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Surgical Case Reports Aug 2023Acinar cell carcinoma of the pancreas is a rare exocrine malignancy representing less than 1% of all pancreatic neoplasms. It has been reported that it responds to...
BACKGROUND
Acinar cell carcinoma of the pancreas is a rare exocrine malignancy representing less than 1% of all pancreatic neoplasms. It has been reported that it responds to treatment differently from pancreatic ductal adenocarcinoma and the treatment algorithm for acinar cell carcinoma usually depends on the stage of the respective tumor and the patient's current status.
CASE PRESENTATION
A 60-year-old man presented with upper abdominal pain and anorexia. Abdominal ultrasonography showed a large-sized hepatic mass and he was referred to our hospital. Contrast-enhanced computed tomography demonstrated a 110-mm low-density area occupying the right hemi-liver and an enhanced mass of 70 × 56 mm in the tail of the pancreas, which seemed to directly infiltrate into the spleen. The case was diagnosed as acinar cell carcinoma with a simultaneous liver metastasis identified by liver biopsy. Upfront resection of pancreatic cancer with distant metastasis might not be considered as an optimal choice, and in this case chemotherapy was administered prior to curative resection. Chemotherapy using the modified FOLFIRINOX regimen was undertaken, resulting in a partial remission; the liver tumor reduced in size from 110 to 47 mm and the pancreatic tumor from 70 to 40 mm. The patient then safely underwent curative hepatic resection with distal pancreato-splenectomy. Histological examinations revealed small-sized atypical cells with large nuclei that had formed acinar patterns, and immunostaining with trypsin was positive in tumor cells, which was in accordance with acinar cell carcinoma. More than 3 years later, the patient is doing well without any recurrence.
CONCLUSION
Aggressive and curative surgery in combination with chemotherapy such as FOLFIRINOX could be a treatment option to achieve long-term survival in cases of acinar cell carcinoma with liver metastases.
PubMed: 37610633
DOI: 10.1186/s40792-023-01729-1 -
Cureus Oct 2023Acute pancreatitis results in inflammation and autodigestion of pancreatic acinar cells leading to the elevation of pancreatic enzymes, namely, amylase and lipase. Serum...
Acute pancreatitis results in inflammation and autodigestion of pancreatic acinar cells leading to the elevation of pancreatic enzymes, namely, amylase and lipase. Serum lipase levels have long been considered a hallmark of acute pancreatitis. However, pancreatitis is not always the cause of elevated serum lipase levels. This series presents four patients who had elevated serum lipase levels without any demonstrable damage to the pancreas on imaging. On further evaluation, one of the patients was found to have acute on chronic kidney disease (CKD) whose lipase levels settled later. A patient presenting with an episode of acute gastroenteritis, later diagnosed to have Crohn's disease, also had hyperlipasemia, which improved after a course of initial antibiotics. Non-gastrointestinal causes, such as lupus nephritis and organophosphate (OP) poisoning, also had elevated lipase levels on presentation, in which the hyperlipasemia settled with supportive treatments. It is important to remember other causes of elevated lipase levels in patients with a normal pancreas on imaging studies.
PubMed: 38021537
DOI: 10.7759/cureus.47781 -
BDJ Open May 2024Salivary gland (SG) hypofunction is a common clinical condition arising from radiotherapy to suppress head and neck cancers. The radiation often destroys the SG... (Review)
Review
OBJECTIVE
Salivary gland (SG) hypofunction is a common clinical condition arising from radiotherapy to suppress head and neck cancers. The radiation often destroys the SG secretory acini, and glands are left with limited regenerative potential. Due to the complex architecture of SG acini and ducts, three-dimensional (3D) bioprinting platforms have emerged to spatially define these in vitro epithelial units and develop mini-organs or organoids for regeneration. Due to the limited body of evidence, this comprehensive review highlights the advantages and challenges of bioprinting platforms for SG regeneration.
METHODS
SG microtissue engineering strategies such as magnetic 3D bioassembly of cells and microfluidic coaxial 3D bioprinting of cell-laden microfibers and microtubes have been proposed to replace the damaged acinar units, avoid the use of xenogeneic matrices (like Matrigel), and restore salivary flow.
RESULTS
Replacing the SG damaged organ is challenging due to its complex architecture, which combines a ductal network with acinar epithelial units to facilitate a unidirectional flow of saliva. Our research group was the first to develop 3D bioassembly SG epithelial functional organoids with innervation to respond to both cholinergic and adrenergic stimulation. More recently, microtissue engineering using coaxial 3D bioprinting of hydrogel microfibers and microtubes could also supported the formation of viable epithelial units. Both bioprinting approaches could overcome the need for Matrigel by facilitating the assembly of adult stem cells, such as human dental pulp stem cells, and primary SG cells into micro-sized 3D constructs able to produce their own matrix and self-organize into micro-modular tissue clusters with lumenized areas. Furthermore, extracellular vesicle (EV) therapies from organoid-derived secretome were also designed and validated ex vivo for SG regeneration after radiation damage.
CONCLUSION
Magnetic 3D bioassembly and microfluidic coaxial bioprinting platforms have the potential to create SG mini-organs for regenerative applications via organoid transplantation or organoid-derived EV therapies.
PubMed: 38816372
DOI: 10.1038/s41405-024-00219-2 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2023To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine...
OBJECTIVE
To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine tumor (PNET) and solid pseudopapillary neoplasm (SPN).
METHODS
To detect the expression of INSM1, SOX11, Syn, CgA, CD56, β-catenin, and CD99 in 56 cases of PNET, 42 cases of SPN, 16 cases of ductal adenocarcinoma (DACC) and 8 cases of acinar cell carcinoma (ACC) by immunohistochemistry. The application value of combination of INSM1 and SOX11 was compared with conventional markers (Syn, CgA, CD56, β-catenin, and CD99) in diagnosis and differential diagnosis of PNET and SPN.
RESULTS
(1) In the 56 cases of PNET, the positive signals of INSM1 were located in the tumor and islet nucleus, the positive expression rate in the tumor tissues was 91.07% (51/56), whereas the signal was absent in 42 cases of SPN, 16 cases of DACC and 8 cases of ACC, and there were significant statistical difference between PNET with SPN, DACC, and ACC respectively ( < 0.001). (2) The positive signals of SOX11 were located in the tumor nucleus, with the positive expression rate was 92.86% (39/42) in SPN, however, the positive expression rate of SOX11 was 8.93% (5/56) in PNET, which included 3 cases of G and 2 cases of G types of PNET, the SOX11 positive signal was absent in 16 cases of DACC, 8 cases of ACC and peritumoral nomal pancreatic tissue, and the differences were statistically significant of positive rate between SPN with PNET, DACC and ACC, respectively ( < 0.001). (3) The sensitivity of INSM1(+)/SOX11(-) immunophenotype for PNET was 85.71%, CD56 (57.14%), the difference was statistically significant (=0.001); Syn (80.36%) and CgA (71.43%), the difference was no statistically significant (>0.05). The specificity of INSM1(+)/SOX11(-) for PNET was 100.00%, Syn (42.86%) and CD56 (47.62%), the difference was statistically significant ( < 0.001); CgA (92.86%), the difference was no statistically significant (>0.05). The sensitivity of INSM1(-)/SOX11(+) immunophenotype for SPN was 92.86%, β-catenin (90.48%) and CD99 (85.71%), the difference was no statistically significant (>0.05). The specificity of INSM1(-)/SOX11(+) for SPN was 96.43%, CD99 (48.21%), the difference was statistically significant ( < 0.001); β-catenin (100.00%), the difference was no statistically significant (>0.05). (4) The positive expression of INSM1 and SOX11 in PNET and SOX11 were not correlated with clinicopathological parameters (age, gender, tumor size, location, grade, and metastasis) (>0.05).
CONCLUSION
The positive expression patterns of INSM1 and SOX11 in PNET and SPN respectively are conductive to distinguish the both tumors. The combination of both take precedence over some corresponding conventional immunohistochemical markers in terms of sensitivity and specificity.
Topics: Humans; Neuroendocrine Tumors; beta Catenin; Biomarkers, Tumor; Repressor Proteins; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive; SOXC Transcription Factors
PubMed: 37534634
DOI: 10.19723/j.issn.1671-167X.2023.04.001 -
Function (Oxford, England) 2024Acute pancreatitis is initiated within pancreatic exocrine cells and sustained by dysregulated systemic inflammatory responses mediated by neutrophils. Store-operated Ca...
Acute pancreatitis is initiated within pancreatic exocrine cells and sustained by dysregulated systemic inflammatory responses mediated by neutrophils. Store-operated Ca entry (SOCE) through ORAI1 channels in pancreatic acinar cells triggers acute pancreatitis, and ORAI1 inhibitors ameliorate experimental acute pancreatitis, but the role of ORAI1 in pancreatitis-associated acute lung injury has not been determined. Here, we showed mice with pancreas-specific deletion of (, ∼70% reduction in the expression of Orai1) are protected against pancreatic tissue damage and immune cell infiltration, but not pancreatitis-associated acute lung injury, suggesting the involvement of unknown cells that may cause such injury through SOCE via ORAI1. Genetic () or pharmacological inhibition of ORAI1 in murine and human neutrophils decreased Ca influx and impaired chemotaxis, reactive oxygen species production, and neutrophil extracellular trap formation. Unlike pancreas-specific deletion, mice with neutrophil-specific deletion of () were protected against pancreatitis- and sepsis-associated lung cytokine release and injury, but not pancreatic injury in experimental acute pancreatitis. These results define critical differences between contributions from different cell types to either pancreatic or systemic organ injury in acute pancreatitis. Our findings suggest that any therapy for acute pancreatitis that targets multiple rather than single cell types is more likely to be effective.
Topics: Animals; Humans; Mice; Acute Disease; Acute Lung Injury; Neutrophils; ORAI1 Protein; Pancreatitis
PubMed: 38020066
DOI: 10.1093/function/zqad061 -
International Journal of Molecular... Dec 2023Cdc42 is a small GTPase essential for the cell cycle, morphogenesis, and cell adhesion, and it is involved in the polarity of epithelial cells. However, the functional...
Cdc42 is a small GTPase essential for the cell cycle, morphogenesis, and cell adhesion, and it is involved in the polarity of epithelial cells. However, the functional roles of Cdc42 in exocrine glands, such as the maintenance of acini and water secretion, are not yet well understood. In this study, we generated acinar-cell-specific conditional knockout () mice to assess their maintenance of acinar cells and physiological functions in the salivary glands (SGs) and lacrimal glands (LGs). Our data revealed that the loss of Cdc42 altered the luminal structures to bulging structures and induced acinar cell apoptosis in both the parotid glands (PGs) and LGs of mice. Interestingly, saliva secretion in response to pilocarpine stimulation was decreased in the group, whereas tear secretion was increased. Consistent with the water secretion results, protein expression of the water channel AQP5 in acinar cells was also decreased in the PGs but conversely increased in the LGs. Moreover, the changes that increased AQP5 expression in LGs occurred in the acinar cells rather than the duct cells. The present study demonstrates that Cdc42 is involved in the structural and survival maintenance of acinar cells in SGs and LGs. On the other hand, depletion of Cdc42 caused the opposite physiological phenomena between PGs and LGs.
Topics: Animals; Mice; Acinar Cells; Saliva; Salivary Glands; Tears; Water
PubMed: 38139048
DOI: 10.3390/ijms242417220 -
Science Advances Feb 2024Acute pancreatitis (AP) is one of the most common gastrointestinal diseases. Bile acids (BAs) were proposed to be a cause of AP nearly 170 years ago, though the...
Acute pancreatitis (AP) is one of the most common gastrointestinal diseases. Bile acids (BAs) were proposed to be a cause of AP nearly 170 years ago, though the underlying mechanisms remain unclear. Here, we report that two G protein-coupled receptors, GPR39 and GHSR, mediated cellular responses to BAs. Our results revealed GPR39 as an evolutionarily conserved receptor for BAs, particularly 3-O-sulfated lithocholic acids. In cultured cell lines, GPR39 is sufficient for BA-induced Ca elevation. In pancreatic acinar cells, GPR39 mediated BA-induced Ca elevation and necrosis. Furthermore, AP induced by BAs was significantly reduced in GPR39 knockout mice. Our findings provide in vitro and in vivo evidence demonstrating that GPR39 is necessary and sufficient to mediate BA signaling, highlighting its involvement in biliary AP pathogenesis, and suggesting it as a promising therapeutic target for biliary AP.
Topics: Animals; Mice; Acute Disease; Bile Acids and Salts; Carrier Proteins; Mice, Knockout; Pancreatitis; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 38306436
DOI: 10.1126/sciadv.adj0146 -
HPB : the Official Journal of the... Nov 2023Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC.
BACKGROUND
Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC.
METHODS
This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols.
RESULTS
59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy.
DISCUSSION
Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting.
PubMed: 37563033
DOI: 10.1016/j.hpb.2023.07.897 -
Cureus Mar 2024Acute pancreatitis, marked by sudden inflammation of the pancreas, presents a complex spectrum of causative factors including gallstone obstruction, alcohol abuse, and... (Review)
Review
Acute pancreatitis, marked by sudden inflammation of the pancreas, presents a complex spectrum of causative factors including gallstone obstruction, alcohol abuse, and viral infections. Recent studies have illuminated the emergence of vaccine-induced acute pancreatitis, notably associated with COVID-19 vaccinations, presenting diverse mechanisms ranging from direct viral-mediated injury to autoimmune reactions. Understanding this link is pivotal for public health, yet challenges persist in identifying and managing cases post-vaccination. Comprehensive literature reviews employing the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement outline the potential pathways and mechanisms leading to vaccine-induced pancreatitis, emphasizing the need for deeper investigations into underlying health conditions and modifications to vaccine components. Notably, the rare occurrences of vaccine-induced pancreatitis extend beyond COVID-19 vaccines, with reports also documenting associations with measles, mumps, and rubella (MMR), human papillomavirus (HPV), and other viral vaccinations. Mechanistically, hypotheses such as molecular mimicry and immunologic injury have been proposed, necessitating ongoing vigilance and exploration. Regulatory agencies play a crucial role in monitoring and communicating vaccine safety concerns, emphasizing transparency to address potential risks and maintain public trust. Understanding and communicating these rare adverse events with transparency remain integral for informed vaccination policies and to allay concerns surrounding vaccine safety.
PubMed: 38571842
DOI: 10.7759/cureus.55426 -
Function (Oxford, England) 2023Glandular pancreatic epithelia of the acinar or ductal phenotype may seem terminally differentiated, but they are characterized by remarkable cell plasticity....
Glandular pancreatic epithelia of the acinar or ductal phenotype may seem terminally differentiated, but they are characterized by remarkable cell plasticity. Stress-induced trans-differentiation of these cells has been implicated in the mechanisms of carcinogenesis. Current consensus links pancreatic ductal adenocarcinoma with onco-transformation of ductal epithelia, but under the presence of driver mutations in and , also with trans-differentiation of pancreatic acini. However, we do not know when, in the course of cancer progression, physiological functions are lost by mutant acinar cells, nor can we assess their capacity for the production of pancreatic juice components. Here, we investigated whether two mutations-Kras and Trp53-present simultaneously in acinar cells of KPC mice (model of oncogenesis) influence cytosolic Ca signals. Since Ca signals control the cellular handling of digestive hydrolases, any changes that affect intracellular signaling events and cell bioenergetics might have an impact on the physiology of the pancreas. Our results showed that physiological doses of acetylcholine evoked less regular Ca oscillations in KPC acinar cells compared to the control, whereas responses to supramaximal concentrations were markedly reduced. Menadione elicited Ca signals of different frequencies in KPC cells compared to control cells. Finally, Ca extrusion rates were significantly inhibited in KPC cells, likely due to the lower basal respiration and ATP production. Cumulatively, these findings suggest that driver mutations affect the signaling capacity of pancreatic acinar cells even before the changes in the epithelial cell morphology become apparent.
Topics: Mice; Animals; Proto-Oncogene Proteins p21(ras); Pancreatic Neoplasms; Carcinogenesis; Mutation; Adenosine Triphosphate
PubMed: 37575483
DOI: 10.1093/function/zqad035