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
BACKGROUND: Conservative treatment of chronic pancreatitis has only a limited effect in most patients. Surgery offers very good long-term results, even in the early stages of the disease. Unfortunately, only a minority of patients undergo surgical treatment. The aim of this work was to summarise the current treatment options for patients with an inflammatory mass of the pancreatic head. Data from patients in our study demonstrates that the surgery is a safe method, and here we compare the perioperative and early postoperative outcomes of patients who underwent a pancreatoduodenectomy and duodenum-preserving pancreatic head resection for chronic pancreatitis. METHODS: All patients who underwent a pancreaticoduodenectomy or a duodenum-preserving pancreatic head resection in our department between 2014 and 2022 were included in this study. Perioperative and early postoperative results were statistically analysed and compared. RESULTS: Thirty-eight pancreaticoduodenectomies and 23 duodenum-preserving pancreatic head resections were performed. The overall mortality was 3%, whereas the in-hospital mortality after pancreaticoduodenectomy was 5%. The mortality after duodenum-preserving pancreatic head resection was 0%. No statistically significant differences in the hospital stay, blood loss, and serious morbidity were found in either surgery. Operative time was significantly shorter in the duodenum-preserving pancreatic head resection group. CONCLUSIONS: Both pancreatoduodenectomy and duodenum-preserving pancreatic head resection are safe treatment options. Duodenum-preserving pancreatic head resection showed a statistically significant superiority in the operative time compared to pancreaticoduodenectomy. Although other monitored parameters did not show a statistically significant difference, the high risk of complications after pancreaticoduodenectomy with a mortality of 5%; maintenance of the duodenum and upper loop of jejunum, and lower risk of metabolic dysfunctions after duodenum-preserving pancreatic head resection may favour duodenum-preserving pancreatic head resection in recommended diagnoses. Attending physicians should be more encouraged to use a multidisciplinary approach to assess the suitability of surgical treatment in patients with chronic pancreatitis.
- Klíčová slova
- Beger, Chronic pancreatitis, Duodenum-preserving pancreatic head resection, Inflammatory pancreatic head mass, Pancreatic surgery, Pancreaticoduodenectomy,
- MeSH
- chronická pankreatitida * chirurgie MeSH
- délka operace * MeSH
- délka pobytu statistika a číselné údaje MeSH
- dospělí MeSH
- duodenum chirurgie patologie MeSH
- léčba šetřící orgány metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mortalita v nemocnicích MeSH
- pankreas * chirurgie patologie MeSH
- pankreatektomie metody škodlivé účinky MeSH
- pankreatoduodenektomie * metody škodlivé účinky MeSH
- pooperační komplikace etiologie epidemiologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare malignancy regarded as a subvariant of pancreatic ductal carcinoma (PDAC) characterized by variable prognosis. UCOGC shows a strikingly similar spectrum of oncogenic DNA mutations to PDAC. In the current work, we analyzed the landscape of somatic mutations in a set of 13 UCOGC cases via next-generation sequencing (NGS). We detected a spectrum of pathogenic or likely pathogenic mutations similar to those observed in PDAC following previously published results (10 KRAS, 9 TP53, 4 CDKN2A, and 1 SMAD4, CIC, GNAS, APC, ATM, NF1, FBXW7, ATR, and FGFR3). Our results support the theory that UCOGC is a variant of PDAC, despite its unique morphology; however, a UCOGC-specific genomic signature as well as predictive markers remain mainly unknown. Programmed death ligand 1 (PD-L1) status remains an important predictive marker based on previous studies.
- Klíčová slova
- DNA, next-generation sequencing, pancreas, undifferentiated carcinoma with osteoclast-like giant cells,
- MeSH
- duktální karcinom slinivky břišní * patologie MeSH
- lidé MeSH
- molekulární biologie MeSH
- mutace MeSH
- nádory slinivky břišní * genetika patologie MeSH
- obrovské buňky patologie MeSH
- osteoklasty patologie MeSH
- pankreas patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection is associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to the low prevalence and potential harms of false positives. Non-contrast computed tomography (CT), routinely performed for clinical indications, offers the potential for large-scale screening, however, identification of PDAC using non-contrast CT has long been considered impossible. Here, we develop a deep learning approach, pancreatic cancer detection with artificial intelligence (PANDA), that can detect and classify pancreatic lesions with high accuracy via non-contrast CT. PANDA is trained on a dataset of 3,208 patients from a single center. PANDA achieves an area under the receiver operating characteristic curve (AUC) of 0.986-0.996 for lesion detection in a multicenter validation involving 6,239 patients across 10 centers, outperforms the mean radiologist performance by 34.1% in sensitivity and 6.3% in specificity for PDAC identification, and achieves a sensitivity of 92.9% and specificity of 99.9% for lesion detection in a real-world multi-scenario validation consisting of 20,530 consecutive patients. Notably, PANDA utilized with non-contrast CT shows non-inferiority to radiology reports (using contrast-enhanced CT) in the differentiation of common pancreatic lesion subtypes. PANDA could potentially serve as a new tool for large-scale pancreatic cancer screening.
- MeSH
- deep learning * MeSH
- duktální karcinom slinivky břišní * diagnostické zobrazování patologie MeSH
- lidé MeSH
- nádory slinivky břišní * diagnostické zobrazování patologie MeSH
- pankreas diagnostické zobrazování patologie MeSH
- počítačová rentgenová tomografie MeSH
- retrospektivní studie MeSH
- umělá inteligence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
The advancement in molecular techniques has been attributed to the quality and significance of cancer research. Pancreatic cancer (PC) is one of the rare cancers with aggressive behavior and a high mortality rate. The asymptomatic nature of the disease until its advanced stage has resulted in late diagnosis as well as poor prognosis. The heterogeneous character of PC has complicated cancer development and progression studies. The analysis of bulk tissues of the disease was insufficient to understand the disease, hence, the introduction of the single-cell separating technique aided researchers to decipher more about the specific cell population of tumors. This review gives an overview of the Laser Capture Microdissection (LCM) technique, one of the single-cell separation methods used in PC research.
- Klíčová slova
- Laser Capture Microdissection (LCM), hypoxia, intraductal papillary mucinous neoplasm (IPMN), metastasis, pancreatic cancer, single-cell separation,
- MeSH
- duktální karcinom slinivky břišní * patologie MeSH
- laserová záchytná mikrodisekce MeSH
- lidé MeSH
- nádory slinivky břišní * patologie MeSH
- pankreas patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Pluripotent pancreatic stellate cells (PSCs) receive growing interest in past decades. Two types of PSCs are recognized -vitamin A accumulating quiescent PSCs and activated PSCs- the main producents of extracellular matrix in pancreatic tissue. PSCs plays important role in pathogenesis of pancreatic fibrosis in pancreatic cancer and chronic pancreatitis. PSCs are intensively studied as potential therapeutical target because of their important role in developing desmoplastic stroma in pancreatic cancer. There also exists evidence that PSC are involved in other pathologies like type-2 diabetes mellitus. This article brings brief characteristics of PSCs and recent advances in research of these cells.
AIMS/HYPOTHESIS: Beta-cell failure plays a fundamental role in type 2 diabetes mellitus (T2DM) development. It has been shown that the beta-cells are among the most sensitive to hypoxia. We aimed to analyze whether decrease in pancreatic perfusion relates to 1/decline in beta-cell function and 2/visceral fat accumulation in patients with T2DM. METHODS: Fifteen women with T2DM on metformin therapy alone and fifteen women of comparable age and BMI without prediabetes/diabetes were cross-sectionally examined: clinical and anthropometric examination, fast sampled intravenous glucose tolerance test (FSIVGTT), dynamic contrast-enhanced magnetic resonance imaging to assess pancreatic perfusion (area under the curve of postcontrast saturation, AUCTSIC), and visceral adiposity (VAT, calculated from transverse sections at the level L2-L5 vertebrae). RESULTS: Pancreatic blood perfusion (AUCTSIC) did not differ between groups (p = 0.273), but it negatively correlated with BMI (r = -0.434, p = 0.017), WHR (r = -0.411, p = 0.024), and VAT (r = -0.436, p = 0.016) in both groups. Moreover, AUCTSIC in the head of the pancreas negatively correlated with the level of fasting glycemia (r = -0.401, p = 0.028) and HOMA-IR (r = -0.376, p = 0.041). DISCUSSION/CONCLUSION: We showed that decreased pancreatic perfusion did not relate to beta-cell dysfunction in early stages of T2DM development, but it was related to VAT, insulin resistance, and higher fasting glycemia. Furthermore, lower pancreatic perfusion was related to VAT, insulin resistance, and higher fasting glycemia.
- Klíčová slova
- Blood perfusion, Obesity, Pancreas, Type 2 diabetes mellitus,
- MeSH
- diabetes mellitus 2. typu * MeSH
- index tělesné hmotnosti MeSH
- inzulin MeSH
- inzulinová rezistence * MeSH
- krevní glukóza MeSH
- lidé MeSH
- nitrobřišní tuk diagnostické zobrazování patologie MeSH
- obezita komplikace MeSH
- pankreas patologie MeSH
- perfuze MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inzulin MeSH
- krevní glukóza MeSH
The diagnosis of the rare disease autoimmune pancreatitis (AIP) is demonstrated in the case of a patient who underwent a series of examinations that were unable to unequivocally prove the diagnosis of benignity. The disease as a form of chronic pancreatitis, and the most important and first objective of the examination is to exclude malignant disease of the pancreas and biliary tract. While imaging led to suspicion of malignancy, repeated histological examinations did not confirm it. After we were able to exclude suspected carcinoma according to the available diagnostic criteria, AIP was confirmed, and a diagnosis of type I was made, which belongs to the group of diseases characterized by high levels of immunoglobulin G4 (IgG4) in the blood serum. Successful treatment with glucocorticoids was initiated with induction of disease remission. However, AIP shows frequent relapses and this should also be borne in mind during treatment. Our case report also describes such a case.
- Klíčová slova
- IgG4, Pancreatic cancer, autoimmune pancreatitis, choledochal stenosis, obstructive icterus, pancreatic cancer,
- MeSH
- autoimunitní nemoci * diagnóza MeSH
- autoimunitní pankreatitida * diagnóza MeSH
- chronická pankreatitida * diagnóza MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- nádory slinivky břišní * diagnóza MeSH
- pankreas patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: Making the distinction between primary mucinous and metastatic ovarian tumors is often difficult, especially in tumors with a primary source from the gastrointestinal tract, pancreas and biliary tree. The aim of the following paper is to provide an overview of the problematics, with a focus on the possibilities of the differential diagnosis at the macroscopic, microscopic and immunohistochemical level. MAIN BODY: The three main aspects of mucinous ovarian tumors are described in detail, including the comparison of the available diagnostic algorithms based on the evaluation of mostly macroscopic features, characterization of the spectrum of microscopic features, and a detailed analysis of the immunophenotype comparing 20 antibodies with the assessment of their statistical significance for differential diagnosis purposes. Specific features, including Krukenberg tumor and pseudomyxoma peritonei, are also discussed. CONCLUSION: Despite the growing knowledge of the macroscopic and microscopic features of ovarian mucinous tumors and the availability of a wide range of immunohistochemical antibodies useful in this setting, there still remains a group of tumors which cannot be precisely classified without close clinical-pathological cooperation.
- Klíčová slova
- Mucinous borderline tumor, Mucinous carcinoma, Ovarian metastases, Ovarian tumors,
- MeSH
- gastrointestinální trakt patologie MeSH
- lidé MeSH
- mucinózní adenokarcinom patologie MeSH
- nádory vaječníků patologie MeSH
- pankreas patologie MeSH
- peritoneální nádory patologie MeSH
- pseudomyxom peritonea diagnóza patologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15 × 10-4 ). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.
- Klíčová slova
- early onset, genome-wide association study, pancreatic cancer, single nucleotide polymorphisms, very early onset pancreatic cancer,
- MeSH
- celogenomová asociační studie metody MeSH
- duktální karcinom slinivky břišní genetika patologie MeSH
- genetická predispozice k nemoci genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory slinivky břišní genetika patologie MeSH
- pankreas patologie MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
