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Surgery Today Jan 2020The current treatment strategy for intraductal papillary mucinous neoplasms (IPMNs), based on the international consensus guideline, has been accepted widely. However,... (Review)
Review
The current treatment strategy for intraductal papillary mucinous neoplasms (IPMNs), based on the international consensus guideline, has been accepted widely. However, reported outcomes after surgical resection for IPMN show that once the tumor progresses to invasive intraductal papillary mucinous carcinoma (IPMC), recurrence is not uncommon. The surgical treatment for IPMN is invasive and sometimes followed by complications. Therefore, the best timing for resection might be at the point when high-grade dysplasia (HGD) is evident. According to previous reports, main duct type IPMN has a high malignant potential and its surgical resection is universally accepted, whereas, the incidence of HGD/invasive IPMC in branch duct and mixed type IPMNs is thought to be lower. In addition to mural nodules and a dilated main pancreatic duct, cytology and measurement of the carcinoembryonic antigen level in the pancreatic juice might be useful to differentiate HGD/invasive IPMC from low-grade dysplasia. The nomogram proposed recently to predict the risk of HGD/invasive IPMC in IPMN patients might help surgeons decide on the best treatment strategy, depending on the patient's age and general condition. Second resection for high-risk lesions in the remnant pancreas might improve the survival of IPMN patients.
Topics: Age Factors; Biomarkers, Tumor; Carcinoembryonic Antigen; Humans; Lymph Node Excision; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Pancreas; Pancreatectomy; Pancreatic Intraductal Neoplasms; Pancreatic Juice; Pancreatic Neoplasms; Reoperation; Risk; Survival Rate; Treatment Outcome
PubMed: 31807871
DOI: 10.1007/s00595-019-01931-5 -
World Journal of Gastroenterology Jul 2019Postoperative pancreatic fistula (POPF) is one of the most severe complications after pancreatic surgeries. POPF develops as a consequence of pancreatic juice leakage... (Review)
Review
Postoperative pancreatic fistula (POPF) is one of the most severe complications after pancreatic surgeries. POPF develops as a consequence of pancreatic juice leakage from a surgically exfoliated surface and/or anastomotic stump, which sometimes cause intraperitoneal abscesses and subsequent lethal hemorrhage. In recent years, various surgical and perioperative attempts have been examined to reduce the incidence of POPF. We reviewed several well-designed studies addressing POPF-related factors, such as reconstruction methods, anastomotic techniques, stent usage, prophylactic intra-abdominal drainage, and somatostatin analogs, after pancreaticoduodenectomy and distal pancreatectomy, and we assessed the current status of POPF. In addition, we also discussed the current status of POPF in minimally invasive surgeries, laparoscopic surgeries, and robotic surgeries.
Topics: Drainage; Humans; Laparoscopy; Pancreas; Pancreatectomy; Pancreatic Fistula; Pancreatic Juice; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Care; Postoperative Complications; Risk Factors; Robotic Surgical Procedures; Somatostatin; Stents; Treatment Outcome
PubMed: 31391768
DOI: 10.3748/wjg.v25.i28.3722 -
World Journal of Gastroenterology Jul 2021Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its... (Review)
Review
Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).
Topics: Biomarkers, Tumor; CA-19-9 Antigen; Humans; MicroRNAs; Pancreatic Neoplasms; Prognosis
PubMed: 34326612
DOI: 10.3748/wjg.v27.i26.4045 -
Nature Cell Biology Mar 2022Pancreatic ductal adenocarcinoma (PDAC) originates from normal pancreatic ducts where digestive juice is regularly produced. It remains unclear how PDAC can escape...
Pancreatic ductal adenocarcinoma (PDAC) originates from normal pancreatic ducts where digestive juice is regularly produced. It remains unclear how PDAC can escape autodigestion by digestive enzymes. Here we show that human PDAC tumour cells use gasdermin E (GSDME), a pore-forming protein, to mediate digestive resistance. GSDME facilitates the tumour cells to express mucin 1 and mucin 13, which form a barrier to prevent chymotrypsin-mediated destruction. Inoculation of GSDME PDAC cells results in subcutaneous but not orthotopic tumour formation in mice. Inhibition or knockout of mucin 1 or mucin 13 abrogates orthotopic PDAC growth in NOD-SCID mice. Mechanistically, GSDME interacts with and transports YBX1 into the nucleus where YBX1 directly promotes mucin expression. This GSDME-YBX1-mucin axis is also confirmed in patients with PDAC. These findings uncover a unique survival mechanism of PDAC cells in pancreatic microenvironments.
Topics: Adenocarcinoma; Animals; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Mucin-1; Mucins; Pancreatic Neoplasms; Pore Forming Cytotoxic Proteins; Tumor Microenvironment; Y-Box-Binding Protein 1
PubMed: 35292781
DOI: 10.1038/s41556-022-00857-4 -
Frontiers in Plant Science 2019Secreted phospholipases (sPLAs) in plants are a growing group of enzymes that catalyze the hydrolysis of glycerophospholipids to lysophospholipids and free fatty acids.... (Review)
Review
Secreted phospholipases (sPLAs) in plants are a growing group of enzymes that catalyze the hydrolysis of glycerophospholipids to lysophospholipids and free fatty acids. Until today, around only 20 sPLAs were reported from plants. This review discusses the newly acquired information on plant sPLAs including molecular, biochemical, catalytic, and functional aspects. The comparative analysis also includes phylogenetic, evolutionary, and tridimensional structure. The observations with emphasis in sPLA are compared with the available data reported for all plants sPLAs and with those described for animals (mainly from pancreatic juice and venoms sources).
PubMed: 31354755
DOI: 10.3389/fpls.2019.00861 -
Biochimica Et Biophysica Acta. Reviews... Jan 2020Pancreatic ductal adenocarcinoma (PDAC) is an incredibly deadly disease with a 5-year survival rate of 9%. The presence of pancreatic cystic lesions (PCLs) confers an... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is an incredibly deadly disease with a 5-year survival rate of 9%. The presence of pancreatic cystic lesions (PCLs) confers an increased likelihood of future pancreatic cancer in patients placing them in a high-risk category. Discerning concurrent malignancy and risk of future PCL progression to cancer must be carefully and accurately determined to improve survival outcomes and avoid unnecessary morbidity of pancreatic resection. Unfortunately, current image-based guidelines are inadequate to distinguish benign from malignant lesions. There continues to be a need for accurate molecular and imaging biomarker(s) capable of identifying malignant PCLs and predicting the malignant potential of PCLs to enable risk stratification and effective intervention management. This review provides an update on the current status of biomarkers from pancreatic cystic fluid, pancreatic juice, and seromic molecular analyses and discusses the potential of radiomics for differentiating PCLs harboring cancer from those that do not.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Disease Progression; Early Detection of Cancer; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Precancerous Conditions; Risk Factors; Survival Analysis
PubMed: 31676330
DOI: 10.1016/j.bbcan.2019.188318 -
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