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HPB : the Official Journal of the... Aug 2020Pancreatic duct occlusion (PDO) without anastomosis is a technique proposed to mitigate the clinical consequences of postoperative pancreatic fistulas (POPF) after... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic duct occlusion (PDO) without anastomosis is a technique proposed to mitigate the clinical consequences of postoperative pancreatic fistulas (POPF) after pancreaticoduodenectomy. The aim of this study was to appraise the morbidity following PDO through a systematic review and meta-analysis.
METHODS
A systematic search of MEDLINE, Embase, and Web Of Science identified studies reporting outcomes of PDO following pancreaticoduodenectomy. Pooled prevalence rates of postoperative complications and mortality were computed using random-effect modeling. Meta-regression analyses were performed to examine the impact of moderators on the overall estimates.
RESULTS
Sixteen studies involving 1000 patients were included. Pooled postoperative mortality was 2.7%. A POPF was reported in 29.7% of the patients. Clinically relevant POPFs occurred in 13.5% of the patients, while intra-abdominal abscess and haemorrhages occurred in 6.7% and 5.5% of the patients, respectively. Re-operation was necessary in 7.6% of the patients. Postoperatively new onset diabetes occurred in 15.8% of patients, more frequently after the use of chemical substances for PDO (p = 0.003).
CONCLUSIONS
PDO is associated with significant morbidity including new onset of post-operative diabetes. The risk of new onset post-operative diabetes is associated with the use of chemical substance for PDO. Further evidence is needed to evaluate the potential benefits of PDO in patients at high risk of POPF.
Topics: Anastomosis, Surgical; Humans; Morbidity; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications
PubMed: 32471694
DOI: 10.1016/j.hpb.2020.04.014 -
STAR Protocols Dec 2021The recapitulation of human developmental processes and pathological manifestations requires access to specific cell types and precursor stages during embryogenesis and...
The recapitulation of human developmental processes and pathological manifestations requires access to specific cell types and precursor stages during embryogenesis and disease. Here, we describe a scalable differentiation protocol to guide human pluripotent stem cells stepwise into pancreatic duct-like organoids. The protocol mimics pancreatic duct development and was successfully used to model the onset and progression of pancreatic ductal adenocarcinoma; the approach is suitable for multiple downstream applications. However, the protocol is cost- and time-intensive. For complete details on the use and execution of this protocol, please refer to Breunig et al. (2021).
Topics: Cell Culture Techniques; Cell Differentiation; Cell Line; Humans; Organoids; Pancreatic Ducts; Pluripotent Stem Cells
PubMed: 34917972
DOI: 10.1016/j.xpro.2021.100913 -
British Journal of Pharmacology Jul 2022The volume regulated anion channel (VRAC) is known to be involved in different aspects of cancer cell behaviour and response to therapies. For this reason, we...
BACKGROUND AND PURPOSE
The volume regulated anion channel (VRAC) is known to be involved in different aspects of cancer cell behaviour and response to therapies. For this reason, we investigated the effect of DCPIB, a presumably specific blocker of VRAC, in two types of cancer: pancreatic duct adenocarcinoma (PDAC) and melanoma.
EXPERIMENTAL APPROACH
We used patch-clamp electrophysiology, supported by Ca imaging, gene expression analysis, docking simulation and mutagenesis. We employed two PDAC lines (Panc-1 and MiaPaCa-2), as well as a primary (IGR39) and a metastatic (IGR37) melanoma line.
KEY RESULTS
DCPIB markedly increased whole-cell currents in Panc-1, MiaPaca2 and IGR39, but not in IGR37 cells. The currents were mostly mediated by K 1.1 channels, commonly known as BK channels. We confirmed DCPIB activation of BK channels also in HEK293 cells transfected with α subunits of this channel. Further experiments showed that in IGR39, and to a smaller degree also in Panc-1 cells, DCPIB induced a rapid Ca influx. This, in turn, indirectly potentiated BK channels and, in IGR39 cells, additionally activated other Ca -dependent channels. However, Ca influx was not required for activation of BK channels by DCPIB, as such activation involved the extracellular part of the protein and we have identified a residue crucial for binding.
CONCLUSION AND IMPLICATIONS
DCPIB directly targeted BK channels and, also, acutely increased intracellular Ca . Our findings extend the list of DCPIB effects that should be taken into consideration for future development of DCPIB-based modulators of ion channels and other membrane proteins.
Topics: Adenocarcinoma; Anions; HEK293 Cells; Humans; Large-Conductance Calcium-Activated Potassium Channels; Melanoma; Pancreatic Ducts
PubMed: 35102550
DOI: 10.1111/bph.15810 -
BMJ Case Reports Nov 2016Disconnected pancreatic duct syndrome is a circumferential interruption of the pancreatic duct. It usually occurs secondary to pancreatitis and carries significant... (Review)
Review
Disconnected pancreatic duct syndrome is a circumferential interruption of the pancreatic duct. It usually occurs secondary to pancreatitis and carries significant diagnostic and management challenges. We present a case of disconnected pancreatic duct syndrome that represented a diagnostic and management dilemma for both medical and surgical teams. The aim of this article is to share a successful management experience of disconnected pancreatic duct syndrome with other physicians and to perform a brief but focused literature review on this challenging condition.
Topics: Abdominal Pain; Adult; Humans; Male; Necrosis; Pancreas; Pancreatic Ducts; Pancreatitis, Alcoholic; Patient Care Team; Syndrome
PubMed: 27803085
DOI: 10.1136/bcr-2016-217099 -
BMC Gastroenterology Aug 2022No previous studies have examined the possible relationship between intraductal papillary mucinous neoplasm (IPMN) and the developmental ductal variations of the...
BACKGROUND
No previous studies have examined the possible relationship between intraductal papillary mucinous neoplasm (IPMN) and the developmental ductal variations of the pancreas, such as an ansa pancreatica and a meandering main pancreatic duct (MMPD).
METHODS
This retrospective cross-sectional study enrolled 214 patients, 108 with IPMN disease and 106 subjects from a community at the tertiary care unit. The main pancreatic duct (MPD) was evaluated in the head of the pancreas by its course, which were non-MMPD: descending, vertical, and sigmoid, or MMPD including loop types, reverse-Z subtypes, and an N-shape, which was identified for the first time in this study. IPMN patients were also evaluated for worrisome features (WF) or high-risk stigmata (HRS), and the extent of IPMN cysts.
RESULTS
Among IPMN patients, 18.4% had MMPD, which we observed in only 3.0% of the control group (P < 0.001). Patients with MMPD were more likely to belong to the IPMN group compared with non-MMPD patients [odds ratio (OR) 6.4, 95% confidence interval (CI) 2.2-24.9]. Compared with a descending shape MPD, IPMN patients with an N-shaped MPD were more likely to have a cystic mural nodule (OR 5.9, 95% CI 1.02-36.0). The presence of ansa pancreatica associated with more extent IPMN disease (OR 12.8, 95% CI 2.6-127.7).
CONCLUSIONS
IPMN patients exhibited an MMPD more often than control patients. Ansa pancreatica associated with multiple cysts. Furthermore, an N-shape in IPMN patients associated with cystic mural nodules, suggesting that this shape serves as a risk factor for more severe IPMN.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Cross-Sectional Studies; Cysts; Digestive System Abnormalities; Humans; Pancreas; Pancreatic Ducts; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Retrospective Studies
PubMed: 35989322
DOI: 10.1186/s12876-022-02465-w -
Pflugers Archiv : European Journal of... Mar 2023Mechanisms of synergistic agonist stimulation and modulation of the electrochemical driving force for anion secretion are still not fully explored in human pancreatic...
Mechanisms of synergistic agonist stimulation and modulation of the electrochemical driving force for anion secretion are still not fully explored in human pancreatic duct epithelial cells. The first objective of this study was therefore to test whether combined agonist stimulation augments anion transport responses in the Capan-1 monolayer model of human pancreatic duct epithelium. The second objective was to test the influence of H,K-ATPase inhibition on anion transport in Capan-1 monolayers. The third objective was to analyze the expression and function of K channels in Capan-1, which could support anion secretion and cooperate with H,K-ATPases in pH and potassium homeostasis. The human pancreatic adenocarcinoma cell line Capan-1 was cultured conventionally or as polarized monolayers that were analyzed by Ussing chamber electrophysiological recordings. Single-cell intracellular calcium was assayed with Fura-2. mRNA isolated from Capan-1 was analyzed by use of the nCounter assay or RT-PCR. Protein expression was assessed by immunofluorescence and western blot analyses. Combined stimulation with different physiological agonists enhanced anion transport responses compared to single agonist stimulation. The responsiveness of Capan-1 cells to histamine was also revealed in these experiments. The H,K-ATPase inhibitor omeprazole reduced carbachol- and riluzole-induced anion transport responses. Transcript analyses revealed abundant TASK-2, TWIK-1, TWIK-2, TASK-5, K, and KCNQ1 mRNA expression. KCNE1 mRNA and TREK-1, TREK-2, TASK-2, and KCNQ1 protein expression were also shown. This study shows that the Capan-1 model recapitulates key physiological aspects of a bicarbonate-secreting epithelium and constitutes a valuable model for functional studies on human pancreatic duct epithelium.
Topics: Humans; Adenocarcinoma; Pancreatic Neoplasms; Pancreatic Ducts; Epithelial Cells; Bicarbonates; RNA, Messenger; Adenosine Triphosphatases
PubMed: 36534232
DOI: 10.1007/s00424-022-02782-9 -
Journal of Veterinary Internal Medicine Jul 2021In human medicine, congenital maljunction of the common bile duct (CBD) and main pancreatic duct (MPD), or pancreatobiliary maljunction (PBM), is a known cause of...
BACKGROUND
In human medicine, congenital maljunction of the common bile duct (CBD) and main pancreatic duct (MPD), or pancreatobiliary maljunction (PBM), is a known cause of cholecystitis.
OBJECTIVE
Pancreatic enzyme activity in the bile (a diagnostic marker for PBM) of healthy cats was measured to determine normal values and evaluate its relationship with biliary morphology.
ANIMALS
Fifty-two healthy cats.
METHODS
Cross-sectional study of the biliary tracts of healthy cats during laparoscopic ovariohysterectomy and measurement of pancreatic enzyme activity in bile. The cats were divided into groups A and B based on the ratio of the diameter of the cystic duct (CD) to the CBD. The normal ratio was 3.4. Pancreatic enzyme activity in bile was compared between the groups.
RESULTS
The CBDs were straight in all cases, whereas the CDs were variably tortuous or dilated. Amylase activity in the bile (median, <100 U/L; range, <100-591 U/L) was lower than in serum in all cases, and group B, which had a CD/CBD ratio >3.4, had significantly higher amylase activity (median, 109 U/L; range, <100-591 U/L) in the bile than did group A (median, <100 U/L; range, <100-238 U/L), which had a CD/CBD ratio <3.4 (P = .0009).
CONCLUSIONS AND CLINICAL IMPORTANCE
The results suggest that a dilated CD is associated with reflux of pancreatic juice. In the future, it will be necessary to examine the clinical usefulness of these findings by measuring pancreatic enzyme activity in the bile of cats with cholangitis.
Topics: Animals; Bile; Bile Ducts; Cats; Common Bile Duct; Cross-Sectional Studies; Pancreas; Pancreatic Ducts
PubMed: 34117814
DOI: 10.1111/jvim.16196 -
Cancer Medicine Jun 2021Determination of the primary tumor in periampullary region carcinomas can be difficult, and the pathological assessment and clinicopathological characteristics remain...
Determination of the primary tumor in periampullary region carcinomas can be difficult, and the pathological assessment and clinicopathological characteristics remain elusive. In this study, we investigated the current recognition and practices for periampullary region adenocarcinoma with an indeterminable origin among expert pathologists through a cognitive survey. Simultaneously, we analyzed a prospective collection of cases with an indeterminable primary tumor diagnosed from 2008 to 2018 to elucidate their clinicopathological features. All cases with pathological indeterminable primary tumors were reported and discussed in a clinicopathological conference to elucidate if it was possible to distinguish the primary tumor clinically and pathologically. From the cognitive survey, over 85% of the pathologists had experienced cases with indeterminable primary tumors; however, 70% of the cases was reported as pancreatic cancer without definitive grounds. Interpretation of the main tumor mass varied, and no standardized method was developed to determine the primary tumor. During a prospective study, 42 of the 392 periampullary carcinoma cases (10.7%) were considered as tumors with a pathological indeterminable origin. After the clinicopathological conferences, 21 (5.4%) remained indeterminable and were considered final indeterminable cases. Histological studies showed that the tumors spread along both the bile duct and main pancreatic duct; this was the most representative finding of the final indeterminable cases. This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin. Adequate assessment of primary tumors in periampullary region carcinomas will help to optimize epidemiological data of pancreatic and bile duct cancer.
Topics: Adenocarcinoma; Aged; Ampulla of Vater; Bile Ducts; Common Bile Duct Neoplasms; Female; Humans; Male; Neoplasms, Unknown Primary; Pancreatectomy; Pancreatic Ducts; Pancreatic Neoplasms; Prospective Studies; Surveys and Questionnaires
PubMed: 34008914
DOI: 10.1002/cam4.3809 -
Annals of Surgery May 2015To describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) with predominant involvement of the main pancreatic duct (MPD), analyzing predictors...
OBJECTIVES
To describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) with predominant involvement of the main pancreatic duct (MPD), analyzing predictors for survival and recurrence.
BACKGROUND
IPMNs involving the MPD harbor a high likelihood of malignancy and different biological features. The appropriateness of including cases with minimal noncircumferential MPD involvement has been challenged because these show clinicopathological features that are similar to branch duct IPMN. Accordingly, their exclusion has led to a redefinition of MPD IPMN (MD-IPMN).
METHODS
Retrospective review of resected MD-IPMN from 1990 to 2013. All slides were reviewed by a single pancreatic pathologist and classified on the basis of epithelial type and invasive component.
RESULTS
A total of 223 patients underwent resection for IPMN involving the MPD. Of these, 50 were excluded because of minimal MPD involvement. Among the 173 patients analyzed, median age was 68 years and 55% were males. Predominant epithelial phenotype was intestinal (50%). Forty-eight patients (28%) had low- or intermediate-grade dysplasia, whereas 125 (72%) had either high-grade dysplasia (33%) or invasive carcinoma (39%). Of the 67 invasive IPMNs, 39 were tubular carcinomas (58%) and invasion was minimal (<5 mm) in 28 (42%). The 5-year overall survival rate was 69% and the disease-specific survival rate was 83%. The estimated recurrence rate at 10 years was 25%. Size and type of the invasive component, lymph node positivity, and a positive resection margin were predictors for both survival and recurrence (P < 0.05).
CONCLUSIONS
MD-IPMN is mainly intestinal-type and malignant. After resection, it has a very favorable prognosis, especially in the absence of macroscopic invasive carcinoma.
Topics: Adenocarcinoma, Mucinous; Aged; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Disease-Free Survival; Humans; Lymph Nodes; Male; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Recurrence, Local; Pancreatic Ducts; Retrospective Studies; Survival Rate
PubMed: 24979607
DOI: 10.1097/SLA.0000000000000813 -
Pancreas Aug 2014The aim of this study was to determine whether radiofrequency ablation (RFA) of the pancreas and subsequent transection of the main pancreatic duct may avoid the risk of...
OBJECTIVE
The aim of this study was to determine whether radiofrequency ablation (RFA) of the pancreas and subsequent transection of the main pancreatic duct may avoid the risk of both necrotizing pancreatitis and postoperative pancreatic fistula (POPF) formation.
METHODS
Thirty-two rats were subjected to RFA and section of the pancreas over their portal vein. Animals were killed at 3, 7, 15, and 21 days (groups 0-3, respectively). Two additional control groups (sham operation and user manipulation only, respectively) of 15 days of postoperative period were considered. Postoperative complications, histological changes (including morphometric and immunohistochemical analysis), and incidence of POPF were evaluated.
RESULTS
A significant increase in serum amylase levels (P < 0.05) on the third postoperative day, which return to baseline levels in the following weeks, was noted in groups 0 to 3. Those groups showed a rapid atrophy of the distal pancreas by apoptosis with no signs of necrotizing pancreatitis or POPF. The distal pancreas in groups 1 to 3 compared with group 0 and control groups showed a significant increase of small islets (<1000 µm).
CONCLUSIONS
The rapid acinar atrophy of the distal pancreas after RFA and section of the pancreatic ducts in this model does not lead to necrotizing pancreatitis.
Topics: Animals; Catheter Ablation; Female; Immunohistochemistry; Insulin; Pancreas; Pancreatic Ducts; Pancreatic Fistula; Pancreatitis, Acute Necrotizing; Portal Vein; Postoperative Complications; Rats, Sprague-Dawley; Reproducibility of Results; Treatment Outcome
PubMed: 24977335
DOI: 10.1097/MPA.0000000000000156