Pancreatic cancer refers to a malignant neoplasm of the pancreas.

The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a neuroendocrine tumor. The symptoms that lead to diagnosis depend on the location, the size, and the tissue type of the tumor. They may include abdominal pain and jaundice (if the tumor compresses the bile duct). Pancreatic cancer is the fourth most common cause of cancer death across the globe. Pancreatic cancer often has a poor prognosis: for all stages combined, the 1- and 5year relative survival rates are 25% and 6%, respectively; for local disease the 5-year survival is approximately 20% while the median survival for locally advanced and for metastatic disease, which collectively represent over 80% of individuals, is about 10 and 6 months respectively. RISK FACTORS: Family history: 510% of pancreatic cancer patients have a family history of pancreatic cancer. The genes have not been identified. Pancreatic cancer has been associated with the following syndromes: autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene and PALB2 gene, Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene, hereditary non-polyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, and the familial atypical multiple mole melanoma-pancreatic cancer syndrome(FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene. There may also be a history of familial pancreatitis.

Age. The risk of developing pancreatic cancer increases with age. Most cases occur after age 60, while cases before age 40 are uncommon.

Smoking. Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer; a decade of nonsmoking after heavy smoking is associated with a risk ratio of 1.2.

Diets low in vegetables and fruits Diets high in red meat

Diets high in sugar-sweetened drinks (soft drinks) - risk ratio 1.87. In particular, the common soft drink sweetener fructose has been linked to growth of pancreatic cancer cells.

Obesity

Diabetes mellitus is both risk factor for pancreatic cancer, and, as noted earlier, new onset diabetes can be an early sign of the disease.

Chronic pancreatitis has been linked, but is not known to be causal. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.

Helicobacter pylori infection Gingivitis or periodontal disease

Alcohol It is controversial whether alcohol consumption is a risk factor for pancreatic cancer. Overall, the association is consistently weak and the majority of studies have found no association. Although drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, chronic pancreatitis associated with alcohol consumption is less frequently a precursor for pancreatic cancer than other types of chronic pancreatitis. Some studies suggest a relationship, the risk increasing with increasing amount of alcohol intake. The risk is greatest in heavy drinkers, mostly on the order of four or more drinks per day. There appears to be no increased risk for people consuming up to 30g of alcohol a day, which is approximately 2 alcoholic beverages/day, so most people who take alcohol do so at a level that "is probably not a risk factor for pancreatic cancer .A pooled analysis concluded, "Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day". Several studies caution that their findings could be due to confounding factors. Even if a link exists, it could be due to the contents of some alcoholic beverages other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk. Risk Factors Factors that may increase your risk of pancreatic cancer include:

Increasing age, especially over age 60 Being African-American Being overweight or obese Chronic inflammation of the pancreas (pancreatitis) Diabetes

Family history of genetic syndromes that can increase cancer risk, including a BRCA2 gene mutation, Peutz-Jeghers syndrome, Lynch syndrome and familial atypical molemalignant melanoma (FAMMM) Personal or family history of pancreatic cancer Smoking

Sign and Symptom Pain in the upper abdomen that typically radiates to the back(seen in carcinoma of the body or tail of the pancreas)

Loss of appetite and/or nausea and vomiting Significant weight loss

Painless jaundice (yellow tint to whites of eyes and/or yellowish skin in serious cases, possibly in combination with darkened urine) when a cancer of the head of the pancreas (about 60% of cases) obstructs the common bile duct as it runs through the pancreas. This may also cause pale-colored stool and steatorrhea. The jaundice may be associated with itching as the salt from excess bile can cause skin irritation. Trousseau sign, 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, is sometimes associated with pancreatic cancer.

Diabetes mellitus, or elevated blood sugar levels. Many patients with pancreatic cancer develop diabetes months to even years before they are diagnosed with pancreatic cancer, suggesting new onset diabetes in an elderly individual may be an early warning sign of pancreatic cancer]

Clinical depression has been reported in association with pancreatic cancer, sometimes presenting before the cancer is diagnosed. However, the mechanism for this association is not known.

Symptoms of pancreatic cancer metastasis. Typically, pancreatic cancer first metastasizes to regional lymph nodes, and later to the liver and, less commonly, to the lungs it occasionally metastasizes to bone or brain.

Surgical treatment Exocrine pancreas cancer

Surgery Treatment of pancreatic cancer depends on the stage of the cancer. The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas. This procedure involves removing the pancreatic head and the curve of the duodenum together (pancreatoduodenectomy), making a bypass for food from stomach to jejunum (gastro-jejunostomy) and attaching a loop of jejunum to the cystic duct to drain bile (cholecysto-jejunostomy). It can be performed only if the patient is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing. It can, therefore, be performed in only the minority of cases. Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy. Recently, localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches. After surgery, adjuvant chemotherapy with gemcitabine has been shown in several large randomized studies to significantly increase the 5-year survival (from approximately 10 to 20%), and should be offered if the patient is fit after surgery (Oettle et al. JAMA 2007, Neoptolemos et al. NEJM 2004, Oettle et al. ASCO proc 2007). Addition of radiation therapy is a hotly debated topic, with groups in the US often favoring the use of adjuvant radiation therapy, while groups in Europe do not, due to the lack of any large randomized studies to show any survival benefit of this strategy. Surgery can be performed for palliation, if the malignancy is invading or compressing the duodenum or colon. In that case, bypass surgery might overcome the obstruction and improve quality of life, but it is not intended as a cure. Chemotherapy In patients not suitable for resection with curative intent, palliative chemotherapy may be used to improve quality of life and gain a modest survival benefit. Gemcitabine was approved by the United States Food and Drug Administration in 1998, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in patients with advanced pancreatic cancer. This marked the first FDA approval of a chemotherapy drug primarily for a nonsurvival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis. A Canadian-led Phase III randomised controlled trial, reported in 2005, involved 569 patients with advanced pancreatic cancer, led the US FDA in 2005 to license erlotinib (Tarceva) in combination withgemcitabine as a palliative regimen for pancreatic cancer. This trial compared the outcome of gemcitabine/erlotinib to gemcitabine/placebo, and demonstrated improved survival rates, improved tumor response and improved progression-free survival rates other

trials are now investigating the effect of the above combination in the adjuvant (post surgery) and neoadjuvant (pre-surgery) settings. Addition of oxaliplatin to Gemcitabine (Gem/Ox) was shown to confer benefit in small trials, but is not yet standard therapy. Endocrine pancreatic tumors The majority of these tumors are histologically benign. Treatment of pancreatic endocrine tumors, including the less common malignant tumors, may include: Watchful waiting: incidentally identified small tumors, for example on a computed tomography (CT) scan performed for other purposes, may conceptually not always need intervention, but criteria for watchful waiting are unclear.

Surgery: tumors within the pancreas only (localized tumors), or with limited metastases, may be removed. For localized tumors, the surgical procedure is much less extensive than the types of surgery used to treat pancreatic adenocarcinoma.

Hormone therapy: if the tumor is not amenable to surgical removal and is causing symptoms by secreting functional hormones, a synthetic hormone analog medication, octreotide, may lessen the symptoms, and sometimes also slows tumor growth.

Radiation therapy: occasionally used if there is pain due to anatomic extension, such as metastasis to bone.

Radiolabeled hormone: some PNETs absorb a hormone called norepinephrine and these may respond to nuclear medicine medication, radiolabeled MIBG therapy (or, experamentally, other hormones), given intravenously.

Radiofrequency ablation (RFA), cryoablation, hepatic artery embolization

Chemotherapy: in a small proportion of PNETs with undifferentiated histological features, or which grow rapidly despite other interventions, may receive chemotherapy. A subtype of PNETs, pancreatic neuroendocrine cancers, has received recent attention in the FDA approval of two medications in 2011 for use in this disease Prognosis

Exocrine pancreatic cancer (adenocarcinoma and less common variants) typically has a poor prognosis, partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis. Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered, and it has been suggested the cancer can also prompt the onset of diabetes and vice versa.[66] It can be associated with pain, fatigue, weight loss, jaundice, and weakness. Additional symptoms are discussed above. For pancreatic cancer: For all stages combined, the 1-year relative survival rate is 25%, and the 5-year survival is estimated less than 5% to 6%.

For local disease, the 5-year survival is approximately 20%.

For locally advanced and for metastatic disease, which collectively represent over 80% to 85-90% of individuals, the median survival is about 10 and 6 months, respectively. Without active treatment, metastatic pancreatic cancer has a median survival of 35months; complete remission is rare. Outcomes with pancreatic endocrine tumors, many of which are benign and completely without clinical symptoms, are much better, as are outcomes with symptomatic benign tumors; even with actual pancreatic endocrine cancers, outcomes are rather better, but variable. In 2010, an estimated 43,000 people in the US were diagnosed with pancreas cancer and almost 37,000 died from the disease; pancreatic cancer has one of the highest fatality rates of all cancers, and is the fourth-highest cancer killer among both men and women worldwide. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year. Diagnosis Most patients with pancreatic cancer experience pain, weight loss, or jaundice. Pain is present in 80% to 85% of patients with locally advanced or advanced metastatic disease. The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back. It may be intermittent and made worse by eating. Weight loss can be profound; it can be associated with anorexia, early satiety, diarrhea, or steatorrhea. Jaundice is often accompanied by pruritus and dark urine. Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion.

The initial presentation varies according to location of the cancer. Malignancies in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhea, weight loss, and jaundice. The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis (Trousseau sign), or a previous attack of pancreatitis are sometimes noted. Courvoisier sign defines the presence of jaundice and a painlessly distended gallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer fromgallstones. Tiredness, irritability and difficulty eating because of pain also exist. Pancreatic cancer is often discovered during the course of the evaluation of aforementioned symptoms. Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, -glutamyl transpeptidase and alkaline phosphatase levels). CA199 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer. However, it lacks sensitivity and specificity. When a cutoff above 37 U/mL is used, this marker has a sensitivity of 77% and specificity of 87% in discerning benign from malignant disease. CA 19-9 might be normal early in the course, and could be elevated because of benign causes of biliary obstruction. Imaging studies, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) can be used to identify the location and form of the cancer. Types of pancreatic ca. Ductal Cancers Merck Manuals, an online medical library, reports that ductal cancers are the most common form of pancreatic cancer. This type of cancer appears 1.5 to 2 times more commonly in men. According to the American Cancer Society, ductal cells are part of the exocrine system, which secrete pancreatic fluid into the intestines to aid in digestion. The most common of ductal cancers is ductal adenocarcinoma; other types of ductal cancers include adenosquamous carcinoma, squamous cell carcinoma, and giant cell carcinoma. These ductal cell cancers can be distinguished from one another based upon their appearance under a microscope. Ampullary Cancer The American Cancer Society reports that this type of cancer affects the cells at the junction of the bile duct and the pancreatic duct, which is the place where these two organs empty their contents into the intestines. These cancers often grow in a manner where they obstruct the bile duct and can cause jaundice, which is characterized by yellowing of the eyes and skin, and the production of very dark urine. Because of this very visible sign, ampullary cancer is usually detected very early, and thus the prognosis is often more optimistic than other types of pancreatic cancer. Pancreatic Neuroendocrine Tumors The American Cancer Society reports that sometimes pancreatic cancer starts in a type of endocrine cell called an islet cell, which makes insulin and other hormones. This type of cancer is much less common than other types of pancreatic cancer. Subtypes of this cancer are named

based upon what hormone the cancerous cell produces. Examples of these cancers include: insulinomas, involving cells that make insulin; glucagonomas, involving cells that make glucagon; gastrinomas, involving cells that make gastrin. Exocrine cancers The vast majority of cancers of the pancreas are exocrine in type. Most of these exocrine pancreatic cancers are ductal adenocarcinomas. These cancers start in the cells lining the ducts of the pancreas. The ducts are the tubes that carry the pancreatic digestive juices to the main pancreatic duct and the duodenum. Other rarer types of exocrine pancreatic cancer are cystic tumours, cancer of the acinar cells and sarcomas. The treatment for these rarer types is similar to that for ductal adenocarcinoma. Endocrine pancreatic tumors These tumors are uncommon and are treated differently to exocrine tumours. Endocrine pancreatic tumors are also called neuroendocrine tumors. About a third of these produce hormones. They are named after the hormone they produce and include gastrinomas, insulinomas, somatostatinomas, VIPomas and glucagonomas. About two thirds of pancreatic neuroendocrine tumours do not produce hormones (called non functioning tumors) Cystic tumors Cystic tumours cause a cyst or fluid filled sac in the pancreas. Most pancreatic cysts are benign, but some are cancerous. Cystic cancers can have a better outlook (prognosis) than other types of exocrine pancreatic cancer. Cancer of the acinar cells

The acinar cells are at the ends of the ducts that produce the pancreatic juices.
Sarcomas of the pancreas

These are cancers of the connective tissue holding together the cells of the pancreas. They are very rare and most often occur in children.
Lymphoma of the pancreas This is very rare. Lymphoma is a cancer of the lymphatic system of the body. As the lymphatic system runs throughout the body, it can crop up anywhere. Because it is a different type of cancer, it is treated differently to the other types of pancreatic cancer. There is more about the treatment of lymphoma in the CancerHelp UK section on treating non Hodgkin's lymphoma.

Alternative treatments to help you cope with distress People with cancer frequently experience distress. Some research suggests distress is more common in people with pancreatic cancer than it is in people with other types of cancer. If you're distressed, you may have difficulty sleeping and find yourself constantly thinking about your cancer. You may feel angry or sad. Discuss your feelings with your doctor. Specialists can help you sort through your feelings and help you devise strategies for coping. In some cases, medications may help. Complementary and alternative therapies may also help you cope with distress. Examples include:

Art therapy Exercise Meditation Music therapy Relaxation exercises Spirituality