Islet Autotransplantation Research Articles

Liraglutide for the Treatment of Severe Hypoglycemia Following Total Pancreatectomy and Islet Autotransplantation

Abstract Total pancreatectomy and islet autotransplantation (TPIAT) is an effective treatment for chronic and recurrent acute pancreatitis, and it provides a significant potential additional benefit of insulin independence. Spontaneous hypoglycemia in the absence of insulin therapy following TPIAT is a recognized complication, which has been attributed to lack of protective glucagon responses to hypoglycemia, following intrahepatic islet autotransplantation. We describe the use of liraglutide to treat spontaneous hypoglycemia following TPIAT. Continuous glucose monitoring was used to identify timing of hypoglycemia in relation to meals and monitor treatment effect. Liraglutide has been used for management of hypoglycemia following bariatric surgery, but, to our knowledge, this is the first application of its effective use to treat spontaneous severe hypoglycemia following TPIAT.

6861 Pre- And Peri-Operative Predictors Of Glycemic Outcomes From Total Pancreatectomy And Islet Auto-Transplantation

Abstract Disclosure: E.N. Haddad: None. M. Lansang: None. H. Xiao: None. R. Walsh: None. R. Simon: None. B.A. Hatipoglu: None. K. Zhou: None. Background: There is a lack of information regarding the immediate post-operative period as a predictor of early and long-term insulin independence after total pancreatectomy and islet auto-transplantation (TPIAT). This study examined the baseline and peri-operative variables that are associated with one-year and longer-term insulin independence following TPIAT. Methods: This was a retrospective study of 46 TPIAT patients in a single hospital system between 2010 and 2022. Perioperative variables were compared between short- (one year) and long-term (last follow up outside of year one) insulin-independent versus dependent patients. Multivariable models were used to adjust for clinically important variables. Results: The median age of the cohort at time of TPIAT was 38.5 years (IQR 30, 49). Patients were predominantly white (91%) and 50% were female. Nine (20%) and seven (15%) patients achieved short- and long-term insulin independence, respectively. The patients were followed for a median of 2.8 years (IQR 1.0, 4.7). There were no significant differences in patient demographics (age, sex, ethnicity), duration of pancreatitis, HbA1c, or mixed meal testing results (area under c-peptide curve from 0 to 4 hours) between those achieving insulin independence and those who did not. Short term insulin-independence was associated with higher median transplanted islet equivalents (IEQ)/kg (6,981 vs 4,493, p=0.02), lower units of basal insulin on discharge (7 vs 12, p=0.009), and lower rates of discharge from the hospital with an insulin regimen (67% vs 100%, p=0.006). Short-term insulin independence was also associated with decreased median insulin use in the immediate 24-hour post-operative period (14.3 vs 45.3 units, p=0.03), though this was not statistically significant when adjusting for patient weight (0.23 vs 0.56 units/kg, p=0.13). The odds of having short term insulin independence increased by 80% for every 1,000 increase in IEQ/kg (OR 1.80, CI 1.18 to 3.12, p=0.005) and decreased by 32% for every additional basal unit of insulin on discharge (OR 0.68, CI 0.42 to 0.91, p=0.003). This was no longer statistically significant after adjusting for sex, age, mixed meal testing area under c-peptide curve at 4 hours, and HbA1c. Long-term insulin independence was also associated with transplanted IEQ/kg and basal insulin units at discharge in univariable analysis. None of the patients on insulin or any other antihyperglycemic medication prior to surgery achieved short- or long-term insulin independence. Conclusion: Short- and long-term insulin independence after TPIAT is associated with a higher transplanted IEQ/kg and fewer units of basal insulin at discharge. Immediate post-operative variables can be used to inform the discussions clinicians have with their patients regarding glycemic prognosis following TPIAT. Presentation: 6/2/2024

Increased kidney stone risk following total pancreatectomy with islet autotransplantation

Background/objectivesChronic pancreatitis (CP) is associated with increased risk of calcium-oxalate kidney stones, likely due to enteric hyperoxaluria. However, the risk of kidney stones for patients with CP after total pancreatectomy with islet autotransplantation (TPIAT) is unknown. We aimed to evaluate kidney stone risk in patients with CP after TPIAT. MethodsA retrospective analysis of 629 patients who underwent TPIAT was conducted to identify patients who developed kidney stones post-TPIAT. Kaplan-Meier analysis estimated time to first event. An Anderson-Gill proportional-hazards analysis of all kidney stone events described key clinical associations. ResultsMean age at TPIAT was 33 years (SD 15.3, range 3–69); 69.8 % (n = 439) were female. The estimated chance of any kidney stone episodes by 5 years post-TPIAT was 12.8 % (95 % CI: 8.8–16.6 %); by 10 years, 23.2 % (CI: 17.5–28.6 %); by 15 years, 29.4 % (CI: 21.8–36.2 %). Significant associations with kidney stones post-TPIAT included older age (HR 1.25 per 10 years), smoking history (HR 1.72), mild chronic kidney disease (HR 1.96), renal cysts (HR 3.67), pre-TPIAT kidney stones (HR 4.06), family history of kidney stones (HR 4.10), and Roux-en-Y reconstruction (HR 2.68). Of the 77 patients who developed kidney stones, 34 (44.1 %) had recurrent episodes. Of 143 total kidney stone events, 35 (24.5 %) required stone removal, 79 (55.2 %) resolved spontaneously, and 29 (20.3 %) were missing this data. ConclusionsPatients with CP post-TPIAT commonly have kidney stones: nearly 3 in 10 have ≥1 kidney stone episodes within 15 years. Clinicians should be aware of this risk and counsel patients on prevention.

443.6: The epidemiology of hereditary pancreatitis in Australia and its effect on patient of total pancreatectomy with islet auto-transplantation (TPIAT).

443.6: The epidemiology of hereditary pancreatitis in Australia and its effect on patient of total pancreatectomy with islet auto-transplantation (TPIAT).

443.9: Glycemic Control after Total Pancreatectomy with Islet Autotransplantation—Results from a Single Center with Large Cohort of Patients.

443.9: Glycemic Control after Total Pancreatectomy with Islet Autotransplantation—Results from a Single Center with Large Cohort of Patients.

Islet Isolation Outcomes in Patients Undergoing Total Pancreatectomy With Islet Autotransplantation in the POST Consortium.

In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes. We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses. In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures (P < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity (P = 0.002) or overweight status pre-TPIAT (P < 0.001) and lower with non-White race (P = 0.03), genetic pancreatitis (P = 0.02), history of lateral pancreaticojejunostomy (P = 0.03), and presence of atrophy (P = 0.006) or ductal changes (P = 0.014) on imaging. IEQ/kg was higher in females (P = 0.01) and Hispanic participants (P = 0.046) and generally lower with older age (nonlinear association, P < 0.001) and pancreatic atrophy (P < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively. Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results.

Longitudinal Quality of Life and Glycemic Outcomes of Total Pancreatectomy With Islet Autotransplantation in Children With Chronic Pancreatitis Followed in a Pediatric Multidisciplinary Pancreas Clinic.

Total pancreatectomy with islet autotransplantation (TPIAT) is a potentially curative treatment for patients with chronic pancreatitis (CP) refractory to medical and endoscopic therapies. Patients often receive the initial follow-up medical care at the surgery-performing center, but then may follow up closer to where they live. We sought to describe the characteristics and outcomes of pediatric patients who underwent TPIAT at a national surgical referral center and were subsequently followed at our regional subspecialty center, the Children's Hospital Colorado. We performed a retrospective analysis of baseline and outcomes data for the 10 pediatric patients who underwent TPIAT from 2007 to 2020 and received follow-up care at our institution. All patients had a diagnosis of CP, and nine of 10 patients had an identified underlying genetic risk factor. Insulin usage was common immediately following TPIAT, but at 1 year of follow-up, five of nine patients (55.6%) were insulin-independent and nine of nine had an HbA1c below 6.5%. For the four patients on insulin 1 year after TPIAT, total daily insulin dose ranged from 0.06 to 0.71 units/kg/day. All patients who underwent mixed meal tolerance testing had a robust peak C-peptide response at 1 year. There were significant improvements in nausea, school/work absences, narcotic dependence, and pancreas-related hospital admissions 1 year after TPIAT. Patients followed at our center had long-term improvements with low-insulin usage, detectable C-peptide, and improved pancreatitis-related outcomes after TPIAT. Pediatric patients who undergo TPIAT can be successfully co-managed in conjunction with the original surgery-performing center.

Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum

Clinical outcomes for total-pancreatectomy followed by intraportal islet autotransplantation (TP-IAT) to treat chronic pancreatitis (CP) are suboptimal due to pancreas inflammation, oxidative stress during islet isolation, and harsh engraftment conditions in the liver’s vasculature. We describe a thermoresponsive, antioxidant macromolecule poly(polyethylene glycol citrate- co - N -isopropylacrylamide) (PPCN) to protect islet redox status and function and to enable extrahepatic omentum islet engraftment. PPCN solution transitions from a liquid to a hydrogel at body temperature. Islets entrapped in PPCN and exposed to oxidative stress remain functional and support long-term euglycemia, in contrast to islets entrapped in a plasma-thrombin biologic scaffold. In the nonhuman primate (NHP) omentum, PPCN is well-tolerated and mostly resorbed without fibrosis at 3 months after implantation. In NHPs, autologous omentum islet transplantation using PPCN restores normoglycemia with minimal exogenous insulin requirements for &gt;100 days. This preclinical study supports TP-IAT with PPCN in patients with CP and highlights antioxidant properties as a mechanism for islet function preservation.

Minimally invasive total pancreatectomy with islet autotransplantation for chronic pancreatitis: the robotic approach.

Total pancreatectomy with islet autotransplantation (TPIAT) treats refractory pain in chronic pancreatitis, prevents episodes of acute exacerbation, and mitigates postoperative brittle diabetes. The minimally invasive (MIS) approach offers a decreased surgical access trauma and enhanced recovery. Having established a laparoscopic TPIAT program, we adopted a robotic approach (R-TPIAT) and studied patient outcomes compared to open TPIAT. Between 2013 and 2021, 61 adult patients underwent TPIAT after a comprehensive evaluation (97% chronic pancreatitis). Pancreatic islets were isolated on-site during the procedure. We analyzed and compared intraoperative surgical and islet characteristics, postoperative morbidity and mortality, and 1-year glycemic outcomes. MIS-TPIAT was performed in 41 patients (67%, 15 robotic and 26 laparoscopic), and was associated with a shorter mean length of intensive care unit stay compared to open TPIAT (2.9 vs 4.5days, p = 0.002). R-TPIAT replaced laparoscopic TPIAT in 2017 as the MIS approach of choice and demonstrated decreased blood loss compared to open TPIAT (324 vs 843mL, p = 0.004), similar operative time (609 vs 562min), 30-day readmission rate (7% vs 15%), and 90-day complication rate (13% vs 20%). The glycemic outcomesincluding C-peptide detection at 1-year (73% vs 88%) and insulin dependence at 1-year (75% vs 92%) did not differ. The mean length of hospital stay after R-TPIAT was 8.6days, shorter than for laparoscopic (11.5days, p = 0.031) and open TPIAT (12.6days, p = 0.017). Both MIS approaches had a 1-year mortality rate of 0%. R-TPIAT was associated with a 33% reduction in length of hospital stay (4-day benefit) compared to open TPIAT. R-TPIAT was similar to open TPIAT on measures of feasibility, safety, pain control, and 1-year glycemic outcomes. Our data suggest that robotic technology, a new component in the multidisciplinary therapy of TPIAT, is poised to develop into the primary surgical approach for experienced pancreatic surgeons.

Total Pancreatectomy with Percutaneous Islet Autotransplant after Remote Islet Processing: A Viable Paradigm?

Total pancreatectomy with islet autotransplant (TPIAT) is important therapy for select chronic pancreatitis (CP) patients. The specialized technique of islet isolation limits widespread TPIAT use. We hypothesized that remote islet isolation provides satisfactory islet yield and perioperative outcomes. Retrospective review of TPIAT patients between 2020 and 2022. Islet isolation was performed off-site, with percutaneous intraportal islet autotransplant (IAT) completed the morning following pancreatectomy. Demographics and perioperative outcomes were analyzed. Fourteen patients underwent TPIAT; median age was 43 [interquartile range 12.5] years. Operation occurred 7.5 [14.8] years after pancreatitis diagnosis. The most common pancreatitis etiology was genetic (50%). All patients underwent preoperative endoscopic therapy; three underwent prior pancreatectomy. Operative time was 236 [51] minutes; subsequent percutaneous IAT time was 87 [35] minutes. The islet equivalent (IEQ)/kilogram (kg) yield was 3,456 [3,815] IEQ/kg. Nine patients had positive islet cultures. Two thromboembolic events and one bacteremia occurred. One perihepatic hematoma occurred after percutaneous portal venous access. Median postoperative length of stay was 14.5 days, and five patients (36%) were readmitted within 90 days. All patients were discharged home on insulin. No mortality occurred. Total pancreatectomy with remote islet isolation provides excellent islet yield for autotransplant and satisfactory perioperative outcomes.

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.

Total pancreatectomy with islet autotransplantation outcomes in patients with pancreatitis of genetic etiology: A single-center experience with a large cohort of patients

PurposeTotal pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for patients with chronic pancreatitis (CP) when other interventions are unsuccessful. CP has many etiologies including heredity. Metabolic and pain relief outcomes after TPIAT are presented among patients with a genetic CP etiology compared with those with a nongenetic etiology in a large cohort of patients who underwent this procedure at our center. MethodsA retrospective analysis was performed of 237 patients undergoing TPIAT between 2006 and 2023. We analyzed the differences in patients with genetic (n = 56) vs nongenetic CP etiologies (n = 181) in terms of pre-TPIAT factors including patient characteristics and disease state, results from the isolation process, and outcomes such as long-term glycemic and pain control. ResultsPatients with genetic CP underwent TPIAT at a significantly younger age (32.3 vs 41.3 years nongenetic; P < .0001) and endured symptoms for a significantly longer period (10 vs 6 years; P < .01). A significantly lower mass of islets was isolated from patients with genetic CP (P < .01), which increased with body mass index in both groups. Despite lower yields, patients with genetic CP maintained metabolic function similar to patients with nongenetic CP, as indicated by insulin independence and C-peptide, blood glucose, and hemoglobin A1C levels after TPIAT. Post-transplant narcotic usage and pain scores significantly decreased compared with those before TPIAT, and more patients with genetic CP were pain free and narcotic free after TPIAT. ConclusionOur data validate TPIAT as a beneficial procedure for patients enduring CP of genetic etiology. Pain that is inevitably recurrent after minor interventions owing to the nature of the disease and favorable TPIAT outcomes should be considered in the decision to perform early TPIAT in cases of genetic CP.

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.

Quality of Life Following Total Pancreatectomy With Islet Autotransplantation: A Patient Experience Survey.

Total pancreatectomy with islet autotransplantation (TPIAT) is performed to improve the quality of life (QOL) of patients with chronic pancreatitis. Few reports have documented QOL following TPIAT, with none using the pancreatitis-specific Pancreatitis Quality of Life Instrument (PANQOLI). We surveyed patients at our center who underwent TPIAT to document postoperative QOL. We collected survey data from 18 adult patients who underwent TPIAT at our medical center from 2012 to 2020. Patients were asked questions assessing QOL following TPIAT and completed the Short-Form Health Survey and PANQOLI instruments. Forty-three patients who underwent TPIAT were mailed surveys, and 18 were returned. The mean age was 45 years, and 67% of respondents were female. Almost half (44%) had hereditary pancreatitis. Sixty-seven percent believed that their overall QOL had improved after surgery. The mean postoperative Short-Form Health Survey physical score was 38.9 and mean mental score was 44. The mean PANQOLI score was 66 (physical function 20, role function 16, emotional function 14, self-worth 15). Following surgery, 33% were using opiate medications and 67% were using antihyperglycemic medications. TPIAT resulted in improved self-reported QOL in most patients, although postoperative physical and mental QOL are less compared to the average healthy United States adult.

Autologous Pancreatic Islet Cell Transplantation Following Pancreatectomy for Pancreas Diseases Other Than Chronic Pancreatitis: A 15-y Study of the Milan Protocol.

Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis. This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases. The analysis evaluates feasibility, efficacy, and safety of IAT. Modified Igls criteria validated through the arginine test and mixed meal tolerance tests were used to assess long-term metabolic outcomes. Between November 2008 and June 2023, IAT procedures were performed on 114 of 147 candidates. IAT-related complications occurred in 19 of 114 patients (16.7%), with 5 being potentially serious. Patients exhibited sustained C-peptide secretion over the 10-y follow-up period, demonstrating a prevalence of optimal and good beta-cell function. Individuals who underwent partial pancreatectomy demonstrated superior metabolic outcomes, including sustained C-peptide secretion and a reduced risk of developing diabetes or insulin dependence compared with those who underwent total pancreatectomy. For patients who had total pancreatectomy, the quantity of infused islets and tissue volume were identified as critical factors influencing metabolic outcomes. An increased risk of recurrence or progression of baseline diseases was not observed in subjects with neoplasms. These findings provide valuable insights into the benefits and applications of IAT as a therapeutic option for pancreatogenic diabetes after pancreatic surgery, expanding its potential beyond painful chronic pancreatitis.

Addressing long-term mortality risk in patients undergoing total pancreatectomy with islet autotransplant (TPIAT): causes of death and risk factors

BackgroundTotal pancreatectomy with islet autotransplant (TPIAT) can improve quality of life for individuals with pancreatitis but creates health risks including diabetes, exocrine insufficiency, altered intestinal anatomy and function, and asplenia. MethodsWe studied survival and causes of death for 693 patients who underwent TPIAT between 2001 and 2020, using the National Death Index with medical records to ascertain survival after TPIAT, causes of mortality, and risk factors for death. We used Kaplan Meier curves to examine overall survival, and Cox regression and competing-risks methods to determine pre-TPIAT factors associated with all-cause and cause-specific post-TPIAT mortality. ResultsMean age at TPIAT was 33.6 years (SD = 15.1). Overall survival was 93.1% (95% CI 91.2, 95.1%) 5 years after surgery, 85.2% (95% CI 82.0, 88.6%) at 10 years, and 76.2% (95% CI 70.8, 82.3%) at 15 years. Fifty-three of 89 deaths were possibly related to TPIAT; causes included chronic gastrointestinal complications, malnutrition, diabetes, liver failure, and infection/sepsis. In multivariable models, younger age, longer disease duration, and more recent TPIAT were associated with lower mortality. ConclusionsFor patients undergoing TPIAT to treat painful pancreatitis, careful long-term management of comorbidities introduced by TPIAT may reduce risk for common causes of mortality.

Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients.

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90mg/kg IV x6 doses, n = 13), etanercept (50mg then 25mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.

Nutrition challenges following total pancreatectomy with islet autotransplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical treatment option for patients with chronic pancreatitis who have not responded to other therapies. TP offers pain relief whereas IAT preserves beta cell mass to reduce endocrine insufficiency. During the surgical procedure, the entire pancreas is removed. Islet cells from the pancreas are then isolated, purified, and infused into the liver via the portal vein. Successful TPIAT relieves pain for a majority of patients but is not without obstacles, specifically gastrointestinal, exocrine, and endocrine challenges. The postoperative phase can be complicated by gastrointestinal symptoms causing patients to have difficulty regaining adequate oral intake. Enteral nutrition is frequently provided as a bridge to oral diet. Patients undergoing TPIAT must be monitored for macronutrient and micronutrient deficiencies following the procedure. Exocrine insufficiency must be treated lifelong with pancreatic enzyme replacement therapy. Endocrine function must be monitored and exogenous insulin provided in the postoperative phase; however, a majority of patients undergoing TPIAT require little or no long-term insulin. Although TPIAT can be a successful option for patients with chronic pancreatitis, nutrition-related concerns must be addressed for optimal recovery.

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.

Real‐World Accuracy of a Continuous Glucose Monitoring System after Radiologic Exposure

Background. The increasing use of continuous glucose monitor (CGM) necessitates a review of variables that impact accuracy and interrupt use. Manufacturer recommendations include removing CGMs before diagnostic imaging, such as X‐ray and computed tomography (CT). Early removal and replacement of CGM components present financial, clinical, and psychosocial burdens to the wearer and interrupt optimal management of diabetes for pediatric patients who receive a total pancreatectomy with islet autotransplantation (TPIAT). The study’s aim was to evaluate the effect of scatter dose exposure during X‐ray or CT if the CGM remained intact but outside the field of view (FoV). Materials and Methods. Participants were followed through the first 3 months after TPIAT surgery, managed diabetes with an insulin pump and CGM, and were routinely exposed to diagnostic imaging. Participants’ CGMs were unshielded by a protective apron during any X‐ray or CT procedures for the duration of the study period, and the transmitter was collected after expiration or removal. Glucometer data was collected from hospital records and home glucometer downloads. Mixed models were used to analyze absolute differences between matched CGM and glucometer values, and Clarke error grid analyses (EGA) were performed. Scatter dose exposure was derived using anthropomorphic phantoms and calculated retrospectively. Results. A total of 14 patients (median 12.2 years, 64% female) received a median of five diagnostic imaging procedures with a median cumulative scatter dose of 559 µGy. The absolute difference between the CGM and glucometer values was not significantly associated with the cumulative scatter dose (p = 0.17) or time from TPIAT (p = 0.24) when analyzed in a mixed model. Regardless of scatter dose exposure, time from TPIAT, or glucometer, ≥98% of glucose values fell within zones A and B on EGA. Conclusion. Scatter dose exposure from diagnostic imaging did not affect the clinical accuracy of CGM values for the duration of transmitter use. Leaving CGM components in place when not in the FoV during diagnostic imaging successfully mitigated interruptions to use and undue burden or cost to participants.