Search

In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence.We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT.We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females.Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment.This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997).

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation. METHODS: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n=84) with adults (n=195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP. RESULTS: Children more commonly underwent splenectomy (100% versus 91%, p=0.002), pylorus preservation (93% versus 67%; p

Background/objectives Pancreatogenic diabetes mellitus has been assumed to result from non-immune beta cell destruction when the pancreas is replaced by fibrotic tissue secondary to acute and chronic pancreatitis. We hypothesize that recurrent episodes of pancreatic inflammation may increase the risk for developing β-cell autoimmunity in susceptible individuals. Methods We describe 11 patients who had both recurrent acute and/or chronic pancreatitis and type 1 diabetes (T1D) requiring insulin therapy. Results All 11 patients had positive autoantibodies and 8 patients tested had minimal to undetectable (7/8) or moderate (1/8) stimulated C-peptide at 12 months after T1D onset. Three had biopsy confirmation of insulitis. Conclusions These cases lend support to the theory that pancreatitis may increase risk for T1D. We postulate that the pro-inflammatory conditions of pancreatitis may increase posttranslational protein modifications of β-cell antigens and neoepitope generation, which are potential initiating events for loss of β-cell self-tolerance.

Background Advances in our understanding of total pancreatectomy with islet autotransplantation (TPIAT) have been made. We aimed to define indications and outcomes of TPIAT. Methods Expert physician-scientists from North America, Asia, and Europe reviewed the literature to address six questions selected by the writing group as high priority topics. A consensus was reached by voting on statements generated from the review. Results Consensus statements were voted upon with strong agreement reached that (Q1) TPIAT may improve quality of life, reduce pain and opioid use, and potentially reduce medical utilization; that (Q3) TPIAT offers glycemic benefit over TP alone; that (Q4) the main indication for TPIAT is disabling pain, in the absence of certain medical and psychological contraindications; and that (Q6) islet mass transplanted and other disease features may impact diabetes mellitus outcomes. Conditional agreement was reached that (Q2) the role of TPIAT for all forms of CP is not yet identified and that head-to-head comparative studies are lacking, and that (Q5) early surgery is likely to improve outcomes as compared to late surgery. Conclusions Agreement on TPIAT indications and outcomes has been reached through this working group. Further studies are needed to answer the long-term outcomes and maximize efforts to optimize patient selection.

Patients undergoing total pancreatectomy and islet cell autotransplant (TPIAT) for treatment of pancreatitis are at risk for complications of over and under resuscitation. We hypothesized that using a goal directed fluid therapy (GDFT) protocol might impact clinical outcomes.A consecutive series of adult patients undergoing TPIAT were managed intraoperatively using either standard fluid therapy (SFT, n = 44) or GDFT (n = 23) as part of a pilot study between January 2013 and May 2015. Patient characteristics, intraoperative, and postoperative data were recorded prospectively, then retrospectively analyzed for differences between the groups.The GDFT group had lower total fluid resuscitation (3,240 cc vs 5,173 cc, p 0.0001) and transfusion requirements (1.0 cc/kg vs 3.3 cc/kg, p = 0.050) compared to the SFT group. The pre to postop nadir hemoglobin change was significantly less for GDFT (4.2 vs 5.1 gm/dl, p = 0.021) despite less transfusion.Compared to SFT, using an intraoperative GDFT protocol in TPIAT patients was associated with significantly decreased intraoperative fluid resuscitation, blood transfusion and less postoperative dilutional anemia, without any difference in complications of underresuscitation. This pilot study suggests that GDFT is likely safe and further investigation is warranted.

Objectives The minimally invasive step-up approach for treatment of walled off necrosis (WON) involves drainage followed by later necrosectomy as needed, and is superior to primary surgical necrosectomy. Reported series of endoscopic transluminal necrosectomy include highly selected patients. We report outcomes of a large series of patients with WON managed by an algorithm based on an endoscopically centered step-up approach. Methods Consecutive patients with necrotizing pancreatitis from 2009 to 2014, with intervention only for infected or persistently symptomatic WON. The primary approach involved endoscopic transluminal drainage plus minus necrosectomy whenever feasible, with percutaneous catheter drainage (PCD) plus minus sinus tract endoscopy if not feasible or sufficient. Surgery was reserved for failures of the step up approach. Results Of 109 consecutive patients with necrotizing pancreatitis, intervention was required in 83, including endoscopic transluminal drainage in 73 (88%) (alone in 49 and combined with PCD in 24), and PCD alone in 10 (12%). 64 (77%) of the 83 patients required endoscopic transluminal and/or sinus tract necrosectomy. Adverse events occurred in 11 (13%). Three patients (4%) failed step up approach and required open surgical necrosectomy. All-cause mortality occurred in 6 (7%) of 83 patients after intervention, including 2 of 3 requiring surgery. Conclusions An algorithm based step-up approach for interventions in necrotizing pancreatitis using primarily endoscopic techniques with adjunctive percutaneous approaches as needed resulted in favorable outcomes with small numbers proceeding to open surgery, and with acceptable rates of major complications and mortality. A purely endoscopic transluminal approach was feasible in approximately 60% of patients requiring intervention in this series.