Background and Aim Post‐pancreaticoduodenectomy hemorrhage (PPH) is a potentially lethal complication. The objective of this study was to explore the risk factors of PPH and to evaluate the treatment options. Methods Clinical data of 739 consecutive patients undergoing pancreaticoduodenectomy between 2009 and 2017 were collected from a prospectively maintained database. Univariate and multivariate analysis was performed by logistic regression model to evaluate potential risk factors associated with early and late PPH. Results The morbidity of PPH was 8.7% (64/739), while the mortality was 12.5% (8/64). Twenty‐two (34.4%) patients developed PPH within postoperative day 1 (early PPH) whereas 42 (65.6%) patients after postoperative day 1 (late PPH). No significant risk factor was identified associated with early PPH, whereas pancreatic duct diameter < 0.4 cm, and intra‐abdominal complications, such as pancreatic fistula, intra‐abdominal abscess, and delayed gastric emptying, were independently correlated with late PPH. There were 10 (15.6%) grade A, 28 (43.8%) grade B, and 26 (40.6%) grade C bleedings. The bleeding sites were verified by endoscopy, angiography, and/or exploratory laparotomy in 23 of 54 (42.6%) patients with grade B or C hemorrhage. Seven out of nine (78%) patients with arterial bleeding were cured by angiography and embolization, while 10 of 11 (90.9%) patients with anastomotic, venous, or retroperitoneum bleeding were rescued by laparotomy. Ten patients with grade A and 22 patients with grade B or C hemorrhage were treated successfully by blood transfusion and hemostatic medications. Conclusions Hemorrhage following pancreaticoduodenectomy is a common and lethal complication. Treatment strategies should be tailored according to different etiologies.

Background Aging skin is characterized by a disturbed structure and lack of blood supply, which makes it difficult to heal once injured. ADSCs secrete large amounts of cytokines, which promote wound healing and vascular regeneration through paracrine secretion, and the number of cytokines can be elevated by hypoxic pretreating. However, the components of ADSCs are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel synthesized from gelatin and has recently emerged as a potentially attractive material for tissue engineering applications. GelMA loaded with concentrated hypoxic pretreated ADSCs conditioned medium could provide a new method of treating wounds in aged skin. Methods Primary ADSCs were isolated from human adipose tissue and characterized by flow cytometry and differentiation test. ADSCs in passages 4-6 were pretreated in the hypoxic and normoxic environments to collect conditioned medium, the conditioned medium was then concentrated to prepare concentrated ADSCs conditioned medium(cADSC-CM)(the one collected from ADSCs under hypoxia was called hypo-CM ,and the one from normoxia was called nor-CM). The concentration of cytokines was detected. After treated with cADSC-CM, the abilities of proliferation, migration, and tube formation of human umbilical vascular endothelial cells (HUVECs) were assayed, and Akt/mTOR and MAPK signal pathway was detected using western blotting. GelMA+hypo-CM hydrogel was prepared, and a comprehensive evaluation of morphology, protein release efficiency, degradation rate, mechanical properties, and rheology properties were performed. Full-thickness skin wounds were created on the backs of 20-month-old mice. After surgery, GelMA, GelMA+F12, GelMA+hypo-CM, and GelMA+nor-CM were applied to the wound surface respectively. H&E, Masson, and immunohistochemistry staining were performed, and a laser Doppler perfusion imager was used to evaluate the blood perfusion. The student’s t-test was used for analysis between two groups and a one-way analysis of variance (ANOVA) was used for analysis among multi groups. Results Our results revealed that 1) wounds in aged skin healed more slowly than that in young skin and exhibited poorer perfusion; 2) hypoxic pretreated ADSCs secreted more cytokines including VEGF by activating HIF1α; 3) hypo-CM promoted proliferation and migration of HUVECs through VEGF/Akt/mTOR and MAPK signal pathway; 4) GelMA-hypoCM accelerated wound healing and angiogenesis in aged skin in vivo. Conclusion GelMA loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells conditioned medium could accelerate wound healing in aged skin by promoting angiogenesis.

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