Total Pancreatectomy With Islet Autotransplantation Research Articles

Portal Vein Thrombosis May Be More Strongly Associated With Islet Infusion Than Extreme Thrombocytosis After Total Pancreatectomy With Islet Autotransplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) involves pancreatectomy, splenectomy, and reinjection of the patient's pancreatic islets into the portal vein. This process triggers a local inflammatory reaction and increase in portal pressure, threatening islet survival and potentially causing portal vein thrombosis. Recent research has highlighted a high frequency of extreme thrombocytosis (platelets ≥1000 × 109/L) after TPIAT, but its cause and association with thrombotic risk remain unclear. This retrospective single-site study of a contemporary cohort of 409 pediatric and adult patients analyzed the frequency of thrombocytosis, risk factors for thrombosis, and antiplatelet and anticoagulation strategies. Of 409 patients, 67% developed extreme thrombocytosis, peaking around postoperative day 16. Extreme thrombocytosis was significantly associated with infused islet volumes. Thromboembolic events occurred in 12.2% of patients, with portal vein thromboses occurring significantly earlier than peripheral thromboses. Portal vein thromboses were associated with infused islet volumes and portal pressures but not platelet counts or other measures. Most thromboembolic events (82.7%) occurred before the postoperative day of maximum platelet count. Only 4 of 27 (14.8%) of portal vein thromboses occurred at platelet counts ≥500 × 109/L. Perioperative heparin was given to all patients. Treatment of reactive thrombocytosis using aspirin in adults and hydroxyurea in children was not associated with significantly decreased thromboembolic risk. These results suggest that post-TPIAT thrombocytosis and portal vein thromboses may be linked to the islet infusion inflammation, not directly to each other, and further reducing this inflammation may reduce thrombosis and thrombocytosis frequencies simultaneously.

Metabolic measures before surgery and long-term diabetes outcomes in recipients of total pancreatectomy and islet autotransplantation

In this single-center, retrospective cohort study, we aimed to elucidate simple metabolic markers or surrogate indices of β-cell function that best predict long-term insulin independence and goal glycemic HbA1c control (HbA1c≤6.5%) after total pancreatectomy with islet autotransplantation (TP-IAT). Patients who underwent TP-IAT (n=371) were reviewed for metabolic measures before TP-IAT and for insulin independence and glycemic control at 1, 3, and 5years after TP-IAT. Insulin independence and goal glycemic control were achieved in 33% and 68% at 1year, respectively. Although the groups who were insulin independent and dependent overlap substantially on baseline measures, an individual who has abnormal glycemia (prediabetes HbA1c or fasting glucose) or estimated IEQs/kg<2500 has a very high likelihood of remaining insulin dependent after surgery. In multivariate logistic regression modelling, metabolic measures correctly predicted insulin independence in about 70% of patients at 1, 3, and 5years after TP-IAT. In conclusion, metabolic testing measures before surgery are highly associated with diabetes outcomes after TP-IAT at a population level and correctly predict outcomes in approximately two out of three patients. These findings may aid in prognostic counseling for chronic pancreatitis patients who are likely to eventually need TP-IAT.

Reduced bone mineral density in the first year after total pancreatectomy with islet autotransplantation (TPIAT)

Background/objectivesThe effect of total pancreatectomy with islet autotransplantation (TPIAT) on bone mineral density (BMD) in patients with CP is unknown. We aimed to assess bone health in patients with CP after TPIAT. MethodsWe measured BMD, BMD Z-score, and bone mineral content (BMC) for total body, lumbar spine, right and left hip in 78 patients before and after TPIAT using dual-energy X-ray absorptiometry (DXA, n = 78 pre-TPIAT, n = 65 paired pre- and 12 months post-TPIAT, n = 33 paired 12 and 18 months post-TPIAT), and tested for association with clinical history including age, smoking status, and medications using paired and two-sample t-tests, linear regression, and Fisher's exact test. Laboratory measures related to bone health were also assessed. ResultsIn the patients with pre-TPIAT DXA, 12% had low BMD (Z-score ≤ −2). BMD, BMD Z-score, and BMC all decreased from pre-to 12 months post-TPIAT. BMD declined by 1.7%–4.1% with the greatest change at the hips. Adjusted for change in lean and fat body mass, DXA changes remained significant for total body and hip. Serum carboxy-terminal collagen crosslinks telopeptide and alkaline phosphatase increased at 12 months post-TPIAT, suggesting possible increased bone remodeling. BMD, BMD Z-score, and BMC did not change between 12 months and 18 months in any of the four regions (p > 0.6). ConclusionsTPIAT is associated with decreases in BMD in the body, lumbar, and hip regions of patients with CP in the first year after TPIAT but these appear to stabilize between 12 and 18 months after TPIAT.

Clinical Significance of Postoperative Antibiotic Treatment for Positive Islet Cultures After Total Pancreatectomy With Islet Autotransplantation.

Islet cultures are routinely performed in total pancreatectomy with islet autotransplantation (TPIAT), and the need for empiric antibiotic treatment based on culture results is unknown. We evaluated the effect of postoperative antibiotic treatment for positive islet cultures on clinical infection. Seventy-nine patients undergoing TPIAT were reviewed. Prophylactic perioperative ceftriaxone and metronidazole were administered, and transplanted islet preparations included ciprofloxacin. Postoperative antibiotics were not routinely given for positive cultures unless a clinical infection was suspected. The primary end point was 30-day infectious complications. Fifty-one patients (65%) had a positive culture. Overall, 39 patients (87%) had organisms susceptible to our perioperative antibiotic regimen. There was no difference in the infectious complication rate between those with positive compared with negative cultures (16% vs 29%, P = 0.17). Patients with a positive culture had similar 30-day postoperative infectious complication rates whether receiving postoperative antibiotics (n = 7) or not (14% vs 16%, P = 0.91). Only 1 patient had a correlation of clinical and islet cultures. Beyond prophylactic antibiotics, empiric antibiotic treatment for a positive culture is not warranted and provides a rationale for the abandonment of routine cultures in TPIAT.

Pain resolution and glucose control in pediatric patients with chronic pancreatitis after total pancreatectomy with islet auto-transplantation.

Chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) in pediatric patients are strongly associated with genetic mutations and lead to pan-parenchymal disease refractory to medical and endoscopic treatment. Our aim was to assess pain resolution and glucose control in patients with CP and ARP following total pancreatectomy with islet auto-transplantation (TPIAT). We retrospectively analyzed prospectively collected clinical data of 12 children who developed CP and ARP and underwent TPIAT when 21years old or younger at the University of Chicago between December 2009 and June 2020. Patients with recurrent or persistent abdominal pain attributed to acute or chronic pancreatic inflammation and a history of medical interventions attempted for the relief of pancreatic pain were selected by a multi-disciplinary team for TPIAT. We followed patients post-operatively and reported data for pre-TPIAT, post-operative day 75, and yearly post-TPIAT. All 12 patients experienced complete resolution of pancreatic pain. The overall insulin-independence rate after 1 year was 66% (8/12) and 50% (3/6) at 4 years. Shorter duration of CP/ARP pre-TPIAT, higher mass of islets infused, and lower BMI, BMI percentile, and BSA were associated with insulin-independence post-TPIAT. TPIAT is a viable treatment option for pediatric patients with CP and ARP. Pediatric patients undergoing TPIAT for CP achieved resolution of pancreatic-type pain and reduced opioid requirements. The majority were able to achieve insulin-independence which was associated with lower pre-TPIAT BMI and higher islet mass transplanted (i.e., over 2000 IEQ/kg), the latter of which can be achieved by earlier TPIAT. Treatment study, Level IV.

Gastrointestinal Bleed After Total Pancreatectomy With Islet Autotransplant.

Gastrointestinal bleeding (GIB) is an uncommon complication after abdominal surgery. Given the unique risks in the total pancreatectomy with islet autotransplant (TPIAT) population, we aimed to describe this population's incidence of postoperative GIB. Prospectively collected data on patients who underwent a TPIAT from 2001 to 2018 at the University of Minnesota were reviewed for postoperative GIB. Each GIB patient was matched to a control patient and compared for medical, medication, and social history and for clinical outcomes. Sixty-eight patients developed a GIB (12.4%) at median time after surgery of 17 months. Etiologies included the following: anastomotic ulcer (35%), Clostridium difficile (4%), gastric or duodenal ulcers (9%), esophagitis/gastritis (10%), hemorrhoids (3%), inflammatory bowel disease (4%), Mallory-Weiss tears (1%), and unknown (29%). During diagnostic workup, 87% had an endoscopic procedure and 3% underwent imaging. Seven patients required an operation (10%), 1 required an open embolization (1%), and 13 required endoscopic treatments (19%). Patients with a GIB were more likely to die (15% vs 5%, P = 0.055). Twelve percent of patients developed a GIB after TPIAT. One third of those had an undefined etiology despite endoscopy. The need for intervention was high (30%).

Painful chronic pancreatitis - new approaches for evaluation and management.

Management of abdominal pain in patients with chronic pancreatitis is often suboptimal. We review recent data on the epidemiology and new approaches for managing pain in chronic pancreatitis. Chronic pancreatitis duration does not appear to affect the pain experience. Pain pattern in chronic pancreatitis patients frequently changes and is not related to traditional patient and disease-related factors. Psychologic comorbidities, i.e. anxiety and depression, are frequent in patients with chronic pancreatitis, and are associated with more severe pain and pain interference. Adjunctive treatments, such as cognitive behavioral therapy, may positively influence pain management in chronic pancreatitis. Total pancreatectomy with islet autotransplantation (TPIAT) is an increasingly adopted treatment option in painful chronic pancreatitis. Ongoing multicenter studies will help define optimal candidates, predictors of successful pain remission and diabetes outcomes after TPIAT. Pancreatic quantitative sensory testing, a promising technique to interrogate nociception and sensory response, holds promise to identify patients with central sensitization. Initial studies show feasibility to stratify patients into defined pain profiles, and future studies will explore if these can help in prognostication of pain therapy. Several lines of investigations currently under evaluation are likely to have a positive impact on the management of pain in chronic pancreatitis.

Improved Glycemic Outcomes with Early Initiation of Insulin Pump Therapy in Pediatric Postoperative Total Pancreatectomy with Islet Autotransplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis and poor quality of life. Euglycemia is critical for islet cell survival and engraftment. We reviewed clinical care practice and hypothesized that early in-hospital transition from intravenous insulin to insulin pump therapy, managed by an endocrine unit trained on post-surgical care, would improve glucose control and impact the length of hospital stay. We completed a retrospective analysis of 40 pediatric patients who underwent TPIAT. Comparative hospitalized postoperative groups included those who received insulin intravenously, followed by multiple daily injections, subsequently managed by pump therapy (n = 14), versus those who received insulin intravenously followed by early pump therapy provided on the endocrine unit trained to manage post-surgical patients (n = 26). The outcomes analyzed included percentage of blood glucoses in target (4.44–6.66 mmol/L (80–120 mg/dL)), hypoglycemia (<3.33 mmol/L (<60 mg/dL)) and hyperglycemia (>7.77 mmol/L (>140 mg/dL)), blood glucose variability, and length of hospital unit stay post-ICU. Hospitalized patients with early transition to pump therapy on a specialized endocrine unit had a higher proportion of glucose values in the target range (61% vs. 51%, p = 0.0003), a lower proportion of hyperglycemia (15% vs. 19%, p = 0.04), and a lower proportion of hypoglycemia, though not statistically significant (3.4% vs. 4.4%, p = 0.33). Early pump users also had lower variability in glucose values over 10 days post-intravenous insulin (p = 0.001), and the post-transition median length of stay was shorter by 5 days (median: 11.5 vs. 16.5 days, p = 0.005). Early in-hospital pump therapy managed by the specialized endocrine unit improved glucose outcomes and reduced the duration of in-unit stay.

Australian experience with total pancreatectomy with islet autotransplantation to treat chronic pancreatitis.

This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP-IAT) in Australia. Individuals selected for TP-IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post-transplantation HbA1c, C-peptide, total daily insulin and analgesic requirement. Sixteen individuals underwent TP-IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290-7300). The median C-peptide 1 month post-TP-IAT was 384 (IQR 210-579) pmol/L and at median 29.5 (IQR 14.5-46.5) months from transplant was 395 (IQR 139-862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P< 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. The TP-IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates.

Atypical Hepatic Steatosis Patterns on MRI After Total Pancreatectomy With Islet Autotransplant.

OBJECTIVE. The purpose of this retrospective study was to investigate the prevalence and patterns of hepatic steatosis after total pancreatectomy with islet autotransplant (TPIAT) and to determine if the unique patterns of steatosis seen in this study correlated with islet graft function. MATERIALS AND METHODS. Fifty-two subjects who had undergone MRI after TPIAT were reviewed for the presence of hepatic steatosis. Patterns of steatosis were categorized into three groups: normal (no steatosis), homogeneous, and atypical. Demographics and outcomes were compared between the groups. Islet graft function 1 year after surgery was classified as full graft function, partial graft function, and graft failure. Statistical analysis was performed using ANOVA, Kruskal-Wallis, and Fisher exact tests. RESULTS. Sixty-three percent of patients had steatosis present on MRI after TPIAT (33 subjects of 52 total), and 48% (25/52) exhibited an atypical pattern. Twenty-four percent of the 37 patients who had MRI examinations before TPIAT showed steatosis preoperatively, yet none of these showed an atypical steatosis pattern. Islet graft function was not statistically different between the groups. The only statistically significant variable difference between the groups was body mass index (p = .02). CONCLUSION. Steatosis is a common finding after TPIAT, and atypical steatosis patterns frequently develop after the procedure, implying that the procedure itself is the causal factor. There was no correlation between islet graft function and the presence or pattern of steatosis. An atypical pattern of hepatic steatosis can therefore be considered an incidental finding after TPIAT and does not require additional workup or treatment.

Continuous Glucose Monitoring in the Intensive Care Unit Following Total Pancreatectomy with Islet Autotransplantation in Children: Establishing Accuracy of the Dexcom G6 Model.

Hyperglycemia is detrimental to postoperative islet cell survival in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT). This makes continuous glucose monitoring (CGM) a useful management tool. We evaluated the accuracy of the Dexcom G6 CGM in pediatric intensive care unit patients following TPIAT. Twenty-five patients who underwent TPIAT had Dexcom G6 glucose values compared to paired serum glucose values. All paired glucose samples were obtained within 5 minutes of each other during the first seven days post TPIAT. Data were evaluated using mean absolute difference (MAD), mean absolute relative difference (MARD), %20/20, %15/15 accuracy, and Clarke Error Grid analysis. Exclusions included analysis during the CGM “warm-up” period and hydroxyurea administration (known drug interference). A total of 183 time-matched samples were reviewed during postoperative days 2–7. MAD was 14.7 mg/dL and MARD was 13.4%, with values of 15.2%, 14.0%, 12.1%, 11.4%, 13.2% and 14.1% at days 2, 3, 4, 5, 6 and 7, respectively. Dexcom G6 had a %20/20 accuracy of 78%, and a %15/15 accuracy of 64%. Clarke Error Grid analysis showed that 77% of time-matched values were clinically accurate, and 100% were clinically acceptable. The Dexcom G6 CGM may be an accurate tool producing clinically acceptable values to make reliable clinical decisions in the immediate post-TPIAT period.

Total pancreatectomy with islet autotransplantation reduces resource utilization in pediatric patients

BackgroundChronic pancreatitis (CP) is associated with poor quality of life. Total pancreatectomy with islet autotransplantation (TPIAT) has traditionally been reserved for patients with refractory disease. We hypothesized TPIAT would lead to decreased costs and resource utilization after operation in children. MethodsRetrospective review of 39 patients who underwent TPIAT at a single children’s hospital was performed. All inpatient admissions, imaging, endoscopic procedures, and operations were recorded for the year prior to and following operation. Costs were determined from Centers for Medicare and Medicaid Services. ResultsMedian hospital admissions before operation was 5 (IQR:2–7) and decreased to 2 (IQR:1–3) after (p < 0.01). Median total cost for the year before operation was $36,006 (IQR:$19,914-$47,680), decreasing to $24,900 postoperatively (IQR:$17,432-$44,005, p = 0.03). Removing cost of TPIAT itself, total cost was further reduced to $10,564 (IQR:$3096-$29,669, p < 0.01). ConclusionIn children with debilitating CP, TPIAT has favorable impact on cost reduction, hospitalizations, and invasive procedures. Early intervention at a specialized pancreas center of excellence should be considered to decrease future resource utilization and costs among children.

Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples (n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p (P = 0.03), hsa-miR-148a-3p (P = 0.04) and hsa-miR-221-3p (P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p (P = 0.04) and hsa-miR-7-5p (P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p (P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p (P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg (r = −0.20, P = 0.02). Also, hsa-miR-200c (r = 0.18, P = 0.03) and hsa-miR-221-3p (r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.

Early use of continuous glucose monitoring in children and adolescents after total pancreatectomy with islet autotransplantation.

Children undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis require intensive insulin therapy early after TPIAT with narrow glycemic targets, which can a present significant care burden. Outpatient use of continuous glucose monitoring (CGM) systems by children and caregivers early after TPIAT is inadequately studied. In this open-label study, we randomized 14 children and adolescents (mean age 15.4 years) after hospital discharge for TPIAT to Dexcom G6 CGM (n = 7) or standard care with a glucometer (n = 7) to assess acceptability and glycemic control with use of CGM versus usual care (glucometer). Participants in the control arm also wore a blinded CGM for 1 week. Children randomized to real-time CGM had lower mean sensor glucose values compared with controls (p = 0.002), and high overall satisfaction with CGM. Our data indicate that CGM is a useful adjunct to diabetes management for children who have recently undergone TPIAT.

Imaging prediction of islet yield and post-operative insulin requirement in children undergoing total pancreatectomy with islet autotransplantation

BackgroundPredicting post-operative glycemic control in children undergoing total pancreatectomy with islet autotransplantation (TPIAT) remains difficult. The purpose of our study was to explore preoperative imaging as a marker for islet yield and insulin need in pediatric patients undergoing TPIAT. MethodsThis was a retrospective study of children (≤18 years) who had undergone TPIAT between April 2015 and December 2018 and had 6 or more months of post-TPIAT follow-up. Patient specific factors (height, weight, body mass index [BMI], body surface area [BSA]) and pancreas volume segmented from the most recent pre-operative cross-sectional imaging were explored as predictors of islet yield (total islet counts [TIC], total islet equivalents [TIE], islet equivalents per kilogram body weight [IEQ/kg]) and glycemic control (total daily dose of insulin per kilogram body weight [TDD/kg], insulin independence) using Pearson correlation and univariate and multiple regression. ResultsThirty-three patients, median age 13 years (IQR: 10–15 years), 64% female (21/33) met inclusion criteria. Nine patients (27%) achieved insulin independence at six months. Median TIE isolated was 310,000 (IQR: 200,000–460,000). Segmented pancreas volume was moderately associated with TIE (coefficient estimate = 0.34, p = 0.034). On multiple regression analysis, there was no significant predictor of insulin independence but number of attacks of pancreatitis (estimate = 0.024; p = 0.018) and segmented pancreas volume by body weight (estimate = −0.71; p < 0.001) were significant predictors of insulin TDD/kg. ConclusionPancreas volume segmented from pre-TPIAT imaging has predictive performance for post-TPIAT insulin need in children.

Body Composition is Associated With Islet Function After Pancreatectomy and Islet Autotransplantation for Pancreatitis.

Body composition in total pancreatectomy with islet autotransplantation (TPIAT) has never been studied. Determine whether presurgical body composition is associated with islet function and insulin sensitivity after TPIAT. In 88 adults undergoing TPIAT (median age 41.0 years, IQR 32.8-48.0), beta-cell function and insulin sensitivity were assessed using mixed meal tolerance test and frequent sample intravenous glucose tolerance test before surgery and 12 and 18 months afterward. Body composition was measured by dual x-ray absorptiometry. Analyses used linear and logistic regression. Before surgery, 8 individuals (9.1%) were underweight, 40 (45.5%) normal weight, 20 (22.7%) overweight, and 20 (22.7%) obese. Overweight/obese patients had higher area under the curve C-peptide and lower insulin sensitivity index. Baseline body weight was positively associated with first-phase insulin secretion (AIRg) at 12 months (average 38.5 [SE 17.1] mU/L/min higher per extra kg; P = 0.03) and 18 months (38.3 [18.5]; P = 0.04), while baseline lean mass was inversely associated with AIRg at 12 months (-0.05 [0.02] per extra kg; P = 0.01) and 18 months (-0.05 [0.02]; P = 0.03). Percent gynoid fat was inversely associated with disposition index at 18 months (-206.0 [97.2] per extra percent; P = 0.04). Percent body fat and percent gynoid fat were associated with glucose effectiveness index at 18 months (1.9 × 10-3 [0.9 × 10-3] per extra percent; P = 0.04 and -1.96 × 10-3 [0.8 × 10-3]; P = 0.02, respectively). Insulin independence was not significantly associated with body weight or composition. Half of these chronic pancreatitis patients were overweight/obese; underweight was uncommon. Preoperative body weight and composition were associated with islet function but not insulin independence after TPIAT.

S0019 Opioid Dependence and Outcomes in Total Pancreatectomy With Islet Autotransplantation in Patients With Chronic Pancreatitis

INTRODUCTION: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for patients living with chronic pancreatitis. Many of these patients are dependent on chronic opioid therapy prior to surgery and we therefore studied the outcomes of these patients in comparison to non-opioid users using a national inpatient database. METHODS: The National Inpatient Sample (NIS) is the largest all-payer inpatient database in the United States. Data from the years 2008 to 2014 were collected. Patients older than 18 years with an admission diagnosis of chronic pancreatitis and who underwent total pancreatectomy with islet autotransplantation were included. Mortality, length of stay, and cost of hospitalization were measured amongst patients that were opioid dependent and those who were not. RESULTS: Between 2008 and 2014, there were 990 patients older than 18 years with chronic pancreatitis that underwent TPIAT. A total of 67 patients had a diagnosis of opioid abuse or dependence. Baseline patient demographics and hospital characteristics is available in Table 1. The majority of patients that underwent TPIAT were women in both groups. Surprisingly the majority of opioid dependence patients that underwent TPIAT were on the western part of the US and none were in the Midwest or Northeast. There was a total of two deaths in the non-opioid abuse group and none in the opioid group though this was not statistically significant. Length of stay (median 12 days vs. 11 days, P = 0.62) and cost of hospitalization ($68,938 vs. $60,412, P = 0.25) was higher in patients without opioid abuse but these outcomes were not statistically significant.Figure 1CONCLUSION: Opioid dependence does not seem to play a major role in some outcomes of TPIAT patients during their incident admission for surgery based on our data. However, this retrospective study does not give us long term outcomes of these patients and therefore prospective studies will need to be investigated to make the appropriate choices.

Fat-soluble Vitamin Deficiency is Common in Children With Chronic Pancreatitis Undergoing Total Pancreatectomy With Islet Autotransplantation.

The prevalence of fat-soluble vitamin (FSV) deficiency in children undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis (CP) is unknown. We quantified FSV deficiency in 100 children (age ≤18) undergoing TPIAT. FSV levels (vitamins A, E, D) and clinical history were abstracted from medical records. Vitamin A was low in 4% before and 7% at 1 year after TPIAT, vitamin E in 17% and 18%, and vitamin D in 22% and 24%, respectively, regardless of pancreatic enzyme or vitamin supplement dosing. Longer duration of CP was associated with pre-TPIAT vitamin D insufficiency (P = 0.0002). This remained significant in a multivariate regression model (adjusted P = 0.01). On multivariate analysis, there were no significant predictors of low FSV levels post-TPIAT. FSV deficiencies are common among children undergoing TPIAT and patients who have had longer disease duration may be at increased risk. All children should be monitored for FSV deficiency after TPIAT.

PHENOTYPIC AND GENOTYPIC ANALYSIS OF HEREDITARY PANCREATITIS IN PATIENTS AND POTENTIAL CANDIDATES FOR TOTAL PANCREATECTOMY WITH ISLET AUTOTRANSPLANTATION (TP-IAT)

Introduction: Hereditary Pancreatitis (HP) is caused by inheritance of genetic mutations in PRSS1/2, SPINK1, CFTR and CTRC gene regions. HP frequently results in inflammation of the pancreas from a young age, chronic abdominal pain, dependency upon opioids, and elevated risk of pancreatic ductal adenocarcinoma (PDAC) at later stages of life. Total Pancreatectomy with Islet Autotransplantation (TP-IAT) effectively treats patients of HP and prevents diabetes and risk of pancreatic cancer later in life. This project aims to identify HP cases and assess the correlation between phenotypic disease outcome and genotypic mutation variant. Methods: Patients with HP were identified from hospital records and interviewed for phenotype. Criteria include: personal and family medical history, pain management, medical prescriptions, previous surgery, smoking and alcohol history, and quality of life. Salivary biosamples were obtained to be whole-exome-sequenced (WES). WES data was filtered using the VariantGrid pipeline with gnomAD pancreas-related disease frequency >1%. Results: 4 families of 42 individuals, plus 33 additional familial probands of HP had been identified thus far. All 4 families possess the mutation PRSS1, albeit different allelic variants (3 with R122H, 1 with A86T). One PRSS1 R122H mutation variant family also possessed SPINK1 N34S mutation, a known HP disease modifier mutation. In these well-phenotyped families, 23 PRSS1 and 5 SPINK1 genetic mutation carriers were identified from our study cohort. 13 of whom suffered from phenotypic symptoms of HP. Interestingly, 12 of the 33 probands have been genotyped and showed no known HP-associated mutation. Conclusion: Phenotypic disparity in mutation carriers suggests possible existence of unknown modifier genes for HP. Disease phenotype in probands with no known mutation also suggest possible existence of novel HP-associated mutations. Bioinformatics analysis studies of acquired WES data are currently underway for further investigation.

Pancreatic volume does not correlate with histologic fibrosis in adult patients with recurrent acute and chronic pancreatitis

ObjectivesReduced pancreatic volume, often referred to as atrophy, is a commonly reported imaging feature of chronic pancreatitis (CP). This study evaluated whether there is an association between pancreatic volume and fibrosis, the criterion standard of CP, in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for recurrent acute pancreatitis (RAP) and CP. MethodsAll adult patients who underwent TPIAT between 2010 and 2019 were categorized into 3 groups: RAP, definite CP and indeterminate CP. Pancreatic volume was calculated by summing up the areas from each thin section of the pancreas on 3D CT imaging. Excisional biopsies of the pancreatic head as well as body/tail region were obtained at the time of TPIAT. Two different fibrosis scores were used for histologic assessment. ResultsA total of 16, 29 and 15 patients underwent TPIAT for RAP, definite CP and indeterminate CP, respectively. The mean pancreatic volumes for patients with RAP, definite CP and indeterminate CP were 65.7 ± 28.5 cc, 54.9 ± 22.9 cc and 61.8 ± 23.6 cc, respectively (p = 0.3). The mean fibrosis scores were significantly higher in patients with definite CP compared to RAP (p < 0.001) and indeterminate CP (p < 0.001). Pancreatic volume was not associated with either fibrosis score after adjusting for age, gender, duration of disease, BMI and diabetes in the multivariable analysis. ConclusionsWhile the fibrosis scores were higher in definite CP compared to both RAP and indeterminate CP, there was no correlation between pancreatic volume and fibrosis. This suggests that atrophy alone cannot be used to diagnose CP.