Improved long-term outcomes after innovative preoperative evaluation and conception of precise surgery for gallbladder cancer.

BACKGROUND: Three-dimensional visualization preoperative evaluation (3D-VPE) and enhanced recovery after surgery (ERAS) have been suggested to improve outcomes of cancer surgery in patients, yet little is known regarding their clinical benefit in patients with gallbladder cancer (GBC). We hypothesized that the combination of 3D-VPE and ERAS would improve the outcome of patients undergoing surgery for GBC. OBJECTIVE: This study aimed to determine if 3D-VPE and ERAS can improve the outcomes and overall survival in patients with GBC, establishing a novel patient management strategy for GBC. METHODS: A total of 227 patients with GBC were recruited and divided into two groups: those who received traditional treatment between January 2000 and December 2010 (n = 86; the control group) and those who underwent 3D-VPE and ERAS between January 2011 and December 2017 (n = 141). Univariate and multivariate analyses were employed to assess the relationship among disease stages, lymph node invasion, and cell differentiation between the two groups. Cox regression analysis was used to investigate patient survival in these groups. RESULTS: Patients who underwent 3D-VPE and ERAS showed a significantly higher R0 resection rate (67.4% vs. 20.9%, p < 0.001) and dissected lymph node number (26.6 ± 12.6 vs. 16.3 ± 7.6 p < 0.001) compared to the control group. The median survival was 27.4 months, and the 1- and 3-year survival rates were 84.4% and 29.8%, respectively, in patients who received combined management; in the control cohort, the median survival was 12.7 months, and the 1- and 3-year survival rates were 53.5% and 15.1%, respectively. In addition, some postoperative complications and risk factors were diminished relative to the traditionally treated patients. CONCLUSION: The implementation of 3D-VPE and ERAS can significantly improve the prognosis and outcomes of patients with GBC and should be considered for wide use in clinical practice.

Case report: A de novo ERBB3 mutation develops in a gallbladder cancer patient carrying BRCA1 mutation after effective treatment with olaparib.

Background: Gallbladder cancer (GBC) is highly lethal and resistant to most chemotherapeutic drugs. GBC was reported to carry multiple genetic mutations such as TP53, K-RAS, and ERBB2/3. Here, we unexpectedly identified a patient with GBC harboring germline BRCA1 p.Arg1325Lys heterozygous mutation. We sought to determine if olaparib, the poly ADP-ribose polymerase inhibitor (PARPi) commonly treated for BRCA mutation, can inhibit cancer development via a therapeutic trial on this patient. Case presentation: The patient received GBC R0 resection after an 8-week olaparib treatment. After surgery and 6-month follow-up treatment with olaparib, the patient's blood carbohydrate antigen 19-9 (CA19-9) level declined from 328 to 23.6 U/ml. No recurrence in CT scanning was observed, indicating a disease-free survival of 6 months with conventional therapy. Two months later, CT examination and CA19-9 level showed cancer relapse. A blood biopsy revealed a new ERBB3 p.Gly337Arg mutation. GBC cell lines ectopically expressing BRCA1 p.Arg1325Lys together with ERBB3 p.Gly337Arg mutations were challenged with olaparib and/or afatinib, an ERBB2/3 inhibitor. The dual mutation cells were more responsive to the combined olaparib with afatinib than a single drug in the cell proliferation assay. Conclusion: Olaparib is effective in a GBC patient with a BRAC1 mutation. The efficacy of olaparib and afatinib in both cultured BRAC1 and ERBB3 mutation cell lines suggests that a combined regimen targeting BRCA1/2 and ERBB2/3 mutations may be an optimal strategy to treat GBC patients who carry both gene mutations.

Clinical efficacy and safety of ultrasound-assisted thrombolysis vs. standard catheter-directed thrombolysis in patients with acute pulmonary embolism: A study level meta-analysis of clinical trials.

Aim: To compare the clinical efficacy of ultrasound-assisted thrombolysis (USAT) vs. standard catheter-directed thrombolysis (SCDT) in patients with acute pulmonary embolism (aPE). Methods: This study analyzed the clinical outcomes of patients with non-low-risk aPE who received USAT or SCDT. The primary outcomes were all-cause death, total bleeding, and major bleeding. Secondary outcomes included pulmonary thrombotic load score (Miller), improvement in right ventricular-to-left ventricular ratio (RV/LV), dose and duration of the thrombolytic drug tissue plasminogen activator (tPA), length of stay (LOS) in the ICU, and total LOS in the hospital. Results: A total of seven articles and 451 patients were included in this study. 241 patients were in the USAT group and 210 patients were in the SCDT group. There were no significant differences in all-cause mortality, total bleeding, and major bleeding between the two groups. Miller scores for pulmonary thrombus also showed no difference between the two groups, but pulmonary artery systolic pressure (PASP) was lower in the SCDT group after-treatment. The reduction of RV/LV from baseline was more pronounced in the SCDT group than in the USAT group (OR: -0.14, 95%CI: -0.20 to 0.07, P < 0.0001, I 2 = 0%). Total dose of tPA and duration of infusion in the USAT group were lower than those in the SCDT group, but there was no significant statistical difference. LOS in the ICU was similar between the two groups, while LOS in the hospital was lower in the SCDT group. Conclusion: This study did not detect any differences in all-cause mortality, total bleeding, and major bleeding between non-low-risk aPE patients treated with USAT or SCDT. Improvement in right ventricular function was better in the SCDT group, and hospital LOS was lower in the SCDT group.

Puerarin protects against myocardial ischemia/reperfusion injury by inhibiting inflammation and the NLRP3 inflammasome: The role of the SIRT1/NF-κB pathway.

AIMS: The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury. MAIN METHODS: C57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinase-MB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blotting were used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-κB pathway. RESULTS: Puerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1ß, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1ß, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-κB pathway, as well as the NLRP3 inflammasome activation. CONCLUSION: Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.