**7. Conventional imaging modalities**

Imaging studies are essential in the management of pancreatic cancer. The most important goal of imaging is to determine tumor resectability. Involvement of adjacent vessels (superior mesenteric vein, portal vein, and superior mesenteric artery), nodal involvement and distant metastatic lesions are paramount in selecting treatment options. The investigation of most patients with pancreatic cancer generally begins with a right upper quadrant ultrasound to evaluate jaundice.

#### **7.1. Abdominal ultrasound**

Abdominal ultrasound (US) examination reliably detects extra-hepatic and intra-hepatic ductal dilatation. However, accurate identification of a pancreatic mass may be compromised by operator experience, bowel gas interference, or obesity, and does not provide information regarding tumor involvement of the vascular structures or lymph node involvement. In advanced disease, ascites and liver metastases (>1 cm) may be seen by abdominal US.

#### **7.2. Computed Tomography**

Computed tomography (CT) has been used routinely for evaluation of pancreatic cancer over the last few decades. However, since the advent of triple phase (noncontrast, arterial, and portal venous) helical multidetector row CT (MDCT) with thin cuts (1 mm slices) through the pancreas along with coronal three dimensional reconstruction (pancreatic protocol), it has become the gold standard initial test for the diagnosis and staging of all pancreatic cancers. The sensitivity for lesions greater than 2 cm is 100% [46]. While the false positive rate is low, it might occur in the setting of focal chronic pancreatitis or autoimmune pancreatitis. The advantage of CT is its wide availability, non-invasive approach, non-operator dependent and easily reproducible images. It is also deliberately used in conjunction with 18F-fluorodeoxy‐ glucose positron emission tomography (PET)/CT for surveillance imaging post treatment.

#### **7.3. Endoscopic ultrasound**

Endoscopic ultrasound (EUS) transmits high-frequency sound waves through the upper GI tract to detect abnormalities in the pancreas (Figure 6). The accuracy of EUS is operator dependent and it is not yet available at many community hospitals. At experienced centers, EUS has been shown to have a similar (or better) sensitivity and specificity for the diagnosis of pancreatic cancer to that of MDCT [47]. Being a dynamic test, it can distinguish subtle abnormalities such as pancreatic duct strictures and small neuroendocrine tumors. Not uncommonly, it can detect small (<1cm) pancreatic cancers, which would escape detection by MDCT. EUS can also evaluate malignant as well as pre-malignant cystic lesions such as intraductal papillary mucinous neoplasms with its characteristic findings of intramural nodules and communication with the main pancreatic duct.

**Figure 6.** Malignant biliary obstruction from mass in head of pancreas causing CBD and PD dilation (double-duct sign) US (A). MRCP in (B) Note the distended gallbladder, seen in patients with malignant biliary obstruction (Courvoisier's sign)

Due to the high sensitivity of EUS in detecting small lesions, it is widely used to screen patients with familial pancreatic cancer or other hereditary syndromes [48]. EUS has the advantage of allowing sampling of the tumor mass, regional nodes, liver lesions, ascites and malignant cyst fluid, as well as assessing tumor resectability during diagnostic evaluation (Figure 7). In one study, the sensitivity, specificity, and accuracy of EUS-FNA for diagnosis of a pancreatic malignancy were 91%, 100%, and 92%, respectively. No mortalities were reported in this analysis and morbidity was only 2% [49]. Recently, the EUS-FNA needles have been employed to introduce sophisticated probes directly into the pancreatic lesions for diagnostic needs, as well as deliver therapeutic approaches such as local injections of cytotoxic agents and probe based application of radiofrequency ablation.

**Figure 7.** Mass in head of pancreas causing biliary obstruction (note both cystic duct and common bile duct are dilat‐ ed)-A; The portal Vein PV-B and PV confluence (C).

EUS is not without limitations in the evaluation of patients with pancreatic cancer. In some cases pancreatic cancer might be indistinguishable from focal chronic pancreatitis (with or without focus of ductal adenocarcinoma), pancreatic intraepithelial neoplasms-PanINs, and patients with autoimmune pancreatitis. The ability of EUS alone in differentiating these from malignant lesions can be challenging and thus a multimodality diagnostic evaluation becomes necessary along with the history and physical exam findings. Tissue sampling for pathological evaluation might also be challenging with EUS as fine needle aspiration provides scant aspirate and core biopsies (by pro-core needles) might not give adequate histological architecture needed to make an accurate diagnosis. Further limitations of EUS are the result of anatomical constraints such as tumors located in the uncinate process because the acute angle of the echoendoscope in the second portion of the duodenum makes this location challenging for FNA sampling.

#### **7.4. Endoscopic retrograde cholangiopancreatography**

**7.1. Abdominal ultrasound**

232 Updates on Cancer Treatment

**7.2. Computed Tomography**

**7.3. Endoscopic ultrasound**

and communication with the main pancreatic duct.

Abdominal ultrasound (US) examination reliably detects extra-hepatic and intra-hepatic ductal dilatation. However, accurate identification of a pancreatic mass may be compromised by operator experience, bowel gas interference, or obesity, and does not provide information regarding tumor involvement of the vascular structures or lymph node involvement. In

Computed tomography (CT) has been used routinely for evaluation of pancreatic cancer over the last few decades. However, since the advent of triple phase (noncontrast, arterial, and portal venous) helical multidetector row CT (MDCT) with thin cuts (1 mm slices) through the pancreas along with coronal three dimensional reconstruction (pancreatic protocol), it has become the gold standard initial test for the diagnosis and staging of all pancreatic cancers. The sensitivity for lesions greater than 2 cm is 100% [46]. While the false positive rate is low, it might occur in the setting of focal chronic pancreatitis or autoimmune pancreatitis. The advantage of CT is its wide availability, non-invasive approach, non-operator dependent and easily reproducible images. It is also deliberately used in conjunction with 18F-fluorodeoxy‐ glucose positron emission tomography (PET)/CT for surveillance imaging post treatment.

Endoscopic ultrasound (EUS) transmits high-frequency sound waves through the upper GI tract to detect abnormalities in the pancreas (Figure 6). The accuracy of EUS is operator dependent and it is not yet available at many community hospitals. At experienced centers, EUS has been shown to have a similar (or better) sensitivity and specificity for the diagnosis of pancreatic cancer to that of MDCT [47]. Being a dynamic test, it can distinguish subtle abnormalities such as pancreatic duct strictures and small neuroendocrine tumors. Not uncommonly, it can detect small (<1cm) pancreatic cancers, which would escape detection by MDCT. EUS can also evaluate malignant as well as pre-malignant cystic lesions such as intraductal papillary mucinous neoplasms with its characteristic findings of intramural nodules

**Figure 6.** Malignant biliary obstruction from mass in head of pancreas causing CBD and PD dilation (double-duct sign) US (A). MRCP in (B) Note the distended gallbladder, seen in patients with malignant biliary obstruction (Courvoisier's sign)

advanced disease, ascites and liver metastases (>1 cm) may be seen by abdominal US.

Endoscopic retrograde cholangiopancreatography (ERCP) has been used historically to allow direct visualization of the duodenum and ampulla, as well as delineation of the biliary and pancreatic ductal systems. ERCP may also be used to obtain "brush" samples for cytology and intra-ductal biopsies in order to increase diagnostic yield, especially in situations where EUS-FNA results are inconclusive. However, ERCP remains an invasive test with potential risks such as post ERCP-pancreatitis, which might result from injecting contrast to delineate a suspected malignant pancreatic duct stricture. Hence, the usefulness of ERCP as a primary diagnostic modality for pancreatic cancer has significantly decreased since the introduction of endoscopic ultrasonography. Currently, ERCP is not favored as an initial test for the diagnosis of adenocarcinoma of the pancreas. On the other hand, ERCP is generally reserved for therapeutic indications such as palliating patients with obstructive jaundice from pancreatic cancer with metastatic or locally advanced disease who are not candidates for resection. These patients benefit from biliary sphincterotomy and/or stent placement (Figure 8). Routine stenting of patients with resectable pancreatic cancer, however, has not shown clear benefits in patients that might be considered candidates for resection as this might lead to unjustified complications [50]. A new role of ERCP is evolving as a means to access the pancreatic duct for endoscopic pancreatic imaging and therapeutics.

**Figure 8.** Malignant pancreatic stricture causing upstream pancreatic duct dilation. Note that the wire was advanced into the bile duct during ERCP to place biliary stent for palliation of obstructive jaundice (A). Placement of metallic biliary stent for palliation of obstructive jaundice in a patient with unresectable pancreatic cancer [fluoroscopic picture (B); endoscopic picture (C)]

#### **7.5. Magnetic resonance cholangiopancreatography**

Magnetic resonance cholangiopancreatography (MRCP) is better than CT in outlining the anatomy of biliary and pancreatic tree and can provide useful information in patients who have suspected biliary or pancreatic strictures. It can also provide a road map for future endoscopic therapy. MRI of the pancreas can provide valuable information about solid tumors of the pancreas as well as cystic neoplasms, and is generally comparable to MDCT in deter‐ mining resectability (Figure 6) [51].

Centers without personnel experienced with EUS-FNA rely on percutaneous fine-needle aspiration (FNA) of pancreatic masses to establish a diagnosis. CT-guided percutaneous FNA performed by interventional radiologist carries a theoretical risk of malignant seeding of the needle tract, but no convincing data has proven this theory conclusively. The CT guided approach is technically easier for masses in the tail of the pancreas rather than the head. A negative result on tissue diagnosis with a suspicious mass on CT scan does not preclude surgical intervention. This approach can be helpful in patients who are considered poor candidates for any endoscopic intervention due to underlying co-morbidities and individuals who have unresectable disease.

#### **7.6. Exploratory laparoscopy**

diagnostic modality for pancreatic cancer has significantly decreased since the introduction of endoscopic ultrasonography. Currently, ERCP is not favored as an initial test for the diagnosis of adenocarcinoma of the pancreas. On the other hand, ERCP is generally reserved for therapeutic indications such as palliating patients with obstructive jaundice from pancreatic cancer with metastatic or locally advanced disease who are not candidates for resection. These patients benefit from biliary sphincterotomy and/or stent placement (Figure 8). Routine stenting of patients with resectable pancreatic cancer, however, has not shown clear benefits in patients that might be considered candidates for resection as this might lead to unjustified complications [50]. A new role of ERCP is evolving as a means to access the pancreatic duct

**Figure 8.** Malignant pancreatic stricture causing upstream pancreatic duct dilation. Note that the wire was advanced into the bile duct during ERCP to place biliary stent for palliation of obstructive jaundice (A). Placement of metallic biliary stent for palliation of obstructive jaundice in a patient with unresectable pancreatic cancer [fluoroscopic picture

Magnetic resonance cholangiopancreatography (MRCP) is better than CT in outlining the anatomy of biliary and pancreatic tree and can provide useful information in patients who have suspected biliary or pancreatic strictures. It can also provide a road map for future endoscopic therapy. MRI of the pancreas can provide valuable information about solid tumors of the pancreas as well as cystic neoplasms, and is generally comparable to MDCT in deter‐

Centers without personnel experienced with EUS-FNA rely on percutaneous fine-needle aspiration (FNA) of pancreatic masses to establish a diagnosis. CT-guided percutaneous FNA performed by interventional radiologist carries a theoretical risk of malignant seeding of the needle tract, but no convincing data has proven this theory conclusively. The CT guided approach is technically easier for masses in the tail of the pancreas rather than the head. A negative result on tissue diagnosis with a suspicious mass on CT scan does not preclude surgical intervention. This approach can be helpful in patients who are considered poor candidates for any endoscopic intervention due to underlying co-morbidities and individuals

for endoscopic pancreatic imaging and therapeutics.

**7.5. Magnetic resonance cholangiopancreatography**

(B); endoscopic picture (C)]

234 Updates on Cancer Treatment

mining resectability (Figure 6) [51].

who have unresectable disease.

Reportedly, 20% to 40% of patients staged by CT, MRI, ERCP or EUS will have undetected disseminated disease during exploratory laparoscopy. The use of laparoscopy has proponents that span usefulness [52-54] to an entirely unnecessary procedure. The main argument against its use emanates from the currently available non-invasive image modalities, which in the view of some clinicians eliminates the need for a further invasive procedure [55]. Laparoscopic exploration for patients with pancreatic lesions is best used selectively rather than routinely and may have a larger role in resectable tumors of the body and tail of the pancreas [56;57]. Selective criteria for patients with pancreatic cancer include tumors larger than 3 cm, a CA 19-9 level above 100 U/ml, and questionable imaging findings.
