Pancreatic cancer diagnosis and screening

Authors:

Details:

  1. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, South Australia, Australia.
  2. Discipline of Medicine, University of Adelaide, South Australia, Australia.
  3. Department of Gastroenterology and Hepatology, Royal Prince Alfred Hospital, Sydney, Australia.
  4. Department of Gastroenterology and Hepatology, Division of Medicine, Johns Hopkins Hospital, Baltimore MD USA.
  5. Department of Gastroenterology, St Vincent’s Hospital, Sydney, Australia.

Abstract

Pancreatic cancer is uncommon, but is projected to become the second leading cause of cancer-related death by 2030. The dismal five year survival of 5% reflects the advanced stage of the disease at presentation, at which time surgery is not possible. The establishment of clinical and pathological diagnosis currently relies on dedicated ‘pancreatic protocol’ CT, MRI/cholangiopancreatography, endoscopic ultrasound and guided fine needle aspiration. Given surgical resection of early stage cancer is curative at least in some cases, the concept of screening high-risk individuals to detect the cancer at its earliest stage has been evaluated over the last 10 years. Although the advances in imaging modalities, particularly those without radiation exposure, such as endoscopic ultrasound and MRI have made screening programs safe and feasible, studies demonstrating the impact of these programs on survival outcomes are lacking. Thus, screening of high-risk individuals is not ready for widespread clinical practice and should be conducted by clinicians who have expertise in endoscopic ultrasound for screening of high-risk individuals in a research setting with prospective data collection.


Despite the reduction in incidence of all other cancers in recent years, there has been an increase in pancreatic cancer incidence over the last three decades and it is projected to be the second most common cause of cancer death by 2030.1 Improvement of survival relies heavily on early detection, with surgical resection perceived as the only curative option.2 Unfortunately, only 20% of patients are suitable for surgery at diagnosis.3 Diagnosis predominantly requires imaging techniques (CT, MRI/cholangiopancreatography [MRCP], endoscopic ultrasound [EUS]) and tissue acquisition. One strategy for improving outcomes in patients with pancreatic cancer is to develop effective screening protocols to identify more patients at an earlier stage, by identifying highly specific biomarkers or ‘high-risk’ individuals for pancreatic cancer. Unfortunately, thus far, there are no reliable tumour markers or biomarkers for the early detection of pancreatic cancer.4 This review focuses on diagnosis and screening of pancreatic cancer.

Diagnosis

Clinical manifestations

The majority of patients with pancreatic cancer present late as they are often asymptomatic in the early stage of their disease. The most common symptoms at diagnosis are either painless jaundice or vague epigastric pain radiating to the back. This is because over two thirds of pancreatic cancers are located in the head of the pancreas and cause obstruction of the biliary tract.5 Other non-specific complaints include anorexia, weight loss, lethargy and change in bowel habit. In advanced disease, symptoms of gastric outlet obstruction (post-prandial nausea and vomiting) can occur secondary to duodenal stricture caused by direct tumour invasion, suggesting that clinical manifestations can be an indicator of disease staging. Abdominal pain and weight loss are more frequently found in patients with later stages of disease.6

Investigations

Although a number of conventional imaging modalities can be used for the work-up of pancreatic cancer (table 1),7 contrast ‘pancreatic protocol’ multi-detector row computed tomography (MDCT) is the best initial imaging modality for both the diagnosis and staging of patients with suspected pancreatic cancer.8 MRI with MRCP has similar sensitivity and specificity in detection of pancreatic cancer and can be used as an alternative to MDCT depending on the local expertise and availability. MRI is most useful in cases where CT fails to show a mass lesion within the pancreas, or tumours are suspected to be smaller than 1cm, either in the pancreas or liver.9 For pancreatic lesions less than 2cm, EUS has a sensitivity of 93%, which is significantly greater than that from MDCT (53%) and MRI (67%) (table 2),10-17 and has a major role in patients who have had cross sectional imaging but were still unable to definitively rule out pancreatic lesions. The sensitivity of trans-abdominal ultrasound is poor and it is therefore not used.18,19 The role of positron emission tomography with CT (PET/CT) in the work-up of pancreatic cancer remains unclear. In a recent prospective study of 56 patients, PET/CT altered management in 16% of patients due to detection of metastases that was not identified by other imaging modalities.20 Given its relatively small impact in the overall management, PET/CT is not routinely recommended in the work-up of pancreatic cancer. 

Serum carbohydrate antigen sialyl Lewis, also known as Ca19-9, greater than 1000U/ml in conjunction with a pancreatic mass is highly diagnostic of pancreatic cancer. However, Ca19-9 is not specific to pancreatic cancer and can be markedly increased in biliary obstruction. The overall sensitivity and specificity of Ca19-9 for predicting the presence of pancreatic cancer in a patient with a pancreatic mass, are both 80%.21 A normal Ca 19-9 result does not exclude pancreatic cancer.22 Monitoring serum Ca19-9 level is also useful in assessing the therapeutic response to various types of treatment in patients with pancreatic cancer. In patients undergoing surgical resection, postoperative decrease to less than 200 U/mL has been shown to be a strong predictor of survival.23 In patients with locally advanced pancreatic cancer undergoing neoadjuvant chemoradiotherapy, a level less than 90 U/mL is associated with increased overall survival with the possibility of surgical resection.24

EUS-FNA has become the preferred technique for establishing tissue diagnosis, with sensitivity of 85% and specificity 98%.25 It is a safe procedure with complication rates of approximately 1%,26 and the risk of tumour seeding is significantly lower than that of the percutaneous approach.27 Contrast enhancement and elastography are adjunctive techniques during EUS evaluation, as both can increase the sensitivity and accuracy of pancreatic cancer detection and help target the best area for FNA.28,29

Table_Summary of imaging modalities Table_Diagnostic accuracy of EUS

Staging of pancreatic cancer

Accurate disease staging is crucial to the management of pancreatic cancer, as surgical resection carries significant morbidities and mortality. MDCT is the imaging modality of choice for the assessment of vascular involvement and distant metastasis.30-32 If MDCT is not available, MRI/MRCP can be considered an appropriate alternative.33 When available, EUS should also be used for tumour (T) and nodal (N) staging, especially as an adjunct examination during EUS guided biopsy. A recent meta-analysis showed that for resectability, EUS has a similar sensitivity (87 vs 90%) and higher specificity (89 vs 69%) compared to MDCT,34 but is superior to CT for detection of tumour invasion at the portal vein confluence (table 3).14,16,35-37 Furthermore, EUS has a higher sensitivity over MDCT for detecting (and sampling) coeliac lymph nodes and small ascites.38,39 EUS however, has limited ultrasound penetration range and cannot detect distant metastatic disease.40 Therefore, EUS and MDCT have complementary roles in the staging of pancreatic cancer.

Table_Accuracy of EUS-CT-MRI

Screening for pancreatic cancer

Most patients with pancreatic cancer remain asymptomatic until the tumour has grown to an unresectable stage.3 Given the five-year survival of patients with resected tumours less than 1cm in size is as high as 78%,41,42 the most logical way to improve survival is via the identification of early disease or precursor lesions by screening asymptomatic individuals. There are three known histologically well-defined precursor lesions involved in pancreatic carcinogenesis called pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms.43 A recent study indicated that there was a 10 year interval between the initial mutation and the birth of the first pancreatic cancer founder cell, and another six years for the development of the clone with metastatic potential.44

Currently, a population based screening program is not feasible due to the low incidence of pancreatic cancer (approx. 11:100,000 in Australia) and the lack of simple, safe, accurate, inexpensive and non-invasive diagnostic tests for early lesions.45 As proposed by the International Cancer of the Pancreas Consortium (CAPS) however, screening individuals with a greater than 5% lifetime risk or five-fold increased relative risk of developing pancreatic cancer (i.e. high-risk individuals) may be cost-effective and is under evaluation.46

A number of inherited and acquired conditions significantly increase the risk of pancreatic cancer (table 4 and 5). Up to 10% of pancreatic cancer results from a genetic susceptibility and/or familial aggregation.47 Although they are rare, Peutz-Jeghers syndrome (PJs), hereditary chronic pancreatitis and familial pancreatic cancer syndrome (FPC) are the three conditions that subject patients and their first-degree relatives to the highest risk of developing pancreatic cancer (table 4) (8-60% lifetime risk). FPC is characterised by two or more first-degree relatives with pancreatic cancer in the absence of a known cancer syndrome, and thus, those with two or more relatives with pancreatic cancer (with at least one being a first degree relative) should be considered for screening.46 Although there is a higher prevalence of patients with Lynch syndrome and hereditary breast-ovarian cancer syndrome, the lifetime risk of developing pancreatic cancer with these syndromes is only approximately 5%.48 

Table_Hereditary conditions Table_Non-genetic risk factors

Of the acquired pancreatic conditions that carry an increased risk of pancreatic cancer, mucinous cystic neoplasm and main- or branch-duct type IPMNs have significant increased lifetime risk of developing pancreatic cancer that warrant interval surveillance (MRI or EUS). Currently, there are a number of guidelines on the management of these high-risk cystic neoplasms and this will not be further discussed in this review. Longstanding chronic pancreatitis is another risk factor for developing pancreatic cancer where screening may be justified. Although smoking, obesity and diabetes (type 1 and new onset type 2) are risk factors for pancreatic cancer, the proportion of attributable disease is small and they are not current indications for screening.49 

EUS and MRI/MRCP are the imaging modalities of choice for screening as they have sufficient sensitivities and specificities to detect small lesions (or early cancer) and do not carry the risks of radiation exposure.46 The high resolution of EUS enables the detection of lesions 5mm (or smaller), which can also be biopsied for tissue diagnosis during the procedure.46,50 MRCP is the best modality for visualising cyst communication with the main pancreatic duct.51 ERCP is not recommended due to risk of pancreatitis and low yield.46 Ca19-9 has no role in detection of precursor lesions or early pancreatic cancer. Currently many biomarkers are under research (serum carcinoembryonic antigen-related cell adhesion molecules [CEACAM], Span -1, MIC-1, pancreatic juice analysis for Kras mutation), but not currently in routine clinical use.

The age with which to commence screening varies depending on the condition and also remains an evidence-free zone. The CAPS consortium recommends patients with hereditary chronic pancreatitis commence screening at 40 years of age, since there is a younger age of onset of pancreatic cancer. Other subjects with high-risk conditions should commence screening at age 50 years or 10 years younger than the youngest pancreatic cancer in the family. Smoking is a strong risk factor in familial pancreatic cancer kindreds, particularly in men and people less than 50 years old, as it increases the risk of pancreatic cancer by 2-3.7 times over the inherited predisposition and lowers the age of onset by 10 years.52 Currently, there is no consensus as to when screening should cease and should be judged on an individual basis. Patient preference and fitness for surgery are important factors, which should be incorporated into the decision-making.

The optimal interval for surveillance also remains unclear. Available data from the CAPS Consortium suggest a 12-month surveillance interval for high risk individuals with no pancreatic lesions found at baseline assessment.46 For those with abnormalities found on baseline imaging, the interval varies dependent on the nature of the lesion. Non-suspicious cysts should have surveillance after 6-12 months, while newly detected indeterminate solid lesions or indeterminate main pancreatic duct strictures should have repeat imaging at three months. Subjects with IPMN should continue surveillance according to the international consensus guidelines.53

Current data supporting screening is limited to prospective observational studies in high-risk individuals (table 6).22,50,51,54-60 Poley et al were the first to evaluate the role of EUS, MRI and/or CT scans in screening of 44 high risk individuals, consisting those with a history of FCP, PJS, familial atypical multiple mole melanoma syndrome (FAMM) and BRCA2.55 Seven patients had branch duct IPMNs and three had pancreatic adenocarcinoma, proven on surgical resection. The largest study to date (n=192) is a multicentre, prospective cohort study (CAPS 3) of high-risk individuals, using CT, MRI and EUS imaging.51 Positive findings were detected in 42% (92/216) of patients. Pancreatic mass (84 cystic and three solid) and dilated pancreatic duct (n=5) were identified by one of the imaging modalities and prevalence of these lesions appeared to increase with age. Of all imaging modalities, EUS appeared to have the highest diagnostic yield (CT, MRI and EUS detected pancreatic abnormality in 11%, 33.3% and 42.6% of patients respectively). Among the pancreatic lesions, 82 were IPMNs and three pancreatic neuroendocrine tumours. Five patients underwent surgery and three of them had high grade dysplasia in <3cm IPMNs and multiple intraepithelial neoplasms, suggesting that screening of asymptomatic high risk individuals can detect curable non-invasive high grade lesions. In contrast, the National German Familial Pancreatic Cancer Registry reported a lower rate of pancreatic abnormalities in their high risk individuals (5%), with the majority of the abnormalities being non-malignant.22,56 This study was the first to raise concern about the potential harm of a screening program and highlights the extreme importance of discussing all positive findings in a pancreatico-biliary multi-disciplinary meeting to determine the optimal surveillance interval, need for biopsy, further investigation or surgery.

Overall, the current data indicate that diagnostic yield of neoplastic pancreatic lesions varies significantly (5% to 50%), whereas the detection rate for pancreatic cancer is only 1% to 2% (table 6).  These data are consistent with the findings from a recent systematic review of 542 high-risk individuals screened.61 The vast range seen in those studies is likely due to differences in the definition of high-risk subjects, measured outcomes and use of varying screening modalities. In particular, the definition of ‘positive yield’ varies from precursor lesion (cysts, branch duct IPMN) to early cancer. As such, most recent studies that defined positive yield as early stage 1 cancer or high-grade dysplastic precursor lesions often have a lower detection rate (1-2%), whereas those that included cystic lesions, IPMNs or PanINs of any grade of dysplasia tend to report a much higher yield (up to 50%).50,54,58,60

The ability to detect ‘PanIN’ lesions by EUS is controversial and the sonographic features of PanIN are non-specific and not well validated. PanIN may have sonographic features similar to that of chronic pancreatitis, as PanINs are multifocal and are often associated with lobular centric atrophy and fibrosis,62 which are also seen in chronic pancreatitis or age related parenchymal fibrosis.46 Furthermore, the ability to recognise ‘lobularity’ on EUS is very operator-dependent, and cannot be distinguished from other disease processes. 

Table_Summary of studies on screening

Several studies have addressed the psychological impact of screening programs. Axilbund et al found genetic counselling to be helpful to more than 90% of high-risk individuals despite the inability to identify a causative gene.63 More importantly, patients who participated in a screening program did not experience increased anxiety or perception of cancer risk,64 and 80% of the participants felt the advantages of screening outweighed the risks.65 Overall, available data suggest that screening is not associated with any adverse impact on the patient’s psychology.

Conclusion 

Pancreatic cancer carries a dismal prognosis, largely due to the late stage of disease at presentation. Early detection is of utmost importance given that surgical resection is the only treatment option that is curative at least in some cases. There are multiple suitable imaging modalities (EUS, MRI/MRCP and MDCT) used for detection and staging of pancreatic cancer, each with its own strengths and weaknesses. EUS FNA is the preferred method for tissue diagnosis of pancreatic masses and may be used in conjunction with pancreas protocol CT for staging. Screening for pancreatic cancer in high-risk individuals is currently driven by consensus guidelines recommended by the International CAPS consortium. Long-term outcome data to determine the clinical impact and utility of a screening program, especially on survival, are awaiting. It is therefore important that all screening programs are conducted in a research setting within centres with the appropriate training and expertise in performing EUS in high-risk individuals.

Conflicts of interest

Dr Phan has no conflicts of interest.

Dr Saxena has received consulting fees from Olympus Australia, Pentax Medical and Cook Medical. She is a consultant for Boston Scientific. She has received research support from Cook Medical and Boston Scientific. She is on the scientific advisory board member for Oncosil Medical Ltd.

Dr Alina Stoita has no conflicts of interest.

A/Prof Nguyen has no conflicts of interest.

References

  1. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer research. 2014 Jun 1;74(11):2913-21. PubMed PMID: 24840647.
  2. Del Chiaro M, Segersvard R, Lohr M, et al. Early detection and prevention of pancreatic cancer: is it really possible today? World journal of gastroenterology : WJG. 2014 Sep 14;20(34):12118-31. PubMed PMID: 25232247. Pubmed Central PMCID: 4161798.
  3. Wood HE, Gupta S, Kang JY, et al. Pancreatic cancer in England and Wales 1975-2000: patterns and trends in incidence, survival and mortality. Alimentary pharmacology & therapeutics. 2006 Apr 15;23(8):1205-14. PubMed PMID: 16611282.
  4. Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. Journal of surgical oncology. 2013 Jan;107(1):15-22. PubMed PMID: 22729569.
  5. Porta M, Fabregat X, Malats N, et al. Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2005 Jun;7(5):189-97. PubMed PMID: 15960930.
  6. Bakkevold KE, Arnesjo B, Kambestad B. 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. 1992 Apr;27(4):317-25. PubMed PMID: 1589710.
  7. Lee ES, Lee JM. Imaging diagnosis of pancreatic cancer: a state-of-the-art review. World journal of gastroenterology : WJG. 2014 Jun 28;20(24):7864-77. PubMed PMID: 24976723. Pubmed Central PMCID: 4069314.
  8. Grenacher L, Klauss M. [Computed tomography of pancreatic tumors]. Der Radiologe. 2009 Feb;49(2):107-23. PubMed PMID: 19137277. Computertomographie bei Pankreastumoren.
  9. Vachiranubhap B, Kim YH, Balci NC, et al. Magnetic resonance imaging of adenocarcinoma of the pancreas. Top Magn Reson Imaging. 2009 Feb;20(1):3-9. PubMed PMID: 19687720.
  10. Muller MF, Meyenberger C, Bertschinger P, et al. Pancreatic tumors: evaluation with endoscopic US, CT, and MR imaging. Radiology. 1994 Mar;190(3):745-51. PubMed PMID: 8115622.
  11. Palazzo L, Roseau G, Gayet B, et al. Endoscopic ultrasonography in the diagnosis and staging of pancreatic adenocarcinoma. Results of a prospective study with comparison to ultrasonography and CT scan. Endoscopy. 1993 Feb;25(2):143-50. PubMed PMID: 8491130.
  12. Yasuda K, Mukai H, Nakajima M, et al. Staging of pancreatic carcinoma by endoscopic ultrasonography. Endoscopy. 1993 Feb;25(2):151-5. PubMed PMID: 8491131.
  13. Nakaizumi A, Uehara H, Iishi H, et al. Endoscopic ultrasonography in diagnosis and staging of pancreatic cancer. Digestive diseases and sciences. 1995 Mar;40(3):696-700. PubMed PMID: 7895567.
  14. Gress FG, Hawes RH, Savides TJ, et al. Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience. Gastrointestinal endoscopy. 1999 Dec;50(6):786-91. PubMed PMID: 10570337.
  15. Mertz HR, Sechopoulos P, Delbeke D, et al. EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc. 2000 Sep;52(3):367-71. PubMed PMID: 10968852.
  16. DeWitt J, Devereaux B, Chriswell M, et al. Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med. 2004 Nov 16;141(10):753-63. PubMed PMID: 15545675.
  17. Borbath I, Van Beers BE, Lonneux M, et al. Preoperative assessment of pancreatic tumors using magnetic resonance imaging, endoscopic ultrasonography, positron emission tomography and laparoscopy. Pancreatology : official journal of the International Association of Pancreatology. 2005;5(6):553-61. PubMed PMID: 16113592.
  18. Rickes S, Unkrodt K, Neye H, et al. Differentiation of pancreatic tumours by conventional ultrasound, unenhanced and echo-enhanced power Doppler sonography. Scandinavian journal of gastroenterology. 2002 Nov;37(11):1313-20. PubMed PMID: 12465731.
  19. Miura F, Takada T, Amano H, et al. Diagnosis of pancreatic cancer. HPB : the official journal of the International Hepato Pancreato Biliary Association. 2006;8(5):337-42. PubMed PMID: 18333085. Pubmed Central PMCID: 2020745.
  20. Burge ME, O’Rourke N, Cavallucci D, et al. A prospective study of the impact of fluorodeoxyglucose positron emission tomography with concurrent non-contrast CT scanning on the management of operable pancreatic and peri-ampullary cancers. HPB : the official journal of the International Hepato Pancreato Biliary Association. 2015 Jul;17(7):624-31. PubMed PMID: 25929273. Pubmed Central PMCID: PMC4474510.
  21. Huang Z, Liu F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2014 Aug;35(8):7459-65. PubMed PMID: 24789274.
  22. Schneider R, Slater EP, Sina M, et al. German national case collection for familial pancreatic cancer (FaPaCa): ten years experience. Familial cancer. 2011 Jun;10(2):323-30. PubMed PMID: 21207249.
  23. Ferrone CR, Finkelstein DM, Thayer SP, et al. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006 Jun 20;24(18):2897-902. PubMed PMID: 16782929. Pubmed Central PMCID: 3817569.
  24. Combs SE, Habermehl D, Kessel KA, et al. Prognostic impact of CA 19-9 on outcome after neoadjuvant chemoradiation in patients with locally advanced pancreatic cancer. Ann Surg Oncol. 2014 Aug;21(8):2801-7. PubMed PMID: 24916745.
  25. Hewitt MJ, McPhail MJ, Possamai L,et al. EUS-guided FNA for diagnosis of solid pancreatic neoplasms: a meta-analysis. Gastrointestinal endoscopy. 2012 Feb;75(2):319-31. PubMed PMID: 22248600.
  26. O’Toole D, Palazzo L, Arotcarena R, et al. Assessment of complications of EUS-guided fine-needle aspiration. Gastrointestinal endoscopy. 2001 Apr;53(4):470-4. PubMed PMID: 11275888.
  27. Micames C, Jowell PS, White R, et al. Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA. Gastrointestinal endoscopy. 2003 Nov;58(5):690-5. PubMed PMID: 14595302.
  28. Park JS, Kim HK, Bang BW, et al. Effectiveness of contrast-enhanced harmonic endoscopic ultrasound for the evaluation of solid pancreatic masses. World journal of gastroenterology : WJG. 2014 Jan 14;20(2):518-24. PubMed PMID: 24574720. Pubmed Central PMCID: 3923026.
  29. Li X, Xu W, Shi J, et al. Endoscopic ultrasound elastography for differentiating between pancreatic adenocarcinoma and inflammatory masses: a meta-analysis. World journal of gastroenterology : WJG. 2013 Oct 7;19(37):6284-91. PubMed PMID: 24115828. Pubmed Central PMCID: 3787361.
  30. Vargas R, Nino-Murcia M, Trueblood W, et al. MDCT in Pancreatic adenocarcinoma: prediction of vascular invasion and resectability using a multiphasic technique with curved planar reformations. AJR American journal of roentgenology. 2004 Feb;182(2):419-25. PubMed PMID: 14736675.
  31. Kaneko OF, Lee DM, Wong J, et al. Performance of multidetector computed tomographic angiography in determining surgical resectability of pancreatic head adenocarcinoma. Journal of computer assisted tomography. 2010 Sep-Oct;34(5):732-8. PubMed PMID: 20861777.
  32. Zamboni GA, Kruskal JB, Vollmer CM, et al. Pancreatic adenocarcinoma: value of multidetector CT angiography in preoperative evaluation. Radiology. 2007 Dec;245(3):770-8. PubMed PMID: 17951353.
  33. Park HS, Lee JM, Choi HK, et al. Preoperative evaluation of pancreatic cancer: comparison of gadolinium-enhanced dynamic MRI with MR cholangiopancreatography versus MDCT. Journal of magnetic resonance imaging : JMRI. 2009 Sep;30(3):586-95. PubMed PMID: 19711405.
  34. Nawaz H, Fan CY, Kloke J, et al. Performance characteristics of endoscopic ultrasound in the staging of pancreatic cancer: a meta-analysis. JOP : Journal of the pancreas. 2013 Sep;14(5):484-97. PubMed PMID: 24018593. Pubmed Central PMCID: 4407641.
  35. Ahmad NA, Lewis JD, Siegelman ES, et al. Role of endoscopic ultrasound and magnetic resonance imaging in the preoperative staging of pancreatic adenocarcinoma. The American journal of gastroenterology. 2000 Aug;95(8):1926-31. PubMed PMID: 10950037.
  36. Ramsay D, Marshall M, Song S, et al. Identification and staging of pancreatic tumours using computed tomography, endoscopic ultrasound and mangafodipir trisodium-enhanced magnetic resonance imaging. Australas Radiol. 2004 Jun;48(2):154-61. PubMed PMID: 15230749.
  37. Soriano A, Castells A, Ayuso C, et al. Preoperative staging and tumor resectability assessment of pancreatic cancer: prospective study comparing endoscopic ultrasonography, helical computed tomography, magnetic resonance imaging, and angiography. The American journal of gastroenterology. 2004 Mar;99(3):492-501. PubMed PMID: 15056091.
  38. DeWitt J, LeBlanc J, McHenry L, et al. Endoscopic ultrasound-guided fine needle aspiration cytology of solid liver lesions: a large single-center experience. The American journal of gastroenterology. 2003 Sep;98(9):1976-81. PubMed PMID: 14499774.
  39. Nguyen PT, Chang KJ. EUS in the detection of ascites and EUS-guided paracentesis. Gastrointestinal endoscopy. 2001 Sep;54(3):336-9. PubMed PMID: 11522974.
  40. Vukobrat-Bijedic Z, Husic-Selimovic A, Bijedic N, et al. Sensitivity of EUS and ERCP Endoscopic Procedures in the Detection of Pancreatic Cancer During Preoperative Staging Correlated with CT and CT Angiography Imaging Methods. Acta informatica medica : AIM : journal of the Society for Medical Informatics of Bosnia & Herzegovina : casopis Drustva za medicinsku informatiku BiH. 2014 Jun;22(3):160-3. PubMed PMID: 25132706. Pubmed Central PMCID: 4130672.
  41. Ahmad NA, Lewis JD, Ginsberg GG, et al. Long term survival after pancreatic resection for pancreatic adenocarcinoma. The American journal of gastroenterology. 2001 Sep;96(9):2609-15. PubMed PMID: 11569683.
  42. Jung KW, Kim MH, Lee TY, et al. Clinicopathological aspects of 542 cases of pancreatic cancer: a special emphasis on small pancreatic cancer. Journal of Korean medical science. 2007 Sep;22 Suppl:S79-85. PubMed PMID: 17923760. Pubmed Central PMCID: 2694379.
  43. Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. The American journal of surgical pathology. 2004 Aug;28(8):977-87. PubMed PMID: 15252303.
  44. Luebeck EG. Cancer: Genomic evolution of metastasis. Nature. 2010 Oct 28;467(7319):1053-5. PubMed PMID: 20981088.
  45. Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an update. Digestive diseases. 2010;28(4-5):645-56. PubMed PMID: 21088417.
  46. Canto MI, Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 Mar;62(3):339-47. PubMed PMID: 23135763. Pubmed Central PMCID: PMC3585492.
  47. Brand RE, Lynch HT. Hereditary pancreatic adenocarcinoma. A clinical perspective. The Medical clinics of North America. 2000 May;84(3):665-75. PubMed PMID: 10872423.
  48. Chang MC, Wong JM, Chang YT. Screening and early detection of pancreatic cancer in high risk population. World journal of gastroenterology : WJG. 2014 Mar 7;20(9):2358-64. PubMed PMID: 24605033. Pubmed Central PMCID: 3942839.
  49. Becker AE, Hernandez YG, Frucht H, et al. Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World journal of gastroenterology : WJG. 2014 Aug 28;20(32):11182-98. PubMed PMID: 25170203. Pubmed Central PMCID: 4145757.
  50. Canto MI, Goggins M, Yeo CJ, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004 Jul;2(7):606-21. PubMed PMID: 15224285.
  51. Canto MI, Hruban RH, Fishman EK, et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology. 2012 Apr;142(4):796-804; quiz e14-5. PubMed PMID: 22245846. Pubmed Central PMCID: PMC3321068.
  52. Rulyak SJ, Lowenfels AB, Maisonneuve P, et al. Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds. Gastroenterology. 2003 May;124(5):1292-9. PubMed PMID: 12730869.
  53. Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology : official journal of the International Association of Pancreatology. 2012 May-Jun;12(3):183-97. PubMed PMID: 22687371.
  54. Canto MI, Goggins M, Hruban RH, et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol. 2006 Jun;4(6):766-81; quiz 665. PubMed PMID: 16682259.
  55. Poley JW, Kluijt I, Gouma DJ, et al. The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. The American journal of gastroenterology. 2009 Sep;104(9):2175-81. PubMed PMID: 19491823.
  56. Langer P, Kann PH, Fendrich V, et al. Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer. Gut. 2009 Oct;58(10):1410-8. PubMed PMID: 19470496.
  57. Verna EC, Hwang C, Stevens PD, et al. Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics. Clin Cancer Res : an official journal of the American Association for Cancer Research. 2010 Oct 15;16(20):5028-37. PubMed PMID: 20876795.
  58. Al-Sukhni W, Borgida A, Rothenmund H, et al. Screening for pancreatic cancer in a high-risk cohort: an eight-year experience. J Gastrointest Surg : official journal of the Society for Surgery of the Alimentary Tract. 2012 Apr;16(4):771-83. PubMed PMID: 22127781.
  59. Vasen HF, Wasser M, van Mil A, et al. Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation. Gastroenterology. 2011 Mar;140(3):850-6. PubMed PMID: 21129377.
  60. Ludwig E, Olson SH, Bayuga S, et al. Feasibility and yield of screening in relatives from familial pancreatic cancer families. Am J Gastroenterol. 2011 May;106(5):946-54. PubMed PMID: 21468009. Pubmed Central PMCID: 3683863.
  61. Capurso G, Signoretti M, Valente R, et al. Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals. World journal of gastrointestinal endoscopy. 2015 Jul 25;7(9):833-42. PubMed PMID: 26240684. Pubmed Central PMCID: 4515417.
  62. Brentnall TA, Bronner MP, Byrd DR, et al. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med. 1999 Aug 17;131(4):247-55. PubMed PMID: 10454945.
  63. Axilbund JE, Brune KA, Canto MI, et al. Patient perspective on the value of genetic counselling for familial pancreas cancer. Hered Cancer Clin Pract. 2005;3(3):115-22. PubMed PMID: 20223036. Pubmed Central PMCID: PMC2837293.
  64. Maheu C, Vodermaier A, Rothenmund H, et al. Pancreatic cancer risk counselling and screening: impact on perceived risk and psychological functioning. Fam Cancer. 2010 Dec;9(4):617-24. PubMed PMID: 20623197. Epub 2010/07/14. eng.
  65. Harinck F, Nagtegaal T, Kluijt I, et al. Feasibility of a pancreatic cancer surveillance program from a psychological point of view. Genet Med. 2011 Dec;13(12):1015-24. PubMed PMID: 21857231. Epub 2011/08/23. eng.

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