Plasma-only circulating tumor DNA analysis detects minimal residual disease and predicts early relapse in hepatocellular carcinoma patients undergoing curative resection.

Background: Minimal residual disease (MRD) is considered an essential factor leading to relapse within 2 years (early relapse) after radical surgery, which is challenging to be detected by conventional imaging. Circulating tumor DNA (ctDNA) provides a novel approach for detecting MRD and predicting clinical outcomes. Here, we tried to construct a fixed panel for plasma-only ctDNA NGS to enable tumor-uninformed MRD detection in hepatocellular carcinoma (HCC). Methods: Here, we performed the followings: (i) profiling genomic alteration spectrum of ctDNA from the Chinese HCC cohort consisting of 493 individuals by NGS; (ii) screening of MRD monitoring genes; and (iii) performance evaluation of MRD monitoring genes in predicting early relapse in the ZJZS2020 cohort comprising 20 HCC patients who underwent curative resection. Results: A total of 493 plasma samples from the Chinese HCC cohort were detected using a 381/733-gene NGS panel to characterize the mutational spectrum of ctDNA. Most patients (94.1%, 464/493) had at least one mutation in ctDNA. The variants fell most frequently in TP53 (45.1%), LRP1B (20.2%), TERT (20.2%), FAT1 (16.2%), and CTNNB1 (13.4%). By customized filtering strategy, 13 MRD monitoring genes were identified, and any plasma sample with one or more MRD monitoring gene mutations was considered MRD-positive. In the ZJZS2020 cohort, MRD positivity presented a sensitivity of 75% (6/8) and a specificity of 100% (6/6) in identifying early postoperative relapse. The Kaplan-Meier analysis revealed a significantly short relapse-free survival (RFS; median RFS, 4.2 months vs. NR, P=0.002) in the MRD-positive patients versus those with MRD negativity. Cox regression analyses revealed MRD positivity as an independent predictor of poor RFS (HR 13.00, 95% CI 2.60-69.00, P=0.002). Conclusions: We successfully developed a 13-gene panel for plasma-only MRD detection, which was effective and convenient for predicting the risk of early postoperative relapse in HCC.

Bloodless Laparoscopic Partial Splenectomy Assisted by Bipolar Radiofrequency Excision Hemostatic Device.

Among the lymphatic system in the human body, the spleen is the most extensive one and has hematopoietic, hemofiltration, blood storage, and immune functions. As a new method of preserving the spleen, laparoscopic partial splenectomy (LPS) has been increasingly applied in clinical practice with people's deeper insights into minimally invasive treatment and the development of technical equipment. Compared with conventional open splenectomy, LPS can preserve normal spleen tissue as much as possible, decrease the occurrence of complications after total splenectomy, and reduce postoperative hospital stay. The bipolar radiofrequency excision hemostatic device used for LPS can solidify the splenic tissue and close the small blood vessels, which reduces the hemorrhage of the spleen cross-section and clears the operative field, thus achieving the ideal effect of "bloodless partial splenectomy". Therefore, under the premise of strictly mastering the indications and fully understanding the vascular anatomy of the spleen, the application of the bipolar radiofrequency excision hemostatic device in LPS is worthy of clinical promotion.

Case report: Primary hepatocellular carcinoma with portal vein tumor thrombus characterized by active tumor immune microenvironment achieving a complete response following treatment of combined immunotherapy.

Portal vein tumor thrombus (PVTT) is a frequent complication in hepatocellular carcinoma (HCC). HCC patients with PVTT have the characteristics of less treatment tolerance and poor prognosis. Immunotherapy, especially combined immunotherapy, has been successfully used in advanced HCC. However, there are no recognized universally indicators that can predict response or resistance to immunotherapy for HCC. Herein, we reported a 58-year-old HCC patient with PVTT, cirrhosis and chronic viral hepatitis, who achieved complete response (CR) after combined immunotherapy (camrelizumab combined with sorafenib or regorafenib), according to his high enrichment of tumor-infiltrating immune cells and tertiary lymphoid structure (TLS). In this case, we revealed the characteristics of the baseline tumor immune microenvironment (TIME) in a HCC patient who responded well to combined immunotherapy, suggesting that TIME can be used to assist in clinical decision making of immunotherapy for HCC.