Complications and Comorbidities> Hematology/Malignancy>

DEFINITION

• Exocrine pancreatic cancers are adenocarcinomas of pancreatic ductal and acinar cells and their stem cells.
• Endocrine (islet-cell) pancreatic cancers are classified by the hormones that they secrete: insulin, gastrin, glucagon, somatostatin, or VIP

EPIDEMIOLOGY

• Fourth leading cause of cancer-related death in the United States among both men and women. (Jemal)
• Rare before the age of 45, but the incidence rises sharply thereafter.
• Incidence is greater in males than females (male-to-female ratio 1.3:1) and in blacks (14.8 per 100,000 in black males compared to 8.8 per 100,000 in the general population).
• Compared to their non-diabetic counterparts, adults with type 1 or type 2 diabetes are two-fold more likely to develop pancreatic cancer. (Everhart)
• Abnormal glucose metabolism and insulin resistance have also been associated with the subsequent risk of pancreatic cancer. (Gapstur)
• Approximately 1% of diabetes subjects over age 50 years will be diagnosed with pancreatic cancer within 3 years of first meeting criteria for diabetes.(Chari)
• There is good evidence that diabetes leads to cancer, not the reverse (i.e. early cancer leading to diabetes due to destruction of islet cells) (Stolzenberg-Solomon)
• Other risk factors: cigarette smoking, obesity, diet, physical inactivity, alcohol, and potentially aspirin use. (Schernhammer)

DIAGNOSIS

• Diagnosis and staging can often be done by imaging rather than exploratory surgery.
• Endoscopic ultrasound: 90% sensitivity, 90% specificity, and useful for staging.
• Pancreas-dedicated CT scan: 90% sensitivity, 95% specificity, and useful for staging.
• Ultrasound: 80% sensitivity, 90% specificity
• Endoscopic retrograde cholangiopancreatography (ERCP): 90% sensitivity, 90% specificity
• MRI scan: 90% sensitivity, 90% specificity
• Fine needle aspirate: 90% sensitivity, 98% specificity
• Serum markers (CA 19-9) have good sensitivity and specificity on larger tumors, but have limited role in diagnosing small, surgically resectable cancers.

SIGNS AND SYMPTOMS

• History: abdominal pain, appetite loss, jaundice, pale-colored stools, unusual belching, weight loss, and unusual bloating.
• Physical findings: abdominal mass, ascites, nontender but palpable gallbladder, left supraclavicular lymphadenopathy (Virchow's node)
• The majority of patients have unresectable disease by the time symptoms occur.
• New onset glucose intolerance or diabetes arising in a thin older adult may raise suspicion of pancreatic cancer (Chari).
• The most common sites of distant metastases include the liver, peritoneum, lungs, and less frequently, bone.
• Many patients with pancreatic cancer have a hypercoagulable state (Trousseau's syndrome).

CLINICAL TREATMENT

• Treatment depends on the stage of cancer, and whether the patient is a good surgical candidate (only 15 - 20 % candidates for pancreatectomy).
• Surgical treatments for pancreatic head tumors: standard pancreaticoduodenectomy (Whipple procedure), total pancreatectomy, regional pancreatectomy, or pylorus-preserving pancreaticoduodenectomy
• Pancreatic tail tumors can be resected by distal subtotal pancreatectomy combined with splenectomy.
• There is no consensus regarding the optimal management (chemotherapy vs. chemoradiotherapy) of patients after resection of a pancreatic adenocarcinoma.
• The optimal management of locally advanced, unresectable nonmetastatic disease is also controversial. Therapeutic options: radiation therapy (RT) alone, chemoradiotherapy, and chemotherapy alone.
• In advanced pancreatic cancer, systemic chemotherapy (gemcitabine monotherapy or 5-FU-based combination therapy can improve disease-related symptoms, and survival when compared to best supportive care alone (Yip).
• Post-pancreatectomy diabetes can occur depending on type of surgery.

FOLLOW UP

• Regardless of the therapy chosen, median survival is approximately 8 to 12 months for patients with locally advanced unresectable disease, and 3-6 months for those who present with metastases.
• The focus for most pancreatic cancer patients eventually becomes palliation of symptoms.
• Palliation of jaundice is usually accomplished by the placement of an expandable metal stent.
• Duodenal obstruction can be addressed by posterior retrocolic gastrojejunostomy whenever biliary bypass is performed.
• Symptomatic gastric outlet obstruction are treated with endoscopically placed expandable metal stents.
• Pain is addressed with opioid analgesics, celiac plexus neurolysis (CPN), or radiation therapy.
• There is a particularly high incidence of thromboembolic (both venous and arterial) events, particularly in the setting of advanced disease.

EXPERT COMMENTS

• Although adults with pre-diabetes or diabetes are at higher risk for developing pancreatic cancer, there is no evidence that control affects risk of pancreatic cancer.
• Inform patients that pancreatectomy may cause diabetes, and follow blood glucose levels carefully.  
• Patients who have both pancreatic cancer and diabetes, either before and after surgery, often have unstable glycemic control.
• While pancreatic cancer may be present in older people with new-onset diabetes, we do not routinely work up new-onset diabetes for possible cancer in the absence of other suggestive evidence. 
• The utility of diagnosing pancreatic cancer in new-onset diabetes (i.e. cure rate) needs further evaluation.
• Although pancreas-dedicated CT scan with three dimensional reconstruction is the preferred method to diagnose and stage pancreatic cancer, endoscopic ultrasound is also reasonable depending on local experience and expertise.

REFERENCES