Total Pancreatectomy and Islet Auto Transplantation (TPIAT) Dhiraj Yadav, MD MPH Professor of Medicine Division of Gastroenterology & Hepatology University of Pittsburgh Medical Center PSG Meeting Sept 2017 Number of TPIATs performed is increasing U Minnesota: 409 cases JACS 2012;214:409-26 Other US sites: Arizona, Baylor, Chicago, Cincinnati, Cleveland Clinic, Dartmouth, Johns Hopkins, Mayo, MUSC, UPMC, Penn 1
Outline Pain in Chronic Pancreatitis (CP) Indications for TPIAT Preoperative considerations TPIAT Procedure Postoperative considerations Outcomes Take home message(s) Pain in Chronic Pancreatitis (CP) 2
Pain in CP: A cross sectional view (NAPS2 CV study, n= 518) Pain Description % Pattern No pain in the past year from 15 pancreatitis A Usually pain free, but have 13 episodes of mild to moderate pain B Constant mild to moderate pain 5 C Usually free of pain, but have 19 episodes of severe pain D Constant mild to moderate pain, 44 plus episodes of severe pain E Constant severe pain that does not change 3 Pain severity Mild moderate:18% Severe: 67% Temporal nature Intermittent: 32% Constant: 53% Disability: 25% Narcotics Intermittent: 23% Constant: 36% Clin Gastroenterol Hepatol 2015;13:552-60 Natural History of CP 3
Determinants of Natural History of CP Age, etiology, genetics, and risk factors Early-Onset Alcoholic Late-Onset Pain +++ +++ + AP +++ ++ + Progression Slow Variable Variable Gastroenterology 1994;107:1481-7 4
Factors and mechanisms of pain in CP Pancreapedia v1.0; Feb 6, 2015 Indications for TPIAT 5
Indication for TPIAT Intractable pain in patients with impaired QOL due to CP or RAP in whom medical, endoscopic or prior surgical therapy has failed Optimal timing will depend on severity, frequency, and duration of pain symptoms, narcotic requirements, disability/qol, residual islet cell function, rate of disease progression, age Pancreatology 2014:27-35 Contraindications for TPIAT Psychological Active alcoholism Active illicit substance use Untreated/uncontrolled psychiatric illness that can impair patient s ability to adhere to complicated medical management Poor support network (Relative) Medical C peptide negative diabetes Type 1 diabetes Portal vein thrombosis, portal hypertension, significant liver disease High risk cardiopulmonary disease Known pancreatic cancer Pancreatology 2014:27-35 6
Who is getting TPIAT? Minnesota (n=581) Cincinnati (n=84) MUSC (n=127) UPMC (n=39) Age (yrs) Adults 35.2 ± 0.7* 36.5 ± 11.8 40.5 (12 62) 37.3 ± 11.3 Age (yrs) Children 12.8 ± 0.5* 11.6 ± 3.1 Sex F (%) 75 66.7 76 51.3 Children (%) 14 28 Etiology Idiopathic 49 69 22.8 20.5 SOD NA 40.2 0 Genetic 14 16.7 15 51.3 Pancreas 18 9.5 13.4 15.4 divisum Alcohol 6 4.8 5.5 7.7 Other 13 2.4 5.1 Ann Surg 2015;262:610-22 HPB 2015;17:232-8 JACS 2015;220:693-8 JACS 2012:214:409-26 (409 patients) UPMC data: Martin Wijkstrom, MD Pre operative considerations 7
Pre TPIAT evaluation Confirm diagnosis of CP Evaluation by multidisciplinary team GI, Surgery, Endocrinology, Psychiatrist, Pain service, Social work, Nurse coordinator Assess beta cell mass Mixed Meal Tolerance Test Assess patency of portal venous system Evaluate for liver disease Determine immunization status Pancreatology 2014:27-35 Islet yield is affected by prior pancreatic surgery Curr Diab Rep 2012;12:580-6 8
Considerations Follow up after TPIAT Pain management specialist Lifelong Diabetes monitoring: at least annually (self monitored fasting blood sugar, hemoglobin A1c, beta cell mass (cpeptide) Nutrition monitoring: assess for steatorrhea, weight, fat soluble vitamins at least annually Oral pancreatic enzyme replacement therapy Pancreatology 2014:27-35 TPIAT Procedure 9
TPIAT Developed by Dr. Sutherland at the U Minn first report 1977 Slide Courtsey: Martin Wijkstrom, MD TPIAT Approaches: Traditional Laparoscopic Robotic Slide Courtsey:Martin Wijkstrom, MD 10
Islet Processing Purification Hood Slide Courtsey:Martin Wijkstrom, MD Complications Reoperation during same admission 15.9% Bleeding Anastomotic leak Intra abdominal infection Bowel obstruction, omental infarction, ischemia, tube perforation, splenic hemorrhage Other complications Motility issues in the long term JACS 2012;214:409-26 11
Outcomes Narcotic use Data in 207/409 patients Duration of narcotic use prior to TPIAT (mean ) 3.6 years JACS 2012;214:409-26 12
Narcotic use Ann Surgery 2015;262:610-22 Insulin independence JACS 2012;214:409-26 13
Insulin independence Ann Surgery 2015;262:610-22 Insulin independence is a function of islet yield C-peptide response, HbA1c and attrition correlate with islet yield Attrition at 5 years after achieving Insulin Independence Overall 46% <2500: 70%, 2500-5000: 54%, >5000: 29% Curr Diab Rep 2012;12:580-6 14
Predictors of response after TPIAT? Other co-variates: age, sex, preoperative DM Ann Surg 2015;262:610-22 Quality of life after TPIAT SF 36 Ann Surgery 2015;262:610-22 15
Predictors of QOL after TPIAT? Ann Surg 2015;262:610-22 Survival N=409 5 in-hospital deaths 53 total deaths Cause known in 14 (CP in 3) Survival similar adults vs. children JACS 2012;214:409-26 16
Take Home Messages TPIAT is indicated in a select subset of patients with chronic and recurrent acute pancreatitis Patient selection is critical for TPIAT Initial results of TPIAT are promising Prospective registries are needed to understand the long term outcomes in patients undergoing TPIAT NIDDK has funded such a registry Future efforts should continue to target measures to improve islet yield and function, and other specific issues related to TPIAT Questions yadavd@upmc.edu 17