Background and AimsImmunotherapy with PD-1 inhibitors combined with tyrosine kinase inhibitors (TKIs) has been proven to be effective against advanced hepatocellular carcinoma (HCC). The aim of this study was to identify the feasibility and safety of subsequent salvage surgery after this combination therapy.Methods and PatientsA retrospective analysis was performed on patients with primary HCC with major vascular invasion between 2018 and 2019. All cases were treated with a combination of a PD-1 inhibitor and TKI agents and subsequent surgery.ResultsA total of 10 HCC cases with major vascular invasion met the successful conversion criteria after the combination therapy, and eight patients underwent subsequent salvage surgery after both radiology and 3D quantitative oncological assessment. Partial response (PR) was recorded in 7 of 10 patients and complete response (CR) in 3 of 10 patients before salvage surgery. Salvage surgery included right hepatectomy, left hepatectomy, and anatomic segmental hepatectomy. The mean intraoperative blood loss was 1,650 ml (50–3,000 ml). No complications beyond Clavien–Dindo level III or postoperative mortality were observed. The viable tumor cell rate of the PR cases (modified response evaluation criteria in solid tumors, mRECIST) varied from 1.5% to 100%, and only one patient had pathology-proven pathological complete response (pCR). The postoperative median follow-up time was 19.7 months (9.1–24.9 months). The 12-month recurrence-free survival rate of all cases who underwent salvage surgery was 75%.ConclusionSalvage surgery was effective and safe after conversion therapy with PD-1 inhibitors plus TKIs and may increase the long-term oncological benefit for patients with unresectable HCC.
Objectives An acute injury is often accompanied by tissue regeneration. In this process, epithelial cells show a tendency of cell proliferation under the induction of injury stress, inflammatory factors, and other factors, accompanied by a temporary decline of cellular function. Regulating this regenerative process and avoiding chronic injury is a concern of regenerative medicine. The severe coronavirus disease 2019 (COVID-19) has posed a significant threat to people’s health caused by the coronavirus. Acute liver failure (ALF) is a clinical syndrome resulting from rapid liver dysfunction with a fatal outcome. We hope to analyze the two diseases together to find a way for acute failure treatment.Methods COVID-19 dataset (GSE180226) and ALF dataset (GSE38941) were downloaded from the Gene Expression Omnibus (GEO) database, and the “Deseq2” package and “limma” package were used to identify differentially expressed genes (DEGs). Common DEGs were used for hub genes exploration, Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to verify the role of hub genes in liver regeneration during in vitro expansion of liver cells and a CCl4-induced ALF mice model.Results: The common gene analysis of the COVID-19 and ALF databases revealed 15 hub genes from 418 common DEGs. These hub genes, including CDC20, were related to cell proliferation and mitosis regulation, reflecting the consistent tissue regeneration change after the injury. Furthermore, hub genes were verified in vitro expansion of liver cells and in vivo ALF model. On this basis, the potential therapeutic small molecule of ALF was found by targeting the hub gene CDC20.Conclusion We have identified hub genes for epithelial cell regeneration under acute injury conditions and explored a new small molecule Apcin for liver function maintenance and ALF treatment. These findings may provide new approaches and ideas for treating COVID-19 patients with ALF.
Background This study aims to retrospectively analyse the safety of ambulatory laparoscopic cholecystectomy (ALC) and identify risk factors for delayed discharge after ALC in the elderly. Methods Consecutive patients who were scheduled to undergo ALC were assigned to the elderly group (age ≥ 65 years) or the non‐elderly group. The primary outcome was postoperative discharge within 24 h (D24). Secondary outcomes were perioperative mortality, reasons for delayed discharge (psychosocial reasons (DP), complications (DC), drainage (DD) and conversion to open surgery (DCO)), intraoperative data and readmission within 30 days after discharge (readmission). Differences were statistically significant when P < 0.05. Results There were 7657 patients assigned to the elderly group (n = 1143) or the non‐elderly group (n = 6514). The differences between elderly patients and non‐elderly patients in the operation time (51.0 (37.0–70.0) versus 50.0 (35.0–65.0) min), blood loss (10.0 (5.0–10.0) versus 5.0 (5.0–10.0) mL), D24 (75.5% versus 81.7%) and DD (7.8% versus 3.2%) were statistically significant (P < 0.05, respectively). The differences between elderly patients and non‐elderly patients in DP (8.2% versus 6.7%), DC (7.8% versus 7.9%), DCO (0.7% versus 0.5%) and readmission (0.5% versus 0.4%) were not statistically significant (P > 0.05, respectively). Independent risk factors for delayed discharge after ALC in the elderly were male sex, octogenarian status, prolonged operation time, arrhythmia, type 2 diabetes mellitus, a previous operation in the upper abdomen, acute inflammation of gallbladder and a gallbladder wall thicker than 3 mm (P < 0.05, respectively). Conclusion ALC in the elderly is feasible and safe.
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