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Initial Diagnosis and Staging of Pancreatic Cancer Including Main Initial Diagnosis and Staging of Pancreatic Cancer Including Main Differentials Axel Dallongeville, MD, Lucie Corno, MD, Stephane Silvera, MD, Isabelle Boulay-Coletta, MD, and Marc Zins, MD Computed tomography (CT) remains the optimal imaging modality for both diagnosis and staging of pancreatic adenocarcinoma. Especially, CT is highly accurate in assessing the relationship of the tumor to critical arterial and venous structures, since their involvement can preclude surgical resection or indicate a neoadjuvant strategy in borderline resectable or locally advanced lesions. MRI provides additional staging information in isodense tumors or regarding presence of small liver metastases not seen at CT. Endoscopic ultrasound is the reference technique to be used for obtaining histologic proof. The introduction of perfu- sion modalities and radiomics may benefit the evaluation of pancreatic lesion parameters, thus helping to rule out differentials. However, these techniques require further investiga- tion and standardization. Semin Ultrasound CT MRI 40:436-468 © 2019 Elsevier Inc. All rights reserved. Introduction Risk Factors ancreatic cancer is the fourth most common source of Mean age at diagnosis is 70 years. Pancreatic cancer is more P cancer mortality and the second cause of death from common in industrialized countries and in males. malignancies involving the digestive system (after colorec- The main risk factors are smoking, type 2 diabetes, tal cancer).1 Furthermore, the current sharp rise in the chronic pancreatitis, obesity, and an inactive lifestyle. Genetic incidence of pancreatic cancer may make the disease the factors associated with pancreatic cancer include the PRSS1 second leading cause of cancer death by 2030, before and SPINK1 mutations responsible for hereditary pancreati- colorectal cancer.2 The many diagnostic and therapeutic tis, Peutz-Jeghers syndrome, and the BRCA1 and BRCA2 advances achieved in recent decades have not reversed mutations that cause familial breast and ovarian cancer.7 the extremely grim prognosis, and fewer than 5% of patients survive beyond 5 years.3,4 Contributors to the high mortality rate include the usually late diagnosis, Clinical Presentation early metastatic dissemination, and often limited response to chemotherapy and radiotherapy.5 Only complete exci- As most patients have no early symptoms and the late symp- sion with tumor-free (R0) margins can provide a cure.6 tomsarevariableandnonspecific, the disease is often advanced Imaging, by establishing the diagnosis, classifying the at firstpresentation.Thetypeandtimingofthesymptoms tumor, and determining the tumor stage plays a decisive depend chieflyonthelocationoftheprimaryandonthestage role in determining whether the best treatment option is of the tumor. Compared to location in the tail of the pancreas primary surgery or À as is increasingly the case À neoad- (20%-30% of cases), location in the head (70%-80% of cases) juvant chemotherapy or radiotherapy. In some cases, the results in earlier symptoms including jaundice due to compres- imaging findings indicate that only palliative treatment is sion of the main bile duct. The most common symptoms are in order. fatigue, anorexia, and weight loss, which are often delayed. Severe abdominal pain radiating toward the back suggests an unresectable tumor that has spread to the peritoneum.8 About 50% of patients with pancreatic cancer have diabe- Radiology Department, Groupe Hospitalier Paris Saint Joseph, Paris, France. 9 Address reprint requests to Marc Zins, MD, Radiology Department, Groupe tes mellitus. The diabetes may be a recent consequence of Hospitalier Paris Saint Joseph, Paris, France. E-mail: [email protected] pancreatic duct obstruction by the tumor with pancreatic 436 https://doi.org/10.1053/j.sult.2019.08.001 0887-2171/© 2019 Elsevier Inc. All rights reserved. Initial Diagnosis and Staging of Pancreatic Cancer 437 tissue atrophy upstream of the blockage or of a paraneoplas- the pancreas in the 7th version. The new version is more objec- tic syndrome. Some patients, in contrast, have longstanding tive and produces a closer correlation with survival.13 uncontrolled diabetes. The N category describes the regional lymph nodes, for which Acute pancreatitis due to obstruction of the main pancre- no consensual definition exists to date. Tumors of the head or atic duct may be the inaugural manifestation. The tumor may isthmus classically drain to nodes located about the hepatic pedi- be challenging to diagnose as it may be masked by the pan- cle, common hepatic artery, portal vein, and pylorus; anterior or creatic infiltration due to the acute disease. posterior to the pancreaticoduodenal vessels; along the superior mesenteric vein; and along the right lateral border of the superior mesenteric artery. Tumors in the body or tail of the pancreas are Laboratory Findings believed to connect to nodes along the common hepatic artery, celiac artery, splenic artery, and splenic hilum. CA 19.9 is the main serum marker for pancreatic cancer. Sen- Involved nodes at other sites are classified as remote sitivity is 80% and specificity in symptomatic patients is about metastases (M). 80%-90%. The positive predictive value is too low, however, Figure 1 illustrates the TNM classification. for diagnostic or screening purposes.10 Furthermore, false- positive results are common, notably in patients with cholesta- sis, diabetes, chronic pancreatitis, or other malignancies. Thus, CA 19.9 assay results must be interpreted with discernment. Diagnostic Imaging Studies The CA 19.9 level may supply prognostic information in 2 Ultrasound situations. At the diagnosis of pancreatic cancer, a value below Indications 200 U/mL suggests resectability and a value above 1000 U/mL Ultrasonography is the first-line imaging study in patients strongly suggests metastatic dissemination. During treatment with jaundice or abdominal pain. This noninvasive and inex- monitoring, reversion to negativity after surgery has favorable pensive investigation14 can visualize bile or pancreatic duct prognostic significance, and declining values during chemother- 11 obstruction, detect the tumor, and contribute to assess apy or radiation therapy suggest satisfactory tumor control. spread by showing local and regional involvement and by detecting remote metastases (eg, liver metastases and retro- peritoneal nodes). Nonetheless, slice imaging must be per- TNM Classification formed to further assess tumor spread. Ultrasonography can be used to guide a percutaneous biopsy (eg, of a liver metas- Pancreatic cancer is currently classified using the 8th version tasis or, more rarely, of the primary tumor). of the American Joint Committee on Cancer (AJCC) staging system (Tables 1 and 2), which introduced several changes in the T and N categories compared to the earlier versions.12 Results The T category describes the size of the primary tumor mea- Published data on diagnostic performance vary considerably, sured along its largest dimension, as opposed to spread beyond in part due to the heavily operator-dependent nature of Table 1 TNM (Tumor/Nodes/Metastasis) Classification for Pancreatic Cancer, Based on the American Joint Committee on Cancer (AJCC), 8th Edition (2010) 438 A. Dallongeville et al. Table 2 Stages of Pancreatic Cancer Based on the AJCC Classification ultrasonography. Thus, sensitivity has ranged from 50% to Indirect signs. The many indirect signs include the following: 90%.15-17 The main limitations of ultrasonography are related to the À Dilation of the main bile duct and intrahepatic bile following factors: ducts (if the tumor is in the head of the pancreas); À Tumor size smaller than 2 cm or causing little com- À Evidence of obstructive chronic pancreatitis upstream of pression of the bile ducts or main pancreatic duct; the tumor such as dilation of the main pancreatic duct À Tumor location in the left side of the pancreas, notably (>3 mm) and atrophy of the pancreatic parenchyma; and the tail, which is less easily accessible by ultrasound; À A pseudocyst due to acute pancreatitis upstream of the À Tumors that cause diffuse infiltration of all or part of the tumor. pancreas without changing the gland contours and/or tumors that are isoechoic to the rest of the gland; and Contribution of contrast-enhanced ultrasound (CEUS). Con- À The usual technical limitations such as obesity and trast-enhanced ultrasound (CEUS) was first evaluated in the bowel gas obscuring the pancreas. late 1990s. The injection of a contrast agent that remains Direct signs. Pancreatic adenocarcinoma is typically visible as within the vascular network provides information on tissue a hypoechoic and ill-defined image (Fig. 2) that may or may blood supply. In several studies, CEUS performed better not modify the contours of the gland.18 than conventional ultrasound and, in some cases, as well as computed tomography (CT).17,18 Pancreatic adenocarcinoma is typically hypovascular, whereas chronic pancreatitis produces moderate and contin- uous enhancement with similar vascularity to that of the adjacent parenchyma; however, in very longstanding cases Figure 1 Staging of pancreatic adenocarcinoma. (a, b) Stage I is defined as a primary tumor confined to the pancreas (T1, <2cmor T2, >2 cm) without nodal involvement or metastatic disease. (c) Stage IIA is disease extending beyond the pancreas without vas- cular involvement (T3), nodal involvement, or metastatic disease. (d) Stage IIB is defined as a primary tumor that has spread to the lymph nodes. (e) Stage III is disease that has spread
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