Study of New Biological Markers for Prediction of Severe Acute Pancreatitis

Acute pancreatitis refers to inflammation of the pancreas and is associated with sudden onset of severe abdominal pain, often accompanied by transient systemic manifestations, including fever. In the majority of cases, the inflammatory process is self limiting and patient recovers uneventfully; however, in about 20% to 30% of the cases, a protracted clinical course ensues and the disease may progress to a severe necrotizing form, often triggering a systemic inflammatory response syndrome during which time, acute respiratory distress syndrome, renal failure, shock, and disseminated intravascular coagulation may occur. In the worst sequelae, multiple organ dysfunctions may follow and death supervene. The clinical outcome of patients suffering from severe acute pancreatitis depends to a great extent on the early diagnosis and prediction of severity and timely therapeutic intervention to prevent local and systemic complications. However, the course of the disease is often difficult to predict from the outset. Currently, there is still no single clinical or laboratory test that can be considered the "gold standard" for diagnosis and/or assessment of severity of acute pancreatitis. For a disease that may progress rapidly without apparent sign, the ideal marker for the prediction of disease severity in a patient would be one that is measurable rapidly and easily, besides being able to fulfill all the other criteria required of a good biological marker. To identify such a potential marker for acute pancreatitis requires understanding of the pathophysiological process underlying the rapid progression of a fulminant course of the disease. Although much remains to be elucidated, recent studies in animals have suggested that inflammatory mediators substance P and hydrogen sulfide may play critical roles. This study will evaluate if inflammatory mediators substance P and hydrogen sulfide are upregulated early on in the disease process, and if the levels of their elevation predict disease severity.

Patients with clinical presentation suggestive of acute pancreatitis

• Acute Pancreatitis Patients
  Patients presenting with clinical features compatible with acute pancreatitis
• Control
  Preoperative patients going for elective cholecystectomy

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Inclusion Criteria:

The patient should fulfill all of the following criteria:

• The subject should be at least 18 years of age.
• Clinical features compatible with acute pancreatitis.
• First symptoms of acute pancreatitis not more than 72 hours before enrolment.
• Serum amylase level above 480 U/dl (normal 60-160 U/dl or 2-hour urinary amylase greater than 1120 U (normal 280 U).
• Serum lipase levels greater than 2 U (normal < 1 U).
• Patient has signed consent form regarding participation in the study.

Exclusion Criteria:

The patient should not present any of the following criteria:

• Symptoms of acute pancreatitis present for more than 72 hours
• Clinical evidence of sepsis or other inflammatory diseases.
• Clinical evidence of disorders/disease known to affect endogenous regulation of substance P, e.g. asthma, immune-complex-mediated lung injury, arthritis.
• Age under 18 years
• Pregnancy

• National University of Singapore, Singapore
• National Medical Research Council (NMRC), Singapore