Current Status of the Diagnosis of Early-Stage Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) can be treated with surgery, chemotherapy, and radiotherapy. Despite medical progress in each field in recent years, it is still insufficient for managing PDAC, and at present, the only curative treatment is surgery. A typical pancreatic cancer is relatively easy to diagnose with imaging. However, it is often not recommended for surgical treatment at the time of diagnosis due to metastatic spread beyond the pancreas. Even if it is operable, it often recurs during postoperative follow-up. In the case of PDAC with a diameter of 10 mm or less, the 5-year survival rate is as good as 80% or more, and the best index for curative treatment is tumor size. The early detection of pancreatic cancer with a diameter of less than 10 mm or carcinoma in situ is critical. Here, we provide an overview of the current status of diagnostic imaging features and genetic tests for the accurate diagnosis of early-stage PDAC.

Keywords: computed tomography; early-stage pancreatic ductal adenocarcinoma; endoscopic retrograde cholangiopancreatography; endoscopic ultrasound; liquid biopsy; magnetic resonance cholangiopancreatography; transabdominal ultrasonography.

Figure 1

The algorithm for the diagnosis of PDAC (from Reference [6]). US, ultrasonography; CT, computed tomography; ENPD, endoscopic nasopancreatic drainage; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasonography; MPD, main pancreatic duct; MRI, magnetic resonance imaging; MRCP, magnetic resonance cholangiopancreatography.

Figure 2

A case in which the main pancreatic duct dilatation was observed by using the drinking water method to fill the gastrointestinal tract with liquid for the observation of the pancreatic body tail. The gastrointestinal tract itself can be used as an acoustic window by instructing the patient to drink degassed water (red arrow); this enables the clear visualization of the tail of the pancreas (yellow arrow).

Figure 3

A case in which no pancreatic tumor was found in the pancreatic body by CT or MRI imaging, but atrophy of the pancreatic parenchyma in the caudal part of the pancreatic body and dilation of the main pancreatic duct in the caudal part were observed, which were later diagnosed as in the body. (a) Magnetic resonance cholangiopancreatography showing stenosis of the MPD (red yellow arrow) and dilation of the MPD in the caudal part. (b) Enhanced CT showing the localized atrophic change (yellow arrow) in the pancreatic body and the dilation of the main pancreatic duct (MPD) in the caudal part.

Figure 4

A case of intraepithelial carcinoma of the pancreas, early-stage PDAC, in which no pancreatic tumor was found by CT or MRI imaging, but severe lipidosis of the pancreatic body was observed, leading to the diagnosis of a pancreatic tumor by pancreatic fluid cytology. (a) Magnetic resonance cholangiopancreatography showing stenosis of the MPD (yellow arrow) and dilation of the MPD and branch ducts in the caudal part. (b) Enhanced CT showing localized atrophic change (yellow arrow) in the pancreatic body and dilation of the MPD in the caudal part. (c) Endoscopic retrograde cholangiography demonstrating stenosis of the MPD in the pancreatic body (yellow arrow) and detailed in the caudal part. (d) In the resected specimens, severe stenosis of the main pancreatic duct was observed in the resected sections 2–8 (yellow frame), and, in particular, severe steatosis was observed in the resected sections 2–11 (out of the blue frames, 4 and 4). Additionally, 5 shows the resected section. High-grade PanIN was detected in the 4, 5, and 6 resected sections of the pancreatic body (red frame). (e) Pathological findings indicated the low papillary proliferation of the pancreatic duct epithelium in the lumen of the main pancreatic duct of pancreatic bodies 4, 5, and 6 and pancreatic lobules associated with chronic pancreatitis in the surrounding pancreatic tissue. Disappearance, fatification, and remaining islets of Langerhans were observed (HE × 40). The pancreatic ductal epithelium exhibited nucleomegaly, a mild chromatin increase, and some clear nucleoli, and high-grade PanIN was detected (HE × 100).

Figure 4

A case of intraepithelial carcinoma of the pancreas, early-stage PDAC, in which no pancreatic tumor was found by CT or MRI imaging, but severe lipidosis of the pancreatic body was observed, leading to the diagnosis of a pancreatic tumor by pancreatic fluid cytology. (a) Magnetic resonance cholangiopancreatography showing stenosis of the MPD (yellow arrow) and dilation of the MPD and branch ducts in the caudal part. (b) Enhanced CT showing localized atrophic change (yellow arrow) in the pancreatic body and dilation of the MPD in the caudal part. (c) Endoscopic retrograde cholangiography demonstrating stenosis of the MPD in the pancreatic body (yellow arrow) and detailed in the caudal part. (d) In the resected specimens, severe stenosis of the main pancreatic duct was observed in the resected sections 2–8 (yellow frame), and, in particular, severe steatosis was observed in the resected sections 2–11 (out of the blue frames, 4 and 4). Additionally, 5 shows the resected section. High-grade PanIN was detected in the 4, 5, and 6 resected sections of the pancreatic body (red frame). (e) Pathological findings indicated the low papillary proliferation of the pancreatic duct epithelium in the lumen of the main pancreatic duct of pancreatic bodies 4, 5, and 6 and pancreatic lobules associated with chronic pancreatitis in the surrounding pancreatic tissue. Disappearance, fatification, and remaining islets of Langerhans were observed (HE × 40). The pancreatic ductal epithelium exhibited nucleomegaly, a mild chromatin increase, and some clear nucleoli, and high-grade PanIN was detected (HE × 100).

Figure 5

A case of early-stage PDAC in the body in which CT and MRCP imaging studies did not show a pancreatic tumor, but an EUS study showed a pancreatic mass. (a) Contrast-enhanced CT showing mild dilation of the main pancreatic duct, but no obvious tumor was detected (yellow arrow). (b) Magnetic resonance cholangiopancreatography showing stenosis of the MPD (yellow arrow) and dilation of the MPD and branch ducts in the caudal part. (c) A hypoechoic lesion with a diameter of 8 mm (yellow arrow) was detected in the pancreas using fundamental B-mode EUS (right), and enhanced-EUS (left) revealed that the lesion (yellow arrow) had a lower echo signal intensity than the surrounding pancreatic tissue.

Figure 6

A case of small ductal carcinoma of the pancreatic tail, imaged as a hard mass by EUS elastography (a), and a case of autoimmune pancreatitis of the pancreatic tail, imaged as a soft mass by EUS elastography. (a) Fundamental B-mode of EUS showing a 13 mm well-defined hypoechoic mass with irregular contours in the tail of the pancreas (yellow arrow). This tumor was shown to be a hard tumor on EUS-EG and was diagnosed as PDAC surgically. (b) Fundamental B-mode of EUS showing a 15 mm hypoechoic mass with an indistinct border and irregular outline in the tail of the pancreas (yellow arrow). This tumor was shown to be a relatively soft tumor on EUS-EG and was diagnosed as autoimmune pancreatitis by EUS-FNA.