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Theranostics 2021Recent studies have proven that the overall pathophysiology of pancreatitis involves not only the pancreatic acinar cells but also duct cells, however, pancreatic duct...
Recent studies have proven that the overall pathophysiology of pancreatitis involves not only the pancreatic acinar cells but also duct cells, however, pancreatic duct contribution in acinar cells homeostasis is poorly known and the molecular mechanisms leading to acinar insult and acute pancreatitis (AP) are unclear. Our previous work also showed that S100A9 protein level was notably increased in AP rat pancreas through iTRAQ-based quantitative proteomic analysis. Therefore, we investigated the actions of injured duct cells on acinar cells and the S100A9-related effects and mechanisms underlying AP pathology in the present paper. In this study, we constructed S100A9 knockout (s100a9) mice and an coculture system for pancreatic duct cells and acinar cells. Moreover, a variety of small molecular inhibitors of S100A9 were screened from ChemDiv through molecular docking and virtual screening methods. We found that the upregulation of S100A9 induces cell injury and inflammatory response via NLRP3 activation by targeting VNN1-mediated ROS release; and loss of S100A9 decreases AP injury and . Moreover, molecular docking and mutant plasmid experiments proved that S100A9 has a direct interaction with VNN1 through the salt bridges formation of Lys57 and Glu92 residues in S100A9 protein. We further found that compounds CHNO and CHFNOS can significantly improve AP injury and through inhibiting S100A9-VNN1 interaction. Our study showed the important regulatory effect of S100A9 on pancreatic duct injury during AP and revealed that inhibition of the S100A9-VNN1 interaction may be a key therapeutic target for this disease.
Topics: Acinar Cells; Amidohydrolases; Animals; Calgranulin B; Cell Line; GPI-Linked Proteins; Humans; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Docking Simulation; NLR Family, Pyrin Domain-Containing 3 Protein; Pancreatic Ducts; Pancreatitis; Reactive Oxygen Species; Small Molecule Libraries
PubMed: 33754072
DOI: 10.7150/thno.54245 -
Saudi Journal of Gastroenterology :... 2019Endoscopic transpapillary or transanastomotic pancreatic duct drainage (PD) is the mainstay of drainage in symptomatic pancreatic duct obstruction or leakage. However,... (Review)
Review
Endoscopic transpapillary or transanastomotic pancreatic duct drainage (PD) is the mainstay of drainage in symptomatic pancreatic duct obstruction or leakage. However, transpapillary or transanastomotic PD can be technically difficult due to the tight stricture or surgically altered anatomy (SAA), and endoscopic ultrasound (EUS)-guided PD (EUS-PD) is now increasingly used as an alternative technique. There are two approaches in EUS-PD: EUS-guided rendezvous (EUS-RV) and EUS-guided transmural drainage (EUS-TMD). In cases with normal anatomy, EUS-RV should be the first approach, whereas EUS-TMD can be selected in cases with SAA or duodenal obstruction. In our literature review, technical success and adverse event rates were 78.7% and 21.8%, respectively. The technical success rate of EUS-RV appeared lower than EUS-TMD due to the difficulty in guidewire passage. In future, development of dedicated devices and standardization of EUS-PD procedure are necessary.
Topics: Drainage; Endosonography; Humans; Pancreatic Diseases; Pancreatic Ducts; Surgery, Computer-Assisted
PubMed: 30632484
DOI: 10.4103/sjg.SJG_474_18 -
Abdominal Radiology (New York) Aug 2022Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic... (Review)
Review
Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic pathology. While often performed with endoscopy, pancreatic mass biopsy obtained via a percutaneous approach may serve as the only feasible option for diagnosis in patients with post-surgical anatomy, severe cardiopulmonary conditions, or prior non-diagnostic endoscopic attempts. Biopsy of pancreatic transplants are commonly performed percutaneously due to inaccessible location of the allograft by endoscopy, usually in the right lower quadrant or pelvis. Percutaneous drainage of collections in acute pancreatitis is primarily indicated for infection with clinical deterioration and may be performed alone or in combination with endoscopic drainage. Post-surgical pancreatic collections related to pancreatic duct fistula or leak also often warrant therapeutic percutaneous drainage. Knowledge of appropriate indications, strategies of approach, technique, and complications associated with these procedures is critical for a successful clinical practice.
Topics: Acute Disease; Biopsy; Drainage; Endoscopy, Gastrointestinal; Humans; Pancreas; Pancreatic Ducts; Pancreatitis; Treatment Outcome
PubMed: 34410433
DOI: 10.1007/s00261-021-03244-z -
Gut Sep 2022
Topics: Cholangiopancreatography, Endoscopic Retrograde; Humans; Pancreatic Ducts; Pancreatic Neoplasms
PubMed: 33963040
DOI: 10.1136/gutjnl-2021-324335 -
HPB : the Official Journal of the... Aug 2021Pancreatic duct disruption or disconnection is a potentially severe complication of necrotizing pancreatitis. With no existing treatment guidelines, it is unclear...
BACKGROUND
Pancreatic duct disruption or disconnection is a potentially severe complication of necrotizing pancreatitis. With no existing treatment guidelines, it is unclear whether there is any consensus among experts in clinical practice. We evaluated current expert opinion regarding the diagnosis and treatment of pancreatic duct disruption and disconnection in an international case vignette study.
METHODS
An online case vignette survey was sent to 110 international expert pancreatologists. Expert selection was based on publications in the last 5 years and/or participation in development of IAP/APA and ESGE guidelines on acute pancreatitis. Consensus was defined as agreement by at least 75% of the experts.
RESULTS
The response rate was 51% (n = 56). Forty-four experts (79%) obtained a MRI/MRCP and 52 experts (93%) measured amylase levels in percutaneous drain fluid to evaluate pancreatic duct integrity. The majority of experts favored endoscopic transluminal drainage for infected (peri)pancreatic necrosis and pancreatic duct disruption (84%, n = 45) or disconnection (88%, n = 43). Consensus was lacking regarding the treatment of patients with persistent percutaneous drain production, and with persistent sterile necrosis.
CONCLUSION
This international survey of experts demonstrates that there are many areas for which no consensus existed, providing clear focus for future investigation.
Topics: Acute Disease; Drainage; Humans; Pancreatic Ducts; Pancreatitis, Acute Necrotizing
PubMed: 33541807
DOI: 10.1016/j.hpb.2020.11.1148 -
Nagoya Journal of Medical Science Feb 2012HCO3- -rich fluid in the pancreatic juice (2-3 L/day) is secreted by epithelial cells lining the pancreatic duct tree, while digestive enzymes are secreted by acinar... (Review)
Review
HCO3- -rich fluid in the pancreatic juice (2-3 L/day) is secreted by epithelial cells lining the pancreatic duct tree, while digestive enzymes are secreted by acinar cells with a small amount of Cl- -rich fluid. Ductal HCO3- secretion is not only regulated by gastrointestinal hormones and cholinergic nerves but is also influenced by luminal factors: intraductal pressure, Ca2+ concentration, pathological activation of protease and bile reflux. The maximum HCO3- concentration of the juice under secretin stimulation reaches 140-150 mM. Thus pancreatic duct cells secrete HCO3- against a approximately 7-fold concentration gradient. HCO3- secretion critically depends on the activity of CFTR, a cAMP-dependent anion channel localized in the apical membrane of various epithelia. In the proximal part of pancreatic ducts close to acinar cells HCO3 secretion across the apical membrane is largely mediated by SLC26A6 CI- -HCO3- exchanger. In distal ducts where the luminal HCO3- concentration is already high, most of the HCO3- secretion is mediated by HCO3- conductance of CFTR. CFTR is the causative gene for cystic fibrosis. Loss of function due to severe mutations in both alleles causes typical cystic fibrosis characterized by dehydrated, thick, and viscous luminal fluid/mucus in the respiratory and gastrointestinal tract, pancreatic duct, and vas deferens. A compound heterozygote of mutations/polymorphisms (causing a mild dysfunction of CFTR) involves a risk of developing CFTR-related diseases such as chronic pancreatitis. In cystic fibrosis and certain cases of chronic pancreatitis, the pancreatic duct epithelium secretes a small amount of fluid with neutral-acidic pH, which causes an obstruction of the duct lumen by a protein plug or viscous mucus.
Topics: Animals; Bicarbonates; Biological Transport, Active; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Ethanol; Glucose; Humans; Pancreatic Diseases; Pancreatic Ducts; Pancreatic Juice
PubMed: 22515107
DOI: No ID Found -
World Journal of Gastroenterology Oct 2011Extraction of large pancreatic and common bile duct (CBD) calculi has always challenged the therapeutic endoscopist. Extracorporeal shockwave lithotripsy (ESWL) is an... (Review)
Review
Extraction of large pancreatic and common bile duct (CBD) calculi has always challenged the therapeutic endoscopist. Extracorporeal shockwave lithotripsy (ESWL) is an excellent tool for patients with large pancreatic and CBD calculi that are not amenable to routine endotherapy. Pancreatic calculi in the head and body are targeted by ESWL, with an aim to fragment them to < 3 mm diameter so that they can be extracted by subsequent endoscopic retrograde cholangiopancreatography (ERCP). In our experience, complete clearance of the pancreatic duct was achieved in 76% and partial clearance in 17% of 1006 patients. Short-term pain relief with reduction in the number of analgesics ingested was seen in 84% of these patients. For large CBD calculi, a nasobiliary tube is placed to help target the calculi, as well as bathe the calculi in saline - a simple maneuver which helps to facilitate fragmentation. The aim is to fragment calculi to < 5 mm size and clear the same during ERCP. Complete clearance of the CBD was achieved in 84.4% of and partial clearance in 12.3% of 283 patients. More than 90% of the patients with pancreatic and biliary calculi needed three or fewer sessions of ESWL with 5000 shocks being delivered at each session. The use of epidural anesthesia helped in reducing patient movement. This, together with the better focus achieved with newer third-generation lithotripters, prevents collateral tissue damage and minimizes the complications. Complications in our experience with nearly 1300 patients were minimal, and no extension of hospital stay was required. Similar rates of clearance of pancreatic and biliary calculi with minimal adverse effects have been reported from the centers where ESWL is performed regularly. In view of its high efficiency, non-invasive nature and low complication rates, ESWL can be offered as the first-line therapy for selected patients with large pancreatic and CBD calculi.
Topics: Calculi; Female; Gallstones; Humans; Lithotripsy; Male; Pancreatic Diseases; Pancreatic Ducts; Treatment Outcome
PubMed: 22110261
DOI: 10.3748/wjg.v17.i39.4365 -
Polski Przeglad Chirurgiczny Feb 2021Postoperative pancreatic fistula is associated with high morbidity and mortality. Studies have reported internal stenting of the pancreaticojejunostomy anastomosis to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postoperative pancreatic fistula is associated with high morbidity and mortality. Studies have reported internal stenting of the pancreaticojejunostomy anastomosis to reduce postoperative pancreatic fistula, but it is still controversial.
MATERIALS AND METHODS
Fifty patients undergoing elective pancreaticoduodenectomy, were included. Patients were divided into 2 groups in randomized fashion; Group A (n-25) without internal stenting across the pancreaticojejunostomy anastomosis and Group B (n-25) with internal stenting of the pancreaticojejunostomy anastomosis. Primary endpoint was the occurrence of postoperative pancreatic fistula.
RESULT
Both the groups were comparable in demographics, co morbidities, pathologies, pancreatic texture and pancreatic duct diameter. Out of 50 patients studied, total 23(46.0%) patients developed postoperative pancreatic fistula. Ten (40%) in group A and 13 (52%) in group B (p 0.156). Sixteen patients (32%) developed Grade A and 7 (14%) patients had Grade B postoperative pancreatic fistula. In group A, 6 patients developed grade A and 4 patients developed grade B postoperative pancreatic fistula. In group B, 10 patients developed grade A and 3 patients developed grade B postoperative pancreatic fistula. There was no Grade C fistula. All patients had satisfactory recovery on conservative management. Eight patients (16%) developed delayed gastric emptying [5 in group A and 3 in group B; p-0.366]. Six patients developed superficial surgical site infection (2 in group A and 4 in group B; p-0.445). The length of hospital stay was comparable in two groups. There was no mortality.
CONCLUSION
Internal stenting of pancreaticojejunostomy anastomosis does not decrease the rate of postoperative pancreatic fistula after pancreaticoduodenectomy.
Topics: Anastomosis, Surgical; Humans; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications
PubMed: 33949332
DOI: 10.5604/01.3001.0014.7225 -
PloS One 2023Although main pancreatic duct dilatation and pancreatic cysts are risk factors for developing pancreatic cancer, limited data exist regarding these findings in relatives...
Although main pancreatic duct dilatation and pancreatic cysts are risk factors for developing pancreatic cancer, limited data exist regarding these findings in relatives and spouses of pancreatic cancer patients. The frequency of these findings was examined using long-term follow-up data and transabdominal ultrasonography focusing on the pancreas. We prospectively enrolled 184 relatives and spouses of pancreatic cancer patients and performed special pancreatic ultrasonography to detect main pancreatic duct dilatation and pancreatic cysts. First-degree relatives (148 participants) of patients with pancreatic cancer were significantly younger than the spouses (36 participants; 41 vs. 65 years old). The frequency of ultrasonographic findings was significantly different between the relative (8.8%) and spouse (33.3%) groups. Main pancreatic duct dilatation and pancreatic cysts were observed in seven (4.7%) and seven (4.7%) participants in the relative group, and in nine (25.0%) and five (13.9%) participants in the spouse group, respectively. On multivariate analysis, age was an independent risk factor for the ultrasonographic findings. The frequency of ultrasonographic findings was significantly higher in spouses than in first-degree relatives of patients with pancreatic cancer and was strongly influenced by the age gap between the groups. Main pancreatic duct dilatation was frequently observed, especially in the spouse group.
Topics: Humans; Aged; Spouses; Dilatation; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatic Cyst; Gastrointestinal Diseases; Dilatation, Pathologic
PubMed: 36630426
DOI: 10.1371/journal.pone.0280403 -
Clinical and Translational... Feb 2022Disconnected pancreatic duct syndrome (DPDS) is a recognized complication of necrotizing pancreatitis (NP). Manifestations include recurrent peripancreatic fluid...
INTRODUCTION
Disconnected pancreatic duct syndrome (DPDS) is a recognized complication of necrotizing pancreatitis (NP). Manifestations include recurrent peripancreatic fluid collections (R-PFC) and pancreatocutaneous fistulae (PC-Fistulae). Pancreatitis of the disconnected pancreatic segment (DPDS-P) and its relationship to new-onset diabetes after pancreatitis (NODAP) are not well characterized.
METHODS
We performed a retrospective cohort study of consecutive patients with NP admitted to University of California, San Francisco from January 2011 to June 2019. A diagnosis of a disconnected pancreatic duct (PD) was confirmed using computed tomography and magnetic resonance cholangiopancreatography/endoscopic retrograde cholangiopancreatography. DPDS was defined as a disconnected PD presenting with R-PFC, PC-Fistulae, or DPDS-P. The primary outcome was NODAP, defined as diabetes mellitus (DM) occurring >3 months after NP. Cox proportional hazards regression was used to evaluate the relationship between DPDS and NODAP.
RESULTS
Of 171 patients with NP in this study, the mean clinical follow-up was 46 ± 18 months and the imaging follow-up was 38 ± 20 months. Twenty-seven patients (16%) developed DPDS-P at a median of 28 months. New-onset DM occurred in 54 of the 148 patients (36%), with 22% developing DM within 3 months of NP and 14% developing NODAP at a median of 31 months after AP. DPDS-P was associated with NODAP when compared with non-DPDS patients (adjusted hazard ratio 5.63 95% confidence interval: 1.69-18.74, P = 0.005) while R-PFCs and PC-Fistulae were not.
DISCUSSION
DPDS and NODAP occurred in 28% and 14% of the patients, respectively. Pancreatitis of the disconnected pancreas occurred in 16% of the patients and was associated with higher rates of NODAP when compared with patients with other manifestations of DPDS and patients without DPDS.
Topics: Diabetes Mellitus; Drainage; Humans; Pancreas; Pancreatic Ducts; Pancreatitis; Retrospective Studies; Treatment Outcome
PubMed: 35060942
DOI: 10.14309/ctg.0000000000000457