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In patients with acute pancreatitis (AP) without an obvious cause, clinicians should first consider a neoplastic etiology in those older than 35-40 years. In contrast, genetic or autoimmune causes are more likely in younger patients, noted Frédérick Moryoussef, MD, gastroenterologist at CHI Poissy-Saint-Germain-en-Laye in Paris, France. These findings were presented at the Francophone Days of Hepato-Gastroenterology and Digestive Oncology (JFHOD 2026).

Approximately 10% of pancreatic cancer cases present with AP during the 2 years preceding diagnosis. After an inconclusive initial workup, “a follow-up MRI at 6 months, then at 1 year and 2 years” is recommended, although the current guidelines do not clearly define the exact timelines.

Monitoring may continue for up to 5 years. “Follow-up is essential to avoid delayed diagnosis of a serious disease. Clinicians must be vigilant to avoid missing cancer or biliary stone disease. Patients should also be advised to seek prompt evaluation if symptoms or warning signs develop.”

AP is an acute inflammation of the pancreas that presents with severe upper abdominal pain, usually accompanied by nausea and vomiting. Although 80% of AP cases are mild, hospitalization is recommended to assess severity. Necrotizing forms may lead to organ failure and death.

Chronic alcohol consumption and biliary diseases are the leading causes. Gallstones obstructing the main pancreatic duct account for 40% of AP cases. Benign or malignant pancreatic tumors are the third leading cause. Other etiologies include severe hypertriglyceridemia, genetic abnormalities, and autoimmune causes.

Diagnosis is based on typical abdominal pain combined with lipase levels exceeding three times the upper limit of normal. Lipase levels, however, may normalize more than 48 hours after pain onset. In such cases, abdominal CT can confirm the diagnosis by identifying characteristic morphologic abnormalities.

“That is when the etiological assessment begins: a ‘three-step clinical and morphological investigation’ when the causes are not immediately apparent,” said Moryoussef.

Upon admission, the initial evaluation includes a medical history, including alcohol consumption, previous episodes of biliary disease, recent trauma, family history, and iatrogenic causes, supplemented “as soon as possible” by liver function tests, triglyceride levels, and serum calcium levels.

An abdominal ultrasound is performed on an emergency basis within 24 hours. A CT scan is then performed to determine the CT Severity Index based on the extent of inflammation and necrosis. “The CT scan also helps ensure that a serious underlying cause, which might otherwise be incorrectly attributed to gallstone disease, is not overlooked.”

According to 2025 recommendations from the International Association of Pancreatology, ultrasonography should be repeated on day 7 to reassess for biliary stones and morphologic abnormalities. “This is not routine practice in France, but it is clearly stated in the latest recommendations,” he said.

In the absence of an identified cause, AP is classified as “presumed idiopathic,” accounting for approximately 20% of the cases. A second evaluation should then be performed within 1-2 months to look for microlithiasis and, primarily, adenocarcinoma in patients older than 35-40 years. Autoimmune and genetic causes should also be investigated at this stage.

“A normal ultrasound does not necessarily rule out a biliary cause,” the specialist noted. Microlithiasis, defined as stones smaller than 5 mm and sludge or thickened bile, which represents the leading cause of idiopathic AP, is missed by more than one third of ultrasound examinations. This supports the value of supplementing the evaluation with digestive endoscopic ultrasound, “a highly effective test” for this indication.

Pancreatic CT or MRI is also indicated to investigate tumors. “Any mass, dilation of the main pancreatic duct, or stenosis should raise suspicion for an underlying tumor.” In the absence of warning signs, clinicians should monitor the patients for anorexia, weight loss, or diabetes.

“Cross-sectional imaging is essential in every case of AP, even when gallstones are present,” Moryoussef emphasized. MRI and endoscopic ultrasonography are recommended in patients older than 40-50 years with idiopathic AP. “In practice, both examinations are necessary in all idiopathic AP cases. They identify the cause in two thirds of patients.”

Laboratory testing should also include triglyceride and calcium measurements. Immunoglobulin G4 (IgG4) levels should be assessed to investigate IgG4-related disease, particularly in patients older than 50 years or with type 2 autoimmune pancreatitis in younger patients, often associated with inflammatory bowel disease.

Regarding genetic causes, “variants are identified in 60% of recurrent or idiopathic AP cases before age 35.” Genetic testing is therefore recommended in idiopathic pancreatitis before the age of 35 and at any age in patients with a family history or recurrent disease.

Drug-related and toxic causes should also be investigated, particularly heavy cannabis, tobacco, or cocaine use.

Idiopathic AP is considered “confirmed” after the second workup. Clinical, biologic, and morphologic follow-up should then be implemented. Abdominal ultrasonography is recommended every 6 months, with MRI performed at 6 months, 1 year, and 2 years. “Examinations should also be repeated in cases of recurrence,” Moryoussef said.

Guidelines regarding these follow-up protocols remain imprecise. During the discussion session, Vinciane Rebours, MD, professor and head of the Department of Pancreatology and Digestive Oncology at Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, in Paris, France, suggested annual MRI or CT follow-up for 5 years. She noted that when cancer is the underlying cause, 90% of cases are diagnosed within the year following pancreatitis, whereas the risk becomes negligible after 5 years.

When asked about management after identification of an intraductal papillary mucinous neoplasm, Moryoussef advised “taking time” to confirm that the cystic lesion is truly responsible for the pancreatitis. “I tend to perform follow-up imaging later, particularly in patients older than 50 years, to avoid missing another possible cause,” he said.

Intraductal papillary mucinous neoplasms are common precancerous pancreatic tumor lesions. Management involves annual monitoring, which may later be spaced out or discontinued after 5 years depending on risk criteria. According to a French observational study, fewer than 1% of these lesions progress to adenocarcinoma within 5 years.

This story was translated from Medscape’s French edition.