The impact of bacterial colonization on graft success after total pancreatectomy with autologous islet transplantation: considerations for early definitive surgical intervention
Abstract:Objective
The purpose of this study was to determine whether bacterial contamination of islets affects graft success after total pancreatectomy with islet autotransplantation (TPIAT).
Background
Factors associated with insulin independence after TPIAT are inconclusive. Although bacterial contamination does not preclude transplantation, the impact of bacterial contamination on graft success is unknown.
Methods
Patients who received TPIAT at the University of Virginia between January 2007 and January 2016 we… Show more
“…In the present study, the rate of posttransplant infectious complications, excluding islet infusion‐related complications such as bleeding, portal vein thrombosis, high portal pressure, and heavy fatty liver, was not significantly different between the two groups, in agreement with previous reports . The rate of posttransplant infectious complications in all patients was 12.9% (14/108), which is quite a bit lower than that in a previous report .…”
Section: Discussionsupporting
confidence: 88%
“…In TPIAT, contamination rates have been reported to range from 39% to 82.2% for pancreas preservation medium and from 22.2% to 64.3% for final islet preparations . Recent studies concluded that microbial contamination does not influence posttransplant complications . For example, Jolissaint et al reported that culture‐positive islets were not related to posttransplant complications but were associated with higher rates of graft failure and poor islet yield in TPIAT .…”
Section: Introductionmentioning
confidence: 99%
“…Recent studies concluded that microbial contamination does not influence posttransplant complications . For example, Jolissaint et al reported that culture‐positive islets were not related to posttransplant complications but were associated with higher rates of graft failure and poor islet yield in TPIAT . Furthermore, Berger et al showed that positive cultures during pediatric TPIAT were not associated with an increase in posttransplant infections .…”
Background:The combined use of interleukin-1β and tumor necrosis factor-α 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-1β 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.
“…In the present study, the rate of posttransplant infectious complications, excluding islet infusion‐related complications such as bleeding, portal vein thrombosis, high portal pressure, and heavy fatty liver, was not significantly different between the two groups, in agreement with previous reports . The rate of posttransplant infectious complications in all patients was 12.9% (14/108), which is quite a bit lower than that in a previous report .…”
Section: Discussionsupporting
confidence: 88%
“…In TPIAT, contamination rates have been reported to range from 39% to 82.2% for pancreas preservation medium and from 22.2% to 64.3% for final islet preparations . Recent studies concluded that microbial contamination does not influence posttransplant complications . For example, Jolissaint et al reported that culture‐positive islets were not related to posttransplant complications but were associated with higher rates of graft failure and poor islet yield in TPIAT .…”
Section: Introductionmentioning
confidence: 99%
“…Recent studies concluded that microbial contamination does not influence posttransplant complications . For example, Jolissaint et al reported that culture‐positive islets were not related to posttransplant complications but were associated with higher rates of graft failure and poor islet yield in TPIAT . Furthermore, Berger et al showed that positive cultures during pediatric TPIAT were not associated with an increase in posttransplant infections .…”
Background:The combined use of interleukin-1β and tumor necrosis factor-α 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-1β 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.
“…Consistent with our findings, in an autotransplantation setting, Jolissaint et al . also found that bacterial contaminants in the final islet preparation were associated with lower islet yield and lower C‐peptide/insulin independence rates in six patients. However, such small number of patients does not allow definitive conclusion and the situation could be different in this latter study because contamination is usually present at a higher load in patient with chronic pancreatitis and pancreatic duct dilatation and obstruction.…”
The microbiological safety of islet preparations is paramount. Preservation medium contamination is frequent, and its impact on islet yield and function remains unclear. Microbiological samples collected during islet isolations from 2006 to 2016 were analyzed and correlated to isolation and allo- and autotransplantation outcomes. Microbial contamination of preservation medium was found in 64.4% of processed donor pancreases (291/452). We identified 464 microorganisms including Staphylococcus (253/464, 54.5%), Streptococcus (31/464, 6.7%), and Candida species (25/464, 5.4%). Microbial contamination was associated with longer warm and cold ischemia times and lower numbers of postpurification islet equivalents, purity, transplant rate, and stimulation index (all P < 0.05). Six percent of the preparations accepted for transplantation showed microbial contamination after isolation (12/200); 9 of 12 were Candida species. Six patients were transplanted with a sample with late microbial growth discovered after the infusion. Insulin independence rate was not affected. This risk of transplanting a contaminated islets preparation was reduced by half following the implementation of an additional sampling after 24 h of islet culture. Pancreas preservation fluid microbial contamination is associated with lower transplant rate and poorer in vitro function, but not with changes in graft survival. Culture medium testing 1 day after isolation reduces the risk of incidental transplantation with contaminated islets.
“…In this study, patients with islets suspected to be positive for cultures ( p = 0.01), and with positive gram stains ( p = 0.02), were associated with worse procedure results [ 71 ]. Jolissaint et al [ 72 ] reported worse results among patients with bacterial contaminants in the final islet preparations. In these patients, a significantly lower islet yield and C-peptide level and no insulin independence following surgery were noted.…”
Section: Pancreatic Islet Isolation and Transplantation—technical Aspectsmentioning
Total pancreatectomy is a major complex surgical procedure involving removal of the whole pancreatic parenchyma and duodenum. It leads to lifelong pancreatic exocrine and endocrine insufficiency. The control of surgery-induced diabetes (type 3) requires insulin therapy. Total pancreatectomy with autologous islet transplantation (TPAIT) is performed in order to prevent postoperative diabetes and its serious complications. It is very important whether it is safe and beneficial for patients in terms of postoperative morbidity and mortality, and long-term results including quality of life. Small duct painful chronic pancreatitis (CP) is a primary indication for TPAIT, but currently the indications for this procedure have been extended. They also include hereditary/genetic pancreatitis (HGP), as well as less frequent indications such as benign/borderline pancreatic tumors (intraductal papillary neoplasms, neuroendocrine neoplasms) and “high-risk pancreatic stump”. The use of TPAIT in malignant pancreatic and peripancreatic neoplasms has been reported in the worldwide literature but currently is not a standard but rather a controversial management in these patients. In this review, history, technique, indications, and contraindications, as well as short-term and long-term results of TPAIT, including pediatric patients, are described.
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