Updates on the Management of Acute and Chronic Pancreatitis

Educational Objectives

The goal of this program is to improve management of patients with acute pancreatitis (AP) and chronic pancreatitis (CP). After hearing and assimilating this program, the clinician will be better able to:

1. Recognize AP based on disease severity.
2. Conduct workup to elicit the cause of AP.
3. Analyze the potential complications for AP and CP.
4. Manage pain for patients with CP.

Summary

Acute Pancreatitis

Incidence of acute pancreatitis (AP): rate has been steadily increasing over the last 4 to 5 decades; in the United States, early incidence occurs in 40,000 to 80,000 cases per 100,000 cases annually, which translates to >250,000 hospitalizations each year; Iannuzzi et al (2022) report a general increase in the incidence of AP; causes for this include increased incidence of obesity and alcohol consumption

Diagnosis: requires 2 of 3 features, which include characteristic upper abdominal pain (typically of sudden onset), elevated serum pancreatic enzymes (≥3 times the upper limit of normal), and imaging evidence of AP or its complications

Severity: the revised Atlanta Classification is based on new knowledge about the role of organ failure and necrosis on the clinical course and stratifies disease severity; mild AP — involves no organ failure or local or systemic complications (eg, necrosis); moderately severe AP — involves transient organ failure (≤48 hr) and/or local or systemic complications; severe AP — involves persistent organ failure (>48 hr); a majority of patients with organ failure have underlying pancreatic necrosis, and 50% to 60% of patients with pancreatic necrosis have organ failure; organ failure with necrosis (typically involves infection) usually portends a high risk for mortality

Types of mild AP: interstitial AP — seen in 80% to 85% of patients; the pancreas may appear normal on contrast-enhanced computed tomography (CECT), or enlarged with surrounding inflammatory changes; patients typically have a short clinical course, start to feel better by day 2 or 3, and are released from the hospital by day 4 or 5; acute necrotizing pancreatitis (ANP) — occurs in 15% to 20% of patients; progresses to acute necrotic collection (evolves over 2-4 wk), then walled-off necrosis (typically >4 wk of illness); treatment (eg, percutaneous drainage, endoscopic drainage, surgery) is deferred to >4 wk unless clinical deterioration is present

Etiology: gallstones are the most common cause, followed by heavy alcohol consumption (usually associated with smoking); other important causes are hypertriglyceridemia, medications, and uncommon causes (eg, postendoscopic retrograde cholangiopancreatography, trauma, hypercalcemia, major upper abdominal surgery); in patients >50 yr of age without traditional risk factors (RFs), pancreatic cancer (PC) may present as AP; some autoimmune diseases (eg, celiac disease) increase risk; patients who experience recurrent attacks require additional workup to rule out, eg, pancreatic ductal abnormalities, genetic factors

Workup for an initial attack: in addition to a good history, the American Pancreatic Association recommends liver function testing (LFTs; elevation ≥3 times beyond the upper limit of normal suggests biliary etiology) and abdominal ultrasonography (US) to assess the gallbladder and common bile duct (CBD); measure serum triglycerides as early as possible, as delay may lead to false normalization and a missed diagnosis; calcium is typically included in metabolic panels; CT is not usually helpful in identifying the etiology, despite it being performed in 70% to 80% of patients with AP; perform celiac panels in patients without an identifiable etiology; order serum immunoglobulin 4 testing for select patients with suggestive morphology; measure phosphatidylethanol levels in the small subset of patients with clinical suspicion (provides an idea of alcohol consumption 2-3 wk prior to the test); endoscopic US can help in uncovering a small PC in patients with idiopathic AP; in recurrent pancreatitis, magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) with secretin can help assess for ductal abnormalities; endoscopic US can help identify sludge in the gallbladder or subtle changes of chronic pancreatitis (CP); commercial genetic testing is now available

Hyperlipidemic AP: under-recognized and underdiagnosed; most frequently seen in patients with poorly-controlled diabetes mellites (DM) who do not have traditional RFs; secondary risk factors (SRFs) include concurrent alcoholic pancreatitis, use of, eg, β-blockers, thiazides, propofol, some HIV medications (which can increase triglyceride levels), or being in the third trimester of pregnancy; the presence of these SRFs in an individual with a predisposition to hypertriglyceridemia (now considered a polygenic trait) can lead to high triglyceride levels (>1000 mg/dL) and development of pancreatitis; hypertriglyceridemia is also an independent, dose-dependent RF for disease severity; the risk for recurrence (ROR) can be significantly reduced by controlling SRFs or by lowering triglyceride levels; Wu et al (2019) — patients with normal triglyceride levels after discharge following initial AP attack had significantly lower risk for developing AP, compared with those who had moderately or significantly elevated ambulatory triglyceride levels

Endoscopic retrograde cholangiopancreatography: needed prior to cholecystectomy (CCY) to clear sludge and stone from the CBD; indicated for patients with cholangitis or suspicion of cholangitis

Cholecystectomy: perform as soon as possible after an episode of AP; da Costa et al (2015) found that same-admission CCY reduced the primary composite outcome for risk for mortality, gallstone-related complications, and recurrent pancreatitis by 75% vs interval CCY

Risk for recurrence: ROR for pancreatitis secondary to, eg, gallstones, hypertriglyceridemia, medication, can be significantly reduced through addressing the primary etiology; ROR for alcoholic or idiopathic AP is greater, but the former can be significantly reduced by abstaining from alcohol and smoking

Pancreatitis and DM: ANP can affect the pancreatic β-cells; Das et al (2014) found that patients with AP (even mild) have a 2-fold increased risk for DM in the following 3 to 5 yr; Eso et al (2020) reported that the risk for DM is 11% at 2 yr after AP and the risk for prediabetes is ≤45%; Petrov et al (2019) found that 1.5% to 2% of all patients with DM following AP have type 1 DM, and ≈2% of patients have disease related to the exocrine pancreas (of which 60%-70% of cases are related to AP or CP, and the remainder are related to, eg, PC, cystic fibrosis); 60% to 70% of cases of DM in patients with pancreatitis occur because of AP; the incidence of AP is 8- to 10-fold greater than CP

Clinical implications of DM after pancreatitis: Woodmansey et al (2017) found that patients who develop new-onset DM following pancreatic disease have a 3-fold increase in the need for insulin during follow-up and poorer glycemic control, compared with patients who have type 2 DM prior to having pancreatitis; type 1 diabetes in acute pancreatitis consortium — initiated the DREAM study to determine the cumulative incidence and clinical characteristics associated with DM development after AP, to comprehensively characterize β-cell function and endocrine alterations after AP and the relationship with DM onset after AP, and to assess for immunologic mechanisms of DM after AP, including β-cell autoimmunity

Chronic Pancreatitis

Background: has a profound impact on quality of life (QOL); the NAPS2 study (Wilcox et al, 2015) — pain is the most important factor decreasing QOL; 90% of patients have pain at some point over the course of CP; ≈66% patients reported severe pain and ≈55% reported constant pain over the past year; ≈50% patients are taking narcotic medication at any given time; Kempeneers et al (2021) — patients reported frequent changes in type and pattern of pain over a median follow-up period of ≈4 yr, regardless of treatment

Pain management: perform cross-sectional imaging and additional evaluation to assess for other factors that might explain the pain, including, eg, pseudocyst, PC, peptic ulcer; in the absence of another cause, an initial trial of conservative management is indicated, including behavioral modification (eg, reducing alcohol intake or smoking) or other adjunctive treatments (eg, pancreatic enzyme treatment) to improve assessment of disease burden; obstructive disease — results from blockage of the pancreatic duct by stones or strictures; endoscopic therapy is usually the first treatment offered; consider surgery in a subset of patients; no duct dilatation — can be medically managed, though a small subset of patients are offered total pancreatectomy with islet autotransplantation; durable pain relief with treatment — Issa et al (2020) found that surgery is better than endoscopic decompression for pain management, but careful evaluation of data showed that patients who had endoscopic decompression and full surgical clearance of the pancreatic duct had similar responses; durable pain relief was achieved in <50% of patients

Pancreatic quantitative sensory testing (P-QST): a series of evaluations that takes 15 to 20 min and can be done in an outpatient setting; consists of temporal summation, pressure detection or tolerance in different areas of the body, and conditioned pain modulation; patients are stratified based on display of normal pain processing, segmental sensitization (T10 dermatome), and central sensitization (who may not respond to therapy)

Pain processing: Phillips et al (2020) — ≈50% of patients have normal pain processing; a large majority of patients with painless CP have normal pain processing; patients with painful CP at the time of evaluation have a higher prevalence of segmental or widespread sensitization, suggesting a modification of pain perception; the PROCEED study (Yadav et al, 2018) — ≈25% of patients report mild to moderate pain and ≈60% report severe pain; patients with severe pain have a higher prevalence of constant pain (66%); most patients with mild to moderate pain have intermittent pain; QOL in patients with CP and no pain was very similar to patients who had mild to moderate or intermittent pain; severe or constant pain significantly decreases QOL; the prevalence of psychological or behavioral comorbidities (ie, moderate to severe anxiety, depression, sleep disturbance, low physical function) was much higher in patients with CP vs control patients; patients with CP and severe or constant pain had a prevalence 3- to 5-fold greater than patients with no pain

IMPACT study (Palermo et al, 2021): found significantly higher composite outcome scores reflecting improvement of pain interference or intensity at 3 mo from baseline in patients participating in Internet-based cognitive behavioral therapy, and a transient improvement in QOL was noted, vs patients who remained on a waitlist; this suggests that evaluation and management of psychological and behavioral comorbidities can improve pain management

Osteopathy in CP (Hart et al, 2022): a very high proportion of patients with CP in the PROCEED study had osteoporosis or osteopenia, including 40% of men; the prevalence of traumatic or spontaneous fractures in patients with osteopathy and definite CP was significantly greater than in patients without osteopathy; 30% to 35% of patients with CP had osteopathy that could be missed without dual-energy X-ray absorptiometry, secondary to age <50 yr; traditional RFs for osteopathy were prevalent, though CP-related factors were not associated, potentially indicative of a systemic effect of chronic inflammation

Pancreatic enzyme replacement therapy (PERT): Forsmark et al (2020) reported that <10% of patients with CP are tested for exocrine pancreatic insufficiency (EPI) through, eg, fecal elastase, fecal chymotrypsin, quantitative fecal fat; <33% of patients receive a prescription for pancreatic enzymes and <10% of patients who receive a prescription are appropriately dosed; assessment and treatment of EPI can improve nutritional status for patients with CP; the standard recommendation for PERT is 50,000 to 70,000 lipase units/meal (half-dose with snacks)

Readings

Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102-11. doi: 10.1136/gutjnl-2012-302779; da Costa DW, Bouwense SA, Schepers NJ, et al. Same-admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO): a multicentre randomised controlled trial. Lancet. 2015;386(10000):1261-1268. doi: 10.1016/S0140-6736(15)00274-3; Das SL, Singh PP, Phillips AR, et al. Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis. Gut. 2014;63(5):818-31. doi: 10.1136/gutjnl-2013-305062; Eso Y, Shimizu T, Takeda H, et al. Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers. J Gastroenterol. 2020;55(1):15-26. doi: 10.1007/s00535-019-01620-7; Forsmark CE, Tang G, Xu H, et al. The use of pancreatic enzyme replacement therapy in patients with a diagnosis of chronic pancreatitis and pancreatic cancer in the US is infrequent and inconsistent. Aliment Pharmacol Ther. 2020;51(10):958-967. doi: 10.1111/apt.15698; Hart PA, Yadav D, Li L, et al. High prevalence of osteopathy in chronic pancreatitis: a cross-sectional analysis from the PROCEED study. Clin Gastroenterol Hepatol. 2022;20(9):2005-2013. doi: 10.1016/j.cgh.2021.09.026; Issa Y, Kempeneers MA, Bruno MJ, et al. Effect of early surgery vs endoscopy-first approach on pain in patients with chronic pancreatitis: the ESCAPE randomized clinical trial. JAMA. 2020;323(3):237-247. doi: 10.1001/jama.2019.20967; Palermo TM, Law EF, Topazian MD, et al. Internet cognitive-behavioral therapy for painful chronic pancreatitis: a pilot feasibility randomized controlled trial. Clin Transl Gastroenterol. 2021;12(6):e00373. doi: 10.14309/ctg.0000000000000373; Petrov MS, Yadav D. Global epidemiology and holistic prevention of pancreatitis. Nat Rev Gastroenterol Hepatol. 2019;16(3):175-184. doi: 10.1038/s41575-018-0087-5; Vipperla K, Papachristou GI, Easler J, et al. Risk of and factors associated with readmission after a sentinel attack of acute pancreatitis. Clin Gastroenterol Hepatol. 2014;12(11):1911-9. doi: 10.1016/j.cgh.2014.04.035; Werner J, Hartwig W, Hackert T, et al. Surgery in the treatment of acute pancreatitis--open pancreatic necrosectomy. Scand J Surg. 2005;94(2):130-4. doi: 10.1177/145749690509400209; Wilcox CM, Yadav D, Ye T, et al. Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings. Clin Gastroenterol Hepatol. 2015;13(3):552-e29. doi: 10.1016/j.cgh.2014.10.015; Woodmansey C, McGovern AP, McCullough KA, et al. Incidence, demographics, and clinical characteristics of diabetes of the exocrine pancreas (type 3c): a retrospective cohort study. Diabetes Care. 2017;40(11):1486-1493. doi: 10.2337/dc17-0542; Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13(4 Suppl 2):e1-15. doi: 10.1016/j.pan.2013.07.063; Wu BU, Batech M, Dong EY, et al. Influence of ambulatory triglyceride levels on risk of recurrence in patients with hypertriglyceridemic pancreatitis. Dig Dis Sci. 2019;64(3):890-897. doi: 10.1007/s10620-018-5226-x; Yadav D, Park WG, Fogel EL, et al. Prospective evaluation of chronic pancreatitis for epidemiologic and translational studies: rationale and study design for PROCEED from the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas. 2018;47(10):1229-1238. doi: 10.1097/MPA.0000000000001170; Yadav D, Slivka A. Managing chronic pancreatitis: the view from medical pancreatology. Am J Gastroenterol. 2018;113(8):1108-1110. doi: 10.1038/s41395-018-0066-z.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Yadav was recorded at the 2022 Update in Internal Medicine (UIM): Advances Changing Practice, held virtually October 6-7, 2022, and presented by the University of Pittsburgh School of Medicine. For information about upcoming CME activities from this presenter, please visit meded.dom.pitt.edu. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

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