User talk:Wiki CRUK John/Pancreatic cancer (version h)

Wiki CRUK John/Pancreatic cancer (version h)

Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors, is adenocarcinoma (tumors exhibiting glandular architecture on light microscopy) arising within the exocrine component of the pancreas. A minority arise from islet cells, and are classified as neuroendocrine tumors. The signs and symptoms that eventually lead to the diagnosis depend on the location, the size, and the tissue type of the tumor, and may include abdominal pain, lower back pain, and jaundice (if the tumor compresses the bile duct), unexplained weight loss, and digestive problems.

Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States[1] and the twelfth worldwide.[2] Pancreatic cancer has an extremely poor prognosis: for all stages combined, the 1- and 5-year relative survival rates are 25% and 6%, respectively;[3] for local disease the 5-year survival is approximately 15% [3][4] while the median survival for locally advanced and for metastatic disease, which collectively represent over 80% of individuals,[4] is about 10 and 6 months respectively.[5] Individuals vary, however - some are only diagnosed when they are already terminally ill and therefore only have a few days or weeks. Others have slower progression and may live a couple of years even if surgery is not possible. Men are 30% more likely to get pancreatic cancer than are women. [citation needed]

Signs and symptoms edit

Early pancreatic cancer often does not cause symptoms,[6] and the later symptoms are usually nonspecific and varied.[6] Therefore, pancreatic cancer is often not diagnosed until it is advanced.[6] Common symptoms include:

  • Pain in the upper abdomen that typically radiates to the back[6] (seen in carcinoma of the body or tail of the pancreas)
  • Heartburn - acid stomach
  • Poor appetite or nausea and vomiting[6]
  • Diarrhea, loose stools.
  • Significant weight loss (cachexia)
  • Painless jaundice (yellow tint to whites of eyes (sclera) or yellowish skin, possibly in combination with darkened urine)[6] when a cancer of the head of the pancreas (75% of cases)[7] obstructs the common bile duct as it runs through the pancreas. This may also cause pale-colored stool and steatorrhea. The jaundice may be associated with itching as the salt from excess bile can cause skin irritation.
  • Trousseau syndrome, 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, may be associated with pancreatic cancer.
  • Pulmonary embolisms due to pancreatic cancers producing blood clotting chemicals.
  • 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.[8]
  • 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.[9]
  • Symptoms of pancreatic cancer metastasis. Typically, pancreatic cancer first metastasizes to regional lymph nodes, and later to the liver or to the peritoneal cavity and, rarely, to the lungs;[10] it rarely metastasizes to bone or brain.[11]

Risk factors edit

Risk factors for pancreatic cancer may include:[6][12]

  • 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 BRCA2 gene and PALB2 gene, Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene, hereditary non-polyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, and the familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene.[13][14] There may also be a history of familial pancreatitis.[13]
  • Age. The risk of developing pancreatic cancer increases with age. Most cases occur after age 60, while cases before age 40 are uncommon.
  • Smoking. Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer; a decade of nonsmoking after heavy smoking is associated with a risk ratio of 1.2.[15]
  • Diets low in vegetables and fruits.[16]
  • Diets high in red meat. Processed meat consumption is positively associated with pancreatic cancer risk, and red meat consumption was associated with an increased risk of pancreatic cancer in men.[17]
  • Diets high in sugar-sweetened drinks (soft drinks).[18] In particular, limited epidemiological studies link the common soft drink sweetener fructose with growth of pancreatic cancer cells.[19]
  • Obesity[20]
  • Diabetes mellitus is both risk factor for pancreatic cancer, and, as noted earlier, new onset diabetes can be an early sign of the disease.
  • Chronic pancreatitis has been linked, but is not known to be causal. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.
  • Helicobacter pylori infection[21][22]
  • Gingivitis or periodontal disease[23]
  • Partial gastrectomy[24][25]

Alcohol edit

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.[26][27][28] Although drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, chronic pancreatitis associated with alcohol consumption is less frequently a precursor for pancreatic cancer than other types of chronic pancreatitis.[29]

Some studies suggest a relationship,[30] the risk increasing with increasing amount of alcohol intake.[31][32] The risk is greatest in heavy drinkers,[33][34][35] mostly on the order of four or more drinks per day.[36] There appears to be no increased risk for people consuming up to 30g of alcohol a day,[28][37][38] which is approximately 2 alcoholic beverages/day,[38] so most people who take alcohol do so at a level that "is probably not a risk factor for pancreatic cancer".[35] 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".[38]

Several studies caution that their findings could be due to confounding factors.[34][39] Even if a link exists, it "could be due to the contents of some alcoholic beverages"[40] other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk.[41]

Diagnosis edit

 
Axial CT image with i.v. contrast. Macrocystic adenocarcinoma of the pancreatic head.

Most patients with pancreatic cancer experience pain, weight loss, or jaundice.[42]

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, diarrhoea, 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 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.[43] Imaging studies, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) can be used to identify the location and form of the cancer. The definitive diagnosis is made by an endoscopic needle biopsy or surgical excision of the radiologically suspicious tissue. Endoscopic ultrasound is often used to visually guide the needle biopsy procedure.[44] Nonetheless, pancreatic cancer is usually staged using a CT scan. In fact, a histologic diagnosis is not usually required for resection of the tumor, rather histologic analysis helps determine which chemotherapeutic regimen to start.[45]

Pathophysiology edit

 
Micrograph of pancreatic ductal adenocarcinoma (the most common type of pancreatic cancer). H&E stain.

The development of pancreatic cancer may involve the over-expression of oncogenes, inactivation of tumor suppressor genes or the deregulation of various signaling proteins.[46] Mutations leading to carcinoma may be accelerated by genetic or environmental factors and other risk factors already described. Specific mutations vary among and even within the cyto-histologic categories discussed below.

Exocrine pancreas cancers edit

 
Micrographs of normal pancreas, pancreatic intraepithelial neoplasia (precursors to pancreatic carcinoma) and pancreatic carcinoma. H&E stain.

The most common form of pancreatic cancer (ductal adenocarcinoma) 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 cancers; thus, it may not always be possible to be certain that a tumour found in the pancreas arose from it.

The genetic events that cause ductal adenocarcinoma have been well characterized. The most common are KRAS mutations (96%), CDKN2A mutations/deletions (75%), TP53 mutations (55%), SMAD4 deletions/mutations (50%), and SWI/SNF mutations/deletions (35%).[47][48]

 
Cross section of a human liver, taken at autopsy examination, showing multiple large pale tumor deposits. The tumor is an adenocarcinoma derived from a primary lesion in the body of the pancreas.

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.[49] The cellular origin of these lesions is debated.

The second most common type of exocrine pancreas cancer is mucinous.[citation needed] [discuss] The prognosis is slightly better. [citation needed] [discuss]

Other exocrine cancers include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells.[50]

Pancreatic cystic neoplasms edit

Pancreatic cystic neoplasms are a broad group of pancreas tumors that have varying malignant potential.[discuss]

Pancreatic neuroendocrine tumors edit

Endocrine pancreatic tumors have been variously called islet cell tumors, pancreas endocrine tumors (PETs), and pancreatic neuroendocrine tumors (PNETs).[51] The annual clinically recognized incidence is low, about five per one million person-years.[50] However, autopsy studies incidentally identify PETs in up to 1.5%[5] most of which would remain inert and asymptomatic.[5]

The majority of PNETs are usually categorized as benign[52][53][54] 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.[50][51] Low- to intermediate-grade neuroendocrine carcinomas of the pancreas may be called islet cell tumors. Some sources have also termed these pancreatic carcinoid,[51] a practice that has sometimes been strongly condemned.[citation needed] Definitional migration has caused some complexity of PNET classification,[51] which has adversely affected what is known about the epidemiology and natural history of these tumors.[51] 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[51][55] but most islet cell carcinomas have been coded as ICD-O-3 system 8150–8155.[51]

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 carcinoma.[citation needed]

Prevention edit

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.[56]

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.[57][58] In 2006, a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[59] The evidence in support of this lies mostly in small case-control studies.[16]

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;[60]

See also edit

References edit

  1. ^ Hariharan D, Saied A, Kocher HM (2008). "Analysis of mortality rates for pancreatic cancer across the world". HPB. 10 (1): 58–62. doi:10.1080/13651820701883148. PMC 2504856. PMID 18695761.
  2. ^ http://globocan.iarc.fr/Pages/fact_sheets_population.aspx
  3. ^ a b "American Cancer Society: Cancer Facts & Figures 2010: see page 4 for incidence estimates, and page 19 for survival percentages" (PDF).
  4. ^ a b National Cancer Institute. General Information About Pancreatic Cancer. http://www.cancer.gov/cancertopics/pdq/treatment/pancreatic/HealthProfessional
  5. ^ a b c Benson AB, Myerson RJ, and Sasson AR. Pancreatic, Neuroendocrine GI, and Adrenal Cancers. Cancer Management 13th edition. http://www.cancernetwork.com/cancer-management/pancreatic/article/10165/1802606
  6. ^ a b c d e f g "What You Need To Know About Cancer of the Pancreas — National Cancer Institute". 16 September 2002. p. 4/5. Retrieved 22 December 2007.
  7. ^ Dragovich, Tomislav (13 September 2011). "Pancreatic Cancer". Medscape Reference.
  8. ^ Pannala R, Basu A, Petersen GM, Chari ST (January 2009). "New-onset Diabetes: A Potential Clue to the Early Diagnosis of Pancreatic Cancer". The Lancet Oncology. 10 (1): 88–95. doi:10.1016/S1470-2045(08)70337-1. PMC 2795483. PMID 19111249.
  9. ^ Carney CP, Jones L, Woolson RF, Noyes R, Doebbeling BN (2003). "Relationship between depression and pancreatic cancer in the general population". Psychosomatic Medicine. 65 (5): 884–8. doi:10.1097/01.PSY.0000088588.23348.D5. PMID 14508036.
  10. ^ Medscape > Pancreatic Cancer Author: Tomislav Dragovich. Chief Editor: Jules E Harris. Updated: 5 May 2011
  11. ^ AJCC Cancer Staging Manual 2nd edition; Chapter 15; Pancreas – original pages 95–98; page 95 for citation regarding "...lesser degree of involvement of bones and brain and other anatomical sites." http://www.cancerstaging.org/products/csmanual2ed.pdf
  12. ^ "ACS :: What Are the Risk Factors for Cancer of the Pancreas?". Archived from the original on 12 October 2007. Retrieved 13 December 2007.
  13. ^ a b Cite error: The named reference pmid17625148 was invoked but never defined (see the help page).
  14. ^ 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. PMC 1728218. PMID 11156628.
  15. ^ Iodice S, Gandini S, Maisonneuve P, Lowenfels AB (July 2008). "Tobacco and the risk of pancreatic cancer: a review and meta-analysis". Langenbeck's Archives of Surgery. 393 (4): 535–45. doi:10.1007/s00423-007-0266-2. PMID 18193270.
  16. ^ a b Chan JM, Wang F, Holly EA (September 2005). "Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area". Cancer Epidemiology, Biomarkers & Prevention. 14 (9): 2093–7. doi:10.1158/1055-9965.EPI-05-0226. PMID 16172215.
  17. ^ Larsson SC, Wolk A (January 2012). "Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies". Br J Cancer. Online first (3): 603–7. doi:10.1038/bjc.2011.585. PMC 3273353. PMID 22240790.
  18. ^ "Soft Drink and Juice Consumption and Risk of Pancreatic Cancer: The Singapore Chinese Health Study".
  19. ^ Liu H, Huang D, McArthur DL, Boros LG, Nissen N, Heaney AP (2010). "Fructose Induces Transketolase Flux to Promote Pancreatic Cancer Growth". Cancer Res. 70 (15): 6368–76. doi:10.1158/0008-5472.CAN-09-4615. PMID 20647326. Retrieved 25 October 2013.
  20. ^ "Obesity Linked to Pancreatic Cancer". American Cancer Society. Cancer Epidemiology, Biomarkers & Prevention (Vol. 14, No. 2: 459–466). 6 March 2005. Archived from the original on 5 February 2008. Retrieved 5 March 2008.
  21. ^ Raderer M, Wrba F, Kornek G, Maca T, Koller DY, Weinlaender G, Hejna M, Scheithauer W (1998). "Association between Helicobacter pylori Infection and Pancreatic Cancer". Oncology. 55 (1): 16–19. doi:10.1159/000011830. PMID 9428370.
  22. ^ Stolzenberg-Solomon RZ, Blaser MJ, Limburg PJ, Perez-Perez G, Taylor PR, Virtamo J, Albanes D (June 2001). "Helicobacter pylori seropositivity as a risk factor for pancreatic cancer". J. Natl. Cancer Inst. 93 (12): 937–41. doi:10.1093/jnci/93.12.937. PMID 11416115.
  23. ^ Michaud DS, Joshipura K, Giovannucci E, Fuchs CS (January 2007). "A prospective study of periodontal disease and pancreatic cancer in US male health professionals". Journal of the National Cancer Institute. 99 (2): 171–5. doi:10.1093/jnci/djk021. PMID 17228001.
  24. ^ van Rees BP, Tascilar M, Hruban RH, Giardiello FM, Tersmette AC, Offerhaus GJ (1999). "Remote partial gastrectomy as a risk factor for pancreatic cancer: potential for preventive strategies". Ann Oncol. 10 Suppl 4: 204–207. PMID 10436823.
  25. ^ Tersmette AC, Giardiello FM, Tytgat GN, Offerhaus GJ (1995). "Carcinogenesis after remote peptic ulcer surgery: the long-term prognosis of partial gastrectomy". Scand J Gastroenterol Suppl. 212: 96–99. doi:10.3109/00365529509090306. PMID 8578237.
  26. ^ National Institute on Alcohol Abuse and Alcoholism Alcohol and Cancer - Alcohol Alert No. 21-1993
  27. ^ Villeneuve PJ, Johnson KC, Hanley AJ, Mao Y (February 2000). "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". European Journal of Cancer Prevention. 9 (1): 49–58. doi:10.1097/00008469-200002000-00007. PMID 10777010.
  28. ^ a b Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS (May 2001). "Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts". Cancer Epidemiology, Biomarkers & Prevention. 10 (5): 429–37. PMID 11352851.
  29. ^ Cancer Research UK Pancreatic cancer risks and causes
  30. ^ Ahlgren JD (April 1996). "Epidemiology and risk factors in pancreatic cancer". Seminars in Oncology. 23 (2): 241–50. PMID 8623060.
  31. ^ Cuzick J, Babiker AG (March 1989). "Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease". International Journal of Cancer. 43 (3): 415–21. doi:10.1002/ijc.2910430312. PMID 2925272.
  32. ^ Harnack LJ, Anderson KE, Zheng W, Folsom AR, Sellers TA, Kushi LH (December 1997). "Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women's Health Study". Cancer Epidemiology, Biomarkers & Prevention. 6 (12): 1081–6. PMID 9419407.
  33. ^ Schottenfeld, D. and J. Fraumeni, ed. Cancer epidemiology and prevention. 2nd ed., ed. Vol. 1996, Oxford University Press: Oxford[page needed]
  34. ^ a b Ye W, Lagergren J, Weiderpass E, Nyrén O, Adami HO, Ekbom A (August 2002). "Alcohol abuse and the risk of pancreatic cancer". Gut. 51 (2): 236–9. doi:10.1136/gut.51.2.236. PMC 1773298. PMID 12117886.
  35. ^ a b Silverman DT, Brown LM, Hoover RN, Schiffman M, Lillemoe KD, Schoenberg JB, Swanson GM, Hayes RB, Greenberg RS, Benichou J (November 1995). "Alcohol and pancreatic cancer in blacks and whites in the United States". Cancer Research. 55 (21): 4899–905. PMID 7585527.
  36. ^ Olsen GW, Mandel JS, Gibson RW, Wattenberg LW, Schuman LM (August 1989). "A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet". American Journal of Public Health. 79 (8): 1016–9. doi:10.2105/AJPH.79.8.1016. PMC 1349898. PMID 2751016.
  37. ^ "Pancreatic cancer risk factors". Info.cancerresearchuk.org. 4 November 2008. Retrieved 15 September 2009.
  38. ^ a b c "In summary, a weak positive association between alcohol intake during adulthood and pancreatic cancer risk was observed in the highest category of intake (≥30g/day or approximately 2 alcoholic beverages/day). Associations with alcohol intake were stronger among individuals who were normal weight. Thus, our findings are consistent with a modest increase in risk of pancreatic cancer for alcohol intakes of at least 30 grams/day." Genkinger JM, Spiegelman D, Anderson KE, Bergkvist L, Bernstein L, van den Brandt PA, English DR, Freudenheim JL, Fuchs CS, Giles GG, Giovannucci E, Hankinson SE, Horn-Ross PL, Leitzmann M, Männistö S, Marshall JR, McCullough ML, Miller AB, Reding DJ, Robien K, Rohan TE, Schatzkin A, Stevens VL, Stolzenberg-Solomon RZ, Verhage BA, Wolk A, Ziegler RG, Smith-Warner SA (March 2009). "ALCOHOL INTAKE AND PANCREATIC CANCER RISK: A POOLED ANALYSIS OF FOURTEEN COHORT STUDIES". Cancer Epidemiology, Biomarkers & Prevention. 18 (3): 765–76. doi:10.1158/1055-9965.EPI-08-0880. PMC 2715951. PMID 19258474.
  39. ^ Zatonski WA, Boyle P, Przewozniak K, Maisonneuve P, Drosik K, Walker AM (February 1993). "Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland". International Journal of Cancer. 53 (4): 601–7. doi:10.1002/ijc.2910530413. PMID 8436433.
  40. ^ Durbec JP, Chevillotte G, Bidart JM, Berthezene P, Sarles H (April 1983). "Diet, alcohol, tobacco and risk of cancer of the pancreas: a case-control study". British Journal of Cancer. 47 (4): 463–70. doi:10.1038/bjc.1983.75. PMC 2011343. PMID 6849792.
  41. ^ Bueno de Mesquita HB, Maisonneuve P, Moerman CJ, Runia S, Boyle P (February 1992). "Lifetime consumption of alcoholic beverages, tea and coffee and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands". International Journal of Cancer. 50 (4): 514–22. doi:10.1002/ijc.2910500403. PMID 1537615.
  42. ^ Bakkevold KE, Arnesjø B, Kambestad B (April 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". Scandinavian Journal of Gastroenterology. 27 (4): 317–25. doi:10.3109/00365529209000081. PMID 1589710.
  43. ^ Frank J. Domino M.D. (2007). 5 minutes clinical suite version 3. Philadelphia, PA: Lippincott Williams & Wilkins.[page needed]
  44. ^ Philip Agop, "Pancreatic Cancer". ACP PIER & AHFX DI Essentials. American College of Physicians. 4 Apr 2008. Accessed 7 Apr 2009.[page needed]
  45. ^ Tempero MA, Arnoletti JP, Behrman S, Ben-Josef E, Benson AB, Berlin JD, Cameron JL, Casper ES, Cohen SJ, Duff M, Ellenhorn JD, Hawkins WG, Hoffman JP, Kuvshinoff BW, Malafa MP, Muscarella P, Nakakura EK, Sasson AR, Thayer SP, Tyler DS, Warren RS, Whiting S, Willett C, Wolff RA (September 2010). "Pancreatic adenocarcinoma". J Natl Compr Canc Netw. 8 (9): 972–1017. PMC 3135380. PMID 20876541.
  46. ^ Sarkar FH, Banerjee S, Li Y (November 2007). "Pancreatic cancer: pathogenesis, prevention and treatment". Toxicol. Appl. Pharmacol. 224 (3): 326–36. doi:10.1016/j.taap.2006.11.007. PMC 2094388. PMID 17174370.
  47. ^ Shain AH, Giacomini CP, Matsukuma K, Karikari CA, Bashyam MD, Hidalgo M, Maitra A, Pollack JR (31 January 2012). "Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer". Proceedings of the National Academy of Sciences of the United States of America. 109 (5): E252–9. doi:10.1073/pnas.1114817109. PMC 3277150. PMID 22233809.
  48. ^ Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (26 September 2008). "Core signaling pathways in human pancreatic cancers revealed by global genomic analyses". Science. 321 (5897): 1801–6. doi:10.1126/science.1164368. PMC 2848990. PMID 18772397.
  49. ^ Delpu Y, Hanoun N, Lulka H, Sicard F, Selves J, Buscail L, Torrisani J, Cordelier P (2011). "Genetic and epigenetic alterations in pancreatic carcinogenesis". Curr Genomics. 12 (1): 15–24. doi:10.2174/138920211794520132. PMC 3129039. PMID 21886451.
  50. ^ a b c Johns Hopkins Medicine; The Sol Goldman Pancreas Cancer Research Center. Types of Pancreas Tumors. http://pathology.jhu.edu/pancreas/BasicTypes1.php
  51. ^ a b c d e f g Yao JC, Eisner MP, Leary C, Dagohoy C, Phan A, Rashid A, Hassan M, Evans DB (2007). "Population-Based Study of Islet Cell Carcinoma". Annals of Surgical Oncology. 14 (12): 3492–3500. doi:10.1245/s10434-007-9566-6. PMC 2077912. PMID 17896148.
  52. ^ "The prognosis of patients with PENs is difficult to predict, in part because the definition of malignancy in PENs has been ambiguous. By some, PENs have been defined as malignant only when lymph nodes are involved or liver metastases are documented. Other investigators have included vascular invasion or invasion of adjacent structures as evidence of malignancy. However, the concept that a PEN removed successfully without recurrence was therefore biologically benign could be challenged. In fact, strict separation of PENs into benign and malignant groups may be less clinically useful than the definition of prognostic factors."Hochwald SN, Zee S, Conlon KC, Colleoni R, Louie O, Brennan MF, Klimstra DS (2002). "Prognostic Factors in Pancreatic Endocrine Neoplasms: An Analysis of 136 Cases with a Proposal for Low-Grade and Intermediate-Grade Groups". Journal of Clinical Oncology. 20 (11): 2633–2642. doi:10.1200/JCO.2002.10.030. PMID 12039924.
  53. ^ "One of the most controversial aspects of PENs has been the prediction of prognosis."Klimstra DS (2007). "Nonductal neoplasms of the pancreas". Modern Pathology. 20: S94–S112. doi:10.1038/modpathol.3800686. PMID 17486055.
  54. ^ "The classification of these tumors remains controversial, and prognosis is difficult to predict" Wendy L. Frankel (2006) Update on Pancreatic Endocrine Tumors. Archives of Pathology & Laboratory Medicine: July 2006, Vol. 130, No. 7, pp. 963–966. http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2006)130[963:UOPET]2.0.CO;2
  55. ^ Modlin http://onlinelibrary.wiley.com/doi/10.1002/cncr.11105/pdf
  56. ^ "Can Cancer of the Pancreas Be Prevented?". American Cancer Society. Archived from the original on 12 October 2007. Retrieved 13 December 2007.
  57. ^ 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. ISSN 0957-5243. PMID 11142526.
  58. ^ Zheng W, McLaughlin JK, Gridley G, Bjelke E, Schuman LM, Silverman DT, Wacholder S, Co-Chien HT, Blot WJ, Fraumeni JF (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.
  59. ^ Larsson SC, Håkansson N, Näslund I, Bergkvist L, Wolk A (February 2006). "Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study". Cancer Epidemiology, Biomarkers & Prevention. 15 (2): 301–05. doi:10.1158/1055-9965.EPI-05-0696. PMID 16492919.
  60. ^ "Health | Vitamin D 'slashes cancer risk'". BBC News. 15 September 2006. Retrieved 15 September 2009. The BBC quoted the lead researcher: "I would make no specific recommendation for vitamin D supplementation to prevent pancreatic cancer until we can carry out a trial to determine definitively clin.57.1.43 }}

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Category:Digestive system neoplasia Category:Pancreas disorders