PURPOSE:Total 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. METHODS:A 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. RESULTS:Patients 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. CONCLUSION:Our 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.

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<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.

In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P < .01), and stimulated C-peptide levels were lower (P < .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P < .0001), with no insulin independence 12 months posttransplant (P < .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P < .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.

Total pancreatectomy with islet autotransplantation (TPIAT) is the treatment of choice to preserve pancreatic endocrine function, alleviate pain, and improve quality of life (QoL) when other strategies are ineffective for chronic pancreatitis (CP) patients. This study utilized pancreatic disease-specific surveys developed by the European Organisation for Research and Treatment of Cancer (EORTC) to conduct a comprehensive, single-center examination of a large cohort of patients to gain understanding of QoL post-TPIAT. Two validated QoL surveys of the EORTC-QLQ-C30 and QLQ-PAN26-were administered in a prospective cohort of CP patients during pre-and post-operative scheduled visits. A total of 116 patients responded to the preoperative survey and were included in this study. The global health scale of QLQ-C30 was significantly improved after TPIAT when compared to baseline with delta scores of 24.26, 20.54, and 26.7 at 1, 2, and 3 years post-TPIAT (p < 0.001). The EORTC-PAN26 revealed significant improvements in symptom scales for pancreatic pain, bloating, digestive symptoms, taste, indigestion, weight loss, body image, and future worries. The comprehensive surveys in such a large cohort expands the QoL criterion in CP patients and indicates significant improvement in QoL post-TPIAT, further validating TPIAT as a treatment option for refractory CP.

Background: Standard 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. Methods: We 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). Results: The 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). Conclusion: TPIAT 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.

Introduction: Total pancreatectomy and intraportal islet autotransplantation (TPIAT) is an effective treatment for patients with refractory chronic pancreatitis. Large volume islet preparations cannot always be infused fully intraportally due to rise in portal vein (PV) pressure and risk of PV thrombosis. We previously showed that dissected preperitoneal pouch (preperitoneal space) can serve as an extrahepatic islet transplant site with long-term graft function in syngeneic mouse model. Here, we evaluated the safety of combined sites of intrahepatic and preperitoneal space in clinical TPIAT and analyzed the outcome. Method: Between 2019 and 2020, patients underwent TPAIT using a combined intraportal and preperitoneal pouch technique (IPV+PP) if the infused intraportal islet mass was >4,000 islet equivalents per kg (IEQ/kg) and PV pressure was > 20mmHg during infusion. Patients were monitored for complications, and metabolic outcome was assessed and compared with controls who received only intraportally transplanted islets (IPV) or combined intraportal and into the peritoneal cavity (IPV+PC). Results: Ten patients underwent TPIAT into the PV and preperitoneal pouch. Baseline demographics (age, sex, BMI, pretransplant C-peptide and HbA1c, duration of symptoms), PV pressure, islet mass by IEQ/kg of each group are shown in Figure 1. There were no serious post-operative complications in the IPV+PP group during the first post-transplant admission. At 6 months after TPIAT, there were no significant differences in glycemic control or graft function among three groups (Figure 1). Conclusion: The preperitoneal space is an alternative supplemental islet infusion site in patients who do not tolerate a full intraportal islet infusion. It is safe, easily accessible and it tolerates large volume islet preparations. Further studies are needed on a larger number of patients to validate our results.

Background The combined use of interleukin-1 beta and tumor necrosis factor-alpha blockers in the peritransplant period has improved outcomes of total pancreatectomy with islet autotransplantation (TPIAT). However, these drugs may suppress the immune system, resulting in severe infection. Methods We retrospectively investigated the impact of microbial-contaminated islet product on posttransplant complications and metabolic outcomes of TPIAT patients receiving the IL-1 beta and TNF-blockade treatment at our center. Results Among 108 TPIAT patients, 37 patients (34%) received contaminated products. Preoperative stent treatment and fibrosis score were independent risk factors for the contamination. There were no significant differences between the contaminated and noncontaminated product groups in posttransplant infectious complication rate, length of hospitalization, or readmission rate. However, islet equivalents (P < .0001) and insulin independence rate (P = .036) at 6 months were significantly lower for patients receiving contaminated product. Conclusions These results suggest that combined anti-inflammatory drug use is safe and well tolerated in TPIAT patients who receive contaminated islet product and does not increase the rate of infectious complications; however, contaminated islet product is associated with poor metabolic outcomes.

Total pancreatectomy with islet autotransplantation is a promising treatment for refractory chronic pancreatitis. We analyzed postoperative complications in 83 TPIAT patients and their impact on islet graft function. We examined patient demographics, preoperative risk factors, intraoperative variables, and 30- and 90-day postoperative morbidity and mortality. Daily insulin requirement, HbA1c, C-peptide levels, and narcotic requirements were analyzed before and after surgery. Adverse events were recorded, with postoperative complications graded according to the Clavien-Dindo classification. There was no mortality in this patient group. Postoperative complications occurred in 38 patients (45.7%). Patients with postoperative complications were readmitted significantly more often within 30 days (p = 0.01) and 90 days posttransplant (p < 0.0003) and had a significantly longer hospital stay (p = 0.004) and intensive care unit stay (p = 0.001). Insulin dependence and graft function assessed by HbA1c, C-Peptide and insulin requirements did not differ significantly by these complications. Postoperative complications after TPIAT are associated with longer hospital and intensive care unit stay and with readmission; however, the surgical complications do not affect islet graft function.

BACKGROUND:Little published data exist examining causes of hospital readmission following total pancreatectomy with islet autotransplantation (TPIAT).METHODS:A retrospective analysis was performed of a prospectively collected institutional TPIAT database. Primary outcome was unplanned readmission to the hospital within 30 days from discharge. Reasons and risk factors for readmission as well as islet function were evaluated and compared by univariate and multivariate analysis.RESULTS:83 patients underwent TPIAT from 2006 to 2014. 21 patients (25.3%) were readmitted within 30 days. Gastrointestinal problems (52.4%) and surgical site infection (42.8%) were the most common reasons for readmission. Initial LOS and reoperation were risk factors for early readmission. Patients with delayed gastric emptying (DGE) were three times more likely to get readmitted. In multivariate analysis, patients undergoing pylorus preservation surgery were nine times more likely to be readmitted than the antrectomy group.CONCLUSION:Early readmission after TPIAT is common (one in four patients), underscoring the complexity of this procedure. Early readmission is not detrimental to islet graft function. Patients undergoing pylorus preservation are more likely to get readmitted, perhaps due to increased incidence of delayed gastric emptying. Decision for antrectomy vs. pylorus preservation needs to be individualized.

Shahbazov, Rauf MD, PhD; Yoshimatsu, Gumpei MD, PhD; Dabous, Ali MD; Lawrence, Michael C. PhD; Kim, Peter T. MD; Onaca, Nicholas MD; Beecherl, Ernest MD; Naziruddin, Bashoo PhD; Levy, Marlon F. MD Author Information

Background: Allogenic blood transfusion (ABT) may be needed for severe bleeding during total pancreatectomy with autotransplantation (TPIAT), but may induce inflammation. This study investigated the impact of ABT. Methods: With a population of 83 patients who underwent TPIAT from 2006 to 2014, this study compared cytokine levels, patient characteristics, islet characteristics, metabolic outcomes, insulin requirements, and hemoglobin A1c for those who received a blood transfusion (BT) versus no blood transfusion (NBT). Results: Initially, proinflammatory cytokines were moderately higher in the BT group than the NBT group. Despite longer procedures and more severe bleeding, the BT group had similar values to the NBT group for insulin requirements, serum C-peptide, hemoglobin A1c, and insulin independence rate. The probability of insulin independence was slightly higher in patients receiving >= 3 units of blood. Conclusion: ABT induced elevation of proinflammatory cytokines during the perioperative period in TPIAT, but these changes did not significantly change posttransplant islet function. (C) 2017 Elsevier Inc. All rights reserved.

Thompson, Traci K. PharmD*; Hutchison, Rob W. PharmD*; Wegmann, Deborrah J. RN, PhD(c)†; Shires, G. Tom III MD‡; Beecherl, Ernest MD‡ Author Information