Background: Most colorectal liver metastases (CRLM) are not candidates for liver resection. Radiofrequency ablation (RFA) plays a key role in selected CRLM patients. Neoadjuvant chemotherapy (NAC) followed by liver resection has been widely used for resectable CRLM. Whether NAC followed by radiofrequency ablation (RFA) can achieve a similar prognosis to NAC followed by hepatectomy remains is unclear. The present study aimed to provide a new treatment modality for CRLM patients. Methods: This comparative retrospective research selected CRLM patients from 2009 to 2022. They were divided into NAC + RFA group and NAC + hepatectomy group. The propensity score matching (PSM) was used to reduce bias. We used multivariate cox proportional hazards regression analysis to explore independent factors affecting prognosis. The primary study endpoint was the difference in the progression-free survival (PFS) between the two groups. Results: A total of 190 locally curable CRLM patients were in line with the inclusion criteria. A slight bias was detected in the comparison of basic clinical characteristics between the two groups. RFA showed a significant advantage in the length of hospital stay (median; 2 days vs. 7 days; p < 0.001). The 1- and 3-year PFS in the liver resection and the RFA groups was 57.4% vs. 86.9% (p < 0.001) and 38.8% vs. 55.3% (p = 0.035), respectively. The 1-year and 3-year OS in the liver resection and RFA groups was 100% vs. 96.7% (p = 0.191) and 73.8% vs. 73.6% (p = 0.660), respectively. Conclusions: NAC followed by RFA has rapid postoperative recovery, fewer complications, and better prognosis.

Background: NADH: ubiquinone oxidoreductase subunit C1(NDUFC1) encodes a subunit of the Complex I, which may support the structural stability of Complex I and assist in its biogenesis. The expression and functional roles of NDUFC1 in hepatocellular carcinoma (HCC) remain unknown.Result: We knocked down the expression of NDUFC1 in HCC cell lines to explore the effects of NDUFC1 downregulation on HCC in vitro. MTT assay determined that downregulation of NDUFC1 significantly inhibited cell proliferation. Flow cytometry with (propidium iodide) PI staining indicated silencing of NDUFC1 arrested cell cycle of BEL-7404 cells at G2 phase and SK-HEP-1 cells at S/G2 phase. Annexin V-PI double staining and flow cytometric analysis showed that the downregulation of NDUFC1 significantly increased the population of apoptotic cells. Wound-healing assay and transwell assay indicated that the downregulation of NDUFC1 suppressed the migration and invasion of HCC cells. According to the detection of complex1 activity, we found that the activity of NDUFC1 silenced group decreased, whereas the content of ROS increased. Furthermore, combined with bioinformatics analysis of senescence-related genes, we found that the silence of NDUFC1 in HCC could induce senescence and inhibit autophagy. In addition, NDUFC1 could correlate positively with cancer-related pathways, among which the p53 pathways and the PI3K/Akt/mTOR pathways. Finally, NDUFC1 is high expression in HCC specimens. High NDUFC1 expression was associated with poor prognosis and was an independent risk factor for reduced overall survival (OS).Conclusions: Our study indicated, for the first time, that NDUFC1 is an independent risk factor for the poor prognosis of HCC patients. NDUFC1 may promote tumor progression by inhibiting mitochondrial Complex I and up-regulating ROS through multiple cancer-related and senescence-related pathways of HCC, including p53 pathways and PI3K/Akt/mTOR pathways. We suppose that NDUFC1 might be a potential target for the mitochondrial metabolism therapy of HCC.

Background: Patients with pancreatic ductal adenocarcinoma (PDAC) display an altered oral, gastrointestinal, and intra-pancreatic microbiome compared to healthy individuals. However, knowledge regarding the bile microbiome and its potential impact on progression-free survival in PDACs remains limited. Methods: Patients with PDAC (n = 45), including 20 matched pairs before and after surgery, and benign controls (n = 16) were included prospectively. The characteristics of the microbiomes of the total 81 bile were revealed by 16 S-rRNA gene sequencing. PDAC patients were divided into distinct groups based on tumor marker levels, disease staging, before and after surgery, as well as progression free survival (PFS) for further analysis. Disease diagnostic model was formulated utilizing the random forest algorithm. Results: PDAC patients harbor a unique and diverse bile microbiome (PCoA, weighted Unifrac, p = 0.038), and the increasing microbial diversity is correlated with dysbiosis according to key microbes and microbial functions. Aliihoeflea emerged as the genus displaying the most significant alteration among two groups (p < 0.01). Significant differences were found in beta diversity of the bile microbiome between long-term PFS and short-term PFS groups (PCoA, weighted Unifrac, p = 0.005). Bacillota and Actinomycetota were identified as altered phylum between two groups associated with progression-free survival in all PDAC patients. Additionally, we identified three biomarkers as the most suitable set for the random forest model, which indicated a significantly elevated likelihood of disease occurrence in the PDAC group (p < 0.0001). The area under the receiver operating characteristic (ROC) curve reached 80.8% with a 95% confidence interval ranging from 55.0 to 100%. Due to the scarcity of bile samples, we were unable to conduct further external verification. Conclusion: PDAC is characterized by an altered microbiome of bile ducts. Biliary dysbiosis is linked with progression-free survival in all PDACs. This study revealed the alteration of the bile microbiome in PDACs and successfully developed a diagnostic model for PDAC.

Background: Currently, guidelines prohibit the addition of targeted drugs in neoadjuvant chemotherapy (NAC) for initially resectable colorectal liver metastasis (CRLM). Objective: Nevertheless, efficacy data of NAC combined with bevacizumab (Bev) for initially resectable CRLM with risk factors for recurrence (RFR) are lacking. Designs: We conducted a multicenter real-world cohort study to retrospectively analyze the efficacy and feasibility of NAC combined with Bev for CRLM with RFR. Methods: The patients were divided into the NAC alone group and NAC combined with the Bev group. We designated progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) as the outcomes. Kaplan–Meier, Cox proportional hazards regression models, and subgroup analysis were utilized. RFR was a clinical risk score of 3–5. Subgroup analysis was applied to explore which subgroup was more suitable for NAC combined with Bev. Results: Between 2015 and 2020, this multicenter real-world study encompassed 335 CRLM patients from six medical centers who underwent curative hepatectomy following NAC. Two hundred seventeen patients were in the NAC alone group, and 118 received NAC combined with Bev. The NAC alone group exhibited an ORR of 51.15%, compared to 66.95% in the NAC combined with Bev ( p = 0.005). The R0 resection rates achieved 91.71% for the NAC alone group and 94.92% for the NAC combined with Bev ( p = 0.276). Three-year PFS rate was 27.6% for NAC alone and 41.5% for the NAC combined with the Bev group ( p = 0.006). Furthermore, the 3-year OS was calculated to be 57.0% for the NAC alone and 66.7% for the NAC combined with Bev patients ( p = 0.079). Conclusion: For initially resectable CRLM patients with RFR, NAC combined with Bev exhibited a higher ORR and longer PFS. Chinese clinical trial registry: ChiCTR2400082966.

Background: Typically, colorectal liver metastasis (CRLM) is not a candidate for hepatectomy. Radiofrequency ablation (RFA) plays a critical role in unresectable CRLM patients. Nevertheless, high local tumor progression (LTP) and distant metastasis limit the development and further adoption and use of RFA. Neoadjuvant chemotherapy (NAC) has been widely used in resectable CRLM and is recommended by the guidelines. There are no studies on whether NAC can improve the prognosis in ablatable CRLM patients. The present study aimed to determine the feasibility and effectiveness of RFA plus NAC.Methods: This retrospective cohort included CRLM patients from Zhejiang Cancer Hospital records, who received RFA from January 2009 to June 2020 and were divided into two groups according to the presence or absence of NAC. The Kaplan–Meier method was used to evaluate the 3-year local tumor progression-free survival (LTPFS), progression-free survival (PFS), and overall survival (OS) of the two groups. The propensity score matching was used to reduce bias when assessing survival. Multivariate Cox proportional hazards regression analysis was used to study the independent factors affecting LTPFS, PFS, and OS.Results: A total of 149 CRLM patients (88 in the RFA alone group and 61 in the plus NAC group) fulfilled the inclusion criteria. Post-RFA complications were 3.4% in the RFA alone group and 16.4% in the plus NAC group. The 3-year LTPFS, PFS, and OS of the RFA only group were 60.9%, 17.7%, and 46.2%, respectively. The 3-year LTPF, PFS, and OS of the plus NAC group were 84.9%, 46.0%, and 73.6%, respectively. In the 29 pairs of propensity score matching cohorts, the 3-year LTPFS, PFS, and OS in the plus NAC group were longer than those in the RFA group (P < 0.05). NAC was an independent protective factor for LTPFS, PFS, and OS (P < 0.05).Conclusions: For ablatable CRLM patients, RFA plus NAC obtained a better prognosis than RFA alone. Based on the current results, the application of NAC before RFA may become the standard treatment.

Neoadjuvant chemotherapy (NAC) is generally accepted for treatment of liver metastasis of colorectal cancer (CRLM), but what is a reasonable interval between the latest NAC and surgery is still unknown. The aim of the current study was to investigate the proper timing of surgery after NAC. Subjects were 141 patients with CRLM who underwent NAC and then surgery were retrospectively identified from 2008 to 2020. They were divided into a short interval group (SIG, ≤ 4 weeks) and long interval group (LIG, > 4 weeks) using the software X-tile. The SIG was subclassified group into 3 time periods (1-2 weeks, 2-3 weeks, and 3-4 weeks) to assess the incidence of complications. Patients in the SIG were more likely to have significantly better recurrence-free survival (RFS) (3-year RFS of 47.4% vs. 20.5%, P = 0.043) and no difference in overall survival (OS) (3-year OS 76.1% vs. 79.9%, P = 0.635). The postoperative complication rate was 23.5% in the SIG and 14.0% in the LIG (P = 0.198). The postoperative complication rate in the 1-2 weeks subgroup was marginally higher than that in the > 4 weeks subgroup (35% vs. 14.3% P = 0.055). Multivariate analysis revealed that chemotherapy-free intervals of 1-2 weeks were an independent predictor of increased postoperative complications (OR = 0.263, 95% CI 0.7-0.985 P = 0.048). Patients who underwent surgery within 4 weeks of NAC had better RFS. In addition, 1-2 weeks was an independent factor influencing the development of more complications. For patients with CRLM, performing surgery within 2-4weeks of NAC was feasible and safe, and it did not increase the incidence of postoperative complications but it did prolong RFS.