Comprehensive review of diagnostic modalities for early chronic pancreatitis

Table 1 Revised TIGAR-O aetiology criteria

Toxic-metabolic
Alcohol-related
0 to < 1 drinks/d
1-2 drinks/d
3-4 drinks/d
5 or more drinks/d
Smoking
Non-smoker (< 100 cigarettes in lifetime)
Past smoker
Current smoker (patients undergoing both past and ongoing cigarette exposure)
Other, not otherwise specified
Hypercalcaemia (total calcium levels > 12.0 mg/dL or 3 mmol/L)
Hypertriglyceridemia
Hypertriglyceridemia risk (fasting glucose > 300 mg/dL; non-fasting glucose > 500 mg/dL)
Hypertriglyceridemia in acute pancreatitis (history of glucose > 500 mg/dL in first 72 h of AP onset)
Medications
Toxins, other
Chronic kidney disease [CKD Stage 5: end-stage renal disease (ESRD)]
Other, not otherwise specified
Idiopathic
Early-onset (< 35 yr of age)
Late-onset (> 35 yr of age)
Genetic
Suspected; no or limited genotyping available
Autosomal dominant (Mendelian inheritance-single gene syndrome)
PRSS1 mutations (hereditary pancreatitis)
Autosomal recessive (Mendelian inheritance-single gene syndrome)
CFTR, 2 severe variants in trans (cystic fibrosis)
CFTR, < 2 severe variants in trans (CFTR-RD)
SPINK1, 2 pathogenic variants in trans (SPINK1-associated familial pancreatitis)
Complex genetics (non-Mendelian, complex genotypes +/- environment)
Modifier Genes (pathogenic genetic variants)
PRSS1-PRSS1 locus
CLDN2 locus
Others
Hypertriglyceridemia
Other, not otherwise specified
Autoimmune pancreatitis (AIP)/ steroid responsive pancreatitis
AIP Type 1—IgG4-related disease
AIP Type 2
Recurrent acute pancreatitis (RAP) and severe acute pancreatitis (SAP)
Acute pancreatitis (single episode, including date of event if available)
AP aetiology—Extra-pancreatic (excluding alcoholic, HTG, hypercalcaemia, genetic)
Biliary pancreatitis
Post-ERCP
Traumatic
Undetermined or not otherwise specified
Recurrent acute pancreatitis (number of episodes, frequency, and dates of events if available)
Obstructive
Pancreas divisum
Ampullary stenosis
Main duct pancreatic stones
Widespread pancreatic calcifications
Main pancreatic duct strictures
Localized mass causing duct obstruction

From the short form of TIGAR-O version 2 risk/aetiology checklist (2019)[13]. AP: Acute pancreatitis; CKD: Chronic kidney disease; HTG: Hyper-triglyceridemia; ERCP: Endoscopic retrograde cholangiopancreatography.

Table 2 Comparisons of diagnostic modalities

Modality	Diagnostic standards	Sensitivity	Specificity
Aetiology	TIGAR-O classification (version 2)[13].	-	-
Clinical presentation	Three or more of the following features: Abnormal serum or urine pancreatic enzyme concentrations; continuous heavy alcohol consumption (> 80 g alcohol/day or more than 5 drinks/day), family history of hereditary chronic pancreatitis, or known sporadic high-risk mutations; recurring epigastric abdominal pain; and abnormal exocrine function. Genetic pancreatitis should be suspected in young patients with clinical presentations but without a history of risk factors.	-	-
TA-US	Irregular main pancreatic duct with a diameter > 3 mm, hyperechoic pancreatic duct wall, or lobularity with stranding.	69% (95%CI: 54-80)	94%(95%CI: 90-100)
CT	Two or more of the following features: MPD within 2-4 mm; mild organ enlargement; irregular main pancreatic duct with ≥ 3 pathological side branches; pseudocysts ≤ 10 mm; and heterogeneous parenchyma.	75% (95%CI: 66-83)	91%(95%CI: 81-96)
MRI/MRCP	Two or more of the following features: MPD 2-4 mm; mild organ enlargement; irregular main pancreatic duct with ≥ 3 pathological side branches; pseudocysts ≤ 10 mm; and heterogeneous parenchyma.	Single-parametric: 77%; Multi-parametric: 91%	Single-parametric: 83%; Multi-parametric: 86%
ERCP	More than three pathological side branches plus a normal MPD.	82% (95% CI: 76-87)	94% (95% CI: 87-98)
EUS	More than two of the following seven criteria, including at least one of criteria 1-4: (1) Stranding; (2) Hyperechoic foci without shadowing; (3) Lobularity with honeycombing; (4) Lobularity without honeycombing; (5) Cysts; (6) Dilated side branches; (7) Hyperechoic main pancreatic duct margin.	61% (non-fibrosis); 84% (for fibrosis)	75% (non-fibrosis); 100% (for fibrosis)
EUS-EG	A strain ratio of > 10 or a mean strain histogram value of < 50 was associated with malignancy.The mean value can be used to diagnose mild or higher-grade fibrosis.	76.4%	91.7%
FE-1	Moderate EPI can be diagnosed based on an abnormal FE-1 level of < 200 μg/g, which has a high false-positive rate.	76.5%; 45.0% (mild ductal changes and insufficiency)	86.0%
ePFT	Peak bicarbonate concentration of < 80 mmol/L is considered abnormal and correlated with early fibrosis.	86% (95%CI: 67-100)	67% (95%CI: 13-100)
FNA	Ruling out malignancy and staging of CP. CEA testing: Cut-off value of 192 ng/mL. Molecular analysis: KRAS and GNAS mutations.	85% (pancreatic cancer)	98% (pancreatic cancer)
nCLE	A complementary modality for detecting subtle changes in early CP and helpful for distinguishing malignancies.	94.3% (cystic lesions); 90.3% (PDAC)	98.1% (cystic lesions); 89.5% (PDAC)

Sen: Sensitivity; Spec: Specificity; TA-US: Transabdominal ultrasound; MPD: Main pancreatic duct; CT: Computed tomography; MRI: Magnetic resonance imaging; EUS: Endoscopic ultrasound; EUS-EG: Endoscopic ultrasound elastography; FE-1: Faecal elastase-1; ePFT: Endoscopic pancreatic function test; nCLE: Endoscopic pancreatic function test; EPI: Exocrine pancreatic insufficiency; CP: Chronic pancreatitis; CEA: Carcinoembryonic antigen; MRCP: Magnetic resonance cholangiopancreatography; ERCP: Endoscopic retrograde cholangiopancreatography; FNA: Fine-needle aspiration; PDAC: Pancreatic ductal adenocarcinoma; AIP: Autoimmune pancreatitis; AP: acute pancreatitis; RAP: Recurrent acute pancreatitis; CKD: Chronic kidney disease; NCCP: Non-calcific chronic pancreatitis; ROC: Receiver operating characteristic; ROI: Region of interest; SD: Standard deviation; SR: Strain ratio.