-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: In the absence of a reliable islet potency assay, nude mice (NM) transplantation is the criterion standard to assess islet quality for clinical transplantation. There are factors other than islet quality that affect the transplant outcome. METHODS: Here, we analyzed the transplant outcomes in 335 NM receiving islets from human (n=103), porcine (n=205), and nonhuman primate (NHP; n=27) donors. The islets (750, 1000, and 2000 islet equivalents [IEQ]) were transplanted under the kidney capsule of streptozotocin-induced diabetic NM. RESULTS: The proportion of mice that achieved normoglycemia was significantly higher in the group implanted with 2000 IEQ of human, porcine, or NHP islets (75% normoglycemic) versus groups that were implanted with 750 IEQ (7% normoglycemic) and 1000 IEQ (30% normoglycemic). In this study, we observed that the purity of porcine islet preparations (P≤0.001), islet pellet size in porcine preparations (P≤ 0.01), and mice recipient body weight for human islet preparations (P=0.013) were independently associated with successful transplant outcome. NHP islets of 1000 IEQ were sufficient to achieve normoglycemic condition (83%). An islet mass of 2000 IEQ, high islet purity, increased recipient body weight, and high islet pellet volume increased the likelihood of successful reversal of diabetes in transplanted mice. Also, higher insulin secretory status of islets at basal stimulus was associated with a reduced mouse cure rate. The cumulative incidence of graft failure was significantly greater in human islets (56.12%) compared with porcine islets (35.57%; P≤0.001). CONCLUSION: Factors affecting NM bioassay were identified (islet mass, islet purity, pellet size, in vitro insulin secretory capability, and mouse recipient body weight) and should be considered when evaluating islet function.
Transplantation 05/2013; · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Persufflation (PSF; gaseous oxygen perfusion) is an organ preservation technique with a potential for use in donor heart preservation. Improved heart preservation with PSF may improve outcomes by maintaining cardiac tissue quality in the setting of longer cold ischemia times and possibly increasing the number of donor hearts available for allotransplant. Published data suggests that PSF is able to extend the cold storage times for porcine hearts up to 14 hours without compromising viability and function, and has been shown to resuscitate porcine hearts following donation after cardiac death. This review summarizes key published work on heart PSF, including prospective implications and future directions for PSF in heart transplantation. We emphasize the potential impact of extending preservation times and expanding donor selection criteria in heart allotransplant. Additionally, the key issues that need to be addressed before PSF were to become a widely utilized preservation strategy prior to clinical heart transplantation are summarized and discussed.
Journal of Cardiothoracic Surgery 03/2013; · 1.19 Impact Factor
-
Thomas M. Suszynski,
Kristen J. Gillingham,
Michael D. Rizzari,
Ty B. Dunn,
William D. Payne,
Srinath Chinnakotla,
Erik B. Finger, David E.R. Sutherland,
John S. Najarian,
Timothy L. Pruett,
Arthur J. Matas,
Raja Kandaswamy
[show abstract]
[hide abstract]
ABSTRACT: Rapid discontinuation of prednisone (RDP) has minimized steroid-related complications following kidney transplant (KT). This trial compares long-term (10-year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n = 440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n = 151); high-level tacrolimus (TAC, 8-12 μg/L) and low-level sirolimus (SIR, 3-7 μg/L) (TAC(H) /SIR(L) , n = 149) or low-level TAC (3-7 μg/L) and high-level SIR (8-12 μg/L) (TAC(L) /SIR(H) , n = 140). Median follow-up was ∼7 years. There were no differences between arms in 10-year actuarial patient, graft and death-censored graft survival or in allograft function. There were no differences in the 10-year actuarial rates of biopsy-proven acute rejection (30%, 26% and 20% in CSA/MMF, TAC(H) /SIR(L) and TAC(L) /SIR(H) ) and chronic rejection (38%, 35% and 31% in CSA/MMF, TAC(H) /SIR(L) and TAC(L) /SIR(H) ). Rates of new-onset diabetes mellitus were higher with TAC(H) /SIR(L) (p = 0.04), and rates of anemia were higher with TAC(H) /SIR(L) and TAC(L) /SIR(H) (p = 0.04). No differences were found in the overall rates of 16 other post-KT complications. These data indicate that RDP-based protocol yield acceptable 10-year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.
American Journal of Transplantation 02/2013; · 6.39 Impact Factor
-
Melena D Bellin,
Gregory J Beilman,
Ty B Dunn,
Timothy L Pruett,
Srinath Chinnakotla,
Joshua J Wilhelm,
Anh Ngo,
David M Radosevich,
Martin L Freeman,
Sarah J Schwarzenberg,
A N Balamurugan,
Bernhard J Hering, David E R Sutherland
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVES: Islet autotransplantation (IAT) is performed in nondiabetic patients with chronic pancreatitis at the time of total pancreatectomy (TP) to minimize risk of postoperative diabetes. The role of TP-IAT in patients with chronic pancreatitis and C-peptide-positive diabetes is not established. We postulate that IAT can preserve beta cell mass and thereby benefit patients with preexisting diabetes undergoing TP. METHODS: Preoperative metabolic testing, islet isolation outcomes, and subsequent islet graft function were reviewed for 27 patients with diabetes mellitus and chronic pancreatitis undergoing TP-IAT. The relationships between the results of preoperative metabolic testing and islet isolation outcomes were explored using regression analysis. RESULTS: Mean islet yield was 2060 (SD, 2408) islet equivalents/kg. Peak C-peptide (from mixed meal tolerance testing) was the strongest predictor of islet yield, with higher stimulated C-peptide levels associated with greater islet mass. Half of the patients who had C-peptide levels measured after transplantation demonstrated C-peptide production at a level that conveys protective benefit in type 1 diabetes (≥0.6 ng/mL). CONCLUSIONS: These findings provide proof of concept that significant islet mass can be isolated in patients with chronic pancreatitis and C-peptide-positive diabetes mellitus undergoing TP-IAT. Stimulated C-peptide may be a useful marker of islet mass before transplantation in these patients.
Pancreas 11/2012; · 2.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Total pancreatectomy with intrahepatic autoislet transplantation (TP/IAT) is a definitive treatment for relentlessly painful chronic pancreatitis. Pain relief is reported to be achieved in approximately 80% of patients. Overall, 30% to 40% achieve insulin independence, and 70% of recipients remain insulin independent for > 2 years, sometimes longer if > 300 000 islets are successfully transplanted. Yet, this approach to chronic pancreatitis is underemphasized in the general medical and surgical literature and vastly underused in the United States. This review emphasizes the history and metabolic outcomes of TP/IAT and considers its usefulness in the context of other, more frequently used approaches, such as operative intervention with partial pancreatectomy and/or lateral pancreaticojejunostomy (Puestow procedure), as well as endoscopic retrograde cholangiopancreatography with pancreatic duct modification and stent placement. Distal pancreatectomy and Puestow procedures compromise isolation of islet mass, and adversely affect islet autotransplant outcomes. Therefore, when endoscopic measures fail to relieve pain in severe chronic pancreatitis, we recommend early intervention with TP/IAT.
Hospital practice (1995). 08/2012; 40(3):80-7.
-
[show abstract]
[hide abstract]
ABSTRACT: For patients with severe chronic pancreatitis refractory to medical interventions, total pancreatectomy can be considered to relieve the root cause of pain. The goal of a simultaneous islet autotransplant is to prevent or minimize the otherwise inevitable surgical diabetes. Islet autotransplant can successfully preserve some endogenous islet function in the majority of recipients, which mediates protection against brittle diabetes. Most maintain reasonably good glycemic control, while 30 %-40 % successfully discontinue insulin therapy. With islet autotransplants reaching a wider clinical audience, refinements in islet isolation techniques and strategies to protect islet grafts post-transplant may further improve the success of this procedure.
Current Diabetes Reports 07/2012; 12(5):580-6. · 2.50 Impact Factor
-
David E R Sutherland,
David M Radosevich,
Melena D Bellin,
Bernard J Hering,
Gregory J Beilman,
Ty B Dunn,
Srinath Chinnakotla,
Selwyn M Vickers,
Barbara Bland,
A N Balamurugan,
Martin L Freeman,
Timothy L Pruett
[show abstract]
[hide abstract]
ABSTRACT: Total pancreatectomy (TP) with intraportal islet autotransplantation (IAT) can relieve pain and preserve β-cell mass in patients with chronic pancreatitis (CP) when other therapies fail. We report on a >30-year single-center series.
Four hundred and nine patients (including 53 children, 5 to 18 years) with CP underwent TP-IAT from February 1977 to September 2011 (etiology: idiopathic, 41%; Sphincter of Oddi dysfunction/biliary, 9%; genetic, 14%; divisum, 17%; alcohol, 7%; and other, 12%; mean age was 35.3 years, 74% were female; 21% has earlier operations, including 9% Puestow procedure, 6% Whipple, 7% distal pancreatectomy, and 2% other). Islet function was classified as insulin independent for those on no insulin; partial, if known C-peptide positive or euglycemic on once-daily insulin; and insulin dependent if on standard basal-bolus diabetic regimen. A 36-item Short Form (SF-36) survey for quality of life was completed by patients before and in serial follow-up since 2007, with an integrated survey that was added in 2008.
Actuarial patient survival post TP-IAT was 96% in adults and 98% in children (1 year) and 89% and 98% (5 years). Complications requiring relaparotomy occurred in 15.9% and bleeding (9.5%) was the most common complication. IAT function was achieved in 90% (C-peptide >0.6 ng/mL). At 3 years, 30% were insulin independent (25% in adults, 55% in children) and 33% had partial function. Mean hemoglobin A1c was <7.0% in 82%. Earlier pancreas surgery lowered islet yield (2,712 vs 4,077/kg; p = 0.003). Islet yield (<2,500/kg [36%]; 2,501 to 5,000/kg [39%]; >5,000/kg [24%]) correlated with degree of function with insulin-independent rates at 3 years of 12%, 22%, and 72%, and rates of partial function 33%, 62%, and 24%. All patients had pain before TP-IAT and nearly all were on daily narcotics. After TP-IAT, 85% had pain improvement. By 2 years, 59% had ceased narcotics. All children were on narcotics before, 39% at follow-up; pain improved in 94%; and 67% became pain-free. In the SF-36 survey, there was significant improvement from baseline in all dimensions, including the Physical and Mental Component Summaries (p < 0.01), whether on narcotics or not.
TP can ameliorate pain and improve quality of life in otherwise refractory CP patients, even if narcotic withdrawal is delayed or incomplete because of earlier long-term use. IAT preserves meaningful islet function in most patients and substantial islet function in more than two thirds of patients, with insulin independence occurring in one quarter of adults and half the children.
Journal of the American College of Surgeons 03/2012; 214(4):409-24; discussion 424-6. · 4.55 Impact Factor
-
Michael D Rizzari,
Thomas M Suszynski,
Kristen J Gillingham,
Ty B Dunn,
Hassan N Ibrahim,
William D Payne,
Srinath Chinnakotla,
Erik B Finger, David E R Sutherland,
Raja Kandaswamy,
John S Najarian,
Timothy L Pruett,
Aleksandra Kukla,
Richard Spong,
Arthur J Matas
[show abstract]
[hide abstract]
ABSTRACT: Rapid discontinuation of prednisone after kidney transplantation potentially allows for minimization of steroid-related side effects. Although intermediate-term data with rapid discontinuation of prednisone have been promising, concern still exists regarding long-term outcomes. The 10-year experience is reported herein.
Between October 1, 1999 and December 31, 2010, 1241 adult primary kidney transplants (791 living donor and 450 deceased donor) were performed using a protocol in which prednisone is discontinued after postoperative day 5. The 10-year actuarial recipient and graft survival rates and prednisone-related side effects were studied.
Ten-year actuarial patient survival was 71% for living donor transplants and 62% for deceased donor transplants; 10-year graft survival was 61% for living donor transplants and 51% for deceased donor transplants, and was comparable to 10-year Scientific Registry of Transplant Recipients national data. Ten-year death-censored graft survival was 79% for living donor transplants and 80% for deceased donor transplants. Ten-year acute rejection rates were 25% for deceased donor transplants and 31% for living donor transplants; 10-year chronic rejection (interstitial fibrosis/tubular atrophy) rates were 39% for deceased donor transplants and 47% for living donor transplants. For nondiabetic recipients of living donor or deceased donor allografts, the incidence of new-onset diabetes was significantly lower than in historical controls on prednisone (P<0.001). We also found significantly reduced rates of cataracts, avascular necrosis, and cytomegalovirus infection in some subgroups.
Prednisone-related side effects can be minimized in a protocol incorporating rapid discontinuation of prednisone for maintenance immunosuppression. Ten-year patient and graft outcomes remain acceptable.
Clinical Journal of the American Society of Nephrology 03/2012; 7(3):494-503. · 5.23 Impact Factor
-
David E.R. Sutherland,
Melena Bellin,
Juan J. Blondet,
Greg J. Beilman,
Ty B. Dunn,
Srinath Chinnakotla,
Timothy L. Pruett,
Martin L. Freeman,
A.N. Balamurugan,
Barbara Bland,
David Radosevich,
Bernhard J. Hering
02/2012; , ISBN: 978-953-51-0011-9
-
A N Balamurugan,
Gopalakrishnan Loganathan,
Melena D Bellin,
Joshua J Wilhelm,
James Harmon,
Takayuki Anazawa,
Sajjad M Soltani,
David M Radosevich,
Takeshi Yuasa,
Mukesh Tiwari,
Klearchos K Papas,
Robert McCarthy, David E R Sutherland,
Bernhard J Hering
[show abstract]
[hide abstract]
ABSTRACT: The optimal enzyme blend that maximizes human islet yield for transplantation remains to be determined. In this study, we evaluated eight different enzyme combinations (ECs) in an attempt to improve islet yield. The ECs consisted of purified, intact or truncated class 1 (C1) and class 2 (C2) collagenases from Clostridium histolyticum (Ch), and neutral protease (NP) from Bacillus thermoproteolyticus rokko (thermolysin) or Ch (ChNP).
We report the results of 249 human islet isolations, including 99 deceased donors (research n=57, clinical n=42) and 150 chronic pancreatitis pancreases. We prepared a new enzyme mixture (NEM) composed of intact C1 and C2 collagenases and ChNP in place of thermolysin. The NEM was first tested in split pancreas (n=5) experiments and then used for islet autologous (n=21) and allogeneic transplantation (n=10). Islet isolation outcomes from eight different ECs were statistically compared using multivariate analysis.
The NEM consistently achieved higher islet yields from pancreatitis (P<0.003) and deceased donor pancreases (P<0.001) than other standard ECs. Using the NEM, islet products met release criteria for transplantation from 8 of 10 consecutive pancreases, averaging 6510 ± 2150 islet equivalent number/gram (IEQ/g) pancreas and 694,681 ± 147,356 total IEQ/transplantation. In autologous isolation, the NEM yielded more than 200,000 IEQ from 19 of 21 pancreases (averaging 422,893 ± 181,329 total IEQ and 5979 ± 1469 IEQ/kg recipient body weight) regardless of the severity of fibrosis.
A NEM composed of ChNP with CIzyme high intact C1 collagenase recovers higher islet yield from deceased and pancreatitis pancreases while retaining islet quality and function.
Transplantation 02/2012; 93(7):693-702. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: More than 160 living donor segmental pancreas/islet transplants have been done since the first in 1977, more than three-quarters at one institution. We review this three-decade experience to project future application. Initially, living donor pancreas transplants were done because the results with deceased donors were poor. As the results with deceased donors improved, the incentive to do living donor transplants declined but never disappeared. A living donor simultaneous pancreas-kidney transplant in a uremic diabetic can correct diabetes and pre-empt dialysis with one operation, obviating the high mortality rate of waiting for a deceased donor. Solitary pancreas transplant candidates with preformed human leukocyte antigen antibodies but a negative cross match to a living donor volunteer also benefit.
The technical failure rate of living donor pancreas transplants was high in the initial cases (>1/3), nearly double that for deceased donors, but has since declined to nearly zero. Living donor segmental pancreatectomy has little surgical morbidity (currently done laparoscopically) with only a small risk for diabetes by strict selection criteria. living donor and deceased donor graft survival rates are equivalent. Islet allografts have been done from three living donors, the last one successfully, showing the potential for further application.
The incentives for living donor transplants are to eliminate long-wait times for a deceased donor organ and to improve outcomes. With both the incentive is high, but either by itself is sufficient. As the number of pancreas transplant candidates increase, so will wait times for a deceased donor organ. For this reason, living donor pancreas/islet transplant volume will likely increase in the years to come.
Current opinion in organ transplantation 02/2012; 17(1):106-15. · 1.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pancreas transplantation provides the only proven method to restore long-term normoglycemia in patients with insulin-dependent diabetes mellitus. Although many studies describe the very important risk factors for short-term survival of a pancreas transplant, there is not a lot of information available about factors that distinguish short-term from long-term graft function.
The analysis of 18,159 pancreas transplants from the International Pancreas Transplant Registry, performed from 25 July 1978 to 31 December 2005, showed an improvement not only in short-term but also in long-term graft function. Most recent 5-year, 10-year and 20-year graft function for transplants with the appropriate follow-up time showed 80, 68 and 45%, respectively, for simultaneous pancreas/kidney transplants; 62, 46 and 16%, respectively, for pancreas after kidney; and 59, 39 and 12%, respectively, for pancreas transplants alone. Important factors influencing long-term function were factors that described the quality of the deceased donor. Pancreas transplants in younger or African-American recipients showed a higher risk of graft failure. Anti-T-cell induction therapy had a significant impact on long-term survival in solitary transplants.
With a careful donor selection, not only short-term but also long-term pancreas graft function and, therefore, good metabolic control can be achieved for the diabetic patient.
Current opinion in organ transplantation 12/2011; 17(1):100-5. · 1.22 Impact Factor
-
Gopalakrishnan Loganathan,
Rajinder K Dawra,
Subbiah Pugazhenthi,
Zhiguang Guo,
Sajjad M Soltani,
Alexander Wiseman,
Mark A Sanders,
Klearchos K Papas,
Kumaravel Velayutham,
Ashok K Saluja, David E R Sutherland,
Bernhard J Hering,
A N Balamurugan
[show abstract]
[hide abstract]
ABSTRACT: Pancreatic acinar cells are commonly cotransplanted along with islets during auto- and allotransplantations. The aims of this study were to identify how acinar cell proteases cause human islet cell loss before and after transplantation of impure islet preparations and to prevent islet loss and improve function with supplementation of α-1 antitrypsin (A1AT).
Acinar cell protease activity, insulin levels, and percent islet loss were measured after culture of pure and impure clinical islet preparations. The effect of proteases on ultrastructure of islets and β-cell insulin granules were examined by transmission electron microscopy. The number of insulin granules and insulin-labeled immunogold particles were counted. The in vivo effect of proteases on islet function was studied by transplanting acinar cells adjacent to islet grafts in diabetic mice. The effects of A1AT culture supplementation on protease activity, insulin levels, and islet function were assessed in pure and impure islets.
Islet loss after culture was significantly higher in impure relative to pure preparations (30% vs. 14%, P<0.04). Lower islet purity was associated with increased protease activity and decreased insulin levels in culture supernatants. Reduced β-cell insulin granules and insulin degradation by proteases were confirmed by transmission electron microscopy. Transplantations in mice showed delayed islet graft function when acinar cells were transplanted adjacent to the islets under the kidney capsule. Supplementation of A1AT to impure islet cultures maintained islet cell mass, restored insulin levels, and preserved islet functional integrity.
Culture of impure human islet fractions in the presence of A1AT prevents insulin degradation and improves islet recovery.
Transplantation 11/2011; 92(11):1222-30. · 4.00 Impact Factor
-
Janine Abouaish,
Melanie Graham,
Pratima Bansal-Pakala,
Gopalakrishnan Loganathan,
Sajjad M Soltani,
Mukesh Tiwari,
Takeshi Yuasa,
Klearchos K Papas, David E R Sutherland,
Robert C McCarthy,
Bernhard J Hering,
A N Balamurugan
Transplantation 10/2011; 92(8):e40-2. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Islet autotransplantation (IAT) is performed at the time of total pancreatectomy (TP) to prevent or minimize post-surgical diabetes. Corticosteroids induce insulin resistance and present a risk to islet autografts, through glucotoxicity and increased metabolic demand on a marginal islet mass. We present four IAT recipients treated with oral or injected corticosteroids after transplant for medical conditions unrelated to chronic pancreatitis or TPIAT. Hyperglycemia or insulin resistance was evident in all four patients, including reversion to long-term insulin therapy in two patients. One patient receiving corticosteroid injections had a transient increase in hemoglobin A1c (+0.6% above baseline), and one patient given a one time dose of oral dexamethasone exhibited hyperglycemia despite high insulin (>200 mU/L) and C-peptide (15.3 ng/mL) production on an oral glucose tolerance test. IAT recipients have insufficient islet mass to compensate for the insulin resistance induced by corticosteroids. Caution should be given to using these agents in IAT recipients. When corticosteroids are medically necessary, insulin therapy should be administered temporarily to compensate for the increased metabolic demand and minimize long-term risks on the islet graft.
Acta Diabetologica 08/2011; · 2.78 Impact Factor
-
Melena D Bellin,
Martin L Freeman,
Sarah Jane Schwarzenberg,
Ty B Dunn,
Gregory J Beilman,
Selwyn M Vickers,
Srinath Chinnakotla,
A N Balamurugan,
Bernhard J Hering,
David M Radosevich,
Antoinette Moran, David E R Sutherland
[show abstract]
[hide abstract]
ABSTRACT: Total pancreatectomy (TP) and islet autotransplant (IAT) have been used to treat patients with painful chronic pancreatitis. Initial studies indicated that most patients experienced significant pain relief, but there were few validated measures of quality of life. We investigated whether health-related quality of life improved among pediatric patients undergoing TP/IAT.
Nineteen consecutive children (aged 5-18 years) undergoing TP/IAT from December 2006 to December 2009 at the University of Minnesota completed the Medical Outcomes Study 36-item Short Form (SF-36) health questionnaire before and after surgery. Insulin requirements were recorded.
Before TP/IAT, patients had below average health-related quality of life, based on data from the Medical Outcomes Study SF-36; they had a mean physical component summary (PCS) score of 30 and mental component summary (MCS) score of 34 (2 and 1.5 standard deviations, respectively, below the mean for the US population). By 1 year after surgery, PCS and MCS scores improved to 50 and 46, respectively (global effect, PCS P < .001, MCS P = .06). Mean scores improved for all 8 component subscales. More than 60% of IAT recipients were insulin independent or required minimal insulin. Patients with prior surgical drainage procedures (Puestow) had lower yields of islets (P = .01) and greater incidence of insulin dependence (P = .04).
Quality of life (physical and emotional components) significantly improve after TP/IAT in subsets of pediatric patients with severe chronic pancreatitis. Minimal or no insulin was required for most patients, although islet yield was reduced in patients with previous surgical drainage operations.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 05/2011; 9(9):793-9. · 5.64 Impact Factor
-
Clinical Journal of the American Society of Nephrology 05/2011; 6(5):957-9. · 5.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Using standard density gradient (SDG) ranges for human islet purification frequently results in islet loss and transplantation of lower islet mass. Measuring the densities of islet and acinar tissue beforehand to customize the gradient range for the actual COBE 2991 cell processor (COBE) purification is likely to maximize the recovery of islets. We developed an analytical test gradient system (ATGS) for predicting pancreatic tissue densities before COBE purification to minimize islet loss during purification.
Human islets were isolated from deceased donor (n=30) and chronic pancreatitis pancreata (n=30). Pancreatic tissue densities were measured before purification by the ATGS, and the density gradient range for islet purification in a COBE was customized based on density profiles determined by the ATGS. The efficiency of custom density gradients (CDGs) to recover high islet yield was compared with predefined SDGs.
Pancreatic tissue densities from autografts were significantly higher than in allograft preparations. In allograft purifications, a higher proportion of islets were recovered using ATGS-guided CDGs (85.9%±18.0%) compared with the SDG method (69.2%±27.0%; P=0.048). Acinar contamination at 60%, 70%, and 80% cumulative islet yield for allografts was significantly lower in the CDG group. In autograft purifications, more islets were recovered with CDGs (81.9%±28.0%) than SDGs (55.8%±22.8%; P=0.03). CDGs effectively reduced islet loss by minimizing islet sedimentation in the COBE bag.
Using ATGS-guided CDGs maximizes the islet recovery for successful transplantations by reducing acinar contamination in allograft preparations and by reducing sedimentation of islets in the COBE bag in autograft preparations.
Transplantation 03/2011; 91(5):508-14. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The number of islets available (yield) is an important predictor of insulin independence after islet autotransplantation (IAT) done at the time of total pancreatectomy to treat painful chronic pancreatitis. The aim of this study was to correlate histopathologic findings with islet yield and graft function.
Pancreatic histopathology was examined in 105 adults who underwent pancreatectomy and IAT; postoperative insulin use was known in 53 cases. Histologic degree of fibrosis, acinar atrophy, inflammation, and nesidioblastosis were scored by a surgical pathologist. The correlation of histopathology with islet yield and graft function was evaluated.
Patients received a median of 2968 islet equivalents per kilogram. Fibrosis and acinar atrophy correlated negatively with islet yield (P < G 0.001, r =0.67), as did inflammation (P < G 0.001, r =0.43). There was a positive correlation of islet yield (P < G 0.0001, r = 0.64) and a negative correlation of fibrosis (P = 0.006, r = 0.43) and acinar atrophy (P = 0.006, r = 0.42) with islet graft function.
More severe histopathologic changes were associated with a lower islet yield and lower likelihood of insulin independence. Total pancreatectomy and IAT should not be delayed in patients with painful chronic pancreatitis refractory to medical therapy; otherwise progressive damage to the pancreas may limit islet yield and increase the risk of diabetes.
Pancreas 03/2011; 40(2):193-9. · 2.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objective: The number of islets available (yield) is an important predictor of insulin independence after islet autotransplantation (IAT) done at the time of total pancreatectomy to treat painful chronic pancreatitis. The aim of this study was to correlate histopathologic findings with islet yield and graft function.
Methods: Pancreatic histopathology was examined in 105 adults who underwent pancreatectomy and IAT; postoperative insulin use was known in 53 cases. Histologic degree of fibrosis, acinar atrophy, inflammation, and nesidioblastosis were scored by a surgical pathologist. The correlation of histopathology with islet yield and graft function was evaluated.
Results: Patients received a median of 2968 islet equivalents per kilogram. Fibrosis and acinar atrophy correlated negatively with islet yield (P < 0.001, r = −0.67), as did inflammation (P < 0.001, r = −0.43). There was a positive correlation of islet yield (P < 0.0001, r = 0.64) and a negative correlation of fibrosis (P = 0.006, r = −0.43) and acinar atrophy (P = 0.006, r = −0.42) with islet graft function.
Conclusion: More severe histopathologic changes were associated with a lower islet yield and lower likelihood of insulin independence. Total pancreatectomy and IAT should not be delayed in patients with painful chronic pancreatitis refractory to medical therapy; otherwise progressive damage to the pancreas may limit islet yield and increase the risk of diabetes.
Abbreviations: IAT - islet autotransplantation, CP - chronic pancreatitis
Pancreas 02/2011; 40(2):193-199. · 2.39 Impact Factor
