Total and immediate pancreatectomy as the mandatory requirement for the ulterior function of autotransplanted islets in dogs.
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Islet autotransplantation prevents diabetes in some patients after total pancreatectomy. Pancreatectomy is done at most hospitals but islets are prepared at only a few centers. We report a case in which the pancreas was sent to a laboratory half a continent distant from the operative site, and islets were prepared and returned to the original hospital for autotransplantation 16 h after resection. At 10 months posttransplantation, the patient is normoglycemic and insulin independent, with an appropriate insulin secretion in response to glucose. Endocrine function can be retained after pancreatectomy even if the islets are isolated at a remote laboratory, and autotransplantation could be offered to patients without the need to travel. This outcome implies that the typical handling and processing of a pancreas destined to yield an islet allograft should not prevent the recovery of a sufficient number of viable β cells to establish insulin independence in type 1 diabetic recipients.
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Pancreatic Islets
Total pancreatectomy
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Pancreatitis, chronic
Total pancreatectomy
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Background. Cystic neoplasms of the pancreas are an increasingly diagnosed entity, and surgical resection of the pancreas is advocated. Islet autotransplantation is a therapeutic approach used to prevent diabetes in cases of pathologically benign neoplasm after major pancreatectomy. Methods. A total of 10 patients underwent pancreatectomy with islet autotransplantation. To evaluate islet transplantation efficiency, the authors compared 23 subjects who did not undergo islet transplantation after partial pancreatectomy with 87 subjects with normal glucose tolerance and with 77 diabetic subjects that did not undergo pancreatectomy. Results. Ten female patients with nine cystic neoplasms and one patient with pancreatic injury underwent transplantation. Their mean islet equivalents (IEQ) was 3,159 IEQ/kg. During follow-up, two recipients required insulin or oral agents. At the 12-month follow-up, homeostasis model assessment (HOMA)-β was 77.36±17.68, the insulinogenic index (INSindex) was 0.49±0.11, and fasting C-peptide and hemoglobin A1c were 1.28±0.18 ng/mL and 5.73±0.26%, respectively. Islet replacement was found to increase HOMA-β by approximately 17% compared with distal pancreatectomy in normal glucose tolerance subjects without islet autotransplantation and by 46% compared with distal pancreatectomy diabetes subjects without islet autotransplantation. Factors different in the two insulin and oral hypoglycemic agent (OHA)-requiring recipients and the eight insulin- and OHA-free recipients were pancreatectomy extent, preoperative glucose metabolism insufficiency, age, and underlying cystic neoplasm disease. Conclusions. Even partial islet graft function can have a beneficial metabolic effect on the recipient in terms of metabolic parameters such as HOMA-β and INSindex. This study suggests that islet replacement should be considered for experimental procedures in benign pancreatic conditions.
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Total pancreatectomy is considered the final resort in the treatment of chronic pancreatitis; however, here we show that simultaneous islet autotransplantation can abrogate the onset of diabetes. Methods: In Leicester, 46 patients have now undergone total pancreatectomy with immediate islet auto transplant, and they have received a median of 2246 islet equivalent (IEQ)/kg body weight (range, 405-20,385 IEQ/kg body weight). Results: Twelve patients have shown periods of insulin independence, for a median of 16.5 months (range, 2-63 months), and 5 remain insulin independent. Over the 10 years of follow-up, there has been a notable increase in insulin requirement per kilogram per day, and percentage of glycosylated hemoglobin levels have increased significantly (r = 0.66, P = 0.01). However, 100% of patients tested were C-peptide positive at their most recent assessment, and high fasting and stimulated C-peptide values recorded at 10 years after transplantation, 1.44 (range, 1.09-1.8 ng/mL) and 2.86 ng/mL (range, 1.19-4.53 ng/mL), respectively, suggest significant graft function in the long term. In addition, median serum creatinine has increased very little after the operation (71 nmol/L [range, 49-125 nmol/L] atpreoperation vs 76.5 nmol/L [range 72-81 nmol/L] at year 10), suggesting no diabetic nephropathy. Conclusions: Although there is a notable decline in islet function after islet auto transplant, there is still evidence of significant long-term insulin secretion and possible protection against diabetic complications. Abbreviations: CP - chronic pancreatitis, HbA1c - glycosylated hemoglobin, IEQ - islet equivalent, OGTT - oral glucose tolerance test, TP - total pancreatectomy
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Total pancreatectomy
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Abstract Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP‐IAT). We assessed if pancreas volume calculated with preoperative MRI could assess islet yield and postoperative outcomes. We reviewed dynamic MRI studies from 154 adult TP‐IAT patients (2009‐2016), and associations between calculated volumes and digest islet equivalents (IEQs) were tested. In multivariate regression analysis, pancreas volume ( P < .001) and preoperative HbA1c levels ( P = .009) were independently associated with digest IEQs. The IEQ prediction formula was calculated according to each preoperative HbA1c level, (a) pancreas volume × 5800 for HbA1c ≥ 6.5, (b) pancreas volume × 10 000 for HbA1c ≥5.7/<6.5 and (iii) pancreas volume × 11 400 for HbA1c < 5.7. The formula was internally validated with 28 TP‐IAT patients between 2017 and 2018 ( r 2 = .657 and r 2 = .710 when restricted to 24 patients without prior pancreatectomy). An estimated IEQs/Body Weight (kg) ≥3700 predicted HbA1c ≤6.5 and insulin independence at 1 year after TP‐IAT with 77% and 88% sensitivity and 55% and 43% specificity, respectively. The combination of pancreas volume and preoperative HbA1c levels may be useful to estimate islet yield. Estimated IEQs were reasonably sensitive to predict acceptable glucose control at 1 year.
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Introduction: Total pancreatectomy with islet autotransplantation (TP-IAT) provides pain relief to highly select patients with recurrent acute and/or chronic pancreatitis. However with variable outcomes and no standardized guideline for patient selection, it is important to refine islet manipulation procedures and patient selection characteristics to optimize outcomes. Success of the procedure depends on a high number of isolated islet equivalents. This study explores the patient and procedural characteristics associated with high islet cell yield. Methods: This study evaluated patients who underwent TP-IAT at Dartmouth Hitchcock Medical Center from 2012 to 2016. 38 patients met inclusion criteria. Odds ratios with 95% confidence intervals were found for various patient and procedural characteristics listed in Table 1. The primary clinical outcome was the number of isolated islet equivalents per kilogram body weight (IEQ/Kg), defined as IEQ/Kg >2,500.Table: Table. Factors Associated with Successful Islet Cell Yield During TPIATResults: All patient factors and procedural fields evaluated are listed in Table 1. Patients with no CT/MRI evidence of chronic pancreatitis showed statistically significant higher odds of success (OR=29, P=0.02). Patients without pancreatic duct stones or parenchymal stones were associated with higher odds of success (OR=23, P=0.02 and OR=55, P=0.002, respectively). Islet cell suspensions positive for cultures or positive gram stains were associated with lower chances of success (OR=0.06, P=0.02, and OR=0.48, P=0.01, respectively). Patients with preoperative HgbA1c greater than 5.6 were associated with lower odds of success (OR=0.13, P=0.02). Conclusion: This investigation found that patients without CT/MRI evidence of chronic pancreatitis, without bacterial infections, and without pancreatic duct or parenchymal stones are more likely to attain successful islet cell yields. Additionally, patients with preoperative HgbA1c less than 5.6 were associated with higher outcomes of success. These factors should be considered when selecting patients for TP-IAT.
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Total pancreatectomy with islet autotransplantation (TPIAT) offers symptom relief to highly selected patients with recurrent acute and/or chronic pancreatitis. However, with variable clinical response, it is important to refine islet manipulation technique and patient selection criteria. This study explores the variables associated with high islet cell yield, a driver of success in TPIAT.This study evaluated patients who underwent TPIAT at Dartmouth-Hitchcock Medical Center from 2012 to 2016. Odds ratios were calculated for various patient and procedural characteristics. The primary clinical outcome was the number of isolated islet equivalents per kilogram body weight.Thirty-eight patients met inclusion criteria. Patients with no computed tomography or magnetic resonance imaging evidence of chronic pancreatitis, without pancreatic duct stones, and without parenchymal stones were associated with higher odds of success (P = 0.02, P = 0.02, and P = 0.002, respectively). Patients with preoperative glycated hemoglobin greater than 5.6, with islet cell suspensions positive for cultures, and with positive gram stains were associated with lower odds of success (P = 0.02, P = 0.01, and P = 0.02, respectively).Factors that diminish a successful islet cell harvest during TPIAT include the presence of infected islets, an elevated preoperative glycated hemoglobin, and the presence of pancreatic duct stones.
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Pancreatitis, chronic
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