Pancreatic cancer
Encyclopedia
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 5-year 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.
, 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.
.
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 from gallstone
s. 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, γ-glutamyl transpeptidase
and alkaline phosphatase
levels). CA19-9
(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.
or surgical excision of the radiologically suspicious tissue. Endoscopic ultrasound is often used to visually guide the needle biopsy procedure.
) is typically characterized by moderately to poorly differentiated glandular structures on microscopic examination. Pancreatic cancer has an immunohistochemical
profile that is similar to hepatobiliary cancers (e.g. cholangiocarcinoma
) and some stomach cancer
s; thus, it may not always be possible to be certain that a tumour found in the pancreas arose from it.
Pancreatic carcinoma is thought to arise from progressive tissue changes. Three types of precancerous lesion are recognised: pancreatic intraepithelial neoplasia - a microscopic lesions of the pancreas, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms both of which are macroscopic lesions. The cellular origin of these lesions is debated.
The second most common type of exocrine pancreas cancer is mucinous. The prognosis is slightly better.
Other exocrine cancers include adenosquamous carcinoma
s, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells.
is low, about five per one million person-years. However, autopsy
studies incidentally identify PETs in up to 1.5% most of which would remain inert and asymptomatic.
The majority of PNETs are usually categorized as benign but the definition of malignancy in pancreas endocrine tumors has been ambiguous. A small subset of endocrine pancreatic tumors are incontrovertible pancreatic endocrine cancers, that make up about 1% of pancreas cancers. Low- to intermediate-grade neuroendocrine carcinomas of the pancreas may be called islet cell tumors. Some sources have also termed these pancreatic carcinoid, a practice that has sometimes been strongly condemned. Definitional migration has caused some complexity of PNET classification, which has adversely affected what is known about the epidemiology and natural history of these tumors. It is probable that some of these tumors have been included in
ICD-O-3
histology classifications 8240–8245, in that they were labeled pancreatic carcinoid tumours but most islet cell carcinomas have been coded as ICD-O-3 system 8150–8155.
The more aggressive endocrine pancreatic cancers are known as pancreatic neuroendocrine carcinomas (PNEC). Similarly, there has likely been a degree of admixture of PNEC and extrapulmonary small cell cancer.
, there are no established guidelines for preventing pancreatic cancer, although cigarette smoking
has been reported as responsible for 20–30% of pancreatic cancers.
The ACS recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing red meat intake, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically.
In 2006, a large prospective cohort study of over 80,000 subjects failed to prove a definite association. The evidence in support of this lies mostly in small case-control studies.
A long-term study found that people who consumed in the range of 300 to 449 international units (IU) of vitamin D daily had a 43% lower risk of pancreatic cancer than those who took less than 150 IU per day; 150 IU is appreciably less than what was then, or is now, recommended. The World Health Organization
(WHO) International Agency for Research on Cancer
(IARC), concluded that there were insufficient studies in pancreatic cancer, and while it found evidence for an inverse association between vitamin D and colorectal cancer to be persuasive, it found evidence for a causal link to be limited, and also found that randomized controlled trials (RCTs) were inconclusive. Taking too much vitamin D may be harmful. Poor general diet, obesity, and relative physical inactivity can be risk factors in some cancers, so the role of vitamin D itself is not certain.
B vitamins
, such as B12
, B6
, and folate, can reduce the risk of pancreatic cancer when consumed in food, but not when ingested in vitamin tablet form.
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 (pancreato-duodenectomy), 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.
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 with gemcitabine 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.
benign
. Treatment of pancreatic endocrine tumors, including the less common malignant
tumors, may include:
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. It can be associated with pain, fatigue, weight loss, jaundice
, and weakness. Additional symptoms are discussed above.
For pancreatic cancer:
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.
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
neoplasm of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
. The most common type of pancreatic cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, accounting for 95% of these tumors is adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
, 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
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
and jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
(if the tumor compresses the bile duct
Bile duct
A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...
).
Pancreatic cancer is the fourth most common cause of cancer death across the globe. Pancreatic cancer often has a poor prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
: for all stages
Cancer staging
The stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...
combined, the 1- and 5-year relative survival rates
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
are 25% and 6%, respectively; for local disease the 5-year survival is approximately 20% while the median
Median
In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...
survival for locally advanced and for metastatic disease, which collectively represent over 80% of individuals, is about 10 and 6 months respectively.
Signs and symptoms
Pancreatic cancer is sometimes referred to as a "silent killer" because early pancreatic cancer often does not cause symptoms, and the later symptoms are usually nonspecific and varied. Therefore, pancreatic cancer is often not diagnosed until it is advanced. Common symptoms include:- Pain in the upper abdomenAbdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
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 lossWeight lossWeight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
- Painless jaundiceJaundiceJaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
(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 (75% of cases) obstructs the common bile ductCommon bile ductThe common bile duct is a tube-like anatomic structure in the human gastrointestinal tract. It is formed by the union of the common hepatic duct and the cystic duct . It is later joined by the pancreatic duct to form the ampulla of Vater...
as it runs through the pancreas. This may also cause pale-colored stool and steatorrheaSteatorrheaSteatorrhea is the presence of excess fat in feces. Stools may also float due to excess lipid, have an oily appearance and be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the...
. The jaundice may be associated with itchItchItch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...
ing as the salt from excess bile can cause skin irritation. - Trousseau signTrousseau sign of malignancyThe Trousseau sign of malignancy is a medical sign found in certain cancers that is associated with venous thrombosis and hypercoagulability. It is also referred to as Trousseau syndrome and is distinct from the Trousseau sign of latent tetany.-History:...
, in which blood clots form spontaneously in the portal blood vesselsPortal venous systemIn human anatomy, the hepatic portal system is the system of veins comprising the hepatic portal vein and its tributaries. It is also called the portal venous system, although it is not the only example of a portal venous system, and splanchnic veins, which is not synonymous with hepatic portal...
, 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 depressionClinical depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
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 liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and, less commonly, to the lungs; it occasionally metastasizes to bone or brain.
Risk factors
Risk factors for pancreatic cancer may include:- Family history: 5–10% 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 BRCA2BRCA2BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....
geneGeneA gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
and PALB2PALB2Partner and localizer of BRCA2, also known as PALB2, is a protein which in humans is encoded by the PALB2 gene.- Function :This gene encodes a protein that functions in genome maintenance...
geneGeneA gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, Peutz-Jeghers syndromePeutz-Jeghers syndromePeutz–Jeghers syndrome, also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa...
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 CDKN2ACDKN2ACDKN2A can refer to:* P16 * p14arf...
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.
- SmokingTobacco smokingTobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
. 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.
- ObesityObesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
- Diabetes mellitusDiabetes mellitusDiabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
is both risk factor for pancreatic cancer, and, as noted earlier, new onset diabetes can be an early sign of the disease. - Chronic pancreatitisChronic pancreatitisChronic pancreatitis is a long-standing inflammation of the pancreas that alters its normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption....
has been linked, but is not known to be causal. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high. - Helicobacter pyloriHelicobacter pyloriHelicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
infection - GingivitisGingivitisGingivitis is a term used to describe non-destructive periodontal disease. The most common form of gingivitis is in response to bacterial biofilms adherent to tooth surfaces, termed plaque-induced gingivitis, and is the most common form of periodontal disease...
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 pancreatitisChronic pancreatitis
Chronic pancreatitis is a long-standing inflammation of the pancreas that alters its normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption....
, 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.
Diagnosis
Most patients with pancreatic cancer experience pain, weight loss, or jaundiceJaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
.
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
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
, early satiety, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, or steatorrhea
Steatorrhea
Steatorrhea is the presence of excess fat in feces. Stools may also float due to excess lipid, have an oily appearance and be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the...
. Jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
is often accompanied by pruritus
Itch
Itch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...
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
Thrombophlebitis
Thrombophlebitis is phlebitis related to a thrombus . When it occurs repeatedly in different locations, it is known as "Thrombophlebitis migrans" or "migrating thrombophlebitis".-Signs and symptoms:...
(Trousseau sign
Trousseau sign of malignancy
The Trousseau sign of malignancy is a medical sign found in certain cancers that is associated with venous thrombosis and hypercoagulability. It is also referred to as Trousseau syndrome and is distinct from the Trousseau sign of latent tetany.-History:...
), or a previous attack of pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
are sometimes noted. Courvoisier sign
Courvoisier's law
Courvoisier's law states that in the presence of an enlarged gallbladder which is nontender and accompanied with mild jaundice, the cause is unlikely to be gallstones. Usually, the term is used to describe the physical examination finding of the right-upper quadrant of the abdomen...
defines the presence of jaundice and a painlessly distended gallbladder
Gallbladder
In vertebrates the gallbladder is a small organ that aids mainly in fat digestion and concentrates bile produced by the liver. In humans the loss of the gallbladder is usually easily tolerated....
as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstone
Gallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...
s. 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, γ-glutamyl transpeptidase
Gamma glutamyl transpeptidase
Gamma-glutamyltransferase or gamma-glutamyl transpeptidase is an enzyme that transfers gamma-glutamyl functional groups...
and alkaline phosphatase
Alkaline phosphatase
Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
levels). CA19-9
CA19-9
CA19-9 is a tumor marker that is used primarily in the management of pancreatic cancer.-History:...
(carbohydrate antigen 19.9) is a tumor marker
Tumor marker
A tumor marker is a substance found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer...
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
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT scan) and endoscopic ultrasound
Endoscopic ultrasound
Endoscopic ultrasound or echo-endoscopy is a medical procedure in endoscopy is combined with ultrasound to obtain images of the internal organs in the chest and abdomen. It can be used to visualize the wall of these organs, or to look at adjacent structures...
(EUS) can be used to identify the location and form of the cancer.
Pathophysiology
The definitive diagnosis is made by an endoscopic needle biopsyNeedle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
or surgical excision of the radiologically suspicious tissue. Endoscopic ultrasound is often used to visually guide the needle biopsy procedure.
Exocrine pancreas cancers
The most common form of pancreatic cancer (ductal adenocarcinomaAdenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
) is typically characterized by moderately to poorly differentiated glandular structures on microscopic examination. Pancreatic cancer has an immunohistochemical
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
profile that is similar to hepatobiliary cancers (e.g. cholangiocarcinoma
Cholangiocarcinoma
Cholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
) and some stomach cancer
Stomach cancer
Gastric cancer, commonly referred to as stomach cancer, can develop in any part of the stomach and may spread throughout the stomach and to other organs; particularly the esophagus, lungs, lymph nodes, and the liver...
s; thus, it may not always be possible to be certain that a tumour found in the pancreas arose from it.
The second most common type of exocrine pancreas cancer is mucinous. The prognosis is slightly better.
Other exocrine cancers include adenosquamous carcinoma
Adenosquamous carcinoma
Adenosquamous carcinoma is a type of cancer that contains two types of cells: squamous cells and gland-like cells.- External links :* entry in the public domain NCI Dictionary of Cancer Terms...
s, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells.
Pancreatic cystic neoplasms
Pancreatic cystic neoplasms are a broad group of pancreas tumors that have varying malignant potential.Endocrine pancreatic cancers
Pancreatic endocrine tumors (PETs) are also called pancreatic neuroendocrine tumors (PNETs) and islet cell tumors. The annual clinically recognized incidenceIncidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
is low, about five per one million person-years. However, autopsy
Autopsy
An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...
studies incidentally identify PETs in up to 1.5% most of which would remain inert and asymptomatic.
The majority of PNETs are usually categorized as benign but the definition of malignancy in pancreas endocrine tumors has been ambiguous. A small subset of endocrine pancreatic tumors are incontrovertible pancreatic endocrine cancers, that make up about 1% of pancreas cancers. Low- to intermediate-grade neuroendocrine carcinomas of the pancreas may be called islet cell tumors. Some sources have also termed these pancreatic carcinoid, a practice that has sometimes been strongly condemned. Definitional migration has caused some complexity of PNET classification, which has adversely affected what is known about the epidemiology and natural history of these tumors. It is probable that some of these tumors have been included in
ICD-O-3
International Classification of Diseases for Oncology
The International Classification of Diseases for Oncology is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. This classification is widely used by cancer registries.It is currently in its third revision ....
histology classifications 8240–8245, in that they were labeled pancreatic carcinoid tumours but most islet cell carcinomas have been coded as ICD-O-3 system 8150–8155.
The more aggressive endocrine pancreatic cancers are known as pancreatic neuroendocrine carcinomas (PNEC). Similarly, there has likely been a degree of admixture of PNEC and extrapulmonary small cell cancer.
Prevention
According to the American Cancer SocietyAmerican Cancer Society
The American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
, there are no established guidelines for preventing pancreatic cancer, although cigarette smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
has been reported as responsible for 20–30% of pancreatic cancers.
The ACS recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing red meat intake, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically.
In 2006, a large prospective cohort study of over 80,000 subjects failed to prove a definite association. The evidence in support of this lies mostly in small case-control studies.
A long-term study found that people who consumed in the range of 300 to 449 international units (IU) of vitamin D daily had a 43% lower risk of pancreatic cancer than those who took less than 150 IU per day; 150 IU is appreciably less than what was then, or is now, recommended. The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) International Agency for Research on Cancer
International Agency for Research on Cancer
The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organisation of the United Nations....
(IARC), concluded that there were insufficient studies in pancreatic cancer, and while it found evidence for an inverse association between vitamin D and colorectal cancer to be persuasive, it found evidence for a causal link to be limited, and also found that randomized controlled trials (RCTs) were inconclusive. Taking too much vitamin D may be harmful. Poor general diet, obesity, and relative physical inactivity can be risk factors in some cancers, so the role of vitamin D itself is not certain.
B vitamins
B vitamins
B vitamins are a group of water-soluble vitamins that play important roles in cell metabolism. The B vitamins were once thought to be a single vitamin, referred to as vitamin B . Later research showed that they are chemically distinct vitamins that often coexist in the same foods...
, such as B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
, B6
Vitamin B6
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
, and folate, can reduce the risk of pancreatic cancer when consumed in food, but not when ingested in vitamin tablet form.
Screening
People who may have a high risk of pancreatic cancer due to a family history can be followed, but there is no consensus on what constitutes optimal monitoring. Several small studies have shown promising preliminary results for new biomarkers, but further validation on a larger scale is needed. People with pancreatic cancer themselves, or family members, may wish to participate in the activities at a research facility, or identify a pancreas tumor registry.Surgery
Treatment of pancreatic cancer depends on the stage of the cancer. The Whipple procedurePancreaticoduodenectomy
A pancreaticoduodenectomy, pancreatoduodenectomy, Whipple procedure, or Kausch-Whipple procedure, is a major surgical operation involving the pancreas, duodenum, and other organs...
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 (pancreato-duodenectomy), making a bypass for food from stomach to jejunum
Jejunum
The jejunum is the middle section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms middle intestine or mid-gut may be used instead of jejunum.The jejunum lies between the duodenum...
(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
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
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
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
or colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
. 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 chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
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
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
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
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
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
Erlotinib
Erlotinib hydrochloride is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor . It is marketed in the United States by Genentech and OSI...
(Tarceva) in combination with gemcitabine 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
Oxaliplatin
Oxaliplatin is a coordination complex that is used in cancer chemotherapy. These platinum-based drugs are usually classified as alkylating agents, although they are not actually alkylating groups ....
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 histologicallyHistology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
. Treatment of pancreatic endocrine tumors, including the less common malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
tumors, may include:
- Watchful waiting: incidentally identified small tumors, for example on a computed tomographyComputed tomographyX-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(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 syntheticSyntheticSynthesis, the combination of two or more parts, whether by design or by natural processes. Furthermore, it may imply being prepared or made artificially, in contrast to naturally.-In the sense of combination:* Synthetic position, a concept in finance...
hormone analog medication, octreotideOctreotideOctreotide is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone...
, may lessen the symptoms, and sometimes also slows tumor growth.
- Radiation therapy: occasionally used if there is pain due to anatomic extension, such as metastasisMetastasisMetastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
to bone.
- Radiolabeled hormoneHormoneA hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
: some PNETs absorb a hormone called norepinephrineNorepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and these may respond to nuclear medicineNuclear medicineIn nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...
medication, radiolabeled MIBG therapy (or, experamentally, other hormones), given intravenously.
- Radiofrequency ablationRadiofrequency ablationRadio frequency ablation is a medical procedure where part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from the high frequency alternating current to treat a medical disorder...
(RFA), cryoablationCryoablationCryoablation is a process that uses extreme cold to remove tissue .Cryoablation is used in a variety of clinical applications using hollow needles through which cooled, thermally conductive, fluids are circulated...
, 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 (adenocarcinomaAdenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
and less common variants) typically has a poor prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
, 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
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
. Insulin production is hampered, and it has been suggested the cancer can also prompt the onset of diabetes and vice versa. It can be associated with pain, fatigue, weight loss, jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, 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 as 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 medianMedianIn probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...
survival is about 10 and 6 months, respectively. Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months; complete remission is rare.
Outcomes with pancreatic endocrine tumors, many of which are benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
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.
See also
- :Category:Deaths from pancreatic cancer
- :Category:Pancreatic cancer survivors
- Gastrointestinal cancerGastrointestinal cancerGastrointestinal cancer refers to malignant conditions of the gastrointestinal tract, including the esophagus, stomach, biliary system, pancreas, bowels, and anus. The symptoms relate to the organ affected, and can include obstruction , abnormal bleeding, or other associated problems...
- Pancreatic Cancer Action Network (organization in the US)
- Pancreatic Cancer ActionPancreatic Cancer ActionPancreatic Cancer Action is a not-for profit organisation based in the UK whose mission it is to raise awareness of pancreatic cancer.Founded by , who is herself a rare survivor of the disease, Pancreatic Cancer Action is dedicated to saving lives...
(organization in the UK)