Acute Pancreatitis Overview

Acute Pancreatitis

• Acute pancreatitis is a reversible inflammatory condition ranging from mild edema to severe hemorrhagic necrosis.
• The annual global incidence is 33 to 74 per 100,000.
• Overall mortality is about 5%.
• Gallstones and excessive alcohol use account for 80% of cases.
• Other factors include duct obstruction, metabolic disorders like hypertriglyceridemia.
• Medications and infections such as mumps or coxsackievirus are also causative.
• 10%-20% of cases are idiopathic.
• Mutations in trypsinogen and trypsin inhibitor genes can be etiologic.
• Three main inciting pathways exist: pancreatic duct obstruction, primary acinar cell injury, and defective intracellular transport.
• Alcohol abuse can transiently increase exocrine secretion and sphincter of Oddi contraction, exert toxic effects on acinar cells and lead to protein-rich plugs in pancreatic ducts.
• Basic morphologic alterations include microvascular leakage, fat necrosis, inflammation, and parenchymal destruction with hemorrhage.
• Severe cases can result in acute necrotizing pancreatitis.
• Diagnosis primarily involves detecting elevated plasma levels of lipase and amylase, and excluding other causes for abdominal pain.
• Mild pancreatitis is self-limiting in 80% of cases.
• Clinical features include sudden abdominal pain, guarding, and absence of bowel sounds.
• Hypocalcemia is considered an indicator of poor prognosis.
• Management includes supportive therapy and restricting oral food and fluids.

Consequences of Pancreatitis

• Pancreatic enzyme release can invoke systemic inflammatory response syndrome.
• Sequelae include sterile or infected pancreatic abscesses or pseudocysts.

Pancreatic Pseudocysts

• A pseudocyst is a walled-off fluid collection, typically occurring after pancreatitis, and is devoid of an epithelial lining
• Pseudocysts usually are solitary and contain pancreatic enzymes.
• Most resolve on their own; however, some persist to cause complications.

Chronic Pancreatitis

• Chronic pancreatitis involves long-standing inflammation leading to irreversible destruction of the exocrine pancreas.
• Recurrent acute pancreatitis can evolve into chronic pancreatitis.
• Prevalence ranges from 0.04% to 5% in the US population.
• Alcohol consumption is a common cause.
• Autoimmune pancreatitis (IgG4-related) is a distinct form.
• Germline mutations in CFTR, PRRSI, and SPINK1 genes relate to "idiopathic" cases.
• Macroscopic evaluation reveals hard glands, that are sometimes dilated, and microscopic evaluation reveals parenchymal fibrosis, reduced acini, and duct dilation.
• Autoimmune pancreatitis is characterized by intense immune response in the pancreas.
• Abdominal pain is a common symptom and can manifest as jaundice.

Pancreatic Neoplasms

• Pancreatic exocrine neoplasms can be cystic or solid.
• Cystic neoplasms range from benign to invasive cancers.

Cystic Neoplasms

• There are three variants of cystic neoplasms: serous cystic neoplasms, intraductal papillary mucinous neoplasms (IPMN), and mucinous cystic neoplasms
• IPMNs account for 38%, mucinous cystic neoplasms for 23%, and serous cystic tumors for 16%.

Serous Cystadenomas

• These tumors are composed of glycogen-rich cuboidal cells with small cysts containing clear fluid.
• Cysts can be small, multiple, or honeycomb-like.
• Surgical resections are commonly curative.
• Most serous cystadenomas carry somatic loss-of-function mutations of VHL tumor suppressor gene.

Mucinous Cystic Neoplasms

• 95% arise in women and they are precursors to invasive carcinomas
• Cystic spaces are filled with thick mucin and the cystic tumor is confined to the tail of the pancreas.
• One-third of these cysts are associated with adenocarcinoma.
• Mucinous cystic neoplasms harbor oncogenic KRAS mutations

Intraductal Papillary Mucinous Neoplasms

• More occur frequently in men that women and commonly occur within the head of the pancreas
• IPMNs arise in the main pancreatic ducts.
• Involve cellular stroma seen in mucinous cystic neoplasms

Pancreatic Carcinoma

• Third leading cause of cancer-related deaths in the United States
• Carries high mortality rate with a 5-year survival of 8%.
• KRAS oncogene is the most altered gene in pancreatic cancer.

PanINs

• Common antecedent lesions of pancreatic cancers arise in small ducts and are termed pancreatic intraepithelial neoplasias (PanINs).
• Four genes are commonly mutated in pancreatic cancer: KRAS, CDKN2A/p16, SMAD4, and TP53
• The strongest environmental influence is smoking, which doubles the risk.

Morphology

• 60% of pancreatic cancers arise in the head of the gland.
• Carcinomas are hard, gray-white masses.
• Pancreatic cancer typically highly invasive.

Clinical Features

• Most carcinomas of the head commonly obstruct the distal bile duct.
• Cancers can remain silent until they impinge on some other structure.
• Weight loss, anorexia, and generalized malaise and weakness are manifestations of advanced disease.
• Migratory thrombophlebitis (Trousseau syndrome) occurs in about 10% of patients with cancer.

Testing

• There is a need for biomarkers that can detect the pancreatic cancer at an early, curable stage.
• High resolution CT scans helpful at detecting cancers.