Chronic pancreatitis

Multifactorial, fibroinflammatory syndrome in which repetitive episodes of pancreatic inflammation lead to extensive fibrotic tissue replacement, resulting in chronic pain, exocrine and endocrine insufficiency, reduced QoL and a shorter life expectancy.

Spectrum: acute, recurrent acute, pancreatic insufficiency alone, autoimmune pancreatitis, and chronic pancreatitis. They have overlapping clinical features and patients may move between them

Aetiology - TIGAR-O

Toxic-metabolic - generally synergistic
- Alcohol (seen in 70-80% of cases)
  - Five drinks a day for five years
  - But less than 5% of chronic drinkers develop it
  - Likely due to protein precipitation and formation of protein plugs and eventually stones. Also, ROS cause injury, and acetaldehyde causes direct acinar injury.
- Smoking
  - Seen in 90% of alcoholics with chronic pancreatitis
- Hypertriglyceridaemia
Idiopathic (20%)
- Early-onset, late-onset, tropical
Genetic
- Hereditary germline mutation PRSS1 gene - often early onset before age of 5, but almost always teenage years at latest
- SPINK-1
- CFTR
Autoimmune pancreatitis (AIP)
- Type 1 - IgG4-related disease - seen in association with biliary strictures, retroperitoneal fibrosis, hilar lymphadenopathy, sclerosing sialadenitis, and interstitial nephrosis. Histology - lymphoplasmacytic sclerosing pancreatitis.
- Type 2 - limited to pancreas - not IgG4 - associated with IBD. "idiopathic duct-centric pancreatitis". Obliteration of epithelium in pancreatic duct.
- Treat with steroids. Often reversible.
- 80% >50yo
Recurrent/severe acute
- 10% of AP progresses to CP
Obstructive
- Chronic obstruction of pancreatic duct - cystic dystrophy of duodenal wall, pancreas divisum, pancreatic neoplasm

Risk factors

Smoking and alcohol are the most obvious reversible RFs for progression from acute to chronic (absolute risk 30% if drinking and smoking)

Presentation

PAIN is the primary symptom. It ranges from mild postprandial to severe debilitating
- Reduces QoL, inhibits ADLs, dependence on narcotics
- Caused by ductal hypertension, and inflammatory cytokines
Weight loss - multifactorial
Pancreatic exocrine insufficiency - if this is present, 90% of pancreatic exocrine function is lost
- Steatorrhoea, diarrhoea, malabsorption
- Fat-soluble vitamin deficiency - bleeding, osteopaenia, osteoporosis
- See separate topic under 'nutrition'
Diabetes 3c - complete loss of islet mass and therefore inability to release insulin and glucagon (can get episodes of severe hypoglycaemia)
- Seen in 40-80% of patients
- Occurs years after onset of abdo pain and exocrine insufficiency
Jaundice and cholangitis
- Seen in 5-10%
- Due to fibrosis of distal CBD

Diagnosis - combination of imaging, clinical history and functional studies

Can be definitively diagnosed on imaging
- CT allows diagnosis, plus assessment for complications (duct disruption, pseudocysts, portal and splenic vein thrombosis, and pseudoaneurysms
- CT first. EUS only when CT/MRI are inconclusive, or to plan interventions.
- Secretin study (MRCP + secretin) gives better visualisation of pancreatic duct.
- EUS is really the gold standard test for CP
  - ERCP not really done any more for diagnostic purposes
Exocrine insufficiency - faecal elastase - see topic under 'nutrition' - easiest test and in most guidelines
- Doesn't matter if they're taking Creon - can still test for it, it's not in the Creon formulation

Treatment

Goals of treatment: removal of predisposing factors, pain management, management of complications, pancreatic replacement therapy. Needs to be multidisciplinary.
For flares: consider differentials (eg, peptic ulcer disease, biliary obstruction, pseudocysts, pancreatic carcinoma, and pancreatic duct stricture or stones) especially early on in the disease course, when it's hard to be sure of the diagnosis
Treating pain:
- General measures - quit smoking, stop drinking, small meals with good hydration, Creon if steatorrhoea or weight loss (give 50,000IU with a PPI)
- Type 3c diabetes is harder to treat than type 1 or 2 due to lack of glucagon - should be managed by endocrinologist
  - Not funded for glucose monitor currently in Australia
- Can try to break pain cycle with a short course of amitryptilline, some NSAIDs, perhaps need a short admission and kept NBM
- Chronic pain may require opioids - and at a certain point intervention may be necessary if they are requiring a lot of opioids
  - Refer to pain specialist at this point
- Non-surgical interventions e.g. coeliac nerve block, ESWL, could best be described as unproved
- Surgery probably has a role (partial/total pancreatectomy, plus others) although no RCTs and timing is controversial
Potential interventions:
- Endoscopic - aim to relieve pressure in PD, facilitate drainage of pancreatic juices to intestines
  - PD stones: can be fished out with ERCP, esp if stones are in head/neck, and there <4 stones.
    - Extracorporeal shockwave therapy can be useful if stones >5mm before ERCP extraction
  - Biliary stenosis with severe pain, suspicion of cancer, or additional local complications - covered SEMS
  - PD obstruction with proximal dilatation - try stenting. Often would do stent exchange/upsize every 3 months for 2 years, with a subsequent 30-40% chance of restenosis
  - Lithotripsy and ERCP for stones
- Surgical - required in 40-75% of patients with CP, probably better outcomes than endo-therapy at this point
  - Brett Knowles
    - Breakdown of options
      - Decompressive
      - Resection - duodenal-preserving pancreatic resections
      - Mixture
    - Indications
      - Small duct (up to 7mm)
        Decompressive surgery
  - Need a thorough pre-op imaging evaluation, assessing for extent of PD dilation, presence and location of PD strictures, existence of any malignant mass
  - Pancreatic duct dilation secondary to duct stones or strictures
    - Defined as main pancreatic duct >=7mm
    - Often caused by multiple strictures and stones - 'chain of lakes'
    - When accompanied by intractable pain, can be treated by side-to-side Roux-en-Y pancreaticojejunostomy (modified Puestow procedure)
  - Pancreatic duct dilation secondary to a single stricture or stone
    - As an alternative to the Puestow procedure, a pancreaticoduodenectomy can be performed
      - Absolutely contraindicated if more than one obstruction is present in the duct
    - Can also occasionally be treated with distal pancreatectomy
  - Focal inflammatory mass without significant dilation of the PD
    - Resection recommended if suspicious for malignancy
    - FNA biopsy first to rule out need for oncologic malignancy
    - Either pancreaticoduodenectomy or duodenum-preserving pancreatic head resection
  - Diffuse glandular involvement without dilation of the pancreatic duct
    - Total pancreatectomy and islet auto-transplantation (not done yet in Victoria)
    - Especially paediatric genetic patients
    - Pain relief not guaranteed. Islet cells are isolated and reimplanted into liver.
    - Contraindications
      - Active alcoholism or ilicit drug use
      - Psychiatric comorbidities that could compromise compliance
      - C-peptide negative diabetes, T1DM, PV thrombosis, portal HTN, end-stage liver disease, high-risk cardiopulmonary disease
    - Results
      - Two thirds of patients achieve narcotic independence
      - Basis for failure in some patients is incompletely understood
      - One third of patients have insulin independence
  - Biliary strictures
    - Roux-en-Y hepaticojejunostomy if causing recurrent problems
  - Pancreatic head enlargement with PD dilatation - pancreatic head resection, either duodenum-preserving or not.
  - Peripancreatic collections/pseudocyst - drain if >4cm or symptomatic or persistent for 3-6 months
    - Spontaneous regression is less likely in CP patients, because there is more likely to be PD obstruction
  - Duodenal stenosis - gastrojejunostomy