Pancreatic cancer


Pancreatic cancer is any cancer with a primary location in the pancreas. It arises when cells in the pancreas, a glandular organ behind the stomach, begin 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 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. The disease is divided into stages, from early to late. 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 most deadly forms of cancer globally, with one of the lowest survival rates. In 2021, pancreatic cancers of all types resulted in 508,532 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 5 years globally and 13% live for five years in the US. For cancers diagnosed early, the five-year survival rate rises to about 20%. Neuroendocrine cancers have better outcomes; at five years from diagnosis, 65% of those diagnosed are living, though survival considerably varies 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 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 tissue of the pancreas have different clinical characteristics and are called pancreatic neuroendocrine tumors, sometimes abbreviated as "PanNETs". Both groups occur mainly in people over 40, and are slightly more common in men, but some rare subtypes mainly occur in women or children.

Exocrine cancers

The exocrine group is dominated by pancreatic adenocarcinoma, 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. 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 within the pancreas. This cancer originates in the ducts that carry secretions 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. Neuroendocrine tumors 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", though they are now known to not actually arise from islet cells as previously thought.

Signs and symptoms

Since pancreatic cancer usually does not cause recognizable symptoms in its early stages, the disease is typically not diagnosed until it has spread beyond the pancreas itself. This is one of the main reasons for the generally poor survival rates. Exceptions to this are the functioning PanNETs, where over-production of various active hormones can give rise to symptoms.
Common presenting symptoms of pancreatic adenocarcinoma include:
  • Pain in the upper abdomen or back, often spreading from around the stomach to the back. The location of the pain can indicate the part of the pancreas where a tumor is located. The pain may be worse at night and may increase over time to become severe and unremitting. It may be slightly relieved by bending forward. In the UK, about half of new cases of pancreatic cancer are diagnosed following a visit to a hospital emergency department for pain or jaundice. In up to two-thirds of people, abdominal pain is the main symptom, for 46% of the total accompanied by jaundice, with 13% having jaundice without pain.
  • Jaundice, a yellow tint to the whites of the eyes or skin, with or without pain, and possibly in combination with darkened urine, results when a cancer in the head of the pancreas obstructs the common bile duct as it runs through the pancreas.
  • Unexplained weight loss, either from loss of appetite, or loss of exocrine function resulting in poor digestion.
  • The tumor may compress neighboring organs, disrupting digestive processes and making it difficult for the stomach to empty, which may cause nausea and a feeling of fullness. The undigested fat leads to foul-smelling, fatty feces that are difficult to flush away. Constipation is also common.
  • At least 50% of people with pancreatic adenocarcinoma have diabetes at the time of diagnosis. While long-standing diabetes is a known risk factor for pancreatic cancer, the cancer can itself cause diabetes, in which case recent onset of diabetes could be considered an early sign of the disease. People over 50 who develop diabetes have eight times the usual risk of developing pancreatic adenocarcinoma within three years, after which the relative risk declines.