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I want to eat your pancreas
\"A high school boy finds the diary of his classmate - only to discover that she's dying. Yamauchi Sakura has been silently suffering from a pancreatic disease, and now exactly one person outside her family knows. He swears to her that he won't tell anyone what he learned, and the shared secret brings them closer together in this deeply moving, first-person story that traces their developing relationship in Sakura's final months of life.\" -- Back cover.
Book
Organisation of the human pancreas in health and in diabetes
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.
Journal Article
A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis
In this randomized trial involving patients with necrotizing pancreatitis, a less invasive step-up approach (percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy) was associated with fewer complications than open necrosectomy.
In patients with necrotizing pancreatitis, a less invasive step-up approach (percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy) was associated with fewer complications than open necrosectomy.
Acute pancreatitis is the third most common gastrointestinal disorder requiring hospitalization in the United States, with annual costs exceeding $2 billion.
1
,
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Necrotizing pancreatitis, which is associated with an 8 to 39% rate of death, develops in approximately 20% of patients.
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The major cause of death, next to early organ failure, is secondary infection of pancreatic or peripancreatic necrotic tissue, leading to sepsis and multiple organ failure.
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Secondary infection of necrotic tissue in patients with necrotizing pancreatitis is virtually always an indication for intervention.
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,
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–
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The traditional approach to the treatment of necrotizing pancreatitis with secondary infection of necrotic . . .
Journal Article
Pancreas Transplantation: Current Challenges, Considerations, and Controversies
Abstract
Pancreas transplantation (PTx) reestablishes an autoregulating source of endogenous insulin responsive to normal feedback controls. In addition to achieving complete β-cell replacement that frees the patient with diabetes from the need to monitor serum glucose and administer exogenous insulin, successful PTx provides counterregulatory hormone secretion and exocrine function. A functioning PTx mitigates glycemic variability, eliminates the daily stigma and burden of diabetes, restores normal glucose homeostasis in patients with complicated diabetes, and improves quality of life and life expectancy. The tradeoff is that it entails a major surgical procedure and requisite long-term immunosuppression. Despite the high likelihood of rendering patients euglycemic independent of exogenous insulin, PTx is considered a treatment rather than a cure. In spite of steadily improving outcomes in each successive era coupled with expansion of recipient selection criteria to include patients with a type 2 diabetes phenotype, a decline in PTx activity has occurred in the new millennium related to a number of factors including: (1) lack of a primary referral source and general acceptance by the diabetes care community; (2) absence of consensus criteria; and (3) access, education, and resource issues within the transplant community. In the author's experience, patients who present as potential candidates for PTx have felt as though they needed to circumvent the conventional diabetes care model to gain access to transplant options. PTx should be featured more prominently in the management algorithms for patients with insulin requiring diabetes who are failing exogenous insulin therapy or experiencing progressive diabetic complications regardless of diabetes type. Furthermore, all patients with diabetes and chronic kidney disease should undergo consideration for simultaneous pancreas-kidney transplantation independent of geography or location.
Journal Article
Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis
A multicenter, randomized trial of patients with infected necrotizing pancreatitis evaluated immediate drainage within 24 hours after infected necrosis was diagnosed as compared with postponed drainage. Immediate drainage was not superior to postponed drainage in reducing complications. Patients assigned to immediate drainage underwent a greater number of invasive procedures.
Journal Article
Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes
Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes. In this 6-month randomized, multicenter trial involving such patients, a closed-loop system led to a greater percentage of time with the glucose level in a target range than did a sensor-augmented insulin pump.
Journal Article
Transluminal endoscopic necrosectomy after acute pancreatitis: a multicentre study with long-term follow-up (the GEPARD Study)
Background:As with endoscopic transmural drainage of peripancreatic fluid collections, the same transluminal access can be expanded to introduce an endoscope through the gastrointestinal wall into the retroperitoneum and remove infected pancreatic necroses under direct visual control. This study reports the first large series with long-term follow-up.Methods:Data for all patients undergoing transluminal endoscopic removal of (peri)pancreatic necroses between 1999 and 2005 in six different centres were collected retrospectively, and the patients were followed up prospectively until 2008. The initial patient and treatment outcome data were recorded, as were long-term results.Results:Ninety-three patients (63 men, 30 women; mean age 57 years) underwent a mean of six interventions starting at a mean of 43 days after an attack of severe acute pancreatitis. After establishment of transluminal access to the necrotic cavity and subsequent endoscopic necrosectomy, initial clinical success was obtained in 80% of the patients, with a 26% complication and a 7.5% mortality rate at 30 days. After a mean follow-up period of 43 months, 84% of the initially successfully treated patients had sustained clinical improvement, with 10% receiving further endoscopic and 4% receiving surgical treatment for recurrent cavities; 16% suffered recurrent pancreatitis.Conclusions:Direct transluminal endoscopic removal of pancreatic necroses is associated with good long-term maintenance of the high initial efficacy; complications can occur, with an associated mortality of around 7.5%. Further studies are necessary in order to optimise endotherapy and define its role in relation to surgery in the clinical management of such patients.
Journal Article
3D genomic mapping reveals multifocality of human pancreatic precancers
Pancreatic intraepithelial neoplasias (PanINs) are the most common precursors of pancreatic cancer, but their small size and inaccessibility in humans make them challenging to study
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. Critically, the number, dimensions and connectivity of human PanINs remain largely unknown, precluding important insights into early cancer development. Here, we provide a microanatomical survey of human PanINs by analysing 46 large samples of grossly normal human pancreas with a machine-learning pipeline for quantitative 3D histological reconstruction at single-cell resolution. To elucidate genetic relationships between and within PanINs, we developed a workflow in which 3D modelling guides multi-region microdissection and targeted and whole-exome sequencing. From these samples, we calculated a mean burden of 13 PanINs per cm
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and extrapolated that the normal intact adult pancreas harbours hundreds of PanINs, almost all with oncogenic
KRAS
hotspot mutations. We found that most PanINs originate as independent clones with distinct somatic mutation profiles. Some spatially continuous PanINs were found to contain multiple
KRAS
mutations; computational and in situ analyses demonstrated that different
KRAS
mutations localize to distinct cell subpopulations within these neoplasms, indicating their polyclonal origins. The extensive multifocality and genetic heterogeneity of PanINs raises important questions about mechanisms that drive precancer initiation and confer differential progression risk in the human pancreas. This detailed 3D genomic mapping of molecular alterations in human PanINs provides an empirical foundation for early detection and rational interception of pancreatic cancer.
Quantitative multimodal 3D reconstruction of human pancreatic tissue at single-cell resolution reveals a high burden of multifocal, genetically heterogeneous pancreatic intraepithelial neoplasias in the normal adult pancreas.
Journal Article
Pancreas regeneration
The pancreas is made from two distinct components: the exocrine pancreas, a reservoir of digestive enzymes, and the endocrine islets, the source of the vital metabolic hormone insulin. Human islets possess limited regenerative ability; loss of islet β-cells in diseases such as type 1 diabetes requires therapeutic intervention. The leading strategy for restoration of β-cell mass is through the generation and transplantation of new β-cells derived from human pluripotent stem cells. Other approaches include stimulating endogenous β-cell proliferation, reprogramming non-β-cells to β-like cells, and harvesting islets from genetically engineered animals. Together these approaches form a rich pipeline of therapeutic development for pancreatic regeneration.
Journal Article