Photodynamic therapy (PDT) is an established palliative treatment for perihilar cholangiocarcinoma that is clinically promising. However, tumors tend to regrow after PDT, which may result from the PDT-induced activation of survival pathways in sublethally afflicted tumor cells. In this study, tumor-comprising cells (i.e., vascular endothelial cells, macrophages, perihilar cholangiocarcinoma cells, and EGFR-overexpressing epidermoid cancer cells) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). The post-PDT survival pathways and metabolism were studied following sublethal (LC50) and supralethal (LC90) PDT. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly HIF-1-, NF-кB-, AP-1-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. PDT-subjected SK-ChA-1 cells downregulated proteins associated with EGFR signaling, particularly at LC90. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor-associated cell types that transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, tumor cells sublethally afflicted by PDT are a major therapeutic culprit. Our multi-omic analysis further unveiled multiple druggable targets for pharmacological co-intervention.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-016-2401-0) contains supplementary material, which is available to authorized users.

Patients undergoing complex gastrointestinal surgery are at high risk of major postoperative complications (e.g., anastomotic leakage, sepsis), classified as Clavien-Dindo (CD) ! IIIa. Identification of preoperative risk factors can lead to the identification of high-risk patients. These risk factors can also be used to design personalized perioperative care. This systematic review focuses on the identification of these factors. The Medline and Embase databases were searched for prospective, retrospective cohort studies and randomized controlled trials investigating the effect of risk factors on the occurrence of major postoperative complications and/or mortality after complex gastrointestinal cancer surgery. Risk of bias was assessed using the Quality in Prognostic Studies tool. The level of evidence was graded based on the number of studies reporting a significant association between risk factors and major complications. A total of 207 eligible studies were retrieved, identifying 33 risk factors for major postoperative complications and 13 preoperative laboratory results associated with postoperative complications. The present systematic review provides a comprehensive overview of preoperative risk factors associated with major postoperative complications. A wide range of risk factors are amenable to actions in perioperative care and prehabilitation programs, which may lead to improved outcomes for high-risk patients. Additionally, the knowledge of this study is important for benchmarking surgical outcomes.

Objective The aim of this study is to identify preoperative patient-related prognostic factors for anastomotic leakage, mortality, and major complications in patients undergoing oncological esophagectomy. Background Esophagectomy is a high-risk procedure with an incidence of major complications around 25% and short-term mortality around 4%. Methods We systematically searched the Medline and Embase databases for studies investigating the associations between patient-related prognostic factors and anastomotic leakage, major postoperative complications (Clavien–Dindo ≥ IIIa), and/or 30-day/in-hospital mortality after esophagectomy for cancer. Results Thirty-nine eligible studies identifying 37 prognostic factors were included. Cardiac comorbidity was associated with anastomotic leakage, major complications, and mortality. Male sex and diabetes were prognostic factors for anastomotic leakage and major complications. Additionally, American Society of Anesthesiologists (ASA) score > III and renal disease were associated with anastomotic leakage and mortality. Pulmonary comorbidity, vascular comorbidity, hypertension, and adenocarcinoma tumor histology were identified as prognostic factors for anastomotic leakage. Age > 70 years, habitual alcohol usage, and body mass index (BMI) 18.5–25 kg/m2 were associated with increased risk for mortality. Conclusions Various patient-related prognostic factors are associated with anastomotic leakage, major postoperative complications, and postoperative mortality following oncological esophagectomy. This knowledge may define case-mix adjustment models used in benchmarking or auditing and may assist in selection of patients eligible for surgery or tailored perioperative care.

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