Total Pancreatectomy And Islet Autotransplantation Research Articles

Preoperative and Postoperative Predictors of Insulin Independence From Total Pancreatectomy and Islet Autotransplantation

ObjectiveThis study examined the preoperative and postoperative variables associated with 1 year and long-term insulin independence following total pancreatectomy and islet autotransplantation (TPIAT). Methods46 TPIAT patients from 2010 to 2022 in a single hospital system were retrospectively analyzed. Pre- and postoperative variables were compared between short-term (1 year) and long-term (last follow-up after year 1) insulin-independent versus -dependent patients. ResultsNine (20%) and seven (15%) patients achieved short- and long-term insulin independence, respectively. The patients were followed up for a median of 2.8 years (interquartile range [IQR] 1.0, 4.7). Short-term insulin independence was associated with higher median transplanted islet equivalents (IEQ) per kg (6981 vs 4493, P = .02), lower units of basal insulin on discharge (7 vs 12, P = .009), and lower rates of discharge with an insulin regimen (67% vs 100%, P = .006). Odds of short-term insulin independence increased by 80% for every 1000 increase in IEQ per kg (OR 1.80, CI 1.18-3.12, P = .005) and decreased by 32% for every additional basal unit of insulin on discharge (OR 0.68, CI 0.42-0.91, P = .003) on average. Long-term insulin independence was also associated with transplanted IEQ per kg. No patient on antihyperglycemic medication before surgery achieved insulin independence. ConclusionShort- and long-term insulin independence after TPIAT is associated with higher transplanted IEQ per kg and immediate postoperative variables that can be used to inform the discussions clinicians have with their patients regarding glycemic prognosis following TPIAT.

Essential Fatty Acid Deficiency Is Common After Total Pancreatectomy and Islet Autotransplantation.

Total pancreatectomy and islet autotransplantation (TPIAT) for pancreatitis may induce risk for essential fatty acid deficiency (EFAD) due to exocrine pancreatic insufficiency and intestinal alterations. The prevalence of EFAD post-TPIAT is currently unknown. We abstracted essential fatty acid (EFA) profiles (n = 332 samples) for 197 TPIAT recipients (72% adult, 33% male). Statistical analyses determined the prevalence of, and associations with, EFAD post-operatively. EFAD was defined as a Triene-to-Tetraene ratio ≥0.05 if <18 years old, or ≥0.038 if ≥18 years old. Prevalence of EFAD was 33%, 49%, and 53.5% at 1, 2, and ≥3 years. At 1-year post-TPIAT, older age at transplant ( P = 0.03), being an adult versus a child ( P = 0.0024), and obstructive etiology ( P = 0.0004) were significant predictors of EFAD. Only 6% of children had EFAD 1-year post-TPIAT versus 46% of adults. The alpha-linolenic acid levels were lower with lower body mass index at transplant ( P = 0.011). EFAD was associated with the presence of other intestinal diseases ( P < 0.0001). One-third of individuals had EFAD 1-year post-TPIAT, highlighting the need for systematic monitoring. Older age at transplant increased risk and adults were more affected than children. Other diagnoses affecting intestinal health may further increase risk for EFAD.

Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study.

Stress-induced islet graft loss during the peri-transplantation period reduces the efficacy of islet transplantation. In this prospective, randomized, double-blind clinical trial, we evaluated the safety and efficacy of 60 mg/kg human alpha-1 antitrypsin (AAT) or placebo infusion weekly for four doses beginning before surgery in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT). Subjects were followed for 12 months post-TP-IAT. The dose of AAT was safe, as there was no difference in the types and severity of adverse events in participants from both groups. There were some biochemical signals of treatment effect with a higher oxygen consumption rate in AAT islets before transplantation and a lower serum C-peptide (an indicator of islet death) in the AAT group at 15 min after islet infusion. Findings per the statistical analysis plan using a modified intention to treat analysis showed no difference in the C-peptide area under the curve (AUC) following a mixed meal tolerance test at 12 months post-TP-IAT. There was no difference in the secondary and exploratory outcomes. Although AAT therapy did not show improvement in C-peptide AUC in this study, AAT therapy is safe in CP patients and there are experiences gained on optimal clinical trial design in this challenging disease.

Early Metabolic Measures Predict Long-term Insulin Independence in Recipients of Total Pancreatectomy and Islet Autotransplantation.

Although diabetes after total pancreatectomy and islet autotransplantation (TP-IAT) is one of the biggest concerns for TP-IAT recipients and physicians, reliable prediction of post-TP-IAT glycemic control remains unestablished. This study was conducted to identify early predictors of insulin independence and goal glycemic control by hemoglobin A1c (HbA1c) ≤ 6.5% after TP-IAT. In this single-center, retrospective study, patients who underwent TP-IAT (n = 227) were reviewed for simple metabolic markers or surrogate indices of β-cell function obtained 3 mo after TP-IAT as part of standard clinical testing. Long-term metabolic success was defined as (1) insulin independence and (2) HbA1c ≤ 6.5% 1, 3, and 5 y after TP-IAT. Single- and multivariate modeling used 3-mo markers to predict successful outcomes. Of the 227 recipients, median age 31 y, 30% male, 1 y after TP-IAT insulin independence, and HbA1c ≤ 6.5% were present in 39.6% and 72.5%, respectively. In single-predictor analyses, most of the metabolic markers successfully discriminated between those attaining and not attaining metabolic goals. Using the best model selected by random forests analysis, we accurately predicted 1-y insulin independence and goal HbA1c control in 77.3% and 86.4% of the patients, respectively. A simpler "clinically feasible" model using only transplanted islet dose and BETA-2 score allowed easier prediction at a small accuracy loss (74.1% and 82.9%, respectively). Metabolic testing measures performed 3 mo after TP-IAT were highly associated with later diabetes outcomes and provided a reliable prediction model, giving valuable prognostic insight early after TP-IAT and help to identify recipients who require early intervention.

Assessment of long-term graft function following total pancreatectomy and autologous islet transplantation: the Leicester experience.

Total pancreatectomy and islet autotransplantation (TPIAT) is a recognised treatment for chronic pancreatitis (CP) with the potential to mitigate or prevent pancreatogenic diabetes. We present our 10-year follow-up of TPIAT patients. The University Hospitals of Leicester performed 60 TPIAT procedures from September 1994 to May 2011. Seventeen patients completed their 10-year assessment and were grouped using the modified Auto-Igls criteria; good response, n=5 (insulin-independent for first 5 years post-TPIAT); partial response, n=6 (insulin requirements <20 iU/day post-TPIAT) and poor response, n=6 (insulin requirements ≥20 iU/day post-TPIAT). C-peptide, haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were undertaken preoperatively (baseline), then at 3, 6 months and then yearly for 10 years. Data was analysed using analysis of variance (ANOVA). Median C-peptide levels were significantly higher, 120 minutes following OGTT, in the "good response" compared to "partial" and "poor" groups (two-way ANOVA test, P<0.0001). All groups demonstrated preservation of C-peptide release. HbA1c levels were significantly lower in the "good response" compared to "partial" and "poor" groups (two-way ANOVA test, P<0.0003 and P<0.0001). Median fasting glucose levels at 30 and 120 min following OGTT, were significantly lower in the "good response" compared to "partial" and "poor" groups (two-way ANOVA test, P<0.0001 and P<0.0001). TPIAT preserves long-term islet graft functions in 10-year follow up. Even in patients in the poor response group, there is evidence of C-peptide release (>0.5 ng/mL) after OGTT stimulation potentially preventing long-term diabetes-related complications.

235.8: Quantitative analysis of microbial contamination in islet isolation for total pancreatectomy and islet auto transplantation (TPIAT): development of bioburden reduction strategies

235.8: Quantitative analysis of microbial contamination in islet isolation for total pancreatectomy and islet auto transplantation (TPIAT): development of bioburden reduction strategies

P.16: Chronic Pancreatitis in children under 18 in New South Wales, Australia: establishing suitable candidates for total pancreatectomy and islet auto transplantation (TPIAT)

P.16: Chronic Pancreatitis in children under 18 in New South Wales, Australia: establishing suitable candidates for total pancreatectomy and islet auto transplantation (TPIAT)

839-P: Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation

Stress-induced islet graft loss reduces the efficacy of islet transplants. In this single-center, randomized, double-blind, and controlled clinical trial, we evaluated the safety and efficacy of human alpha-1 antitrypsin (AAT) infusion in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT) at the Medical University of South Carolina. Among 48 qualified subjects randomized in a 1:2 (placebo vs AAT) ratio, 43 received TP-IAT. Subjects were given saline or AAT infusion at 60mg/kg weekly for 4 weeks and were followed for 12 months. The primary efficacy endpoint was the islet function measured by the C-peptide area under the curve during a mixed meal tolerance test (MMTT) at Month 12 (M12). Adverse events (AEs) were measured throughout the study. Safety, glycemic control, insulin use, and quality of life (QoL) were compared between groups. Safety evaluation showed no significant differences in the types and severity of participant AEs. The primary efficacy outcome was not significantly different between groups. Baseline characteristics including age, body weight, BMI, HbA1C, etc, were comparable in the randomized populations. The oxygen consumption rate before the transplant was higher in the AAT group. Serum C-peptide (an indicator of islet death) was lower in the AAT group, suggesting less islet injury. AAT subjects trended toward better SF-12 physical QoL and lower insulin use at both 75 and 365 days post-IAT. Despite intensive efforts to get participants to return for the Day 365 MMTT, only 10/14 (71%) in the placebo group and 18/29 (62%) in the AAT group returned for this test. Although we did not observe a statistical difference in islet function using AAT therapy, we gained a better understanding of this patient population. Minimizing numbers of follow-up visits, use of fewer doses of medication with higher doses, and providing travel are all important for future clinical trials in TP-IAT. Disclosure H. Wang: None. W. Gou: None. D. Adams: None. K. Morgan: Speaker's Bureau; Johnson &amp; Johnson Medical Devices Companies. P.J. Nietert: None. J. Hirsch: None. C. Strange: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK105183, DK120394, DK118529); U.S. Department of Veterans Affairs (I01BX004536 to H.W.)

239-OR: Glycemic Control after Total Pancreatectomy with Islet Autotransplantation—Results from a Single Center with Large Cohort of Patients

Total pancreatectomy and islet autotransplantation (TPIAT) for refractory chronic pancreatitis has been performed at our center from 2006. We employed anti-inflammatory treatment using IL-1β and TNF-α blockers to improve graft outcomes. We present results on islet characteristics and glycemic control post-TPIAT from this large cohort of patients. Our database of 200 consecutive TPIAT procedures performed were retrospectively reviewed. We collected demographics, pancreas and islet characteristics. Patient follow-ups were performed at 3, 6, 12 m and then annually. Outcomes measures included glycemic control, pain relief and narcotic use. Baseline patient characteristics (age, sex, BMI, etiology, C-peptide and HbA1c, duration of symptoms) and isolation results were shown in Table 1A and post-TPIAT fasting glucose, HbA1c, C-peptide and daily insulin use in Table 1B. The insulin independence rate at 3, 6 and 12 months increased with time from 15%, 24 % and 27%, respectively). At 1 year, pain score was significantly improved (p&amp;lt;0.0001). Narcotic free rate also increased to 47% at 6 months and 56% at 1 year. Most post-TPIAT patients preserved hypoglycemic awareness and good pain relief. A cohort of patients remained normoglycemic without insulin and this group can be further studied to identify the factors that prevent the incidence of T3cDM after TPIAT. Disclosure A.Hakim mohammed: None. C.Darden: None. J.Kirkland: None. J.Kuncha: None. J.D.Mattke: None. M.C.Lawrence: None. B.Naziruddin: None.

Quality of life after total pancreatectomy with islet autotransplantation for chronic pancreatitis in Japan

ABSTRACT Background Patients with chronic pancreatitis (CP) often have severe and intractable abdominal pain, leading to decreased quality of life (QOL), inability to work or attend school, and increased health care costs due to repeated emergency room visits and hospitalizations. Methods We evaluated the efficacy of total pancreatectomy and islet autotransplantation (TPIAT) in terms of pain control and QOL in CP patients treated at our center in Japan. To evaluate QOL, we used the Short-Form 36 Health Survey version 2 (SF-36v2® Standard, Japanese), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and Quality of Life Questionnaire-Pancreatic Modification (QLQ-PAN28). Results Between August 2016 and June 2019, we performed this procedure in 5 patients. All patients were followed up for 12 months and all transplanted islets were still functioning at the 1-year follow-up. The major adverse events were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization; no case had sequelae. No major complications were due to islet transplantation. Pain scores improved postoperatively in all patients. Three QOL item dimensions role-physical (p = 0.03125), general health perception (p = 0.03125) and vitality (p = 0.03125) in the SF-36 were significantly improved 12 months after TPIAT. Mean values of many other QOL items improved, though not significantly. Conclusion The QOL improvement after TPIAT for CP suggests its effectiveness in the Japanese population.

Spleen-preserving total pancreatectomy and islet autotransplantation with complete preservation of the splenic arterial and venous supply does not impact islet yield and function

BackgroundStandard total pancreatectomy and islet autotransplantation (TPIAT) for chronic pancreatitis includes splenectomy, but TPIAT can be performed without splenectomy by full preservation of the blood supply to the spleen. MethodsWe compared the metabolic and clinical outcomes of patients who underwent TPIAT at our center between 2015 and 2021 with or without splenectomy. A total of 89 patients were included in the study, and 17 of them underwent spleen-preserving total pancreatectomy (SPTP). ResultsThe two study groups had similar demographic and metabolic parameters. Short-term morbidity and long-term outcomes were similar. The operative time was significantly shorter with splenectomy: a median of 9.91 h (interquartile range [IQR] 8.89–10.83) compared to 10.78 h (IQR 10.2–11.6) for SPTP (P = 0.021). There was no difference between the groups in postoperative morbidity. Metabolic outcomes at 1 year were better in the SPTP group compared to the splenectomy group, with a median daily insulin requirement of 7 units (IQR 4–12) vs 15 units (IQR 7–26; P = 0.049) and a median C-peptide at 1 year of 0.65 (IQR 0.40–1.26) vs 1.00 (IQR 0.80–1.90; P = 0.63). The reduction in morphine milligram equivalents per day over time was significantly better in the SPTP group (P < 0.001), as was the decrease in pain score (P < 0.001). ConclusionTPIAT with full arterial and venous preservation of the spleen had no adverse impact on islet yield or function. TPIAT can be safely and effectively performed with preservation of the spleen and the entire splenic artery and vein. The spleen should be preserved when feasible in every TPIAT surgery.

Intraportal Islet Autotransplantation Independently Improves Quality of Life After Total Pancreatectomy in Patients With Chronic Refractory Pancreatitis.

To determine if islet autotransplantation (IAT) independently improves the quality of life (QoL) in patients after total pancreatectomy and islet autotransplantation (TP-IAT). TP-IAT is increasingly being used for intractable chronic pancreatitis. However, the impact of IAT on long-term islet function and QoL is unclear. TP-IAT patients at our center >1 year after TP-IAT with ≥1 Short Form-36 QoL measure were included. Patients were classified as insulin-independent or insulin-dependent, and as having islet graft function or failure by C-peptide. The associations of insulin use and islet graft function with QoL measures were analyzed by using a linear mixed model, accounting for time since transplant and within-person correlation. Among 817 islet autograft recipients, 564 patients [median (interquartile range) age: 34 (20, 45) years, 71% female] and 2161 total QoL surveys were included. QoL data were available for >5 years after TP-IAT for 42.7% and for >10 years for 17.3%. Insulin-independent patients exhibited higher QoL in 7 of 8 subscale domains and for Physical Component Summary and Mental Component Summary scores ( P <0.05 for all). Physical Component Summary was 2.91 (SE=0.57) higher in insulin-independent patients ( P <0.001). No differences in QoL were observed between those with and without graft function, but islet graft failure was rare (15% of patients). However, glycosylated hemoglobin was much higher with islet graft failure. QoL is significantly improved when insulin independence is present, and glycosylated hemoglobin is lower with a functioning islet graft. These data support offering IAT, rather than just performing total pancreatectomy and treating with exogenous insulin.

The Association of Smoking and Alcohol Abuse on Anxiety and Depression in Patients With Recurrent Acute or Chronic Pancreatitis Undergoing Total Pancreatectomy and Islet Autotransplantation: A Report From the Prospective Observational Study of TPIAT Cohort.

Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown. We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes. Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005). Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed.

Immediate Postoperative Insulin Requirements May Predict Metabolic Outcome after Total Pancreatectomy and Islet Autotransplantation.

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.

Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort

Background and aimsMany patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield. MethodsUsing data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders. Results175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement. ConclusionsERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.

Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study.

The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites. Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test. Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001). This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored.

59 Pancreas Enzyme Replacement Dosing Before and After Total Pancreatectomy and Islet Autotransplantation

INTRODUCTION: Pancreas enzyme replacement therapy (PERT) is used to improve nutrient digestion, especially of lipids, in patients with exocrine pancreas insufficiency who otherwise may experience maldigestion, malabsorption, malnutrition, and steatorrhea. Although underdosage of PERT is common, adequate dosing is particularly important in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT). Current PERT dosing guidelines do not explicitly provide recommendations following TPIAT so we determined the adequacy of PERT dosing in a cohort of patients with TPIAT. METHODS: The TPIAT database from 2009-2018 was searched to determine PERT dosing in subjects before TPIAT (n = 14), immediately after TPIAT and at 6 and 12 months (n = 11). Adequate weight based dosing was established using Cystic Fibrosis Foundation guidelines. Average PERT dose was calculated and the ranges were reported, P &lt; 0.05 was significant. RESULTS: Data was available in 14 patients, and 6 and 12 month data was available in 11 patients. Indication for TPIAT included 6 idiopathic chronic pancreatitis (CP), 4 genetic CP (4 PRSS1, 1 CFTR), 3 idiopathic recurrent AP, 1 alcohol induced CP. 3 patients were not using PERT before TPIAT, 7 were underdosed (average 62,000 U/day, range 6,000–108,000), and 4 were adequate (205,250 U/day; 125,000–228,000). At discharge 9 patients were underdosed (72,222 U/day; 6000–108,000), and 5 were adequate (248,200 U/day; 125,000–360,000). At 6 months 3/11 pts (27%) were underdosed (56,666 U/day; 30,000–80,000) and 8/11 pts (73%) were adequate (228,000 U/day; 144,000–432,000). At 12 months 2/11 pts (18%) were underdosed (108,000 U/day each) and 9/11 (82%) pts were adequate (430,222 U/day; 144,000–384,000). PERT dose increase was significant for the period post-TPIAT to 6 months (P = 0.04). The graph shows the trend of PERT during the study period. CONCLUSION: Underdosing of PERT was common before and immediately after TPIAT. It is possible that poor oral intake dictated the immediate low post TPIAT dose. Significant PERT dose increase was noted in the first 6 months, and was sustained at 12 months. PERT dosing needs to be monitored closely and weight based dosing should be considered to achieve optimal nutritional benefit.

Omental Pouch Technique for Combined Site Islet Autotransplantation Following Total Pancreatectomy

Total pancreatectomy and islet autotransplantation (TPIAT) is an effective treatment for selected patients with chronic pancreatitis. The portal circulation is the standard infusion site for islet transplant, but marked elevation of portal pressures may prevent complete islet infusion. Herein we report a novel technique of combined site islet autotransplantation using an omental pouch. This technique may be useful when technical limitations prevent complete intraportal transplantation. In four TPIAT recipients with intraoperative issues precluding the complete intraportal infusion of islets, an omental pouch was created to contain the remaining islet mass. Patients were monitored for complications, and islet graft function was assessed using mixed meal tolerance testing and compared with matched controls who received only intraportally transplanted islets. All patients had decreasing insulin requirements as their recovery progressed. At 3 months follow-up there were no significant differences in glycemic control or graft function for the combined site recipients compared with their matched controls who only received an intraportal islet infusion. The omentum has potentially desirable qualities such as accessibility, capacity, and systemic/portal vascularity comparable to the native pancreas. The omental pouch technique may represent a safe and effective alternate site for islet autotransplantation. Further study is needed to confirm these findings.

Australian Experience of Total Pancreatectomy and Islet Auto Transplant (TPIAT) Utilizing a Remote Isolation Center

Introduction In 2015 we performed the first TPIAT in Australia on a 7 year old paediatric patient suffering hereditary chronic pancreatitis due to a PRSS1 mutation. We have since performed a further 4 TPIAT procedures, 2 paediatric and 2 adult recipients. All 5 TPIAT procedures were performed in Adelaide, South Australia at the Women’s and Children’s Hospital (paediatric patients) or the Royal Adelaide Hospital (adult patients). The islet isolation procedure was performed at a remote isolation center, St Vincent’s Institute (SVI), Melbourne Victoria. SVI is a 1hr15min commercial flight from Adelaide or approximately 470 miles by road. Following isolation, the islets were infused back into each patient on the same day in Adelaide. Materials and Methods In the first 2 patients a total pancreatectomy, splenectomy, cholecystectomy, and biliary and enteric reconstruction was performed. In patients 3-5 the spleen was spared during the total pancreatectomy. Once removed, the pancreas was placed in preservation solution and escorted from Adelaide to Melbourne by commercial airline. Pancreatic digestion and islet isolation were performed using Serva enzyme and standard protocols. Islet infusion into the liver was performed by cannulation of the portal vein with concomitant portal vein pressure monitoring. Results The cold ischaemic time for all 5 pancreas was similar, ranging from 5hr to 5hr21min. The pancreas weights varied significantly, however this did not correlate with islet yield. Total IEQ ranged from 28,254 to 653,222 and the time from placing the islets into transplant bags through to infusion into the recipient was relatively consistent, ranging from 4-5hrs. To date, patients 1 & 3 have ceased all pre-operative pain medication and patient 4 has significantly reduced his opiate usage and is currently undergoing a controlled withdrawal and detoxification program with medical guidance to cease the remaining analgesia. Patient 5 the most recent TPIAT is in the process of weaning off her pre-operative analgesia and patient 2 suffered complications following TPIAT and is deceased. All 4 surviving patients are c-peptide positive with daily insulin requirements ranging from 10-20U and HbA1c levels of 5-8. Conclusion We have successfully completed a pilot study involving 5 patients undergoing TPIAT for the management of chronic pancreatitis. All 5 isolations were performed at a facility remote to the hospital where the total pancreatectomy and subsequent islet infusion was performed. All surviving recipients have experienced a reduction or complete resolution of their chronic pain following TPIAT with two patients no longer requiring any form of analgesia. They are all c-peptide positive, requiring minimal doses of exogenous insulin with excellent management of their diabetes. Recently, we secured additional funding to perform 6 more TPIATs with the long-term goal of establishing TPIAT as a government funded procedure for the treatment of chronic pancreatitis. The Hospital Research Foundation South Australia. MedVet Sciences South Australia. Women’s and Children’s Hospital.

Liver Doppler Findings in Pediatric Patients After Total Pancreatectomy and Islet Autotransplantation.

This study was intended to establish normal values for velocities in the hepatic artery and portal veins in pediatric patients after total pancreatectomy and islet autotransplantation (TPIAT). A retrospective review was performed of liver Doppler studies in pediatric patients after TPIAT over 6 years at an academic children's hospital. Doppler velocities in the liver vasculature and the hepatic artery resistive index were recorded. Sixty-five pediatric patients were evaluated. There were no cases of portal vein thrombosis or other hepatic vascular complications. The mean hepatic artery peak systolic velocity was 157.6 cm/s (SE, 60.9 cm/s), with a mean resistive index of 0.57 (SE, 0.09). The mean main portal vein velocity was 31.9 cm/s (SE, 12.9 cm/s). Portal vein thrombosis is rare in pediatric patients after TPIAT. A wide range of hepatic artery and portal vein velocities are encountered in children immediately after TPIAT without hepatic vascular complications and can be considered normal.