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World J Gastrointest Endosc. Mar 16, 2015; 7(3): 258-264
Published online Mar 16, 2015. doi: 10.4253/wjge.v7.i3.258
Head mass in chronic pancreatitis: Inflammatory or malignant
Amit K Dutta, Ashok Chacko
Amit K Dutta, Department of Gastrointestinal Sciences, Christian Medical College, Vellore 632 004, India
Ashok Chacko, Institute of Gastroenterology and Liver Disease, the Madras Medical Mission, Chennai 600037, India
Author contributions: Dutta AK was involved in the search and review of literature and preparation of manuscript; Chacko A was involved in the concept of this study, search and review of literature, preparation of manuscript and critical appraisal.
Conflict-of-interest: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ashok Chacko, Professor, Director, Institute of Gastroenterology and Liver Disease, the Madras Medical Mission, 4-A, Dr J Jayalalitha Nagar, Mogappair, Chennai 600037, India. chacko.ashok@gmail.com
Telephone: +91-44-26565961 Fax: +91-44-26565906
Received: August 27, 2014
Peer-review started: August 28, 2014
First decision: September 30, 2014
Revised: November 15, 2014
Accepted: December 16, 2014
Article in press: December 17, 2014
Published online: March 16, 2015

Abstract

Chronic pancreatitis increases the risk of developing pancreatic cancer. This often presents as a mass lesion in the head of pancreas. Mass lesion in the head of pancreas can also occur secondary to an inflammatory lesion. Recognising this is crucial to avoid unnecessary surgery. This is sometimes difficult as there is an overlap in clinical presentation and conventional computed tomography (CT) abdomen findings in inflammatory and malignant mass. Advances in imaging technologies like endoscopic ultrasound in conjunction with techniques like fine needle aspiration, contrast enhancement and elastography as well as multidetector row CT, magnetic resonance imaging and positron emission tomography scanning have been shown to help in distinguishing inflammatory and malignant mass. Research is ongoing to develop molecular techniques to help characterise focal pancreatic mass lesions. This paper reviews the current status of imaging and molecular techniques in differentiating a benign mass lesion in chronic pancreatitis and from malignancy.

Key Words: Chronic pancreatitis, Pseudotumour, Imaging, Endoscopic ultrasonography, Molecular tool

Core tip: Evaluating head mass in chronic pancreatitis is clinically challenging. Advances in pancreatic imaging including endoscopic ultrasonography and molecular tools have been reviewed.



INTRODUCTION

The risk of developing pancreatic cancer in patients with chronic pancreatitis is about fifteen times higher than in the average population[1]. A meta analysis has shown that 5% of the patients with chronic pancreatitis develop pancreatic cancer over a 20 year period[2]. About 70% of these tumours are located in the head region of pancreas[3]. Patients with chronic pancreatitis also tend to develop inflammatory lesions in the head of pancreas which appears like tumour mass and is referred to as pseudotumour[4]. Confirming the diagnosis preoperatively is crucial because confusion may lead to either major pancreatic resection for benign disease or rejection of surgery for a potentially curable lesion.

Clinical features and biochemical parameters that suggest malignant mass in head of pancreas are older age, persistent jaundice, worsening abdominal pain, gastric outlet obstruction, significant weight loss and elevated CA 19:9 greater than 300 U/mL[5]. Conventional Imaging techniques like Ultrasound abdomen, CT and MRI provide useful information that helps in differentiating benign from malignant mass in head of pancreas[6]. Unfortunately, due to an overlap in clinical, biochemical and conventional imaging parameters, it is sometimes difficult to differentiate an inflammatory mass from cancer in head of pancreas[6]. This is supported by the fact that most large series of pancreatic resections for carcinoma head of pancreas show that 5%-10% of cases of inflammatory mass masquerade as pancreatic carcinoma[7,8].

The advent of endoscopic ultrasound (EUS) has been a major development in assessment of pancreatic disease including mass lesions in the head of pancreas[9]. High frequency EUS probes in the stomach located close to the pancreas, provide detailed images with no intervening bowel gas[9]. In addition, fine needle aspiration (FNA) performed for obtaining tissue sample further helps in diagnosis. New EUS based techniques like Digital Image analysis, EUS Elastography and Contrast enhanced EUS have shown promise in better characterisation of pancreatic mass lesion. In this paper we review the role of EUS in assessing pancreatic head mass in chronic pancreatitis and also briefly look at other radiological and molecular tools available for evaluation of this entity.

ENDOSCOPIC ULTRASONOGRAPHY

Endoscopic ultrasonography has been found to be very useful in detecting small pancreatic mass lesions and has been shown to be better than other modalities for assessing vascular invasion and local spread[10,11]. EUS in association with other techniques like FNA or contrast enhancement has also been found to be useful in distinguishing benign from malignant pancreatic mass lesions. The data from studies evaluating the role of EUS in assessing pancreatic mass lesion has been summarised in Tables 1 and 2. Table 1 shows only studies which have included patients with background chronic pancreatitis. Most studies show that EUS alone is not capable of precisely differentiating between a pseudotumoral mass and carcinoma in the setting of chronic pancreatitis[12-14]. Presence of multilobularity, homogenous pattern, hyperechoic septa and Doppler signal within a lesion favour pseudotumour[12]. One of the limitations with EUS is the subjective nature of image assessment and performance which varies depending on experience. As the architectural changes are better detected by computer based methods than naked eye, it is possible that digital image analysis (DIA) obtained during EUS can remove the error of subjective assessment. Two studies with adequate number of subjects have shown that digital image analysis has sensitivity and specificity of above 90% in differentiating malignant and benign pancreatic mass lesion[15,16].

Table 1 Endoscopic ultrasound in evaluating pancreatic mass lesions in patients with chronic pancreatitis.
Ref.Study subjectsProcedureOutcome1
Fritscher-Ravens et al[19]74 patients with focal pancreatic lesions and chronic pancreatitisEUS FNASn-54%
Vardarajulu et al[17]75 patients with CP and focal pancreatic mass lesionEUS FNASn-73.9%
Sp-100%
Iordache et al[18]CP-55 CP and PC-17EUS FNASn-50%
Sp-73.7%
Hocke et al[13]86 patients with CP and pancreatic lesionEUSSn-73.2%
Sp-83.3%
CE-EUSSn-91.1%
Sp-93.3%
Table 2 Data from other studies on role of endoscopic ultrasound in evaluating pancreatic mass lesions.
Ref.Study subjectsProcedureOutcome1
Ardengh et al[12]69 patients with pancreatic head massEUSSn-63.63%
Sp-75.86%
EUS FNASn-72.7%
Sp-100%
Das et al[16]Normal-22CP-12PC-22EUS, Digital image analysisSn-93%
Sp-92%
Zhu et al[15]CP-262EUS, Digital image analysisSn-96.25%
PC-126Sp-93.38%
Hirsche et al[32]70 patients with focal pancreatic lesionEUSSn-41%
ElastographySp-53%
Giovannini et al[33]121 patients with pancreatic mass lesionEUSSn-92.3%
Sp-68.9%
EUS ElastographySn-92.3%
Sp-80%
Iglesias-Garcia et al[35]78 patients with malignant pancreatic tumourEUS ElastographySn-100%
42 patients with inflammatory pancreatic massSp-85.5%
Iglesias-Garcia et al[30]86 patients with pancreatic mass (27 of them had inflammatory mass)Quantitative EUS ElastographySn-100%
Sp-92.9%
Seicean et al[38]30 patients with pancreatic lesion (12 had pseudotumour)CE harmonic-EUSSn-80%
Sp-91.7%
Saftoui et al[41]Focal pancreatic mass lesion (21 had pseudotumour)CE + elastography during EUSSn-75.85
Sp-95.2%
Saftoui et al[34]258 patients with focal pancreatic massQuantitative EUS ElastographySn-93.4%
Sp-66%
Hocke et al[14]Focal CP-39EUSSn-61.5%
Sp-73.7%
EUS elastographySn-33.4%
Sp-94.7%
PC-19CELMI-EUSSn-76.9%
Sp-84.2%
CEHMI-EUSSn-89.5%
Sp-84.2%
Gheona et al[40]PC-32Quantitative CE-EUSSn-93.7%
Pseudotumoural pancreatitis-19Sp-89.4%

The limitations of conventional B mode EUS can be overcome by performing FNA which gives a tissue diagnosis. FNA is relatively safe as it does not traverse peritoneal cavity and avoids seeding of peritoneum. Unfortunately, FNA which has a sensitivity of above 90% in detecting pancreatic malignancy in pancreas with normal parenchyma, underperforms in the presence of chronic pancreatitis with sensitivity dropping to below 75%[12,17-19]. Vardarajulu and colleagues reported that in the 300 EUS FNA performed for pancreatic mass lesions, sensitivity was 91.3% in pancreas with normal parenchyma but only 73.9% when chronic pancreatitis was present[17]. Other studies have shown even poorer performance. In a study from Romania on 72 patients with Chronic Pancreatitis (17 had Pancreatic Carcinoma), EUS FNA had a sensitivity of only 50%[18]. Similarly, in another report from Germany on 13 patients with Chronic Pancreatitis and carcinoma, EUS FNA was able to detect carcinoma in only 7 of them[19]. Making more number of passes during FNA or repeating FNA may improve the yield[17,20].

Using molecular tools to detect mutation in tissue sample may be a useful adjunct to improve diagnostic yield[21-23]. Khalid et al[21], studied microsatellite markers and mutation in K-ras gene on EUS-FNA samples from patients with benign and malignant pancreatic masses. The mean fractional mutation rate was higher in pancreatic malignancy and use of molecular tool improved the diagnostic performance of FNA[21]. In another study from Czech Republic which included 101 subjects, mutations in K-ras and allelic loss in tumour suppressor genes were determined on EUS-FNA specimen[22]. Detection of mutation in k-ras gene, allelic loss of p16 and DPC4 gene improved the sensitivity of cancer detection to 100%[22]. A large prospective multicenter study which only looked at k-ras mutations in addition to cytopatholgy on FNA samples, found that assessing for k-ras mutation improved the diagnostic sensitivity for malignancy to 88% which was only marginally better than cytopathology alone (83%)[24]. However, absence of K-ras mutation was a strong indicator of benign lesion[24]. This study also highlights the importance of studying multiple markers rather than single one. Other studies have shown that absence of k-ras mutation in FNA samples from patients with chronic pancreatitis and mass lesion strongly suggest a benign lesion[24,25]. Data from the above studies suggest that molecular tests can play a significant role in diagnosing pancreatic cancer in FNA samples and one should assess for k-ras mutations along with loss of tumour suppressor genes to improve yield.

Recent advances in EUS based technology like EUS Elastography, Contrast Enhanced EUS and computer software in interpreting images have shown promise in better characterisation of pancreatic mass lesions[26-28]. EUS elastography measures tissue stiffness[26,29]. The stiffness in malignant tumour is different from benign lesion or normal tissue and this is represented as different colour regions on the conventional real time EUS images. Usually blue colour indicates hard tissue, red suggests soft tissue and green represents tissue with intermediate stiffness. To remove subjective error, tissue strain can be quantitatively measured by software to provide strain ratios which are different for benign and malignant lesions[29,30]. The results of earlier studies with EUS elastography were disappointing showing low sensitivity and specificity[31,32]. This was probably due to fibrous architecture in both tumour and chronic pancreatitis[31]. Subsequent studies after the introduction of quantitative assessment methods including measurement of strain ratio have shown better outcomes (sensitivity > 90%)[30,33-35]. In a study measuring strain ratio during EUS elastography, ratio was 1.68 for normal pancreas, 3.38 for inflammatory mass and a very high ratio of 18.12 for pancreatic adenocarcinoma[30].

Contrast enhanced (CE) EUS makes use of injected contrast to assess vascularity of lesion and low mechanical index technique enables this to be done in real time without problem of artefacts[36]. Arterial phase lasts for about 30 s and venous phase for the next 90 s[37]. Pancreatic tumours are hypovascular with delayed contrast uptake and usually lack venous structure[13,38,39]. A time intensity curve can be generated using image software and the peak characteristics can give a clue to the underlying diagnosis. Results from most studies using CE EUS have been encouraging with sensitivity and specificity greater than 90%[13,14,38,40,41]. Seicean et al[38] measured the contrast uptake ratio index during CE EUS and found it to be significantly lower in pancreatic cancer than in mass forming chronic pancreatitis. A cut-off ratio of 0.17 had good discriminatory value[38]. The contrast enhancement and elastography techniques can also be used in combination. In a study using combination of above techniques, the positive predictive value was 96.7% in evaluating pseudotumour of chronic pancreatitis and pancreatic cancer[41]. The results of elastography, CE EUS and digital image analysis are encouraging but are affected by equipment characteristics and type of contrast used. Development of consensus guidelines and uniformity in performing these procedures will make it easier to integrate their use in clinical practice.

OTHER IMAGING MODALITIES
Computed tomography

Computed tomography (CT) was considered to be the gold standard for pancreatic parenchymal imaging. Conventional CT however has difficulty in differentiating between inflammatory and neoplastic masses as well as detecting lesions < 2 cm in diameter as small tumours are sometimes isoattenuated to background pancreatic parenchyma. Recent developments including 64 slice multidetector row CT (MDCT) have shown promise in evaluating pancreatic mass lesion[42,43]. During triple phase pancreatic protocol CT, normal pancreas shows early washout (first phase) while there is delayed washout in chronic pancreatitis[44]. On the other hand pancreatic cancer shows an increasing pattern without washout[44]. This can be quantitatively assessed using time attenuation curve and Yamada et al[44] have shown this technique to have 90.4% accuracy in differentiating pancreatic cancer from chronic pancreatitis. Lu et al[45] evaluated 15 patients with pancreatic pseudotumor and 64 patients with pancreatic cancer and quantitative hemodynamic information obtained using time density curve was useful in distinguishing the two conditions.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) has traditionally been considered less sensitive than CT scan for assessing pancreatic mass lesions. T1 weighted images have similar features in both chronic pancreatitis and pancreatic cancer but T2 weighted images show different signal intensity pattern in inflammatory and neoplastic tissue[46]. Assessment of pancreatic ductal structures can sometimes provide a clue as pancreatic cancers may lack pancreatic ductal structures while a pseudotumour may contain dilated side branches[47]. Recent advances in techniques and technology have been effective in distinguishing between inflammatory and malignant mass of pancreas[42,43,48,49]: (1) Diffusion weighted MRI: Huang et al[50] studied 37 patients with pancreatic cancer and 14 patients with mass forming chronic pancreatitis using diffusion weighted MRI imaging with quantification techniques and showed that this technique can differentiate mass forming chronic pancreatitis from pancreatic cancer; (2) Gadolinium (Gd) enhanced 3D- Gradient echo: Kim et al[51] studied 22 patients with pancreatic mass (pancreatic cancer: 14; chronic pancreatitis: 8) using Gd enhanced 3D-GE and found that this technique differentiated pancreatic cancer from inflammatory mass with a sensitivity and specificity of 93% (13/14) and 75% (6/8), respectively; (3) Time signal intensity curve obtained during contrast enhanced MRI is another technique that helps in differentiating between malignant and inflammatory lesions[50]; and (4) Magnetic resonance spectroscopy: Focal pancreatitis has lower lipid content compared to cancer due to difference in fibrous tissue content in the two conditions. This can be detected by magnetic resonance spectroscopy and helps distinguish inflammatory mass from cancer[52].

Positron emission tomography

The sensitivity of FDG-positron emission tomography (PET) for differentiating pancreatic cancer from chronic pancreatitis is more than that of CT or MRI[53]. Singer and colleagues have shown that pancreatic cancer causes focal tracer enhancement while chronic pancreatitis causes diffuse enhancement[54]. This feature had 86.4% sensitivity and 78.9% specificity in distinguishing cancer from benign mass in their study on 41 patients. PET-CT detects unsuspected metastasis to liver, lung and bone which aids in discriminating between inflammatory mass and cancer. The sensitivity of PET is superior to CT in detecting lesions less than 2 cm in diameter, but CT scanning is superior to PET for diagnosing cancers larger than 4 cm in diameter because of lower metabolic rates in larger tumors[55].

Molecular techniques

Advances in molecular techniques and tools like microarray, nuclear magnetic resonance and mass spectrometry have enabled detection of a large number of molecules rapidly. At cellular level genetic information gets transcribed into m RNA which gets translated into proteins and subsequently metabolised. Alteration of genes at cellular level in neoplastic cells leads to changes in protein and metabolites and this can be detected using “omics” technology[56-58]. Genomics aims at detecting genes, proteomics at detecting set of expressed proteins and metabolomics the metabolic profile. While molecular techniques can detect a large array of products, filtering out the specific markers useful for diagnosing different conditions remains a challenge. A proteomics based study from United States, aimed to identify the plasma protein profile in subjects with chronic pancreatitis, pancreatic cancer and non-pancreatic disease controls[59]. They identified more than 1300 proteins and found that a composite marker of TIMP1 and ICAM1 performed better than CA19-9 in differentiating pancreatic cancer from rest of the group. They also suggested that a protein called AZGP1 could serve as a biomarker for chronic pancreatitis[59]. Paulo et al[60] studied expressed proteins in chronic pancreatitis, pancreatic cancer and autoimmune pancreatitis and found a range of differentially expressed proteins in the three different groups. Using liquid chromatography with tandem mass spectrometry, they found that 29 proteins were exclusively expressed in chronic pancreatitis and 53 protein in pancreatic cancer[60]. These tests were conducted on tissue samples and hence can serve as an adjunct to histology but require validation in larger cohort.

Zhang et al[61] used NMR based metabolomics strategy to distinguish pancreatic cancer from chronic pancreatitis and healthy individuals and found the results promising. Patients with pancreatic cancer had a number of abnormalities in amino acid and lipid metabolism including elevated levels of N-acetyl glycoprotein and dimethylamine and reduced levels of citrate, alanine, glutamine. In another metabolomics based study done employing gas chromatography mass spectrometry on subjects with chronic pancreatitis, pancreatic cancer and healthy volunteers, Kobayashi and colleagues were able to develop a model which performed reasonably well in differentiating PC from CP. Other studies have shown, Ca 242, M2 pyruvate kinase, PBF-4, PNA binding glycoprotein, nTert, MMP-2, Synuclein-gamma, and neopterin to be useful biomarkers in differentiating pancreatic cancer from chronic pancreatitis[59,62,63]. A study from Germany has shown that micro RNA abundance measured in tissue and blood performs well in distinguishing chronic pancreatitis and pancreatic cancer[64]. Overall, molecular tools appear promising but are not yet ready for clinical application.

CONCLUSION

There have been a number of developments in imaging and molecular technologies to aid in differentiating benign from malignant mass lesion in patients with chronic pancreatitis. While some like EUS-FNA and advanced CT/MRI techniques are already in clinical use, technologies like CE EUS, EUS elastography and digital image analysis require development of standardised protocol, consensus and operator training facilities before they can be inducted into regular clinical usage. The molecular techniques are still in the early stage of development. Continued research and development is required to help in the correct diagnosis of this challenging condition.

Footnotes

P- Reviewer: Gurkan A, Richardson WS, Sofi A S- Editor: Tian YL L- Editor: A E- Editor: Zhang DN

References
1.  McKay CJ, Glen P, McMillan DC. Chronic inflammation and pancreatic cancer. Best Pract Res Clin Gastroenterol. 2008;22:65-73.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Raimondi S, Lowenfels AB, Morselli-Labate AM, Maisonneuve P, Pezzilli R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol. 2010;24:349-358.  [PubMed]  [DOI]  [Cited in This Article: ]
3.  Jimenez E, Castillo CF. Tumors of Pancreas. Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management. 9th ed. Philadelphia: Saunders Elsevier 2010; 1017-1024.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Oto A, Eltorky MA, Dave A, Ernst RD, Chen K, Rampy B, Chaljub G, Nealon W. Mimicks of pancreatic malignancy in patients with chronic pancreatitis: correlation of computed tomography imaging features with histopathologic findings. Curr Probl Diagn Radiol. 2006;35:199-205.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Bedi MM, Gandhi MD, Jacob G, Lekha V, Venugopal A, Ramesh H. CA 19-9 to differentiate benign and malignant masses in chronic pancreatitis: is there any benefit? Indian J Gastroenterol. 2009;28:24-27.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Evans JD, Morton DG, Neoptolemos JP. Chronic pancreatitis and pancreatic carcinoma. Postgrad Med J. 1997;73:543-548.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Perumal S, Palaniappan R, Pillai SA, Velayutham V, Sathyanesan J. Predictors of malignancy in chronic calcific pancreatitis with head mass. World J Gastrointest Surg. 2013;5:97-103.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Taylor B. Carcinoma of the head of the pancreas versus chronic pancreatitis: diagnostic dilemma with significant consequences. World J Surg. 2003;27:1249-1257.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Irisawa A, Sato A, Sato M, Ikeda T, Suzuki R, Ohira H. Early diagnosis of small pancreatic cancer: role of endoscopic ultrasonography. Dig Endosc. 2009;21 Suppl 1:S92-S96.  [PubMed]  [DOI]  [Cited in This Article: ]
10.  Gress FG, Hawes RH, Savides TJ, Ikenberry SO, Cummings O, Kopecky K, Sherman S, Wiersema M, Lehman GA. Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience. Gastrointest Endosc. 1999;50:786-791.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Sreenarasimhaiah J. Efficacy of endoscopic ultrasound in characterizing mass lesions in chronic pancreatitis. J Clin Gastroenterol. 2008;42:81-85.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Ardengh JC, Lopes CV, Campos AD, Pereira de Lima LF, Venco F, Módena JL. Endoscopic ultrasound and fine needle aspiration in chronic pancreatitis: differential diagnosis between pseudotumoral masses and pancreatic cancer. JOP. 2007;8:413-421.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Hocke M, Schulze E, Gottschalk P, Topalidis T, Dietrich CF. Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer. World J Gastroenterol. 2006;12:246-250.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Hocke M, Ignee A, Dietrich CF. Advanced endosonographic diagnostic tools for discrimination of focal chronic pancreatitis and pancreatic carcinoma--elastography, contrast enhanced high mechanical index (CEHMI) and low mechanical index (CELMI) endosonography in direct comparison. Z Gastroenterol. 2012;50:199-203.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Zhu M, Xu C, Yu J, Wu Y, Li C, Zhang M, Jin Z, Li Z. Differentiation of pancreatic cancer and chronic pancreatitis using computer-aided diagnosis of endoscopic ultrasound (EUS) images: a diagnostic test. PLoS One. 2013;8:e63820.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Das A, Nguyen CC, Li F, Li B. Digital image analysis of EUS images accurately differentiates pancreatic cancer from chronic pancreatitis and normal tissue. Gastrointest Endosc. 2008;67:861-867.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  Varadarajulu S, Tamhane A, Eloubeidi MA. Yield of EUS-guided FNA of pancreatic masses in the presence or the absence of chronic pancreatitis. Gastrointest Endosc. 2005;62:728-736; quiz 751, 753.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Iordache S, Săftoiu A, Cazacu S, Gheonea DI, Dumitrescu D, Popescu C, Ciurea T. Endoscopic ultrasound approach of pancreatic cancer in chronic pancreatitis patients in a tertiary referral centre. J Gastrointestin Liver Dis. 2008;17:279-284.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Fritscher-Ravens A, Brand L, Knöfel WT, Bobrowski C, Topalidis T, Thonke F, de Werth A, Soehendra N. Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis. Am J Gastroenterol. 2002;97:2768-2775.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Eloubeidi MA, Varadarajulu S, Desai S, Wilcox CM. Value of repeat endoscopic ultrasound-guided fine needle aspiration for suspected pancreatic cancer. J Gastroenterol Hepatol. 2008;23:567-570.  [PubMed]  [DOI]  [Cited in This Article: ]
21.  Khalid A, Nodit L, Zahid M, Bauer K, Brody D, Finkelstein SD, McGrath KM. Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses. Am J Gastroenterol. 2006;101:2493-2500.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  Salek C, Benesova L, Zavoral M, Nosek V, Kasperova L, Ryska M, Strnad R, Traboulsi E, Minarik M. Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer. World J Gastroenterol. 2007;13:3714-3720.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Chen Y, Zheng B, Robbins DH, Lewin DN, Mikhitarian K, Graham A, Rumpp L, Glenn T, Gillanders WE, Cole DJ. Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration. Int J Cancer. 2007;120:1511-1517.  [PubMed]  [DOI]  [Cited in This Article: ]
24.  Bournet B, Souque A, Senesse P, Assenat E, Barthet M, Lesavre N, Aubert A, O’Toole D, Hammel P, Levy P. Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with KRAS mutation assay to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis. Endoscopy. 2009;41:552-557.  [PubMed]  [DOI]  [Cited in This Article: ]
25.  Takahashi K, Yamao K, Okubo K, Sawaki A, Mizuno N, Ashida R, Koshikawa T, Ueyama Y, Kasugai K, Hase S. Differential diagnosis of pancreatic cancer and focal pancreatitis by using EUS-guided FNA. Gastrointest Endosc. 2005;61:76-79.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  Seicean A. Endoscopic ultrasound in chronic pancreatitis: where are we now? World J Gastroenterol. 2010;16:4253-4263.  [PubMed]  [DOI]  [Cited in This Article: ]
27.  Pei Q, Zou X, Zhang X, Chen M, Guo Y, Luo H. Diagnostic value of EUS elastography in differentiation of benign and malignant solid pancreatic masses: a meta-analysis. Pancreatology. 2012;12:402-408.  [PubMed]  [DOI]  [Cited in This Article: ]
28.  Iglesias-García J, Lindkvist B, Lariño-Noia J, Domínguez-Muñoz JE. The role of EUS in relation to other imaging modalities in the differential diagnosis between mass forming chronic pancreatitis, autoimmune pancreatitis and ductal pancreatic adenocarcinoma. Rev Esp Enferm Dig. 2012;104:315-321.  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Giovannini M. Endoscopic ultrasound elastography. Pancreatology. 2011;11 Suppl 2:34-39.  [PubMed]  [DOI]  [Cited in This Article: ]
30.  Iglesias-Garcia J, Larino-Noia J, Abdulkader I, Forteza J, Dominguez-Munoz JE. Quantitative endoscopic ultrasound elastography: an accurate method for the differentiation of solid pancreatic masses. Gastroenterology. 2010;139:1172-1180.  [PubMed]  [DOI]  [Cited in This Article: ]
31.  Janssen J, Schlörer E, Greiner L. EUS elastography of the pancreas: feasibility and pattern description of the normal pancreas, chronic pancreatitis, and focal pancreatic lesions. Gastrointest Endosc. 2007;65:971-978.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  Hirche TO, Ignee A, Barreiros AP, Schreiber-Dietrich D, Jungblut S, Ott M, Hirche H, Dietrich CF. Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions. Endoscopy. 2008;40:910-917.  [PubMed]  [DOI]  [Cited in This Article: ]
33.  Giovannini M, Thomas B, Erwan B, Christian P, Fabrice C, Benjamin E, Geneviève M, Paolo A, Pierre D, Robert Y. Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: a multicenter study. World J Gastroenterol. 2009;15:1587-1593.  [PubMed]  [DOI]  [Cited in This Article: ]
34.  Săftoiu A, Vilmann P, Gorunescu F, Janssen J, Hocke M, Larsen M, Iglesias-Garcia J, Arcidiacono P, Will U, Giovannini M. Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study. Endoscopy. 2011;43:596-603.  [PubMed]  [DOI]  [Cited in This Article: ]
35.  Iglesias-Garcia J, Larino-Noia J, Abdulkader I, Forteza J, Dominguez-Munoz JE. EUS elastography for the characterization of solid pancreatic masses. Gastrointest Endosc. 2009;70:1101-1108.  [PubMed]  [DOI]  [Cited in This Article: ]
36.  Seicean A, Badea R, Stan-Iuga R, Gulei I, Pop T, Pascu O. The added value of real-time harmonics contrast-enhanced endoscopic ultrasonography for the characterisation of pancreatic diseases in routine practice. J Gastrointestin Liver Dis. 2010;19:99-104.  [PubMed]  [DOI]  [Cited in This Article: ]
37.  Claudon M, Cosgrove D, Albrecht T, Bolondi L, Bosio M, Calliada F, Correas JM, Darge K, Dietrich C, D’Onofrio M. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) - update 2008. Ultraschall Med. 2008;29:28-44.  [PubMed]  [DOI]  [Cited in This Article: ]
38.  Seicean A, Badea R, Stan-Iuga R, Mocan T, Gulei I, Pascu O. Quantitative contrast-enhanced harmonic endoscopic ultrasonography for the discrimination of solid pancreatic masses. Ultraschall Med. 2010;31:571-576.  [PubMed]  [DOI]  [Cited in This Article: ]
39.  Dietrich CF, Ignee A, Braden B, Barreiros AP, Ott M, Hocke M. Improved differentiation of pancreatic tumors using contrast-enhanced endoscopic ultrasound. Clin Gastroenterol Hepatol. 2008;6:590-597.e1.  [PubMed]  [DOI]  [Cited in This Article: ]
40.  Gheonea DI, Streba CT, Ciurea T, Săftoiu A. Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer. BMC Gastroenterol. 2013;13:2.  [PubMed]  [DOI]  [Cited in This Article: ]
41.  Săftoiu A, Iordache SA, Gheonea DI, Popescu C, Maloş A, Gorunescu F, Ciurea T, Iordache A, Popescu GL, Manea CT. Combined contrast-enhanced power Doppler and real-time sonoelastography performed during EUS, used in the differential diagnosis of focal pancreatic masses (with videos). Gastrointest Endosc. 2010;72:739-747.  [PubMed]  [DOI]  [Cited in This Article: ]
42.  Chaudhary V, Bano S. Imaging of the pancreas: Recent advances. Indian J Endocrinol Metab. 2011;15:S25-S32.  [PubMed]  [DOI]  [Cited in This Article: ]
43.  Bipat S, Phoa SS, van Delden OM, Bossuyt PM, Gouma DJ, Laméris JS, Stoker J. Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis and determining resectability of pancreatic adenocarcinoma: a meta-analysis. J Comput Assist Tomogr. 2005;29:438-445.  [PubMed]  [DOI]  [Cited in This Article: ]
44.  Yamada Y, Mori H, Matsumoto S, Kiyosue H, Hori Y, Hongo N. Pancreatic adenocarcinoma versus chronic pancreatitis: differentiation with triple-phase helical CT. Abdom Imaging. 2010;35:163-171.  [PubMed]  [DOI]  [Cited in This Article: ]
45.  Lu N, Feng XY, Hao SJ, Liang ZH, Jin C, Qiang JW, Guo QY. 64-slice CT perfusion imaging of pancreatic adenocarcinoma and mass-forming chronic pancreatitis. Acad Radiol. 2011;18:81-88.  [PubMed]  [DOI]  [Cited in This Article: ]
46.  Ragozzino A, Scaglione M. Pancreatic head mass: what can be done? Diagnosis: magnetic resonance imaging. JOP. 2000;1:100-107.  [PubMed]  [DOI]  [Cited in This Article: ]
47.  Schima W. MRI of the pancreas: tumours and tumour-simulating processes. Cancer Imaging. 2006;6:199-203.  [PubMed]  [DOI]  [Cited in This Article: ]
48.  Hakimé A, Giraud M, Vullierme MP, Vilgrain V. [MR imaging of the pancreas]. J Radiol. 2007;88:11-25.  [PubMed]  [DOI]  [Cited in This Article: ]
49.  Sandrasegaran K, Lin C, Akisik FM, Tann M. State-of-the-art pancreatic MRI. AJR Am J Roentgenol. 2010;195:42-53.  [PubMed]  [DOI]  [Cited in This Article: ]
50.  Huang WC, Sheng J, Chen SY, Lu JP. Differentiation between pancreatic carcinoma and mass-forming chronic pancreatitis: usefulness of high b value diffusion-weighted imaging. J Dig Dis. 2011;12:401-408.  [PubMed]  [DOI]  [Cited in This Article: ]
51.  Kim JK, Altun E, Elias J, Pamuklar E, Rivero H, Semelka RC. Focal pancreatic mass: distinction of pancreatic cancer from chronic pancreatitis using gadolinium-enhanced 3D-gradient-echo MRI. J Magn Reson Imaging. 2007;26:313-322.  [PubMed]  [DOI]  [Cited in This Article: ]
52.  Cho SG, Lee DH, Lee KY, Ji H, Lee KH, Ros PR, Suh CH. Differentiation of chronic focal pancreatitis from pancreatic carcinoma by in vivo proton magnetic resonance spectroscopy. J Comput Assist Tomogr. 2005;29:163-169.  [PubMed]  [DOI]  [Cited in This Article: ]
53.  Bares R, Klever P, Hauptmann S, Hellwig D, Fass J, Cremerius U, Schumpelick V, Mittermayer C, Büll U. F-18 fluorodeoxyglucose PET in vivo evaluation of pancreatic glucose metabolism for detection of pancreatic cancer. Radiology. 1994;192:79-86.  [PubMed]  [DOI]  [Cited in This Article: ]
54.  Singer E, Gschwantler M, Plattner D, Kriwanek S, Armbruster C, Schueller J, Feichtinger H, Roka R, Moeschl P, Weiss W. Differential diagnosis of benign and malign pancreatic masses with 18F-fluordeoxyglucose-positron emission tomography recorded with a dual-head coincidence gamma camera. Eur J Gastroenterol Hepatol. 2007;19:471-478.  [PubMed]  [DOI]  [Cited in This Article: ]
55.  Delbeke D, Rose DM, Chapman WC, Pinson CW, Wright JK, Beauchamp RD, Shyr Y, Leach SD. Optimal interpretation of FDG PET in the diagnosis, staging and management of pancreatic carcinoma. J Nucl Med. 1999;40:1784-1791.  [PubMed]  [DOI]  [Cited in This Article: ]
56.  Thomas JK, Kim MS, Balakrishnan L, Nanjappa V, Raju R, Marimuthu A, Radhakrishnan A, Muthusamy B, Khan AA, Sakamuri S. Pancreatic Cancer Database: an integrative resource for pancreatic cancer. Cancer Biol Ther. 2014;15:963-967.  [PubMed]  [DOI]  [Cited in This Article: ]
57.  Bramhall SR. The use of molecular technology in the differentiation of pancreatic cancer and chronic pancreatitis. Int J Pancreatol. 1998;23:83-100.  [PubMed]  [DOI]  [Cited in This Article: ]
58.  Fang F, He X, Deng H, Chen Q, Lu J, Spraul M, Yu Y. Discrimination of metabolic profiles of pancreatic cancer from chronic pancreatitis by high-resolution magic angle spinning 1H nuclear magnetic resonance and principal components analysis. Cancer Sci. 2007;98:1678-1682.  [PubMed]  [DOI]  [Cited in This Article: ]
59.  Pan S, Chen R, Crispin DA, May D, Stevens T, McIntosh MW, Bronner MP, Ziogas A, Anton-Culver H, Brentnall TA. Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling. J Proteome Res. 2011;10:2359-2376.  [PubMed]  [DOI]  [Cited in This Article: ]
60.  Paulo JA, Kadiyala V, Brizard S, Banks PA, Steen H, Conwell DL. A proteomic comparison of formalin-fixed paraffin-embedded pancreatic tissue from autoimmune pancreatitis, chronic pancreatitis, and pancreatic cancer. JOP. 2013;14:405-414.  [PubMed]  [DOI]  [Cited in This Article: ]
61.  Zhang L, Jin H, Guo X, Yang Z, Zhao L, Tang S, Mo P, Wu K, Nie Y, Pan Y. Distinguishing pancreatic cancer from chronic pancreatitis and healthy individuals by (1)H nuclear magnetic resonance-based metabonomic profiles. Clin Biochem. 2012;45:1064-1069.  [PubMed]  [DOI]  [Cited in This Article: ]
62.  Kobayashi T, Nishiumi S, Ikeda A, Yoshie T, Sakai A, Matsubara A, Izumi Y, Tsumura H, Tsuda M, Nishisaki H. A novel serum metabolomics-based diagnostic approach to pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2013;22:571-579.  [PubMed]  [DOI]  [Cited in This Article: ]
63.  Talar-Wojnarowska R, Gasiorowska A, Olakowski M, Lekstan A, Lampe P, Malecka-Panas E. Clinical value of serum neopterin, tissue polypeptide-specific antigen and CA19-9 levels in differential diagnosis between pancreatic cancer and chronic pancreatitis. Pancreatology. 2010;10:689-694.  [PubMed]  [DOI]  [Cited in This Article: ]
64.  Bauer AS, Keller A, Costello E, Greenhalf W, Bier M, Borries A, Beier M, Neoptolemos J, Büchler M, Werner J. Diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis by measurement of microRNA abundance in blood and tissue. PLoS One. 2012;7:e34151.  [PubMed]  [DOI]  [Cited in This Article: ]