Advance care planning in patients undergoing surgery to resect pancreatic adenocarcinoma: Underlying tension between balancing hope and realism.

BACKGROUND: The timing and the dose of Advanced Care Planning in patients with pancreatic ductal adenocarcinoma undergoing curative-intent resection are generally dictated by the surgeon performing the operation. METHODS: A qualitative investigation using 1:1 interviews with 40 open-ended questions was conducted with a convenience sample of 10 high-volume pancreatic surgeons from across the country. The grounded theory approach was used for data analysis. RESULTS: A total of 10 interviews were conducted with expert pancreatic surgeons-6 males and 4 females. During preoperative counseling, all surgeons attempt to motivate patients by emphasizing hope, optimism, and the fact that surgery offers the only opportunity for cure. All surgeons discuss the possibility of recurrence as well as postoperative complications; however, a majority perceived that patients do not fully appreciate the likelihood of recurrence or postoperative complications. All surgeons acknowledged the importance of end-of-life conversations when death is imminent. Seventy percent of surgeons had mixed opinions regarding benefits of preoperative Advanced Care Planning in the preoperative setting, while 20% felt it was definitely beneficial, particularly that delivery of care aligned with patient goals. All surgeons emphasized that Advanced Care Planning should be led by a physician who both knows the patient well and understands the nuances of pancreatic ductal adenocarcinoma management. Most common barriers to in-depth Advanced Care Planning discussion reported by surgeons include taking away hope, lack of time, and concern for sending "mixed messages." CONCLUSION: We identified that surgeons experience a fundamental tension between promoting realistic long-term goals and expectations versus focusing on hope and enabling an overly optimistic perception of prognosis.

Protein-Nucleic Acid Conjugation with Sterol Linkers Using Hedgehog Autoprocessing.

Hedgehog (Hh) precursor proteins contain an autoprocessing domain called HhC whose native function is protein cleavage and C-terminal glycine sterylation. The transformation catalyzed by HhC occurs in cis from a precursor protein and exhibits wide tolerance toward both sterol and protein substrates. Here, we repurpose HhC as a 1:1 protein-nucleic acid ligase, with the sterol serving as a molecular linker. A procedure is described for preparing HhC-active sterylated DNA, called steramers, using aqueous compatible chemistry and commercial reagents. Steramers have KM values of 7-11 µM and reaction t1/2 values of ∼10 min. Modularity of the HhC/steramer method is demonstrated using four different proteins along with structured and unstructured sterylated nucleic acids. The resulting protein-DNA conjugates retain the native solution properties and biochemical function. Unlike self-tagging domains, HhC does not remain fused to the conjugate; rather, enzymatic activity is mechanistically coupled to conjugate release. That unique feature of HhC, coupled with efficient kinetics and substrate tolerance, may ease access and open new applications for these suprabiological chimeras.