Practice EssentialsPancreatic cancer is the fourth leading cause of cancer deaths among men and women, being responsible for 6% of all cancer-related deaths. Approximately 75% of all pancreatic carcinomas occur within the head or neck of the pancreas, 15-20% occur in the body of the pancreas, and 5-10% occur in the tail.

Essential update: Pancreatoduodenectomy may be done without biopsy proof in select cases

According to a consensus statement from the International Study Group of Pancreatic Surgery (ISGPS), pancreatoduodenectomy may be performed in the absence of positive histology in patients with a solid mass suspicious for malignancy.[1,

2] Pancreatoduodenectomy can also be recommended for patients with chronic pancreatitis without histologic proof of malignancy.

The ISGPS states that a positive biopsy for malignancy is mandatory if neoadjuvant chemotherapy is administered before exploration is performed.[2] In patients with suspected autoimmune pancreatitis, biopsy and testing of serum levels of immunoglobulin G4 (IgG4) should be performed. If no malignancy is found, corticosteroid treatment may eliminate the need for surgery.

Signs and symptoms

The initial symptoms of pancreatic cancer are often quite nonspecific and subtle in onset. Patients typically report the gradual onset of nonspecific symptoms such as anorexia, malaise, nausea, fatigue, and midepigastric or back pain.

Patients with pancreatic cancer may present with the following signs and symptoms:

Significant weight loss: Characteristic feature of pancreatic cancer Midepigastric pain: Common symptom of pancreatic cancer, sometimes with radiation of

the pain to the midback or lower-back region Often, unrelenting pain: Nighttime pain often a predominant complaint Onset of diabetes mellitus within the previous year Painless obstructive jaundice: Most characteristic sign of cancer of head of the pancreas Pruritus: Often the patient's most distressing symptom Depression Migratory thrombophlebitis (ie, Trousseau sign) and venous thrombosis: May be the first

presentation Palpable gallbladder (ie, Courvoisier sign) Developing, advanced intra-abdominal disease: Presence of ascites, a palpable abdominal

mass, hepatomegaly from liver metastases, or splenomegaly from portal vein obstruction Advanced disease: Paraumbilical subcutaneous metastases (or Sister Mary Joseph nodule

or nodules) Possible presence of palpable metastatic mass in the rectal pouch (Blumer's shelf) Possible presence of palpable metastatic cervical nodes: Nodes may be palpable behind

the medial end of the left clavicle (Virchow's node) and other areas in the cervical regionSee Clinical Presentation for more detail.

Diagnosis

Pancreatic cancer is notoriously difficult to diagnose in its early stages.

Testing

The laboratory findings in patients with pancreatic cancer are usually nonspecific. Patients with advanced pancreatic cancers and weight loss may have general laboratory evidence of malnutrition (eg, low serum albumin or cholesterol level).

Potentially useful tests in patients with suspected pancreatic cancer include the following:

CBC count Hepatobiliary tests: Patients with obstructive jaundice show significant elevations in

bilirubin (conjugated and total), ALP, GGT, and, to a lesser extent, AST and ALT Serum amylase and/or lipase levels: Elevated in less than 50% of patients with resectable

pancreatic cancers and in only 25% of patients with unresectable tumors Tumor markers such as CA 19-9 antigen and CEA: 75-85% have elevated CA 19-9 levels;

40-45% have elevated CEA levelsImaging studies

Imaging studies that aid in the diagnosis of pancreatic cancer include the following:

CT scanning Transcutaneous ultrasonography Endoscopic ultrasonography Magnetic resonance imaging Endoscopic retrograde cholangiopancreatography Positron emission tomography scanning

See Workup for more detail.

Management

Surgery is the primary mode of treatment for pancreatic cancer. However, an important role exists for chemotherapy and/or radiation therapy.

Surgical options

Curative resection options include the following:

Pancreaticoduodenectomy (Whipple Procedure), with/without sparing of the pylorus Total pancreatectomy Distal pancreatectomy

Chemotherapy

Antineoplastic agents and combinations of agents used in managing pancreatic carcinoma include the following:

Gemcitabine monotherapy: For symptomatic patients with metastatic or locally advanced unresectable disease with poor performance status[3]

GTX regimen (gemcitabine, docetaxel and capecitabine)[3]

Gemcitabine and nab-paclitaxel[3]

FOLFIRINOX (LV5-FU [leucovorin/5-fluorouracil] plus oxaliplatin plus irinotecan): National Comprehensive Cancer Network recommends as first-line treatment for patients with metastatic or locally advanced unresectable disease with good performance status[3, 4]

Paclitaxel protein bound 125 mg/m2 plus gemcitabine 1000 mg/m2 IV over 30-40 min on Days 1, 8, and 15 of each 28-day cycle[5, 6]

5-FU Erlotinib plus gemcitabine Capecitabine monotherapy or capecitabine plus erlotinib: May provide second-line therapy

benefit in patient's refractory to gemcitabine[7]

Adjuvant therapy with gemcitabine is accepted as standard therapy for surgically resected pancreatic cancer.[8]

Neoadjuvant therapy

The use of chemotherapy and/or radiation therapy in the neoadjuvant setting has been a source of controversy. The rationale for using neoadjuvant therapy includes the assertions that (1) pancreatic cancer is a systemic disease and should be treated systemically from the start, (2) patients will be able to tolerate the toxic effects of chemotherapy more readily before undergoing major pancreatic resection than after, and (3) the tumor will shrink with neoadjuvant therapy, and the resection will be less cumbersome, leading to an improved overall survival.

Palliative Therapy

Palliative therapy may be administered for the following conditions associated with pancreatic cancer:

Pain: Pain relief is crucial for patients not undergoing resection for pancreatic cancer; narcotic analgesics should be used early and in adequate dosages

Jaundice: Obstructive jaundice warrants palliation if the patient has pruritus or right upper quadrant pain or has developed cholangitis

Duodenal obstruction secondary to pancreatic carcinoma: Can be palliated operatively with a gastrojejunostomy or an endoscopic procedure