Islet autotransplantation for the prevention of surgical diabetes after extended pancreatectomy for the resection of benign tumors of the pancreas

OBJECTIVE: The objective of this article is to report a single-center experience with islet autotransplantation after extensive pancreatic resection for benign tumors of the pancreas. MATERIALS AND METHODS: Seven patients underwent extensive left pancreatectomy for benign lesions located at the neck of the pancreas. Once an unequivocal diagnosis of a benign nature was ascertained, the rest of the specimen was processed and the unpurified pancreatic digest was infused into the portal vein. The results were compared with those of 8 autotransplantations performed for chronic pancreatitis over the same period. RESULTS: Tumors were 4 cystadenomas, 2 insulinomas and 1 neuroendocrine tumor. Mean islet yields were 275,000 islet equivalents (IEQ) versus 129,000 in chronic pancreatitis (P =.04) or 6700 IEQ/g of tissue versus 1900 (P =.002), resulting in transplantation of 4200 IEQ/kg body weight vs 2150 in chronic pancreatitis (P =.03), respectively at 4-month to 7.5-year follow-up, all patients are alive and 6 of 7 are off insulin. All patients off insulin after at least 1 year currently have a normal IVGTT, with K values ranging between -1.19 and -2.36 (normal < -1.00). All patients, including 1 on insulin, display positive basal and glucagon-stimulated C-peptide levels. CONCLUSIONS: Compared with chronic pancreatitis tissue resected for benign tumors is more likely to achieve good islet yields, and thus insulin independence after autotransplantation. Islet autotransplantation should be considered when extensive pancreatectomy is required for resection of a benign tumor, and only if the benign nature of the lesion is demonstrated unequivocally.     

Islet yield remains a problem in islet autotransplantation.

For patients with chronic pancreatitis whose pain is inadequately controlled with opiate analgesia, surgical resection offers a good chance of symptomatic relief. However, the inevitable sequela is type 1 diabetes mellitus and its attendant long-term complications. Islet cell autotransplantation offers a theoretical "cure" for this iatrogenic diabetes but this end point has not been produced consistently in clinical practice. The main factor determining the likelihood of insulin independence after islet autotransplantation is the islet mass that is transplanted. This review examines the factors that affect the functional islet mass available for transplantation. Original articles and reviews from peer-reviewed journals were analyzed following a computer search of the MEDLINE database from 1966 to the present, we extracted mainly level 2 and level 3 data. Although improvements in collagenase consistency and purification techniques and reductions in cold ischemic times have all been shown to improve islet yield, there is still the need to optimize every stage in the islet isolation process. Increasing the proportion of potential islets in the final isolate is of particular importance in chronic pancreatitis because the total mass of islets initially available in the gland might be just sufficient to produce insulin independence after islet autotransplantation. We believe that reducing the warm ischemic time might significantly increase the likelihood of insulin independence after islet autotransplantation.     

The role of total pancreatectomy and islet autotransplantation for chronic pancreatitis

Total pancreatectomy and islet autotransplantation are done for chronic pancreatitis with intractable pain when other treatment measures have failed, allowing insulin secretory capacity to be preserved, minimizing or preventing diabetes, while at the same time removing the root cause of the pain. Since the first case in 1977, several series have been published. Pain relief is obtained in most patients, and insulin independence preserved long term in about a third, with another third having sufficient beta cell function so that the surgical diabetes is mild. Islet autotransplantation has been done with partial or total pancreatectomy for benign and premalignant conditions. Islet autotransplantation should be used more widely to preserve beta cell mass in major pancreatic resections.     

Islet autotransplantation after pancreatectomy for chronic pancreatitis with a new method of islet preparation

Near-total (95 percent) pancreatectomy with intraportal islet autotransplantation was performed in five patients with chronic pancreatitis. Two patients are completely insulin-independent 7 and 14 months after autotransplantation; the other three patients obtained partial independence. A new method of islet cell preparation is described. Islet cell autotransplantation after total or near-total pancreatectomy should at present be viewed with cautious optimism. Additional cases need to be studied and followed up before its role in the surgery of chronic pancreatitis will be clear.     

Prevention of diabetes for up to 13 years by autoislet transplantation after pancreatectomy for chronic pancreatitis

Patients with chronic pancreatitis who undergo total pancreas resection inevitably become diabetic unless their islets are autotransplanted to prevent diabetes. We studied patients who underwent this procedure to assess its long-term efficacy in providing stable glucose regulation. Six patients were followed for up to 13 (6.2 +/- 1.7) years after intrahepatic islet autotransplantation. From 290,000 to 678,000 islets were transplanted and no patients received drugs to control glucose levels postoperatively. Islet function was assessed by measurements of fasting plasma glucose (FPG), intravenous glucose disappearance rate (KG), HbA1c, insulin responses to intravenous glucose and to arginine, and insulin secretory reserve. Patients were studied two to four times each to obtain longitudinal data. Five of six patients remained free of insulin treatment and maintained FPG <126 mg/dl and HbA1c levels <6.5%. As a group, they maintained stable insulin secretory reserve, but insulin responses to glucose tended to decrease over time in three patients. KG values correlated significantly with the number of islets originally transplanted. These data indicate that intrahepatic autoislet transplantation can successfully maintain stable beta-cell function and normal levels of blood glucose and HbA1c for up to 13 years after total pancreatectomy as treatment for chronic painful pancreatitis. This usually overlooked procedure of intrahepatic islet transplantation designed to prevent diabetes in patients undergoing pancreatectomy for chronic pancreatitis should be considered more often.     

Institutional indications for islet transplantation after total pancreatectomy

BACKGROUND/PURPOSE: This study was designed to establish institutional indications for pancreatic islet transplantation by examining patients with total pancreatectomy as candidates for islet allotransplantation. METHODS: In 12 patients who underwent total pancreatectomy, we compared pre-and postoperative plasma glucose level, body mass index, HbA1c, and daily insulin use; we examined candidacy for islet allotransplantation based on the guidelines of Japan's islet transplantation registry. RESULTS: Eight of the 12 patients with total pancreatectomy were operated for intraductal papillary mucinous neoplasm. At our institution, the 5-year survival of patients with intraductal papillary mucinous neoplasm was far better (76.3%) than that of patients with pancreatic cancer. Postoperatively, plasma glucose level, HbA1c, and daily insulin use were increased in all patients with total pancreatectomy. Of the 12 patients treated with total pancreatectomy, 4 (intraductal papillary mucinous neoplasm, n = 2; islet cell tumor, n = 1; and acute pancreatitis due to arteriovenous malformation, n = 1) showed deteriorated diabetic control and therefore were considered to be candidates for islet allotransplantation according to the guidelines. CONCLUSIONS: Islet allotransplantation could be indicated for patients with favorable postoperative survival who have had a total pancreatectomy for either benign or neoplastic disease.     

Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis

Chronic pancreatitis is difficult to treat in patients with a nondilated duct. Patients experiencing intractable pain unresponsive to or judged untreatable by lesser procedures must decide between total pancreatectomy and resultant diabetes or a continuation of their pancreatitis. From 1977 through 1990, 26 patients underwent extensive pancreatectomy and dispersed pancreatic islet tissue autotransplantation for treatment of chronic pancreatitis pain and prophylaxis of surgical diabetes. Of these 26 patients, total (Whipple) or near-total (greater than 95%) pancreatectomy was performed in 24 patients. Of these 24 patients, pain relief could be assessed in 21 patients at 5 to 155 months (mean, 5.7 years), and 19 patients (90%) reported partial or complete remission. Of the patients who underwent total or near-total pancreatectomy, islets were injected intraportally in 22 patients and into the renal subcapsule in two patients. The latter two patients have required insulin since surgery. Of the other 22, one patient died from a complication of the pancreatectomy. Nine of the 21 evaluable recipients of intraportal islet autografts were insulin independent for at least several months after surgery. Five patients are currently insulin independent at 6 years, 4 years, 1.5 years, 9 months, and 5 months after surgery. Of the other four patients, one patient died insulin independent at 6 years, and three patients required insulin beginning 8 to 18 months after surgery. Insulin independence correlated with the number of islets recovered, which in turn correlated inversely with the degree of pancreatic fibrosis. Of our four most recent patients, three patients had mildly to moderately fibrotic glands, and higher numbers of islets were obtained. After total (Whipple) pancreatectomy, these three patients are insulin independent. A liver biopsy was performed in one patient 8 months after total pancreatectomy and islet autotransplantation; numerous clusters of islet cells staining strongly for insulin and glucagon were detected within portal triads on both wedge and needle biopsy specimens. Morbidity related to the intraportal-dispersed pancreatic islet tissue transplantation was low (no disseminated intravascular coagulation, significant portal hypertension, or hepatic dysfunction). Islet autotransplantation can be an effective and safe adjunct to extensive pancreatic resection for those patients who risk surgical diabetes for relief of their chronic pancreatitis pain.     

Pancreas‐After‐Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence

Islet transplantation offers a minimally invasive approach for β cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long‐term follow‐up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow‐up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas‐after‐islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure.     

Autologous islet transplantation to prevent diabetes after pancreatic resection.

BACKGROUND: Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. OBJECTIVE: Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. PATIENTS AND METHODS: Of the 48 patients, 43 underwent total or near-total (> 95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. RESULTS: One perioperative death occurred. Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received > 300,000 islets, 74% were insulin independent at > 2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = -0.52, p = 0.006) and the dispersion method (p = 0.005). CONCLUSION: Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.     

Insulin independence and normalization of oral glucose tolerance test after islet cell allotransplantation

To achieve permanent normoglycemia in patients with type I diabetes, it is necessary to renew the insulin-producing β-cells by transplantation of either a vascularized pancreatic graft or isolated islets of Langerhans. Presently, about 10 % of patients with type I diabetes undergoing islet allotransplantation achieve insulin independence; however, glucose intolerance remains in the majority of cases. We report a case of long-term insulin independence after islet allotransplantation in a type I diabetic patient. Three years after islet transplantation, the patient remains insulin-independent with a normal oral glucose tolerance test (OGTT). The patient therefore no longer meets the World Health Organization criteria for the diagnosis of diabetes mellitus and demonstrates that islet transplantation can cure diabetes in type I diabetic patients. Received: 28 December 1999 Revised: 18 August 2000 Accepted: 24 April 2001     

Pancreatectomy with islet autotransplantation for the treatment of severe chronic pancreatitis: the first 40 patients at the leicester general hospital

BACKGROUND: Surgical resection of the pancreas is considered a final resort in the treatment of chronic pancreatitis. However, the opportunity to perform an islet autotransplant at the same time provides the potential to prevent the onset of diabetes. METHODS: Pancreatectomy together with islet autotransplantation has been offered in our center since 1994. A total of 40 patients have now undergone this procedure. The follow-up times range from 6 months to 7 years. The data presented here include the annual postoperative oral glucose tolerance test and glycosylated hemoglobin (HbA(1c)) results, together with insulin and opiate requirements. RESULTS: Nineteen male and 21 female patients (median age 44, range 21-65) have been transplanted. Pancreatitis was related to alcohol in 45% and was idiopathic in 40%. A median of 130108 (24332-1, 165538) islet equivalent (IEQ) were transplanted, which related to 2020 (320-23311) IEQ per kilogram of body weight. At 2 years posttransplant, 18 patients had a median HbA(1c) of 6.6% (5.2-19.3%), fasting C-peptide of 0.66 ng/mL (0.26-2.65 ng/mL), and required a median of 12 (0-45) units of insulin per day. At 6 years, these figures were 8% (6.1-11.1%), 1.68 ng/mL (0.9-2.78 ng/ml) and 43 U/day (6-86 U/day), respectively. The majority of patients no longer require opiate analgesia, 68% have been able to return to work, and one patient has had a baby. CONCLUSIONS: Islet autotransplantation offers a valuable addition to surgical resection of the pancreas, as a treatment for chronic pancreatitis; and even in cases in which insulin independence is not achieved, the potential beneficial effects of C-peptide make the procedure worthwhile.     

Comparative study of different pancreas transplantation modalities: Islet cell vs organ pancreas transplantation in pancreatectomized dogs

This report confirms the satisfactory results obtained with splenic autotransplantation of islet cells or organ pancreas transplantation. When the allotransplantation technique was utilized, the islet cells rejected significantly faster than the organ pancreas grafts. Rejection in the allotransplant model was correlated with high levels of glucose and amylase at the onset of this phenomenon in the organ graft group and only elevation of glucose in the islet cell group. A progressive increase of these levels was continued after the first rejection was established and this persisted until death. Our data in the dog appear to indicate that islet cell allotransplantation is not justified clinically until better methods to control rejection are introduced. However, islet cell autotransplantation appears to be a good technical advancement in cases with pancreatitis undergoing total or near total pancreatectomy. Organ pancreas transplantation appears to be a good technique for allotransplantation in virtue of our results observed in the dog that has been moderately immunosuppressed.     

Islet Transplantation and Glucose Regulation

Transplantation of isolated islets of Langerhans for treatment of diabetes has been developed through experimental research in several species and is now being applied to humans with some success albeit limited. A significant problem for human islet allotransplantation or autotransplantation (following pancreatectomy) is the relatively poor yield of islets available for transplantation. The metabolic function of islet transplant recipients that have achieved insulin independence reflects the relatively small mass of insulin-secreting tissue implanted and the fact that only the intraportal site of transplantation appears to allow sufficient graft function to achieve insulin independence. The long-term function of such grafts has been poor, with most grafts showing deterioration in function within 5 years. Studies of islet transplantation in other species showed a similar result, although other sites for islet graft implantation, such as the spleen or kidney capsule, may be associated with a better outcome. These studies, however, also suffer from problems of relatively limited islet mass. Only in the rodent model where isogeneic strains are available is it possible to transplant sufficient numbers of islets to obtain an equivalent functional islet mass similar to that found in the normal pancreas; and in this case near-normal glucose metabolism is obtained and is maintained for the life-span of the animal.     

Transplant options for patients undergoing total pancreatectomy for chronic pancreatitis

BACKGROUND: Total pancreatectomy to treat chronic pancreatitis is associated with severe diabetic control problems in 15% to 75% of patients, causing up to 50% of deaths late postoperatively. We report our experience with islet autotransplants at the time of, or with pancreas allotransplants after, total pancreatectomy. STUDY DESIGN: Between February 1, 1977, and June 30, 2003, we performed 112 islet autotransplants at the time of total pancreatectomy; we also performed 20 pancreas allotransplants in 13 patients who had already undergone total pancreatectomy months to years earlier. RESULTS: Islet autotransplants at the time of total pancreatectomy in patients who had not had previous operations on the body and tail of the pancreas were associated with a high islet yield (>2,500 islet equivalents/kg body weight), and >70% of the recipients achieved complete insulin independence. In contrast, a previous distal pancreatectomy or a Puestow drainage procedure was associated with a low islet yield in 75% of them and with complete insulin independence in <20%. A pancreas allotransplant after total pancreatectomy was not associated with any transplant-related mortality at 1 and 3 years posttransplant. The pancreas graft survival rate at 1 year posttransplant was 77% with tacrolimus-based immunosuppression (versus 67% with cyclosporine). Enteric (over bladder) drainage was preferred to manage exocrine graft secretions, to cure pancreatectomy-induced endocrine and exocrine insufficiency. CONCLUSIONS: Our series shows that pancreas allotransplants can be performed without transplant-related mortality and, when tacrolimus-based immunosuppression is used, with 1-year pancreas graft survival rates >75%. In contrast to a simultaneous islet autotransplant, a pancreas allotransplant has the disadvantage of requiring lifelong immunosuppression, but the advantage of not only curing endocrine but also exocrine insufficiency. Both transplant options, if successful, improve the recipient's quality of life.     

BETA‐2 score is an early predictor of graft decline and loss of insulin independence after pancreatic islet allotransplantation

This study aimed to evaluate whether the BETA‐2 score is a reliable early predictor of graft decline and loss of insulin independence after islet allotransplantation. Islet transplant procedures were stratified into 3 groups according to clinical outcome: long‐term insulin independence without islet graft decline (group 1, N = 9), initial insulin independence with subsequent islet graft decline and loss of insulin independence (group 2, N = 13), and no insulin independence (group 3, N = 13). BETA‐2 was calculated on day 75 and multiple times afterwards for up to 145 months posttransplantation. A BETA‐2 score cut‐off of 17.4 on day 75 posttransplantation was discerned between group 1 and groups 2 and 3 (area under the receiver operating characteristic 0.769, P = .005) with a sensitivity and negative predictive value of 100%. Additionally, BETA‐2 ≥ 17.4 at any timepoint during follow‐up reflected islet function required for long‐term insulin independence. While BETA‐2 did not decline below 17.4 for each of the 9 cases from group 1, the score decreased below 17.4 for all transplants from group 2 with subsequent loss of insulin independence. The reduction of BETA‐2 below 17.4 predicted 9 (1.5‐21) months in advance subsequent islet graft decline and loss of insulin independence (P = .03). This finding has important implications for posttransplant monitoring and patient care.     

Defining optimal immunosuppression for islet transplantation based on reduced diabetogenicity in canine islet autografts

BACKGROUND: The recent results of clinical islet transplantation have improved substantially with the introduction of a more potent but less diabetogenic immunosuppressant protocol. The successful development of this protocol was based in part on the outcomes of studies reported herein, addressing the diabetogenic potential of a series of immunosuppressant agents used alone or in combination in a canine islet autograft model. Although it is recognized that failure to achieve long-term insulin independence in human islet allotransplantation has been multifactorial, with low engraftment mass, acute or chronic rejection, autoimmune recurrence, loss of islet-acinar integrity, heterotopic site, denervation, and insulin resistance all being implicated to varying degrees, avoidance of diabetogenic immunosuppression has been pivotal to the enhanced outcomes of clinical islet transplantation. We here explore the effects of clinically relevant doses of cyclosporine or tacrolimus when given alone or in combination with glucocorticoids on long-term canine islet autograft function. METHOD: Dogs (n=8) underwent total pancreatectomy, islet isolation, and intrasplenic autotransplantation and were normoglycemic with stable long-term graft function 3 months to 8 years posttransplant. The frequently sampled intravenous glucose tolerance test (FSIGT) was performed predrug (baseline), at 1 month of therapy (on drug), and again 1 month after withdrawal of therapy (postdrug). RESULTS: Monotherapy treatments with low- or high-dose prednisone, Neoral, or tacrolimus had minimal impact on islet autograft function. The combination of Neoral and prednisone led to a marked impairment in glucose decay (25% decline from 1.77+/-0.2 to 1.24+/-0.2, P<0.05), without significant change in insulin responsiveness or glucose effectiveness. However, insulin sensitivity was markedly impaired while on therapy (7.10+/-1.2 to 3.10+/-0.5, P<0.01). Importantly, glucose decay and insulin sensitivity failed to return to baseline after withdrawal of therapy. The combination of tacrolimus and glucocorticoids led to permanent and irreversible diabetes in all recipients (n=6, P<0.001). Similar treatment of healthy control dogs led to a 44% decrease in glucose decay (P<0.01). CONCLUSIONS: Immunosuppression must be specifically tailored for islet transplantation and be glucocorticoid free if insulin independence is to be sustained clinically.     

Islet cell transplantation today

Introduction Long-term studies strongly suggest that tight control of blood glucose can prevent the development and retard the progression of chronic complications of type 1 diabetes mellitus. In contrast to conventional insulin treatment, replacement of a patient’s islets of Langerhans either by pancreas organ transplantation or by isolated islet transplantation is the only treatment to achieve a constant normoglycemic state and avoiding hypoglycemic episodes, a typical adverse event of multiple daily insulin injections. However, the cost of this benefit is still the need for immunosuppressive treatment of the recipient with all its potential risks. Materials and methods Islet cell transplantation offers the advantage of being performed as a minimally invasive procedure in which islets can be perfused percutaneously into the liver via the portal vein. Between January 1990 and December 2004, 458 pancreatic islet transplants worldwide have been reported to the International Islet Transplant Registry (ITR) at our Third Medical Department, University of Giessen/Germany. Results Data analysis of islet cell transplants performed in the last 5 years (1999–2004) shows at 1 year after adult islet transplantation a patient survival rate of 97%, a functioning islet graft in 82% of the cases, whereas insulin independence was meanwhile achieved in 43% of the cases. However, using a novel protocol established by the Edmonton Center/Canada, the insulin independence rates have improved significantly reaching meanwhile a 50–80% level. Conclusion Finally, the concept of islet cell or stem cell transplantation is most attractive, as it offers many perspectives: islet cell availability could become unlimited and islet or stem cells my be transplanted without life-long immunosuppressive treatment of the recipient, just to mention two of them.     

The start of an islet transplantation program in Japan

In Japan, pancreas donation had become possible from cadaveric donor sources, both heart-beating or non-heart-beating (NHB). Pancreas allografts have been distributed in the organ allocation system of the Japan Organ Transplant Network. Meanwhile, islet transplantation has been categorized as a tissue transplantation; it is free from legal restraints. Thus, pancreata for islet isolation must be obtained from NHB donors. Herein we report the starting program and preliminary results of islet transplantation in Japan. Selection and listing criteria for transplantation include regional priority, ABO blood type, previous islet transplant status with insulin independence, and a longer waiting time. Five institutes in Japan (Fukushima, Chiba, Kyoto, Kobe, and Fukuoka) are prepared to start programs. A two-layer cold storage method using perfluorocarbons and UW solution is recommended for pancreas preservation. Islet isolation and purification procedures are performed according to institute-specific protocol. Immunosuppression is based on sirolimus/tacrolimus combined with basiliximab induction. Two or three consecutive infusions of >5000 IE/kg are planned for each recipient until achieving insulin independence. Twenty-seven isolations and 14 transplants were performed in eight non-insulin-dependent diabetes mellitus (IDDM) recipients. Almost all (26 of 27) were NHB donors. All recipients are free from hypoglycemic episode after transplantation. One of these recipients is insulin independent; the others are currently on minimal doses of exogenous insulin. The feasibility of islet transplantation using NHB donors was confirmed using a two-layer cold storage method and a steroid-free immunosuppressive protocol, with a high rate of graft function.     

Preliminary data on post-pancreatectomy diabetes mellitus treated by islet-cell autotransplantation

The present study describes the first islet autotransplant program in Romania, and the first 3 cases of subtotal pancreatectomy for chronic pancreatitis combined with islet autotransplant. The primary objective was to pain relief by pancreatic resection, but also to preserve the endocrine function by islet autotransplant. Extensive distal pancreatectomy is effective in relieving pain, but should be limited to patients with small duct disease, in whom more conservative methods have failed, because of severe metabolic consequences. Islets were prepared by Liberase digestion of the excised pancreas, and infused unpurified into the portal vein in one case and in the omental pouch and peritoneum in two cases. All patients were relieved of pain, have achieved insulin independence, and positive C peptide levels, but one patient died of a acute bronchopneumonia 60 days post-transplantation. The mean islet yields were 2100 islet equivalents/Kg body weight. Islet autotransplantation can be considered a useful therapeutic option serving to prevent the occurrence of surgically-induced diabetes. The results have indicate that the omental pouch is a viable site for islet autotransplantation, that can accommodate a large tissue volume, is easy to access to implant, and the IBMIR (instant blood mediated inflammatory reaction) may be less severe.     

Distant processing of pancreas islets for autotransplantation following total pancreatectomy.

BACKGROUND: Small duct chronic pancreatitis is associated with intractable pain and failure to thrive, usually unresponsive to conventional management approaches. Total pancreatectomy is considered after failure of medical intervention. The major morbidity following total pancreatectomy is diabetes mellitus with its associated complications. This adverse outcome can be mitigated through autotransplantation of islets recovered from the pancreatectomy specimen. This approach has been limited historically owing to the absence of an on-site islet processing facility. We present the results from 5 pancreatectomized patients whose islets were prepared 1,500 miles away. METHODS: Five patients (4 women, 1 man, average age 42 years) who failed medical therapy and were not candidates for longitudinal pancreaticojejunostomy underwent total/completion pancreatectomy (4 total, 1 completion) for intractable symptoms from idiopathic small duct chronic pancreatitis. The resected pancreata were preserved in ViaSpan solution and were transferred to an islet processing laboratory by commercial airliner and returned. The dispersed pancreatic islet tissue was infused into a portal vein tributary through an operatively placed catheter after systemic heparinization. RESULTS: All 5 patients experienced complete relief from pancreatic pain; 2 had significant residual discomfort from underlying Crohn's disease. Three of the 5 patients had minimal or no insulin requirement after autotransplantation (median follow-up of 23 months); 1 patient continued with glycemic control difficulties related to Crohn's disease. One patient died 17 months following autotransplantation from an unrelated pneumonia. CONCLUSION: Total pancreatectomy with autologous islet transplantation can offer patients with idiopathic small duct chronic pancreatitis pain relief without the sequelae of diabetes mellitus and can be performed without an on-site islet processing facility. All patients undergoing total/ completion pancreatectomy should be considered candidates for this procedure.