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Endoscopic Ultrasound 2021EUS has opened a new frontier in endoscopic techniques for accessing pancreatic ducts in patients with failed ERCP. The major indications of EUS-guided pancreatic duct... (Review)
Review
EUS has opened a new frontier in endoscopic techniques for accessing pancreatic ducts in patients with failed ERCP. The major indications of EUS-guided pancreatic duct intervention (EUS-PDI) are main pancreatic duct (MPD) strictures due to chronic pancreatitis or strictures of pancreaticojejunal or pancreaticogastric anastomosis after Whipple resection, which lead to recurrent acute pancreatitis. EUS-guided pancreaticogastro or duodenostomy offers an alternative to surgery when transpapillary drainage fails or is not possible. We provide an expert commentary and a brief overview on this relatively novel technique utilizing EUS-PDI creation in patients with impaired drainage of the MPD who have failed other conventional endoscopic techniques for MPD drainage and either are poor surgical candidates or are reluctant to undergo surgery.
PubMed: 33463554
DOI: 10.4103/eus.eus_67_20 -
Revista Espanola de Enfermedades... Mar 2021Direct endoscopic visualization of biliary and pancreatic ducts represents one step further in the journey of digestive endoscopy. It allows the identification of...
Direct endoscopic visualization of biliary and pancreatic ducts represents one step further in the journey of digestive endoscopy. It allows the identification of lesions that were previously attainable through indirect means. Directed biopsy taking has permitted a better characterization of the lesions. The use of power sources through the cholangiopancreatoscope means that it is now possible to fragment and remove refractory lithiases using traditional endoscopic systems. This document aims to define the advisable workflow when using a single-use, flexible cholangiopancreatoscope with the commercial name of SpyGlass®. Penning a set of guidelines to provide instructions on the technique, as well as tips and tricks related with the operation of these endoscopes will be a useful resource.
Topics: Biliary Tract Diseases; Cholangiopancreatography, Endoscopic Retrograde; Endoscopy, Digestive System; Equipment Design; Humans; Pancreatic Ducts
PubMed: 33267604
DOI: 10.17235/reed.2020.7531/2020 -
Cell Stem Cell Jun 2021In this issue of Cell Stem Cell, Huang et al. (2021) and Breunig et al. (2021) developed human stem-cell-derived organoid culture systems to recapitulate pancreatic...
In this issue of Cell Stem Cell, Huang et al. (2021) and Breunig et al. (2021) developed human stem-cell-derived organoid culture systems to recapitulate pancreatic acinar and ductal lineages. This provides opportunities to study cellular plasticity and transformation in pancreatic cancer initiation and progression.
Topics: Acinar Cells; Humans; Organoids; Pancreas; Pancreas, Exocrine; Pancreatic Ducts; Pancreatic Neoplasms; Pluripotent Stem Cells
PubMed: 34087158
DOI: 10.1016/j.stem.2021.05.006 -
Clinical Cancer Research : An Official... Oct 2021Metabolic reprogramming and cancer stem cells drive the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). However, the metabolic and stemness programs of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Metabolic reprogramming and cancer stem cells drive the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). However, the metabolic and stemness programs of pancreatic precursor lesions (PPL), considered early PDAC development events, have not been thoroughly explored.
EXPERIMENTAL DESIGN
Meta-analyses using gene expression profile data from NCBI Gene Expression Omnibus and IHC on tissue microarrays (TMA) were performed. The following animal and cellular models were used: cerulean-induced KrasG12D; Pdx1 Cre (KC) acinar-to-ductal metaplasia (ADM) mice, KrasG12D; Smad4Loss; Pdx-1 Cre (KCSmad4-) intraductal papillary mucinous neoplasm (IPMN) mice, LGKC1 cell line derived from the doxycycline-inducible Gnas IPMN model, and human IPMN organoids. Flow cytometry, Seahorse extracellular flux analyzer, qRT-PCR, and sphere assay were used to analyze metabolic and stemness features. SR18292 was used to inhibit PGC1α, and short hairpin RNA was used to knockdown (KD) PGC1α.
RESULTS
The meta-analysis revealed a significant upregulation of specific stemness genes in ADM-mediated pancreatic intraepithelial neoplasms (PanIN) and IPMN. Meta- and TMA analyses followed by in vitro and in vivo validation revealed that ADM/PanIN exhibit increased PGC1α and oxidative phosphorylation (OXPhos) but reduced CPT1A. IPMN showed elevated PGC1α, fatty acid β-oxidation (FAO) gene expression, and FAO-OXPhos. PGC1α was co-overexpressed with its coactivator NRF1 in ADM/PanINs and with PPARγ in IPMN. PGC1α KD or SR18292 inhibited the specific metabolic and stemness features of PPLs and repressed IPMN organoid growth.
CONCLUSIONS
ADM/PanINs and IPMNs show specific stemness signatures with unique metabolisms. Inhibition of PGC1α using SR18292 diminishes the specific stemness by targeting FAO-independent and FAO-dependent OXPhos of ADM/PanINs and IPMNs, respectively.
Topics: Animals; Carcinoma, Pancreatic Ductal; Humans; Mice; Pancreas; Pancreatic Ducts; Pancreatic Neoplasms; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
PubMed: 34172498
DOI: 10.1158/1078-0432.CCR-20-5020 -
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 -
Acta Medica Lituanica 2023Intraductal papillary mucinous neoplasms (IPMNs) are the most frequent cystic pancreatic neoplasm. They derive from the main pancreatic duct or branch ducts. (Review)
Review
INTRODUCTION
Intraductal papillary mucinous neoplasms (IPMNs) are the most frequent cystic pancreatic neoplasm. They derive from the main pancreatic duct or branch ducts.
AIM
This narrative review aims to present and compare the current guidelines on the management of IPMNs.
MATERIALS AND METHODS
We reviewed the most important scientific literature on the management of IPMNs.
DISCUSSION
The clinical presentation of IPMNs is usually nonspecific; common symptoms are abdominal pain, weight loss, and jaundice. There are no sex differences, and the incidence increases with age. It is considered a premalignant lesion associated with synchronous or metachronous carcinomas. Multifocal sites within the pancreas and the presence of solid components, like mural nodules, are predictive factors for developing malignancy. Magnetic resonance imaging (MRI) is the imaging technique of choice. However, computed tomography (CT) and endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) can also contribute to the diagnosis. Resection is the optimal treatment for IPMNs that arise from the main duct, while several indications are suggested for the surgery on IPMNs of branch ducts.
CONCLUSION
The decision on surgery is not always a simple task and should be based on high-risk features of the neoplasm. In any case, re-examination and follow-up are highly recommended.
PubMed: 37575378
DOI: 10.15388/Amed.2023.30.1.6 -
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 -
Gastroenterology Mar 2021Advances in cross-sectional imaging have resulted in increased detection of intraductal papillary mucinous neoplasms (IPMNs), and their management remains controversial.... (Observational Study)
Observational Study
BACKGROUND AND AIMS
Advances in cross-sectional imaging have resulted in increased detection of intraductal papillary mucinous neoplasms (IPMNs), and their management remains controversial. At present, there is no reliable noninvasive method to distinguish between indolent and high risk IPMNs. We performed extracellular vesicle (EV) analysis to identify markers of malignancy in an attempt to better stratify these lesions.
METHODS
Using a novel ultrasensitive digital extracellular vesicle screening technique (DEST), we measured putative biomarkers of malignancy (MUC1, MUC2, MUC4, MUC5AC, MUC6, Das-1, STMN1, TSP1, TSP2, EGFR, EpCAM, GPC1, WNT-2, EphA2, S100A4, PSCA, MUC13, ZEB1, PLEC1, HOOK1, PTPN6, and FBN1) in EV from patient-derived cell lines and then on circulating EV obtained from peripheral blood drawn from patients with IPMNs. We enrolled a total of 133 patients in two separate cohorts: a clinical discovery cohort (n = 86) and a validation cohort (n = 47).
RESULTS
From 16 validated EV proteins in plasma samples collected from the discovery cohort, only MUC5AC showed significantly higher levels in high-grade lesions. Of the 11 patients with invasive IPMN (inv/HG), 9 had high MUC5AC expression in plasma EV of the 11 patients with high-grade dysplasia alone, only 1 had high MUC5AC expression (sensitivity of 82%, specificity of 100%). These findings were corroborated in a separate validation cohort. The addition of MUC5AC as a biomarker to imaging and high-riskstigmata allowed detection of all cases requiring surgery, whereas imaging and high-risk stigmata alone would have missed 5 of 14 cases (36%).
CONCLUSIONS
MUC5AC in circulating EV can predict the presence of invasive carcinoma within IPMN. This approach has the potential to improve the management and follow-up of patients with IPMN including avoiding unnecessary surgery.
Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Extracellular Vesicles; Female; Healthy Volunteers; Humans; Liquid Biopsy; Male; Mice; Middle Aged; Mucin 5AC; Neoplasm Invasiveness; Pancreatic Ducts; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Proof of Concept Study; Xenograft Model Antitumor Assays
PubMed: 33301777
DOI: 10.1053/j.gastro.2020.11.046 -
Current Oncology (Toronto, Ont.) Aug 2023Anemia and iron deficiency (ID) are common complications in patients with pancreatic ductal adenocarcinoma (PDAC), but their underlying causes remain unclear. This study...
Anemia and iron deficiency (ID) are common complications in patients with pancreatic ductal adenocarcinoma (PDAC), but their underlying causes remain unclear. This study investigated the incidence and characteristics of anemia and micronutrient deficiencies in PDAC patients before initiating chemotherapy. A total of 103 PDAC patients were included, comprising 67 in the palliative and 36 in the adjuvant groups. The overall incidence of anemia was 42.7% ( = 44), with comparable rates in both groups. Normocytic and normochromic anemia were predominant, with mild and moderate cases observed in 32% and 10.7% of the cohort, respectively. ID was evident in 51.4% of patients, with absolute ID more frequent in the adjuvant than in the palliative group (19.4% vs. 13.4%). Functional ID occurred more often in the palliative than in the adjuvant group (41.8% vs. 25%). Vitamin B12 and folate deficiency occurred in <5% ( = 5) of patients. Furthermore, 8.7% ( = 9) of patients had chronic kidney disease and anemia. To elucidate mechanisms of iron deficiency, the study explored the expression of iron regulators (hepcidin (HEP), ferroportin (FPN), and ZIP14 protein) and mitochondrial mass in PDAC tissue with immunohistochemical (IHC) staining and Perl's Prussian blue to detect iron deposits on available tumor samples ( = 56). ZIP14 expression was significantly higher in less advanced tumors ( = 0.01) and correlated with mitochondrial mass ( < 0.001), potentially indicating its role in local iron homeostasis. However, no significant impact of tissue iron regulators on patient survival was observed. Perl's Prussian blue staining revealed iron deposits within macrophages, but not in pancreatic duct cells. Furthermore, the GEPIA database was used to compare mRNA expression of iron regulators (HEP, FPN, and ZIP14) and other genes encoding iron transport and storage, including Transferrin Receptor Protein 1 (TfR1) and both ferritin chain subunits (FTH and FTL), in PDAC and normal pancreatic samples. FPN, TfR1, FTH, and FTL showed higher expression in tumor tissues, indicating increased iron usage by cancer. ZIP14 expression was higher in the pancreas than in PDAC and was correlated with FPN expression. The study highlights the importance of baseline iron status assessment in managing PDAC patients due to the high incidence of anemia and iron deficiency. Furthermore, ZIP14, in addition to HEP and FPN, may play a crucial role in local iron homeostasis in PDAC patients, providing valuable insights into the underlying mechanisms of iron dysregulation.
Topics: Humans; Iron; Anemia, Iron-Deficiency; Anemia; Iron Deficiencies; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Pancreatic Ducts
PubMed: 37623041
DOI: 10.3390/curroncol30080560