Clinical Application of Metabolomics in Pancreatic Diseases

A Mini-Review

Wang Gu, MS; Zhong Tong, MS

Disclosures

Lab Med. 2020;51(2):116-121. 

In This Article

Limitations of Current Diagnostic Methods for Pancreatic Disease

The methods of diagnosis and treatment of pancreatic diseases, including pancreatic cancer (PC), acute pancreatitis (AP), and chronic pancreatitis (CP), lack specificity. AP is a common acute abdominal disease with an increasing incidence in recent years—the disease harbored by approximately 80% of patients with acute pancreatitis, symptoms can be managed and alleviated. In contrast, 20% of patients have disease that shows a more dangerous clinical course, with a total mortality rate of approximately 5% to 10%.[8] AP often begins quickly and progresses to a critical stage rapidly.[9]

Current diagnosis of AP is usually based on clinical examination, patient history, and the results of serum lipase and serum amylase assays. However, this combined method lacks specificity and sensitivity, and the diagnostic threshold changes over time after the initial pancreatic injury.[10] Imaging modalities such as ultrasonography and computed tomography (CT) can also be used to determine the diagnosis of AP.[11] However, ultrasonography is nonspecific, and CT is only used to evaluate the severity of the condition within 72 hours of its onset or to exclude other diagnoses due to organ failure and cell necrosis. Also, the clinical phenotype of AP is highly complex; this type of pathological damage will affect the metabolism of patients, which may lead to difficulties in early diagnosis and treatment.[12,13]

AP is a common acute abdominal disease; however, the conventional therapeutic method for AP includes supportive medical treatments, such as fluids and nutritional supplements, as well as pancreatic protease inhibitors.[14] Therefore, it is necessary to find more sensitive methods for the diagnosis of and new drugs for the treatment of pancreatitis.

Persistent inflammation of the pancreas is a characteristic of CP, resulting in progressive loss of endocrine and exocrine function due to atrophy and fibrous-tissue replacement, including recurrent or persistent abdominal pain, diabetes mellitus, and dyspepsia.[15] Although many risk factors have been studied, such as the use of alcohol and tobacco in patients with gallstones, the exact cause of CP is still unknown to a large extent;[16] still, it is clear that CP is caused by many factors. The current diagnosis of CP depends on the clinical symptoms of pancreatic exocrine function testing and imaging techniques.[17] However, most imaging methods, such as endoscopic retroperitoneal cholangiopancreatography (ERCP) and magnetic retroperitoneal cholangiopancreatography (MRCP), can only partially reflect the changes in the ductal structure of CP, and most of the changes occur in the late stages of the disease.

The results of pancreatic function tests have also revealed similar limitations, in that they have insensitivity for early detection of CP.[18] Therefore, we need to improve our ability to CP at its earliest stages, to prevent disease damage to the glands; doing so will require us to develop new diagnostic methods.

PC involves highly malignant tumors. Due to the lack of effective early diagnosis of PC, the prognosis for patients with PC is poor and the mortality rate is particularly high.[19] Patients with PC generally do not have obvious clinical symptoms in the early stages of their disease, and the late-stage symptoms are usually nonspecific and diverse. Once diagnosed, most patients are found to have advanced metastasis, which brings great difficulty to the early treatment of PC.[20] The current imaging examination for PC lacks sensitivity in early diagnosis. Also, although the sensitivity of the traditional tumor marker ca19-9 to PC can reach 80%, the specificity of ca19-9 is greatly reduced, due to a similar increase in the sensitivity to numerous nonneoplastic diseases such as AP and CP hepatitis and biliary-tract obstruction.[21] In addition, CP is an important factor leading to PC,[22] so it is also important to distinguish CP from early PC.

Currently, the existing diagnostic and therapeutic methods for pancreatic diseases are limited, so we need to constantly explore new, more efficient, and more sensitive diagnostic methods. Metabonomics may be a potential breakthrough, and related research is already under way.

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