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Cellular Oncology (Dordrecht) Apr 2024Excessive fibrosis is a predominant feature of pancreatic stroma and plays a crucial role in the development and progression of pancreatic ductal adenocarcinoma (PDAC)... (Review)
Review
Excessive fibrosis is a predominant feature of pancreatic stroma and plays a crucial role in the development and progression of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Emerging evidence showed diversity and heterogeneity of fibroblasts play crucial and somewhat contradictory roles, the interactions between fibroblasts and pancreatic cells or infiltrating immune cells are of great importance during PDAC and CP progression, with some promising therapeutic strategies being tested. Therefore, in this review, we describe the classification of fibroblasts and their functions in PDAC and pancreatitis, the mechanisms by which fibroblasts mediate the development and progression of PDAC and CP through direct or indirect interaction between fibroblast and pancreatic parenchymal cells, or by remodeling the pancreatic immune microenvironment mediates the development and progression of PDAC and CP. Finally, we summarized the current therapeutic strategies and agents that directly target subtypes of fibroblasts or interfere with their essential functions.
Topics: Humans; Pancreatic Neoplasms; Fibroblasts; Pancreatitis; Carcinoma, Pancreatic Ductal; Animals; Tumor Microenvironment; Pancreatitis, Chronic; Pancreas
PubMed: 37721678
DOI: 10.1007/s13402-023-00874-x -
American Family Physician Mar 2024Pancreatic cancer is relatively uncommon and carries a poor prognosis because patients often develop signs or symptoms at a late stage of illness. Patients with a family... (Review)
Review
Pancreatic cancer is relatively uncommon and carries a poor prognosis because patients often develop signs or symptoms at a late stage of illness. Patients with a family history, especially those with genetic syndromes, are at a significantly increased risk of pancreatic cancer. Modifiable risk factors include smoking, heavy alcohol use, and obesity. Although patients at increased risk should be screened, screening is not recommended for asymptomatic people at average risk. The differential diagnosis for a symptomatic patient is broad, including gastroesophageal reflux disease, gastritis, peptic ulcer disease, chronic pancreatitis, biliary dyskinesia, cholelithiasis, gastroparesis, or constipation. Initial serologic testing should include transaminase and bilirubin levels, and in patients with midepigastric pain, lipase levels. Pancreas-protocol, contrast-enhanced abdominal computed tomography is the imaging test of choice. Carbohydrate antigen 19-9 is the most studied cancer marker and moderately accurate in patients suspected of having cancer; however, the positive predictive value is 0.9% in asymptomatic patients. Treatment includes neoadjuvant or adjuvant chemotherapy and surgery if the cancer is resectable. The treatment approach is best determined by a multidisciplinary, high-volume center. For a patient undergoing chemotherapy, nutritional and psychosocial support and palliation of symptoms should be goals during treatment.
Topics: Humans; Pancreas; Pancreatic Neoplasms; Pancreatitis, Chronic; Risk Factors; Tomography, X-Ray Computed
PubMed: 38574214
DOI: No ID Found -
Signal Transduction and Targeted Therapy Oct 2023Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is...
Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.
Topics: Humans; Pancreatic Cyst; Cyst Fluid; Proteomics; Pancreatic Neoplasms; Glycoproteins; Neoplasms, Cystic, Mucinous, and Serous
PubMed: 37848412
DOI: 10.1038/s41392-023-01645-8 -
Journal of Experimental & Clinical... Oct 2023Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers worldwide, mainly due to its late diagnosis and lack of effective therapies, translating... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers worldwide, mainly due to its late diagnosis and lack of effective therapies, translating into a low 5-year 12% survival rate, despite extensive clinical efforts to improve outcomes. International cooperative studies have provided informative multiomic landscapes of PDAC, but translation of these discoveries into clinical advances are lagging. Likewise, early diagnosis biomarkers and new therapeutic tools are sorely needed to tackle this cancer. The study of poorly explored molecular processes, such as splicing, can provide new tools in this regard. Alternative splicing of pre-RNA allows the generation of multiple RNA variants from a single gene and thereby contributes to fundamental biological processes by finely tuning gene expression. However, alterations in alternative splicing are linked to many diseases, and particularly to cancer, where it can contribute to tumor initiation, progression, metastasis and drug resistance. Splicing defects are increasingly being associated with PDAC, including both mutations or dysregulation of components of the splicing machinery and associated factors, and altered expression of specific relevant gene variants. Such disruptions can be a key element enhancing pancreatic tumor progression or metastasis, while they can also provide suitable tools to identify potential candidate biomarkers and discover new actionable targets. In this review, we aimed to summarize the current information about dysregulation of splicing-related elements and aberrant splicing isoforms in PDAC, and to describe their relationship with the development, progression and/or aggressiveness of this dismal cancer, as well as their potential as therapeutic tools and targets.
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Biomarkers; RNA
PubMed: 37880792
DOI: 10.1186/s13046-023-02858-z -
Radiologie (Heidelberg, Germany) Dec 2023Autoimmune pancreatitis (AIP) is classified as a distinct form of pancreatitis according to the guidelines. It is characterized by imaging morphologic and histologic... (Review)
Review
CLINICAL ISSUE
Autoimmune pancreatitis (AIP) is classified as a distinct form of pancreatitis according to the guidelines. It is characterized by imaging morphologic and histologic features and is associated with extrapancreatic manifestations in type 1 IgG 4-associated disease. Symptoms and findings almost always improve with administration of steroids. Differentiation from pancreatic ductal adenocarcinoma is required, particularly in the presence of AIP with focal parenchymal involvement.
STANDARD RADIOLOGIC PROCEDURES
If AIP is suspected, abdominal ultrasound and/or endosonography, computed tomography (CT), and preferably magnetic resonance imaging (MRI) are indicated. A distinction is made between parenchymal and ductal changes that specifically indicate the presence of AIP.
METHODOLOGICAL INNOVATIONS AND EVALUATION
The diagnosis of autoimmune pancreatitis should be made based on the International Consensus Criteria (ICDC), in which the five main features (imaging, serology, histology, other organ involvement, response to steroid medication) are assessed. In type 1 AIP, typical imaging changes are sufficient to establish the diagnosis even with negative histology, whereas for type 2 AIP, histologic evidence is required. Imaging changes help in the differential diagnosis from pancreatic cancer.
PRACTICAL RECOMMENDATIONS
The following article addresses and evaluates crucial imaging diagnostic CT and MRI criteria for correct classification of findings, description of results, and differentiation of autoimmune pancreatitis from pancreatic cancer.
Topics: Humans; Autoimmune Pancreatitis; Autoimmune Diseases; Pancreatic Neoplasms; Pancreatitis; Steroids
PubMed: 37947862
DOI: 10.1007/s00117-023-01240-6 -
Gastrointestinal Endoscopy Clinics of... Oct 2023Chronic pancreatitis (CP) is an ongoing inflammatory disease with most patients developing pancreatic calculi during their course of disease. Extracorporeal shock wave... (Review)
Review
Chronic pancreatitis (CP) is an ongoing inflammatory disease with most patients developing pancreatic calculi during their course of disease. Extracorporeal shock wave lithotripsy (ESWL) is a first-line treatment option in patients with large lumen obstructing pancreatic duct (PD) stones. In patients with CP and PD dilatation, digital single-operator pancreatoscopy (DSOP)-guided lithotripsy seems to be an appealing option to ESWL and surgery. DSOP-guided lithotripsy for the treatment of large symptomatic PD-stones has been demonstrated to be safe, technically, and clinically effective, and should be regarded as an alternative endoscopic treatment of certain patients.
Topics: Humans; Pancreatic Diseases; Pancreatitis, Chronic; Lithotripsy; Endoscopes, Gastrointestinal; Pancreatic Ducts
PubMed: 37709413
DOI: 10.1016/j.giec.2023.04.001 -
Current Opinion in Gastroenterology Sep 2023Patients with pancreatic tumors may have limited treatment options. Pancreatic tumor ablation is a novel and emerging treatment modality which can now be performed using... (Review)
Review
PURPOSE OF REVIEW
Patients with pancreatic tumors may have limited treatment options. Pancreatic tumor ablation is a novel and emerging treatment modality which can now be performed using endoscopic ultrasound (EUS) guidance. This modality is well suited to guide energy delivery for radiofrequency ablation (RFA) and microwave ablation. These approaches provide minimally invasive, nonsurgical methods for delivering energy to ablate pancreatic tumors in situ . This review summarizes the current data and safety profile for ablation in managing pancreatic cancer and pancreatic neuroendocrine tumors.
RECENT FINDINGS
RFA uses thermal energy to induce cell death by coagulative necrosis and protein denaturation. Studies have reported increased overall survival in patients with pancreatic tumors treated with EUS-guided RFA in a multimodality systemic approach and when used in palliative surgeries. Radiofrequency ablation may have corollary benefits in inducing an immune-modulatory effect. Tumor marker carbohydrate antigen 19-9 has been reported to decrease in response to RFA. Microwave ablation is an emerging modality.
SUMMARY
RFA utilizes focal thermal energy to induce cell death. RFA has been applied through open, laparoscopic, and radiographic modalities. EUS-guided approaches are now allowing RFA and microwave ablation to be performed for pancreatic tumors in situ .
Topics: Humans; Pancreatic Neoplasms; Radiofrequency Ablation; Pancreas; Endosonography; Laparoscopy; Catheter Ablation
PubMed: 37097824
DOI: 10.1097/MOG.0000000000000939 -
International Journal of Public Health 2023To evaluate excess deaths of gastrointestinal, liver, and pancreatic diseases in the United States during the COVID-19 pandemic. We retrieved weekly death counts from...
To evaluate excess deaths of gastrointestinal, liver, and pancreatic diseases in the United States during the COVID-19 pandemic. We retrieved weekly death counts from National Vital Statistics System and fitted them with a quasi-Poisson regression model. Cause-specific excess deaths were calculated by the difference between observed and expected deaths with adjustment for temporal trend and seasonality. Demographic disparities and temporal-spatial patterns were evaluated for different diseases. From March 2020 to September 2022, the increased mortality (measured by excess risks) for colitis, gastrointestinal hemorrhage, and acute pancreatitis were 35.9%; 24.8%; and 20.6% higher than the expected. For alcoholic liver disease, fibrosis/cirrhosis, and hepatic failure, the excess risks were 1.4-2.8 times higher among younger inhabitants than older inhabitants. The excess deaths of selected diseases were persistently observed across multiple epidemic waves with fluctuating trends for gastrointestinal hemorrhage and fibrosis/cirrhosis and an increasing trend for colitis. The persistently observed excess deaths of digestive diseases highlights the importance for healthcare authorities to develop sustainable strategies in response to the long-term circulating of SARS-CoV-2 in the community.
Topics: United States; Humans; Acute Disease; Clostridioides difficile; Pandemics; COVID-19; Pancreatitis; SARS-CoV-2; Pancreatic Diseases; Liver Cirrhosis; Gastrointestinal Hemorrhage; Colitis
PubMed: 37649691
DOI: 10.3389/ijph.2023.1606305 -
Biochemical Pharmacology Nov 2023Pancreatic cancer is highly metastatic and lethal with an increasing incidence globally and a 5-year survival rate of only 8%. One of the factors contributing to the...
Pancreatic cancer is highly metastatic and lethal with an increasing incidence globally and a 5-year survival rate of only 8%. One of the factors contributing to the high mortality is the lack of effective drugs in the clinical setting. We speculated that effective compounds against pancreatic cancer exist in natural herbs and explored active small molecules among traditional Chinese medicinal herbs. The small molecule lycorine (MW: 323.77) derived from the herb Lycoris radiata inhibited pancreatic cancer cell growth with an IC value of 1 μM in a concentration-dependent manner. Lycorine markedly reduced pancreatic cancer cell viability, migration, invasion, neovascularization, and gemcitabine resistance. Additionally, lycorine effectively suppressed tumor growth in mouse xenograft models without obvious toxicity. Pharmacological studies revealed that the levels and half-life of Notch1 oncoprotein in the pancreatic cancer cells Panc-1 and Patu8988 were notably reduced. Moreover, the expression of the key vasculogenic genes Semaphorin 4D (Sema4D) and angiopoietin-2 (Ang-2) were also significantly inhibited by lycorine. Mechanistically, lycorine strongly triggered the degradation of Notch1 oncoprotein through the ubiquitin-proteasome system. In conclusion, lycorine effectively inhibits pancreatic cancer cell growth, migration, invasion, neovascularization, and gemcitabine resistance by inducing degradation of Notch1 oncoprotein and downregulating the key vasculogenic genes Sema4D and Ang-2. Our findings provide a new therapeutic candidate and treatment strategy against pancreatic cancer.
Topics: Animals; Mice; Humans; Cell Line, Tumor; Amaryllidaceae Alkaloids; Pancreatic Neoplasms; Cell Transformation, Neoplastic; Oncogene Proteins; Cell Proliferation
PubMed: 37769714
DOI: 10.1016/j.bcp.2023.115833 -
World Journal of Gastroenterology May 2024Contrast-enhanced endoscopic ultrasound (CH-EUS) can overcome the limitations of endoscopic ultrasound-guided acquisition by identifying microvessels inside... (Review)
Review
Contrast-enhanced endoscopic ultrasound (CH-EUS) can overcome the limitations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours. Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions, further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS. This review details the knowledge based on the available data on contrast-guided procedures. The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions, which occur in select cases. Additionally, the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage, and patients who have nonvisualized vessels that need to be highlighted Doppler EUS are presented. Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours, in which case CH-EUS can be used to reveal the incomplete tumour destruction.
Topics: Humans; Contrast Media; Pancreatic Neoplasms; Endosonography; Pancreas; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Ultrasonography, Interventional; Drainage; Pancreatic Diseases
PubMed: 38813054
DOI: 10.3748/wjg.v30.i17.2311