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Diabetologia Oct 2020For much of the last century, our knowledge regarding the pancreas in type 1 and type 2 diabetes was largely derived from autopsy studies of individuals with these... (Review)
Review
For much of the last century, our knowledge regarding the pancreas in type 1 and type 2 diabetes was largely derived from autopsy studies of individuals with these disorders or investigations utilising rodent models of either disease. While many important insights emanated from these efforts, the mode for investigation has increasingly seen change due to the availability of transplant-quality organ-donor tissues, improvements in pancreatic imaging, advances in metabolic assessments of living patients, genetic analyses, technological advances for laboratory investigation and more. As a result, many long-standing notions regarding the role for and the changes that occur in the pancreas in individuals with these disorders have come under question, while, at the same time, new issues (e.g., beta cell persistence, disease heterogeneity, exocrine contributions) have arisen. In this article, we will consider the vital role of the pancreas in human health and physiology, including discussion of its anatomical features and dual (exocrine and endocrine) functions. Specifically, we convey changes that occur in the pancreas of those with either type 1 or type 2 diabetes, with careful attention to the facets that may contribute to the pathogenesis of either disorder. Finally, we discuss the emerging unknowns with the belief that understanding the role of the pancreas in type 1 and type 2 diabetes will lead to improvements in disease diagnosis, understanding of disease heterogeneity and optimisation of treatments at a personalised level. Graphical abstract.
Topics: Adipose Tissue; Amyloidosis; Autoimmunity; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucagon-Secreting Cells; Humans; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Islets of Langerhans; Pancreas; Pancreas, Exocrine; Somatostatin-Secreting Cells
PubMed: 32894306
DOI: 10.1007/s00125-020-05203-7 -
Expert Review of Gastroenterology &... Nov 2019: Pancreas divisum is the most common congenital malformation of the pancreas with the majority asymptomatic. The etiological role, pathogenesis, clinical significance... (Review)
Review
: Pancreas divisum is the most common congenital malformation of the pancreas with the majority asymptomatic. The etiological role, pathogenesis, clinical significance and management of pancreas divisum in pancreatic disease has not been clearly defined and our understanding is yet to be fully elucidated.: This review describes the role of pancreas divisum in the development of pancreatic disease and the ambiguity related to it. In our attempt to offer clarity, a comprehensive search on PubMed, Ovid, Embase and Cochrane Library from inception to May 2019 was undertaken using key words "pancreas divisum", "idiopathic recurrent acute pancreatitis" and "chronic pancreatitis".: Current research fails to define a clear association between pancreas divisum and pancreatic disease. Though debatable, several studies do suggest a pathological role of pancreas divisum in pancreatic disease and a benefit of minor papilla therapy in the setting of acute recurrent pancreatitis. Surgical and endoscopic therapeutic modalities have not been directly compared. With the current data available, it would be imprudent to advise a definitive line of management for pancreatic disease associated with pancreas divisum and should involve a comprehensive discussion with the individual patient to define expectations before embarking on any medical and/or interventional therapy.
Topics: Digestive System Abnormalities; Humans; Pancreas; Pancreatitis; Pancreatitis, Chronic; Predictive Value of Tests; Prognosis; Recurrence; Risk Assessment; Risk Factors
PubMed: 31663403
DOI: 10.1080/17474124.2019.1685871 -
The Journal of Clinical Investigation Jan 20212021 to 2022 marks the one hundredth anniversary of ground-breaking research in Toronto that changed the course of what was, then, a universally fatal disease: type 1... (Review)
Review
2021 to 2022 marks the one hundredth anniversary of ground-breaking research in Toronto that changed the course of what was, then, a universally fatal disease: type 1 diabetes. Some would argue that insulin's discovery by Banting, Best, Macleod, and Collip was the greatest scientific advance of the 20th century, being one of the first instances in which modern medical science was able to provide lifesaving therapy. As with all scientific discoveries, the work in Toronto built upon important advances of many researchers over the preceding decades. Furthermore, the Toronto work ushered in a century of discovery of the purification, isolation, structural characterization, and genetic sequencing of insulin, all of which influenced ongoing improvements in therapeutic insulin formulations. Here we discuss the body of knowledge prior to 1921 localizing insulin to the pancreas and establishing insulin's role in glucoregulation, and provide our views as to why researchers in Toronto ultimately achieved the purification of pancreatic extracts as a therapy. We discuss the pharmaceutical industry's role in the early days of insulin production and distribution and provide insights into why the discoverers chose not to profit financially from the discovery. This fascinating story of bench-to-beside discovery provides useful considerations for scientists now and in the future.
Topics: Animals; Drug Industry; History, 20th Century; History, 21st Century; Humans; Insulin; Pancreas
PubMed: 33393501
DOI: 10.1172/JCI142239 -
Cell Metabolism Jan 2023Current differentiation protocols have not been successful in reproducibly generating fully functional human beta cells in vitro, partly due to incomplete understanding...
Current differentiation protocols have not been successful in reproducibly generating fully functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single-cell RNA sequencing with spatial transcriptomics at multiple developmental time points and revealed distinct temporal-spatial gene cascades. Cell trajectory inference identified endocrine progenitor populations and branch-specific genes as the progenitors differentiate toward alpha or beta cells. Spatial differentiation trajectories indicated that Schwann cells are spatially co-located with endocrine progenitors, and cell-cell connectivity analysis predicted that they may interact via L1CAM-EPHB2 signaling. Our integrated approach enabled us to identify heterogeneity and multiple lineage dynamics within the mesenchyme, showing that it contributed to the exocrine acinar cell state. Finally, we have generated an interactive web resource for investigating human pancreas development for the research community.
Topics: Humans; Transcriptome; Pancreas; Gene Expression Profiling; Cell Differentiation; Pancreas, Exocrine; Single-Cell Analysis; Gene Expression Regulation, Developmental
PubMed: 36513063
DOI: 10.1016/j.cmet.2022.11.009 -
Digestive Surgery 2020The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological... (Review)
Review
BACKGROUND
The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological entities with different potential for malignant transformation. The clinician must balance his or her practice between the risk of surgical overtreatment and the error of keeping a malignant lesion under surveillance.
METHODS
We review and discuss the clinical management of PCNs. Specifically, we analyze the main features of PCNs from the surgeon's point of view, as they present in the outpatient clinic. We also review the different consensus guidelines, address recent controversies in the literature, and present the current clinical practice at 4 different European Centers for pancreatic surgery.
RESULTS
The main features of PCNs were analyzed from the surgeon's point of view as they present in the outpatient clinic. All aspects of surgical management were discussed, from indications for surgery to intraoperative management and surveillance strategies.
CONCLUSIONS
Management of PCNs requires a selective approach with the aim of minimizing clinically relevant diagnostic mistakes. Through the evaluation of clinical and radiological features of a PCN, the surgeon can elaborate on a diagnostic hypothesis and assess malignancy risk, but the final decision should be tailored to the individual patient's need.
Topics: Humans; Pancreas; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Practice Guidelines as Topic; Precancerous Conditions
PubMed: 30636253
DOI: 10.1159/000496509 -
Developmental Cell May 2023Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem-cell-derived and primary...
Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem-cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and pancreas from childhood and adult donors for comparison. We delineate major cell types, define their regulomes, and describe spatiotemporal gene regulatory relationships between transcription factors. CDX2 emerged as a regulator of enterochromaffin-like cells, which we show resemble a transient, previously unrecognized, serotonin-producing pre-β cell population in fetal pancreas, arguing against a proposed non-pancreatic origin. Furthermore, we observe insufficient activation of signal-dependent transcriptional programs during in vitro β cell maturation and identify sex hormones as drivers of β cell proliferation in childhood. Altogether, our analysis provides a comprehensive understanding of cell fate acquisition in stem-cell-derived islets and a framework for manipulating cell identities and maturity.
Topics: Adult; Humans; Islets of Langerhans; Pancreas; Cell Differentiation; Insulin-Secreting Cells; Pluripotent Stem Cells
PubMed: 37040771
DOI: 10.1016/j.devcel.2023.03.011 -
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 -
BMC Surgery Jul 2023
Topics: Humans; Pancreatic Neoplasms; Pancreas; Pancreatectomy
PubMed: 37420195
DOI: 10.1186/s12893-023-02091-7 -
Frontiers in Endocrinology 2022
Topics: Islets of Langerhans; Pancreas; Pancreas, Exocrine
PubMed: 35966106
DOI: 10.3389/fendo.2022.967066 -
Annals of Surgery Mar 2023The aim of this study was to develop a classification system for pancreas-associated risk factors in pancreatoduodenectomy (PD). (Meta-Analysis)
Meta-Analysis
A Simple Classification of Pancreatic Duct Size and Texture Predicts Postoperative Pancreatic Fistula: A classification of the International Study Group of Pancreatic Surgery.
OBJECTIVE
The aim of this study was to develop a classification system for pancreas-associated risk factors in pancreatoduodenectomy (PD).
SUMMARY BACKGROUND DATA
Postoperative pancreatic fistula (POPF) is the most relevant PD-associated complication. A simple standardized surgical reporting system based on pancreas-associated risk factors is lacking.
METHODS
A systematic literature search was conducted to identify studies investigating clinically relevant (CR) POPF (CR-POPF) and pancreas-associated risk factors after PD. A meta-analysis of CR-POPF rate for texture of the pancreas (soft vs not-soft) and main pancreatic duct (MPD) diameter was performed using the Mantel-Haenszel method. Based on the results, the International Study Group of Pancreatic Surgery (ISGPS) proposes the following classification: A, not-soft (hard) texture and MPD >3 mm; B, not-soft (hard) texture and MPD ≤3 mm; C, soft texture and MPD >3 mm; D, soft texture and MPD ≤3 mm. The classification was evaluated in a multi-institutional, international cohort.
RESULTS
Of the 2917 articles identified, 108 studies were included in the analyses. Soft pancreatic texture was significantly associated with the development of CR-POPF [odds ratio (OR) 4.24, 95% confidence interval (CI) 3.67-4.89, P < 0.01) following PD. Similarly, MPD diameter ≤3 mm significantly increased CR-POPF risk compared with >3 mm diameter MPDs (OR 3.66, 95% CI 2.62-5.12, P < 0.01). The proposed 4-stage system was confirmed in an independent cohort of 5533 patients with CR-POPF rates of 3.5%, 6.2%, 16.6%, and 23.2% for type A-D, respectively ( P < 0.001).
CONCLUSION
For future pancreatic surgical outcomes studies, the ISGPS recommends reporting these risk factors according to the proposed classification system for better comparability of results.
Topics: Humans; Pancreatic Fistula; Pancreas; Pancreatic Ducts; Pancreaticoduodenectomy; Risk Factors; Postoperative Complications
PubMed: 33914473
DOI: 10.1097/SLA.0000000000004855