetes. Pancreas. 2006;32(3):231-243.
Centers for Medicare and Medicaid Services (CMS). Decision memo for pancreas transplants (CAG-00295R). Medicare Coverage Database. Baltimore, MD: CMS; April 26, 2006.
Pichon Riviere A, Augustovski F, Alcaraz A, et al. Pancreas islet stem cells and transplant for the treatment of diabetes mellitus [summary]. IRR No. 93. Buenos Aires, Argentina: Institute for Clinical Effectiveness and Health Policy (IECS); 2006.
Sansalone CV, Maione G, Rossetti O, et al. Pancreas retransplantation: Ideal timing and early and late results. Transplant Proc. 2006;38(4):1153-1155.
Genzini T, Crescentini F, Torricelli FC, et al. Pancreas retransplantation: Outcomes of 20 cases. Transplant Proc. 2006;38(6):1937-1938.
Bertuzzi F, Ricordi C. Prediction of clinical outcome in islet allotransplantation. Diabetes Care. 2007;30(2):410-417.
Boudreau R, Hodgson A. Pancreas transplantation to restore glucose control: Review of clinical and economic evidence. Technology Report No. 84. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health (CADTH); 2007.
Barr ML, Belghiti J, Villamil FG, et al. A report of the Vancouver Forum on the care of the live organ donor: Lung, liver, pancreas, and intestine data and medical guidelines. Transplantation. 2006;81(10):1373-1385.
Mineo D, Ricordi C, Xu X, et al. Combined islet and hematopoietic stem cell allotransplantation: A clinical pilot trial to induce chimerism and graft tolerance. Am J Transplant. 2008;8(6):1262-1274.
Guo B, Corabian P, Harstall C. Islet transplantation for the treatment of type 1 diabetes: An update. IHE Report. Edmonton, AB: Institute of Health Economics (IHE); December 2008.
Froud T, Faradji RN, Pileggi A, et al. The use of exenatide in islet transplant recipients with chronic allograft dysfunction: Safety, efficacy, and metabolic effects. Transplantation. 2008;86(1):36-45.
Gangemi A, Salehi P, Hatipoglu B, et al. Islet transplantation for brittle type 1 diabetes: The UIC protocol. Am J Transplant. 2008;8(6):1250-1261.
Tan J, Yang S, Cai J, et al. Simultaneous islet and kidney transplantation in seven patients with type 1 diabetes and end-stage renal disease using a glucocorticoid-free immunosuppressive regimen with alemtuzumab induction. Diabetes. 2008;57(10):2666-2671.
Berman A, Pawelec K, Fiedor P. Allogeneic transplantation of isolated islet cells in clinical practice. Pol Arch Med Wewn. 2009;119(5):326-332.
Cooper DK, Casu A. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes -- chapter 4: Pre-clinical efficacy and complication data required to justify a clinical trial. Xenotransplantation. 2009;16(4):229-238.
O'Connell PJ. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes -- chapter 6: Patient selection for pilot clinical trials of islet xenotransplantation. Xenotransplantation. 2009;16(4):249-254.
Eriksson O, Eich T, Sundin A, et al. Positron emission tomography in clinical islet transplantation. Am J Transplant. 2009;9(12):2816-2824.
Vardanyan M, Parkin E, Gruessner C, Rodriguez Rilo HL. Pancreas vs. islet transplantation: A call on the future. Curr Opin Organ Transplant. 2010;15(1):124-130.
Hermann M, Margreiter R, Hengster P. Human islet autotransplantation: The trail thus far and the highway ahead. Adv Exp Med Biol. 2010;654:711-724.
Halban PA, German MS, Kahn SE, Weir GC. Current status of islet cell replacement and regeneration therapy. J Clin Endocrinol Metab. 2010;95(3):1034-1043.
Saudek F, Girman P, Kríz J, et al. Islet transplantation for treatment of type-1 diabetes mellitus. Cas Lek Cesk. 2011;150(1):49-55.
Dong M, Parsaik AK, Erwin PJ, et al. Systematic review and meta-analysis: Islet autotransplantation after pancreatectomy for minimizing diabetes. Clin Endocrinol. 2011;75(6):771-779.
Marigliano M, Bertera S, Grupillo M, et al. Pig-to-nonhuman primates pancreatic islet xenotransplantation: An overview. Curr Diab Rep. 2011;11(5):402-412.
Bramis K, Gordon-Weeks AN, Friend PJ, et al. Systematic review of total pancreatectomy and islet autotransplantation for chronic pancreatitis. Br J Surg. 2012;99(6):761-766.
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.