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ELife Oct 2023The splicing factor SF3B1 is recurrently mutated in various tumors, including pancreatic ductal adenocarcinoma (PDAC). The impact of the hotspot mutation SF3B1 on the...
The splicing factor SF3B1 is recurrently mutated in various tumors, including pancreatic ductal adenocarcinoma (PDAC). The impact of the hotspot mutation SF3B1 on the PDAC pathogenesis, however, remains elusive. Here, we demonstrate that Sf3b1 alone is insufficient to induce malignant transformation of the murine pancreas, but that it increases aggressiveness of PDAC if it co-occurs with mutated KRAS and p53. We further show that Sf3b1 already plays a role during early stages of pancreatic tumor progression and reduces the expression of TGF-β1-responsive epithelial-mesenchymal transition (EMT) genes. Moreover, we found that SF3B1 confers resistance to TGF-β1-induced cell death in pancreatic organoids and cell lines, partly mediated through aberrant splicing of . Overall, our findings demonstrate that SF3B1 acts as an oncogenic driver in PDAC, and suggest that it promotes the progression of early stage tumors by impeding the cellular response to tumor suppressive effects of TGF-β.
Topics: Animals; Humans; Mice; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Mutation; Pancreatic Ducts; Pancreatic Neoplasms; Phosphoproteins; RNA Splicing Factors; Transcription Factors; Transforming Growth Factor beta1
PubMed: 37823551
DOI: 10.7554/eLife.80683 -
Journal of Ayub Medical College,... 2019Hemosuccus pancreaticus (HP) defined as bleeding into the pancreatic duct was first described in 1931 by Lower and Farell. HP also popularly known as wirsungorrhaghia... (Review)
Review
Hemosuccus pancreaticus (HP) defined as bleeding into the pancreatic duct was first described in 1931 by Lower and Farell. HP also popularly known as wirsungorrhaghia and pseudohemobilia is a rare cause of gastrointestinal bleed. The unfamiliarity of this condition makes HP a diagnostic challenge. HP should be considered in patients with chronic pancreatitis presenting with acute gastrointestinal bleeding. The diagnosis is usually confirmed with a computerized tomography (CT) scan of the abdomen. A mesenteric angiogram with coil embolization can be performed to arrest the bleeding. The literature on this condition is restricted to case reports, case series and retrospective studies. We describe a case of HP in a patient with gastrointestinal bleeding and take this opportunity to review the literature outlining the diagnosis and management of HP.
Topics: Angiography; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Pancreatic Diseases; Pancreatic Ducts; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 31933323
DOI: No ID Found -
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 -
Journal of Translational Internal... Mar 2022The basic pancreatic lesions include location, size, shape, number, capsule, calcification/calculi, hemorrhage, cystic degeneration, fibrosis, pancreatic duct...
The basic pancreatic lesions include location, size, shape, number, capsule, calcification/calculi, hemorrhage, cystic degeneration, fibrosis, pancreatic duct alterations, and microvessel. One or more basic lesions form a kind of pancreatic disease. As recognizing the characteristic imaging features of pancreatic basic lesions and their relationships with pathology aids in differentiating the variety of pancreatic diseases. The purpose of this study is to review the pathological and imaging features of the basic pancreatic lesions.
PubMed: 35702187
DOI: 10.2478/jtim-2022-0003 -
The Korean Journal of Gastroenterology... Oct 2023The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary... (Review)
Review
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.
Topics: Humans; Ampulla of Vater; Adenocarcinoma; Pancreatic Neoplasms; Common Bile Duct Neoplasms; Duodenal Neoplasms
PubMed: 37876255
DOI: 10.4166/kjg.2023.110 -
Gut Sep 2022
Topics: Cholangiopancreatography, Endoscopic Retrograde; Humans; Pancreatic Ducts; Pancreatic Neoplasms
PubMed: 33963040
DOI: 10.1136/gutjnl-2021-324335 -
The Lancet. Gastroenterology &... Dec 2022Pancreatic intraductal papillary mucinous neoplasms (IPMNs) have gained substantial attention because they represent one of the only radiographically identifiable... (Review)
Review
Pancreatic intraductal papillary mucinous neoplasms (IPMNs) have gained substantial attention because they represent one of the only radiographically identifiable precursors of invasive pancreatic ductal adenocarcinoma. Although most of these neoplasms have low-grade dysplasia and will remain indolent, a subset of IPMNs will progress to invasive cancer. The role of the immune system in the progression of IPMNs is unclear, but understanding its role could reveal the mechanism of neoplastic progression and targets for immunotherapy to inhibit progression or treat invasive disease. The available evidence supports a shift in the immune composition of IPMNs during neoplastic progression. Although low-grade lesions contain a high proportion of effector T cells, high-grade IPMNs, and IPMNs with an associated invasive carcinoma lose the T-cell infiltrate and are characterised by a predominance of immunosuppressive elements. Several possible therapeutic strategies emerge from this analysis that are unique to IPMNs and its microbiome.
Topics: Humans; Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Pancreatic Ducts; Microbiota; Tumor Microenvironment
PubMed: 36057265
DOI: 10.1016/S2468-1253(22)00235-7 -
Deutsches Arzteblatt International Oct 2023Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform... (Review)
Review
BACKGROUND
Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform treatment recommendations are lacking both for the adjuvant situation and for palliative care.
METHODS
A selective literature search was carried out in PubMed in order to identify the most informative publications concerning the epidemiology, clinico-pathological background, and surgical and medical treatment of this condition.
RESULTS
Ampullary carcinoma has an incidence of 0.5 to 0.9 per 100 000 persons and a poor prognosis, with a 5-year survival rate of 41% to 45% for locally confined and 4% to 7% for metastatic disease. Most such tumors are of an intestinal or a pan - creaticobiliary immunohistochemical subtype; the latter has a worse prognosis (median survival, 72-80 vs. 33-41 months). Targeted treatment is not yet available for either subtype, nor is there enough scientific evidence available for the formulation of specific therapeutic recommendations in either the adjuvant or the palliative situation. The treatment of choice for ampullary carcinoma is radical oncological resection of the head of the pancreas with systematic lymphadenectomy. Five-year overall survival is between 10% and 75% depending on the stage. No definitive recommendation for adjuvant therapy can be given. Palliative therapy can be oriented to the published treatment strategies for cancer of the colon, pancreas, and bile duct.
CONCLUSION
The current state of the evidence on the treatment of ampullary carcinoma is poor. Therapeutic decisions should be discussed in an interdisciplinary tumor board and should, in our opinion, take the histological subtype into account.
Topics: Humans; Ampulla of Vater; Adenocarcinoma; Prognosis; Pancreatic Neoplasms; Combined Modality Therapy
PubMed: 37656482
DOI: 10.3238/arztebl.m2023.0195 -
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