Pancreatic Cancer in Chronic Pancreatitis: Pathogenesis and Diagnostic Approach

Abstract

Chronic pancreatitis is one of the main risk factors for pancreatic cancer, but it is a rare event. Inflammation and oncogenes work hand in hand as key promoters of this disease. Tobacco is another co-factor. During alcoholic chronic pancreatitis, the cumulative risk of cancer is estimated at 4% after 15 to 20 years. This cumulative risk is higher in hereditary pancreatitis: 19 and 12% in the case of PRSS1 and SPINK1 mutations, respectively, at an age of 60 years. The diagnosis is difficult due to: (i) clinical symptoms of cancer shared with those of chronic pancreatitis; (ii) the parenchymal and ductal remodeling of chronic pancreatitis rendering imaging analysis difficult; and (iii) differential diagnoses, such as pseudo-tumorous chronic pancreatitis and paraduodenal pancreatitis. Nevertheless, the occurrence of cancer during chronic pancreatitis must be suspected in the case of back pain, weight loss, unbalanced diabetes, and jaundice, despite alcohol withdrawal. Imaging must be systematically reviewed. Endoscopic ultrasound-guided fine-needle biopsy can contribute by targeting suspicious tissue areas with the help of molecular biology (search for KRAS, TP53, CDKN2A, DPC4 mutations). Short-term follow-up of patients is necessary at the clinical and paraclinical levels to try to diagnose cancer at a surgically curable stage. Pancreatic surgery is sometimes necessary if there is any doubt.

Keywords: alcohol consumption; chronic pancreatitis; hereditary pancreatitis; pancreatic ductal adenocarcinoma; screening; tobacco consumption.

Figure 1

Natural history of pancreatic carcinogenesis in the specific context of inflammation.

Figure 2

Cerulein experimental model of pancreatic carcinogenesis in genetically engineered mice.

Figure 3

CT scan pictures of paraduodenal pancreatitis and pseudo-tumorous chronic pancreatitis. (A): paraduodenal pancreatitis developed on chronic pancreatitis. Hypodensity of the duodenal groove (white arrow) and hypertrophy of the calcified head of pancreas (dashed white arrow) (white star: duodenal wall). (B): paraduodenal pancreatitis with duodenal cysts (white arrow) associated with chronic pancreatitis with irregular caliper of Wirsung duct (white dashed arrow); (C): pseudotumorous chronic pancreatitis on the head of the pancreas (white arrow) without vessel infiltration; (D): pseudotumorous chronic pancreatitis on the head of the pancreas (white arrow) with stenosis of the common bile duct (white dashed arrow).

Figure 4

MRI cholangiopancreatography pictures of alcoholic chronic pancreatitis, pancreatic carcinoma, and obstructive chronic pancreatitis. (A): Alcoholic chronic pancreatitis with dilatated Wirsung duct and one or two pancreatic lithiasis (white arrow). (B): Mixed IPMN (white arrow) with upstream signs of obstructive chronic pancreatitis (dashed white arrow). (C): Pancreatic ductal adenocarcinoma (tumoral stenosis of the isthmus showed by the white arrow) with upstream regular Wirsung duct dilatation (dashed white arrow). (D): Pancreatic ductal adenocarcinoma (tumoral stenosis of the head showed by the white arrow) with upstream signs of obstructive chronic pancreatitis (dashed white arrow).

Figure 5

CT scan and EUS pictures of a case of pancreatic carcinoma developed on chronic pancreatitis. A 47-year-old man with alcoholic chronic pancreatitis and recurrence of abdominal pain despite alcohol abstinence. (A): CT scan pictures of tissue mass on the head of the pancreas (white arrow) and dilatation of Wirsung duct (dashed white arrow); (B): tissue infiltration at the anterior part of the head of the pancreas (white arrow); (C): EUS view of the hypertrophic head of the pancreas (white arrows) with tissue infiltration of the duodenum (white stars); (D): EUS view of the hypertrophic head of the pancreas with lymphadenopathy (white arrow) and fine-needle aspiration biopsy (white dashed arrow) which was non-contributive but displayed KRAS mutation. A carcinoma was found on the surgical resected specimen.

Figure 6

Proposed screening algorithm for pancreatic ductal adenocarcinoma in patients with chronic pancreatitis. DM: diabetes mellitus; CT scan: computed tomography scan; MRI: magnetic resonance imaging; PDAC: pancreatic ductal adenocarcinoma.