Sections

Workup

Approach Considerations

The laboratory findings in patients with pancreatic cancer are usually nonspecific. However, a number of continually evolving imaging modalities are available to help diagnose pancreatic carcinoma in patients in whom the disease is suggested clinically. These include the following:

Computed tomography (CT)
Transcutaneous ultrasonography (TUS)
Endoscopic ultrasonography (EUS)
Magnetic resonance imaging (MRI)
Endoscopic retrograde cholangiopancreatography (ERCP)
Positron emission tomography (PET)

Which of these modalities is used at a particular institution may depend largely on the local availability of and expertise with the procedure, as well as local cancer protocols. Additional considerations in the choice of diagnostic modality include the following:

Accuracy for providing staging information
Allowance for simultaneous collection of tissue samples for cytologic or histologic confirmation of the diagnosis
Capacity to facilitate therapeutic procedures, such as biliary stent placement or celiac neurolysis

The diagnosis of pancreatic carcinoma is most difficult in patients with underlying chronic pancreatitis. In such cases, all of the above imaging studies may show abnormalities that may not help to differentiate between pancreatic carcinoma and chronic pancreatitis. Even tumor markers can be elevated in patients with chronic pancreatitis. In these patients, one must often combine multiple imaging modalities, close clinical follow-up, serial imaging studies, and, occasionally, empiric resection, to diagnose an underlying pancreatic carcinoma.

Go to Radiologic Diagnosis and Staging of Pancreatic Carcinoma for complete information on this topic.

Laboratory Findings

The laboratory findings in patients with pancreatic cancer are usually nonspecific. As with many chronic diseases, a mild normochromic anemia may be present.

Patients presenting with obstructive jaundice show significant elevations in bilirubin (conjugated and total), alkaline phosphatase, gamma-glutamyl transpeptidase, and to a lesser extent, aspartate aminotransferase and alanine aminotransferase.

Serum amylase and/or lipase levels are elevated in less than half of patients with resectable pancreatic cancers and are elevated in only one quarter of patients with unresectable tumors. However, about 5% of patients with pancreatic cancer present initially with acute pancreatitis, in which case amylase and lipase would be uniformly elevated. Thus, pancreatic cancer should be in the differential diagnosis of an elderly patient presenting for the first time with acute pancreatitis without any known precipitating factors.

Liver metastases alone are not associated with clinical jaundice but may result in relatively low-grade elevations of serum alkaline phosphatase and transaminase levels.

Patients with advanced pancreatic cancers and weight loss will also have general laboratory evidence of malnutrition (eg, low serum albumin or cholesterol level).

Carbohydrate antigen 19-9

Carbohydrate antigen 19-9 (CA 19-9) is a sialylated oligosaccharide that is most commonly found on circulating mucins in cancer patients.^[54]It is also normally present within the cells of the biliary tract and can be elevated in acute or chronic biliary disease. Some 5-10% of patients lack the enzyme necessary to produce CA 19-9; in these patients with low or absent titer of CA 19-9, monitoring disease with this tumor marker will not be possible.

The reference range of CA 19-9 is less than 33-37 U/mL in most laboratories. Of patients with pancreatic carcinoma, 75-85% have elevated CA 19-9 levels. In the absence of biliary obstruction, intrinsic liver disease, or benign pancreatic disease, a CA 19-9 value of greater than 100 U/mL is highly specific for malignancy, usually pancreatic.

Evaluation of CA 19-9 levels has been used as an adjunct to imaging studies for helping to determine the resectability potential of pancreatic carcinoma. Fewer than 4% of patients with a CA 19-9 level of more than 300 U/mL have been found to have resectable tumors.

Unfortunately, CA 19-9 is least sensitive for small, early-stage pancreatic carcinomas and thus has not proven to be effective for the early detection of pancreatic cancer or as a screening tool.^[54]

An elevated CA 19-9 level is found in 0.2% of an asymptomatic population older than 40 years. Of these elevations, 80% are false-positive results. If only symptomatic patients are studied, 4.3% have elevated CA 19-9 levels. Two thirds of these results are false positive.

Although no standardized role has been set for CA 19-9 in the diagnosis of pancreatic carcinoma, it has growing importance in the staging and follow-up of patients with this disease. Patients presenting with low levels of CA 19-9 (< 100 IU) are unlikely to have occult metastatic disease and therefore may not need a staging laparoscopy prior to resection if other imaging shows no advanced disease.

Additionally, during surgical, chemotherapeutic, and/or radiotherapeutic treatment for pancreatic cancer, a falling CA 19-9 seems to be a useful surrogate finding for clinical response to the therapy. If biliary obstruction is not present, a rising CA 19-9 suggests progressive disease.

Preoperative CA 19-9 levels may be of prognostic value, with high levels indicating poorer outcome and less chance of resectability.^{[55, 56]}Preoperative values above 50 U/mL have been shown to be associated with higher chances of recurrence. In contrast, a decrease in CA 19.9 levels during neoadjuvant therapy in locally advanced or borderline advanced pancreatic cancer is strong predictor of resectability and improved survival.^[57]

Carcinoembryonic antigen

Carcinoembryonic antigen (CEA) is a high–molecular weight glycoprotein found normally in fetal tissues. The reference range is 2.5 mg/mL or less. CEA has commonly been used as a tumor marker in other gastrointestinal malignancies, but only 40-45% of patients with pancreatic carcinoma have elevated CEA levels. In addition, benign and malignant conditions other than pancreatic cancer can lead to elevated CEA levels. Thus, CEA is not a sensitive or specific marker for pancreatic cancer.

Research

Many other tumor markers have been studied in pancreatic cancer, but none has yet been shown to have general clinical utility in this disorder. As with all cancers, there is growing interest in molecular diagnosis using powerful techniques, such as gene expression microarrays and proteomics. These novel tests are adding to the understanding of the basic defects causing pancreatic neoplasms and pathobiology. However, these are still research tools at present.

Computed Tomography

Because of its ubiquitous availability and its ability to image the whole abdomen and pelvis, abdominal CT scanning continues to be the mainstay of initial diagnostic modalities used for assessing patients suspected to have pancreatic carcinoma. (See the images below.)

Pancreatic cancer. Computerized tomographic scan showing a pancreatic adenocarcinoma of the pancreatic head. The gallbladder (gb) is distended because of biliary obstruction. The superior mesenteric artery (sma) is surrounded by tumor, making this an unresectable T4 lesion.

View Media Gallery

Pancreatic cancer. Abdominal CT scan of a small, vaguely seen, 2-cm pancreatic adenocarcinoma (mass) causing obstruction of both the common bile duct (cbd) and pancreatic duct (pd).

View Media Gallery

The quality of CT scanners has been rapidly evolving. The speed of image acquisition, 3D imaging, and slices as thin as 2-3 mm have revolutionized the technology.

Newer scanner models, using spiral (ie, helical) CT scanning with multiple detectors and dual or triple-phase contrast enhancement, have significantly improved the sensitivity and specificity of abdominal CT-scan findings in patients with pancreatic carcinoma.

Multidetector CT scanning (MDCT) using a pancreas protocol is at least as accurate as EUS in the overall determination of the resectability of pancreatic carcinoma. In fact, CT scanning may be more accurate than EUS in predicting involvement of the superior mesenteric artery.^[58]

National Comprehensive Cancer Network (NCCN) guidelines recommend MDCT angiography as the preferred imaging tool for dedicated pancreatic imaging. Thin (preferably sub-millimeter) axial sections should be acquired using a dual-phase pancreatic protocol, with images obtained in the pancreatic and portal venous phase of contrast enhancement. Coverage may be extended to cover the chest and pelvis for complete staging, depending on institutional preferences.^[30]

Other features of CT imaging include the following:

Because of a higher rate of enhancement by the normal pancreas, malignant tumors appear as lower-density lesions ^[59]; these are often associated with obstruction of the pancreatic duct
When lesions are visible, CT scanning can also be used to direct fine-needle aspiration of pancreatic masses
Small tumors can still be missed even with the most advanced CT-scanning techniques.

Go to Radiologic Diagnosis and Staging of Pancreatic Carcinoma for complete information on this topic.

Transcutaneous Ultrasonography

Even though it is less expensive and generally more readily available than CT scanning, TUS has less utility in pancreatic carcinoma than CT scanning, because the pancreas is often obscured by overlying gas from the stomach, duodenum, and colon.

Additionally, the depth of the pancreas from the abdominal wall limits transcutaneous ultrasonic imaging to lower frequency (2-5 MHz), and thus, a lower-resolution ultrasonogram is obtained. Therefore, TUS can help to detect only 60-70% of pancreatic carcinomas, and similar to CT scanning, more than 40% of the lesions smaller than 3 cm are missed.

However, TUS is very useful as an initial screening test in evaluating patients who present with possible obstructive jaundice. By helping to detect intrahepatic or extrahepatic bile duct dilation, abdominal ultrasonography can rapidly and accurately assess whether or not a patient has biliary obstruction. However, other studies, such as abdominal CT scanning, EUS, ERCP, or magnetic resonance cholangiopancreatography (MRCP), usually should then be performed to definitively diagnose the source of biliary obstruction.

Go to Radiologic Diagnosis and Staging of Pancreatic Carcinoma for complete information on this topic.

Endoscopic Ultrasonography

EUS obviates the physical limitations of TUS by placing a high-frequency, ultrasonographic transducer on an endoscope (see the first image below), which is then positioned in the stomach or duodenum endoscopically to help visualize the head, body, and tail of the pancreas. Unlike CT, the patient requires conscious sedation for this procedure. (Adenocarcinoma of the pancreatic head is seen in the second image below.)

Pancreatic cancer. Tip of linear array echoendoscope (Pentax FG 36UX) with 22-gauge aspiration needle exiting from biopsy channel. Insert shows magnification of aspiration needle tip. Note that the needle exits from the biopsy channel such that it appears continuously in the view of the ultrasonic transducer on the tip of the echoendoscope.

View Media Gallery

Pancreatic cancer. Endoscopic ultrasound of a 2.2-cm pancreatic adenocarcinoma of the head of the pancreas obstructing the common bile duct (CBD) but not invading the portal vein (PV) or superior mesenteric vein (SMV). Findings from endoscopic ultrasound–guided fine-needle aspiration revealed a moderately to poorly differentiated adenocarcinoma. Abdominal CT findings did not show this mass, and an attempt at endoscopic retrograde cholangiopancreatography at another institution was unsuccessful.

View Media Gallery

Additionally, because of the proximity of the pancreas to the EUS transducer, high-frequency ultrasonography (7.5-12 MHz) can be used to produce very high-resolution (submillimeter) images. Where expert EUS is available, it has proven to be the most sensitive and specific diagnostic test for pancreatic cancer. A negative endoscopic ultrasonogram is nearly 100% specific at ruling out the presence of a pancreatic neoplasm.

In numerous series, EUS has been found to have detection rates of 99-100% for all pancreatic carcinomas, including those smaller than 3 cm. EUS is as accurate as ERCP or MRCP for assessing the etiology of obstructive jaundice.

An additional significant diagnostic advantage is EUS-guided fine-needle aspiration, which allows for the simultaneous cytologic confirmation of pancreatic carcinoma at the time of EUS diagnosis.

EUS appears to be equivalent to dual-phase, spiral CT scanning for assessing tumor-resectability potential. It is probably superior to CT scanning as a means of assessing the T stage of the tumor, especially when the clinician is looking for portal vein involvement in pancreatic head lesions.

EUS is probably inferior to CT scanning in assessing arterial involvement and distant metastases.^[58]EUS and CT scanning are poor at detecting occult nodal involvement.

On the whole, the NCCN guidelines recommend EUS as complementary to CT. However, if no mass is evident in the pancreas on CT protocol imaging, the NCCN recommends EUS before other evaluation options. EUS is also valuable if there is possible involvement of blood vessels or lymph nodes.^[30]

Go to Radiologic Diagnosis and Staging of Pancreatic Carcinoma for complete information on this topic.

Endoscopic Retrograde Cholangiopancreatography

ERCP is a highly sensitive means of detecting pancreatic and/or biliary ductal abnormalities in pancreatic carcinoma. Among patients with pancreatic adenocarcinoma, 90-95% have abnormalities on ERCP findings. However, the changes observed on ERCP are not always highly specific for pancreatic carcinoma and can be difficult to differentiate from changes observed in patients with chronic pancreatitis.

ERCP is more invasive than the other diagnostic imaging modalities available for pancreatic carcinoma. ERCP also carries a 5-10% risk of significant complications. Because of this morbidity, it is usually reserved as a therapeutic procedure for biliary obstruction or for the diagnosis of unusual pancreatic neoplasms, such as intraductal pancreatic mucinous neoplasms (IPMN).

Brush cytology and forceps biopsy at the time of ERCP have been used to diagnose pancreatic carcinoma histologically; in most series, however, the yield of a cytologic diagnosis with these procedures has been less than 50%.

ERCP findings provide only limited staging information, but ERCP does have the advantage of allowing for therapeutic palliation of obstructive jaundice with either a plastic or metal biliary stent.

Magnetic Resonance Imaging

Interest in using MRI for abdominal imaging continues to grow. The role of MRI in pancreatic cancer has been less well studied than has the role of CT scanning, although the modality does not appear to be superior to spiral CT scanning. Dynamic, gadolinium-enhanced, 3D, gradient-echo MRI may offer enhanced sensitivity in the detection of small pancreatic lesions. However, in patients with jaundice, MRCP can be used as a noninvasive method for imaging the biliary tree and pancreatic duct.

Whether MRCP is as sensitive and specific for pancreaticobiliary pathology as other procedures is still being investigated.

Because of the difficulty of working within intense magnetic fields, MRI is limited in performing MRI-directed needle aspirations; however, this technology is undergoing rapid change.

The NCCN notes that MRI is most often used as a problem-solving tool, particularly for characterization of liver lesions that are indeterminate on CT; when pancreatic tumors are suspected, but are not visible on CT; or when contrast-enhanced CT cannot be obtained (eg, because of severe allergy to iodinated intravenous contrast material).^[30]

Go to Radiologic Diagnosis and Staging of Pancreatic Carcinoma for complete information on this topic.

PET Scanning

PET scanning uses 18F-fluorodeoxyglucose (FDG) to image the primary tumor and metastatic disease.

PET scanning appears to be especially useful in detecting occult metastatic disease. Its role in pancreatic cancer evaluation management is still under investigation. False-positive PET scans have been reported in pancreatitis.

By itself, PET scanning does not seem to offer additional benefits to high-quality CT scanning. However, studies in which PET scanning was combined with simultaneous CT scanning (PET-CT) suggested that PET-CT scanning is more sensitive than conventional imaging for the detection of pancreatic cancer and that PET-CT–scan findings sometimes change clinical management.^{[60, 61]}

The NCCN guidelines consider PET-CT an evolving technology; its role in the diagnosis of pancreatic cancer is not yet established.^[30]

Go to Radiologic Diagnosis and Staging of Pancreatic Carcinoma for complete information on this topic.

Needle Aspiration

The necessity of obtaining a cytologic or tissue diagnosis of pancreatic cancer prior to surgery remains controversial and is highly dependent on the institution.^[62]

Arguments in favor of preoperative biopsy include its ability to provide proof of pathology prior to surgery, exclude unusual pathology, and provide evidence of disease before the initiation of multidisciplinary treatment, such as neoadjuvant chemotherapy.

Arguments against preoperative biopsy of pancreatic lesions are that the biopsy results will not alter therapy, that biopsy may result in seeding and interfere with definitive surgery, and that the procedure increases the cost of care.

Studies of the risk of peritoneal contamination with CT-guided biopsy have suggested that this risk is actually very low. EUS-guided fine-needle aspiration provides the additional advantage of aspiration through tissue that would ultimately be included in the operative field should the patient undergo resection.

EUS-guided fine-needle aspiration has proven to be the most effective means for making a definitive cytologic diagnosis of pancreatic carcinoma.

Using EUS-guided fine-needle aspirations, a cytologic diagnosis can be made in 85-95% of patients. For example, a retrospective study by Turner et al found that EUS-guided fine needle aspiration was 80% accurate for the detection of pancreatic carcinoma and was 94% accurate when atypical and suspicious samples are considered positive.^[63]

A study by Micames et al suggested that percutaneous aspiration may be associated with a higher risk of peritoneal tumor spread than is aspiration with EUS.^[64]

Thus, for potentially resectable tumors, EUS-guided fine-needle aspiration is the preferred biopsy technique, if it is available and if a biopsy needs to be obtained. Cost-benefit analyses have also confirmed that it is the most cost-effective mode of tissue acquisition in suspected pancreatic cancer.

In a presentation delivered at the 2013 annual meeting of the American Society for Clinical Pathology, Huffman et al described a new risk-stratification system for EUS–guided fine-needle aspiration cytology results that can help determine when pancreatic lesions are malignant.^[65]The researchers identified the following 3 morphologic characteristics as being significantly associated with pancreatic malignancy:

Anisonucleosis
Single atypical epithelial cells
Mucinous metaplasia

The risk of malignancy was low when none of these 3 criteria are met, moderate when 1 was met, and high when 2 or 3 were met.^[65]

The yield of CT-guided fine-needle aspiration or biopsy findings is approximately 50-85% in the lesions that are visible on CT scanning.

Histologic Findings

As previously mentioned, of all pancreatic cancers, 80% are adenocarcinomas of the ductal epithelium. Only 2% of tumors of the exocrine pancreas are benign. Less common histologic appearances of exocrine pancreatic cancers include giant cell carcinoma, adenosquamous carcinoma, microglandular adenocarcinoma, mucinous carcinoma, cystadenocarcinoma, papillary cystic carcinoma, acinar cystadenocarcinoma, and acinar cell cystadenocarcinoma. Very rarely, primary connective tissue cancers of the pancreas can occur. The most common of these is primary pancreatic lymphoma. (See the images below.)

Pancreatic cancer. Hematoxylin and eosin stain of a pancreatic carcinoma. Note the intense desmoplastic response around the neoplastic cells. The large amount of fibrotic reaction in these tumors can make obtaining adequate tissue by fine-needle aspiration difficult.

View Media Gallery

Pancreatic cancer. Cytologic samples from fine-needle aspirations (rapid Papanicolaou stain) of pancreatic adenocarcinomas. (A) Well differentiated, (B) moderately differentiated, (C) moderate to poorly differentiated, (D) poorly differentiated tumor.

View Media Gallery

Cystic neoplasms of the pancreas account for fewer than 5% of all pancreatic tumors. These consist of benign serous cystadenomas, premalignant mucinous cystadenomas, and cystadenocarcinomas. Intraductal, mucinous pancreatic neoplasms can be benign or malignant and usually manifest as a cystic dilation of the pancreatic ductal system.

Patients can also develop tumors of the islet cells of the pancreas. These can be functionally inactive islet cell carcinomas or benign or malignant functioning tumors, such as insulinomas, glucagonomas, and gastrinomas. An estimated 40% of pancreatic endocrine tumors are nonfunctional; of these, up to 90% are malignant.^[66]

Islet cell tumors in patients with inherited syndromes such as multiple endocrine neoplasia are less likely to occur singly than in patients without these syndromes, and in the case of multiple endocrine neoplasia type 1, are more frequently gastrinomas than insulinomas. These variations of tumor function affect diagnosis and treatment strategies.^[66]

Germline Testing and Molecular Analysis

Pancreatic cancer is associated with numerous hereditary syndromes and the results of germline testing can help guide treatment selection. Whole-exome sequencing has been shown to find genomic lesions that are theoretically actionable in almost 50% of tumors and to result in a change in clinical management in up to 30% of cases. Although the main driver mutation is KRAS, molecular profiling can identify numerous other potentially actionable mutations.^[67]

National Comprehensive Cancer Network (NCCN) guidelines recommend considering germline testing in any patient diagnosed with pancreatic cancer and considering molecular analysis of tumors in those with metastatic disease. The NCCN panel has also strongly recommended molecular profiling of tumor tissue for actionable somatic mutations in patients with locally advanced or metastatic disease who are candidates for anticancer therapy, including (but not limited to) ALK, NRG1, NTRK, and ROS1 fusions; and BRAF, BRCA 1/2, HER2, KRAS, and PALB2 mutations.^[30]

Molecular profiling can detect mismatch repair deficiency (dMMR) and microsatellite instability–high (MSI-H) status. Across tumor types, patients with this phenotype may respond to pembrolizumab, which is now approved for patients with metastatic cancer of any type and dMMR/MSI-H status. Although dMMR/MSI-H is present in only 1% of patients with pancreatic cancer, in the pivotal trial of pembrolizumab, 83% of patients with dMMR pancreatic cancer showed a response.^[7]

jAmerican Society of Clinical Oncology (ASCO) guidelines recommend early testing for actionable genomic alterations (both germline and tumor) for patients who are likely to be potential candidates for additional treatment after first-line therapy.^[6]This includes testing for the following;

MSI/dMMR/
BRCA mutations (excluding variants of unknown significance)
NTRK gene fusions

Staging

Once an imaging modality has helped to establish a probable diagnosis of pancreatic cancer, the next issue is whether the lesion is amenable to surgical resection. Pancreatic masses are characterized as resectable, unresectable, or borderline resectable, on the basis of CT and/or EUS criteria.^[68]The designation of a mass as borderline resectable is usually based on the experience and technical skill of the surgeon involved in treatment, as well as on the overall health of the patient and on his or her wishes.

Only 20% of all patients presenting with pancreatic cancer are ultimately found to have easily resectable tumors with no evidence of local advancement. Noncurative resections for pancreatic carcinoma provide no survival benefit. Thus, to avoid operating on patients who cannot benefit from the operation, accurate preoperative staging is very important.

TNM classification

Cancer of the exocrine pancreas is classified by the tumor, node, metastasis (TNM) staging system. The staging for pancreatic cancer was modified by the American Joint Committee on Cancer (AJCC) in 2002.

Go to Radiologic Diagnosis and Staging of Pancreatic Carcinoma for complete information on this topic.

AJCC staging of pancreatic tumors is shown below.^[69]

Tumor (T):

TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
Tis - Carcinoma in situ
T1 - Tumor limited to the pancreas, 2 cm or smaller in greatest dimension
T2 - Tumor limited to the pancreas, larger than 2 cm in greatest dimension
T3 - Tumor extension beyond the pancreas (eg, duodenum, bile duct, portal or superior mesenteric vein) but not involving the celiac axis or superior mesenteric artery
T4 - Tumor involves the celiac axis or superior mesenteric arteries

Regional lymph nodes (N):

NX - Regional lymph nodes cannot be assessed
N0 - No regional lymph node metastasis
N1 - Regional lymph node metastasis

Distant metastasis (M):

MX - Distant metastasis cannot be assessed
M0 - No distant metastasis
M1 - Distant metastasis

Stage grouping for pancreatic cancer is as follows:

Stage 0 - Tis, N0, M0
Stage IA - T1, N0, M0
Stage IB - T2, N0, M0
Stage IIA - T3, N0, M0
Stage IIB - T1-3, N1, M0
Stage III - T4, Any N, M0
Stage IV - Any T, Any N, M1

At initial presentation, only 12% of patients present with stage I disease; 30% present with locally advanced disease and 52% present with disease metastatic to nodes or distant sites.^[44]

The image below visually demonstrates the stages of pancreatic cancer.

Pancreatic cancer. T staging for pancreatic carcinoma. T1 and T2 stages are confined to the pancreatic parenchyma. T3 lesions invade local structures such as the duodenum, bile duct, and/or major peripancreatic veins, and T4 lesions invade surrounding organs (eg, stomach, colon, liver) or invade major arteries such as the superior mesenteric or celiac arteries.

View Media Gallery

Imaging studies for staging

To date, studies show that EUS is approximately 70-80% accurate for correctly staging pancreatic carcinoma. EUS appears to better assess involvement of the portal vein/superior mesenteric vein.

NCCN guidelines recommend multi-detector computed tomography (MDCT) angiography, using a dual-phase pancreatic protocol, as the preferred modality for dedicated pancreatic imaging.^[30]This technique is especially good for assessing major arterial involvement or distant metastases.

EUS is better than CT scanning for detection of abnormal lymph nodes around the pancreas and celiac axis. Furthermore, with the addition of EUS-guided fine-needle aspiration, EUS can help cytologically document metastatic disease in suggestive lymph nodes.

Clinical staging

Although the TNM staging is important, it has limited practical use for non-metastatic pancreatic cancer. The clinical staging system (Evans et al), which is often used to determine resectability, relies on radiographic evidence of abutment or encasement of vascular structures, and the degree of narrowing of the superior mesenteric vein and/or portal vein, to categorize localized pancreatic cancer as resectable or borderline resectable, and also to define locally advanced unresectable pancreatic cancer. Those authors note that the majority of localized and borderline resectable cases proceed to surgery, but few cases of locally advanced pancreatic cancer become resectable after neoadjuvant therapy.^[70]

Preoperative staging laparoscopy

Some centers advocate performing a staging laparoscopy before proceeding to attempted resection. The purpose of the laparoscopic staging is to avoid subjecting patients with liver or peritoneal metastases to unnecessary surgery.

Some surgeons advocate the use of routine staging laparoscopy in all patients with pancreatic cancer. Their argument is that up to 20% of attempted pancreatic resections can be prevented because of the laparoscopic findings.

Others, including the NCCN panel, advise more a selective approach to staging laparoscopy, recommending its use in patients with any of the following indications^{[71, 72, 73, 30]}:

CA 19-9 level >150 U/mL
Low volume ascites
Tumors in the body of the pancreas
Borderline resectable tumors,
Tumor size > 3 cm
Common bile duct lymphadenopathy

Another argument for selective versus routine staging laparoscopy is the fact that in many cases where the tumor is deemed unresectable, laparoscopy would not have shown the vascular invasion or retroperitoneal invasion that ultimately leads to unresectability of tumor.

Evaluation Algorithm

Most patients suspected of having pancreatic carcinoma are initially studied with transcutaneous abdominal ultrasonography and/or spiral CT scanning (best done with dual-phase contrast, thin-cut pancreatic protocols). Patient management thereafter can vary from institution to institution, depending on local expertise, interest, and protocols. (See the image below.)

Algorithm for evaluation of a patient with suspected pancreatic cancer. CT scanning for definitive diagnosis and staging must be with thin-cut, multidetector, spiral CT scanning using dual-phase contrast imaging to allow for maximal information. This schema varies among institutions depending on local expertise, research interest, and therapeutic protocols for pancreatic carcinoma.

View Media Gallery

If patients have obvious hepatic metastatic disease based on initial TUS or CT findings, they undergo a CT- or TUS-guided biopsy of one of the liver metastases and then proceed to palliative therapy.

Patients with a suggested or definite pancreatic mass observed on abdominal CT scanning or TUS or those who are still considered to have pancreatic cancer but do not have an obvious pancreatic mass need to have more definitive imaging studies. This can be done using high-quality, thin-cut, multidetector CT scanning with dual-phase contrast and/or by using other procedures, such as EUS.

In the author's institution, where high-quality EUS and EUS-guided fine-needle aspiration are readily available, EUS plays a central role in the definitive diagnosis and staging of patients with pancreatic carcinoma.

If a pancreatic mass is observed on EUS images, EUS-guided fine-needle aspiration is performed to confirm the disease cytologically. At the same time, the condition is staged using EUS to determine resectability potential. Patients thought to have resectable tumors based on EUS findings proceed directly to operative intervention.

If tumors are deemed unresectable based on EUS findings and if patients have obstructive jaundice, they proceed directly to therapeutic stent placement with ERCP while under the same endoscopic sedation. Most patients then undergo dedicated pancreas protocol multidetector CT scanning to complete preoperative staging if the initial CT scan was not of the highest quality.

MRI, MRCP, and PET scanning are rarely used in the authors' evaluation algorithm unless other procedures are still nondiagnostic in a patient with a high suspicion of pancreatic cancer or if altered gastric anatomy precludes endoscopic ultrasonographic examination.

Patients with unresectable disease are offered chemotherapy for their disease. In institutions without EUS and EUS-guided fine-needle aspiration capabilities, spiral CT scanning with CT-guided pancreatic fine-needle aspiration or biopsy plays the central role in evaluation.

Abdominal TUS can also be used as an initial diagnostic study, especially in the jaundiced patient. However, this approach rarely obviates eventually performing abdominal CT scanning or EUS in patients in whom disease is a strong possibility.

ERCP is also used frequently for evaluating patients with jaundice or patients with possible pancreatic masses based on findings from imaging modalities if EUS is not available.

Treatment & Management

Cancer Facts & Figures 2022. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf. Accessed: May 27, 2022.
PDQ Adult Treatment Editorial Board. Pancreatic Cancer Treatment (PDQ®): Health Professional Version. February 3, 2021. [QxMD MEDLINE Link]. [Full Text].
Von Hoff DD, Arena FP, Chiorean EG, Infante JR, Moore MJ, Seay TE, et al. Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT). J Clin Oncol 30: 2012 (suppl 34; abstr LBA148), Presented January 25, 2013 at the 2013 Gastrointestinal Cancers Symposium, San Francisco, CA.
Mulcahy N. FDA Approves Nab-Paclitaxel for Pancreatic Cancer. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/810564. September 06, 2013; Accessed: September 09, 2018.
Yang ZY, Yuan JQ, Di MY, Zheng DY, Chen JZ, Ding H, et al. Gemcitabine plus erlotinib for advanced pancreatic cancer: a systematic review with meta-analysis. PLoS One. 2013. 8 (3):e57528. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Sohal DPS, Kennedy EB, Cinar P, Conroy T, Copur MS, Crane CH, et al. Metastatic Pancreatic Cancer: ASCO Guideline Update. J Clin Oncol. 2020 Aug 5. JCO2001364. [QxMD MEDLINE Link]. [Full Text].
Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28. 357 (6349):409-413. [QxMD MEDLINE Link]. [Full Text].
Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25. 381 (4):317-327. [QxMD MEDLINE Link].
Glazer ES, Neill KG, Frakes JM, Coppola D, Hodul PJ, Hoffe SE, et al. Systematic Review and Case Series Report of Acinar Cell Carcinoma of the Pancreas. Cancer Control. 2016 Oct. 23 (4):446-454. [QxMD MEDLINE Link]. [Full Text].
Hackeng WM, Hruban RH, Offerhaus GJ, Brosens LA. Surgical and molecular pathology of pancreatic neoplasms. Diagn Pathol. 2016 Jun 7. 11 (1):47. [QxMD MEDLINE Link]. [Full Text].
Abraham SC, Wu TT, Hruban RH, Lee JH, Yeo CJ, Conlon K, et al. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway. Am J Pathol. 2002 Mar. 160 (3):953-62. [QxMD MEDLINE Link]. [Full Text].
Chmielecki J, Hutchinson KE, Frampton GM, Chalmers ZR, Johnson A, Shi C, et al. Comprehensive genomic profiling of pancreatic acinar cell carcinomas identifies recurrent RAF fusions and frequent inactivation of DNA repair genes. Cancer Discov. 2014 Dec. 4 (12):1398-405. [QxMD MEDLINE Link]. [Full Text].
Jiao Y, Yonescu R, Offerhaus GJ, Klimstra DS, Maitra A, Eshleman JR, et al. Whole-exome sequencing of pancreatic neoplasms with acinar differentiation. J Pathol. 2014 Mar. 232 (4):428-35. [QxMD MEDLINE Link]. [Full Text].
Hsu JT, Yeh CN, Chen YR, Chen HM, Hwang TL, Jan YY, et al. Adenosquamous carcinoma of the pancreas. Digestion. 2005. 72 (2-3):104-8. [QxMD MEDLINE Link].
Borazanci E, Millis SZ, Korn R, Han H, Whatcott CJ, Gatalica Z, et al. Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review. World J Gastrointest Oncol. 2015 Sep 15. 7 (9):132-40. [QxMD MEDLINE Link]. [Full Text].
Katz MH, Taylor TH, Al-Refaie WB, Hanna MH, Imagawa DK, Anton-Culver H, et al. Adenosquamous versus adenocarcinoma of the pancreas: a population-based outcomes analysis. J Gastrointest Surg. 2011 Jan. 15 (1):165-74. [QxMD MEDLINE Link]. [Full Text].
Molina-Montes E, et al; PanGenEU Study Investigators. Pancreatic Cancer Risk in Relation to Lifetime Smoking Patterns, Tobacco Type, and Dose-Response Relationships. Cancer Epidemiol Biomarkers Prev. 2020 May. 29 (5):1009-1018. [QxMD MEDLINE Link]. [Full Text].
Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol. 2009 Dec. 6(12):699-708. [QxMD MEDLINE Link].
Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an update. Dig Dis. 2010. 28 (4-5):645-56. [QxMD MEDLINE Link].
Kirkegård J, Mortensen FV, Cronin-Fenton D. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis. Am J Gastroenterol. 2017 Sep. 112 (9):1366-1372. [QxMD MEDLINE Link].
Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML, et al. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA. 2009 Jun 24. 301(24):2553-62. [QxMD MEDLINE Link]. [Full Text].
Genkinger JM, Spiegelman D, Anderson KE, et al. A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int J Cancer. 2011 Oct 1. 129(7):1708-17. [QxMD MEDLINE Link]. [Full Text].
Urayama KY, Holcatova I, Janout V, et al. Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case-control study. Int J Cancer. 2011 Dec 15. 129(12):2875-84. [QxMD MEDLINE Link]. [Full Text].
Nkondjock A, Ghadirian P, Johnson KC, Krewski D. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr. 2005 Mar. 135(3):592-7. [QxMD MEDLINE Link].
Risch HA. Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity. J Natl Cancer Inst. 2003 Jul 2. 95(13):948-60. [QxMD MEDLINE Link].
Nöthlings U, Wilkens LR, Murphy SP, Hankin JH, Henderson BE, Kolonel LN. Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst. 2005 Oct 5. 97(19):1458-65. [QxMD MEDLINE Link].
Lin Y, Tamakoshi A, Kawamura T, et al. Risk of pancreatic cancer in relation to alcohol drinking, coffee consumption and medical history: findings from the Japan collaborative cohort study for evaluation of cancer risk. Int J Cancer. 2002 Jun 10. 99(5):742-6. [QxMD MEDLINE Link].
Ben Q, Xu M, Ning X, Liu J, Hong S, Huang W, et al. Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies. Eur J Cancer. 2011 Sep. 47 (13):1928-37. [QxMD MEDLINE Link].
Bosetti C, Rosato V, Li D, Silverman D, Petersen GM, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol. 2014 Oct. 25 (10):2065-72. [QxMD MEDLINE Link]. [Full Text].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Version 1.2022 — February 24, 2022; Accessed: June 3, 2022.
Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993 May 20. 328(20):1433-7. [QxMD MEDLINE Link].
Cowgill SM, Muscarella P. The genetics of pancreatic cancer. Am J Surg. 2003 Sep. 186(3):279-86. [QxMD MEDLINE Link].
Whitcomb DC. Genetics and alcohol: a lethal combination in pancreatic disease?. Alcohol Clin Exp Res. 2011 May. 35(5):838-42. [QxMD MEDLINE Link].
Mintziras I, Bartsch DK. Progress report: familial pancreatic cancer. Fam Cancer. 2019 Feb 22. 102(11):2564-9. [QxMD MEDLINE Link].
Kojima K, Vickers SM, Adsay NV, et al. Inactivation of Smad4 accelerates Kras(G12D)-mediated pancreatic neoplasia. Cancer Res. 2007 Sep 1. 67(17):8121-30. [QxMD MEDLINE Link].
Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26. 321(5897):1801-6. [QxMD MEDLINE Link]. [Full Text].
Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010 Oct 28. 467(7319):1114-7. [QxMD MEDLINE Link].
Campbell PJ, Yachida S, Mudie LJ, et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 2010 Oct 28. 467(7319):1109-13. [QxMD MEDLINE Link].
Kouvaraki MA, Shapiro SE, Cote GJ, Lee JE, Yao JC, Waguespack SG, et al. Management of pancreatic endocrine tumors in multiple endocrine neoplasia type 1. World J Surg. 2006 May. 30(5):643-53. [QxMD MEDLINE Link].
Blansfield JA, Choyke L, Morita SY, Choyke PL, Pingpank JF, Alexander HR, et al. Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs). Surgery. 2007 Dec. 142(6):814-8; discussion 818.e1-2. [QxMD MEDLINE Link].
Groen EJ, Roos A, Muntinghe FL, Enting RH, de Vries J, Kleibeuker JH, et al. Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol. 2008 Sep. 15(9):2439-50. [QxMD MEDLINE Link].
Lynch HT, Fusaro RM, Lynch JF, Brand R. Pancreatic cancer and the FAMMM syndrome. Fam Cancer. 2008. 7(1):103-12. [QxMD MEDLINE Link].
[Guideline] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf. Version 2.2022 — March 9, 2022; Accessed: June 1, 2022.
Cancer Stat Facts: Pancreatic Cancer. National Cancer Institute. Available at https://seer.cancer.gov/statfacts/html/pancreas.html. Accessed: May 31, 2022.
Arnold LD, Patel AV, Yan Y, Jacobs EJ, Thun MJ, Calle EE, et al. Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity?. Cancer Epidemiol Biomarkers Prev. 2009 Sep. 18(9):2397-405. [QxMD MEDLINE Link].
Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol. 2019 Feb. 10 (1):10-27. [QxMD MEDLINE Link]. [Full Text].
Key Statistics for Pancreatic Cancer. American Cancer Society. Available at https://www.cancer.org/cancer/pancreatic-cancer/about/key-statistics.html. January 21, 2022; Accessed: May 27, 2022.
Tingle SJ, Severs GR, Goodfellow M, Moir JA, White SA. NARCA: A novel prognostic scoring system using neutrophil-albumin ratio and Ca19-9 to predict overall survival in palliative pancreatic cancer. J Surg Oncol. 2018 Sep 9. [QxMD MEDLINE Link].
Can Pancreatic Cancer Be Prevented?. American Cancer Society. Available at https://www.cancer.org/cancer/pancreatic-cancer/causes-risks-prevention/prevention.html. June 9, 2020; Accessed: June 2, 2022.
Ferreira M, Moreira H, Esperto H, Carvalho A. Depression preceding the diagnosis of pancreatic cancer. BMJ Case Rep. 2021 Feb 4. 14 (2):[QxMD MEDLINE Link].
Jarrin Jara MD, Gautam AS, Peesapati VSR, Sadik M, Khan S. The Role of Interleukin-6 and Inflammatory Cytokines in Pancreatic Cancer-Associated Depression. Cureus. 2020 Aug 23. 12 (8):e9969. [QxMD MEDLINE Link]. [Full Text].
Turaga KK, Malafa MP, Jacobsen PB, Schell MJ, Sarr MG. Suicide in patients with pancreatic cancer. Cancer. 2011 Feb 1. 117(3):642-7. [QxMD MEDLINE Link].
Epstein AS, O'Reilly EM. Exocrine pancreas cancer and thromboembolic events: a systematic literature review. J Natl Compr Canc Netw. 2012 Jul 1. 10 (7):835-46. [QxMD MEDLINE Link].
[Guideline] Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006 Nov 20. 24(33):5313-27. [QxMD MEDLINE Link].
Fujioka S, Misawa T, Okamoto T, Gocho T, Futagawa Y, Ishida Y, et al. Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels for the evaluation of curability and resectability in patients with pancreatic adenocarcinoma. J Hepatobiliary Pancreat Surg. 2007. 14(6):539-44. [QxMD MEDLINE Link].
Kang CM, Kim JY, Choi GH, Kim KS, Choi JS, Lee WJ. The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer. J Surg Res. 2007 Jun 1. 140(1):31-5. [QxMD MEDLINE Link].
Boone BA, Steve J, Zenati MS, Hogg ME, Singhi AD, Bartlett DL, et al. Serum CA 19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol. 2014 Dec. 21 (13):4351-8. [QxMD MEDLINE Link].
Horton KM, Fishman EK. Multidetector CT angiography of pancreatic carcinoma: part I, evaluation of arterial involvement. AJR Am J Roentgenol. 2002 Apr. 178(4):827-31. [QxMD MEDLINE Link].
Horton KM, Fishman EK. Adenocarcinoma of the pancreas: CT imaging. Radiol Clin North Am. 2002 Dec. 40(6):1263-72. [QxMD MEDLINE Link].
Kauhanen SP, Komar G, Seppänen MP, Dean KI, Minn HR, Kajander SA, et al. A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer. Ann Surg. 2009 Dec. 250(6):957-63. [QxMD MEDLINE Link].
Farma JM, Santillan AA, Melis M, Walters J, Belinc D, Chen DT, et al. PET/CT fusion scan enhances CT staging in patients with pancreatic neoplasms. Ann Surg Oncol. 2008 Sep. 15(9):2465-71. [QxMD MEDLINE Link].
Itani KM, Taylor TV, Green LK. Needle biopsy for suspicious lesions of the head of the pancreas: pitfalls and implications for therapy. J Gastrointest Surg. 1997 Jul-Aug. 1(4):337-41. [QxMD MEDLINE Link].
Turner BG, Cizginer S, Agarwal D, Yang J, Pitman MB, Brugge WR. Diagnosis of pancreatic neoplasia with EUS and FNA: a report of accuracy. Gastrointest Endosc. 2010 Jan. 71(1):91-8. [QxMD MEDLINE Link].
Micames C, Jowell PS, White R, Paulson E, Nelson R, Morse M, et al. Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA. Gastrointest Endosc. 2003 Nov. 58(5):690-5. [QxMD MEDLINE Link].
Louden K. New risk factors proposed for pancreatic cancer. Medscape Medical News. September 26, 2013. [Full Text].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Neuroendocrine Tumors. Available at http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Version 3.2021 — August 13, 2021; Accessed: October 6, 2021.
Tempero MA. NCCN Guidelines Updates: Pancreatic Cancer. J Natl Compr Canc Netw. 2019 May 1. 17 (5.5):603-605. [QxMD MEDLINE Link]. [Full Text].
Hong SB, Lee SS, Kim JH, Kim HJ, Byun JH, Hong SM, et al. Pancreatic Cancer CT: Prediction of Resectability according to NCCN Criteria. Radiology. 2018 Dec. 289 (3):710-718. [QxMD MEDLINE Link].
Katz MH, Hwang R, Fleming JB, Evans DB. Tumor-node-metastasis staging of pancreatic adenocarcinoma. CA Cancer J Clin. 2008 Mar-Apr. 58(2):111-25. [QxMD MEDLINE Link].
Evans DB, George B, Tsai S. Non-metastatic Pancreatic Cancer: Resectable, Borderline Resectable, and Locally Advanced-Definitions of Increasing Importance for the Optimal Delivery of Multimodality Therapy. Ann Surg Oncol. 2015 Oct. 22 (11):3409-13. [QxMD MEDLINE Link].
Callery MP, Strasberg SM, Doherty GM, Soper NJ, Norton JA. Staging laparoscopy with laparoscopic ultrasonography: optimizing resectability in hepatobiliary and pancreatic malignancy. J Am Coll Surg. 1997 Jul. 185(1):33-9. [QxMD MEDLINE Link].
Vollmer CM, Drebin JA, Middleton WD, Teefey SA, Linehan DC, Soper NJ. Utility of staging laparoscopy in subsets of peripancreatic and biliary malignancies. Ann Surg. 2002 Jan. 235(1):1-7. [QxMD MEDLINE Link].
Jarnagin WR, Bodniewicz J, Dougherty E, Conlon K, Blumgart LH, Fong Y. A prospective analysis of staging laparoscopy in patients with primary and secondary hepatobiliary malignancies. J Gastrointest Surg. 2000 Jan-Feb. 4(1):34-43. [QxMD MEDLINE Link].
Al-Haddad M, Martin JK, Nguyen J, Pungpapong S, Raimondo M, Woodward T. Vascular resection and reconstruction for pancreatic malignancy: a single center survival study. J Gastrointest Surg. 2007 Sep. 11(9):1168-74. [QxMD MEDLINE Link].
de Rooij T, Klompmaker S, Abu Hilal M, Kendrick ML, Busch OR, Besselink MG. Laparoscopic pancreatic surgery for benign and malignant disease. Nat Rev Gastroenterol Hepatol. 2016 Apr. 13 (4):227-38. [QxMD MEDLINE Link].
Pisters PW, Abbruzzese JL, Janjan NA, Cleary KR, Charnsangavej C, Goswitz MS. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998 Dec. 16(12):3843-50. [QxMD MEDLINE Link].
Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol. 2002 May 15. 20(10):2537-44. [QxMD MEDLINE Link].
Dhir M, Zenati MS, Hamad A, Singhi AD, Bahary N, Hogg ME, et al. FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma. Ann Surg Oncol. 2018 Jul. 25 (7):1896-1903. [QxMD MEDLINE Link].
Kadera BE, Sunjaya DB, Isacoff WH, Li L, Hines OJ, Tomlinson JS, et al. Locally Advanced Pancreatic Cancer: Association Between Prolonged Preoperative Treatment and Lymph-Node Negativity and Overall Survival. JAMA Surg. 2013 Dec 4. [QxMD MEDLINE Link].
Boggs W. Preop Chemo for Locally Advanced Pancreatic Cancer Associated With 'Excellent' Survival. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/817801. Accessed: December 22, 2013.
Loehrer PJ Sr, Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2011 Nov 1. 29(31):4105-12. [QxMD MEDLINE Link].
Sohal DPS, Duong M, Ahmad SA, Gandhi NS, Beg MS, Wang-Gillam A, et al. Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Mar 1. 7 (3):421-427. [QxMD MEDLINE Link]. [Full Text].
McPhee JT, Hill JS, Whalen GF, Zayaruzny M, Litwin DE, Sullivan ME. Perioperative mortality for pancreatectomy: a national perspective. Ann Surg. 2007 Aug. 246(2):246-53. [QxMD MEDLINE Link].
Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007 Nov. 142(5):761-8. [QxMD MEDLINE Link].
van der Gaag NA, Rauws EA, van Eijck CH, Bruno MJ, van der Harst E, Kubben FJ, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010 Jan 14. 362(2):129-37. [QxMD MEDLINE Link].
Limongelli P, Pai M, Bansi D, Thiallinagram A, Tait P, Jackson J. Correlation between preoperative biliary drainage, bile duct contamination, and postoperative outcomes for pancreatic surgery. Surgery. 2007 Sep. 142(3):313-8. [QxMD MEDLINE Link].
Pawlik TM, Gleisner AL, Cameron JL, Winter JM, Assumpcao L, Lillemoe KD. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007 May. 141(5):610-8. [QxMD MEDLINE Link].
House MG, Gonen M, Jarnagin WR, DAngelica M, DeMatteo RP, Fong Y. Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer. J Gastrointest Surg. 2007 Nov. 11(11):1549-55. [QxMD MEDLINE Link].
Gallagher S, Zervos E, Murr M. Distal Pancreatectomy. Von Hoff, Evans, Hruban. Pancreatic Cancer. Sudbury, Mass: Jones and Bartlett; 2005. 20.
Muller MW, Friess H, Kleeff J, Dahmen R, Wagner M, Hinz U, et al. Is there still a role for total pancreatectomy?. Ann Surg. 2007 Dec. 246(6):966-74; discussion 974-5. [QxMD MEDLINE Link].
Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985 Aug. 120(8):899-903. [QxMD MEDLINE Link].
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18. 350(12):1200-10. [QxMD MEDLINE Link].
Yang R, Cheung MC, Byrne MM, Jin X, Montero AJ, Jones C, et al. Survival effects of adjuvant chemoradiotherapy after resection for pancreatic carcinoma. Arch Surg. 2010 Jan. 145(1):49-56. [QxMD MEDLINE Link].
Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007 Jan 17. 297(3):267-77. [QxMD MEDLINE Link].
Neuhaus P, Riess H, Post S. CONKO-001:Final results of the randomized, prospective multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancratic cancer. J Clin Oncol. 2008. 26(15S):204s(abstract LBA4504).
Conroy T, Hammel P, Hebbar M, et al, Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018 Dec 20. 379 (25):2395-2406. [QxMD MEDLINE Link]. [Full Text].
Neoptolemos JP, et al; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11. 389 (10073):1011-1024. [QxMD MEDLINE Link]. [Full Text].
Nelson R. Best Survival Ever in Resectable Pancreatic Cancer. Medscape Medical News. Available at https://www.medscape.com/viewarticle/897600. June 04, 2018; Accessed: January 10, 2020.
Tempero M, O'Reilly E, Van Cutsem E, et al. LBA-1 Phase 3 APACT trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P + Gem) vs gemcitabine (Gem) alone in patients with resected pancreatic cancer (PC): Updated 5-year overall survival. Ann Oncol. July 01, 2021. 32 (suppl 3):S226. [Full Text].
[Guideline] eUpdate – Cancer of the Pancreas Treatment Recommendations. European Society for Medical Oncology. Available at https://www.esmo.org/guidelines/guidelines-by-topic/gastrointestinal-cancers/pancreatic-cancer/eupdate-cancer-of-the-pancreas-treatment-recommendations. March 15, 2019; Accessed: June 3, 2022.
Wan G, Sun X, Li F, Wang X, Li C, Li H, et al. Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients: a Systematic Review and Meta-Analysis. Cell Physiol Biochem. 2018 Sep 5. 49 (3):I. [QxMD MEDLINE Link]. [Full Text].
Frere C, Crichi B, Bournet B, Canivet C, Abdallah NA, Buscail L, et al. Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cancers (Basel). 2020 Jul 24. 12 (8):[QxMD MEDLINE Link]. [Full Text].
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12. 364(19):1817-25. [QxMD MEDLINE Link]. [Full Text].
Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, et al. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007 Oct 20. 25(30):4787-92. [QxMD MEDLINE Link].
Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2015 Nov 29. [QxMD MEDLINE Link].
Jameson GS, Borazanci E, Babiker HM, Poplin E, Niewiarowska AA, Gordon MS, et al. Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment Among Patients With Advanced Pancreatic Cancer: A Phase 1b/2 Pilot Clinical Trial. JAMA Oncol. 2019 Oct 3. [QxMD MEDLINE Link]. [Full Text].
O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, et al. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 1. 38 (13):1378-1388. [QxMD MEDLINE Link]. [Full Text].
Chalasani P, Kurtin S, Dragovich T. Response to a third-line mitomycin C (MMC)-based chemotherapy in a patient with metastatic pancreatic adenocarcinoma carrying germline BRCA2 mutation. JOP. 2008 May 8. 9 (3):305-8. [QxMD MEDLINE Link].
Shroff RT, Hendifar A, McWilliams RR, Geva R, Epelbaum R, Rolfe L, et al. Rucaparib Monotherapy in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation. JCO Precis Oncol. 2018. 2018:JCO2001364. [QxMD MEDLINE Link]. [Full Text].
O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, et al. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 1. 38 (13):1378-1388. [QxMD MEDLINE Link]. [Full Text].
Chiorean EG, Guthrie KA, Philip PA, Swisher EM, Jalikis F, Pishvaian MJ, et al. Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513. Clin Cancer Res. 2021 Dec 1. 27 (23):6314-6322. [QxMD MEDLINE Link].
[Guideline] U.S. Preventive Services Task Force. Final Recommendation Statement: Pancreatic Cancer: Screening. Available at https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/pancreatic-cancer-screening1. October 2019; Accessed: January 10, 2020.
American Academy of Family Physicians. Summary of Recommendations for Clinical Preventive Services. Leawood KS: American Academy of Family Physicians; November 2015. [Full Text].
Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 Mar. 62 (3):339-47. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Goggins M, et al; International Cancer of the Pancreas Screening (CAPS) consortium. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020 Jan. 69 (1):7-17. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Aslanian HR, Lee JH, Canto MI. AGA Clinical Practice Update on Pancreas Cancer Screening in High Risk Individuals: Expert Review. Gastroenterology. 2020 May 13. [QxMD MEDLINE Link].
[Guideline] Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2015 Sep. 26 Suppl 5:v56-v68. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, et al. Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Jul 20. 34 (21):2541-56. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Khorana AA, McKernin SE, Berlin J, Hong TS, Maitra A, Moravek C, et al. Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2019 Aug 10. 37 (23):2082-2088. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Balaban EP, Mangu PB, Khorana AA, Shah MA, Mukherjee S, Crane CH, et al. Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Aug 1. 34 (22):2654-68. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Sohal DP, Mangu PB, Khorana AA, Shah MA, Philip PA, O'Reilly EM, et al. Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Aug 10. 34 (23):2784-96. [QxMD MEDLINE Link]. [Full Text].
[Guideline] eUpdate – Cancer of the Pancreas Treatment Recommendations. European Society for Medical Oncology. Available at https://www.esmo.org/guidelines/gastrointestinal-cancers/pancreatic-cancer/eupdate-cancer-of-the-pancreas-treatment-recommendations2. June 20, 2017; Accessed: October 6, 2021.
Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV, et al. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2012 Jan-Feb. 62 (1):30-67. [QxMD MEDLINE Link].
Soto JL, Barbera VM, Saceda M, Carrato A. Molecular biology of exocrine pancreatic cancer. Clin Transl Oncol. May 2006. 8:306-12. [QxMD MEDLINE Link].
Hahn SA, Kern SE. Molecular genetics of exocrine pancreatic neoplasms. Surg Clin North Am. 1995 Oct. 75(5):857-69. [QxMD MEDLINE Link].
Shi C, Daniels JA, Hruban RH. Molecular characterization of pancreatic neoplasms. Adv Anat Pathol. 2008 Jul. 15(4):185-95. [QxMD MEDLINE Link].
Goggins M, Schutte M, Lu J, et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 1996 Dec 1. 56(23):5360-4. [QxMD MEDLINE Link].
Yan L, McFaul C, Howes N, Leslie J, Lancaster G, Wong T, et al. Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups. Gastroenterology. June 2005. 128:2124-30. [QxMD MEDLINE Link].
Rombouts SJ, Vogel JA, van Santvoort HC, van Lienden KP, van Hillegersberg R, Busch OR, et al. Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer. Br J Surg. 2015 Feb. 102 (3):182-93. [QxMD MEDLINE Link].
Dreyer SB, Upstill-Goddard R, Paulus-Hock V, et al. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. 2020 Oct 8. [QxMD MEDLINE Link].
Vervenne W, Bennouna J, Humblett Y. A randomized double-blind, placebo (P) controlled, multicenter phase III trial to evaluate the efficacy and safety of adding bevacizumab (B) to erlotinib (E) and gemcitabine (G) in patients (pts) with metastatic pancreatic cancer. J Clin Oncol. 2008. 26(15S):214s(abstract 4507).
Loehrer P, Powell M, Cardenes H. A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer:E4201. J Clin Oncol. 2008. 26(15S):214(abstract 4506).
Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, et al. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol. 2008 Aug 1. 26(22):3695-701. [QxMD MEDLINE Link].
Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20. 27(33):5513-8. [QxMD MEDLINE Link].

Media Gallery

Pancreatic cancer. Gross section of an adenocarcinoma of the pancreas measuring 5 × 6 cm resected from the pancreatic body and tail. Although the tumor was considered to have been fully resected and had not spread to any nodes, the patient died of recurrent cancer within 1 year.
Pancreatic cancer. Hematoxylin and eosin stain of a pancreatic carcinoma. Note the intense desmoplastic response around the neoplastic cells. The large amount of fibrotic reaction in these tumors can make obtaining adequate tissue by fine-needle aspiration difficult.
Pancreatic cancer. T staging for pancreatic carcinoma. T1 and T2 stages are confined to the pancreatic parenchyma. T3 lesions invade local structures such as the duodenum, bile duct, and/or major peripancreatic veins, and T4 lesions invade surrounding organs (eg, stomach, colon, liver) or invade major arteries such as the superior mesenteric or celiac arteries.
Pancreatic cancer. Computerized tomographic scan showing a pancreatic adenocarcinoma of the pancreatic head. The gallbladder (gb) is distended because of biliary obstruction. The superior mesenteric artery (sma) is surrounded by tumor, making this an unresectable T4 lesion.
Pancreatic cancer. Abdominal CT scan of a small, vaguely seen, 2-cm pancreatic adenocarcinoma (mass) causing obstruction of both the common bile duct (cbd) and pancreatic duct (pd).
Pancreatic cancer. Endoscopic ultrasound of a 2.2-cm pancreatic adenocarcinoma of the head of the pancreas obstructing the common bile duct (CBD) but not invading the portal vein (PV) or superior mesenteric vein (SMV). Findings from endoscopic ultrasound–guided fine-needle aspiration revealed a moderately to poorly differentiated adenocarcinoma. Abdominal CT findings did not show this mass, and an attempt at endoscopic retrograde cholangiopancreatography at another institution was unsuccessful.
Algorithm for evaluation of a patient with suspected pancreatic cancer. CT scanning for definitive diagnosis and staging must be with thin-cut, multidetector, spiral CT scanning using dual-phase contrast imaging to allow for maximal information. This schema varies among institutions depending on local expertise, research interest, and therapeutic protocols for pancreatic carcinoma.
Pancreatic cancer. Tip of linear array echoendoscope (Pentax FG 36UX) with 22-gauge aspiration needle exiting from biopsy channel. Insert shows magnification of aspiration needle tip. Note that the needle exits from the biopsy channel such that it appears continuously in the view of the ultrasonic transducer on the tip of the echoendoscope.
Pancreatic cancer. Cytologic samples from fine-needle aspirations (rapid Papanicolaou stain) of pancreatic adenocarcinomas. (A) Well differentiated, (B) moderately differentiated, (C) moderate to poorly differentiated, (D) poorly differentiated tumor.

of 9

Pancreatic Cancer Workup

Approach Considerations

Laboratory Findings