Pancreas allotransplants in patients with a previous total pancreatectomy for chronic pancreatitis

BACKGROUND: A total pancreatectomy is the last resort in the treatment of chronic pancreatitis because it results in complete endocrine and exocrine pancreatic insufficiency. More than 50% of total pancreatectomy patients experience severe glucose control problems, which cause up to 50% of late deaths. STUDY DESIGN: Between June 1, 1986, and May 15, 2007, we performed 26 pancreas allotransplants (18 primary, 8 retransplants) in 18 patients who had previously undergone a total pancreatectomy for chronic pancreatitis. All patients had a history of labile diabetes mellitus with hypoglycemic unawareness; secondary diabetic complications developed in 12. The median time interval from the total pancreatectomy to the pancreas allotransplant was 5 years (range 9 months to 22 years). Of the 26 transplants, 6 were performed in the cyclosporine (CSA) era, 15 in the tacrolimus (TAC) era, and 5 in the calcineurin inhibitor (CNI)-free era. RESULTS: Patient survival rates at 1 and 3 years in both the CSA and TAC eras were 100% and 100%; in the CNI-free era, at 1 year, the survival rate was 40%. Pancreas graft survival rates in the CSA era were 67% and 50% at 1 and 3 years, respectively; in the TAC era, 73% and 51%, respectively; and in the CNI-free era, at 1 year, 40% (p=0.13). The mean number of rejection episodes in the CSA era was 2.1; in the TAC era, 1.4; and in the CNI-free era, 0.6. CONCLUSIONS: Our series of pancreas allotransplants in patients with a previous total pancreatectomy for chronic pancreatitis showed that pancreas graft survival rates of more than 70% can be achieved with TAC-based immunosuppression; pancreas transplants can successfully treat both endocrine and exocrine insufficiency; and sequential pancreas allotransplants should be considered a treatment option in patients with pancreatectomy-induced brittle diabetes mellitus or with progression of secondary complications of diabetes mellitus.     

High Risk of Sensitization After Failed Islet Transplantation

Human Leukocyte Antigen (HLA) antibodies posttransplant have been associated with an increased risk of early graft failure in kidney transplants. Whether this also applies to islet transplantation is not clear. To achieve insulin independence after islet transplants multiple donor infusions may be required. Hence, islet transplant recipients are at risk of sensitization after transplantation. Islet transplant recipients were screened for HLA antibodies posttransplant by flow-based methods. A total of 98 patients were studied. Twenty-nine patients (31%) developed de novo donor specific antibodies (DSA) posttransplant. Twenty-three patients developed DSA while on immunosuppression (IS). Among recipients who have discontinued IS, 10/14 (71%) are broadly sensitized with panel reactive antibody (PRA) >or=50%. The risk of becoming broadly sensitized after transplant was 11/69 (16%) if the recipient was unsensitized prior to transplant. The majority of these antibodies have persisted over time. Appearance of HLA antibodies posttransplant is concerning, and the incidence rises abruptly in subjects weaned completely from IS. This may negatively impact the ability of these individuals to undergo further islet, pancreas or kidney transplantation and should be discussed upfront during evaluation of candidates for islet transplantation.     

Results of our first nine intraportal islet allografts in type 1, insulin-dependent diabetic patients

With the first demonstration of insulin independence following intraportal islet transplantation into a patient with type 1 diabetes, a new era of clinical islet transplantation will begin. This report provides our initial experience of clinical islet transplantation with a total of nine consecutive portal vein islet transplants in seven diabetic recipients. The first three transplants were done in nonrenal failure diabetics (NRFI) using 6319 +/- 2173 islets/kg body weight with islets processed from single pancreas and cultured for 7 days at 24 degrees C. Prednisone, azathioprine, and cyclosporine were initiated prior to transplant. While all three recipients demonstrated C-peptide function posttransplant, all three rejected their grafts at 2 weeks. Five days of OKT3 treatment failed to recover more than 10% of their rejecting islet grafts. The studies were then shifted to established kidney transplant recipients (EKI) maintaining their basal immunosuppression while adding 7 days of Minnesota antilymphoblast globulin (MALG) to the recipient using islets from single donor pancreas that had been cultured for 7 days at 24 degrees C. There were an average of 6161 +/- 911 islets transplanted intraportally into three EKI recipients. All three had C-peptide response from the transplant, but none achieved insulin independence. While the first patient rejected his graft at 2 weeks, two recipients demonstrated long-term islet function up to 10 months posttransplant. Sustacal challenge testing demonstrated C-peptide responsiveness, but in a delayed pattern suggesting insufficient islet mass had been transplanted. The next three kidney transplant recipients received islets from more than one donor pancreas averaging 13,916 +/- 556 islets/kg body weight. The first of these was the first to achieve insulin independence from 10 to day 25 posttransplant when she appeared to have a rejection episode. The second and third recipients were retransplanted with islets from multiple donors having achieved partial islet function from single pancreas donor. The first patient on triple immunosuppression is demonstrating long-term partial function at 184 days but is not insulin independent. The third patient on prednisone and azathioprine received one half his islets after 7-day culture and the other half after 7-day culture combined with cryopreservation. He is continuing to demonstrate insulin independence for 154 days post-transplant with a glycated hemoglobin value of 5.6%. Sustacal challenge data demonstrate a total stimulated C-peptide response of 155 rhomol/ml at 4 months post-transplant compared with 148 +/- 12 rhomol/ml for normal controls (NC) and 425 rhomol/ml for nondiabetic, established kidney transplant recipients on triple immunosuppression.(ABSTRACT TRUNCATED AT 400 WORDS)     

Central pancreatectomy revisited

Central pancreatectomy is a surgical procedure that removes the middle segment of the pancreas and preserves the distal pancreas and spleen. This limited resection has the advantage of conserving normal, uninvolved pancreatic parenchyma, thus reducing the possibility of postoperative exocrine and endocrine dysfunction. While the incidence of postoperative endocrine insufficiency may be as low as 4%, procedural morbidity, specifically pancreatic fistula, appears to exceed the published rates for standard resections (i.e., distal/subtotal pancreatectomy or pancreaticoduodenectomy). We have reviewed our prospective pancreatic cancer database to determine the utilization of central pancreatectomy in a major cancer center with expertise in pancreatic surgery. We identified only 10 cases of central pancreatectomy over the past 13 years. Six (60%) had postoperative complications including three cases (30%) of pancreatic fistula. No patients died as a result of the procedure. At a median follow-up of 13.6 months (mean, 25.2 months), only one patient had mild endocrine insufficiency and no patients had clinically significant exocrine dysfunction. The associated morbidity of central pancreatectomy may outweigh any potential benefit in long-term pancreatic secretory function. We suggest that such a procedure be used selectively, where preservation of the pancreas appears essential.     

A new indication for pancreas transplantation: high grade pancreatic dysplasia

A 42-yr-old male presented with a family history of pancreatic carcinoma inherited an autosomal dominant pattern. The development of endocrine and exocrine pancreatic insufficiency served as early markers for neoplastic transformation. Screening endoscopic ultrasound and ERCP showed abnormalities suggestive of pancreatic dysplasia. Total pancreatectomy was performed and pathology confirmed carcinoma in situ, also known as high-grade pancreatic ductal dysplasia or Pan IN-3. The patient's post-operative course was complicated by life threatening, brittle diabetes. Pancreas transplantation was successfully performed. One year following transplantation, the patient has excellent pancreas graft function. He remains insulin free and has no signs of malignancy. Total pancreatectomy followed by pancreas transplantation is a viable therapeutic option for patients in the dysplastic but still pre-malignant phase of familial pancreatic adenocarcinoma who develop hypoglycemic unawareness following total pancreatectomy.     

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.     

Human Islet Isolation for Autologous Transplantation: Comparison of Yield and Function Using SERVA/Nordmark Versus Roche Enzymes

Islet autotransplantation (IAT) is used to preserve as much insulin-secretory capacity as possible in patients undergoing total pancreatectomy for painful chronic pancreatitis. The enzyme used to dissociate the pancreas is a critical determinant of islet yield, which is correlated with posttransplant function. Here, we present our experience with IAT procedures to compare islet product data using the new enzyme SERVA/Nordmark (SN group; n = 46) with the standard enzyme Liberase-HI (LH group; n = 40). Total islet yields (mean ± standard deviation; 216 417 ± 79 278 islet equivalent [IEQ] in the LH group; 227 958 ± 58 544 IEQ in the SN group; p = 0.67) were similar. However, the percentage of embedded islets is higher in the SN group compared to the LH group. Significant differences were found in pancreas digestion time, dilution time, and digested pancreas weight between the two groups. Multivariate linear regression analysis showed the two groups differed in portal venous pressure changes. The incidence of graft function and insulin independence was not different between the two groups. The SN and LH enzymes are associated with similar outcomes for IAT. Further optimization of the collagenase/neutral protease ratio is necessary to reduce the number of embedded islets obtained when using the SN enzyme.     

Middle pancreatectomy: indications, short- and long-term operative outcomes

OBJECTIVE: To evaluate the indications, perioperative, and long-term outcomes of a large cohort of patients who underwent middle pancreatectomy (MP). SUMMARY BACKGROUND DATA: MP is a parenchyma-sparing technique aimed to reduce the risk of postoperative exocrine and endocrine insufficiency. Reported outcomes after MP are conflicting. METHODS:: Patients who underwent MP between 1990 and 2005 at the Massachusetts General Hospital and at the University of Verona were identified. The outcomes after MP were compared with a control group that underwent extended left pancreatectomy (ELP) for neoplasms in the mid pancreas. RESULTS: A total of 100 patients underwent MP. The most common indications were neuroendocrine neoplasms, serous cystadenoma, and branch-duct IPMNs. Comparison with 45 ELP showed that intraoperative blood loss and transfusions were significantly higher for ELP. The 2 groups showed no differences in overall morbidity, abdominal complications, overall pancreatic fistula, and grade B/C pancreatic fistula rate (17% in MP and 13% in ELP), but the mean hospital-stay was longer for MP patients (P = 0.005). Mortality was zero. In the MP group, 5 patients affected by IPMNs had positive resection margins and 3 had recurrence. After a median follow-up of 54 months, incidence of new endocrine and exocrine insufficiency were significantly higher in the ELP group (4% vs. 38%, P = 0.0001 and 5% vs. 15.6%, P = 0.039, respectively). CONCLUSIONS: MP is a safe and effective procedure for treatment of benign and low-grade malignant neoplasms of the mid pancreas and is associated with a low risk of development of exocrine and endocrine insufficiency. MP should be avoided in patients affected by main-duct IPMN.     

The case for pancreas after kidney transplantation

Abstract:  Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.     

De Novo Donor‐Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes

Outcomes after islet transplantation continue to improve but etiology of graft failure remains unclear. De novo donor‐specific human leukocyte antigen (HLA) antibodies (DSA) posttransplant are increasingly recognized as a negative prognostic marker. Specific temporal associations between DSA and graft function remain undefined particularly in programs undertaking multiple sequential transplants. Impact of de novo DSA on graft function over 12 months following first islet transplant was determined prospectively in consecutive recipients taking tacrolimus/mycophenolate immunosuppression at a single center. Mixed‐meal tolerance test was undertaken in parallel with HLA antibody assessment pretransplant and 1–3 months posttransplant. Sixteen participants received a total of 26 islet transplants. Five (19%) grafts were associated with de novo DSA. Five (31%) recipients were affected: three post–first transplant; two post–second transplant. DSA developed within 4 weeks of all sensitizing grafts and were associated with decreased stimulated C‐peptide (median [interquartile range]) at 3 months posttransplant (DSA negative: 613(300–1090); DSA positive 106(34–235) pmol/L [p = 0.004]). De novo DSA directed against most recent islet transplant were absolutely associated with loss of graft function despite maintained immunosuppression at 12 months in the absence of a rescue nonsensitizing transplant. Alemtuzumab induction immunosuppression was associated with reduced incidence of de novo DSA formation (p = 0.03).     

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.     

Median pancreatectomy for tumors of the neck and body of the pancreas

Background: When enucleation is too risky because of possible damage of the main pancreatic duct, benign tumors located in the neck or body of the pancreas are usually removed by a left (spleno)-pancreatectomy or by a pancreatoduodenectomy. But standard pancreatic resection results in an important loss of normal pancreatic parenchyma and may cause impairment of exocrine and endocrine function. The aim of this study was to evaluate early and longterm results of median pancreatectomy, a limited resection of the midportion of the pancreas, in selected patients with benign or borderline tumors of the pancreas.

Study Design: Records of patients at Ospedale Busonera between November 1985 and September 1998 were reviewed. Ten patients with tumors of the neck or body of the pancreas underwent median pancreatectomy; the cephalic stump was sutured and the distal stump was anastomosed with a Roux-en-Y jejunal loop. Followup included clinical evaluation and routine laboratory tests: abdominal ultrasonography, exocrine and endocrine pancreatic function with fecal chymotrypsin, and an oral glucose tolerance test.

Results: Pathologic examination showed: insulinoma (n = 3), mucinous cystadenoma (n = 3), nonfunctioning endocrine tumor (n = 1), papillary-cystic neoplasm (n = 1), serous cystadenoma (n = 1), and intraductal mucinous tumor (n = 1). Operative mortality and morbidity were 0% and 40%, respectively; pancreatic fistula occurred in three patients. At mean followup of 62.7 months, no recurrence was found and no patient had exocrine insufficiency or glucose metabolism impairment.

Conclusions: Median pancreatectomy is a safe and effective alternative to major pancreatic resection in selected patients with benign or low-malignant lesions of the pancreas. This procedure carries a surgical risk similar to that of the standard operation, but avoids extensive pancreatic resection and pancreatic function impairment.     

Long-term normoglycemia in pancreatectomized dogs following pancreatic islet allotransplantation and cyclosporine immunosuppression

Pancreatectomized dogs received intrasplenic autotransplants or allotransplants of unpurified islets prepared from the pancreata of unrelated outbred dogs, by a standard collagenase ductal perfusion method. Allograft immunosuppression consisted of tapering azathioprine-prednisone (AP), low level cyclosporine (CsA, through whole blood high-pressure liquid chromatography (HPLC) level 300-600 micrograms/L), or high CsA (600-1000 micrograms/L). While AP and low CsA failed to delay rejection, high CsA achieved prolonged (greater than 100 days) graft function in 5 of 12 dogs, with a median duration of 85.5 days. (P less than .01 vs. AP and low CsA). While no interference with islet engraftment was seen in CsA-treated dogs, late graft failure (greater than 30 days) was seen in 3 of 6 CsA autografts and 5 of 12 high CsA allografts. CsA at whole-blood HPLC levels of 600-1000 micrograms/L can achieve prolonged normoglycemia in pancreatectomized canine recipients of islet allografts. The effects of such doses of CsA on islet function may be substantial.     

HLA class I sensitization in islet transplant recipients: report from the Collaborative Islet Transplant Registry

Pancreatic islet transplantation is a promising treatment option for patients severely affected with type 1 diabetes. This report from CITR presents pre- and posttransplant human leukocyte antigen (HLA) class I sensitization rates in islet-alone transplantation. Data came from 303 recipients transplanted with islet-alone between January 1999 and December 2008. HLA class I sensitization was determined by the presence of anti-HLA class I antibodies. Panel-reactive antibodies (PRA) from prior to islet infusion and at 6 months, and yearly posttransplant was correlated to measures of islet graft failure. The cumulative number of mismatched HLA alleles increased with each additional islet infusion from a median of 3 for one infusion to 9 for three infusions. Pretransplant PRA was not predictive of islet graft failure. However, development of PRA >20% posttransplant was associated with 3.6-fold (p < 0.001) increased hazard ratio for graft failure. Patients with complete graft loss who had discontinued immunosuppression had significantly higher rate of PRA ≥ 20% compared to those with functioning grafts who remained on immunosuppression. Exposure to repeat HLA class I mismatch at second or third islet infusions resulted in less frequent development of de novo HLA class I antibodies when compared to increased class I mismatch. The development of HLA class I antibodies while on immunosuppression is associated with subsequent islet graft failure. The risk of sensitization may be reduced by minimizing the number of islet donors used per recipient, and in the absence of donor-specific anti-HLA antibodies, repeating HLA class I mismatches with subsequent islet infusions.     

Variability in endocrine cell identity in patients with chronic pancreatitis undergoing islet autotransplantation

Beta‐cell dedifferentiation as shown by cellular colocalization of insulin with glucagon and/or vimentin, and decreased expression of MAFA and/or urocortin3 has been suggested to contribute to metabolic decompensation in type 2 diabetes, and was recently described postimplantation in islet allotransplant patients. Dysglycaemia and diabetes mellitus are often encountered preoperatively in patients undergoing pancreatectomy and islet autotransplantation (PIAT). In this series of case reports, we document variation in islet phenotypic identity in three patients with chronic pancreatitis (CP) without diabetes or significant insulin resistance who subsequently underwent PIAT. Pancreas histology was examined using colocalization of endocrine hormones, mesenchymal and pan‐endocrine markers in islets, and the relative expression of MAFA and urocortin3 in insulin‐expressing cells as compared to that of nondiabetic and type 2 diabetic donors. We present results of pre‐ and posttransplant clinical metabolic testing. Varying degrees of islet‐cell dedifferentiation are identified in nondiabetic patients with CP at the time of PIAT, and may need further investigation.     

Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations

BACKGROUND: A series of 13 islet autotransplantations and 13 islet allotransplantations performed between 1992 and 1999 at the University Hospital of Geneva are presented. Factors affecting the outcome are analyzed. METHODS: Islet autotransplantation has been performed in seven patients with chronic pancreatitis and in six patients with benign tumors undergoing extensive pancreatectomy. Islet allografts were performed in C-peptide-negative patients simultaneously or after a kidney or lung transplantation. Each recipient received islets from one to four donors. Panel-reactive antibodies were monitored by microlymphocytotoxicity test. RESULTS: Eleven of 13 patients who underwent autotransplantation maintained insulin independence for 6 months to 5 years. Two years after autologous islet transplantation, five of nine patients were insulin independent with an glycosylated hemoglobin of 5.9%. Three late islet failures occurred in patients with chronic pancreatitis. Islet yield was significantly lower in patients with chronic pancreatitis than in patients with benign tumors (2044 equivalent islet number/gram resected pancreas versus 5184 equivalent islet number/gram; P=0.037). In islet allotransplantation, no early graft loss was found. All 13 patients who underwent allotransplantation had basal C-peptide levels above 0.3 nmol/L for 3 months to 5 years. Mean glycosylated hemoglobin decreased from 9.1% before transplantation to 5.5% at month 3. Insulin independence was achieved in two type I diabetic patients. In four of six patients with graft failure, the graft had induced panel-reactive antibodies. CONCLUSIONS: In islet autotransplantation, the reduced number of islets that can be isolated from fibrotic pancreata may be the major limiting factor. In islet allotransplantation, early graft function can now be consistently achieved. Islet allografts seem to be highly immunogenic, and chronic islet failure cannot be prevented consistently by conventional immunosuppression.     

Addition of a total pancreatectomy and pancreas transplantation in a liver transplant recipient with intraductal papillary mucinous neoplasm of the pancreas

Abstract: Background: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are increasingly recognized in clinical practice. There are no published data suggesting a management approach for the potential organ transplant recipient with the incidental finding of this pre‐malignant lesion. Methods: The recipient was a 65‐yr‐old man with hepatocellular carcinoma in a background of Laennec’s cirrhosis. During evaluation for transplant, he was found to have diffuse IPMN. This patient underwent liver transplantation with a planned simultaneous total native pancreatectomy and pancreas transplant from the same donor. Results: The patient has had normal liver function and has been free of diabetes and exocrine insufficiency at 18 months post‐transplant. Conclusion: IPMN in the potential transplant recipient should be managed more aggressively than in the general population because these patients will be committed to life‐long immunosuppression. If a total pancreatectomy is contemplated, this is a unique opportunity to replace the pancreas with an allograft at the time of transplantation.     

Total Pancreatectomy: Indications,Operative Technique,and Postoperative Sequelae

Total pancreatectomy has been used to treat both benign and malignant disease of the pancreas, but its use has been limited by concerns about management of the apancreatic state with its attendant total endocrine and exocrine insufficiency. Here, we review the indications for total pancreatectomy, operative technique, and improvements in the postoperative management of patients. Total pancreatectomy remains a viable option in the treatment of intractable pain associated with chronic pancreatitis, multicentric or extensive neuroendocrine tumors, patients with familial pancreatic cancer with premalignant lesions, and in patients with intraductal papillary mucinous neoplasia with diffuse ductal involvement or invasive disease. Improvements in postoperative management include auto-islet cell transplantation, advances in insulin formulations, and the use of glucagon rescue therapy which allow much tighter control of blood glucose than previously possible. This markedly lessens the risk of life-threatening hypoglycemia and decreases the risk of long-term complications, resulting in improved quality of life for these patients.     

Canine pancreatic endocrine function after interruption of pancreatic exocrine drainage

Pancreatic endocrine function was studied in forty dogs after ligation or free i.p. drainage of the pancreatic duct, with or without simultaneous partial pancreatectomy. Shrinkage and fibrosis of the pancreas occurred in all dogs, with equal severity in the open duct and duct-tied groups. Fasting blood sugars remained within the normal range but fasting levels of plasma insulin and glucagon were reduced. Dynamic tests of endocrine function indicated that partial pancreatectomy reduced the insulin response to i.v. injection of dextrose or glucagon and delayed the reestablishment of glucose homeostasis. Glucose tolerance was normal in dogs with intact pancreases, but duct ligation was associated with deteriorating recovery after glucagon injection. The precise coordination of circulating glucose, insulin, and glucagon levels seen in normal dogs was lost in both partial and intact pancreas groups and these disturbances were attributed to the fibrotic changes arising from interference with the ductal drainage. Both ligation and free i.p. drainage of the pancreatic duct therefore resulted in abnormalities of islet function. When combined with partial pancreatectomy, both techniques were associated with significant pancreatic endocrine insufficiency.     

A Comparative Analysis of the Safety,Efficacy, and Cost of Islet Versus Pancreas Transplantation in Nonuremic Patients With Type 1 Diabetes

Few current studies compare the outcomes of islet transplantation alone (ITA) and pancreas transplantation alone (PTA) for type 1 diabetes (T1D). We examined these two beta cell replacement therapies in nonuremic patients with T1D with respect to safety, graft function and cost. Sequential patients received PTA (n = 15) or ITA (n = 10) at our institution. Assessments of graft function included duration of insulin independence; glycemic control, as measured by hemoglobin A1c; and elimination of severe hypoglycemia. Cost analysis included all normalized costs associated with transplantation and inpatient management. ITA patients received one (n = 6) or two (n = 4) islet transplants. Mean duration of insulin independence in this group was 35 mo; 90% were independent at 1 year, and 70% were independent at 3 years. Mean duration of insulin independence in PTA was 55 mo; 93% were insulin independent at 1 year, and 64% were independent at 3 years. Glycemic control was comparable in all patients with functioning grafts, as were overall costs ($138 872 for ITA, $134 748 for PTA). We conclude that with advances in islet isolation and posttransplant management, ITA can produce outcomes similar to PTA and represents a clinically viable option to achieve long‐term insulin independence in selected patients with T1D.