Chronic pancreatitis: Medical vs Surgical treatment 소화기내과 R4 김경엽 / Prof. 동석호

Chronic pancreatitis Progressive inflammatory changes in the pancreas –Permanent structural damage → impairment of exocrine and endocrine function

Acute pancreatitis Acute inflammatory response to pancreatic injury Usually nonprogressive

Chronic vs Acute pancreatits Mononuclear infiltrate and fibrosis May be asymptomatic over long periods of time Serum amylase and lipase concentrations tend to be normal Neutrophilic inflammatory response Almost always painful Almost always elevated serum amylase and lipase concentrations

Chronic vs Acute pancreatits

Chronic pancreatitis

ETIOLOGY Alcohol abuse Genetic causes (mutations in the cystic fibrosis gene, hereditary pancreatitis) Ductal obstuction (e.g., trauma, pseudocysts, stones, tumors, possibly pancreas divisum) Tropical pancreatitis Systemic disease such as hypertriglyceridemia, SLE, possibly hyperparathyroidism) Autoimmune and idiopathic pancreatitis

PATHOGENESIS No complete understanding Two consistent findings –Hypersecretion of protein which is not compensated for by an increase in ductal bicarbonate secretion (impairment in ductal bicarbonate secretion: basis for the secretin pancreatic function test) –Patchy inflammatory changes within the exocrine pancreas

Proteinaceous ductal plugs Increased secretion of pancreatic proteins → proteinaceous plugs within the interlobular and intralobular ducts → nidus for calcification → stone formation within the duct system → formation of ductal epithelial lesions which scar and obstruct the ducts → inflammatory changes and cell loss Formation of plugs within some but not all of the ducts explains the patchy nature of this disease

Ischemia (1) Experimental canine model –Ligation and separation of branches flowing into the left pancreatic lobe from the splenic artery → chronic ischemia of pancreas → chronic pancreatitis –3 and 6 months after → pancreas was hard, with severe inflammatory change

Ischemia (2) Ischemia is important in exacerbating or perpetuating rather than initiating disease Canine and feline models of partial pancreatic duct ligation (may be analogous to plug and stone formation in human chronic pancreatitis) → ductal hypertension –Vascular perfusion decreased further following secretory stimuli –This model explains why ductal decompression improves chronic pancreatitis

Antioxidants Nutritionally depleted in patients with chronic pancreatitis –Antioxidants such as selenium, vitamins C and E, and methionine Imbalance between a decrease in antioxidants and an increased demand for them in “stressed cells” → elevations in free radical formation → lipid peroxidation and cellular impairment Controlled trials are needed

CLINICAL FEATURES Two primary clinical manifestations of chronic pancreatitis –Abdominal pain –Pancreatic insufficiency

Clinical course of chronic pancreatitis

J Gastroenterol 2003;38:

Abdominal pain Cardinal feature of chronic pancreatitis Typically epigastric, often radiates to the back Pain pattern in chronic pancreatitis varies among patients

Pancreatic insufficiency Fat malabsorption –Loose, greasy, foul smelling stools –Malabsorption of the fat soluble vitamins (A, D, E, K) and vitamin B12 (clinically symptomatic vitamin deficiency is rare) Pancreatic diabetes

Complications Pseudocyst formation Bile duct or duodenal obstruction Pancreatic ascites or pleural effusion Splenic vein thrombosis Pseudoaneurysms Pancreatic cancer

TREATMENTS Pain management Pancreatic exocrine insufficiency

PAIN MANAGEMENT

AGA guideline for treatment of pain in chronic pancreatitis

Establish a secure diagnosis Rule out other potential etiologies, including peptic ulcer disease, biliary obstruction, pseudocysts, pancreatic carcinoma,and pancreatic duct stricture or stones

Cessation of alcohol intake Abstinence does not always lead to symptomatic improvement Patients with alcohol-induced chronic pancreatitis who continue to drink have increased mortality

Small meals Small meals that are low in fat may help to varying degrees

Pancreatic enzyme supplements Relieve pain in some patinets Not very effective Rationale –Suppression of feedback loops in the duodenum that regulate the release of cholecystokinin (CCK), the hormone that stimulates digestive enzyme secretion from the exocrine pancreas

Analgesics Analgesia can be considered if pancreatic enzyme therapy fails to control pain Chronic opioid analgesia may be required in patients with persistent significant pain

Celiac nerve block Percutaneous or endoscopic celiac nerve blocks with either alcohol or steroids –Limited success –Unproven therapy –Even among responders, symptoms frequently recur within two to six months

Extracorporeal shock wave lithotripsy 22 to 60% of patients with chronic pancreatitis have pancreatic duct stones Stones → obstruction of the outflow of pancreatic secretions → increased intraductal pressure ESWL creates millimetric fragmentation of pancreatic stones, which has improved the results of endoscopic therapy

Endoscopic therapy (1) Decompressing an obstructed pancreatic duct can be associated with pain relief in some patients Rationale –The hypothesis that ductal hypertenstion due to sphincter of Oddi dysfunction or strictures of the main pancreatic duct lead to pain Objection –Spontaneous pain relief in some chronic pancreatitis

Endoscopic therapy (2) Long-term follow-up (average 5 years), 1018 patients, 8 centers –Obstruction of the pancreatic duct Strictures (47%), stones (18%), strictures plus stones (32%) –60% had completed endoscopic therapy –16% were still undergoing some form of endoscopic follow-up –24% had undergone surgery –Pain relief: 65% of patients on intention-to-treat analysis –No improvement of pancreatic function

Endoscopic therapy (3) Best Pract Res Clin Gastroenterol 2004

Endoscopic therapy (4) Pancreatic duct stenting

Endoscopic therapy (5) Issues –Retrospective studies –Good early response –No effectiveness in long-term periods –Relatively safe, but risk of complications –Need experienced and skillful endoscopic techniques –Expensive instruments (e.g., ESWL)

Surgery

PAIN MANAGEMENT Medical vs Surgical treatment

Risk factors of treatment failure of biliary stent in chronic pancreatitis Biliary stent insertion (61 patients) (prospective) –Replacement of stent every 3 months –Removal of stent after 1 year –40 months long-term treatment success rate 26% Calcification of panreatic head portion treatment success rate (+) 7.7% (-) 59.1% Calcification of pancreatic head portion –Predictive factor for treatment success rate Am J Gastroenterol 2003

Long-term effect of biliary stent in chronic pancreatitis Biliary stent insertion (58 patients) (retrospective) –Replacement of stent every 3 months –Removal of stent after 1 year –45 months long-term treatment success rate 38% –Combined with acute pancreatitis: treatment success rate 92% (biliary compression by inflammation) –Stenosis due to fibrosis Low success rate (24%) Eur J Gastroenterol Hepatol 2005

Surgical drainage operations Gastroenterology 1998;115:

A prospective, randomized trial: endoscopic and surgical therapy 140 patients (randomized 72 patients), 5 years long-term follow-up OperationEndoscopic therapy Loss of pain37(34)%14(15)% Relief of pain49(52)%51(46)% Long-term effect of treatment –Surgery > endoscopic therapy 1 st line therapy: non-invasive endoscopic therapy Endoscopy 2003

요 약요 약 만성췌장염의 치료는 현재까지 전향적 대조 연구가 부족하므 로 치료방침이 담당의사의 경험에 따르게 된다. 췌관석, 췌관협착, 담관협착, 가성낭 등의 치료방법으로 내시경 적 치료와 수술적 치료 중 어느 것을 선택할 것인지는 환자의 상태뿐 아니라 의사의 경험도 많이 작용하게 된다. 내과적 치료에 반응하지 않는 통증의 경우 수술을 계획하기 전 에 celiac plexus block 이나 epidural block 을 먼저 고려해야 한 다.