Predictive Factors for Postoperative Pancreatic Fistula-A Swedish Nationwide Register-Based Study.

BACKGROUND: A serious complication after pancreatoduodenectomy (PD) is postoperative pancreatic fistula (POPF). The aim of this study was to analyse the incidence and predictive factors for POPF by using a large nationwide cohort. METHODS: Data from the Swedish National Registry for Pancreatic and Periampullary Cancer for all patients undergoing a PD from 2010 until 30th June 2018 were collected. The material was analysed in two groups, no POPF and clinically relevant (grade B and C) POPF. RESULTS: A total of 2503 patients underwent PD, of which 245 (10%) developed POPF. Patients with POPF had significantly more overall complications (Clavien Dindo ≥3a, 75% vs. 21%, p < 0.001) and longer hospital stay (median 23 [16-35] vs. 11 [8-15], p < 0.001) than patients without POPF. The risk of POPF was higher with increased BMI (OR 1.08, p < 0.001). Preoperative presence of diabetes (OR 0.52, p = 0.012) and preoperative biliary drainage (OR 0.34, p < 0.001) reduced the risk of POPF. Reconstruction with pancreaticojejunostomy caused a more than two folded increase in POPF compared with pancreaticogastrostomy (OR 2.41, p < 0.001). Weight gain ≥2 kg on postoperative day 1 was also a risk factor (OR 1.76, p < 0.001). CONCLUSION: A high BMI, a pancreaticojejunostomy and postoperative weight gain were risk factors for developing POPF. Diabetes or preoperative biliary drainage was protective.

Convergent synthesis of neoglycopeptides by coupling of 2-bromoethyl glycosides to cysteine and homocysteine residues in T cell stimulating peptides.

The 2-bromoethyl beta-glycosides of the disaccharide galabiose [Gal(alpha1-4)Gal] and the trisaccharides globotriose [Gal(alpha1-4)Gal(beta1-4)Glc] and 3'-sialyllactose [Neu5Ac(alpha2-3)Gal(beta1-4)Glc] have been prepared by improved routes. The 2-bromoethyl glycosides were then used in cesium carbonate promoted alkylations of the sulfhydryl groups of cysteine and homocysteine residues in T cell stimulating peptides. This convergent and general approach was used to prepare 16 neoglycopeptides which were obtained in 52-95% yields after purification by HPLC. 1H NMR spectroscopy revealed that beta-elimination and epimerization of neoglycopeptide stereocentres did not occur during the synthesis.

Major histocompatibility complex class I-binding peptides are recycled to the cell surface after internalization.

Cytotoxic T lymphocytes (CTL) recognize target antigens as short, processed peptides bound to major histocompatibility complex class I (MHC-I) heavy and light chains (beta 2-microglobulin; beta 2-m). The heavy chain, which comprise the actual peptide binding alpha-1 and alpha-2 domains, can exist at the cell surface in different forms, either free, bound to beta 2-m or as a ternary complex with beta 2-m and peptides. MHC-I chains are also known to internalize, and recycle to the cell surface, and this has been suggested to be important in peptide presentation. Whether MHC-I-bound peptides also can recycle is not known. We have investigated this by using both peptide transporter mutant RMA-S cells and EL4 cells loaded with Db-binding peptides, by two different approaches. First, peptides were covalently linked with galabiose (Gal alpha 4Gal) at a position which did not interfere with Db binding or immunogenicity, and peptide recycling tested with Gal2-specific monoclonal antibodies. By flow cytometry, a return of Gal2 epitopes to the cell surface was found, after cellular internalization and cell surface clearance by pronase treatment. This peptide recycling could be discriminated from free fluid-phase uptake and was inhibited by methylamine, chloroquine and low temperature (18 degrees C) but not by leupeptin. Second, specific CTL were reacted with peptide-loaded target cells after complete removal of surface Db molecules by pronase, and after different times of incubation at 37 degrees C to allow reexpression. By this procedure, reappearance of target cell susceptibility was confirmed. The results are in agreement with a model for optimizing peptide presentation by recycling through an intracellular compartment similar to early endosomes in certain antigen-presenting cells.