question: How and why is pancreatic cancer so deadly?
comment: It doesn't cause any really obvious/worrisome symptoms until stage 4. Before that, if you feel anything at all, it's easy to write off as something unimportant. The pancreas is deep in the gut, so cancer there is harder to detect with X rays and CT scans if the doctors aren't looking for it. Most cancers can be found by accident when the patient gets a scan for some other reason. The cancer itself is quickly grows around a bunch of major blood vessels near the pancreas. This makes the cancer inoperable most of the time; they can't cut into it without risking huge internal bleeding which could be lethal. This particular cancer tends to be shielded by non-malignant cells that block chemotherapy drugs. So chemo isn't a good option either. By the time it's detected at stage 4, the cancer has already metastasized to other things in the guy and death is almost completely inevitable. Surviving in that situation is what the media would call a "medical miracle".
passages: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. It has been estimated that PDAC causes 34000 deaths per year in the EU alone. Despite considerable research efforts in the past decades, conventional treatment approaches, including surgery, radiation, chemotherapy, and combinations of these, have close to no impact on the course of this aggressive neoplasm. Therefore, virtually all of the patients diagnosed with PC develop metastases and die 
   In 2015, pancreatic cancers of all types resulted in 411,600 deaths globally. Pancreatic cancer 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, 25% of people survive one year and 5% live for five years. 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 varies considerably depending on the type of tumor.
   Section::::Outcomes.
  
  Pancreatic adenocarcinoma and the other less common exocrine cancers have a very poor prognosis, as they are normally diagnosed at a late stage when the cancer is already locally advanced or has spread to other parts of the body. Outcomes are much better for PanNETs: many are benign and completely without clinical symptoms, and even those cases not treatable with surgery have an average five-year survival rate of 16%, although the outlook varies considerably according to the type.
   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 (which depend on the type of hormone).
  
  Bearing in mind that the disease is rarely diagnosed before the age of 40, common symptoms of pancreatic adenocarcinoma occurring before diagnosis include:
   Small precancerous neoplasms for many pancreatic cancers are being detected at greatly increased rates by modern medical imaging. One type, the intraductal papillary mucinous neoplasm (IPMN) was first described by Japanese researchers in 1982. It was noted in 2010 that: "For the next decade, little attention was paid to this report; however, over the subsequent 15 years, there has been a virtual explosion in the recognition of this tumor."
  
  Section::::Research directions.
   Section::::Types.:Exocrine cancers.
   Cancers in the pancreas may also be secondary cancers that have spread from other parts of the body. This is uncommon, found in only about 2% of cases of pancreatic cancer. Kidney cancer is by far the most common cancer to spread to the pancreas, followed by colorectal cancer, and then cancers of the skin, breast, and lung. Surgery may be performed on the pancreas in such cases, whether in hope of a cure or to alleviate symptoms.
  
  Section::::Risk factors.
  
  Risk factors for pancreatic adenocarcinoma include:
   BULLET::::- Chronic pancreatitis appears to almost triple risk, and as with diabetes, new-onset pancreatitis may be a symptom of a tumor. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.
  
  BULLET::::- Diabetes mellitus is a risk factor for pancreatic cancer and (as noted in the Signs and symptoms section) new-onset diabetes may also be an early sign of the disease. People who have been diagnosed with Type 2 diabetes for longer than ten years may have a 50% increased risk, as compared with individuals without diabetes.
   HP is characterised by attacks of epigastric pain, which are often associated with nausea and vomiting. Symptoms may start shortly after birth but onset varies periodically, with some patients not exhibiting symptoms until adulthood. There is usually progression to chronic pancreatitis with endocrine and exocrine failure and a mortally increased risk of pancreatic cancer. Lifetime risk of cancer has been variously calculated as 35–54% to the age of 75 years and screening for early pancreatic cancer is being offered to HP sufferers on a scientific basis. Some patients may choose to have their pancreas surgically removed to prevent pancreatic cancer from developing in the future.
   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. There are usually no symptoms 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.
   A fourth type of cancer that arises in the pancreas is the intraductal tubulopapillary neoplasm. This type was recognised by the WHO in 2010 and constitutes about 1–3% of all pancreatic neoplasms. Mean age at diagnosis is 61 years (range 35–78 years). About 50% of these lesions become invasive. Diagnosis depends on histology as these lesions are very difficult to differentiate from other lesions on either clinical or radiological grounds.
  
  Section::::Pathophysiology.:Invasive cancer.
   The first is pancreatic intraepithelial neoplasia. These lesions are microscopic abnormalities in the pancreas and are often found in autopsies of people with no diagnosed cancer. These lesions may progress from low to high grade and then to a tumor. More than 90% of cases at all grades carry a faulty "KRAS" gene, while in grades 2 and 3 damage to three further genes – "CDKN2A" ("p16"), "p53" and "SMAD4" – are increasingly often found.
   BULLET::::- Family history; 5–10% of pancreatic cancer cases have an inherited component, where people have a family history of pancreatic cancer. The risk escalates greatly if more than one first-degree relative had the disease, and more modestly if they developed it before the age of 50. Most of the genes involved have not been identified. Hereditary pancreatitis gives a greatly increased lifetime risk of pancreatic cancer of 30–40% to the age of 70. Screening for early pancreatic cancer may be offered to individuals with hereditary pancreatitis on a research basis. Some people may choose to have their pancreas surgically removed to prevent cancer from developing in the future.
   Section::::Clinical significance.:Cancer.
   Pancreatic cancer has a poor prognosis, with a five-year survival rate of less than 5%. By the time the cancer is diagnosed, it is usually at an advanced, inoperable stage. Only one in about fifteen to twenty patients is curative surgery attempted. Pancreatic cancer tends to be aggressive, and it resists radiotherapy and chemotherapy.
  
  Section::::Upper digestive tract.:Liver cancer.
   Most pancreatic NETs are sporadic. However, neuroendocrine tumors can be seen in several inherited familial syndromes, including:
  
  BULLET::::- multiple endocrine neoplasia type 1 (MEN1)
  
  BULLET::::- multiple endocrine neoplasia type 2 (MEN2)
  
  BULLET::::- von Hippel-Lindau (VHL) disease
  
  BULLET::::- neurofibromatosis type 1
  
  BULLET::::- tuberous sclerosis
  
  BULLET::::- Carney complex
  
  Given these associations, recommendations in NET include family history evaluation, evaluation for second tumors, and in selected circumstances testing for germline mutations such as for MEN1.
  
  Section::::Pathophysiology.
   Section::::Types.
   In 2015, pancreatic cancers of all types resulted in 411,600 deaths globally. In 2014, an estimated 46,000 people in the US are expected to be diagnosed with pancreatic cancer and 40,000 to die of it. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year. It is the seventh highest cause of death from cancer worldwide. Pancreatic cancer is the fifth most common cause of death from cancer in the United Kingdom, and the third most common in the United States.
   BULLET::::- Cigarette smoking is the best-established avoidable risk factor for pancreatic cancer, approximately doubling risk among long-term smokers, the risk increasing with the number of cigarettes smoked and the years of smoking. The risk declines slowly after smoking cessation, taking some 20 years to return to almost that of non-smokers.
  
  BULLET::::- Obesity; a BMI greater than 35 increases relative risk by about half.
   BULLET::::8. Marked responsiveness to treatment with corticosteroids.
  
  Two-thirds of patients present with either obstructive painless jaundice or a "mass" in the head of the pancreas mimicking carcinoma. It is mandatory to rule out carcinoma prior to making a diagnosis of AIP.
  
  Section::::Histopathology.
   Pancreatic cancer is the fifth-most-common cause of cancer deaths in the United States, and the seventh most common in Europe. In 2008, globally there were 280,000 new cases of pancreatic cancer reported and 265,000 deaths. These cancers are classified as endocrine or nonendocrine tumors. The most common is ductal adenocarcinoma. The most significant risk factors for pancreatic cancer are advanced age (over 60) and smoking. Chronic pancreatitis, diabetes or other conditions may also be involved in their development. Early pancreatic cancer does not tend to result in any symptom, but when a tumor is advanced, a patient may experience severe pain in the upper abdomen, possibly radiating to the back. Another symptom might be jaundice, a yellowing of the skin and eyes.
   There are several types of pancreatic cancer, involving both the endocrine and exocrine tissue. The many types of pancreatic endocrine tumors are all uncommon or rare, and have varied outlooks. However the incidence of these cancers has been rising sharply; it is not clear to what extent this reflects increased detection, especially through medical imaging, of tumors that would be very slow to develop. Insulinomas (largely benign) and gastrinomas are the most common types. For those with neuroendocrine cancers the number alive after five years is much better at 65%, varying considerably with type.
   Other common manifestations of the disease include: weakness and tiring easily; dry mouth; sleep problems; and a palpable abdominal mass.
  
  Section::::Signs and symptoms.:Symptoms of spread.
  
  The spread of pancreatic cancer to other organs (metastasis) may also cause symptoms. Typically, pancreatic adenocarcinoma first spreads to nearby lymph nodes, and later to the liver or to the peritoneal cavity, large intestine or lungs. It is uncommon for it to spread to the bones or brain.
   For locally advanced and metastatic pancreatic adenocarcinomas, which together represent over 80% of cases, numerous recent trials comparing chemotherapy regimes have shown increased survival times, but not to more than one year. Overall five-year survival for pancreatic cancer in the US has improved from 2% in cases diagnosed in 1975–77, and 4% in 1987–89 diagnoses, to 6% in 2003–09. In the less than 20% of cases of pancreatic adenocarcinoma with a diagnosis of a localized and small cancerous growth (less than 2 cm in Stage T1), about 20% of Americans survive to five years.
   BULLET::::- Trousseau's syndrome, in which blood clots form spontaneously in the portal blood vessels, the deep veins of the extremities, or the superficial veins anywhere on the body, may be associated with pancreatic cancer, and is found in about 10% of cases.
  
  BULLET::::- Clinical depression has been reported in association with pancreatic cancer in some 10–20% of cases, and can be a hindrance to optimal management. The depression sometimes appears before the diagnosis of cancer, suggesting that it may be brought on by the biology of the disease.
  