Liver resection with two-step vascular exclusion, in situ hypothermic portal perfusion for the treatment of end-stage hepatic alveolar echinococcosis.

PURPOSE: To evaluate the safety and efficacy of two-step vascular exclusion and in situ hypothermic portal perfusion in patients with end-stage hepatic hydatidosis. METHODS: This study involved patients with advanced hepatic hydatid disease undergoing surgical treatment between 2022 and 2023, which included resection and reconstruction of the hepatic veins, inferior vena cava (IVC), and portal vein (PV). We described the technical details of liver resection and vascular reconstruction, as well as the use of two-step vascular exclusion and in situ hypothermic portal perfusion techniques during the vascular reconstruction process. RESULT: We included 7 patients with advanced hepatic hydatid disease who underwent surgical resection using two-step vascular exclusion and in situ hypothermic portal perfusion. The mean duration of surgery was 12.5 h (range, 7.5-15.0 h). The average hepatic ischemia time was 45 min (range, 25-77 min), while the occlusion time of the IVC was 87 min (range, 72-105 min). The total blood loss was 1000 milliliters (range, 500-1250 milliliters). Postoperatively, patients exhibited good recovery of liver and renal function. The mean ICU stay was 2 days (range, 1-3 days), and the mean postoperative hospital stay was 13 days (range, 9-16 days), with no Grade III or above complications observed during a mean follow-up period of 15 months (range, 9-24 months), CONCLUSION: two-step vascular exclusion and in situ hypothermic portal perfusion for surgical resection of end-stage hepatic hydatid disease is safe and effective. This significantly reduces the anhepatic time.

Development and validation of a selenium metabolism regulators associated prognostic model for hepatocellular carcinoma.

BACKGROUND: Selenium metabolism has been implicated in human health. This study aimed to identify a selenium metabolism regulator-based prognostic signature for hepatocellular carcinoma (HCC) and validate the role of INMT in HCC. METHODS: Transcriptome sequencing data and clinical information related to selenium metabolism regulators in TCGA liver cancer dataset were analysed. Next, a selenium metabolism model was constructed by multiple machine learning algorithms, including univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses. Then, the potential of this model for predicting the immune landscape of different risk groups was evaluated. Finally, INMT expression was examined in different datasets. After knockdown of INMT, cell proliferation and colony formation assays were conducted. RESULTS: A selenium metabolism model containing INMT and SEPSECS was established and shown to be an independent predictor of prognosis. The survival time of low-risk patients was significantly longer than that of high-risk patients. These two groups had different immune environments. In different datasets, including TCGA, GEO, and our PUMCH dataset, INMT was significantly downregulated in HCC tissues. Moreover, knockdown of INMT significantly promoted HCC cell proliferation. CONCLUSIONS: The current study established a risk signature of selenium metabolism regulators for predicting the prognosis of HCC patients. INMT was identified as a biomarker for poor prognosis of HCC.

Differentially expressed liver exosome-related genes as candidate prognostic biomarkers for hepatocellular carcinoma.

Background: Exosomes are involved in cell-to-cell communication, neovascularization, cancer metastasis, and drug resistance, which all play an important role in the occurrence and progression of hepatocellular carcinoma (HCC). Because there are few mechanistic studies about the function of exosomes in HCC, the goals of this study were to identify exosome-related genes in HCC, to establish a reliable prognostic model for HCC, and to explore underlying mechanisms. Methods: The exoRBase and The Cancer Genome Atlas (TCGA) databases were used to analyze differentially expressed genes (DEGs). Cox regression and least absolute shrinkage and selection operator analyses were used to identify DEGs closely related to the overall survival of patients with HCC. An exosome-related prognostic model was then constructed in TCGA and validated in the International Cancer Genome Consortium database. A nomogram was developed to predict survival. CIBERSORT was used to estimate the abundance of different types of immune cells. Immunotherapy-related DEGs were used to predict the effect of immunotherapy. Results: Forty-eight exosome-related DEGs were obtained; of them, five [exportin 1 (XPO1), lysosomal thiol reductase (IFI30), F-box protein 16 (FBXO16), calmodulin 1 (CALM1), MORC family CW-type zinc finger 3 (MORC3)] were selected to construct a predictive model. Patients with HCC were then divided into low- and high-risk groups using the best cut-off value, as determined by the X-tile software. Prognosis was significantly poorer in the high-risk than in the low-risk group (P=0.009; hazard ratio =2.65). Features related to exosomes were found to positively regulate immune response. Further analysis showed a higher risk score was associated with higher expression of immune checkpoint molecules, including programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), T cell Ig and ITIM domain (TIGIT), and indoleamine-2,3-dioxygenase 1 (IDO1). Conclusions: This study has identified a novel signature based on exosome-related genes that has potential as a prognostic biomarker for HCC. Our research provides an immunological perspective for the development of precision treatment for HCC.

A real-world study of the efficacy and safety of anti-PD-1 antibodies plus lenvatinib in patients with advanced gallbladder cancer.

BACKGROUND: Anti-PD-1 antibodies plus lenvatinib therapeutic regimens have demonstrated a relatively high antitumor response in many solid cancers; however, the efficacy and safety of anti-PD-1 antibodies plus lenvatinib in patients with advanced gallbladder cancer (GBC) has not been reported. METHODS: Advanced GBC patients who received anti-PD-1 antibodies plus lenvatinib were retrospectively screened. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), PD-L1 expression and safety were evaluated to identify efficacy biomarkers. RESULTS: A total of 31 GBC patients were included in this study. After a median follow-up of 8 months and 23 deaths were observed. The median PFS was 5.0 months (95% CI: 4.1-8.0 months), and the median OS was 11.3 months (95% CI: 7.5-20.9 months). Overall, the ORR was 32.3%, the DCR was 83.9%, and the CBR was 41.9%. Moreover, after treatment, 3 patients received conventional surgery, in which 1 patient achieved a pathological complete response. All patients (100%) experienced adverse events (AEs), and 58.1% of the patients experienced grade 3 AEs. The most commonly observed grade 3 AEs included fatigue (5/31, 16.1%), decreased appetite (5/31, 16.1%), hypertension (4/31, 12.9%) and bilirubin elevation (4/31, 12.9%). Subgroup analysis revealed that positive PD-L1 expression maybe associate with a longer PFS. CONCLUSION: Anti-PD-1 antibodies plus lenvatinib represent an effective and tolerable therapy for patients with advanced gallbladder cancer.

Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers.

BACKGROUND: The gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers. METHODS: Patients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy. RESULTS: In total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance. CONCLUSIONS: We demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.

Downstaging and resection of hepatocellular carcinoma in patients with extrahepatic metastases after stereotactic therapy.

BACKGROUND: A combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma (HCC) with extrahepatic metastases. Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported. METHODS: Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed. RESULTS: Nine patients with localized disease who received first-line systemic therapy were enrolled. At baseline, all of them had oligometastatic disease, namely, Barcelona Clinic Liver Cancer stage C (or Chinese Liver Cancer stage IIIB). The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization, and the median time span from systemic therapy to surgery was 3.2 (IQR, 2.8-6.2) months. Three patients achieved a pathological complete response. Six patients underwent laparoscopic surgery, and the other 3 patients underwent open surgery. After a median follow-up of 10.2 (IQR, 8.6-20.0) months, 7 patients survived without disease recurrence, and 2 experienced tumour recurrence. All patients had any-grade AEs, and 55.6% of the patients experienced grade 3 AEs. Fatigue was the most common AE, followed by elevated aminotransferase levels and hypertension. CONCLUSIONS: Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable. This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.

CMTTdb: the cancer molecular targeted therapy database.

BACKGROUND: The cancer molecular targeted therapy has achieved unprecedented progress in the past decade and is thought to be the most promising direction for cancer treatment in future. As the fast growing of the clinical trials of targeted anticancer agents for different cancer types, it is critical to collect and integrate such information to guide clinical practice. METHODS: We constructed the Cancer Molecular Targeted Therapy database (CMTTdb) to store and retrieve molecular targeted therapy data about randomized clinical trials (RCTs) of targeted agents and also accompanied targets, biomarkers, targeted cancer subtypes, etc. RESULTS: Different with some existing resources, CMTTdb particularly focuses on clinical application of the trails. Design of the trails, such as treatment modalities (monotherapy or combination with other therapies), as well as results on clinical efficacy parameters, adverse events are also collected. In this current version, CMTTdb contains data for 1,088 clinical trials which cover 165 agents, 80 targets, 15 cancer types (95 molecular subtypes and 56 histological or cytological subtypes) from public literatures. This database is freely available at http://www.biosino.org/CMTTdb. A user-friendly web interface was designed so that these data can be easily retrieved. CONCLUSIONS: CMTTdb will be a valuable source for providing access to information of clinical trials on the rapidly growing number of novel targeted agent and be useful in guiding oncologists for the optimization of the therapy strategy for cancer treatment.