Chronic Pancreatitis: Surgical Options. W. Charles Conway MD, FACS Upper GI/HPB Surgical Oncology Ochsner Medical Center New Orleans, LA

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1 Chronic Pancreatitis: Surgical Options W. Charles Conway MD, FACS Upper GI/HPB Surgical Oncology Ochsner Medical Center New Orleans, LA

2 Chronic Pancreatitis Recurrent, debilitating abdominal pain with significant affects on QoL Pancreatic insufficiency Multidisciplinary management Surgical Options Drainage Resection Combined TP + AIT

3 CP Pain Ductal hypertension Other factors Local, Central Pain management specialist part of multidisciplinary team Antioxidants, Pregabalin Narcotic management

4 RCT Pain control better with surgery Fewer procedures in surgery arm Equivalent QoL and pancreatic function 47% endoscopic arm eventually had surgery Lower overall cost in surgery arm

5 Yang et al. J GI Surg 2014 Meta-analysis of early surgery indicates benefit Multidisciplinary input essential

6 Resectional Procedures Whipple Treat inflammatory head mass Does not decompress body/tail 76% pain control at 1 year 32% new DM 0% mortality

7 Drainage Procedures Ductal hypertension Ductal calculi

8 Drainage Procedures Lateral Pancreaticojejunostomy Drainage of the entire ductal system? Treatment of inflammatory head mass? Patients without dilated ductal system 30%+ with recurrent pain at 5 years

9 Combined Procedures Removal of inflammatory head mass with drainage of entire ductal system RCT s indicate superiority over Whipple Lower complications, improved QoL Izbicki et al. Ann Surg 1998 Improved pain control, less endo/exocrine dysfunction Buchler et al. Am J Surg 1995 Lower long term mortality Bachmann et al. Ann Surg 2013

10 Beger (DPPHR) Frey

11 Frey Duodenum PD

12 Anderson, Frey. Ann Surg 2010

13 Many patients have recurrent pain after resectional/drainage procedures for chronic pancreatitis

14 Total Pancreatectomy + Autoislet Transplant (TP+AIT) Remove entire local source of pain Minimize post-resection diabetes

15 Pancreas completely removed (TP) Islet cells (insulin producing) separated from specimen Islet cells given back to the patient via portal vein infusion TP+AIT First case 1977 U Minn Now >500 cases Several centers in USA/Europe

Patient Selection Confirm diagnosis Imaging, clinical history, genetic mutations Indications for TP+AIT Intractable pain Impaired QoL SF-36

16 Patient Selection Confirm diagnosis Imaging, clinical history, genetic mutations Indications for TP+AIT Intractable pain Impaired QoL SF-36 medical survey Failed medical/surgical therapy Special consideration for genetic abnormalities with predicted disease progression (PRSS1, etc.)

17 Patient Selection Contraindications Psychosocial Alcohol 6 months abstinence Illicit drug use Untreated psychiatric illness Poor social support Medical C peptide negative diabetes Fasting blood glucose and HbA1c PVT/PHTN Liver disease Cardiopulmonary disease/poor performance status Pancreatic neoplasia

18 Patient Selection Multidisciplinary selection committee GI Surgery Psychology Endocrine Pain Management Formal meeting to discuss each candidate with input from each discipline and review of clinical studies

19 Total Pancreatectomy Surgical Risks TP likely drives morbidity Bleeding, infection, anastomotic leak, cardiopulmonary complications of anesthesia, post-splenectomy risks

Islet Isolation TP immediately into cold preservation solution and transferred to lab hood/ricordi chamber Pancreas debrided, weighed/assessed, cut at neck, and duct cannulated Enzymes introduced

20 Islet Isolation TP immediately into cold preservation solution and transferred to lab hood/ricordi chamber Pancreas debrided, weighed/assessed, cut at neck, and duct cannulated Enzymes introduced intraductally Ricordi chamber for digestion Samples obtained and monitored q 2-4min When islets free of exocrine tissue, circuit opened and tissue collected Several washes with cold RPMI Islets suspended in albumin and heparin solution and transferred back to OR Practice harvest x 2 (partial pancreas) Very good islet yield (146k, 204k)

Islet Infusion Islets received in IV bags 70 U/kg heparin PV or tributary canulated Islet mixture delivered via gravity Portal pressure (PP) monitored Infusion held for 30 min

21 Islet Infusion Islets received in IV bags 70 U/kg heparin PV or tributary canulated Islet mixture delivered via gravity Portal pressure (PP) monitored Infusion held for 30 min if PP>35cmH2O or change PP>25cmH2O If pressure won t normalize, remaining tissue dispersed in peritoneal cavity Small amount always put in peritoneal cavity (alpha cell function)

22 Post-operative Care ICU for 3 days Continue anticoagulation 3 U/kg/hour for next 4 hours after infusion 48 hour heparin infusion to maintain PTT 50-60s Thereafter, prophylactic Lovenox dosing Routine U/S monitoring of portal flow Strict euglycemia with endocrine support (CBG<120) Early ambulation and other pieces of ERAS protocol for total pancreatectomy Post-discharge planning/follow-up

23 TP+AIT Outcomes: Islet Function Sutherland et al. JACS 2012

24 TP+AIT Outcomes: Islet Function Sutheralnd et al. JACS 2012

25 TP+AIT: Previous surgery and Islet Yield Wang et al. Transplantation 2013

26 TP+AIT Outcomes Sutheralnd et al. JACS 2012

27 TP+AIT Outcomes: QoL Sutheralnd et al. JACS 2012

28 TP+AIT Outcomes: QoL Sutheralnd et al. JACS 2012

29 TP+AIT Outcomes: QoL Sutheralnd et al. JACS 2012

30 Summary Surgical and endoscopic procedures can be effective in treating chronic pancreatitis Multidisciplinary input with individualized therapy plan I look forward to reporting our early TP+AIT results next year

31 Thank You (cell)

Total Pancreatectomy and Islet Auto Transplantation (TPIAT)

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