Impact of Tissue Volume and Purification on Clinical Autologous Islet Transplantation for the Treatment of Chronic Pancreatitis

Abstract

Autologous islet transplantation after total pancreatectomy is an excellent treatment for painful chronic pancreatitis. Traditionally, islets have been isolated without purification; however, purification is applied when the tissue volume is large. Nevertheless, the impact of tissue volume and islet purification on clinical outcomes of autologous islet transplantation has not been well examined. We analyzed 27 cases of autologous islet transplantation performed from October 2006 to January 2011. After examining the relationship between tissue volume and portal pressure at various time points, we compared islet characteristics and clinical outcomes between cases with complications (complication group) and without (noncomplication group), as well as cases with purification (purification group) and without (nonpurification group). Tissue volume significantly correlated with maximum (R = 0.61), final (R = 0.53), and delta (i.e., difference between base and maximum; R = 0.71) portal pressure. The complication group had a significantly higher body mass index, tissue volume, islet yield, and portal pressure (maximum, final, delta), suggesting that complications were associated with high tissue volume and high portal pressure. Only one of four patients (25%) in the complication group became insulin free, whereas 11 of 23 patients (49%) in the noncomplication group became insulin free with smaller islet yields. The purification group had a higher islet yield and insulin independence rate but had similar final tissue volume, portal pressure, and complication rates compared with the nonpurification group. In conclusion, high tissue volume was associated with high portal pressure and complications in autologous islet transplantation. Islet purification effectively reduced tissue volume and had no negative impact on islet characteristics. Therefore, islet purification can reduce the risk of complications and may improve clinical outcome for autologous islet transplantation when tissue volume is large.

Evidence for Instant Blood-Mediated Inflammatory Reaction in Clinical Autologous Islet Transplantation

“…Further, we have demonstrated the adverse impact of tissue volume on AIT outcome (18). Importantly, analysis of serum samples collected during the peritransplant period after AIT showed increased release of high-mobility group box 1 protein, which is a marker for islet damage (19).…”

“…If the pellet volume was >20 mL, islets were purified with a COBE 2991 cell processor (CaridianBCT, Inc., Lakewood, CO) with continuous iodixanol-based density gradient centrifugation. The final preparation of islets was assessed for counts, purity, viability and sterility (18) prior to infusion without any culture.…”

Islet Autotransplantation and Total Pancreatectomy

“…At this point, the pellet containing acinar and endocrine tissue is collected and assessed for islet count, viability, purity, and endotoxin content, and a sample is sent for Gram stain followed by microbiology culture. Direct infusion of large amounts of tissue into the portal vein leads to intrahepatic microembolization and inflammation [12, 13]. To prevent this, many islet centers further purify islets from acinar tissue when the pellet volume exceeds 0.25mL/kg body weight [14].…”

Strategies in Preventing Diabetes after Pancreatectomy Using Islet Auto- and Allo-Transplantation

“…In addition to improved outcomes being linked to higher volume centers, several studies have been published examining various factors that predicted positive outcomes for TP-IAT [53][54][55][56]. Important outcomes that are most commonly measured after TP-IAT include postoperative islet graft survival and function, narcotic use, persistence pain, and changes to quality of life.…”

“…Important outcomes that are most commonly measured after TP-IAT include postoperative islet graft survival and function, narcotic use, persistence pain, and changes to quality of life. The factors that have been found to be most influential of clinical outcomes include islet cell yield, transplant tissue volume [56], isolation and purification techniques [54], and duration of narcotic use and physical health prior to surgery. Low islet yield is the strongest independent risk factor for islet graft failure postoperatively [53].…”