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Science Signaling Oct 2022The tumor microbiome is increasingly implicated in cancer progression and resistance to chemotherapy. In pancreatic ductal adenocarcinoma (PDAC), high intratumoral loads...
The tumor microbiome is increasingly implicated in cancer progression and resistance to chemotherapy. In pancreatic ductal adenocarcinoma (PDAC), high intratumoral loads of correlate with shorter survival in patients. Here, we investigated the potential mechanisms underlying this association. We found that infection induced both normal pancreatic epithelial cells and PDAC cells to secrete increased amounts of the cytokines GM-CSF, CXCL1, IL-8, and MIP-3α. These cytokines increased proliferation, migration, and invasive cell motility in both infected and noninfected PDAC cells but not in noncancerous pancreatic epithelial cells, suggesting autocrine and paracrine signaling to PDAC cells. This phenomenon occurred in response to infection regardless of the strain and in the absence of immune and other stromal cells. Blocking GM-CSF signaling markedly limited proliferative gains after infection. Thus, infection in the pancreas elicits cytokine secretion from both normal and cancerous cells that promotes phenotypes in PDAC cells associated with tumor progression. The findings support the importance of exploring host-microbe interactions in pancreatic cancer to guide future therapeutic interventions.
Topics: Humans; Fusobacterium nucleatum; Granulocyte-Macrophage Colony-Stimulating Factor; Paracrine Communication; Interleukin-8; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Cell Proliferation; Pancreas
PubMed: 36256708
DOI: 10.1126/scisignal.abn4948 -
International Journal of Surgery... Apr 2018Pancreaticoduodenectomy (PD) is one of the most difficult and complex surgery that carries a high rate of major complications, including delayed gastric emptying (DGE),...
BACKGROUND
Pancreaticoduodenectomy (PD) is one of the most difficult and complex surgery that carries a high rate of major complications, including delayed gastric emptying (DGE), pancreatic fistula, bleeding, intra-abdominal collection, and pulmonary complications. In this study, we have tried to demonstrate the outcomes, and rates of complications from patients who had undergone this procedure by our surgical team.
MATERIALS AND METHODS
This retrospective study has been constructed on 98 patients who underwent pancreaticoduodenectomy from May 2010 to November 2017 in three different hospitals of the Sulaimanyah governorate in the Kurdistan region of Iraq by the same surgical team. Data was collected from the medical records of patients. A preoperative work up had done for all patients, including those who are necessary for anesthesia fitness and those for staging assessment. None of the operated patients received any types of neoadjuvant therapy.
RESULT
Out of all 98 patients who underwent PD, the most common complication was wound infection (23.5%), followed by pancreatic leak (21.4%). The pulmonary complication rate was 17.3%, while the intra-abdominal collection rate was 12.2%. In 12.2% of our patients we faced postoperative bleeding, with five patients having to be reopened for this reason. About 77.3% of patients that underwent preoperative ERCP had difficult bile duct dissection. There was an association between preoperative ERCP and difficult bile duct dissection (P Value < 0.001).
CONCLUSION
Outcomes of our surgical team compared to the published data of some other centers. Preoperative ERCP seems to make difficulty in bile duct dissection during PD.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Humans; Iraq; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Retrospective Studies; Young Adult
PubMed: 29438817
DOI: 10.1016/j.ijsu.2018.01.041 -
The American Journal of Emergency... Sep 2022
Topics: Abdomen; COVID-19; Humans; Pancreas; SARS-CoV-2
PubMed: 35644682
DOI: 10.1016/j.ajem.2022.04.023 -
Clinical and Experimental Immunology Dec 2019In recent years, there have been exciting new insights into pathogenesis of type 1 diabetes in a number of areas of immunology. In this edition, a collection of four...
In recent years, there have been exciting new insights into pathogenesis of type 1 diabetes in a number of areas of immunology. In this edition, a collection of four review articles are presented, which encompass new findings presented at the Immunology of Diabetes Society meeting in London 2018. The articles are focused particularly in 4 related areas of investigation, which include autoantibodies in type 1 diabetes, new autoantigenic targets for CD4 T cells, trafficking of immune cells to the pancreas and islet-immune interactions in the pancreas.
Topics: Autoantibodies; Autoantigens; CD4-Positive T-Lymphocytes; Diabetes Mellitus, Type 1; Humans; Islets of Langerhans; Pancreas
PubMed: 31729755
DOI: 10.1111/cei.13396 -
Nature Reviews. Endocrinology Aug 2022Enteroviruses are believed to trigger or accelerate islet autoimmunity in genetically susceptible individuals, thereby resulting in loss of functional insulin-producing... (Review)
Review
Enteroviruses are believed to trigger or accelerate islet autoimmunity in genetically susceptible individuals, thereby resulting in loss of functional insulin-producing β-cells and type 1 diabetes mellitus (T1DM). Although enteroviruses are primarily involved in acute and lytic infections in vitro and in vivo, they can also establish a persistent infection. Prospective epidemiological studies have strongly associated the persistence of enteroviruses, especially coxsackievirus B (CVB), with the appearance of islet autoantibodies and an increased risk of T1DM. CVB can persist in pancreatic ductal and β-cells, which leads to structural or functional alterations of these cells, and to a chronic inflammatory response that promotes recruitment and activation of pre-existing autoreactive T cells and β-cell autoimmune destruction. CVB persistence in other sites, such as the intestine, blood cells and thymus, has been described; these sites could serve as a reservoir for infection or reinfection of the pancreas, and this persistence could have a role in the disturbance of tolerance to β-cells. This Review addresses the involvement of persistent enterovirus infection in triggering islet autoimmunity and T1DM, as well as current strategies to control enterovirus infections for preventing or reducing the risk of T1DM onset.
Topics: Diabetes Mellitus, Type 1; Enterovirus; Enterovirus B, Human; Humans; Insulin-Secreting Cells; Prospective Studies
PubMed: 35650334
DOI: 10.1038/s41574-022-00688-1 -
Biomolecules Dec 2023Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar... (Review)
Review
Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar cells. Secondary infection and sepsis are independent prognosticators for AP progression and increased mortality. Accumulating anatomical and epidemiological evidence suggests that the dysbiosis of gut microbiota affects the etiology and severity of AP through intestinal barrier disruption, local or systemic inflammatory response, bacterial translocation, and the regulatory role of microbial metabolites in AP patients and animal models. Recent studies discussing the interactions between gut microbiota and the pancreas have opened new scopes for AP, and new therapeutic interventions that target the bacteria community have received substantial attention. This review concentrates on the alterations of gut microbiota and its roles in modulating gut-pancreas axis in AP. The potential therapies of targeting microbes as well as the major challenges of applying those interventions are explored. We expect to understand the roles of microbes in AP diagnosis and treatment.
Topics: Animals; Humans; Pancreatitis; Acute Disease; Pancreas; Microbiota; Gastrointestinal Microbiome
PubMed: 38254659
DOI: 10.3390/biom14010059 -
International Journal of Molecular... Jan 2022Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the... (Review)
Review
Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. This review presents a summary of the molecular mechanisms involved in the development of pancreatic dysfunction during the course of COVID-19, the comparison of the effects of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic function, and a summary of how drugs used in COVID-19 treatment may affect this organ. It appears that diabetes is not only a condition that predisposes a patient to suffer from more severe COVID-19, but it may also develop as a consequence of infection with this virus. Some SARS-CoV-2 inpatients experience acute pancreatitis due to direct infection of the tissue with the virus or due to systemic multiple organ dysfunction syndrome (MODS) accompanied by elevated levels of amylase and lipase. There are also reports that reveal a relationship between the development and treatment of pancreatic cancer and SARS-CoV-2 infection. It has been postulated that evaluation of pancreatic function should be increased in post-COVID-19 patients, both adults and children.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Diabetes Complications; Diabetes Mellitus; Humans; Middle East Respiratory Syndrome Coronavirus; Pancreas; Pancreatic Neoplasms; Pancreatitis; Severe acute respiratory syndrome-related coronavirus; Serine Endopeptidases; Sodium-Hydrogen Exchangers; COVID-19 Drug Treatment
PubMed: 35055050
DOI: 10.3390/ijms23020864 -
Diabetologia Jul 2023'The clock to type 1 diabetes has started when islet antibodies are first detected', commented George Eisenbarth with regard to the pathogenesis of type 1 diabetes. This... (Review)
Review
'The clock to type 1 diabetes has started when islet antibodies are first detected', commented George Eisenbarth with regard to the pathogenesis of type 1 diabetes. This review focuses on 'starting the clock', i.e. the initiation of pre-symptomatic islet autoimmunity/the first appearance of islet autoantibodies. In particular, this review addresses why susceptibility to developing islet autoimmunity is greatest in the first 2 years of life and why beta cells are a frequent target of the immune system during this fertile period. A concept for the development of beta cell autoimmunity in childhood is discussed and three factors are highlighted that contribute to this early predisposition: (1) high beta cell activity and potential vulnerability to stress; (2) high rates of and first exposures to infection; and (3) a heightened immune response, with a propensity for T helper type 1 (Th1) immunity. Arguments are presented that beta cell injury, accompanied by activation of an inflammatory immune response, precedes the initiation of autoimmunity. Finally, the implications for strategies aimed at primary prevention for a world without type 1 diabetes are discussed.
Topics: Female; Humans; Diabetes Mellitus, Type 1; Islets of Langerhans; Autoimmunity; Autoantibodies; Insulin-Secreting Cells; Genetic Predisposition to Disease
PubMed: 37231274
DOI: 10.1007/s00125-023-05927-2 -
Trends in Endocrinology and Metabolism:... Nov 2021The widespread extrapulmonary complications of coronavirus disease 2019 (COVID-19) have gained momentum; the pancreas is another major target for severe acute... (Review)
Review
The widespread extrapulmonary complications of coronavirus disease 2019 (COVID-19) have gained momentum; the pancreas is another major target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we take a closer look into potential pathological interactions. We provide an overview of the current knowledge and understanding of SARS-CoV-2 infection of the pancreas with a special focus on pancreatic islets and propose direct, indirect, and systemic mechanisms for pancreas injury as result of the COVID-19-diabetes fatal bidirectional relationship.
Topics: Acinar Cells; Angiotensin-Converting Enzyme 2; COVID-19; Diabetes Mellitus; Glucagon-Secreting Cells; Humans; Insulin-Secreting Cells; Islets of Langerhans; Pancreas; Receptors, Coronavirus; SARS-CoV-2; Serine Endopeptidases; Viral Tropism
PubMed: 34373155
DOI: 10.1016/j.tem.2021.07.004 -
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