Pancreatic cancer is any cancer with a primary location in the pancreas, a glandular organ lying behind the stomach. It arises when cells in the pancreas start to multiply out of control and form a mass. These cancerous cells have the ability to invade or spread to other parts of the body. A number of types of pancreatic cancer are known.
The most common type of pancreatic cancer, pancreatic adenocarcinoma, accounts for about 90% of cases, and the term "pancreatic cancer" is sometimes used to refer only to that type. These adenocarcinomas start within the ductal part of the pancreas that makes digestive enzymes. Several other types of cancer, which collectively represent the majority of the non-adenocarcinomas, can also arise from these cells.
About 1–2% of cases of pancreatic cancer are neuroendocrine tumors, which arise from the hormone-producing cells of the pancreas. These are generally less aggressive than pancreatic adenocarcinoma.
Signs and symptoms of the most-common form of pancreatic cancer may include yellow skin, abdominal or back pain, unexplained weight loss, light-colored stools, dark urine, and loss of appetite. Usually, no symptoms are seen in the disease's early stages, and symptoms that are specific enough to suggest pancreatic cancer typically do not develop until the disease has reached an advanced stage. By the time of diagnosis, pancreatic cancer has often spread to other parts of the body.
Pancreatic cancer rarely occurs before the age of 40, and more than half of cases of pancreatic adenocarcinoma occur in those over 70. However, early-onset pancreatic cancer (defined as pancreatic cancer diagnosed in someone <50 years of age) is becoming more prevalent, disproportionally so in younger women.
Risk factors for pancreatic cancer include tobacco smoking, obesity, diabetes, and certain rare genetic conditions. About 25% of cases are linked to smoking, and 5–10% are linked to inherited genes.
Pancreatic cancer is usually diagnosed by a combination of medical imaging techniques such as ultrasound or computed tomography, blood tests, and examination of tissue samples (biopsy). The disease is divided into stages, from early (stage I) to late (stage IV). Screening the general population has not been found to be effective.
The risk of developing pancreatic cancer is lower among non-smokers, and people who maintain a healthy weight and limit their consumption of red or processed meat; the risk is greater for men, smokers, and those with diabetes. There are some studies that link high levels of red meat consumption to increased risk of pancreatic cancer, though meta-analyses typically find no clear evidence of a relationship. Smokers' risk of developing the disease decreases immediately upon quitting, and almost returns to that of the rest of the population after 20 years. Pancreatic cancer can be treated with surgery, radiotherapy, chemotherapy, palliative care, or a combination of these. Treatment options are partly based on the cancer stage. Surgery is the only treatment that can cure pancreatic adenocarcinoma, and may also be done to improve quality of life without the potential for cure. Pain management and medications to improve digestion are sometimes needed. Early palliative care is recommended even for those receiving treatment that aims for a cure.
Pancreatic cancer is among the deadliest forms of cancer globally, with one of the lowest survival rates. In 2021, pancreatic cancers of all types resulted in 508,532 (up from 411,600 in 2013) deaths globally. It is the fifth-most-common cause of death from cancer in the United Kingdom, and the third most-common in the United States.
The disease occurs most often in the developed world, where about 70% of the new cases in 2012 originated. Pancreatic adenocarcinoma typically has a very poor prognosis; after diagnosis, 9% survive after five years globally and 14% live for five years in the US. For cancers diagnosed early, the five-year survival rate rises to about 20%. "The highest cure rate occurs if the tumor is truly localized to the pancreas; however, this stage of disease accounts for less than 20% of cases. In cases with localized disease and small cancers (<2 cm) with no lymph-node metastases and no extension beyond the capsule of the pancreas, complete surgical resection is still associated with a low actuarial five-year survival rate of 18% to 24%." Neuroendocrine cancers have better outcomes; at five years from diagnosis, 65% of those diagnosed are living, though survival varies considerably depending on the type of tumor.
Types
The many types of pancreatic cancer can be divided into two general groups. The vast majority of cases (about 95%) occur in the part of the pancreas that produces digestive enzymes, known as the exocrine component. Several subtypes of exocrine pancreatic cancers are described, but their diagnosis and treatment have much in common.
The small minority of cancers that arise in the hormone-producing (endocrine) tissue of the pancreas have different clinical characteristics and are called pancreatic neuroendocrine tumors, sometimes abbreviated as "PanNETs". Both groups occur mainly (but not exclusively) in people over 40, and are slightly more common in men, but some rare subtypes mainly occur in women or children. (Table 5 outlines the proposed TNM staging system for PanNETs.)
Exocrine cancers The exocrine group is dominated by pancreatic adenocarcinoma (variations of this name may add "invasive" and "ductal"), which is by far the most common type, representing about 85% of all pancreatic cancers. Nearly all these start in the ducts of the pancreas, as pancreatic ductal adenocarcinoma (PDAC). This is despite the fact that the tissue from which it arises – the pancreatic ductal epithelium – represents less than 10% of the pancreas by cell volume, because it constitutes only the ducts (an extensive but capillary-like duct-system fanning out) within the pancreas. Online edition, with updates to 2014 This cancer originates in the ducts that carry secretions (such as enzymes and bicarbonate) away from the pancreas. About 60–70% of adenocarcinomas occur in the head of the pancreas.
The next-most common type, acinar cell carcinoma of the pancreas, arises in the clusters of cells that produce these enzymes, and represents 5% of exocrine pancreas cancers. Like the 'functioning' endocrine cancers described below, acinar cell carcinomas may cause over-production of certain molecules, in this case digestive enzymes, which may cause symptoms such as skin rashes and joint pain.
Cystadenocarcinomas account for 1% of pancreatic cancers, and they have a better prognosis than the other exocrine types.
Pancreatoblastoma is a rare form, mostly occurring in childhood, and with a relatively good prognosis. Other exocrine cancers include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells. Solid pseudopapillary tumor is a rare low-grade neoplasm that mainly affects younger women, and generally has a very good prognosis.
Pancreatic mucinous cystic neoplasms are a broad group of pancreas tumors that have varying malignant potential. They are being detected at a greatly increased rate as CT scans become more powerful and common, and discussion continues as how best to assess and treat them, given that many are benign.
Neuroendocrine
The small minority of tumors that arise elsewhere in the pancreas are mainly pancreatic neuroendocrine tumors (PanNETs).The PanNET denomination is in line with WHO guidelines for the classification of tumors of the digestive system published in 2010. Historically, PanNETs have also been referred to by a variety of terms, and are still commonly called "pancreatic endocrine tumors". See: Neuroendocrine tumors (NETs) are a diverse group of benign or malignant tumors that arise from the body's neuroendocrine cells, which are responsible for integrating the nervous and endocrine systems. NETs can start in most organs of the body, including the pancreas, where the various malignant types are all considered to be rare. PanNETs are grouped into 'functioning' and 'nonfunctioning' types, depending on the degree to which they produce hormones.
The functioning types secrete hormones such as insulin, gastrin, and glucagon into the bloodstream, often in large quantities, giving rise to serious symptoms such as low blood sugar, but also favoring relatively early detection. The most common functioning PanNETs are insulinomas and gastrinomas, named after the hormones they secrete. The nonfunctioning types do not secrete hormones in a sufficient quantity to give rise to overt clinical symptoms, so nonfunctioning PanNETs are often diagnosed only after the cancer has spread to other parts of the body.
As with other neuroendocrine tumors, the history of the terminology and classification of PanNETs is complex. PanNETs are sometimes called "islet cell cancers",The Medical Subject Headings indexing system refers to "islet cell carcinoma", which is subdivided into gastrinoma, glucagonoma, somatostatinoma, and VIPoma. See: 2014 MeSH tree at "Pancreatic Neoplasms C04.588.322.475.500" 16 October 2014 though they are now known to not actually arise from islet cells as previously thought.
Signs and symptoms
Since pancreatic cancer rarely causes recognizable symptoms in its early stages, the disease is typically not diagnosed until tumors are large or have spread beyond the pancreas. The first symptom that most people notice is jaundice (yellowing of the skin and eyes) as the tumor grows large enough to block the bile duct, causing a buildup of yellow bilirubin in the body. People with jaundice can also have noticeably dark urine, light-colored or gray stools, and itchy skin.
A blocked bile duct can also cause the gallbladder to enlarge, which can sometimes be felt as a swollen lump just under the ribs on the right side. Tumors can also start to press on nearby organs, causing pain in the upper abdomen or back. Tumors that press on the stomach can result in nausea, vomiting, and pain that worsens after eating. Damage to the pancreas as tumors grow can reduce the organ's ability to make insulin resulting in diabetes, which typically manifests as increased thirst, hunger, and frequency of urination.
People with pancreatic cancer often experience general whole-body symptoms, most commonly fatigue and reduced appetite leading to unintended weight loss. Pancreatic cancer, as well as some other cancers, can increase one's risk of blood clots. Clots of the blood vessels under the skin (superficial thrombophlebitis) cause pain, redness, and swelling at the clot sites.
Clots can seem to resolve on their own, then reappear at nearby sites, called migratory thrombophlebitis or Trousseau's syndrome. Clots in larger blood vessels deeper in the body (called deep vein thromboses) cause pain and swelling of the affected body area). Clots in the blood vessels of the lung (called pulmonary embolism) can cause chest pain and difficulty breathing.
Metastastic disease
Signs and symptoms of pancreatic cancer can also be due to the spread of tumors to nearby lymph nodes or other organs. Spread to lymph nodes can cause lymph node enlargement that can be felt over the skin, most prominently in the left-side lower neck (called Virchow's node) or near the navel, called Sister Mary Joseph's node.
The metastasis of pancreatic cancer to other organs may also cause symptoms. Typically, pancreatic cancer spreads to the liver, lungs, peritoneum (tissue layer that envelopes abdominal organs), and less frequently to the bones.