RESUMO
Background: Postoperative acute pancreatitis (POAP) is a specific complication after pancreatectomy. The acute inflammatory response of the residual pancreas may affect the healing of pancreatoenteric anastomoses, leading to postoperative pancreatic fistulas (POPFs), abdominal infections, and even progressive systemic reactions, conditions that negatively affect patients' prognoses and can cause death. However, to the best of our knowledge, no systematic reviews or meta-analytic studies have assessed the incidence and risk factors of POAP after pancreaticoduodenectomy (PD). Method: We searched PubMed, Web of Science, Embase, and Cochrane Library databases for relevant literature describing the outcomes of POAP after PD until November 25, 2022, and we used the Newcastle-Ottawa Scale to assess the quality of the studies. Next, we pooled the incidence of POAP and the odds ratios (ORs) and 95% confidence intervals (CIs) of the risk factors using a random-effect meta-analysis. I2 tests were used to assess heterogeneity between the studies. Results: We analyzed data from 7,164 patients after PD from 23 articles that met the inclusion criteria for this study. The subgroup results of the meta-analysis by different POAP diagnostic criteria showed that the incidences of POAP were 15% (95% CI, 5-38) in the International Study Group for Pancreatic Surgery group, 51% (95% CI, 42-60) in the Connor group, 7% (95% CI, 2-24) in the Atlanta group, and 5% (95% CI, 2-14) in the unclear group. Being a woman [OR (1.37, 95% CI, 1.06-1.77)] or having a soft pancreatic texture [OR (2.56, 95% CI, 1.70-3.86)] were risk factors of POAP after PD. Conclusion: The results showed that POAP was common after PD, and its incidence varied widely according to different definitions. Large-scale reports are still needed, and surgeons should remain aware of this complication. Systematic Review Registration: identifier: CRD42022375124.
RESUMO
The recently described role of RNA methylation in regulating immune cell infiltration into tumors has attracted interest, given its potential impact on immunotherapy response. YTHDF1 is a versatile and powerful m6A reader, but the understanding of its impact on immune evasion is limited. Here, we reveal that tumor-intrinsic YTHDF1 drives immune evasion and immune checkpoint inhibitor (ICI) resistance. Additionally, YTHDF1 deficiency converts cold tumors into responsive hot tumors, which improves ICI efficacy. Mechanistically, YTHDF1 deficiency inhibits the translation of lysosomal genes and limits lysosomal proteolysis of the major histocompatibility complex class I (MHC-I) and antigens, ultimately restoring tumor immune surveillance. In addition, we design a system for exosome-mediated CRISPR/Cas9 delivery to target YTHDF1 in vivo, resulting in YTHDF1 depletion and antitumor activity. Our findings elucidate the role of tumor-intrinsic YTHDF1 in driving immune evasion and its underlying mechanism.
