The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study.

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.

Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes.

BACKGROUND: Hepatitis B virus (HBV) infection is one of the most common risk factors for intrahepatic cholangiocarcinoma (ICC). However, there is no direct evidence of a causal relationship between HBV infection and ICC. In this study, we attempted to prove that ICC may originate from hepatocytes through a pathological study involving ICC tissue-derived organoids. METHOD: The medical records and tumor tissue samples of 182 patients with ICC after hepatectomy were collected. The medical records of 182 patients with ICC were retrospectively analyzed to explore the prognostic factors. A microarray of 182 cases of ICC tumor tissue and 6 cases of normal liver tissue was made, and HBsAg was stained by immunohistochemistry (IHC) to explore the factors closely related to HBV infection. Fresh ICC tissues and corresponding adjacent tissues were collected to make paraffin sections and organoids. Immunofluorescence (IF) staining of factors including HBsAg, CK19, CK7, Hep-Par1 and Albumin (ALB) was performed on both fresh tissues and organoids. In addition, we collected adjacent nontumor tissues of 6 patients with HBV (+) ICC, from which biliary duct tissue and normal liver tissue were isolated and RNA was extracted respectively for quantitative PCR assay. In addition, the expression of HBV-DNA in organoid culture medium was detected by quantitative PCR and PCR electrophoresis. RESULTS: A total of 74 of 182 ICC patients were HBsAg positive (40.66%, 74/182). The disease-free survival (DFS) rate of HBsAg (+) ICC patients was significantly lower than that of HBsAg (-) ICC patients (p = 0.0137). IF and IHC showed that HBsAg staining was only visible in HBV (+) ICC fresh tissues and organoids, HBsAg expression was negative in bile duct cells in the portal area. Quantitative PCR assay has shown that the expression of HBs antigen and HBx in normal hepatocytes were significantly higher than that in bile duct epithelial cells. Combined with the IF and IHC staining, it was confirmed that HBV does not infect normal bile duct epithelial cells. In addition, IF also showed that the staining of bile duct markers CK19 and CK7 were only visible in ICC fresh tissue and organoids, and the staining of hepatocyte markers Hep-Par1 and ALB was only visible in normal liver tissue fresh tissue. Real-time PCR and WB had the same results. High levels of HBV-DNA were detected in the culture medium of HBV (+) organoids but not in the culture medium of HBV (-) organoids. CONCLUSION: HBV-related ICC might be derived from hepatocytes. HBV (+) ICC patients had shorter DFS than HBV (-) ICC patients.

The Virtual Nose: Assessment of Static Nasal Airway Obstruction Using Computational Simulations and 3D-Printed Models.

Background: The use of virtual noses to predict the outcome of surgery is of increasing interests, particularly, as detailed and objective pre- and postoperative assessments of nasal airway obstruction (NAO) are difficult to perform. The objective of this article is to validate predictions using virtual noses against their experimentally measured counterpart in rigid 3D-printed models. Methods: Virtual nose models, with and without NAO, were reconstructed from patients' cone beam computed tomography scans, and used to evaluate airflow characteristics through computational fluid dynamics simulations. Prototypes of the reconstructed models were 3D printed and instrumented experimentally for pressure measurements. Results: Correlation between the numerical predictions and experimental measurements was shown. Analysis of the flow field indicated that the NAO in the nasal valve increases significantly the wall pressure, shear stress, and incremental nasal resistance behind the obstruction. Conclusions: Airflow predictions in static virtual noses correlate well with detailed experimental measurements on 3D-printed replicas of patient airways.

Cluster-Delay Mean Square Consensus of Stochastic Multi-Agent Systems with Impulse Time Windows.

This paper investigates the cluster-delay mean square consensus problem of a class of first-order nonlinear stochastic multi-agent systems with impulse time windows. Specifically, on the one hand, we have applied a discrete control mechanism (i.e., impulsive control) into the system instead of a continuous one, which has the advantages of low control cost, high convergence speed; on the other hand, we considered the existence of impulse time windows when modeling the system, that is, a single impulse appears randomly within a time window rather than an ideal fixed position. In addition, this paper also considers the influence of stochastic disturbances caused by fluctuations in the external environment. Then, based on algebraic graph theory and Lyapunov stability theory, some sufficiency conditions that the system must meet to reach the consensus state are given. Finally, we designed a simulation example to verify the feasibility of the obtained results.