Chronic Pancreatitis

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Gastro Foundation Fellows Weekend 2017 Chronic Pancreatitis Jose Ramos University of the Witwatersrand Donald Gordon Medical Centre

Aetiology in SA Alcohol (up to 80%) Idiopathic Tropical Obstruction Autoimmune Miscellaneous

Diagnosis of CP Clinical symptoms Pain Endocrine insufficiency Exocrine insufficiency Complications Imaging Pancreatic calcification Ductal dilatation/strictures

Classification of CP

Problems in CP Pain Endocrine insufficiency Exocrine insufficiency Biliary obstruction Pseudocysts / fluid collections Duodenal obstruction Vascular complications Venous thrombosis False aneurysms Pancreatic cancer

Management options Problem Surgery Medical Interventional Pain Yes Yes Yes Endocrine insufficiency No Yes No Exocrine insufficiency Yes/No? Yes No Biliary obstruction Yes No Yes Pseudocysts / fluid collections Yes No Yes Duodenal obstruction Yes No Yes Vascular complications No Yes Yes Pancreatic cancer / Suspicion Yes Yes No

Endocrine insufficiency HbA1c most reliable test Oral agents of limited benefit Cause is impaired insulin secretion Best managed with insulin replacement

Exocrine insufficiency

Diagnosis of PEI: Pancreatic Function Tests Co-efficient of fat absorption (CFA) 1 Carbon 13 ( 13 C)- mixed triglyceride ( 13 C-MTG) breath test 1 Faecal elastase tests (FE-1) 2 1. Dominguez-Munoz JE et al. J Gastroenterol Hepatol. 2011;26(2):12-16. 2. Sikkens ECM, et al. Best Pract Res Clin Gastroenterol. 2010:(24);337-347.

Faecal Elastase Test Faecal elastase tests are becoming more prevalent in clinical practice 1 In 2010, it was reported to be the most popular test used to evaluate PEI 2 Requires a single stool sample 2 Measures the amount of elastase enzyme left in the stool 1,2 Specificity: Approximately 93% Compromised in patients with small bowel disease and type 1 diabetes Risk of false positive result in diarrhoea and other intestinal disorders 2 >200 µg/g stool: normal value 2 <200 µg/g stool: mild PEI 1 <100 µg/g stool: severe PEI 1 1, Australasian treatment guidelines for the management of pancreatic exocrine insufficiency. 2010:1-89. 2. Sikkens ECM et al. Best Pract Res Clin Gastroenterol. 2010:(24);337-347.

Diagnosis of PEI: Practical Approaches ( or Non-Pancreatic Function Tests ) In certain conditions, where these tests are not widely available in clinical practice, some practical approaches may aid diagnosis Assessment of symptoms 1 Pancreatic morphology in patients with CP 2 Nutritional parameters in patients with CP 3 High probability of PEI in specific patients groups 1 Trials of PERT 4,5 1. Dominguez-Munoz JE et al. J Gastroenterol Hepatol. 2011;26(2):12-16. 2. Dominguez-Munoz JE et al. Pancreas 2012;41(5):724-8. 3. Lindkvist B et al. Pancreatology 2012;12:305-310. 4. Sikkens ECM et al. Best Pract Res Clin Gastroenterol. 2010;(24):337-347. 5. Toouli J et al. MJA. 2010;93(8):461-467.

Diagnosis of PEI: Assessment of Symptoms Common symptoms Abdominal pain 1 Flatulence in adults 1 Weight loss 1 Lack of weight gain in children 1 Steatorrhoea 1 Lack of energy 2 Diagnosis of PEI is commonly based on an assessment of the individual s clinical state and a self-report of bowel movements and weight loss in adults or failure to thrive in children 1 1. Australasian treatment guidelines for the management of pancreatic exocrine insufficiency. 2010:1-89 2. Ockenga J. HPB. 2009. 11(suppl.3):11-15.

Proportion of Patients Assessment of Symptoms: PEI May be Missed in Asymptomatic Patients Diagnosis of PEI are often missed in the absence of clinical steatorrhoea 1 Many patients with malabsorption are asymptomatic 2 Presence of Steatorrhoea and Malabsorption in CP Patients Every patient with PEI and maldigestion, independent of the degree of steatorrhoea and presence or absence of associated symptoms, should receive PERT 3 1. Imrie CW et al. Aliment Pharmacol Ther.2010;32(Suppl. 1):1 25. 2. Dumasy V et al. Am J Gastroenterol. 2004; 99(7): 1350-1354. 3. Sikkens ECM et al. Best Pract Res Clin Gastroenterol. 2010:(24);337-347.

High Probability of PEI in Specific Patient Groups Patient groups who have a high likelihood of PEI (>80%) 1 Chronic pancreatitis with dilated pancreatic duct and/or calcifications 2 Severe necrotising pancreatitis 1 GI or pancreatic surgery 1 Unresectable cancer of the pancreatic head 1 In patients where the likelihood of PEI is higher than 80%, PERT could be started even in the absence of confirmatory diagnostic test. 1. Domínguez-Muñoz JE. J Gastroenterol Hepatol. 2011; 26(2):12-16. 2. Dominguez-Munoz JE et al. Pancreas 2012;41(5):724-728. GI, gastrointestinal

Treatment of exocrine insufficiency

CP indications for intervention Chronic pain not responding to non-opiate analgesia Biliary obstruction Duodenal obstruction Confirmed or suspected cancer Surgery vs interventional endoscopy/radiology?

CONCLUSIONS: In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery.

Surgical Procedures Drainage Ductal drainage (Puestow) Cyst-drainage Duodenal preserving resection + drainage (DPPHR) Frey Beger Various options (Izbicki, Berne) Head resection Whipple PPPD Distal pancreatectomy Total pancreatectomy

Puestow

Frey operation

Beger operation

Izbicki operation

Berne operation

Distal pancreatectomy

Pancreaticoduodenenctomy Classical Whipple Pylorus-preserving PD

Which operation should we perform for chronic pain?

What factors cause pain? Ductal and parenchymal hypertension Ductal dilatation Inflammatory mass Parenchymal ischaemia Neurogenic inflammation Peripheral and central nerve sensitization Parenchymal and ductal calcification Biliary and duodenal obstruction

The ideal operation? Resolve pain Decompress parenchyma and ductal system Reduce volume of or remove inflammatory mass Low morbidity and mortality Limited impact on pancreatic function Exocrine insufficiency Endocrine insufficiency Improve QOL in short and long term

Frey Operation Johannesburg Hospital series 1997 Interim analysis of Late outcome Pain relief 35 / 38 (92%) Jaundice 0 / 38 Pancreatitis 2 (?) Pain 4 Diabetes initial 12 (29%) new 1 Steatorrhoea initial 11 (27%) new 2

Conclusion DPPHR and PD result in equal pain relief, mortality, and pancreatic function; however, DPPHR provides superior long-term outcomes.

Comments: Both Beger and Frey procedures compare favorably with the (pylorus-preserving) pancreaticoduodenectomy in terms of morbidity and mortality, length of hospital stay, weight gain, nutrition, and quality of life. Pylorus preserving pancreaticoduodenectomy should be reserved for patients suspected of carcinoma. Given the lower morbidity rate with a comparable effect on pain control and quality of life, a Frey procedure is preferred over a Beger procedure

Conclusions In patients with pancreatic disease, diagnosis determined QoL preoperatively and late after surgery, while in the early postoperative period, type and extent of surgery was the leading factor. Total pancreatectomy had a profound negative effect on QoL and should be reserved for carefully selected patients only.

Timing of Surgery

266 patients Conclusions: The timing of surgery is an important risk factor for clinical outcome in CP. Surgery may need to be considered at an earlier phase than it is now, preferably within 3 years of symptomatic CP

506 patients who were followed-up for at least 2 years after diagnosis of chronic pancreatitis. 19 developed pancreatic cancer (3.7%)

Occurrence of pancreatic cancer: 5.1% in pts not undergoing surgery 0.7% in pts undergoing surgery Higher in pts who continued to drink

Conclusions Important to diagnose the presence of CP and to detect and treat endocrine and exocrine dysfunction Surgery plays a major role in the management of symptomatic CP Combination or head resection with ductal drainage (Frey) best option Early surgery with avoidance of opiate use and multiple endoscopic intervention beneficial Surgery may help to maintain pancreatic function and possibly reduce cancer risk