Pancreatic cancer

Pancreatic cancer is a malignant neoplasm of the pancreas. Each year in the United States, about 42,470 individuals are diagnosed with this condition and 35,240 die from the disease.[1] The prognosis is generally poor; less than 5 percent of those diagnosed are still alive five years after diagnosis. Complete remission is still extremely rare.[2] About 95% of exocrine pancreatic cancers are adenocarcinomas (M8140/3). The remaining 5% include adenosquamous carcinomas, squamous cell carcinomas, and giant cell carcinomas.[3] Exocrine pancreatic cancers are far more common than endocrine pancreatic cancers (islet cell carcinomas), which make up about 1% of total cases.[4]

Signs and symptoms

Presentation

Pancreatic cancer is sometimes called a “silent killer” because early pancreatic cancer often does not cause symptoms,[5] and the later symptoms are usually non-specific and varied.[5] Therefore, pancreatic cancer is often not diagnosed until it is advanced.[5] Common symptoms include:

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.[6]

Predisposing factors

Risk factors for pancreatic cancer include: [5][7]

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.[14] Overall, the association is consistently weak and the majority of studies have found no association.[15][16][17][18]

Some studies suggest a relationship,[19] with risk increasing with increasing amount of alcohol intake.[20][21] Risk is greatest in heavy drinkers[22][23][24] mostly on the order of four or more drinks per day.[25] But there appears to be no increased risk for people consuming up to 30g of alcohol a day,[18][26] so most of the U.S. consumes alcohol at a level that “is probably not a risk factor for pancreatic cancer.”[24]

Several studies caution that their findings could be due to confounding factors.[23][27] Even if a link exists, it “could be due to the contents of some alcoholic beverages”[28] other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk.[29]

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.”[30]

Diagnosis

Most patients with pancreatic cancer experience pain, weight loss, or jaundice.[31]

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 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.[32]

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.[33]

Treatment

Surgery

Treatment of pancreatic cancer depends on the stage of the cancer.[34] 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.[citation needed] Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy.[35] Recently, localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches.[33]

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.[36]

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.[33]

Chemotherapy

In patients not suitable for resection with curative intent, palliative chemotherapy may be used to improve quality of life and gain a modest survival benefit. Gemcitabine was approved by the United States Food and Drug Administration in 1998 after a clinical trial reported improvements in quality of life 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.[37] 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.[38] 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.

Ongoing trials of gemcitabine combined with nab-Paclitaxel (Abraxane) have shown significant promise with substantially higher response rates, and even some remissions, compared to other therapies in patients with metastatic pancreatic adenocarcinoma.

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%.[39] 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.[40]

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.[41] 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.[42]

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.[43][44] In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[45] The evidence in support of this lies mostly in small case-control studies. [46]

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%.[47][48][49]

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.[50][51]

References

  1. ^ Pancreatic Cancer – National Cancer Institute, U.S. National Institutes of Health (Accessed 10 May 2009)
  2. ^ a b 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.
  3. ^ Detailed Guide, Pancreatic Cancer, What is Cancer of the Pancreas?. http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_pancreatic_cancer_34.asp?sitearea=. Retrieved on 2009-21-2.
  4. ^ Yao, J.C., Eisner, M.P., et al. “Population-Based Study of Islet Cell Carcinoma”. Ann Surg Oncol. 2007 Dec; 14(12): 3492–3500.
  5. ^ a b c d e f g h i What You Need To Know About Cancer of the Pancreas – National Cancer Institute“. 2002-09-16. 4/5. http://www.cancer.gov/cancertopics/wyntk/pancreas/page4. Retrieved on 2007-12-22.
  6. ^ Carney, C. P.; Jones, L.; Woolson, R. F.; Noyes, R. Jr.; Doebbeling, B. N. (2003). “Relationship between depression and pancreatic cancer in the general population”. Psychosom Med 65 (5): 884–888. doi:10.1097/01.PSY.0000088588.23348.D5. PMID 14508036.
  7. ^ ACS :: What Are the Risk Factors for Cancer of the Pancreas?. http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_factors_for_pancreatic_cancer_34.asp?sitearea=. Retrieved on 2007-12-13.
  8. ^ Iodice S, Gandini S, Maisonneuve P, Lowenfels AB (2008). “Tobacco and the risk of pancreatic cancer: a review and meta-analysis”. Langenbecks Arch Surg 393: 535. doi:10.1007/s00423-007-0266-2. PMID 18193270.
  9. ^ 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. http://www.ncbi.nlm.nih.gov/pubmed/16172215. Retrieved on 2009-01-14.
  10. ^ Red Meat May Be Linked to Pancreatic Cancer“. Journal of the National Cancer Institute. WebMD. 2005-10-05. http://www.medscape.com/viewarticle/514268. Retrieved on 2008-03-05.
  11. ^ Obesity Linked to Pancreatic Cancer“. American Cancer Society. Cancer Epidemiology, Biomarkers & Prevention (Vol. 14, No. 2: 459-466). 2005-03-06. http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Obesity_Linked_to_Pancreatic_Cancer.asp. Retrieved on 2008-03-05.
  12. ^ Efthimiou E, Crnogorac-Jurcevic T, Lemoine NR, Brentnall TA (February 2001). “Inherited predisposition to pancreatic cancer”. Gut 48 (2): 143–7. doi:10.1136/gut.48.2.143. PMID 11156628.
  13. ^ 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.
  14. ^ Cancer Research UK Pancreatic cancer risks and causes
  15. ^ National Institute on Alcohol Abuse and Alcoholism Alcohol and Cancer – Alcohol Alert No. 21-1993
  16. ^ American Cancer Society Coffee and Alcohol Do Not Pose a Risk for Pancreatic Cancer
  17. ^ 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
  18. ^ a b 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
  19. ^ Ahlgren, J. D., et al. Epidemiology and risk factors in pancreatic cancer Seminars in Oncology, 1996, 23(2), 241-250.
  20. ^ Cuzick J, Babiker AG Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease Int J Cancer 1989 Mar 15;43(3):415-21
  21. ^ 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
  22. ^ Schottenfeld, D. and J. Fraumeni, ed. Cancer epidemiology and prevention. 2nd ed., ed. Vol. 1996, Oxford University Press: Oxford
  23. ^ a b 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
  24. ^ a b 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
  25. ^ 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
  26. ^ Pancreatic cancer risk factors
  27. ^ 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
  28. ^ 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.
  29. ^ 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
  30. ^ Jeanine M. Genkinger, Donna Spiegelman, Kristin E. Anderson, Leif Bergkvist, Leslie Bernstein, Piet A. van den Brandt, Dallas R. English, Jo L. Freudenheim, Charles S. Fuchs, Graham G. Giles, Edward Giovannucci, Susan E. Hankinson, Pamela L. Horn-Ross, Michael Leitzmann, Satu Männistö, James R. Marshall, Marjorie L. McCullough, Anthony B. Miller, Douglas J. Reding, Kim Robien, Thomas E. Rohan, Arthur Schatzkin, Victoria L. Stevens, Rachael Z. Stolzenberg-Solomon, Bas A.J. Verhage, Alicja Wolk, Regina G. Ziegler and Stephanie A. Smith-Warner Alcohol Intake and Pancreatic Cancer Risk: A Pooled Analysis of Fourteen Cohort Studies Cancer Epidemiology Biomarkers & Prevention 18, 765, March 1, 2009. doi: 10.1158/1055-9965.EPI-08-0880
  31. ^ 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.
  32. ^ Frank J. Domino M.D.etc. (2007). 5 minutes clinical suite version 3. Philadelphia, PA: Lippincott Williams & Wilkins.
  33. ^ a b c Philip, Philip Agop. “Pancreatic Cancer.” ACP PIER & AHFX DI Essentials. American College of Physicians. 4 Apr 2008. Accessed 7 Apr 2009.
  34. ^ Pancreatic Cancer – Johns Hopkins Medicine: Surgical Treatment of Pancreatic Cancer
  35. ^ Retrieved from http://pathology.jhu.edu/pancreas/TreatmentSurgery.php.
  36. ^ 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.
  37. ^ 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.
  38. ^ FDA approval briefing
  39. ^ WHO | Cancer
  40. ^ Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007). “Cancer statistics, 2007“. CA Cancer J Clin 57 (1): 43–66. doi:10.3322/canjclin.57.1.43. PMID 17237035. http://caonline.amcancersoc.org/cgi/content/full/57/1/43.
  41. ^ Wang F, Herrington M, Larsson J, Permert J (January 2003). “The relationship between diabetes and pancreatic cancer“. Mol. Cancer 2: 4. doi:10.1186/1476-4598-2-4. PMID 12556242. PMC: 149418. http://www.molecular-cancer.com/content/2/1/4.
  42. ^ ACS :: Can Cancer of the Pancreas be Prevented?. http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_Can_pancreatic_cancer_be_prevented_34.asp?rnav=cri. Retrieved on 2007-12-13.
  43. ^ Coughlin, SS; Calle EE, Patel AV, Thun MJ. (December 2000). “Predictors of pancreatic cancer mortality among a large cohort of United States adults”. Cancer Causes Control. 11 (10): 915–23.. doi:10.1023/A:1026580131793. PMID 11142526.
  44. ^ Zheng, W; et al. (September 1993). “A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States)”. Cancer Causes Control. 4 (5): 477–82.. doi:10.1007/BF00050867. PMID 8218880.
  45. ^ Larsson, Susanna; Niclas Håkansson, Ingmar Näslund, Leif Bergkvist and Alicja Wolk (February 2006). “Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study”. Cancer Epidemiology Biomarkers & Prevention 15: 301–305. doi:10.1158/1055-9965.EPI-05-0696. PMID 16492919.
  46. ^ 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. http://www.ncbi.nlm.nih.gov/pubmed/16172215. Retrieved on 2009-01-14.
  47. ^ BBC NEWS | Health | Vitamin D ‘slashes cancer risk’
  48. ^ Vitamin D May Cut Pancreatic Cancer
  49. ^ http://www.forbes.com/forbeslife/health/feeds/hscout/2006/09/14/hscout534925.html
  50. ^ Schernhammer E, Wolpin B, Rifai N, et al. (June 2007). “Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts“. Cancer Res. 67 (11): 5553–60. doi:10.1158/0008-5472.CAN-06-4463. PMID 17545639. http://cancerres.aacrjournals.org/cgi/content/abstract/67/11/5553.
  51. ^ United Press International – Consumer Health Daily – Briefing. http://www.upi.com/Consumer_Health_Daily/Briefing/2007/06/01/pancreatic_cancer_risk_cut_by_b6_b12/3712/. Retrieved on 2007-06-04.
  1. alcohol, tobacco and risk of cancer of the pancreas: a case-control study Br J Cancer 1983 Apr;47(4):463-70.
  2. ^ 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
  3. ^ Jeanine M. Genkinger, Donna Spiegelman, Kristin E. Anderson, Leif Bergkvist, Leslie Bernstein, Piet A. van den Brandt, Dallas R. English, Jo L. Freudenheim, Charles S. Fuchs, Graham G. Giles, Edward Giovannucci, Susan E. Hankinson, Pamela L. Horn-Ross, Michael Leitzmann, Satu Männistö, James R. Marshall, Marjorie L. McCullough, Anthony B. Miller, Douglas J. Reding, Kim Robien, Thomas E. Rohan, Arthur Schatzkin, Victoria L. Stevens, Rachael Z. Stolzenberg-Solomon, Bas A.J. Verhage, Alicja Wolk, Regina G. Ziegler and Stephanie A. Smith-Warner Alcohol Intake and Pancreatic Cancer Risk: A Pooled Analysis of Fourteen Cohort Studies Cancer Epidemiology Biomarkers & Prevention 18, 765, March 1, 2009. doi: 10.1158/1055-9965.EPI-08-0880
  4. ^ 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.
  5. ^ Frank J. Domino M.D.etc. (2007). 5 minutes clinical suite version 3. Philadelphia, PA: Lippincott Williams & Wilkins.
  6. ^ a b c Philip, Philip Agop. “Pancreatic Cancer.” ACP PIER & AHFX DI Essentials. American College of Physicians. 4 Apr 2008. Accessed 7 Apr 2009.
  7. ^ Pancreatic Cancer – Johns Hopkins Medicine: Surgical Treatment of Pancreatic Cancer
  8. ^ Retrieved from http://pathology.jhu.edu/pancreas/TreatmentSurgery.php.
  9. ^ 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.
  10. ^ 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.
  11. ^ FDA approval briefing
  12. ^ WHO | Cancer
  13. ^ Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007). “Cancer statistics, 2007“. CA Cancer J Clin 57 (1): 43–66. doi:10.3322/canjclin.57.1.43. PMID 17237035. http://caonline.amcancersoc.org/cgi/content/full/57/1/43.
  14. ^ Wang F, Herrington M, Larsson J, Permert J (January 2003). “The relationship between diabetes and pancreatic cancer“. Mol. Cancer 2: 4. doi:10.1186/1476-4598-2-4. PMID 12556242. PMC: 149418. http://www.molecular-cancer.com/content/2/1/4.
  15. ^ ACS :: Can Cancer of the Pancreas be Prevented?. http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_Can_pancreatic_cancer_be_prevented_34.asp?rnav=cri. Retrieved on 2007-12-13.
  16. ^ Coughlin, SS; Calle EE, Patel AV, Thun MJ. (December 2000). “Predictors of pancreatic cancer mortality among a large cohort of United States adults”. Cancer Causes Control. 11 (10): 915–23.. doi:10.1023/A:1026580131793. PMID 11142526.
  17. ^ Zheng, W; et al. (September 1993). “A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States)”. Cancer Causes Control. 4 (5): 477–82.. doi:10.1007/BF00050867. PMID 8218880.
  18. ^ Larsson, Susanna; Niclas Håkansson, Ingmar Näslund, Leif Bergkvist and Alicja Wolk (February 2006). “Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study”. Cancer Epidemiology Biomarkers & Prevention 15: 301–305. doi:10.1158/1055-9965.EPI-05-0696. PMID 16492919.
  19. ^ 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. http://www.ncbi.nlm.nih.gov/pubmed/16172215. Retrieved on 2009-01-14.
  20. ^ BBC NEWS | Health | Vitamin D ‘slashes cancer risk’
  21. ^ Vitamin D May Cut Pancreatic Cancer
  22. ^ http://www.forbes.com/forbeslife/health/feeds/hscout/2006/09/14/hscout534925.html
  23. ^ Schernhammer E, Wolpin B, Rifai N, et al. (June 2007). “Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts“. Cancer Res. 67 (11): 5553–60. doi:10.1158/0008-5472.CAN-06-4463. PMID 17545639. http://cancerres.aacrjournals.org/cgi/content/abstract/67/11/5553.
  24. ^ United Press International – Consumer Health Daily – Briefing. http://www.upi.com/Consumer_Health_Daily/Briefing/2007/06/01/pancreatic_cancer_risk_cut_by_b6_b12/3712/. Retrieved on 2007-06-04.

About zeep19

Mencari arti sebuah kehidupan.... Ingin lebih mendalami kehidupan di dunia maya... Gx muluk-muluk, tp terpenuhi semuanya:-D Yang terpenting c.. bisa memperbanyak tali silahturahmi...

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