Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed in its late stages when treatment options are limited. Unlike other common cancers, there are no population-wide screening programmes for PDAC. Thus, early disease detection, although urgently needed, remains elusive. Individuals in certain high-risk groups are, however, offered screening or surveillance. Here we explore advances in understanding high-risk groups for PDAC and efforts to implement biomarker-driven detection of PDAC in these groups. We review current approaches to early detection biomarker development and the use of artificial intelligence as applied to electronic health records (EHRs) and social media. Finally, we address the cost-effectiveness of applying biomarker strategies for early detection of PDAC.
- Klíčová slova
- Artificial intelligence, Biomarkers, Early detection, Omics, Pancreatic cancer,
- MeSH
- časná detekce nádoru * metody MeSH
- duktální karcinom slinivky břišní diagnóza genetika MeSH
- genomika metody MeSH
- lidé MeSH
- nádorové biomarkery * MeSH
- nádory slinivky břišní * diagnóza genetika MeSH
- umělá inteligence * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- nádorové biomarkery * MeSH
BACKGROUND: Only a limited number of biomarkers guide personalized management of pancreatic neuroendocrine tumors (PanNETs). Transcriptome profiling of microRNA (miRs) and mRNA has shown value in segregating PanNETs and identifying patients more likely to respond to treatment. Because miRs are key regulators of mRNA expression, we sought to integrate expression data from both RNA species into miR-mRNA interaction networks to advance our understanding of PanNET biology. METHODS: We used deep miR/mRNA sequencing on six low-grade/high-risk, well-differentiated PanNETs compared with seven non-diseased tissues to identify differentially expressed miRs/mRNAs. Then we crossed a list of differentially expressed mRNAs with a list of in silico predicted mRNA targets of the most and least abundant miRs to generate high probability miR-mRNA interaction networks. RESULTS: Gene ontology and pathway analyses revealed several miR-mRNA pairs implicated in cellular processes and pathways suggesting perturbed neuroendocrine function (miR-7 and Reg family genes), cell adhesion (miR-216 family and NLGN1, NCAM1, and CNTN1; miR-670 and the claudins, CLDN1 and CLDN2), and metabolic processes (miR-670 and BCAT1/MPST; miR-129 and CTH). CONCLUSION: These novel miR-mRNA interaction networks identified dysregulated pathways not observed when assessing mRNA alone and provide a foundation for further investigation of their utility as diagnostic and predictive biomarkers.
- Klíčová slova
- Biomarkers, MicroRNA, Pancreatic neuroendocrine tumors, mRNA, miR-mRNA interaction networks,
- MeSH
- genové regulační sítě MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA * genetika MeSH
- mikro RNA * genetika MeSH
- nádorové biomarkery genetika MeSH
- nádory slinivky břišní * genetika patologie diagnóza MeSH
- neuroendokrinní nádory * genetika patologie diagnóza MeSH
- pankreas * metabolismus patologie MeSH
- regulace genové exprese u nádorů MeSH
- stanovení celkové genové exprese MeSH
- transkriptom MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- messenger RNA * MeSH
- mikro RNA * MeSH
- nádorové biomarkery MeSH
Pancreatic ductal adenocarcinoma is a cancer disease with a very poor prognosis, which poses the third-leading cause of cancer-related deaths and whose incidence and mortality have been predicted to increase significantly in the upcoming years. Almost 80% of patients are diagnosed with advanced unresectable disease and therefore rely on palliative anticancer treatment with limited efficacy. However, even in case of 10-20 % of patients who have successfully undergone radical surgical resection of the localized disease and subsequent adjuvant chemotherapy, the vast majority will relapse within 2-3 years of surgery. The reasons can be found in late diagnosis due to the prolonged clinically asymptomatic course of the disease, complicated anatomical localization, significant tumor heterogeneity, which makes it difficult to test new drugs and, last but not least, in the presence of dense tumor stroma, that complicates the access of cytostatics and targeted drugs into the tumor tissue. Here we present a summary of current treatment options of localized and advanced pancreatic cancer, including molecular diagnostics and targeted treatment of small patients subgroups.
- Klíčová slova
- pancreatic cancer, BRCA 1/2, FOLFIRINOX, molecular targeted therapy, pancreatic cancer, targeted therapy,
- MeSH
- duktální karcinom slinivky břišní * diagnóza terapie patologie MeSH
- lidé MeSH
- nádory slinivky břišní * diagnóza terapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Preoperative cytopathology of pancreatobiliary neoplastic lesions is a sensitive and specific method and is irreplaceable in the diagnosis and clinical management of these diseases. Pathologists should make every attempt to provide diagnosis as precise as possible and minimize the rate of "atypical" results, which create management dilemmas. The diagnostic accuracy of cytopathology can be significantly improved by judicious use of ancillary studies, including immunohistochemistry and molecular genetics. Next generation sequencing (NGS) is the latest addition to pancreatobiliary cytopathology diagnostic arsenal. NGS is not only a very robust diagnostic tool, but also carries significant prognostic and therapeutic information.
- Klíčová slova
- pancreas, Genetics, biliary tract, cytology, genetics, immunohistochemistry, pancreas,
- MeSH
- imunohistochemie * metody MeSH
- lidé MeSH
- nádory slinivky břišní * diagnóza genetika patologie MeSH
- nádory žlučového ústrojí diagnóza genetika patologie MeSH
- vysoce účinné nukleotidové sekvenování * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The current WHO classification of digestive system tumours (2019) has presented the concept of diagnostics of intraductal and cystic neoplasms of the pancreas mostly based on integrated molecular data and evaluations of their malignant potential. Intraductal pancreatic neoplasms with ductal phenotype include microscopic precursor lesions of pancreatic ductal adenocarcinoma - the pancreatic intraepithelial neoplasia and macroscopic precursor lesions of pancreatic cancer, where intraductal papillary mucinous neoplasm represents the most common neoplasm of the pancreas with cystic appearance. Both intraductal oncocytic papillary neoplasm and intraductal tubulopapillary neoplasm are now classified as separate entities associated with less aggressive subtypes of pancreatic carcinoma and better prognosis. Clinical significance of microscopic pancreatic intraepithelial neoplasias is limited, in contrast to other intraductal neoplasms, which are presented as cystic and/or solid tumours by imaging methods with important consequences for further treatment and indication of surgical therapy (resection versus "watch and wait" strategies). Neoplasms of nonductal origin, such as acinar cell carcinomas and neuroendocrine neoplasms, can uncommonly display an intraductal growth and their correct classification has a great clinical importance. Moreover, differential diagnostics of cystic pancreatic lesions include not only cystic and pseudocystically transformed neoplasms, but also a large spectrum of reactive, inflammatory and dysontogenetic cystic lesions.
- Klíčová slova
- pancreatic tumors, cystic, intraductal,
- MeSH
- diferenciální diagnóza MeSH
- duktální karcinom slinivky břišní patologie diagnóza MeSH
- intraduktální nádory pankreatu * patologie diagnóza MeSH
- lidé MeSH
- nádory slinivky břišní * patologie diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Pancreatic carcinoma is a relatively common malignant tumor with increasing incidence and mortality. The tumor is usually diagnosed at an advanced stage and generally has a poor prognosis, with only 5% of patients surviving 5 years from the time of diagnosis. The stage of the disease at the time of diagnosis is a crucial factor for the prognosis; 25% of patients with localized tumors survive 3 years from diagnosis, compared to only 1% of those with generalized tumors. Radical surgical removal of the tumor (partial or total pancreatectomy) is a key factor in improving survival. Therefore, the topic is highly relevant to surgeons. Statistics on pancreatic carcinoma mainly focus on ductal adenocarcinoma, which is the most common and least favorable malignant tumor of the pancreas. This review focuses on ductal adenocarcinoma, its variants, and precancerous lesions. The article summarizes information from the latest WHO classification of 2019, which was released 11 years after the previous edition. Compared to the previous version, this new WHO classification introduced rather minor changes in the field of ductal adenocarcinoma. The delineation of rare variants of ductal adenocarcinoma is justified based on genetic and morphological similarities and clinical relevance, as individual subtypes significantly differ in prognosis. The article also includes a description of macroscopic and microscopic precursors of ductal adenocarcinoma and their definitions. Genetic and immunohistochemical differential diagnostic aspects are briefly discussed, as these are more relevant to pathologists than to surgeons.
- Klíčová slova
- Adenocarcinoma, Dysplasia, Pancreas, ductal, pancreas, pancreatic intraepithelial neoplasia,
- MeSH
- duktální karcinom slinivky břišní * klasifikace patologie diagnóza chirurgie MeSH
- lidé MeSH
- nádory slinivky břišní * klasifikace patologie diagnóza chirurgie MeSH
- prekancerózy patologie klasifikace MeSH
- prognóza MeSH
- Světová zdravotnická organizace * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Pancreatic cancer remains one of the most challenging malignancies to treat, with consistently low survival rates despite advances in medical research. The identification and validation of effective prognostic biomarkers are crucial for improving diagnostic accuracy and treatment outcomes. OBJECTIVE: The aim of the work is to analyze the latest data of the pancreatic cancer incidence and mortality, comparing them with global epidemiological data. The narrative review also aims to summarize current knowledge about various prognostic biomarkers in the pancreatic cancer treatment, including indicators of performance status, nutritional and inflammatory markers. METHODS: The most recently available national epidemiological data on pancreatic cancer are analyzed. The literature review is focused on markers that evaluate the general condition of patients, such as performance status, body mass index, prognostic nutritional index and markers of the inflammatory response, such as Glasgow prognostic score, C-reactive protein, neutrophil to lymphocyte ratio, systemic inflammatory response index and systemic immune inflammation index. These biomarkers are analyzed for their role in predicting prognosis and response to systemic therapy for pancreatic cancer. RESULTS: Both the Slovak Republic and the Czech Republic are globally ranked in the leading places in terms of pancreatic cancer incidence and mortality, both in estimates and real data. Indicators of nutritional and performance status play a critical role in patient assessment and influence treatment decisions, with potential impact on treatment outcomes. Inflammatory markers have shown significant prognostic value, correlating with the patient's immune response to the tumor and inflammatory processes that may promote disease progression. However, despite their promising predictive capabilities, these biomarkers are not routinely used in clinical practice due to the need for further validation. CONCLUSION: Integration of new biomarkers into clinical practice could lead to more personalized therapeutic decisions and improved treatment outcomes. Further research is needed for a more comprehensive assessment of the validity of these biomarkers and their use in common clinical conditions.
- Klíčová slova
- Pancreatic cancer, incidence, mortality, neutrophil to lymphocyte ratio, prognostic nutritional index, systemic immune inflammation index, systemic inflammatory response index,
- MeSH
- incidence MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory slinivky břišní * epidemiologie diagnóza MeSH
- nutriční stav MeSH
- prognóza MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- nádorové biomarkery MeSH
Surgery is the only potentially curative treatment of pancreatic cancer. Imaging methods, especially computed tomography (CT), play an essential role in the detection and staging of pancreatic cancer. The primary CT finding determines the treatment strategy, namely the resectability of the cancer with a potentially curative outcome. Imaging (CT) assessments are important also throughout oncological treatment of the patients and after the surgery, as well. Our paper summarizes the current state of the art of computed tomography and magnetic resonance imaging in pancreatic cancer, including a structured CT report proposal in pancreatic cancer.
- Klíčová slova
- Pancreatic cancer, computed tomography, magnetic resonance, magnetic resonance imaging, pancreatic cancer,
- MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- nádory slinivky břišní * diagnostické zobrazování chirurgie diagnóza terapie MeSH
- počítačová rentgenová tomografie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The recent introduction of the WHO cytology classification of pancreatobiliary tumours aimed to improve the diagnosis and management of these tumours. The present paper briefly describes the methods of diagnosis. Emphasis is then put on a detailed comparison of the previous Papanicolaou classification and the new WHO classification and description of the changes brought about by the introduction of the WHO classification. In the last part of the paper, we present interesting cases from our practice illustrating possible diagnostic pitfalls of cytological evaluation.
- Klíčová slova
- Pancreatobiliary pathology, Papanicolaou system, WHO Classification system, cytology,
- MeSH
- cytodiagnostika metody MeSH
- lidé MeSH
- nádory slinivky břišní * patologie diagnóza MeSH
- nádory žlučového ústrojí * patologie diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
BACKGROUND: ATP-binding cassette (ABC) transporters translocate various substances across cellular membranes. Their deregulation may cause cancer drug resistance or perturbations in the supply of building blocks for cancer cells and modify patients' prognosis. This study investigated protein expression and cellular localization of the previously suggested putative prognostic biomarkers - ABCB2/TAP1, ABCC7/CFTR, ABCC8/SUR1, and ABCD4 in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Protein expression and localization were assessed by immunohistochemistry in formalin-fixed paraffin-embedded primary tumor tissue blocks of 61 PDAC patients and associated with clinical data and the survival of patients. RESULTS: No CFTR protein expression was observed in PDAC, while TAP1 and ABCC8 were expressed predominantly in the cytoplasm of tumor cells. Most samples (81 %) had detectable both membranous and cytoplasmic ABCD4 staining and 42 % had ABCD4 expressed in the apical orientation. Negative membranous ABCD4 staining was significantly more frequent in advanced stage III or IV tumors (p = 0.022). Small or medium counts of individual ABCC8-positive cells in the stroma surrounding tumor tubules were also more often found in stage III or IV (p = 0.044). Patients with moderate or strong ABCC8 cytoplasmic staining intensity in tumor cells had a 3.5-fold higher risk of disease progression than those with weak staining (p = 0.002). CONCLUSIONS: The study shows for the first time that the cytoplasmic ABCC8 protein expression has prognostic value in PDAC.
- Klíčová slova
- ATP-Binding cassette transporters, Adenocarcinoma, Immunohistochemistry, Pancreas, Prognosis,
- MeSH
- ABC transportéry genetika MeSH
- adenokarcinom * patologie MeSH
- duktální karcinom slinivky břišní * patologie MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory slinivky břišní * diagnóza patologie MeSH
- prognóza MeSH
- progrese nemoci MeSH
- receptory sulfonylurey * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ABC transportéry MeSH
- ABCC8 protein, human MeSH Prohlížeč
- ABCD4 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- receptory sulfonylurey * MeSH
