Intramuscular Autotransplantation of Pancreatic Islets in a 7-Year-Old Child: A 2-Year Follow-Up

Abstract

A 7-year-old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160 000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C-peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5-and 27-months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C-peptide levels were 0.67 ± 0.07 and 3.36 ± 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long-term clinically significant metabolic control.

Optimising islet engraftment is critical for successful clinical islet transplantation

“…The intramuscular site would also allow transplantation of composite isletendothelial cell grafts [46,48] or the application of various matrices carrying growth factors that would facilitate the formation of a new endocrine organ at the new site of implantation. Indeed, in autotransplants, we have successfully transplanted isolated islets of Langerhans intramuscularly into the forearm of a patient undergoing total pancreatectomy because of recurrent life-threatening pancreatitis [49].…”

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

“…Other sites used, such as the renal capsule (Gray et al, 1988;Gray et al, 1989;Matarazzo et al, 2002;Vargas et al, 2001), spleen (Gray, 1990;Gustavson et al, 2005;Sutton et al, 1989), omentum (Ao et al, 1993;Gustavson et al, 2005) and peritoneal cavity (Wahoff et al, 1994a;Wahoff et al, 1994b) rarely have been associated with function of islet autografts in people (Fontana et al, 1994;White et al, 2000b) . A recent clinical case report from Sweden demonstrated function (C-peptide positive) of an intramuscular IAT in a 7 year old child undergoing TP for CP (Rafael et al, 2008). The islet yield was high (6400 IE/kg), an amount that usually results in insulin-independence in children if embolized to the liver via the portal vein , suggesting that better islet function might have been achieved if the islets has been placed intra-hepatic.…”

“…Including the cases done outside the University Of Minnesota, IATs have been performed in at least 50 children (not all published) with the majority of islet grafts infused intraportally (Bellin et al, 2008a;Bellin et al, 2011b;Sutherland et al, 2011a). There is one case report of intramuscular autoislet transplant in a 7 year old child; this patient had documented graft function and good metabolic control for over 2 years post-IAT but did not achieve insulin independence (Rafael et al, 2008). In children undergoing intraportal IAT, 40-50% of patients achieve insulin independence in the first 1 year after IAT, with the highest rate of insulin independence in preadolescent children .…”

“…The main criterion for success of the islet autograft per se is whether insulin independence is maintained or surgical diabetes made milder. The overall outcome, however, depends as much on the clinical response as on the metabolic results, specifically whether the patient's pain is reduced or eliminated, narcotic analgesics withdrawn, and the quality of life (QOL) improved (Bellin et al, 2010b;Bellin et al, 2011b;Bellin et al, 2011c;Billings et al, 2011;Rafael et al, 2008;Sutton et al, 2010).…”

Noninvasive Imaging of Islet Transplants with 111In-Exendin-3 SPECT/CT

“…A suitable location for islet transplantation is muscle. Muscle is already used in clinical islet transplantation (10)(11)(12)(13), and since all islets are clustered in one location, tracer uptake can be determined by quantitative analysis of PET and SPECT images, and islet survival can easily be verified histologically.…”