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Pancreatic cancer

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Pancreatic cancer
SpecialtyOncology, gastroenterology Edit this on Wikidata

Pancreatic cancer is a malignant tumor of the pancreas. Each year in the United States, about 37,680 individuals are diagnosed with this condition and 34,290 die from the disease each year.[citation needed] In Europe more than 60,000 are diagnosed each year. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with less than 5 percent of those diagnosed are still alive five years after diagnosis, and complete remission is still extremely rare.[1]. About 95% of cancers of the exocrine pancreas are adenocarcinomas (M8140/3) [2]. The remaining 5 percent include other tumors of the exocrine pancreas (e.g., serous cystadenomas), acinar cell cancers, and pancreatic neuroendocrine tumors (such as insulinomas, M8150/1, M8150/3). These tumors have a completely different diagnostic and therapeutic profile, and generally a more favorable prognosis.[1]

Joe im oftin curious about you

Presentation

Pancreatic cancer is sometimes called a "silent killer" because early pancreatic cancer often does not cause symptoms,[3] and the later symptoms are usually non-specific and varied.[3] Common symptoms include:

All of these symptoms can have multiple other causes. Therefore, pancreatic cancer is often not diagnosed until it is advanced.[3]

Jaundice occurs when the tumor grows and obstructs the common bile duct, which runs partially through the head of the pancreas. Tumors of the head of the pancreas (approximately 60% of cases) are more likely to cause jaundice by this mechanism.

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.

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.[4]

Predisposing factors

Risk factors for pancreatic cancer include: [5][3]

Alcohol

Drinking alcohol is a possible risk factor. Cancer Research UK states, "About 7 out of 10 cases of chronic pancreatitis are due to long term heavy drinking. Chronic pancreatitis is a known risk factor for cancer of the pancreas. But chronic pancreatitis that is due to alcohol doesn't increase risk as much as other types of chronic pancreatitis. So if there is a link with alcohol and pancreatic cancer risk, it is only very slight."[12]

"A few studies have linked chronic heavy drinking with cancers of the stomach, pancreas, and lungs. However, the association is consistently weak and the majority of studies have found no association", write the NIAAA,[13] citing the International Agency for Research on Cancer.[14] Alcohol has been reported as a possible risks in some (but not in most) studies.[15] Drinking alcohol excessively is a cause of acute pancreatitis and chronic pancreatitis.

"Chronic heavy alcohol consumption is a risk factor for pancreatitis, but evidence for an association with pancreatic cancer is inconsistent. Overall, research suggests an increased risk in heavy drinkers[16][17][18] , but no increased risk for people consuming up to 30g of alcohol a day[19]."[20]

A study found, "An index of total alcohol consumption showed a greater than two-fold risk for pancreatic cancer for heavy alcohol consumption (four or more drinks per day), primarily due to heavy beer and hard liquor consumption.[21]

"Our findings indicate that alcohol drinking at the levels typically consumed by the general population of the United States is probably not a risk factor for pancreatic cancer. Our data suggest, however, that heavy alcohol drinking may be related to pancreatic cancer risk."[18]

The Iowa Women's Health Study found that, "Relative risks of pancreatic cancer increased with the amount of alcohol consumed (Ptrend = 0.11) after adjustment for age, smoking status, and pack-years of smoking."[22]

"Cases [people with pancreatic cancer] drank significantly more beer than controls (p = 0.005) and there was evidence of a positive trend in risk with total alcohol consumption."[23]

A Swedish study found "Alcoholics had only a modest 40% excess risk of pancreatic cancer … The excess risk for pancreatic cancer among alcoholics is small and could conceivably be attributed to confounding by smoking."[17]

A British study stated, "It was shown that the relative risk of cancer of the pancreas increases with fat and alcohol intakes, … Alcohol may be not directly involved in the aetiology of cancer of the pancreas: its effect could be due to the contents of some alcoholic beverages."[24]

A Dutch study found that, "When compared with data from non-drinkers, the cumulative lifetime consumption of all types of alcohol in grams of ethanol … beer, spirits, red wine and fortified wine was not related to risk. The consumption of white wine was inversely associated with risk …. The uniformly reduced risk estimates for the lifetime number of drinks of white wine were based on small numbers …."[25]

A Polish study concluded, "The findings regarding alcoholic beverages were overall null, although the weakly positive trend in risk with spirits consumption (p = 0.71) may deserve further investigation in view of the special nature of the source of spirits (vodka) in Poland."[26]

"For the most part, consumption of total alcohol, wine, liquor and beer was not associated with pancreatic cancer."[27]

"Data from these two large cohorts do not support any overall association between coffee intake or alcohol intake and risk of pancreatic cancer."[19]

Diagnosis

History — Most patients with pancreatic cancer experience pain, weight loss, or jaundice.[28]

Pain is present in 80 to 85 percent of patients with locally advanced or advanced metastic 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 tumor location. Tumors 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's 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 gallstones.[citation needed]

Tiredness, irritability and difficulty eating due to pain also exist.

Pancreatic cancer is usually 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 due to benign causes of biliary obstruction.[29]

Imaging studies, such as ultrasound or abdominal CT, can be used to identify tumors. Endoscopic ultrasound (EUS) is another procedure that can help visualize the tumor and obtain tissue to establish the diagnosis. Endoscopic retrograde cholangiopancreatography (ERCP) is also used.[citation needed]

Treatment

Surgery

Treatment of pancreatic cancer depends on the stage of the cancer.[30] The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas. It can only be performed if the patient is likely to survive major surgery and if the tumor is localised without invading local structures or metastasizing. It can therefore only be performed in the minority of cases. Recent advances have made possible resection (surgical removal) of tumors that were previously unresectable due to blood vessel involvement.[citation needed]

Spleen-preserving distal pancreatectomy can also be used as a method to remove a neoplasm or tumour running through centre of pancreas; this is invasive surgery, resulting in loss of body and tail.[citation needed]

Tumors of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy.[31] Recently, localized tumors of the pancreas have been resected using minimally invasive (laparoscopic) approaches.[citation needed]

After surgery, adjuvant chemotherapy with gemcitabine may be offered to eliminate whatever tumor tissue may remain in the body. This has been shown to increase 5-year survival rates. 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.[32]

Surgery can be performed for palliation, if the tumor 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.[citation needed]

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 US FDA in 1998 after a clinical trial reported improvements in quality of life in patients with advanced pancreatic cancer. This marked the first FDA approval of a chemotherapy drug for a non-survival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis. Addition of oxaliplatin (Gem/Ox) conferred benefit in small trials, but is not yet standard therapy.[33] Fluorouracil (5FU) may also be included.

On the basis of a Canadian led Phase III Randomised Controlled trial involving 569 patients with advanced pancreatic cancer, the US FDA has licensed the use of erlotinib (Tarceva) in combination with gemcitabine as a palliative regimen for pancreatic cancer. This trial compared the action of gemcitabine/erlotinib vs gemcitabine/placebo and demonstrated improved survival rates, improved tumor response and improved progression-free survival rates. The survival improvement with the combination is on the order of less than four weeks, leading some cancer experts to question the incremental value of adding erlotinib to gemcitabine treatment. New trials are now investigating the effect of the above combination in the adjuvant and neoadjuvant setting.[34] A trial of anti-angiogenesis agent bevacizumab (Avastin) as an addition to chemotherapy has shown no improvement in survival of patients with advanced pancreatic cancer. It may cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.

Nutritional supplements

A phase II clinical trial studying the effect of curcumin on pancreatic cancer was completed in 2007 and the results were published in 2008. The study used eight grams per day in 21 patients and stopped treatment if the tumor size increased. The conclusion of the study was "Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer."[35][36]

Prognosis

Patients diagnosed with pancreatic cancer typically have a poor prognosis partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis. Median survival from diagnosis is around 3 to 6 months; 5-year survival is less than 5%.[37] With 37,170 cases diagnosed in the United States in 2007, and 33,700 deaths, pancreatic cancer has one of the highest fatality rates of all cancers and is the fourth highest cancer killer in the United States among both men and women. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year.[38]

Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered and it has been suggested that the cancer can also prompt the onset of diabetes and vice versa.[39] Thus diabetes is both a risk factor for the development of pancreatic cancer and diabetes can be an early sign of the disease in the elderly.

Prevention

According to the American Cancer Society, there are no established guidelines for preventing pancreatic cancer, although cigarette smoking has been reported as responsible for 20-30% of pancreatic cancers.[40]

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 that this will prevent or reduce pancreatic cancer specifically.[41][42] In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[43] The evidence in support of this lies mostly in small case-control studies. [44]

In September 2006, a long-term study concluded that taking Vitamin D can substantially cut the risk of pancreatic cancer (as well as other cancers) by up to 50%.[45][46][47]

Several studies, including one published on 1 June 2007, indicate that 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.[48][49]

See also

References

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  44. ^ "Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area". Cancer epidemiology, biomarkers & prevention. pubMed.gov. 2005-08. Retrieved 2009-01-14. {{cite web}}: Check date values in: |date= (help)
  45. ^ BBC NEWS | Health | Vitamin D 'slashes cancer risk'
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