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Cell Stem Cell Apr 2023Understanding the origin of pancreatic β cells has profound implications for regenerative therapies in diabetes. For over a century, it was widely held that adult...
Understanding the origin of pancreatic β cells has profound implications for regenerative therapies in diabetes. For over a century, it was widely held that adult pancreatic duct cells act as endocrine progenitors, but lineage-tracing experiments challenged this dogma. Gribben et al. recently used two existing lineage-tracing models and single-cell RNA sequencing to conclude that adult pancreatic ducts contain endocrine progenitors that differentiate to insulin-expressing β cells at a physiologically important rate. We now offer an alternative interpretation of these experiments. Our data indicate that the two Cre lines that were used directly label adult islet somatostatin-producing ∂ cells, which precludes their use to assess whether β cells originate from duct cells. Furthermore, many labeled ∂ cells, which have an elongated neuron-like shape, were likely misclassified as β cells because insulin-somatostatin coimmunolocalizations were not used. We conclude that most evidence so far indicates that endocrine and exocrine lineage borders are rarely crossed in the adult pancreas.
Topics: Insulin-Secreting Cells; Evidence Gaps; Cell Differentiation; Pancreas; Pancreatic Ducts; Insulin; Somatostatin
PubMed: 37028408
DOI: 10.1016/j.stem.2023.03.003 -
Gut and Liver Nov 2016Pancreatolithiasis, or pancreatic calculi (PC), is a sequel of chronic pancreatitis (CP) and may occur in the main ducts, side branches or parenchyma. Calculi are the... (Review)
Review
Pancreatolithiasis, or pancreatic calculi (PC), is a sequel of chronic pancreatitis (CP) and may occur in the main ducts, side branches or parenchyma. Calculi are the end result, irrespective of the etiology of CP. PC contains an inner nidus surrounded by successive layers of calcium carbonate. These calculi obstruct the pancreatic ducts and produce ductal hypertension, which leads to pain, the cardinal feature of CP. Both endoscopic therapy and surgery aim to clear these calculi and decrease ductal hypertension. In small PC, endoscopic retrograde cholangiopancreatography (ERCP) followed by sphincterotomy and extraction is the treatment of choice. Large calculi require fragmentation by extracorporeal shock wave lithotripsy (ESWL) prior to their extraction or spontaneous expulsion. In properly selected cases, ESWL followed by ERCP is the standard of care for the management of large PC. Long-term outcomes following ESWL have demonstrated good pain relief in approximately 60% of patients. However, ESWL has limitations. Per oral pancreatoscopy and intraductal lithotripsy represent techniques in evolution, and in current practice their use is limited to centers with considerable expertise. Surgery should be offered to all patients with extensive PC, associated multiple ductal strictures or following failed endotherapy.
Topics: Calculi; Cholangiopancreatography, Endoscopic Retrograde; Constriction, Pathologic; Humans; Lithotripsy; Pancreas; Pancreatic Ducts; Pancreatitis, Chronic; Sphincterotomy, Endoscopic; Treatment Outcome
PubMed: 27784844
DOI: 10.5009/gnl15555 -
Journal of Visceral Surgery Aug 2016Pancreatic trauma (PT) is associated with high morbidity and mortality; the therapeutic options remain debated.
INTRODUCTION
Pancreatic trauma (PT) is associated with high morbidity and mortality; the therapeutic options remain debated.
MATERIAL AND METHODS
Retrospective study of PT treated in the University Hospital of Grenoble over a 22-year span. The decision for initial laparotomy depended on hemodynamic status as well as on associated lesions. Main pancreatic duct lesions were always searched for. PT lesions were graded according to the AAST classification.
RESULTS
Of a total of 46 PT, 34 were grades II or I. Hemodynamic instability led to immediate laparotomy in 18 patients, for whom treatment was always drainage of the pancreatic bed; morbidity was 30%. Eight patients had grade III injuries, six of whom underwent immediate operation: three underwent splenopancreatectomy without any major complications while the other three who had simple drainage required re-operation for peritonitis, with one death related to pancreatic complications. Four patients had grades IV or V PT: two pancreatoduodenectomies were performed, with no major complication, while one patient underwent duodenal reconstruction with pancreatic drainage, complicated by pancreatic and duodenal fistula requiring a hospital stay of two months. The post-trauma course was complicated for all patients with main pancreatic duct involvement. Our outcomes were similar to those found in the literature.
CONCLUSION
In patients with distal PT and main pancreatic duct involvement, simple drainage is associated with high morbidity and mortality. For proximal PT, the therapeutic options of drainage versus pancreatoduodenectomy must be weighed; pancreatoduodenectomy may be unavoidable when the duodenum is injured as well. Two-stage (resection first, reconstruction later) could be an effective alternative in the emergency setting when there are other associated traumatic lesions.
Topics: Abdominal Injuries; Adolescent; Adult; Aged; Combined Modality Therapy; Drainage; Female; Follow-Up Studies; Humans; Laparotomy; Male; Middle Aged; Pancreas; Pancreatectomy; Pancreatic Ducts; Pancreaticoduodenectomy; Retrospective Studies; Splenectomy; Tomography, X-Ray Computed; Trauma Severity Indices; Treatment Outcome; Young Adult
PubMed: 26995532
DOI: 10.1016/j.jviscsurg.2016.02.006 -
International Journal of Surgery... Dec 2016Duct-to-mucosa and invagination are two commonly used techniques of pancreaticojejunostomy (PJ) after pancreaticoduodenectomy. Previously, we conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Duct-to-mucosa and invagination are two commonly used techniques of pancreaticojejunostomy (PJ) after pancreaticoduodenectomy. Previously, we conducted a systematic review comparing the safety and efficacy of the two PJ techniques. Here, we added new evidence and updated our previous conclusion.
METHODS
We systematically searched multiple databases and included randomized controlled trials (RCTs) comparing duct-to-mucosa and invagination techniques of PJ. The quality of evidence was assessed using Jadad score, and reporting bias was evaluated using funnel plots. Meta-analysis was performed using a random-effects model. Risk ratio (RR) and 95% confidence interval (CI) were calculated. The primary outcome was pancreatic fistula, and the secondary outcomes included mortality, reoperation, morbidity and postoperative hospital stay. Trial sequential analysis was performed to calculate the required information size.
RESULTS
Seven RCTs with 850 participants were included. No significant difference was detected in the rates of pancreatic fistula (RR 0.98, 95% CI 0.63 to 1.53), mortality (RR 0.94, 95% CI 0.40 to 2.18), reoperation (RR 1.23, 95% CI 0.69 to 2.20) and morbidity (RR 0.98, 95% CI 0.82 to 1.16) between the two groups. However, patients who underwent duct-to-mucosa PJ had a significantly shorter postoperative hospital stay (mean difference -2.80, 95% CI -5.08 to -0.52). Trial sequential analysis showed that another 279 participants were needed for conclusive results.
CONCLUSIONS
Given the current evidence, duct-to-mucosa PJ did not decrease the rates of pancreatic fistula and other adverse events as compared to invagination PJ; however, it did reduce postoperative hospital stay. Further RCTs are needed.
Topics: Anastomosis, Surgical; Humans; Intestinal Mucosa; Length of Stay; Mortality; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications; Randomized Controlled Trials as Topic; Reoperation; Safety
PubMed: 27826046
DOI: 10.1016/j.ijsu.2016.11.008 -
International Journal of Molecular... Aug 2021The production of pancreatic β cells is the most challenging step for curing diabetes using next-generation treatments. Adult pancreatic endocrine cells are thought to...
The production of pancreatic β cells is the most challenging step for curing diabetes using next-generation treatments. Adult pancreatic endocrine cells are thought to be maintained by the self-duplication of differentiated cells, and pancreatic endocrine neogenesis can only be observed when the tissue is severely damaged. Experimentally, this can be performed using a method named partial duct ligation (PDL). As the success rate of PDL surgery is low because of difficulties in identifying the pancreatic duct, we previously proposed a method for fluorescently labeling the duct in live animals. Using this method, we performed PDL on neurogenin3 (Ngn3)-GFP transgenic mice to determine the origin of endocrine precursor cells and evaluate their potential to differentiate into multiple cell types. Ngn3-activated cells, which were marked with GFP, appeared after PDL operation. Because some GFP-positive cells were aligned proximally to the duct, we hypothesized that Ngn3-positive cells arise from the pancreatic duct. Therefore, we next developed an in vitro pancreatic duct culture system using Ngn3-GFP mice and examined whether Ngn3-positive cells emerge from this duct. We observed GFP expressions in ductal organoid cultures. GFP expressions were correlated with Ngn3 expressions and endocrine cell lineage markers. Interestingly, tuft cell markers were also correlated with GFP expressions. Our results demonstrate that in adult mice, Ngn3-positive endocrine precursor cells arise from the pancreatic ducts both in vivo and in vitro experiments indicating that the pancreatic duct could be a potential donor for therapeutic use.
Topics: Animals; Antigens, Differentiation; Basic Helix-Loop-Helix Transcription Factors; Green Fluorescent Proteins; Insulin-Secreting Cells; Mice; Mice, Transgenic; Nerve Tissue Proteins; Organoids; Pancreatic Ducts; Stem Cells
PubMed: 34445257
DOI: 10.3390/ijms22168548 -
Revista Espanola de Enfermedades... Sep 2023Due to low incidence rate of pancreatic duct stones,Authoritative consensus has not been reached regarding therapeutic choices in clinical practice. This article...
Due to low incidence rate of pancreatic duct stones,Authoritative consensus has not been reached regarding therapeutic choices in clinical practice. This article reports the treatment of a young woman with chronic pancreatitis complicated with refractory multiple pancreatic duct stones, which provides clinical experience for treatment and provides a new way to study the pathogenesis of chronic pancreatitis complicated with pancreatic duct stones.
Topics: Female; Humans; Pancreatic Ducts; Lithotripsy; Pancreatic Diseases; Pancreatitis, Chronic; Cholangiopancreatography, Endoscopic Retrograde
PubMed: 36562526
DOI: 10.17235/reed.2022.9378/2022 -
Frontiers in Immunology 2023Patients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the...
BACKGROUND
Patients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the latent impact of ubiquitination-related genes (URGs) on determining PDAC patients' prognoses.
METHODS
The URGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO) regression analysis of data from TCGA-PAAD. Verification analyses were conducted across TCGA-PAAD, GSE57495 and ICGC-PACA-AU to show the robustness of the signature. RT-qPCR was used to verify the expression of risk genes. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool.
RESULTS
The URGs signature, comprised of three genes, was developed and was shown to be highly correlated with the prognoses of PAAD patients. The nomogram was established by combining the URGs signature with clinicopathological characteristics. We discovered that the URGs signature was remarkably superior than other individual predictors (age, grade, T stage, et al). Also, the immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, and StromalScores were elevated in the low-risk group. The immune cells that infiltrated the tissues were different between the two groups, as did the expression of immune-related genes.
CONCLUSION
The URGs signature could act as the biomarker of prognosis and selecting appropriate therapeutic drugs for PDAC patients.
Topics: Humans; Prognosis; Carcinoma, Pancreatic Ductal; Ubiquitination; Pancreatic Neoplasms; Pancreatic Ducts; Tumor Microenvironment
PubMed: 37359528
DOI: 10.3389/fimmu.2023.1171811 -
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 -
Surgical Endoscopy May 2023Postoperative pancreatic fistula (POPF) is often associated with significant morbidity and mortality after the Whipple operation. Patient-related factors associated with...
BACKGROUND
Postoperative pancreatic fistula (POPF) is often associated with significant morbidity and mortality after the Whipple operation. Patient-related factors associated with POPF include soft pancreatic texture and a small main pancreatic duct (MPD). The traditional duct-to-mucosa anastomosis was modified to be easily performed. The aim of the study was to evaluate the simplified pancreaticojejunostomy (PJ) method in the prevention of POPF after minimally invasive pancreaticoduodenectomy (PD).
METHODS
Ninety-eight patients who underwent laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD) with a simplified PJ procedure containing only two duct-to-mucosa sutures and four penetrating-sutures to anastomose the pancreatic parenchyma and jejunal seromuscular layer in our center were retrospectively studied. Demographics and clinical short-term safety were assessed.
RESULTS
All LPD and RPD procedures were successfully performed. The median time of PJ was 17 min, and the median blood loss was 60 mL, with only one patient requiring transfusion. Four patients (4.1%) suffered from clinically relevant POPF (CR-POPF), including four grade B cases and no grade C cases. For patients with an MPD diameter of 3 mm or less, POPF was noted in two (4%) of the fifty patients, with all cases being grade B. Of the patients with a soft pancreas, only two (4.5%) patients suffered from grade B POPF. One patient (1.0%) experienced a 90-day mortality. Neither the main pancreatic diameter nor pancreatic texture had an impact on postoperative outcomes.
CONCLUSIONS
Our technique is a simple, safe and efficient alternative to prevent POPF after LPD and RPD. This method is suitable for almost all pancreatic conditions, including cases with a small main pancreatic duct and soft pancreas, and has the potential to become the preferred procedure in low-volume pancreatic surgery centers. Our modified duct-to-mucosa PJ, which contains only two duct-to-mucosa sutures and four penetrating-sutures to anastomose the pancreatic parenchyma and jejunal seromuscular layer, is ideal for small MPD and soft pancreas when performing minimally invasive PD and has a low rate of POPF. PJ pancreaticojejunostomy, MPD main pancreatic diameter, PD pancreaticoduodenectomy, POPF postoperative pancreatic fistula.
Topics: Humans; Pancreaticojejunostomy; Pancreaticoduodenectomy; Pancreatic Fistula; Retrospective Studies; Pancreas; Pancreatic Ducts; Anastomosis, Surgical; Postoperative Complications; Mucous Membrane
PubMed: 36624217
DOI: 10.1007/s00464-022-09830-6 -
European Review For Medical and... Nov 2023This study aimed to examine the factors linked to the development of clinically significant pancreatic fistulas following distal pancreatectomy (DP) and to assess the...
Effect of main pancreatic duct suture ligation on the prevention of clinically relevant pancreatic fistula after distal pancreatectomy: analysis of 82 consecutive patients.
OBJECTIVE
This study aimed to examine the factors linked to the development of clinically significant pancreatic fistulas following distal pancreatectomy (DP) and to assess the efficacy of suture ligation of the main pancreatic duct.
PATIENTS AND METHODS
A single-center retrospective study was performed on the medical records of 82 patients who underwent DP in our institution between January 2011 and December 2019.
RESULTS
There were 28 males (34.1%) and 54 females (65.9%). The patients' age ranged from 18 to 86 years (median: 55.5 years). Indications for DP included primary pancreatic disease (n=63, 76.8%) and non-pancreatic disease (n=19, 23.2%). Postoperative mortality and morbidity rates were 3.7% and 48%, respectively. Pancreatic parenchymal closure was accomplished by a hand-sewn technique or mechanical stapling in 89 and 13 patients, respectively. Identification of the pancreatic duct and suture ligation was performed in 46 patients (56.1%). Pancreatic fistula was developed in 20 patients (24.4%); 12 fistulas were classified as Grade B, and 8 as Grade C. Biochemical leaks (Grade A) were identified in 8 patients (9.8%). Multivariate analysis indicated that failure to ligate the main pancreatic duct was the only variable associated with an increased risk for pancreatic leak (p=0.031; odds ratio=0.233; 95% confidence interval, 0.062-0.879).
CONCLUSIONS
Pancreatic leak remains a common complication after DP. The incidence of leaks is reduced significantly when the main pancreatic duct is identified and directly ligated during DP.
Topics: Male; Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Pancreatic Fistula; Pancreatectomy; Retrospective Studies; Risk Factors; Pancreatic Ducts; Sutures
PubMed: 37975375
DOI: 10.26355/eurrev_202311_34328