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Journal of Gastroenterology Sep 2023Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, and developing an efficient and reliable approach for its early-stage diagnosis... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, and developing an efficient and reliable approach for its early-stage diagnosis is urgently needed. Precancerous lesions of PDAC, such as pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN), arise through multiple steps of driver gene alterations in KRAS, TP53, CDKN2A, SMAD4, or GNAS. Hallmark mutations play a role in tumor initiation and progression, and their detection in bodily fluids is crucial for diagnosis. Recently, liquid biopsy has gained attention as an approach to complement pathological diagnosis, and in addition to mutation signatures in cell-free DNA, cell-free RNA, and extracellular vesicles have been investigated as potential diagnostic and prognostic markers. Integrating such molecular information to revise the diagnostic criteria for pancreatic cancer can enable a better understanding of the pathogenesis underlying inter-patient heterogeneity, such as sensitivity to chemotherapy and disease outcomes. This review discusses the current diagnostic approaches and clinical applications of genetic analysis in pancreatic cancer and diagnostic attempts by liquid biopsy and molecular analyses using pancreatic juice, duodenal fluid, and blood samples. Emerging knowledge in the rapidly advancing liquid biopsy field is promising for molecular profiling and diagnosing pancreatic diseases with significant diversity.
Topics: Humans; Pathology, Molecular; Early Detection of Cancer; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Mutation; Liquid Biopsy
PubMed: 37470859
DOI: 10.1007/s00535-023-02024-4 -
International Journal of Molecular... Aug 2023Molecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment....
Molecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact with the pancreatic ductal system, from which pancreatic cancer cells originate, and higher overall cell-free DNA (cfDNA) concentrations. In this study, we included patients with pathology-proven PC or intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) from two prospective clinical trials (KRASPanc and PACYFIC) for whom both PJ and plasma were available. We performed next-generation sequencing on PJ, plasma, and tissue samples and described the presence (and concordance) of mutations in these biomaterials. This study included 26 patients (25 PC and 1 IPMN with HGD), of which 7 were women (27%), with a median age of 71 years (IQR 12) and a median BMI of 23 kg/m (IQR 4). Ten patients with PC (40%) were (borderline) resectable at baseline. Tissue was available from six patients (resection = 5, biopsy = 1). A median volume of 2.9 mL plasma (IQR 1.0 mL) and 0.7 mL PJ (IQR 0.1 mL, < 0.001) was used for DNA isolation. PJ had a higher median cfDNA concentration (2.6 ng/μL (IQR 4.2)) than plasma (0.29 ng/μL (IQR 0.40)). A total of 41 unique somatic mutations were detected: 24 mutations in plasma (2 , 15 , 2 , 3 1 , and 1 ), 19 in PJ (3 , 15 , and 1 ), and 8 in tissue (2 , 2 , and 4 ). The mutation detection rate (and the concordance with tissue) did not differ between plasma and PJ. In conclusion, while the concentration of cfDNA was indeed higher in PJ than in plasma, the mutation detection rate was not different. A few cancer-associated genetic variants were detected in both biomaterials. Further research is needed to increase the detection rate and assess the performance and suitability of plasma and PJ for PC (early) detection.
Topics: Humans; Female; Child; Male; Pancreatic Juice; Pancreatic Intraductal Neoplasms; Prospective Studies; Proto-Oncogene Proteins p21(ras); Pancreatic Neoplasms; Biocompatible Materials; Cell-Free Nucleic Acids
PubMed: 37685923
DOI: 10.3390/ijms241713116 -
Diagnostics (Basel, Switzerland) Aug 2023Pathological examination is essential for the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Moreover, a reliable pathological diagnosis is...
Diagnostic Ability and Safety of Repeated Pancreatic Juice Cytology Using an Endoscopic Nasopancreatic Drainage Catheter for Pancreatic Ductal Adenocarcinoma: A Multicenter Prospective Study.
Pathological examination is essential for the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Moreover, a reliable pathological diagnosis is extremely important for improving prognosis, especially in early-stage PDAC. This study prospectively evaluated the usefulness of repeated pancreatic juice cytology (PJC) using an endoscopic nasopancreatic drainage (ENPD) catheter for the diagnosis of PDAC. We enrolled 82 patients suspected of having resectable PDAC, based on imaging studies, and judged the necessity for cytology. The diagnostic yield of up to six repeated PJCs and the incidence of complications, such as pancreatitis, was evaluated. A total of 60 patients were diagnosed with PDAC. The overall sensitivity and specificity were 46.7% and 95.5%, respectively. The cumulative positivity rate increased with the number of sampling sessions, reaching 58.3% in the sixth session. The sensitivity was significantly higher in the pancreatic head than in the pancreatic tail ( = 0.043). Additionally, it was 100% in four patients with a tumor size ≤10 mm. Pancreatitis occurred in six patients (7.3%), all of whom were treated conservatively. In the diagnosis of PDAC, repeated PJC using an ENPD catheter revealed a cumulative effect of sensitivity up to six times and an excellent diagnostic yield for small PDAC.
PubMed: 37627955
DOI: 10.3390/diagnostics13162696 -
Plant Foods For Human Nutrition... Sep 2023Obesity and diabetes are some of the most important modern health problems requiring simple preventative or palliative measures using dietary means. This study...
Obesity and diabetes are some of the most important modern health problems requiring simple preventative or palliative measures using dietary means. This study investigated the impact of strawberry juice on diabetic rats. Diabetes was induced in rats using a single intraperitoneal injection of 50 mg/kg streptozotocin (STZ). Fifty male rats were divided into five groups: normal control (NC), strawberry juice only (S), diabetic control (DC), and two diabetic groups treated with strawberry juice (DC + S) or metformin (DC + met). Rats were administered a single dose of both strawberry juice and oral metformin, and biochemical and histological analyses were conducted. The experiment was conducted in compliance with the Ethics Committee's regulations for the care and utilization of animals, microorganisms, and living cell cultures in education and scientific research at the Faculty of Agriculture, Minia University (MU/FA/006/12/22). Treatment of diabetic rats with strawberry juice led to a significant decrease in blood glucose. Insulin levels were also significantly increased, while lipid profiles were lowered in the diabetic rats treated with strawberry juice. Carbohydrate metabolism enzymes and antioxidant enzyme activities in the treated rats were restored to normal levels, and the levels of lipid peroxidation and proinflammatory cytokines were notably reduced. The microstructure of pancreatic and liver cells in diabetic rats was also improved with strawberry juice treatment. In addition, HPLC analysis revealed that strawberry juice was rich in flavonoids and phenolic compounds and exhibited potent antioxidant activity. These findings suggest that strawberry juice has considerable hypoglycemic and hypolipidemic effects on rats with diabetes which may be used in human after further investigations.
Topics: Humans; Rats; Animals; Hypoglycemic Agents; Fragaria; Diabetes Mellitus, Experimental; Polyphenols; Plant Extracts; Metformin; Antioxidants; Blood Glucose; Streptozocin; Oxidative Stress
PubMed: 37462847
DOI: 10.1007/s11130-023-01079-1 -
Magnetic Resonance in Medical Sciences... Jul 2023This study evaluated the dependence of the signal characteristics of time-spatial labeling inversion pulse (time-SLIP) on flow velocity and tag thickness to depict the...
This study evaluated the dependence of the signal characteristics of time-spatial labeling inversion pulse (time-SLIP) on flow velocity and tag thickness to depict the pancreatic juice flow by analyzing signal profile using a tube phantom study. The tag edge property was evaluated by edge rise distance (ERD). For various slow flow velocities and tag thicknesses, the signal profile characteristics were evaluated using two indices: the tag center value (R) reduction rate and the total signal value along the tube (T). ERD, which was about 10% of the tag thickness, was higher for thicker tags, making slow flow detection difficult. T was proportional to the thickness of the tag and was preserved irrespective of the flow velocity. R became lower with higher flow velocity and decreased significantly with thinner tags. These results suggest that the visualization of pancreatic juice flow might improve stability by considering the appropriate tag thickness.
Topics: Spin Labels; Pancreatic Juice; Magnetic Resonance Imaging; Phantoms, Imaging
PubMed: 35354711
DOI: 10.2463/mrms.tn.2022-0018 -
Gastrointestinal Endoscopy Jan 2024The diagnostic performance of EUS-guided fine-needle aspiration/biopsy sampling (EUS-FNAB) for pancreatic ductal adenocarcinoma (PDAC) ≤10 mm in diameter is...
True diagnostic ability of EUS-guided fine-needle aspiration/biopsy sampling for small pancreatic lesions ≤10 mm and salvage diagnosis by pancreatic juice cytology: a multicenter study.
BACKGROUND AND AIMS
The diagnostic performance of EUS-guided fine-needle aspiration/biopsy sampling (EUS-FNAB) for pancreatic ductal adenocarcinoma (PDAC) ≤10 mm in diameter is relatively low. Pancreatic juice cytology (PJC) has gained attention because of its high sensitivity for small PDACs. We aimed to clarify the diagnostic ability of EUS-FNAB and the salvage ability of PJC for PDAC ≤10 mm.
METHODS
Data obtained from attempted EUS-FNAB for patients with EUS-confirmed pancreatic tumors ≤10 mm (excluding pancreatic metastases/malignant lymphomas) were retrospectively analyzed. Patients who experienced technical failure or had a negative EUS-FNAB result and had a strong likelihood of PDAC based on imaging characteristics underwent PJC. PDAC was diagnosed using resected histologic specimens, EUS-FNAB-positive tumor growth on the imaging examination, or additional EUS-FNAB-positive results after increase in tumor size. The primary endpoint was the diagnostic ability of EUS-FNAB for PDAC ≤10 mm. The salvage ability of PJC was also assessed.
RESULTS
Overall, 86 of 271 patients with pancreatic tumors ≤10 mm who underwent attempted EUS-FNAB were diagnosed with PDAC. The technical success rate, sensitivity, specificity, and accuracy of EUS-FNAB for PDAC ≤10 mm were 80.8%, 82.3%, 94.9%, and 91.3%, respectively. Among the 35 PDAC patients who experienced technical failure or false-negative results of EUS-FNAB, 26 (74.3%) were correctly diagnosed using salvage PJC.
CONCLUSIONS
The true success rate and sensitivity of EUS-FNAB for PDAC ≤10 mm were relatively low. When EUS-FNAB for a pancreatic lesion ≤10 mm strongly suspected to be PDAC is unsuccessful or yields a negative result, PJC is recommended. (Clinical trial registration number: UMIN000049965.).
Topics: Humans; Biopsy, Fine-Needle; Pancreatic Juice; Retrospective Studies; Pancreas; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Endoscopic Ultrasound-Guided Fine Needle Aspiration
PubMed: 37598865
DOI: 10.1016/j.gie.2023.08.006 -
Function (Oxford, England) 2023Glandular pancreatic epithelia of the acinar or ductal phenotype may seem terminally differentiated, but they are characterized by remarkable cell plasticity....
Glandular pancreatic epithelia of the acinar or ductal phenotype may seem terminally differentiated, but they are characterized by remarkable cell plasticity. Stress-induced trans-differentiation of these cells has been implicated in the mechanisms of carcinogenesis. Current consensus links pancreatic ductal adenocarcinoma with onco-transformation of ductal epithelia, but under the presence of driver mutations in and , also with trans-differentiation of pancreatic acini. However, we do not know when, in the course of cancer progression, physiological functions are lost by mutant acinar cells, nor can we assess their capacity for the production of pancreatic juice components. Here, we investigated whether two mutations-Kras and Trp53-present simultaneously in acinar cells of KPC mice (model of oncogenesis) influence cytosolic Ca signals. Since Ca signals control the cellular handling of digestive hydrolases, any changes that affect intracellular signaling events and cell bioenergetics might have an impact on the physiology of the pancreas. Our results showed that physiological doses of acetylcholine evoked less regular Ca oscillations in KPC acinar cells compared to the control, whereas responses to supramaximal concentrations were markedly reduced. Menadione elicited Ca signals of different frequencies in KPC cells compared to control cells. Finally, Ca extrusion rates were significantly inhibited in KPC cells, likely due to the lower basal respiration and ATP production. Cumulatively, these findings suggest that driver mutations affect the signaling capacity of pancreatic acinar cells even before the changes in the epithelial cell morphology become apparent.
Topics: Mice; Animals; Proto-Oncogene Proteins p21(ras); Pancreatic Neoplasms; Carcinogenesis; Mutation; Adenosine Triphosphate
PubMed: 37575483
DOI: 10.1093/function/zqad035