Cuproptosis regulatory genes greatly contribute to clinical assessments of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common abdominal cancer with dissatisfactory therapeutic effects. The discovery of cuproptosis lights on new approach for cancer treatment and assessment. So far, there is extremely limited research investigating the roles of cuproptosis-related (CR) genes in cancers. METHODS: A novel CR risk signature was constructed using the Lasso regression analysis. Its prognostic value was assessed via a series of survival analyses and validated in three GEO cohorts. The effects of CR risk signature on tumor immune microenvironment (TIM) were explored through CIBERSORT, ESTIMATE, and ssGSEA algorithms. Using GESA, we investigated its impacts on various metabolism process. The somatic mutation features of CR signature genes were also explored via cBioPortal database. Using tumor mutation burden, expressions of immune checkpoints, TIDE score, IMvigor 210 cohort, and GSE109211 dataset, we explored the potential associations of CR risk score with the efficacy of immune checkpoint inhibitors (ICIs) and sorafenib. Finally, the biofunctions of DLAT in HCC cells were ascertained through qPCR, immunohistochemistry, colony formation, and Transwell assays. RESULTS: FDX1, DLAT, CDKN2A and GLS constituted the CR risk signature. CR risk signature possessed high prognostic value and was also applicable to three validation cohorts. Meanwhile, it could improve the accuracy and clinical making-decision benefit of traditional prognostic model. Moreover, high CR risk was indicative of unfavorable anti-tumor immune response and active metabolisms of glycolysis and nucleotide. As for therapeutic correlation, CR risk score was a potential biomarker for predicting the efficacy of ICIs and sorafenib. Through qPCR and immunohistochemistry detection in clinical samples, we reconfirmed DLAT was significantly upregulated in HCC samples. Overexpression of DLAT could promote the proliferation, migration, and invasion of HepG2 and HuH-7 cells. CONCLUSIONS: The novel CR risk signature greatly contributed to the clinical assessment of HCC. Cuproptosis regulatory gene DLAT possessed cancer-promoting capacities and was expected to be a promising therapeutic target for HCC.

Comparison of laparoscopic cholecystectomy and delayed laparoscopic cholecystectomy in aged acute calculous cholecystitis: a cohort study.

BACKGROUND: In elderly patients with calculous acute cholecystitis, the risk of emergency surgery is high, and percutaneous cholecystostomy tube drainage (PC) combined with delayed laparoscopic cholecystectomy (DLC) may be a good choice. We retrospectively compared laparoscopic cholecystectomy (LC) to DLC after PC to determine which is the better treatment strategy. METHOD: We performed a retrospective cohort analysis of 752 patients with acute calculous cholecystitis. Patients with the following conditions were included: (1) age > 65 years old; (2) patients with a grade 2 or 3 severity of cholecystitis according to the 2013 Tokyo Guidelines (TG13); (3) the surgeons who performed the LC were professors or associate professors and (4) the DLC was performed in our hospital after PC. Patients who missed their 30-day follow-up; were diagnosed with bile duct stones, cholangitis or gallstone pancreatitis or were pregnant were excluded from the study. A total of 51 of 314 patients who underwent LC and 73 of 438 patients who underwent PC + DLC were assessed. PC + DLC and LC patients were matched by cholecystitis severity grade according to the TG13, and the National Surgical Quality Improvement Program (NSQIP) calculator was used to predict mortality (n = 21/group). Preoperative characteristics and postoperative outcomes were analysed. RESULTS: Compared to the matched LC group, the DLC group had less intraoperative bleeding (42.2 vs 75.3 mL, p = 0.014), shorter hospital stays (4.9 vs 7.4 days, p = 0.010) and lower rates of type A bile duct injury (4.8% vs 14.3%, p = 0.035) and type D (0 vs 9.5%, p = 0.002) according to Strasberg classification, residual stones (4.8 vs 14.3%, p = 0.035) and gastrointestinal organ injury (0 vs 3.6%, p < 0.001). Patients in the DLC group had lower incidences of ICU admission and death and a significantly lower incidence of repeat surgery. CONCLUSION: In elderly patients treated for acute calculous cholecystitis, the 30-day mortality and complication rates were lower for PC + DLC than for LC. However, the total hospitalisation time was significantly prolonged and the costs were significantly higher for PC + DLC.

Comparison of Emergency Cholecystectomy with Delayed Cholecystectomy After Percutaneous Transhepatic Gallbladder Drainage in Patients with Moderate Acute Cholecystitis.

INTRODUCTION: Patients with moderate (grade II) acute cholecystitis patients, as defined by the 2013 Tokyo Guidelines, were retrospectively compared with respect to emergency cholecystectomy (EC) and delayed cholecystectomy (DC) after percutaneous transhepatic gallbladder drainage (PTGBD) to determine the better treatment strategy. METHODS: Forty-nine of 103 patients with PTGBD and 47 of 54 patients with EC were assessed for eligibility from January 2013 to January 2017. Patients with the following conditions were included: (i) moderate (grade II) acute cholecystitis diagnosed by the 2013 Tokyo Guidelines; (ii) no common bile duct stones; (iii) no atrophic cholecystitis; (iv) no decompensated liver cirrhosis and massive ascites; (v) no diffuse peritonitis; (vi) surgeons are professors or associate professors; and (vii) PTGBD is not the only procedure for the patient defined by clinicians. The preoperative characteristics and postoperative outcomes were analyzed. PTGBD was performed by experienced interventional radiologists and cholecystectomy was performed by professors or associate professors. RESULTS: Patients in the EC and PTGBD + DC groups had similar demographic, clinical, preoperative laboratory, and imaging characteristics. Both PTGBD and EC resolved the cholecystitis quickly. Compared to the PTGBD + DC group, EC patients had more intraoperative bleeding (101 ± 125 mL versus 33 ± 37 mL, P = .003), longer duration of postoperative abdominal drainage (9.0 ± 12.9 days versus 3.4 ± 2.1 days, P = .041), more patients converted to open cholecystectomy (OC; 19.1% versus 4.1%, P = .021), more OC patients (14.9% versus 0%, P = .005), more patients with gangrenous cholecystitis (40.4% versus 8.2%, P < .001), more cholecystitis patients with perforation (12.8% versus 0%, P = .012), a higher incidence of respiratory failure (14.8% versus 2.0%, P = .029), more admissions to the intensive care unit (ICU) (21.3% versus 2.0%, P = .003), and longer postoperative hospital stays (8.2 ± 3.2 days versus 11.6 ± 4.6 days, P < .001) in the PTGBD + DC group. In addition, there were statistically more OC patients (63.2% versus 14.3%, P = .001) in the nonbiliary surgeon group than the biliary surgeon group. CONCLUSION(S): In patients with moderate (grade II) acute cholecystitis, PTGBD and EC were highly efficient in resolving cholecystitis. DC patients after PTGBD had better outcomes with a lower rate of OC, less intraoperative bleeding, shorter duration of postoperative abdominal drainage, shorter hospital stays after cholecystectomy, a lower incidence of respiratory failure, fewer admissions to the ICU than EC, and reversed the pathologic process affecting the gallbladder. The total postoperative hospital stay was longer in the PTGBD + DC group.