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Singh, M.; Anvekar, P.; Baraskar, B.; Pallipamu, N.; Gadam, S.; Cherukuri, A.S.S.; Damani, D.N.; Kulkarni, K.; Arunachalam, S.P. Diagnostic Techniques of Pancreatic Cancer. Encyclopedia. Available online: https://encyclopedia.pub/entry/48093 (accessed on 07 August 2024).
Singh M, Anvekar P, Baraskar B, Pallipamu N, Gadam S, Cherukuri ASS, et al. Diagnostic Techniques of Pancreatic Cancer. Encyclopedia. Available at: https://encyclopedia.pub/entry/48093. Accessed August 07, 2024.
Singh, Mansunderbir, Priyanka Anvekar, Bhavana Baraskar, Namratha Pallipamu, Srikanth Gadam, Akhila Sai Sree Cherukuri, Devanshi N. Damani, Kanchan Kulkarni, Shivaram P. Arunachalam. "Diagnostic Techniques of Pancreatic Cancer" Encyclopedia, https://encyclopedia.pub/entry/48093 (accessed August 07, 2024).
Singh, M., Anvekar, P., Baraskar, B., Pallipamu, N., Gadam, S., Cherukuri, A.S.S., Damani, D.N., Kulkarni, K., & Arunachalam, S.P. (2023, August 15). Diagnostic Techniques of Pancreatic Cancer. In Encyclopedia. https://encyclopedia.pub/entry/48093
Singh, Mansunderbir, et al. "Diagnostic Techniques of Pancreatic Cancer." Encyclopedia. Web. 15 August, 2023.
Diagnostic Techniques of Pancreatic Cancer
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This entry is adapted from the peer-reviewed paper 10.3390/jimaging9080149

Pancreatic carcinoma (Ca Pancreas) is the third leading cause of cancer-related deaths in the world. The malignancies of the pancreas can be diagnosed with the help of various imaging modalities. An endoscopic ultrasound with a tissue biopsy is so far considered to be the gold standard in terms of the detection of Ca Pancreas, especially for lesions <2 mm. However, other methods, like computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), are also conventionally used. Moreover, newer techniques, like proteomics, radiomics, metabolomics, and artificial intelligence (AI), are slowly being introduced for diagnosing pancreatic cancer.

pancreatic cancer MRI CT

1. Introduction

Pancreatic cancer (Ca Pancreas) is one of the leading causes of cancer-related deaths. The GLOBOCAN, in 2018, estimated pancreatic cancer to be the 11th most common cancer in the world. It is estimated that 355,317 additional instances will occur by 2040 [1]. Pancreatic cancers arise mainly from the ductal epithelial cells of the exocrine pancreas. The activation of oncogenes or deactivation of tumor-suppressing genes leads to the evolution and progression of pancreatic cancer [2]. Moreover, the molecular pathogenesis of pancreatic cancer is influenced by the disruption of several cell-regulating pathways [2][3]. There are various modifiable and non-modifiable risk factors that potentially lead to its development. However, the mutations in the biochemical makeup account for one of the strongest non-modifiable risk factors [4]. To date, several methods have been employed to diagnose Ca Pancreas. Even though using an endoscopic ultrasound with a tissue biopsy is considered the gold standard in terms of diagnosing pancreatic carcinoma, imaging modalities, like CT scanning, magnetic resonance imaging (MRI), ultrasound, and positron emission tomography (PET-CT), are also used in clinical practice.
Although the imaging modalities in use today can aid in the diagnosis and detection of pancreatic malignancies, they suffer from the limitation of identifying the disease at an advanced stage in its course. Owing to the high mortality caused by pancreatic neoplasms, there is a need to understand the impact of the tumor on the various organ systems with the hope of early diagnosis, enabling prompt treatment and improved outcomes in these patients. The heart is a four-chambered electromechanical organ responsible for blood flow and oxygen supply to the entire body. An interruption in cardiac function can cause irreversible impairments, such as brain injury, heart failure, stroke, or even sudden cardiac death [5]. Malignancies have had a significant impact on the cardiovascular system; for example, lung cancer has been shown to disrupt the conduction system [6]. Similarly, several case studies in the past have demonstrated fluctuations in the cardiac functions of patients with carcinoma of the pancreas [7][8][9]. A significant association between the heart and Ca Pancreas could be a remarkable milestone for researchers and clinicians. 

2. Pathophysiology of Pancreatic Cancer

In the pancreas, a wide range of exocrine neoplasms develop, ranging from benign to malignant. In terms of pancreatic carcinoma, many genes are somatically altered or epigenetically silenced, corresponding with their sequential progression from precursor lesions. Kirsten rat sarcoma virus (KRAS) is the most frequently (>95%) altered oncogene in Ca Pancreas. It functions as a membrane-bound GTP-operated protein that normally participates in the downstream growth signaling pathway. The most often inactivated tumor-suppressor gene in this malignancy is cyclin-D kinase 2A (CDKN2A). Another commonly mutated tumor-suppressor gene in Ca Pancreas is suppressor of mothers against decapentaplegic (SMAD4), which is a member of the TGF family of surface-bound signal transduction receptors. Tumor protein 53 (TP53), a well-known cell-cycle regulator, has also been reported to be altered in the late stages of Ca Pancreas pathogenesis. All of them work together in a well-orchestrated pathway called the RAS-RAF-MEK-ERK pathway, more commonly known as the MAPK pathway. These are downstream kinases that induce various intracellular metabolic changes in response to a variety of extracellular stimuli, including growth factors, cytokines, stress, etc. These changes eventually correspond to cellular growth, proliferation, differentiation, or apoptosis [10][11]. A growing number of less common, but nonetheless important, genetic loci in Ca Pancreas have been reported to be altered, including oncogenes (AKT2: RAC-beta serine/threonine-protein kinase 2, MYB: Myeloblastosis, and MAPK: Mitogen-activated protein kinase), tumor-suppressor genes, and DNA-repair genes (GATA6, RB: Retinoblastoma, STK: Serine/Threonine kinase 11), to name a few.
Environmental factors also have a role in the pathogenesis of Ca Pancreas, with cigarette smoking being the most significant risk factor. Other factors that have a causal relationship include chronic pancreatitis, diabetes mellitus, a high-fat diet, alcohol usage, etc. Pancreatic cancer aggregation has also been reported and a rising number of inherited genetic abnormalities are known to enhance the risk. BRCA2/1, STK-11 mutations in Peutz-Jeghers Syndrome, PRSS1, SPINK1 mutations in Hereditary pancreatitis, and MLH1/MSH2 mutations in Hereditary non-polyposis colorectal cancer all increase the likelihood of developing Ca Pancreas when compared to the general population [12][13].

3. Diagnostic Techniques of Pancreatic Cancer

Exocrine pancreatic cancer is one of the deadliest cancers. It is responsible for 3% of all malignancies and 8% of cancer-related deaths in the United States [14][15]. Pancreatic cancer symptoms are usually non-specific, such as asthenia, stomach discomfort, nausea/vomiting, and anorexia. The appearance of these symptoms at the late stage of the disease [16] makes early illness identification critical for rapid diagnosis and treatment.
Computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), and endoscopic ultrasonography (EUS) are the current modalities available for the detection of suspected pancreatic cancer and high-risk screening. The National Comprehensive Cancer Network (NCCN) guidelines for pancreatic cancer recommend germline testing for all patients with pancreatic cancer and molecular analysis for those with metastatic disease [17].

3.1. Computed Tomography (CT) Scan

For the initial evaluation of suspected pancreatic cancer, intravenous contrast-enhanced CT with pancreatic protocol is chosen over magnetic resonance imaging (MRI) as the first-line imaging modality. CT sensitivity varies from 76% to 96%, with larger tumors having higher levels of sensitivity. Classic CT characteristics include hypoattenuating pancreatic mass, pancreatic duct dilatation, and upstream pancreatic atrophy. Other early features of pancreatic cancer include primary pancreatic duct dilatation, sudden changes in pancreatic duct caliber, and pancreatic parenchymal alteration. In total, 5.4% to 18.4% of cases may be iso-attenuating in terms of the CT and may require an MRI or positron emission tomography (PET/CT) scan for confirmation [16].

3.2. Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI) has been observed to have similar or slightly lower levels of sensitivity and accuracy than a CT scan. On non-contrast-enhanced and contrast-enhanced T1 images, pancreatic cancer appears as a hypointense mass; meanwhile, on T2-weighted images, it appears as a modestly hyperintense mass [16].

3.3. Positron Emission Tomography (PET/CT)

FDG (18F-fluoro-2-deoxy-D-glucose) is used as a radiotracer in positron emission tomography (PET/CT). FDG accumulates in cells with a strong glycolytic metabolism. PET/CT is not deemed an alternative to CT in the diagnosis of pancreatic cancer since its relevance is uncertain. PET is not effective for staging pancreatic cancer due to the lack of spatial resolution necessary in the locoregional assessment [16].

3.4. Endoscopic Ultrasound

An endoscopic ultrasound is very accurate and is the gold standard for the diagnosis of pancreatic cancer; it appears hypoechoic with ductal obstruction and local invasion. Small neuroendocrine pancreatic tumors that are not seen on MRI can be detected using an endoscopic ultrasound [16].

3.5. Emerging Techniques for the Diagnosis of Pancreatic Cancer

Newer techniques, like radiomics/molecular imaging and machine learning, are being used to identify malignant precursors, as well as being used for earlier disease diagnoses of pancreatic cancer using computers. A considerable number of genetic anomalies in Ca Pancreas have recently been identified as a result of advances in genomic approaches. These techniques include genetic, epigenetic, non-coding RNA (ncRNA), metabolomics (study of low-molecular-weight substances and their processes), and microbiome markers. Furthermore, liquid biopsies, circulating tumor cells (CTCs), cell-free circulating tumor DNA (ctDNA), and exosomes were discovered in body fluids and are being investigated as potential tools to detect Ca Pancreas at an early stage. All of these markers, however, are in the stages of infancy and their diagnostic efficacy is yet to be validated [18].
Additionally, novel approaches based on artificial intelligence (AI) are being developed to increase the diagnostic accuracy of well-established techniques, like imaging (CT/MRI), pathological tissue sample analysis, and biomarker discovery. Several studies have proved the success of AI in diagnosing pancreatic carcinoma [19][20][21][22][23]. It is important to explore these emerging techniques as many methods could offer varying levels of performance. Extensive research and validation of these novel techniques will be of paramount importance in the early detection of pancreatic malignancies.

References

  1. Rawla, P.; Sunkara, T.; Gaduputi, V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J. Oncol. 2019, 10, 10–27.
  2. Mimeault, M.; Brand, R.E.; Sasson, A.A.; Batra, S.K. Recent Advances on the Molecular Mechanisms Involved in Pancreatic Cancer Progression and Therapies. Pancreas 2005, 31, 301–316.
  3. Jimeno, A.; Hidalgo, M. Molecular biomarkers: Their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer. Mol. Cancer Ther. 2006, 5, 787–796.
  4. McGuigan, A.; Kelly, P.; Turkington, R.C.; Jones, C.; Coleman, H.G.; McCain, R.S. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J. Gastroenterol. 2018, 24, 4846–4861.
  5. Rehman, I.; Rehman, A. Anatomy, Thorax, Heart. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022. Available online: https://www.ncbi.nlm.nih.gov/books/NBK470256/ (accessed on 29 August 2022).
  6. Al-Juburi, S.; Rafizadeh, S.; Zeki, A.A. Heart of the Matter: Syncope as a Rare Presentation of Lung Cancer Invading the Heart. J. Investig. Med. High Impact Case Rep. 2021, 9, 23247096211053709.
  7. Nunnery, S.; Bottinor, W.; Das, S. Cardiac Masses in a Patient With Pancreatic Adenocarcinoma and a History of Breast Carcinoma. JAMA Oncol. 2020, 6, 917–918.
  8. Kiryu, S.; Ito, Z.; Ishikawa, M.; Akasu, T.; Matsumoto, Y.; Hirooka, S.; Saruta, M.; Koido, S. Cancerous pericarditis presenting as cardiac tamponade in a 68-year-old man with pancreatic adenocarcinoma: A case report. J. Med. Case Rep. 2020, 14, 213.
  9. Dang, G.; Haddad, T.M.; Thibodeau, J. Pancreatic Cancer Presenting as Recurrent Endocarditis—American College of Cardiology. American College of Cardiology. 2019. Available online: https://www.acc.org/education-and-meetings/patient-case-quizzes/2019/01/31/09/21/pancreatic-cancer-presenting-as-recurrent-endocarditis (accessed on 9 August 2022).
  10. Sarkar, F.H.; Banerjee, S.; Li, Y. Pancreatic cancer: Pathogenesis, prevention and treatment. Toxicol. Appl. Pharmacol. 2007, 224, 326–336.
  11. Neureiter, D.; Jäger, T.; Ocker, M.; Kiesslich, T. Epigenetics and pancreatic cancer: Pathophysiology and novel treatment aspects. World J. Gastroenterol. 2014, 20, 7830–7848.
  12. Krishnan, T.; Roberts-Thomson, R.; Broadbridge, V.; Price, T. Targeting Mutated KRAS Genes to Treat Solid Tumours. Mol. Diagn. Ther. 2022, 26, 39–49.
  13. Lowery, M.A.; Wong, W.; Jordan, E.J.; Lee, J.W.; Kemel, Y.; Vijai, J.; Mandelker, D.; Zehir, A.; Capanu, M.; Salo-Mullen, E.; et al. Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. J. Natl. Cancer Inst. 2018, 110, 1067–1074.
  14. Zhao, Z.; Liu, W. Pancreatic Cancer: A Review of Risk Factors, Diagnosis, and Treatment. Technol. Cancer Res. Treat. 2020, 19, 1533033820962117.
  15. Cancer Facts & Figures 2022. Atlanta: American Cancer Society. 2022; p. 10. Available online: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html (accessed on 9 August 2022).
  16. Chu, L.C.; Goggins, M.G.; Fishman, E.K. Diagnosis and Detection of Pancreatic Cancer. Cancer J. 2017, 23, 333–342.
  17. Tempero, M.A. NCCN Guidelines Updates: Pancreatic Cancer. J. Natl. Compr. Cancer Netw. 2019, 17, 603–605.
  18. Wu, H.; Ou, S.; Zhang, H.; Huang, R.; Yu, S.; Zhao, M.; Tai, S. Advances in biomarkers and techniques for pancreatic cancer diagnosis. Cancer Cell. Int. 2022, 22, 220.
  19. Le Berre, C.; Sandborn, W.J.; Aridhi, S.; Devignes, M.-D.; Fournier, L.; Smaïl-Tabbone, M.; Danese, S.; Peyrin-Biroulet, L. Application of Artificial Intelligence to Gastroenterology and Hepatology. Gastroenterology 2020, 158, 76–94.e2.
  20. Das, A.; Nguyen, C.C.; 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.
  21. Săftoiu, A.; Vilmann, P.; Gorunescu, F.; Janssen, J.; Hocke, M.; Larsen, M.; Iglesias–Garcia, J.; Arcidiacono, P.; Will, U.; Giovannini, M.; et al. Efficacy of an Artificial Neural Network–Based Approach to Endoscopic Ultrasound Elastography in Diagnosis of Focal Pancreatic Masses. Clin. Gastroenterol. Hepatol. 2012, 10, 84–90.e1.
  22. 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, e6382.
  23. Kurt, M.; Ozkan, M.; Cakiroglu, M.; Kocaman, O.; Yilmaz, B.; Can, G.; Korkmaz, U.; Dandil, E.; Eksi, Z. Age-based computer-aided diagnosis approach for pancreatic cancer on endoscopic ultrasound images. Endosc. Ultrasound 2016, 5, 101–107.
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Subjects: Integrative & Complementary Medicine
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Mansunderbir Singh
,
Priyanka Anvekar
,
Bhavana Baraskar
,
Namratha Pallipamu
,
Srikanth Gadam
,
Akhila Sai Sree Cherukuri
,
Devanshi N. Damani
,
Kanchan Kulkarni
,
Shivaram P. Arunachalam
View Times: 246
Revisions: 3 times (View History)
Update Date: 16 Aug 2023
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