Supramolecular Polymer Hydrogels for Drug-Induced Tissue Regeneration.

Supramolecular polymers self-assemble into nanofibers, micelles, and other nanostructures through weak noncovalent interactions between subunits. Such systems possess attractive properties for use in a variety of practical settings such as energy, sustainability, and healthcare. In regenerative medicine, a common approach involves implanting a supramolecular material containing cell and growth factor binding motifs directly into a diseased or traumatized tissue defect, whereupon it interacts with and/or recruits components of the biological system to induce tissue healing. Here we introduce a supramolecular therapeutic in which tissue regeneration is orchestrated by a supramolecular polymer prodrug implanted subcutaneously in a remote tissue. Our approach exploits a hydrophobic small-molecule inhibitor of prolyl hydroxylase enzyme as both a regeneration-inducing therapeutic and a structure-directing agent in a supramolecular polymer that forms shear-thinning nanofiber hydrogels. Subcutaneous injection of the supramolecular hydrogel in the back of mice wounded with a critical-sized defect in the ear led to transient upregulation of hypoxia inducible factor-1α and regeneration of ear tissue in a manner reminiscent of epimorphic regeneration. This drug-induced regeneration strategy utilizes a simple and translatable supramolecular design, eliminates the need for delivery of biologics ( e. g., growth factors, cells), and avoids implantation of a foreign material directly in a tissue defect.

Surgeon-Led Imaging Review for Patients with Periampullary Disease: An Important Aspect of the Preoperative Consultation.

Background: The perceived benefit of utilizing patients' own imaging studies as a preoperative educational tool has not been studied. Methods: Pancreaticobiliary surgeons reviewed key findings of imaging studies with patients to educate about their diagnosis and inform treatment recommendations. Patient surveys were administered pre- and postvisit by an independent researcher to assess the impact of this practice. Results: Only 55% of patients stated that it was important to see their imaging studies before the consultation. However, after the visit, 90% of patients understood their disease process better, and 86% of patients had a clearer understanding of their planned operation having seen their imaging studies. This represents significant improvement in patients' understanding of their medical condition (p < 0.05). Conclusion: Reviewing imaging findings with patients is an underappreciated aspect of the surgical consultation. It is a powerful educational tool that takes little time, improves patient understanding, and enhances patient experience.

Modified Appleby Procedure with Arterial Reconstruction for Locally Advanced Pancreatic Adenocarcinoma: A Literature Review and Report of Three Unusual Cases.

BACKGROUND: Pancreatic body and tail ductal adenocarcinomas are often diagnosed with local vascular invasion of the celiac axis (CA) and its various branches. With such involvement, these tumors have traditionally been considered unresectable. The modified Appleby procedure allows for margin negative resection of some such locally advanced tumors. This procedure involves distal pancreatectomy with en bloc splenectomy and CA resection and relies on the presence of collateral arterial circulation via an intact pancreaticoduodenal arcade and the gastroduodenal artery to maintain prograde hepatic arterial perfusion. When the resultant collateral circulation is inadequate to provide sufficient hepatic and gastric arterial inflow, arterial reconstruction (AR) is necessary to "supercharge" the inflow. Herein, we review all reported cases of AR with modified Appleby procedures that we have identified in the literature, and we report our experience of three recent cases with arterial reconstruction including two cases with arterial bypasses not requiring interposition grafting. METHODS: Perioperative and oncologic outcomes from our Institutional Review Board-approved database of pancreatic resections at the Thomas Jefferson University were reviewed. Additionally, PubMed search for cases of distal or total pancreatectomy with celiac axis resection and concurrent AR was performed. RESULTS: From the literature, 12 reports involving 28 patients were identified of distal and total pancreatectomy with AR after CA resection. The most common AR in the literature, performed in 12 patients, was a bypass from the aorta to the common hepatic artery (CHA) using a variety of interposition conduits. In our institutional experience, patient #1 had a primary side-to-end aorto-CHA bypass, patient #2 had a primary end-to-end bypass of the transected distal CHA to the left gastric artery in the setting a replaced left hepatic artery, and patient #3 required an aortic to proper hepatic artery bypass with saphenous vein graft and portal venous reconstruction. All patients recovered from their operations without ischemic complications, and they are currently 16, 15, and 13 months post-op, respectively. CONCLUSIONS: The criteria for resectability in patients with locally advanced pancreatic body and tail neoplasms are expanding due to increasing experience with AR in the setting of the modified Appleby procedure. When performing AR, primary arterial re-anastomosis may be considered preferable to interposition grafting as it decreases the potential for the infectious and thrombotic complications associated with conduits and it reduces the number of vascular anastomoses from two to one. Consideration must also be given to normal variant anatomy of the hepatic circulation during operative planning as the origin of the left gastric artery is resected with the CA. The modified Appleby procedure with AR, when used in appropriately selected patients, offers the potential for safe, margin negative resection of locally advanced pancreatic body and tail tumors.