Outcomes of total pancreatectomy with islet autotransplantation:A systematic review and meta-analysis

BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,EMBASE,and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes.Data were extracted and analyzed using comprehensive meta-analysis software.The random-effects model was used for all variables.Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic.Publication bias was assessed using Egger’s test.RESULTS Twenty-one studies published between 1980 and 2017 examining 1011 patients were included.Eighteen studies were of adults,while three studied pediatric populations.Narcotic independence was achieved in 53.5%[95% Confidence Interval(CI):45-62,P<0.05,I2=81%]of adults compared to 51.9%(95%CI:17-85,P<0.05,I2=84%)of children.Insulinindependence post-procedure was achieved in 31.8%(95%CI:26-38,P<0.05,I2=64%)of adults with considerable heterogeneity compared to 47.7%(95%CI:20-77,P<0.05,I2=82%)in children.Glycated hemoglobin(HbA1C)12 mo post-surgery was reported in four studies with a pooled value of 6.76%(P=0.27).Neither stratification by age of the studied population nor metaregression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies.CONCLUSION These results indicate acceptable success for TPIAT.Future studies should evaluate the discussed measures before and after surgery for comparison.

Gastric Submucosa Is Inferior to the Liver as Transplant Site for Autologous Islet Transplantation in Pancreatectomized Diabetic Beagles

Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa（GS） and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS（GS group, n=8） or intrahepatic via portal vein（PV group, n=5）. Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation（mean survival time, 7.16±0.69 days）. However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group（mean survival time, 120±28.58 days; P〈0.01 vs. GS group）. The results of intravenous glucose tolerance test（IVGTT） confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles.

Assessment of long-term graft function following total pancreatectomy and autologous islet transplantation:the Leicester experience

Background:Total pancreatectomy and islet autotransplantation(TPIAT)is a recognised treatment for chronic pancreatitis(CP)with the potential to mitigate or prevent pancreatogenic diabetes.We present our 10-year follow-up of TPIAT patients.Methods:The University Hospitals of Leicester performed 60 TPIAT procedures from September 1994 to May 2011.Seventeen patients completed their 10-year assessment and were grouped using the modified Auto-Igls criteria;good response,n=5(insulin-independent for first 5 years post-TPIAT);partial response,n=6(insulin requirements<20 iU/day post-TPIAT)and poor response,n=6(insulin requirements≥20 iU/day post-TPIAT).C-peptide,haemoglobin A1c(HbA1c)and oral glucose tolerance test(OGTT)were undertaken preoperatively(baseline),then at 3,6 months and then yearly for 10 years.Data was analysed using analysis of variance(ANOVA).Results:Median C-peptide levels were significantly higher,120 minutes following OGTT,in the“good response”compared to“partial”and“poor”groups(two-way ANOVA test,P<0.0001).All groups demonstrated preservation of C-peptide release.HbA1c levels were significantly lower in the“good response”compared to“partial”and“poor”groups(two-way ANOVA test,P<0.0003 and P<0.0001).Median fasting glucose levels at 30 and 120 min following OGTT,were significantly lower in the“good response”compared to“partial”and“poor”groups(two-way ANOVA test,P<0.0001 and P<0.0001).Conclusions:TPIAT preserves long-term islet graft functions in 10-year follow up.Even in patients in the poor response group,there is evidence of C-peptide release(>0.5 ng/mL)after OGTT stimulation potentially preventing long-term diabetes-related complications.