Pancreatic cancer is the most malignant tumor of the digestive system and its incidence is increasing year by year. According to the data of 32 national tumor registries from 2003 to 2007, Nanhu District, Jiashan County and Haining City in Jiaxing are the three areas with the highest incidence of pancreatic cancer in China. The prognosis of pancreatic cancer is extremely poor, with a five-year survival rate of <5%, and early diagnosis is difficult, and often when there is a positive finding, the vast majority of cases are already advanced, with only 10%-20% chance of surgical resection. Therefore, finding valuable molecular markers of pancreatic cancer, imaging tests and molecular level tests such as whole genome, transcriptome and proteome, strengthening the prevention of pancreatic cancer and monitoring of high-risk groups, and timely detection of early cases are the keys to improve the diagnosis and treatment of pancreatic cancer and its prognosis.
1.Serological tumor markers
CA199 is a glycoprotein of the carrier protein type, which is a glycolipid on the cell membrane. CA199 is present on the cell membrane of pancreatic duct, gallbladder epithelium, bile duct epithelium and part of gastrointestinal epithelium, and is the most important serum tumor marker for pancreatic cancer diagnosis. CA19-9 is not a specific biomarker for pancreatic cancer, but it can also be significantly increased in biliary obstruction and biliary inflammation, so it cannot be used for early diagnosis of pancreatic cancer alone.
1.2 CA242 CA242 is a sialylated mucoglycoprotein-like gastrointestinal tumor-associated antigen, which is often used in the diagnosis, screening and monitoring of malignant tumors, and CA242 is significantly elevated in patients with pancreatic cancer and colorectal cancer. CA242 has the advantage that its expression is not affected by liver function and bile secretion, and its discovery is considered an important complement to the 3rd generation pancreatic cancer marker CA199.
1.3 Carcinoembryonic antigen (CEA) CEA is a polysaccharide-rich protein complex. The literature reports that the positive rate for pancreatic and biliary tract tumors can reach 60%-70%, but the sensitivity of CEA is low and its increase can also be seen in other gastrointestinal tumors and benign diseases, and it is more common in the middle and late stages of pancreatic cancer. Therefore, the value of CEA is limited in the early diagnosis of pancreatic cancer and the differential diagnosis with benign tumors.
2. Imaging examination
Ultrasound is non-invasive, inexpensive, simple and reproducible compared with other imaging examinations. It is sensitive to the dilatation of biliopancreatic ducts and can clarify the site of obstruction, and has similar sensitivity and specificity to local and systemic metastases in lymph nodes as CT. However, ultrasound is more dependent on the subjective feeling of the operator and is easily affected by ascites, intestinal distension and patient’s body size, and it is difficult to detect pancreatic tumors less than 2 cm in diameter. In addition, the use of Doppler ultrasound and vascular enhancement contrast agent can greatly improve its sensitivity and specificity, which is promising to improve the early diagnosis rate of pancreatic cancer.
Ultrasound endoscopy (EUS) is a new technology applied to clinical practice in recent years. Through the combination of gastroscopy and ultrasound probe, not only the lesion itself can be directly observed, but also the depth of tumor infiltration can be detected by ultrasound probe. Pancreatic cancer often appears as hypoechoic nodules with irregular contours, rough edges and dilated proximal pancreatic ducts on EUS images. One literature compared the sensitivity of different imaging targets for pancreatic cancer (less than 2 cm) and found that the diagnostic sensitivity was 52.4% for abdominal ultrasound, 42.8% for CT, and up to 95.2% for ultrasound endoscopy.
Another foreign paper also suggested that ultrasound endoscopy can screen out 6%-8% of pancreatic cancers in asymptomatic pancreatic cancer high-risk groups. In addition, ultrasound endoscopy can accurately determine whether the anterior envelope of the pancreas is invaded by tumor and can guide tumor staging. At present, ultrasound endoscopy has been carried out in our hospital since 2012, and we have accumulated certain experience in the early diagnosis of pancreatic cancer.
2.2 CT diagnosis of pancreatic cancer Multi-layer spiral CT enhancement scan improves the diagnostic accuracy of pancreatic cancer and can detect whether there are obvious abdominal implantation, liver metastasis, lymph node metastasis and ascites in pancreatic cancer. Ultra-thin multi-detector CT (MDCT) is considered to be the preferred method for diagnosis and staging of pancreatic cancer. It is one of the imaging examinations currently used for early diagnosis and screening because it can provide three-dimensional reconstruction of pancreatic occupancy and surrounding organs through reconstruction techniques.
Domestic studies have reported that MDCT examination can better evaluate the size of pancreatic occupancy tumor, more accurately determine the surrounding tissues and blood vessels of the pancreas, and has higher accuracy and reference value for the assessment of tumor staging and resectability of surgery, which is a more ideal examination technique in the diagnosis of pancreatic cancer.
2.3 MR examination of pancreatic cancer Magnetic resonance imaging (MRI) is one of the fastest developing diagnostic imaging techniques in recent years, and its detection rate of small lesions of pancreatic cancer is better than that of CT, but its qualitative diagnosis of pancreatic cancer is slightly worse than that of CT. Dynamic enhancement MRI is more advantageous than plain scan, and contrast enhances the signal intensity difference of pancreatic tumors, which is beneficial for the detection of small pancreatic cancers, as well as for the detection of early pancreatic cancers less than 25px in diameter.
Magnetic resonance cholangiopancreaticography (MRCP) can show the three-dimensional structure of the biliopancreatic duct system and clarify the site, extent and degree of obstruction, and can show bile duct obstruction (91%-100%) and the level of obstruction (85%-100%). It has been shown that MRI, MRA and MRCP have high accuracy and specificity in determining the relationship between pancreatic cancer and blood vessels, as well as the degree and extent of infiltration, and can be the first choice for evaluating the relationship between pancreatic cancer and peripheral blood vessels.
2.4 ERCP examination of pancreatic cancer Transendoscopic retrograde cholangiopancreatography (ERCP) is a duodenoscopic intubation through the mouth to the duodenal papilla and injection of contrast agent, which in turn shows the main pancreatic duct, branch pancreatic ducts, bile ducts and pot belly, and can directly observe the duodenal papilla and collect pancreatic fluid for cytological examination. The sensitivity of pancreatic cancer diagnosis is 70%-94% and the specificity is 50%-94.3%.
Most pancreatic cancers originate from the epithelium of the pancreatic duct, and tumor cells are less adherent than normal cells, so they can be easily peeled off and appear in the pancreatic fluid. The sensitivity of pancreatic fluid cytology in the diagnosis of pancreatic cancer is 76% and the specificity is 100%. However, ERCP is less useful for tumor staging, and as an invasive test, the possible intraoperative complications such as bleeding, perforation and acute pancreatitis limit its clinical application.
Our hospital has accumulated profound clinical experience in ERCP operation, and published a paper “The value of DNA ploidy analysis of exfoliated cells from biliary and pancreatic fluid in the diagnosis of benign and malignant diseases of the biliary tract and pancreas” in the Chinese Journal of Laboratory Medicine in 2004.
2.5 PET examination of pancreatic cancer Positron emission tomography/X-ray computed tomography (PET) shows radioactive concentration at the pancreatic tumor site, manifesting as a hypermetabolic lesion, with high sensitivity (85%-95%) but low specificity. The cost of PET is expensive, which limits its use in clinical practice.
3.Genetic testing
The occurrence and development of pancreatic cancer involves a series of genetic and epigenetic changes. A large number of studies have found genomic instability in pancreatic cancer patients. The genetic study of pancreatic cancer includes K-ras gene, P53 oncogene, SMAD4/DPC4 gene, DCC gene and P16 gene. K-ras has been studied more frequently, and it regulates cell proliferation and differentiation by binding to tyrosine kinase receptors on cell membranes, and mutations can induce pancreatic ductal epithelial cell metaplasia, endomatosis and transformation into invasive ductal adenocarcinoma.
However, K-ras gene usually appears in the late stage of pancreatic cancer, so it is not significant for early diagnosis. Based on this situation, we are currently undertaking the public welfare project of Zhejiang Provincial Science and Technology Department, “Study on the detection of fecal K-ras gene mutation in the early diagnosis and postoperative recurrence of pancreatic cancer by nano-probe”. “We expect to make a breakthrough in the early diagnosis of pancreatic cancer.
At present, a large number of serological tests, imaging tests, proteomic and genomic methods have been applied in the study of early diagnosis of pancreatic cancer, and the techniques of various tests are in progress, but so far there is no test with sufficient sensitivity and specificity for screening and detection of early cancerous lesions. With continuous research, increased vigilance, and enhanced multidisciplinary and multidisciplinary cooperation, the early diagnosis rate of pancreatic cancer can be improved.