Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it a durable operation?

OBJECTIVE: Total pancreatectomy and islet cell autotransplantation (TPIAT) has been increasingly utilized for the management of chronic pancreatitis (CP) with early success. However, the long-term durability of this operation remains unclear. METHODS: All patients undergoing TPIAT for the treatment of CP with 5-year or greater follow-up were identified for inclusion in this single-center observational study. End points included narcotic requirements, glycemic control, islet function, quality of life (QOL), and survival. RESULTS: Between 2000 and 2013, 166 patients underwent TPIAT; 112 of these patients had 5-year follow-up data to analyze. All patients underwent successful IAT with a mean of 6027 ± 595 islet equivalents per body weight. There was no perioperative mortality and actuarial survival at 5 years was 94.6%. The narcotic independence rate at 1 year was 55% and continued to improve to 73% at 5-year follow-up (P < 0.05). The insulin independence rate declined over time (38% at 1 year vs 27% at more than 5 years), but insulin requirements remained similar (21.4 vs 24.3 units per day, P = 0.6). All patients achieved stable glycemic control with a median hemoglobin A1C (HgA1C) of 6.9% (range: 5.85%-8.3%). The short form 36-item QOL assessment of a subset of patients available for contact demonstrated continued improvements in all tested modules in patients with at least 5-year follow-up. Two patients developed diabetic complications requiring whole organ pancreas transplant for salvage. CONCLUSIONS: This represents one of the largest series examining long-term outcomes after TPIAT. This operation produces durable pain relief and improvement in QOL parameters. Insulin independence rates decline over time, but most patients maintain stable glycemic control.

Immunomodulation by Mesenchymal Stromal Cells and Their Clinical Applications.

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that can be isolated and expanded from various sources. MSCs modulate the function of immune cells, including T and B lymphocytes, dendritic cells, and natural killer cells. An understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms involved in MSCs-mediated therapeutic effects, and for designing more practical protocols for the clinical use of these cells. In this review we describe the current knowledge of the unique biological properties of MSCs, the immunosuppressive effects on immune-competent cells and the paracrine role of soluble factors. A summary of the participation of MSCs in preclinical and clinical studies in treating autoimmune diseases and other diseases is described. We also discuss the current challenges of their use and their potential roles in cell therapies.

Factors associated with insulin and narcotic independence after islet autotransplantation in patients with severe chronic pancreatitis.

BACKGROUND: For patients who suffer from severe chronic pancreatitis, total pancreatectomy can alleviate pain, and islet autotransplantation (IAT) might preserve endocrine function and circumvent the complications of diabetes. Factors that determine success after this operation have not been clearly defined. STUDY DESIGN: From 2000 to 2004, 45 total or subtotal pancreatectomies with IAT were performed. Patient characteristics, narcotic usage and insulin requirements were recorded at routine followup. Narcotic usage was standardized by conversion to morphine equivalents (MEs). Univariate and multivariate statistical analyses were performed to determine factors associated with insulin and narcotic independence. RESULTS: Forty-five patients (30 women, 15 men), with a mean age of 39 years (range 16 to 62 years) underwent total or completion (n=41) or subtotal (n=4) pancreatectomies with IAT. Forty percent of patients were insulin free after a mean followup of 18months (range 1 to 46months). Factors associated in univariate analyses with insulin independence included female gender (p=0.004), lower body weight (kg) (p=0.04), more islet equivalents per kg body weight (IEQ/kg) transfused (<0.05), lower mean insulin requirement for the first 24hours postoperation (p=0.002), and lower mean insulin requirement at discharge (p=0.0005). A multiple logistic regression using gender, body mass index, and IEQ/kg identified female gender as the only notable variable associated with insulin independence. There was a notable reduction (p < 0.0001) of postoperative MEs (mean 90 mg) compared with preoperative MEs (mean 206 mg) for the entire cohort; 58% of patients are narcotic independent. In the subset of patients with>5months followup (n=32), 23 (72%) are narcotic free, with a substantial decrease in ME usage (p=0.01). CONCLUSIONS: The likelihood of glycemic control after IAT is related to both patient characteristics and islet cell mass. Based on these data, more islet cells may be required for insulin independence than previously thought.

Continuous glucose monitoring analysis as predictor of islet yield and insulin requirements in autologous islet transplantation after complete pancreatectomy.

We analyzed the pretransplant continuous glucose monitoring (CGM) data of 45 patients that underwent total pancreatectomy followed by autologous islet transplantation (AIT) at the University of Arizona Medical Center. Traditional and novel metrics of CGM time series were correlated to the total islet count (TIC), islet equivalents (IEQs), and weight-normalized IEQs (IEQ/kg). In a subset cohort (n = 26) we analyzed the relationship among the infused number of islets, the CGM indicators, and the first recorded insulin requirement after the procedure. We conclude that receiving a high islet yield is sufficient yet not necessary to achieve low or null insulin requirements within the first 50 days after surgery. Furthermore, CGM inertia and CGM length of curve (2 novel CGM indicators) are shown to be correlated to islet yield, and the CGMs normalized area (Ao) and time ratio above hyperglycemic level (To) are strongly correlated to insulin requirement. A screening test based on To is shown to have 100% sensitivity and 88% specificity discriminating insulin independence upon discharge.