Locally Advanced Pancreatic Cancer
Measurement of glycated hemoglobin (HBA1C) is an emerging and important diagnostic test in the diagnosis of pancreatic cancer. Recently, data has emerged to suggest that new-onset diabetes is present in about 50% of patients diagnosed with pancreatic cancer.39 The temporal relationship of pancreatic cancer and diabetes is supported by evidence showing that patients who undergo resection commonly have resolution of their diabetes.17 This study suggested that hyperglycemia, elevated HBA1C, and symptoms of diabetes in patients older than 50 years may identify patients who have early pancreatic cancer. The entity of pancreatic cancer–associated diabetes needs to be better defined and the algorithmic approach to evaluation and diagnosis, utilizing signs, symptoms, and laboratory values associated with diabetes, needs to be clearly established.
The only serum marker for PDA is carbohydrate antigen 19-9 (CA 19-9), also known as sialylated Lewis antigen or cancer-associated antigen. It was first identified in pancreatic cancer patients in 1981.40,41 The sensitivity and specificity of CA 19-9 ranges from 70% to approximately 90%.42,43 Hereditary predispositions and comorbid disease cross-reactivity contribute to the diminished sensitivity and specificity of CA 19-9. In about 5% to 10% of the population, CA 19-9 is not expressed (Lewis antigen A and B negative). Additionally, since CA 19-9 is expressed in the cells that line the biliary tree, diseases that lead to pancreatic or liver inflammation may falsely elevate CA 19-9.44 As a result, CA 19-9 is not an ideal screening test. However, data has shown that CA 19-9 may have prognostic value postoperatively and serve as a marker for therapeutic response.45,46
Is biopsy needed for this patient and if so, what is the most appropriate technique?
,
ENDOSCOPIC ULTRASOUND
Generally, diagnosis with tissue is not necessary for patients who clearly have resectable disease and will proceed directly to surgery for management. Nevertheless, it is still commonly obtained in this group of patients. However, in patients with LAPC or with features suggestive of LAPC, such as tumor approximation to critical vessels such as the superior mesenteric artery (SMA) or celiac axis, biopsy is necessary. These patients will receive neoadjuvant therapy, and biopsy is important in establishing a diagnosis. The ideal way to obtain a biopsy is through fine-needle aspiration (FNA) or biopsy (FNB) utilizing endoscopic ultrasound (EUS). Percutaneous and computed tomography (CT)–guided FNB can also be used to obtain a biopsy for diagnosis. In comparison to percutaneous and CT-guided FNB, EUS-FNA/FNB has low rates of complications, a decreased rate of peritoneal seeding, and is cost effective.47,48
CASE CONTINUED
Abdominal CT obtained following abdominal ultrasound reveals a 3.5-cm mass in the head of the pancreas in close approximation to the SMA and celiac axis.
Does the patient have borderline resectable or unresectable disease?
IMAGING
Abdominal ultrasound is a reasonable, inexpensive, and safe alternative to abdominal CT as it does not utilize ionizing radiation. It is particularly useful in patients who present with jaundice or have concern for biliary obstruction based on laboratory evaluation. It is particularly sensitive for detecting tumors greater than 3 cm in size.49,50 In patients whose abdominal ultrasound is unrevealing and whose index of suspicion remains high for PDA, abdominal CT should be the next imaging modality.
Abdominal CT obtained utilizing a pancreatic protocol is ideal for detection and staging of pancreatic tumors. By implementing a triple-phase protocol with arterial, late arterial, and venous phases, tumors, which have a density different from that of the pancreatic parenchyma, are accentuated. Abdominal CT is also able to provide critical information about tumor resectability.51 By revealing the degree of tumor encasement around the aorta, level of destruction of the superior mesenteric vein, or degree of involvement of the SMA or celiac vessels, abdominal CT determines if a patient should be deemed resectable, borderline resectable, or unresectable (Table 2).52,53 Resectability is based on thorough imaging evaluation, expert opinion of a multidisciplinary team, and guidelines proposed by American Hepatopancreaticobiliary Association, Society of Surgical Oncology, Society for Surgery of the Alimentary Tract, and the NCCN.54
Other imaging modalities have a less clearly established role in the diagnostic approach to PDA. In patients who have contraindications to obtaining CT, magnetic resonance imaging can be utilized as a secondary imaging modality.55 The role of positron emission tomography 18F-fluorodeoxyglucose (PET-FDG) is not clearly defined among clinicians, nor reflected in consensus guidelines by the National Comprehensive Cancer Network (NCCN). In clinical practice, it is still often combined with CT to detect metastatic disease, particularly in high-risk patients such has those with LAPC. The role of PET-CT in staging and its impact on clinical outcomes has not been fully established.
Endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) can also assist in the diagnosis and management of PDA. In patients with obstructive jaundice, both MRCP and ERCP visualize obstructions and dilations within the biliary tree, with the latter having the ability to intervene. ERCP allows for the collection of tissue to aid in diagnosis, and has the ability to relieve biliary obstruction via stenting.56
