Pancreatic cancer: Difference between revisions

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'''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
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   Name          = Pancreatic cancer |
   Name          = Pancreatic cancer |
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   OMIM          = 260350 |
   OMIM          = 260350 |
   MedlinePlus    = 000236 |
   MedlinePlus    = 000236 |
  eMedicineSubj  = med |
  eMedicineTopic = 1712 |
   MeshID        = D010190 |
   MeshID        = D010190 |
}}
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[[Category:Types of cancer]]
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[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Mature chapter]]
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Revision as of 01:17, 29 July 2011

For patient information click here

Pancreatic cancer
ICD-10 C25
ICD-9 157
OMIM 260350
DiseasesDB 9510
MedlinePlus 000236
MeSH D010190

WikiDoc Resources for Pancreatic cancer

Articles

Most recent articles on Pancreatic cancer

Most cited articles on Pancreatic cancer

Review articles on Pancreatic cancer

Articles on Pancreatic cancer in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Pancreatic cancer

Images of Pancreatic cancer

Photos of Pancreatic cancer

Podcasts & MP3s on Pancreatic cancer

Videos on Pancreatic cancer

Evidence Based Medicine

Cochrane Collaboration on Pancreatic cancer

Bandolier on Pancreatic cancer

TRIP on Pancreatic cancer

Clinical Trials

Ongoing Trials on Pancreatic cancer at Clinical Trials.gov

Trial results on Pancreatic cancer

Clinical Trials on Pancreatic cancer at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Pancreatic cancer

NICE Guidance on Pancreatic cancer

NHS PRODIGY Guidance

FDA on Pancreatic cancer

CDC on Pancreatic cancer

Books

Books on Pancreatic cancer

News

Pancreatic cancer in the news

Be alerted to news on Pancreatic cancer

News trends on Pancreatic cancer

Commentary

Blogs on Pancreatic cancer

Definitions

Definitions of Pancreatic cancer

Patient Resources / Community

Patient resources on Pancreatic cancer

Discussion groups on Pancreatic cancer

Patient Handouts on Pancreatic cancer

Directions to Hospitals Treating Pancreatic cancer

Risk calculators and risk factors for Pancreatic cancer

Healthcare Provider Resources

Symptoms of Pancreatic cancer

Causes & Risk Factors for Pancreatic cancer

Diagnostic studies for Pancreatic cancer

Treatment of Pancreatic cancer

Continuing Medical Education (CME)

CME Programs on Pancreatic cancer

International

Pancreatic cancer en Espanol

Pancreatic cancer en Francais

Business

Pancreatic cancer in the Marketplace

Patents on Pancreatic cancer

Experimental / Informatics

List of terms related to Pancreatic cancer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [3] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

Overview

Pancreatic cancer is a malignant tumour within the pancreatic gland. Each year about 33,000 individuals in the United States are diagnosed with this condition, and more than 60,000 in Europe. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with few victims still alive five years after diagnosis, and complete remission still extremely rare.[1]

About 95 percent of pancreatic tumors are adenocarcinomas (Template:ICDO). 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, Template:ICDO, Template:ICDO). These tumors have a completely different diagnostic and therapeutic profile, and generally a more favorable prognosis.[1]

Signs and symptoms

Presentation

Early diagnosis of pancreatic cancer is difficult because the symptoms are so non-specific and varied. Common symptoms include pain in the upper abdomen that typically radiates to the back and is relieved by leaning forward (seen in carcinoma of the body or tail of the pancreas), loss of appetite, significant weight loss and painless jaundice related to bile duct obstruction (carcinoma of the head of the pancreas). All of these symptoms can have multiple other causes. Therefore, pancreatic cancer is often not diagnosed until it is advanced.

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

Trousseau's 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.[2].

Predisposing factors

Risk factors for pancreatic cancer include:[3]

Alcohol

It is controversial whether alcohol consumption is a risk factor for pancreatic cancer. Drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, but "chronic pancreatitis that is due to alcohol doesn't increase risk as much as other types of chronic pancreatitis.[6] Overall, the association is consistently weak and the majority of studies have found no association.[7][8][9][10]

Some studies suggest a relationship,[11] with risk increasing with increasing amount of alcohol intake.[12][13] Risk is greatest in heavy drinkers[14][15][16] mostly on the order of four or more drinks per day.[17] But there appears to be no increased risk for people consuming up to 30g of alcohol a day,[10][18] so most of the U.S. consumes alcohol at a level that "is probably not a risk factor for pancreatic cancer."[16]

Several studies caution that their findings could be due to confounding factors.[15][19] Even if a link exists, it "could be due to the contents of some alcoholic beverages"[20] other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk.[21]

Diagnosis

Most patients with pancreatic cancer experience pain, weight loss, or jaundice.[22]

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 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'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.

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.[23]

Imaging studies, such as computed tomography (CT scan) can be used to identify the location of the cancer. Endoscopic ultrasound (EUS) is another procedure that can help visualize the location and can serve to guide a percutaneous needle biopsy, which is necessary to establish a definitive diagnosis.[24]

Recent research indicates that in pancreatic cancer malignancies, the tumor contains markedly higher levels of certain microRNAs (miRNA) than does the patient's benign pancreatic tissue or that found in other healthy pancreases. This paves the way for two possibilities:

1) a more early but likely expensive genetic and biochemical molecular screening test profile, which would be an innovation in this cancer;

2) also possible new, creative and more effective therapies based on the various microRNA levels. This opens an exciting new front in confronting a very deadly disease.

As a summary; tests that examine the pancreas are used to detect (find), diagnose, and stage pancreatic cancer as follow:

  • Physical exam and history
  • Tumor markers
  • Chest x-ray
  • CT scan (CAT scan)
  • MRI (magnetic resonance imaging)
  • PET scan (positron emission tomography scan)
  • Endoscopic ultrasound (EUS): This procedure is also called endosonography.
  • Laparoscopy
  • Endoscopic retrograde cholangiopancreatography (ERCP)
  • Percutaneous transhepatic cholangiography (PTC): This test is done only if ERCP cannot be done.
  • Biopsy

Diagnostic Findings

Images courtesy of RadsWiki

Treatment

Surgery

Treatment of pancreatic cancer depends on the stage of the cancer.[25] 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 cancer is localised without invading local structures or metastasizing. It can therefore only be performed in the minority of cases.

Spleen-preserving distal pancreatectomy can also be used as a method to remove a cancer running through centre of pancreas; this is invasive surgery, resulting in loss of body and tail. Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy.[26] Recently, localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches.[24]

After surgery, adjuvant chemotherapy with gemcitabine may be offered to eliminate whatever cancerous 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.[27]

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.[24]

Criteria for unresectability:

  • Tumor larger than 5 cm
  • Tumor invades adjacent tissue of organs (excluding duodenum)
  • Encasement, stenosis, or occlusion of the celiac artery, celiac artery branches, and/or SMA.
  • PV and/or SMV encasement (some centers will operate with venous invasion)
  • Hepatic metastases
  • Distant metastases (i.e. non regional lymph nodes)
  • Peritoneal carcinomatosis

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.[28] 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.[29] 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."[30][31]

Treatment Options by Stage

Stages I and II Pancreatic Cancer

Treatment of stage I and stage II pancreatic cancer may include the following:

  • Surgery alone.
  • Surgery with chemotherapy and radiation therapy.

Stage III Pancreatic Cancer

Treatment of stage III pancreatic cancer may include the following:

  • Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine.
  • Chemotherapy with gemcitabine.

Stage IV Pancreatic Cancer

Treatment of stage IV pancreatic cancer may include the following:

  • Chemotherapy with gemcitabine with or without erlotinib.
  • Palliative treatments for pain, such as nerve blocks, and other supportive care.
  • Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine.

Treatment Options for Recurrent Pancreatic Cancer

Treatment of recurrent pancreatic cancer may include the following:

  • Chemotherapy.
  • Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine.
  • Palliative radiation therapy.
  • Other palliative medical care to reduce symptoms, such as nerve blocks to relieve pain.

Prognosis

Patients diagnosed with pancreatic cancer typically have a poor prognosis partly because the cancer usually causes no symptoms early on, leading to metastatic disease at time of diagnosis. Median survival from diagnosis is around 3 to 6 months; 5-year survival is much less than 5%[32] With 32,180 new diagnoses in the United States every year, and 31,800 deaths, mortality approaches 99%, giving pancreatic cancer the highest fatality rate of all cancers and the fourth highest cancer killer in the United States amongst both men and women.[33]

Pancreatic cancer occasionally may 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.[34]

Prevention

Prevention of pancreatic cancer consists of avoiding risk factors when possible[35] Cigarette smoking is considered to be the most significant and avoidable risk factor for pancreatic cancer. Maintaining a healthy weight and exercising may be helpful.

The American Cancer Society recommends increasing consumption of fruits, vegetables, and whole grains while decreasing red meat intake. This has been questioned by several research groups.[36][37] In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[38] The evidence in support of this lies mostly in small case-control studies.

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%.[39][40][41] More studies of this have been called for.

Several studies, including one published June 1, 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.[42][43]

Awareness

  • November is Pancreatic Cancer Awareness ribbon|Awareness Month
  • Purple is the traditional color chosen to represent pancreatic cancer awareness.
  • The National Cancer Institute’s cancer research budget was $4.824 billion in 2004, an estimated $52.7 million of which was devoted to pancreatic cancer.[44]
  • Research spending per pancreatic cancer patient is $1145, the lowest of any leading cancer.[45]
  • For a list of celebrities who have succumbed to this disease, see
  • The Pancreatic Cancer Action Network (PanCAN) was created as an advocacy group for pancreatic cancer.
  • The national charity Pancreatic Cancer UK works to raise awareness in the UK

External links

References

  1. 1.0 1.1 1.2 Ghaneh P, Costello E, Neoptolemos JP (2007). "Biology and management of pancreatic cancer". Gut. 56 (8): 1134–52. doi:10.1136/gut.2006.103333. PMID 17625148.
  2. Carney CP, Jones L, Woolson RF, Noyes R Jr, Doebbeling BN. Relationship between depression and pancreatic cancer in the general population. Psychosom Med 2003;65:884-8. PMID 14508036.
  3. http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_factors_for_pancreatic_cancer_34.asp?sitearea=
  4. Efthimiou E, Crnogorac-Jurcevic T, Lemoine NR, Brentnall TA (2001). "Inherited predisposition to pancreatic cancer". Gut. 48 (2): 143–7. PMID 11156628. Unknown parameter |month= ignored (help)
  5. Michaud DS, Joshipura K, Giovannucci E, Fuchs CS (2007). "A prospective study of periodontal disease and pancreatic cancer in US male health professionals". J. Natl. Cancer Inst. 99 (2): 171–5. doi:10.1093/jnci/djk021. PMID 17228001.
  6. Cancer Research UK Pancreatic cancer risks and causes
  7. National Institute on Alcohol Abuse and Alcoholism Alcohol and Cancer - Alcohol Alert No. 21-1993
  8. American Cancer Society Coffee and Alcohol Do Not Pose a Risk for Pancreatic Cancer
  9. Villeneuve PJ, Johnson KC, Hanley AJ, Mao Y Alcohol, tobacco and coffee consumption and the risk of pancreatic cancer: results from the Canadian Enhanced Surveillance System case-control project. Canadian Cancer Registries Epidemiology Research Group Eur J Cancer Prev 2000 Feb;9(1):49-58. PMID: 10777010
  10. 10.0 10.1 Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts Cancer Epidemiol Biomarkers Prev 2001 May;10(5):429-37 PMID: 11352851
  11. Ahlgren, J. D., et al. Epidemiology and risk factors in pancreatic cancer Seminars in Oncology, 1996, 23(2), 241-250.
  12. Cuzick J, Babiker AG Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease Int J Cancer 1989 Mar 15;43(3):415-21
  13. Harnack LJ, Anderson KE, Zheng W, Folsom AR, Sellers TA, Kushi LH Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women's Health Study Cancer Epidemiol Biomarkers Prev 1997 Dec;6(12):1081-6 PMID: 9419407
  14. Schottenfeld, D. and J. Fraumeni, ed. Cancer epidemiology and prevention. 2nd ed., ed. Vol. 1996, Oxford University Press: Oxford
  15. 15.0 15.1 W Ye, J Lagergren, E Weiderpass, O Nyrén, H-O Adami, A Ekbom Alcohol abuse and the risk of pancreatic cancer Gut 2002;51:236-239
  16. 16.0 16.1 Silverman DT, Brown LM, Hoover RN, Schiffman M, Lillemoe KD, Schoenberg JB, Swanson GM, Hayes RB, Greenberg RS, Benichou J, et al Alcohol and pancreatic cancer in blacks and whites in the United States Cancer Res, 1995. 55(21): p. 4899-905. PMID: 7585527
  17. G W Olsen, J S Mandel, R W Gibson, L W Wattenberg and L M Schuman A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet American Journal of Public Health Vol. 79, Issue 8 1016–1019
  18. Pancreatic cancer risk factors
  19. Zatonski WA, Boyle P, Przewozniak K, Maisonneuve P, Drosik K, Walker AM Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland Int J Cancer 1993 Feb 20;53(4):601-7 PMID: 8436433
  20. Durbec JP, Chevillotte G, Bidart JM, Berthezene P, Sarles H. Diet, alcohol, tobacco and risk of cancer of the pancreas: a case-control study Br J Cancer 1983 Apr;47(4):463-70.
  21. Bueno de Mesquita HB, Maisonneuve P, Moerman CJ, Runia S, Boyle P. Lifetime consumption of alcoholic beverages, tea and coffee and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands Int J Cancer 1992 Feb 20;50(4):514-22 PMID: 1537615
  22. Bakkevold KE, Arnesjø B, Kambestad B (1992). "Carcinoma of the pancreas and papilla of Vater: presenting symptoms, signs, and diagnosis related to stage and tumour site. A prospective multicentre trial in 472 patients. Norwegian Pancreatic Cancer Trial". Scand. J. Gastroenterol. 27 (4): 317–25. doi:10.3109/00365529209000081. PMID 1589710.
  23. Frank J. Domino M.D.etc. (2007). 5 minutes clinical suite version 3. Philadelphia, PA: Lippincott Williams & Wilkins.
  24. 24.0 24.1 24.2 Philip, Philip Agop. "Pancreatic Cancer." ACP PIER & AHFX DI Essentials. American College of Physicians. 4 Apr 2008. Accessed 7 Apr 2009.
  25. Pancreatic Cancer - Johns Hopkins Medicine: Surgical Treatment of Pancreatic Cancer
  26. Retrieved from http://pathology.jhu.edu/pancreas/TreatmentSurgery.php.
  27. Neoptolemos JP, Stocken DD, Friess H; et al. (2004). "A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer". N. Engl. J. Med. 350 (12): 1200–10. doi:10.1056/NEJMoa032295. PMID 15028824.
  28. Demols A, Peeters M, Polus M; et al. (2006). "Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study". Br. J. Cancer. 94 (4): 481–5. doi:10.1038/sj.bjc.6602966. PMID 16434988.
  29. FDA approval briefing
  30. Dhillon N, Aggarwal BB, Newman RA; et al. (2008). "Phase II trial of curcumin in patients with advanced pancreatic cancer". Clin. Cancer Res. 14 (14): 4491–9. doi:10.1158/1078-0432.CCR-08-0024. PMID 18628464. Unknown parameter |month= ignored (help)
  31. De Leon D. "Cancer News and Information: Curcumin Temporarily Slows Pancreatic Cancer". CancerWise.
  32. http://www.who.int/tobacco/research/cancer/en/
  33. http://pancan.org/About/pancreaticCancerStats.html
  34. http://www.molecular-cancer.com/content/2/1/4
  35. http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_Can_pancreatic_cancer_be_prevented_34.asp?rnav=cri
  36. Coughlin, SS (2000 Dec). "Predictors of pancreatic cancer mortality among a large cohort of United States adults". Cancer Causes Control. 11 (10): 915-23. PMID 11142526. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help); |access-date= requires |url= (help)
  37. Zheng, W (1993 Sep). "A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States)". Cancer Causes Control. 4 (5): 477-82. PMID 8218880. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help); |access-date= requires |url= (help)
  38. Larsson, Susanna (February 2006). "Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study". Cancer Epidemiology Biomarkers & Prevention. 15: 301–305. PMID 16492919. Unknown parameter |coauthors= ignored (help); |access-date= requires |url= (help)
  39. http://news.bbc.co.uk/1/hi/health/5334534.stm
  40. http://www.webmd.com/content/article/127/116673.htm
  41. http://www.forbes.com/forbeslife/health/feeds/hscout/2006/09/14/hscout534925.html
  42. "Plasma Folate, Vitamin B6, Vitamin B12, and Homocysteine and Pancreatic Cancer Risk in Four Large Cohorts -- Schernhammer et al. 67 (11): 5553 -- Cancer Research". Retrieved 2007-06-04.
  43. "United Press International - Consumer Health Daily - Briefing". Retrieved 2007-06-04.
  44. http://pancan.org/About/pancreaticCancerStats.html
  45. http://pancan.org/About/pancreaticCancerStats.html

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