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Pflugers Archiv : European Journal of... Aug 2014A central function of epithelia is the control of the volume and electrolyte composition of bodily fluids through vectorial transport of electrolytes and the obligatory... (Review)
Review
A central function of epithelia is the control of the volume and electrolyte composition of bodily fluids through vectorial transport of electrolytes and the obligatory H2O. In exocrine glands, fluid and electrolyte secretion is carried out by both acinar and duct cells, with the portion of fluid secreted by each cell type varying among glands. All acinar cells secrete isotonic, plasma-like fluid, while the duct determines the final electrolyte composition of the fluid by absorbing most of the Cl(-) and secreting HCO3 (-). The key transporters mediating acinar fluid and electrolyte secretion are the basolateral Na(+)/K(+) /2Cl(-) cotransporter, the luminal Ca(2+)-activated Cl(-) channel ANO1 and basolateral and luminal Ca(2+)-activated K(+) channels. Ductal fluid and HCO3 (-) secretion are mediated by the basolateral membrane Na(+)-HCO3 (-) cotransporter NBCe1-B and the luminal membrane Cl(-)/HCO3 (-) exchanger slc26a6 and the Cl(-) channel CFTR. The function of the transporters is regulated by multiple inputs, which in the duct include major regulation by the WNK/SPAK pathway that inhibit secretion and the IRBIT/PP1 pathway that antagonize the effects of the WNK/SPAK pathway to both stimulate and coordinate the secretion. The function of these regulatory pathways in secretory glands acinar cells is yet to be examined. An important concept in biology is synergism among signaling pathways to generate the final physiological response that ensures regulation with high fidelity and guards against cell toxicity. While synergism is observed in all epithelial functions, the molecular mechanism mediating the synergism is not known. Recent work reveals a central role for IRBIT as a third messenger that integrates and synergizes the function of the Ca(2+) and cAMP signaling pathways in activation of epithelial fluid and electrolyte secretion. These concepts are discussed in this review using secretion by the pancreatic and salivary gland ducts as model systems.
Topics: Animals; Body Fluids; Electrolytes; Epithelium; Humans; Pancreatic Ducts; Salivary Ducts; Signal Transduction; Water-Electrolyte Balance
PubMed: 24240699
DOI: 10.1007/s00424-013-1390-1 -
Journal of Hepato-biliary-pancreatic... Feb 2021Pancreatic trauma is reportedly associated with high morbidity and mortality. Main pancreatic duct (MPD) injury is critical for treatment.
BACKGROUND
Pancreatic trauma is reportedly associated with high morbidity and mortality. Main pancreatic duct (MPD) injury is critical for treatment.
METHODS
As a study project of the Japanese Society for Abdominal Emergency Medicine (JSAEM), we collected the data of 163 patients with pancreatic trauma who were diagnosed and treated at JSAEM board-certified hospitals from 2006 to 2016. Clinical backgrounds, diagnostic approaches, management strategies, and outcomes were evaluated.
RESULTS
Sixty-four patients (39%) were diagnosed as having pancreatic trauma with MPD injury that resulted in 3% mortality. Blunt trauma and isolated pancreatic injury were independent factors predicting MPD injury. Nine of 11 patients with MPD injury who were initially treated nonoperatively had serious clinical sequelae and five (45%) required surgery as a secondary treatment. Among all cases, the detectability of MPD injury of endoscopic retrograde pancreatography (ERP) was superior to that of other imaging modalities (CT or MRI), with higher sensitivity and specificity (sensitivity = 0.96; specificity = 1.0).
CONCLUSIONS
Acceptable outcomes were observed in pancreatic trauma patients with MPD injury. Nonoperative management should be carefully selected for MPD injury. ERP is recommended to be performed in patients with suspected MPD injury and stable hemodynamics.
Topics: Abdominal Injuries; Cholangiopancreatography, Endoscopic Retrograde; Humans; Japan; Pancreatic Ducts; Wounds, Nonpenetrating
PubMed: 33280257
DOI: 10.1002/jhbp.877 -
Scientific Reports Mar 2022Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and early diagnosis is challenging. Because patients who present with symptoms generally have advanced-stage...
Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and early diagnosis is challenging. Because patients who present with symptoms generally have advanced-stage diseases, analysis of asymptomatic PDAC provides invaluable information for developing strategies for early diagnosis. Here, we reviewed 577 patients with PDAC (372 diagnosed with symptoms [symptomatic group] and 205 without symptoms [asymptomatic group]) diagnosed at our institute. Among the 205 asymptomatic PDAC patients, 109 were detected during follow-up/work-up for other diseases, 61 because of new-onset or exacerbation of diabetes mellitus, and 35 in a medical check-up. Asymptomatic PDAC is characterized by smaller tumor size, earlier disease stage, and higher resectability than those of symptomatic PDAC. In 22.7% of asymptomatic cases, indirect findings, e.g., dilatation of the main pancreatic duct, triggered PDAC detection. Although pancreatic tumors were less frequently detected, overall abnormality detection rates on imaging studies were nearly 100% in asymptomatic PDAC. Asymptomatic PDAC had a better prognosis (median survival time, 881 days) than symptomatic PDAC (342 days, P < 0.001). In conclusion, diagnosis of PDAC in the asymptomatic stage is associated with early diagnosis and a better prognosis. Incidental detection of abnormal findings during the follow-up/work-up for other diseases provides important opportunities for early diagnosis of asymptomatic PDAC.
Topics: Carcinoma, Pancreatic Ductal; Humans; Pancreatic Ducts; Pancreatic Neoplasms; Prognosis
PubMed: 35277545
DOI: 10.1038/s41598-022-08083-6 -
Tissue Engineering. Part C, Methods Aug 2018Proper identification of pancreatic ducts is a major challenge for researchers performing partial duct ligation (PDL), because pancreatic ducts, which are covered with...
Proper identification of pancreatic ducts is a major challenge for researchers performing partial duct ligation (PDL), because pancreatic ducts, which are covered with acinar cells, are translucent and thin. Although damage to pancreatic ducts may activate quiescent ductal stem cells, which may allow further investigation into ductal stem cells for therapeutic use, there is a lack of effective techniques to visualize pancreatic ducts. In this study, we report a new method for identifying pancreatic ducts. First, we aimed to visualize pancreatic ducts using black, waterproof fountain pen ink. We injected the ink into pancreatic ducts through the bile duct. The flow of ink was observed in pancreatic ducts, revealing their precise architecture. Next, to visualize pancreatic ducts in live animals, we injected fluorescein-labeled bile acid, cholyl-lysyl-fluorescein into the mouse tail vein. The fluorescent probe clearly marked not only the bile duct but also pancreatic ducts when observed with a fluorescent microscope. To confirm whether the pancreatic duct labeling was successful, we performed PDL on Neurogenin3 (Ngn3)-GFP transgenic mice. As a result, acinar tissue is lost. PDL tail pancreas becomes translucent almost completely devoid of acinar cells. Furthermore, strong activation of Ngn3 expression was observed in the ligated part of the adult mouse pancreas at 7 days after PDL.
Topics: Animals; Cholic Acids; Fluoresceins; Fluorescent Dyes; Ligation; Mice, Inbred C57BL; Pancreatic Ducts; Tissue Engineering
PubMed: 29993334
DOI: 10.1089/ten.TEC.2018.0127 -
Stem Cell Reports Mar 2018Pancreatic duct epithelial cells have been suggested as a source of progenitors for pancreatic growth and regeneration. However, genetic lineage-tracing experiments with...
Pancreatic duct epithelial cells have been suggested as a source of progenitors for pancreatic growth and regeneration. However, genetic lineage-tracing experiments with pancreatic duct-specific Cre expression have given conflicting results. Using immunofluorescence and flow cytometry, we show heterogeneous expression of both HNF1β and SOX9 in adult human and murine ductal epithelium. Their expression was dynamic and diminished significantly after induced replication. Purified pancreatic duct cells formed organoid structures in 3D culture, and heterogeneity of expression of Hnf1β and Sox9 was maintained even after passaging. Using antibodies against a second cell surface molecule CD51 (human) or CD24 (mouse), we could isolate living subpopulations of duct cells enriched for high or low expression of HNF1β and SOX9. Only the CD24 (Hnfβ/Sox9) subpopulation was able to form organoids.
Topics: Adult; Aged; Animals; CD24 Antigen; Epithelial Cells; Hepatocyte Nuclear Factor 1-beta; Humans; Integrin alphaV; Male; Mice; Mice, Inbred C57BL; Middle Aged; Organoids; Pancreatic Ducts; SOX9 Transcription Factor
PubMed: 29478894
DOI: 10.1016/j.stemcr.2018.01.028 -
BMC Gastroenterology Apr 2018Pancreatic duct obstructions are common in patients with pancreaticoduodenectomy. However, it is often neglected in follow up. This study was to review the outcomes of...
BACKGROUND
Pancreatic duct obstructions are common in patients with pancreaticoduodenectomy. However, it is often neglected in follow up. This study was to review the outcomes of pancreatic duct obstruction and explore the prevention of pancreatic duct obstruction.
METHODS
A retrospective analysis of 78 patients undergoing pancreaticojejunostomy without reccurence of disease within 24 months between 2004 and 2014. Pancreatic duct obstruction and long-term pancreatic complications were analysed.
RESULTS
Twenty-five patients developed pancreatic duct obstruction following pancreaticojejunostomy, 13 of whom were found to have long-term pancreatic complications. The presence of pancreatic duct obstruction and early pancreatic obstruction were associated with long-term pancreatic complications, respectively (p = 0.002, p = 0.002). There are 10 patients with pancreatic duct stent more than 24 months, the postoperative median pancreatic parenchymal thickness in these 10 patients (17.1 mm, range 8.0 to 24.7 mm) was not significantly change than the median in them preoperative (16.4 mm, range 7.2 to 24.7 mm; p = 0.747). All of them have no long-term pancreatic complications, though the difference was not significantly (p = 0.068).
CONCLUSIONS
Early pancreatic duct obstruction is associated with postoperative pancreatic long-term complications. Sustained internal pancreatic stent may improve pancreatic duct obstruction.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Pain; Pancreatic Diseases; Pancreatic Ducts; Pancreaticojejunostomy; Postoperative Complications; Retrospective Studies; Stents; Young Adult
PubMed: 29688844
DOI: 10.1186/s12876-018-0777-z -
BMC Gastroenterology Jan 2021This study evaluates preliminary results of image-guided percutaneous direct pancreatic duct intervention in the management of pancreatic fistula after surgery or...
BACKGROUND
This study evaluates preliminary results of image-guided percutaneous direct pancreatic duct intervention in the management of pancreatic fistula after surgery or pancreatitis when initially ineligible for surgical or endoscopic therapy.
METHODS
Between 2001 and 2018 the medical records of all patients that underwent percutaneous pancreatic duct intervention for radiographically confirmed pancreatic fistula initially ineligible for surgical or endoscopic repair were reviewed for demographics, clinical history, procedure details, adverse events, procedure related imaging and laboratory results, ability to directly catheterized the main pancreatic duct, and whether desired clinical objectives were met.
RESULTS
In 10 of 11patients (6 male and 5 female with mean age 60.5, range 39-89) percutaneous pancreatic duct cannulation was possible. The 10 duct interventions included direct ductal suction drainage in 7, percutaneous duct closure in 3 and stent placement in 1. Pancreatic fistulas closed in 7 of 10, 2 were temporized until elective surgery, and 1 palliated until death from malignancy. The single patient with failed duct cannulation resolved the fistula with prolonged catheter drainage of the peri-pancreatic cavity. There were no major adverse events related to intervention.
CONCLUSION
In patients with pancreatic fistulas initially ineligible for endoscopic therapy or elective surgery, direct percutaneous pancreatic duct interventions are possible, can achieve improvement without major morbidity or mortality, and can improve and maintain the medical condition of patients in preparation for definitive surgery.
Topics: Cholangiopancreatography, Endoscopic Retrograde; Drainage; Female; Humans; Male; Middle Aged; Pancreatic Ducts; Pancreatic Fistula; Treatment Outcome
PubMed: 33509111
DOI: 10.1186/s12876-021-01620-z -
Laboratory Investigation; a Journal of... Feb 2021Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States. Despite the high prevalence of Kras mutations in...
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States. Despite the high prevalence of Kras mutations in pancreatic cancer patients, murine models expressing the oncogenic mutant Kras (Kras) in mature pancreatic cells develop PDAC at a low frequency. Independent of cell of origin, a second genetic hit (loss of tumor suppressor TP53 or PTEN) is important for development of PDAC in mice. We hypothesized ectopic expression and elevated levels of oncogenic mutant Kras would promote PanIN arising in pancreatic ducts. To test our hypothesis, the significance of elevating levels of K-Ras and Ras activity has been explored by expression of a CAG driven LGSL-Kras allele (cKras) in pancreatic ducts, which promotes ectopic Kras expression. We predicted expression of cKras in pancreatic ducts would generate neoplasia and PDAC. To test our hypothesis, we employed tamoxifen dependent CreER mediated recombination. Hnf1b:CreER;Kras (cKras) mice received 1 (Low), 5 (Mod) or 10 (High) mg per 20 g body weight to recombine cKras in low (cKras), moderate (cKras), and high (cKras) percentages of pancreatic ducts. Our histologic analysis revealed poorly differentiated aggressive tumors in cKras mice. cKras mice had grades of Pancreatic Intraepithelial Neoplasia (PanIN), recapitulating early and advanced PanIN observed in human PDAC. Proteomics analysis revealed significant differences in PTEN/AKT and MAPK pathways between wild type, cKras, cKras, and cKras mice. In conclusion, in this study, we provide evidence that ectopic expression of oncogenic mutant K-Ras in pancreatic ducts generates early and late PanIN as well as PDAC. This Ras rheostat model provides evidence that AKT signaling is an important early driver of invasive ductal derived PDAC.
Topics: Animals; Carcinoma, Pancreatic Ductal; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Mice; Mice, Transgenic; Mutation Rate; Pancreatic Ducts; Pancreatic Neoplasms; Precancerous Conditions; Proto-Oncogene Proteins p21(ras); Recombination, Genetic
PubMed: 33009500
DOI: 10.1038/s41374-020-00490-5 -
BMC Gastroenterology Nov 2022Main pancreatic duct (MPD) dilation is a high-risk stigmata/worrisome feature of malignancy in intraductal papillary mucinous neoplasms (IPMNs). The threshold of MPD...
BACKGROUND
Main pancreatic duct (MPD) dilation is a high-risk stigmata/worrisome feature of malignancy in intraductal papillary mucinous neoplasms (IPMNs). The threshold of MPD diameter in predicting malignancy may be related to the lesion location. This study aimed to separately identify the thresholds of MPD for malignancy of IPMNs separately for the head-neck and body-tail.
MATERIALS AND METHODS
A total of 185 patients with pathologically confirmed IPMNs were included. Patient demographic information, clinical data, and pathological features were obtained from the medical records. Those IPMNs with high-grade dysplasia or with associated invasive carcinoma were considered as malignant tumor. Radiological data including lesion location, tumor size, diameter of the MPD, mural nodule, and IPMN types (main duct, MD; branch duct, BD; and mixed type, MT), were collected on computed tomography or magnetic resonance imaging. Serum carbohydrate antigen 19-9 levels, serum carcinoembryonic antigen levels, and the medical history of diabetes mellitus, chronic cholecystitis, and pancreatitis were also collected.
RESULTS
Malignant IPMNs were detected in 31.6% of 117 patients with lesions in the pancreatic head-neck and 20.9% of 67 patients with lesions in the pancreatic body-tail. In MPD-involved IPMNs, malignancy was observed in 54.1% of patients with lesions in the pancreatic head-neck and 30.8% of patients with lesions in the pancreatic body-tail (p < 0.05). The cutoff value of MPD diameter for malignancy was 6.5 mm for lesions in the head-neck and 7.7 mm for lesions in the body-tail in all type of IPMNs. In MPD-involved IPMNs, the threshold was 8.2 mm for lesion in pancreatic head-neck and 7.7 mm for lesions in the body-tail. Multivariate analysis confirmed that MPD diameter ≥ 6.5 mm (pancreatic head-neck) and MPD diameter ≥ 7.7 mm (pancreatic body-tail) were independent predictors of malignancy (p < 0.05). Similar results were observed in MPD-involved IPMNs using 8.2 mm as a threshold.
CONCLUSION
The thresholds of the dilated MPD may be associated with IPMNs locations. Thresholds of 6.5 mm for lesions in the head-neck and 7.7 mm for lesions in the body-tail were observed. For MPD-involved IPMNs alone, threshold for lesions in the head-neck was close to that in the body-tail.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Ducts; Pancreatic Neoplasms; Head; Tomography, X-Ray Computed
PubMed: 36402960
DOI: 10.1186/s12876-022-02577-3 -
Journal of Gastrointestinal and Liver... Jun 2017Smaller endoscopes and catheters have been developed that permit direct visualization of the bile and pancreatic ducts (cholangioscopy and pancreatoscopy, respectively).... (Review)
Review
Smaller endoscopes and catheters have been developed that permit direct visualization of the bile and pancreatic ducts (cholangioscopy and pancreatoscopy, respectively). These endoscopes and catheters are passed through the working channel of a standard therapeutic duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). The SpyGlass Direct Visualization System (Boston Scientific Corp, Natick, MA, USA) is currently the most widely used and studied device. Cholangioscopy with intraductal lithotripsy has become an established modality in the treatment of difficult biliary lithiasis. When used in the evaluation of indeterminate biliary strictures by experienced endoscopists in recognizing intraductal pathology, it increases the diagnostic yield of tissue sampling. Pancreatoscopy is complementary to other imaging modalities in the evaluation of intraductal papillary mucinous neoplasms of the pancreas and is emerging as a sole or adjunctive therapy to extracorporeal shock wave lithotripsy for the treatment of main pancreatic duct stones. It remains investigational in the diagnosis of pancreatic adenocarcinoma. Complications specific to the performance of cholangiopancreatoscopy include cholangitis, which is related to intraductal fluid irrigation.
Topics: Bile Ducts; Biliary Tract Diseases; Cholangiopancreatography, Endoscopic Retrograde; Endoscopes; Endoscopy, Digestive System; Equipment Design; Humans; Pancreatic Diseases; Pancreatic Ducts; Predictive Value of Tests; Treatment Outcome
PubMed: 28617887
DOI: 10.15403/jgld.2014.1121.262.cho