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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 -
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 -
Gastrointestinal Endoscopy Nov 2022To date, surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) has not lived up to expectations, as identification of curable stages through...
BACKGROUND AND AIMS
To date, surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) has not lived up to expectations, as identification of curable stages through imaging remains challenging. Biomarkers are therefore needed. Pancreatic juice (PJ) may be a promising source, because it is in direct contact with the ductal epithelial lining from which PDAC arises. We aimed to develop a panel of biomarkers from serum and PJ to detect PDAC for future surveillance purposes.
METHODS
All patients who underwent PJ collection on secretin stimulation at the Erasmus MC were included. Both PJ and serum were evaluated. Protein levels were determined by the Lowry assay. Potential biomarkers (interleukin-8, interferon-γ, neutrophil gelatinase-associated lipocalin [NGAL], mucin 5, subtype AC [MUC5AC], mucin 2, phospholipase A group IB) were selected based on previously reported outcomes and assessed with enzyme-linked immunosorbent assay. Serum carbohydrate antigen 19-9 (CA19-9) values were determined by electrochemiluminescence immunoassay.
RESULTS
This study included 59 cases and 126 surveilled control subjects (who underwent PJ collection), of whom 71 had a hereditary predisposition (35 genetic, 36 familial) and 55 had (suspected neoplastic) pancreatic cysts. CA19-9 values were available for 53 cases and 48 control subjects. Serum CA19-9, as well as PJ interleukin-8, NGAL and MUC5AC, were associated with PDAC independent of age, gender, and presence of diabetes mellitus. Serum CA19-9 had a significantly higher area under the curve (AUC; .86; 95% confidence interval [CI], .79-.94) than individual PJ markers (AUC, .62-.70). A combination of PJ markers and serum CA19-9 (panel 2: sensitivity 42% [95% CI, 29-57] and specificity 96% [95% CI, 86-100]) did not improve diagnostic performance compared with CA19-9 alone (sensitivity 70% [95% CI, 56-82] and specificity 85% [95% CI, 72-94]).
CONCLUSIONS
High levels of serum CA19-9 and PJ-derived proteins are associated with PDAC. Prospective surveillance studies including individuals at risk of developing PDAC are required to validate these findings.
Topics: Humans; CA-19-9 Antigen; Lipocalin-2; Pancreatic Juice; Mucin-2; Secretin; Interleukin-8; Prospective Studies; Interferon-gamma; Biomarkers, Tumor; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Phospholipases; Carbohydrates
PubMed: 35537661
DOI: 10.1016/j.gie.2022.04.1342 -
Surgery Mar 2008Bile and pancreatic juice exclusion from gut activates acinar stress kinases and exacerbates gallstone pancreatitis as evidenced by the ameliorating effects of... (Review)
Review
Bile and pancreatic juice exclusion from gut activates acinar stress kinases and exacerbates gallstone pancreatitis as evidenced by the ameliorating effects of replacement therapy in an experimental model of duct ligation-induced acute pancreatitis. In the early stages of gallstone pancreatitis, bile-pancreatic juice cannot enter the gut. Enteral exclusion worsens pancreatitis by causing feedback hyperstimulation of the exocrine pancreas that activates acinar cell stress kinases. Investigations using a unique surgical model, the Donor Rat Model, showed that duodenal replacement of bile-pancreatic juice in rats with duct ligation attenuates pancreatic stress kinase activation, reduces pancreatic cytokine production, and ameliorates pancreatic morphologic changes. These findings suggest that exclusion-induced acinar hyperstimulation, in the presence of duct obstruction, exacerbates acute pancreatitis via stress kinase activation. Although acinar hyperstimulation has often been implicated in the pathogenesis of acute pancreatitis, the lack of supporting evidence remains a conspicuous void. The proposed hypothesis draws on fresh evidence to present a new paradigm that reexamines the role of exocrine pancreatic hyperstimulation in gallstone pancreatitis pathogenesis.
Topics: Acute Disease; Animals; Bile; Enzyme Activation; Gallstones; Humans; Pancreas, Exocrine; Pancreatic Juice; Pancreatitis; Protein Kinases
PubMed: 18291265
DOI: 10.1016/j.surg.2007.06.004 -
Clinical Gastroenterology and... Mar 2020Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer....
BACKGROUND & AIMS
Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls).
METHODS
We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees.
RESULTS
We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83-0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%-93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%-95%).
CONCLUSIONS
We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed.
Topics: Carcinoma, Pancreatic Ductal; DNA; Early Detection of Cancer; Humans; Pancreatic Juice; Pancreatic Neoplasms
PubMed: 31323382
DOI: 10.1016/j.cgh.2019.07.017 -
World Journal of Gastroenterology Oct 2015Pancreatic cancer is usually diagnosed at an advanced stage and curative resection is feasible in only a small minority of patients at the time of diagnosis. Diagnosis... (Review)
Review
Pancreatic cancer is usually diagnosed at an advanced stage and curative resection is feasible in only a small minority of patients at the time of diagnosis. Diagnosis at an early stage is unequivocally associated with better long-term survival. Several candidate molecular markers for early detection are currently under investigation in different phases of discovery and validation. Recent advances in the technology for whole genome, methylome, ribonucleome, and proteome interrogation has enabled rapid advancements in the field of biomarker discovery. In this review we discuss the current status of molecular markers for detection of pancreatic cancer in blood, pancreatic cyst fluid, pancreatic juice and stool and briefly highlight some promising preliminary results of new approaches that have the potential of advancing this field in the near future.
Topics: Biomarkers, Tumor; Diffusion of Innovation; Early Detection of Cancer; Feces; Forecasting; Genetic Predisposition to Disease; Humans; Molecular Diagnostic Techniques; Neoplasm Staging; Neoplastic Cells, Circulating; Pancreatic Juice; Pancreatic Neoplasms; Phenotype; Predictive Value of Tests; Risk Factors
PubMed: 26526068
DOI: 10.3748/wjg.v21.i40.11387 -
Gut Apr 1977
Review
Topics: Carcinoma, Papillary; Catheterization; Cholangiography; Diagnosis, Differential; Endoscopes; Endoscopy; Humans; Jaundice; Pancreas; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Sphincter of Oddi
PubMed: 324875
DOI: 10.1136/gut.18.4.316 -
Internal Medicine (Tokyo, Japan) 2009Lactoferrin, a major whey protein, is a red iron-binding protein present mainly in external secretions such as breast milk and in polymorphonuclear neutrophils. The... (Review)
Review
Lactoferrin, a major whey protein, is a red iron-binding protein present mainly in external secretions such as breast milk and in polymorphonuclear neutrophils. The presence of lactoferrin in body fluids is proportional to the flux of neutrophils and its assessment can provide a reliable biomarker for inflammation. In gastrointestinal diseases increased fecal lactoferrin is a sensitive and specific surrogate marker for inflammatory bowel diseases in patients with chronic diarrhea and pain, and ascites lactoferrin can also provide a promising and reliable biomarker for bacterial peritonitis. Lactoferrin in pancreatic juice and stone could provide pathophysiological information of protein plug and stone formation in the pancreatic duct. Serum anti-lactoferrin autoantibody might contribute to the clarification of the pathogenetic mechanisms of autoimmune pancreatitis and liver diseases, although its diagnostic and prognostic value appears to be limited. Further studies will be necessary to elucidate the exact details.
Topics: Ascitic Fluid; Autoantibodies; Biomarkers; Calculi; Carrier Proteins; Feces; Gastrointestinal Diseases; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Lactoferrin; Pancreatic Juice
PubMed: 19652425
DOI: 10.2169/internalmedicine.48.2199 -
Molecular & Cellular Proteomics : MCP Oct 2011Pancreatic cancer is one of the leading causes of cancer-related deaths, for which serological biomarkers are urgently needed. Most discovery-phase studies focus on the...
Pancreatic cancer is one of the leading causes of cancer-related deaths, for which serological biomarkers are urgently needed. Most discovery-phase studies focus on the use of one biological source for analysis. The present study details the combined mining of pancreatic cancer-related cell line conditioned media and pancreatic juice for identification of putative diagnostic leads. Using strong cation exchange chromatography, followed by LC-MS/MS on an LTQ-Orbitrap mass spectrometer, we extensively characterized the proteomes of conditioned media from six pancreatic cancer cell lines (BxPc3, MIA-PaCa2, PANC1, CAPAN1, CFPAC1, and SU.86.86), the normal human pancreatic ductal epithelial cell line HPDE, and two pools of six pancreatic juice samples from ductal adenocarcinoma patients. All samples were analyzed in triplicate. Between 1261 and 2171 proteins were identified with two or more peptides in each of the cell lines, and an average of 521 proteins were identified in the pancreatic juice pools. In total, 3479 nonredundant proteins were identified with high confidence, of which ∼ 40% were extracellular or cell membrane-bound based on Genome Ontology classifications. Three strategies were employed for identification of candidate biomarkers: (1) examination of differential protein expression between the cancer and normal cell lines using label-free protein quantification, (2) integrative analysis, focusing on the overlap of proteins among the multiple biological fluids, and (3) tissue specificity analysis through mining of publically available databases. Preliminary verification of anterior gradient homolog 2, syncollin, olfactomedin-4, polymeric immunoglobulin receptor, and collagen alpha-1(VI) chain in plasma samples from pancreatic cancer patients and healthy controls using ELISA, showed a significant increase (p < 0.01) of these proteins in plasma from pancreatic cancer patients. The combination of these five proteins showed an improved area under the receiver operating characteristic curve to CA19.9 alone. Further validation of these proteins is warranted, as is the investigation of the remaining group of candidates.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Carrier Proteins; Cell Line, Tumor; Collagen Type IV; Culture Media, Conditioned; Gene Expression Regulation, Neoplastic; Granulocyte Colony-Stimulating Factor; Humans; Membrane Proteins; Mucoproteins; Oncogene Proteins; Pancreatic Juice; Pancreatic Neoplasms; Proteins; Proteome; ROC Curve; Receptors, Polymeric Immunoglobulin
PubMed: 21653254
DOI: 10.1074/mcp.M111.008599 -
Pancreatology : Official Journal of the... Nov 2022Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice.
METHODS
A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated.
RESULTS
Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS, TP53, CDKN2A, GNAS and SMAD4 mutations were evaluated most. Of these, TP53 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31-54%), specificity of 98% (95%-CI: 92%-100%) and diagnostic odds ratio of 36 (95% CI: 9-133). Of DNA methylation patterns, hypermethylation of CDKN2A, NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39-70% and specificity of 94-100% for distinguishing pancreatic cancer from controls.
CONCLUSIONS
This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53, SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Mutation; Pancreatic Juice; Pancreatic Neoplasms
PubMed: 35864067
DOI: 10.1016/j.pan.2022.06.260