| Pancreatic cancer |
| Classification and external resources |
|
| ICD-10 |
C25 |
| ICD-9 |
157.0-157.9 |
| OMIM |
260350 |
| DiseasesDB |
9510 |
| MedlinePlus |
000236 |
| eMedicine |
med/1712 |
| MeSH |
D010190 |
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).
Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States[1] and the eighth 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. Persons of African nationality or descent are more likely to develop pancreatic cancer than white persons.
Contents
- 1 Signs and symptoms
- 2 Risk factors
- 3 Diagnosis
- 4 Pathophysiology
- 4.1 Exocrine pancreas cancers
- 4.2 Pancreatic cystic neoplasms
- 4.3 Pancreatic neuroendocrine tumors
- 5 Prevention
- 6 Treatment
- 6.1 Exocrine pancreas cancer
- 6.1.1 Surgery
- 6.1.2 Radiation
- 6.1.3 Chemotherapy
- 6.2 Pancreatic neuroendocrine tumors
- 7 Prognosis
- 8 Epidemiology
- 9 See also
- 10 References
- 11 External links
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, the common soft drink sweetener fructose has been linked to 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][29] 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.[30]
Some studies suggest a relationship,[31] the risk increasing with increasing amount of alcohol intake.[32][33] The risk is greatest in heavy drinkers,[34][35][36] mostly on the order of four or more drinks per day.[37] There appears to be no increased risk for people consuming up to 30g of alcohol a day,[29][38][39] which is approximately 2 alcoholic beverages/day,[39] so most people who take alcohol do so at a level that "is probably not a risk factor for pancreatic cancer".[36] 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".[39]
Several studies caution that their findings could be due to confounding factors.[35][40] Even if a link exists, it "could be due to the contents of some alcoholic beverages"[41] other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk.[42]
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.[43]
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.[44] 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.[45] 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.[46]
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.[47] 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%).[48][49]
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.[50] 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.[51]
Pancreatic cystic neoplasms[edit]
Pancreatic cystic neoplasms are a broad group of pancreas tumors that have varying malignant potential.[discuss]
Pancreatic neuroendocrine tumors[edit]
Main article: Neuroendocrine tumor
Endocrine pancreatic tumors have been variously called islet cell tumors, pancreas endocrine tumors (PETs), and pancreatic neuroendocrine tumors (PNETs).[52] The annual clinically recognized incidence is low, about five per one million person-years.[51] 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[53][54][55] 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.[51][52] Low- to intermediate-grade neuroendocrine carcinomas of the pancreas may be called islet cell tumors. Some sources have also termed these pancreatic carcinoid,[52] a practice that has sometimes been strongly condemned.[citation needed] Definitional migration has caused some complexity of PNET classification,[52] which has adversely affected what is known about the epidemiology and natural history of these tumors.[52] 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[52][56] but most islet cell carcinomas have been coded as ICD-O-3 system 8150–8155.[52]
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.[57]
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.[58][59] In 2006, a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[60] 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;[61][62] 150 IU is appreciably less than what was then, or is now, recommended.[63] The World Health Organization (WHO) International Agency for Research on Cancer (IARC) concluded that there were insufficient studies in pancreatic cancer. Furthermore, while the IARC found evidence for an inverse association between vitamin D and colorectal cancer to be persuasive, it found evidence for a causal link to be limited, and also found that randomized controlled trials (RCTs) were inconclusive.[64] Taking too much vitamin D may be harmful.[63] Poor general diet, obesity, and relative physical inactivity can be risk factors in some cancers, so the role of vitamin D itself is not certain.[65]
A Harvard study from 2007 showed a modest inverse trend between blood circulation of B vitamins, such as B12, B6, and folate and pancreatic cancer incidence, but not when the vitamins were ingested in tablet form.[66] However, the results of a meta-analysis of randomized trials by Rothwell and colleagues indicate that taking a daily low-dose aspirin regimen for more than five years decreases the risk of developing pancreatic adenocarcinoma (ductal pancreatic cancer) by 75%.[67]
Screening[edit]
People who may have a high risk of pancreatic cancer due to a family history can be followed, but there is no consensus on what constitutes optimal monitoring. Several small studies have shown promising preliminary results for new biomarkers, but further validation on a larger scale is needed. People with pancreatic cancer themselves, or family members, may wish to participate in the activities at a research facility, or identify a pancreas tumor registry.
A possible 'dipstick screen', developed by 15-year-old Jack Andraka with the collaboration of Johns Hopkins University, detects the level of a protein called mesothelin in the urine or blood, which is a biomarker for pancreatic cancer. Experts believe it stands a chance of becoming a cheap test for the disease but will take years to develop.[68][69]
Treatment[edit]
Exocrine pancreas cancer[edit]
Surgery[edit]
Treatment of pancreatic cancer depends on the stage of the cancer.[70] Although only localized cancer is considered suitable for surgery with curative intent at present, only 20% of cases present with localised disease at diagnosis.[71] Surgery can also be performed for palliation, if the malignancy is invading or compressing the duodenum or colon. In such cases, bypass surgery might overcome the obstruction and improve quality of life but is not intended as a cure.[45]
The Whipple procedure is the most common attempted curative surgical treatment for cancers involving the head of the pancreas. This procedure involves removing the pancreatic head and the curve of the duodenum together (pancreato-duodenectomy), making a bypass for food from stomach to jejunum (gastro-jejunostomy) and attaching a loop of jejunum to the cystic duct to drain bile (cholecysto-jejunostomy). It can be performed only if the patient is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing. It can, therefore, be performed in only the minority of cases.
Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy.[70] Recently, localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches.[72]
After surgery, adjuvant chemotherapy with gemcitabine has been shown in several large randomized studies to significantly increase the 5-year survival (from approximately 10 to 20%), and should be offered if the patient is fit after surgery (Oettle et al. JAMA 2007, Neoptolemos et al. NEJM 2004, Oettle et al. ASCO proc 2007).
Radiation[edit]
Principles of radiation therapy in pancreas adenocarcinoma are reviewed extensively in guidelines by the National Comprehensive Cancer Network.[73] Radiation can be considered in several situations. One situation is the addition of radiation therapy after potentially curative surgery. Groups in the US have been more apt to use adjuvant radiation therapy than groups in Europe.[74]
Chemotherapy[edit]
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 and a 5-week improvement in median survival duration in patients with advanced pancreatic cancer. This marked the first FDA approval of a chemotherapy drug primarily for a nonsurvival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis.
A Canadian-led Phase III randomised controlled trial, reported in 2005, involved 569 patients with advanced pancreatic cancer, led the US FDA in 2005 to license erlotinib (Tarceva) in combination with gemcitabine as a palliative regimen for pancreatic cancer. This trial compared the outcome of gemcitabine/erlotinib to gemcitabine/placebo, and demonstrated improved survival rates, improved tumor response and improved progression-free survival rates.[75][76] Other trials are now investigating the effect of the above combination in the adjuvant (post surgery) and neoadjuvant (pre-surgery) settings.
Addition of oxaliplatin to Gemcitabine (Gem/Ox) was shown to confer benefit in small trials, but is not yet standard therapy.[77]
Pancreatic neuroendocrine tumors[edit]
Main article: Neuroendocrine tumor
The majority of these tumors are histologically benign. Treatment of pancreatic endocrine tumors, including the less common malignant tumors, may include:
- Watchful waiting: incidentally identified small tumors, for example on a computed tomography (CT) scan performed for other purposes, may conceptually not always need intervention, but criteria for watchful waiting are unclear.
- Surgery: tumors within the pancreas only (localized tumors), or with limited metastases, may be removed. For localized tumors, the surgical procedure is much less extensive than the types of surgery used to treat pancreatic adenocarcinoma.
- Hormone therapy: if the tumor is not amenable to surgical removal and is causing symptoms by secreting functional hormones, a synthetic hormone analog medication, octreotide, may lessen the symptoms, and sometimes also slows tumor growth.
- Radiation therapy: occasionally used if there is pain due to anatomic extension, such as metastasis to bone.
- Radiolabeled hormone: some PNETs absorb a hormone called norepinephrine and these may respond to nuclear medicine medication, radiolabeled MIBG therapy (or, experamentally, other hormones), given intravenously.
- Radiofrequency ablation (RFA), cryoablation, hepatic artery embolization
- Chemotherapy and targeted medication for PNETs receive Wikipedia discussion in the relevant section of that article.
Prognosis[edit]
Age-standardized death from pancreatic cancer per 100,000 inhabitants in 2004.
[78]
no data
<1
1
2
3
4
5
6
7
8
9
10
>10
Exocrine pancreatic cancer (adenocarcinoma and less common variants) typically has a poor prognosis, partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis.
Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered, and it has been suggested the cancer can also prompt the onset of diabetes and vice versa.[79] It can be associated with pain, fatigue, weight loss, jaundice, and weakness. Additional symptoms are discussed above.
For pancreatic cancer:
- For all stages combined, the 1-year relative survival rate is 25%, and the 5-year survival is estimated as less than 5% [80] to 6%.[3]
- For local disease, the 5-year survival is approximately 20%.[3][4]
- For locally advanced and for metastatic disease, which collectively represent over 80%[4] to 85-90%[13] of individuals, the median survival is about 10 and 6 months, respectively.[5] Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months;[13] complete remission is rare.[13]
Outcomes with pancreatic endocrine tumors, many of which are benign and completely without clinical symptoms, are much better, as are outcomes with symptomatic benign tumors; even with actual pancreatic endocrine cancers, outcomes are rather better, but variable.[52][81]
Epidemiology[edit]
Globally, as of 2010, pancreatic cancer resulted in 310,000 deaths up from 200,000 in 1990.[82] In 2010, an estimated 43,000 people in the US were diagnosed with pancreas cancer[3] and almost 37,000 died from the disease. [3] Pancreatic cancer has one of the highest fatality rates of all cancers, and is the fourth-highest cancer killer among both men and women worldwide.[83] Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year.[84]
See also[edit]
- Category:Deaths from pancreatic cancer
- Category:Pancreatic cancer survivors
- Gastrointestinal cancer
- Pancreatic Cancer Action (organisation in the UK)
- Lustgarten Foundation for Pancreatic Cancer Research (organization in the US)
References[edit]
- ^ Hariharan, D.; Saied, A.; Kocher, H. M. (2008). "Analysis of mortality rates for pancreatic cancer across the world". HPB 10 (1): 58–62. doi:10.1080/13651820701883148. PMC 2504856. PMID 18695761. edit
- ^ http://www.cancerresearchuk.org/cancer-info/cancerstats/world/the-global-picture/cancer-overall-world#source2
- ^ a b c d e f "American Cancer Society: Cancer Facts & Figures 2010: see page 4 for incidence estimates, and page 19 for survival percentages".
- ^ a b c d National Cancer Institute. General Information About Pancreatic Cancer. http://www.cancer.gov/cancertopics/pdq/treatment/pancreatic/HealthProfessional
- ^ a b c d 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
- ^ a b c d e f g "What You Need To Know About Cancer of the Pancreas — National Cancer Institute". 2002-09-16. p. 4/5. Retrieved 2007-12-22.
- ^ Dragovich, Tomislav (13 September 2011). "Pancreatic Cancer". Medscape Reference.
- ^ 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.
- ^ 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.
- ^ Medscape > Pancreatic Cancer Author: Tomislav Dragovich. Chief Editor: Jules E Harris. Updated: May 5, 2011
- ^ 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
- ^ "ACS :: What Are the Risk Factors for Cancer of the Pancreas?". Archived from the original on October 12, 2007. Retrieved 2007-12-13.
- ^ a b c d e Ghaneh P, Costello E, Neoptolemos JP (August 2007). "Biology and management of pancreatic cancer". Gut 56 (8): 1134–52. doi:10.1136/gut.2006.103333. PMC 1955499. PMID 17625148.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. doi:10.1038/bjc.2011.585. PMID 22240790.
- ^ "Soft Drink and Juice Consumption and Risk of Pancreatic Cancer: The Singapore Chinese Health Study".
- ^ "Cancer cells slurp up fructose, U.S. study says". Reuters. 2010-08-02. Retrieved 2010-08-02.
- ^ "Obesity Linked to Pancreatic Cancer". American Cancer Society. Cancer Epidemiology, Biomarkers & Prevention (Vol. 14, No. 2: 459–466). 2005-03-06. Archived from the original on February 5, 2008. Retrieved 2008-03-05.
- ^ Raderer, M.; Wrba, F.; Kornek, G.; Maca, T.; Koller, D.Y.; 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. edit
- ^ Stolzenberg-Solomon, R. Z.; Blaser, M. J.; Limburg, P. J.; Perez-Perez, G.; Taylor, P. R.; Virtamo, J.; Albanes, D. (2001). "Helicobacter pylori Seropositivity as a Risk Factor for Pancreatic Cancer". JNCI Journal of the National Cancer Institute 93 (12): 937–941. doi:10.1093/jnci/93.12.937. edit
- ^ 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.
- ^ 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.
- ^ 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. PMID 8578237.
- ^ National Institute on Alcohol Abuse and Alcoholism Alcohol and Cancer - Alcohol Alert No. 21-1993
- ^ American Cancer SocietyCoffee and Alcohol Do Not Pose a Risk for Pancreatic Cancer
- ^ 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.
- ^ 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.
- ^ Cancer Research UK Pancreatic cancer risks and causes
- ^ Ahlgren JD (April 1996). "Epidemiology and risk factors in pancreatic cancer". Seminars in Oncology 23 (2): 241–50. PMID 8623060.
- ^ 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.
- ^ 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.
- ^ Schottenfeld, D. and J. Fraumeni, ed. Cancer epidemiology and prevention. 2nd ed., ed. Vol. 1996, Oxford University Press: Oxford[page needed]
- ^ 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.
- ^ a b Silverman DT, Brown LM, Hoover RN, et al. (November 1995). "Alcohol and pancreatic cancer in blacks and whites in the United States". Cancer Research 55 (21): 4899–905. PMID 7585527.
- ^ 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.
- ^ "Pancreatic cancer risk factors". Info.cancerresearchuk.org. 2008-11-04. Retrieved 2009-09-15.
- ^ 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, et al. (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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Frank J. Domino M.D. (2007). 5 minutes clinical suite version 3. Philadelphia, PA: Lippincott Williams & Wilkins. [page needed]
- ^ a b Philip Agop, "Pancreatic Cancer". ACP PIER & AHFX DI Essentials. American College of Physicians. 4 Apr 2008. Accessed 7 Apr 2009.[page needed]
- ^ Tempero MA, Arnoletti JP, Behrman S, et al. (September 2010). "Pancreatic adenocarcinoma". J Natl Compr Canc Netw 8 (9): 972–1017. PMC 3135380. PMID 20876541.
- ^ 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.
- ^ Shain, AH; Giacomini, CP; Matsukuma, K; Karikari, CA; Bashyam, MD; Hidalgo, M; Maitra, A; Pollack, JR (2012 Jan 31). "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. PMID 22233809.
- ^ 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 (2008 Sep 26). "Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.". Science (New York, N.Y.) 321 (5897): 1801–6. PMID 18772397.
- ^ 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.
- ^ a b c Johns Hopkins Medicine; The Sol Goldman Pancreas Cancer Research Center. Types of Pancreas Tumors. http://pathology.jhu.edu/pancreas/BasicTypes1.php
- ^ a b c d e f g h Yao, J. C.; Eisner, M. P.; Leary, C.; Dagohoy, C.; Phan, A.; Rashid, A.; Hassan, M.; Evans, D. B. (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. edit
- ^ "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, S. N.; Zee, S.; Conlon, K.; Colleoni, R.; Louie, O.; Brennan, M.; Klimstra, D. (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. edit
- ^ "One of the most controversial aspects of PENs has been the prediction of prognosis."Klimstra, D. S. (2007). "Nonductal neoplasms of the pancreas". Modern Pathology 20: S94–S112. doi:10.1038/modpathol.3800686. PMID 17486055. edit
- ^ "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
- ^ Modlin http://onlinelibrary.wiley.com/doi/10.1002/cncr.11105/pdf
- ^ "Can Cancer of the Pancreas Be Prevented?". American Cancer Society. Archived from the original on October 12, 2007. Retrieved 2007-12-13.
- ^ 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.
- ^ Zheng W, McLaughlin JK, Gridley G, 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.
- ^ 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.
- ^ "Health | Vitamin D 'slashes cancer risk'". BBC News. 2006-09-15. Retrieved 2009-09-15. 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 who might benefit from such an intervention." The BBC quoted Henry Scowcroft, science information officer at the charity Cancer Research UK: "The results of this study don't mean that people should take vitamin D supplements to ward off pancreatic cancer, especially as vitamin D can be harmful in large quantities...As the authors themselves point out, this is the very first study to find any association between the disease and vitamin D intake...So this result needs to be repeated in other large studies, and scientists need to show exactly how vitamin D might prevent pancreatic cancer before we could issue any specific lifestyle advice."
- ^ "Vitamin D May Cut Pancreatic Cancer". Webmd.com. 2006-09-12.
- ^ a b Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx Dietary Reference Intakes for Calcium and Vitamin D IOM, November 30, 2010: "The IOM finds that the evidence supports a role for vitamin D and calcium in bone health but not in other health conditions. Further, emerging evidence indicates that too much of these nutrients may be harmful, challenging the concept that "more is better."
- ^ World Health Organization; International Agency for Research on Cancer (IARC). Vitamin D and Cancer. IARC Working Group Reports Vol.5, International Agency for research on Cancer, Lyon, 25 November 2008
- ^ Lipson P. Vitamin D: Still more questions than answers. http://blogs.forbes.com/sciencebiz/2010/08/18/vitamin-d-still-more-questions-than-answers/ "Vitamin D deficiency is common in people with poor diets (including obese people) and in people who are relatively inactive. These are independent risk factors for... some cancers. And while some cellular mechanisms have been discovered that may lend plausibility to a vitamin D hypothesis, there are as... yet no convincing data that allow us to draw conclusions about vitamin D and these diseases."
- ^ 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 Research 67 (11): 5553–60. doi:10.1158/0008-5472.CAN-06-4463. PMID 17545639.
- ^ Rothwell P, Fowkes F, Belch, J.n B, Rifai N, et al. (Jan 2011). "Effect of daily aspirin on long term risk of death due to cancer: analysis of individual patient data from randomised trials". Lancet 337 (9759): 31–41. doi:10.1016/S0140-6736(10)62110-1. PMID 21144578.
- ^ The Independent, 5 May 2013
- ^ http://www.bbc.com/future/story/20130701-perfecting-early-cancer-detection
- ^ a b "Surgical Treatment of Pancreatic Cancer". Johns Hopkins University. Retrieved 5 September 2009.
- ^ Corbo V, Tortora G, Scarpa A (2012) Molecular pathology of pancreatic cancer: from bench-to-bedside translation. Curr Drug Targets
- ^ "Laparoscopic Pancreas Surgery". Johns Hopkins University. Retrieved 5 September 2009.
- ^ Pancreatic Adenocarcinoma (access to the guideline section of the website is free, but may require registration; see sections "PANC-F" and "MS") http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf
- ^ Neoptolemos JP, Stocken DD, Friess H, et al. (March 2004). "A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer". The New England Journal of Medicine 350 (12): 1200–10. doi:10.1056/NEJMoa032295. PMID 15028824.
- ^ "Tarceva (erlotinib) Tablets. NDA 21-743, S003. Supplemental NDA: Pancreatic Cancer, Briefing Document, ODAC Meeting 13 September 2005". September 2005. Retrieved 2009-09-15.
- ^ Moore MJ, et al. (May 2007). "Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group.". Journal of Clinical Oncology 25 (15): 1960–1966. doi:10.1200/JCO.2006.07.9525. PMID 17452677.
- ^ Demols A, Peeters M, Polus M, et al. (February 2006). "Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study". British Journal of Cancer 94 (4): 481–85. doi:10.1038/sj.bjc.6602966. PMC 2361170. PMID 16434988.
- ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov. 11, 2009.
- ^ Wang F, Herrington M, Larsson J, Permert J (January 2003). "The relationship between diabetes and pancreatic cancer". Molecular Cancer 2: 4. doi:10.1186/1476-4598-2-4. PMC 149418. PMID 12556242.
- ^ "WHO | Cancer". Who.int. Retrieved 2009-09-15.
- ^ Fesinmeyer, M. D.; Austin, M. A.; Li, C. I.; De Roos, A. J.; Bowen, D. J. (2005). "Differences in Survival by Histologic Type of Pancreatic Cancer". Cancer Epidemiology Biomarkers & Prevention 14 (7): 1766–1773. doi:10.1158/1055-9965.EPI-05-0120. edit
- ^ Lozano, R (2012 Dec 15). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.". Lancet 380 (9859): 2095–128. PMID 23245604.
- ^ "Pancreatic Cancer — National Cancer Institute, U.S. National Institutes of Health (Accessed 28 April 2011)". Cancer.gov. Retrieved 2009-09-15.
- ^ Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007). "Cancer statistics, 2007". CA 57 (1): 43–66. doi:10.3322/canjclin.57.1.43. PMID 17237035.
External links[edit]
- Pancreatic cancer at the Open Directory Project
|
Tumors: digestive system neoplasia (C15–C26/D12–D13, 150–159/211)
|
|
| GI tract |
| Upper GI tract |
| Esophagus |
- Squamous cell carcinoma
- Adenocarcinoma
|
|
| Stomach |
- Gastric carcinoma
- Signet ring cell carcinoma
- Gastric lymphoma
- Linitis plastica
|
|
|
| Lower GI tract |
| Small intestine |
|
|
| Appendix |
- Carcinoid
- Pseudomyxoma peritonei
|
|
| Colon/rectum |
- colorectal polyp: Peutz–Jeghers syndrome
- Juvenile polyposis syndrome
- Familial adenomatous polyposis/Gardner's syndrome
- Cronkhite–Canada syndrome
- neoplasm: Adenocarcinoma
- Familial adenomatous polyposis
- Hereditary nonpolyposis colorectal cancer
|
|
| Anus |
|
|
|
| Upper and/or lower |
- Gastrointestinal stromal tumor
- Krukenberg tumor (metastatic)
|
|
|
| Accessory |
| Liver |
- malignant: Hepatocellular carcinoma
- Hepatoblastoma
- benign: Hepatocellular adenoma
- Cavernous hemangioma
- hyperplasia: Focal nodular hyperplasia
- Nodular regenerative hyperplasia
|
|
| Biliary tract |
- bile duct: Cholangiocarcinoma
- Klatskin tumor
- gallbladder: Gallbladder cancer
|
|
| Pancreas |
- exocrine pancreas: Adenocarcinoma
- Pancreatic ductal carcinoma
- cystic neoplasms: Serous microcystic adenoma
- Intraductal papillary mucinous neoplasm
- Mucinous cystic neoplasm
- Solid pseudopapillary neoplasm
|
|
|
| Peritoneum |
- Primary peritoneal carcinoma
- Peritoneal mesothelioma
- Desmoplastic small round cell tumor
|
|
|
|
anat (t, g, p)/phys/devp/enzy
|
noco/cong/tumr, sysi/epon
|
proc, drug (A2A/2B/3/4/5/6/7/14/16), blte
|
|
|
|
|
Tumors: endocrine gland neoplasia (C73–C75/D34–D35, 193–194/226–227)
|
|
Pancreas/
islets of Langerhans |
- neuroendocrine tumors/islet cell carcinoma: α: Glucagonoma
- β: Insulinoma
- δ: Somatostatinoma
- G: Gastrinoma
- VIPoma
|
|
Hypothalamic/
pituitary axes
+parathyroid |
| Pituitary |
- Pituitary adenoma: Prolactinoma
- ACTH-secreting pituitary adenoma
- GH-secreting pituitary adenoma
|
|
| Thyroid |
- Thyroid cancer (malignant): epithelial cell carcinoma
- Papillary
- Follicular/Hurthle cell
- parafollicular cell
- Anaplastic
- Lymphoma
- Squamous cell carcinoma
- Benign: Thyroid adenoma
- Struma ovarii
|
|
| Parathyroid |
- Parathyroid adenoma
- Parathyroid carcinoma
|
|
| Adrenal tumor |
- adrenal cortex
- Adrenocortical adenoma
- Adrenocortical carcinoma
- adrenal medulla
- Pheochromocytoma
- Neuroblastoma
- see also: Paraganglioma
|
|
| Gonads |
|
|
|
| Pinealoma |
- Pinealoblastoma
- Pineocytoma
|
|
| MEN |
|
|
|
|
|
noco (d)/cong/tumr, sysi/epon
|
proc, drug (A10/H1/H2/H3/H5)
|
|
|
|