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Objectives:
The following module was designed following the objectives of the Oncology Goals and Objectives for Medical Students for pancreatic cancer. Information on epidemiology, risk factors, prevention, screening, presentation, diagnosis, and prognosis for pancreatic cancer is provided.
By the end of the tutorial, the following objectives should be addressed:
The pancreas is a glandular, mainly retroperitoneal organ. It has both exocrine function (production of digestive enzymes that are secreted into the duodenum via the pancreatic duct) and endocrine function (production of hormones such as insulin and glucagon).
Main Regions of the Pancreas:
Organs in Close Proximity:
Vascular Supply:
The pancreas receives its blood supply from the pancreatic branches of the splenic artery. The head of the pancreas receives additional blood supply from the superior and inferior pancreaticoduodenal arteries (branches of the gastroduodenal and superior mesenteric arteries respectively).
There are also several vessels in the vicinity of the pancreas, including:
This knowledge becomes particularly important when considering potential sources of hematogenous spread or in the case of determining tumor resectability.
Innervation:
The pancreas is innervated by three nerve bundles:
The celiac plexus (also commonly known as the “solar plexus”) is a complex network of nerves located at T12 that surrounds the celiac trunk (arises from the aorta). It is responsible for transmitting the sensation of pain for the pancreas. In the case of pancreatic cancer, this region is often irritated by the presence of a growing mass, leading to severe and often refractory pain.
Pancreatic cancer is a disease with a high mortality rate. In 2018, 5139 cases were reported in Canada, and 50 846 were reported in the United States. Worldwide, it is the eighth leading cause of cancer-related death in men and the ninth leading cause in women. Overall, it is the seventh cause of cancer-related death in the world.
The incidence of pancreatic cancer varies by sex and race. However, it tends to be greater in males than females (1:3:1) and in African Americans than in Caucasians. Incidence of pancreatic cancer does seem to be affected by geography, with the highest incidence seen in developed parts of the world, including North America, New Zealand and Hawaii. The lowest incidence is seen in India and Nigeria.
Risk factors for pancreatic cancer can be separated into two categories: modifiable and non-modifiable. Modifiable risk factors imply the patient can take measures to change them and reduce their overall risk of pancreatic cancer. In total, modifiable risk factors make up 85-90% of all pancreatic cancer risk factors. The remaining 10-15% are deemed non-modifiable, implying they make up the innate risk a particular patient has for developing pancreatic cancer and cannot be changed.
The risk of pancreatic cancer can be reduced by addressing modifiable risk factors the patient has. Common ways of accomplishing this include:
The goal of pancreatic cancer screening is to detect pre-invasive and early invasive tumors in asymptomatic patients. Screening is typically reserved for patients with non-modifiable risk factors (such as genetic predispositions) and should only be done in patients who are good surgical candidates.
Candidates for pancreatic cancer screening include:
Screening typically begins at age 45-50, or 10-15 years prior to the youngest age of diagnosis of pancreatic cancer in the family. Imaging can be done annually until a lesion is detected or screening is no longer deemed appropriate (no longer a surgical candidate, decreased life expectancy, or patient no longer wishes to have screening). There are a number of different screening modalities that can be used which are discussed in the table below.
It is important to consider the risks and benefits of screening and discuss them with the patient prior to screening.
Like most cancers, pancreatic cancer can spread in a local, lymphatic or hematogenous fashion. Signs and/or symptoms the patient presents with may provide information about the extent of cancer spread. However, the signs and symptoms of pancreatic cancer are often non-specific in nature and similar clinical findings may be present in both local and metastatic disease. As a result, we cannot use a patient’s clinical presentation alone to diagnose or stage pancreatic cancer.
Initially, patients are asymptomatic due to the small size of the pancreatic lesion. As the mass becomes larger and begins to spread, signs and symptoms become more apparent. The most common symptoms associated with pancreatic cancer are:
Other common signs/symptoms of pancreatic cancer are described in the tables below.
As with any patient complaint, begin with a detailed history and a focused physical exam.
The following are important aspects of a history for suspected pancreatic cancer:undefined
A physical exam should be done to find clinical signs of pancreatic cancer. A focused abdominal exam is appropriate, with emphasis on palpation of an epigastric or right upper quadrant mass (may or may not be tender) and other findings such as hepatomegaly or ascites. Extra-abdominal physical findings should also be assessed such as jaundice of the skin and/or membranes and weight loss (cachexia).
Absence of clinically significant findings on physical exam does not rule out the diagnosis of pancreatic cancer. If the history is suspicious for pancreatic cancer, initial diagnostic testing, such as laboratory investigations and imaging, are initiated.
Laboratory investigations may include:
The imaging modality chosen will depend on the patient’s presenting symptoms:
A summary of these modalities can be found in the table below.
If a patient presents with painless jaundice, the imaging modality of choice is often a transabdominal ultrasound of the right upper quadrant to assess for causes of biliary-pancreatic disease. Ultrasound is beneficial in this case because of its wide availability and low-cost to the health care system. It also has a high sensitivity for detecting masses in the head of the pancreas and biliary tract dilation, both important findings to assess for in a patient presenting with jaundice.
If a patient presents with epigastric pain and weight loss, a transabdominal ultrasound of the epigastrium and right upper quadrant may be done initially. However, because these clinical findings are more sinister, the imaging modality of choice is typically a CT scan due to its higher sensitivity for detecting small masses (<3cm) and its ability to detect metastatic disease.
The “positive” findings of pancreatic cancer on transabdominal US include a hypoechoic mass, dilatation of the pancreatic duct, and dilatation of the bile duct. Note that these findings are typically in keeping with a mass in the head of the pancreas. Masses in the body/tail of the pancreas are harder to detect by US due to lack of biliary dilatation and bowel gas obstructing the view.
If a transabdominal U/S is considered positive, the presence of a mass needs to be confirmed by a CT scan and disease extent needs to be assessed. The CT scan alone may provide enough information about the disease and resectability that surgical intervention can be carried out without a biopsy to confirm the diagnosis of pancreatic cancer. However, if there is uncertainty about the diagnosis or resectability, a biopsy +/- additional procedures may be carried out. Biopsies can be done through endoscopic ultrasound guidance or percutaneously.
If a transabdominal U/S is negative despite clinical suspicions of pancreatic cancer, a CT scan must be done. If the patient has signs of cholestasis (elevated ALP, GGT, bilirubin), an ERCP may be done instead to assess for choledocholithiasis. If either is found to be negative, no additional testing is required and the physician must consider an alternative diagnosis for the patient’s symptoms.
It is important to remember that although this module presents a pancreatic mass as pancreatic cancer, there is a differential diagnosis of a pancreatic mass. This is presented in the table below.
Once the diagnosis of pancreatic cancer has been made, classification of the presenting neoplasm is necessary. Exocrine pancreatic neoplasms (arising from ductal and acinar cells and their stem cells) make up more than 95% of all pancreatic neoplasms. The remaining percentage are endocrine pancreatic neoplasms (arising from islet cells) and will not be covered in detail in this module.
Exocrine pancreatic neoplasms can be separated into benign and malignant, and are summarized in the table below. Note that the literature mentions a “pre-malignant” classification, which focuses on the potential of a neoplasm to progress to malignancy. This is determined by degree of dysplasia (low or high grade) and does not represent a specific type of neoplasm.
A biopsy is required to characterize the pancreatic neoplasm. This can be accomplished percutaneously or by endoscopic ultrasound.
Once the pancreatic neoplasm has been characterized, staging is necessary for treatment planning and prognosis. This is commonly accomplished by CT-scan, as it allows for both local and distant assessment of cancer spread. The preferred staging system for all pancreatic neoplasms is the Tumour, Node, Metastasis (TNM) System. AJCC Cancer Staging Manual, Eighth Edition, was used to summarize the following TNM staging for exocrine pancreatic neoplasms.
The treatment options are discussed below briefly for completeness:
Prognosis for patients with pancreatic cancer is poor. Even in cases where pancreatic tumors are completely resected and there is no nodal involvement, there is a high incidence of recurrence in the first few years post-treatment (poor five-year survival rate) and the majority of patients die from the disease.
However, it is important to remember that survival estimates are dynamic and can change based on how long the patient has survived to date. For example, a patient’s five-year survival rate may be 18% immediately after surgery/treatment due to the high incidence of recurrence in pancreatic cancer. However, if the patient has had no recurrence three years post-surgery, their survival estimate can increase up to 66% (a 66% chance of an additional two years of life, or a “conditional two-year survival”).
It is also important to note that prognosis appears to continuously improve after five years of survival. Between years 9-13 post-surgery, a patient’s risk of death due to pancreatic cancer decreases to 10% per year. After year 13, their risk of death decreases to 3% per year as late as 20 years post-surgery. Therefore, in some cases, long-term survival is possible for patients diagnosed with pancreatic cancer.
Overall, a patient’s prognosis can be affected by many factors, which are summarized in the table below.
Use your mouse to click through the slides and answer each question in the text box provided.
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Anatomy
Epidemiology, Risk Factors, Prevention, Screening
Presentation, Diagnosis
Classification, Pathology, Staging, Treatment, Prognosis
