Surgical and Endoscopic Intervention for Chronic Pancreatitis in Children: The Kings College Hospital Experience.

Paediatric chronic pancreatitis (CP) is a rare and debilitating pathology that often requires invasive diagnostics and therapeutic interventions either to address a primary cause such as a pancreaticobiliary malunion or to deal with secondary complications such as chronic pain. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are two endoscopic modalities that have an established diagnostic role in paediatric CP, and their therapeutic utilisation is increasing in popularity. Surgical decompression of the obstructed and dilated pancreatic duct plays a role in alleviating pancreatic duct hypertension, a common association in CP. Surgery equally has a role in certain anatomical abnormalities of the pancreaticobiliary draining system, or occasionally in some CP complications such as drainage of a symptomatic pancreatic pseudocyst.

Modulation of sirtuins during monolayer chondrocyte culture influences cartilage regeneration upon transfer to a 3D culture environment.

This study examined the role of sirtuins in the regenerative potential of articular chondrocytes. Sirtuins (SIRT1-7) play a key role in regulating cartilage homeostasis. By inhibiting pro-inflammatory pathways responsible for cartilage degradation and promoting the expression of key matrix components, sirtuins have the potential to drive a favourable balance between anabolic and catabolic processes critical to regenerative medicine. When subjected to osmolarity and glucose concentrations representative of the in vivo niche, freshly isolated bovine chondrocytes exhibited increases in SIRT1 but not SIRT3 gene expression. Replicating methods adopted for the in vitro monolayer expansion of chondrocytes for cartilage regenerative therapies, we found that SIRT1 gene expression declined during expansion. Manipulation of sirtuin activity during in vitro expansion by supplementation with the SIRT1-specific activator SRT1720, nicotinamide mononucleotide, or the pan-sirtuin inhibitor nicotinamide, significantly influenced cartilage regeneration in subsequent 3D culture. Tissue mass, cellularity and extracellular matrix content were reduced in response to sirtuin inhibition during expansion, whilst sirtuin activation enhanced these measures of cartilage tissue regeneration. Modulation of sirtuin activity during monolayer expansion influenced H3K27me3, a heterochromatin mark with an important role in development and differentiation. Unexpectedly, treatment of primary chondrocytes with sirtuin activators in 3D culture reduced their matrix synthesis. Thus, modulating sirtuin activity during the in vitro monolayer expansion phase may represent a distinct opportunity to enhance the outcome of cartilage regenerative medicine techniques.