ACG Clinical Guideline—Chronic Pancreatitis

Updated March 2020

Heidi Ahmed, May 12th 2020

Note: Recommendations in italics

New Mechanistic Definition in 2016: confirms end-
stage chronic pancreatitis (CP) as pancreatic atrophy,
fibrosis, pain syndromes, duct distortion and
strictures, calcifications, pancreatic exocrine
dysfunction, pancreatic endocrine dysfunction, and
dysplasia
- Disease mechanism: pathologic
fibroinflammatory syndrome of the pancreas
in individuals with genetic, environmental,
and/or other risk factors who develop
persistent pathologic responses to
parenchymal injury or stress.

DIAGNOSIS:
- First-line testing to evaluate for chronic pancreatitis should be either CT or MRI (strong rec,
low quality evidence)
o EUS should be second-line due to invasiveness and lack of specificity—consider
after cross-sectional imaging (no RCTs comparing EUS to imaging)
- History and physical exam, laboratory values (including direct and indirect pancreatic
function tests) still key
- Secretin-enhanced MRCP (s-MRCP) can be used in patients who have had EUS or cross-
sectional imaging that is non-diagnostic, but clinical suspicion is high (conditional rec, low
quality)
o Improved visualization of main and side-branch ducts due to increased release of
bicarb from pancreatic ductal cells
o Quantification of degree of filling in duodenum—can help quantify degree of
pancreatic exocrine function and severity of chronic pancreatitis
- Pancreatic function testing—not necessary to diagnose CP, but can be helpful to diagnose
exocrine pancreatic insufficiency (EPI)
o Typically require >90% loss of function to manifest in clinically apparent symptoms
(i.e. steatorrhea, azotorrhea, vitamin deficiencies)
o Hormonal tests:
 CCK stimulation test (acinar cells stimulated to produce trypsin or lipase)
 2-3 hour test
 Uncomfortable for patients (catheter placed in duodenum), not
widely available
 Secretin stimulation test (ductal cells stimulated to produce bicarb)
 60-minute test
 Performed endoscopically—increased risk and cost
o Non-hormonal tests:
 Fecal-elastase-1—limited specificity in diarrhea, limited use in mild disease
ACG Clinical Guideline—Chronic Pancreatitis
Updated March 2020
Heidi Ahmed, May 12th 2020

 72-hour fecal fat—recommended over Sudan stain for fecal fat, but
cumbersome
 13C-mixed triglyceride test—90% sensitivity
 4-6 hour test
 Serum trypsinogen/trypsin
 Quantifiable—can track over time
 Does not measure GI tract enzymes
 Increased in pancreatic pain
- Histology: If imaging has been inconclusive and patient is high-risk for CP, histological
examination is gold standard for diagnosis (conditional, very low quality)
o Easier to do now with EUS
o Sensitivity is poor—limited due to sampling error, complications in obtaining
biopsy, patchy nature of pancreatic inflammation
- Genetic testing:
o Recommended in patients with clinical evidence of pancreatitis-associated disorder or
possible CP in which the etiology is unclear, especially in younger patients (strong, low
quality)
o Can help distinguish whether patients are likely to develop progressive, severe
chronic pancreatitis and pathways involved, even if no immediate treatment change
o Autosomal dominant
 PRSS1 mutations (hereditary pancreatitis)
 CTRC (chymotrypsin C)
o Autosomal recessive
 CFTR with 2 severe variants (cystic fibrosis)
 CFTR with <2 severe variants (CFTR-RD)
 SPINK1
o Hypertriglyceridemia
o Idiopathic CP patients should have at least germline mutation evaluation for PRSS1,
CTRC, CFTR, and SPINK1
NATURAL HISTORY:
- Primary clinical outcomes: Abdominal pain, exocrine insufficiency (fat-soluble vitamin
deficiency, malnutrition, osteoporosis), pancreatic malignancy, endocrine insufficiency
(diabetes)
o Typically irreversible, very little is modifiable
- 10% of acute pancreatitis progresses to CP, and 30% of recurrent acute pancreatitis (RAP)
progress to CP
o Progression from EtOH is twice as likely than genetic or idiopathic etiology
- Exocrine insufficiency:
o 40-75% of patients with CP will have exocrine insufficiency
o Risk highest in patients with alcoholic use, tobacco use, or fibrocalcific/tropical
pancreatitis
o Recommend using pancreatic enzyme replacement therapy to improve malnutrition
complications
ACG Clinical Guideline—Chronic Pancreatitis
Updated March 2020
Heidi Ahmed, May 12th 2020

 At least 40,000-50,000 USP units lipase with each meal

o Should have periodic evaluation for osteoporosis and fat-soluble vitamin deficiency
- Higher risk of adenocarcinoma
o Lifetime risk 5-10%, but limited to case series and retrospective cohort studies
o No recommendation for screening given invasive nature of testing, high cost,
difficulty in interpretation due to structural changes from CP, inability to alter
natural progression of the disease
- Endocrine pancreatic insufficiency—type 3c diabetes mellitus
o No etiology is more likely for development
o Duration of disease (CP) is most important risk factor
o Tobacco use can play a role
- Recommend alcohol and smoking cessation in patients with CP
PAIN MANAGEMENT:
- Medium-chain triglycerides
o ?in decrease in CCK levels or antioxidant effects
o Not discussed in ACG guideline
o Small pilot study of 8 patients: received 10 weeks of MCTs with resulting
improvement of pain
- Analgesics:
o Amitriptyline or nortriptyline have been trialed to reduce neuropathic pain
o Not discussed in ACG guideline
- Antioxidant therapy:
o Mechanism of action is not clear, but thought to be beneficial by reducing oxidative
stress and inflammation
o Several studies with varying results (2009 RCT with 5 antioxidants vs placebo for 6
months—patients in treatment arm had less use of analgesics and more patients
who were pain-free; 2012 similar RCT with no difference in pain scores, opiate use,
hospital admissions)
o Consider use of antioxidants, although the benefit of pain reduction is likely limited
o The formulations that showed some benefit included selenium, ascorbic acid, beta-
carotene, and methionine
 No FDA-regulated preparations
- Opiate use:
o Avoid if possible given risks of addiction, abuse, tolerance
o Can be considered as treatment in refractory pain when all other reasonable
therapeutic options have been exhausted
- Pancreatic enzymes:
o Useful in patients with symptomatic exocrine pancreatic insufficiency
o Several older studies and meta-analyses have not found any meaningful difference
o Don’t use pancreatic enzymes to treat pain from CP (particularly related to ductal
obstruction, etc.), but can consider in patients with discomfort from cramping or
diarrhea
- Pain due to pancreatic ductal obstruction:
ACG Clinical Guideline—Chronic Pancreatitis
Updated March 2020
Heidi Ahmed, May 12th 2020

o Due to pancreatic duct stones, strictures, or both

o Data suggests that surgical options provide better long-term pain relief, but
currently endoscopic interventions are first-line given ease and less-invasiveness
o First-line endoscopic options:
 ERCP with pancreatic sphincterotomy, stone clearance, stricture dilation,
and PD stenting
 EUS with transluminal stent for PD decompression
o Surgical options: Puestow, Frey, Breger

- Celiac plexus block:

o Consider celiac plexus block in patients (condition, very low quality evidence)
o Injection in celiac ganglia, typically local anesthetic + steroid (i.e. bupivacaine and
triamcinolone)
o Via EUS, IR, surgical approach (similar efficacy in studies)
o Pain reduction for 3-6 moths, reduce or eliminate need for oral pain medication,
quick
- Total pancreatectomy with islet autotransplantation (TPIAT)
o Should be reserved for highly selected patients with refractory chronic pain in whom
all other symptom control measures have failed
o Only case series and cohort studies available
o Risk of type 3c DM and lifelong intestinal dysmotility
- What do we offer patients who have active alcohol abuse?
o Caution should be taken for elective interventional (surgical or endoscopic)
therapies
o Urgent interventions should always be performed as medically necessary
ACG Clinical Guideline—Chronic Pancreatitis
Updated March 2020
Heidi Ahmed, May 12th 2020