Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy.

PURPOSE: The prognostic and predictive value of RAS mutations in patients with colorectal liver metastases (CRLM) who have undergone hepatectomy holds substantial importance. The present study aimed to investigate the impact of different RAS codon mutations on long-term survival in CRLM patients. METHODS: A retrospective analysis was conducted on clinicopathological data from 399 CRLM patients with RAS mutations who underwent hepatectomy between January 2000 and December 2020. The RAS mutation gene status was assessed in KRAS codons (G12, G13, Q61, and A146) and NRAS codons (G12, G13, and Q61). Survival curves were generated using the Kaplan-Meier plotter and compared using the log-rank test. Univariate and multivariate analyses were performed to analyze the clinicopathological data. RESULTS: In the entire cohort, patients with KRAS G12 mutations exhibited the most favorable prognosis (p = 0.018). Comparatively, patients harboring KRAS Q61 mutations experienced poorer overall survival (OS) with a median of 15 months versus 33 months (p = 0.011) when compared to those with KRAS G12 mutations. Moreover, patients with NRAS Q61 mutations also showed decreased OS with a median of 26 months versus 33 months (p = 0.020) in comparison to KRAS G12 mutation patients. The results of multivariate analysis showed that both KRAS Q61 mutation (HR 2.130; 95% CI 1.088-4.168; p = 0.027) and NRAS Q61 mutation (HR 2.877; 95% CI 1.398-5.922; p = 0.004) were independent influencing factors of OS. Based on all identified risk factors, patients with RAS mutation were divided into high-risk and low-risk groups. Notably, in the high-risk group, the incorporation of postoperative chemotherapy was associated with longer OS, while it did not improve the survival of patients in the low-risk group. CONCLUSIONS: KRAS Q61 and NRAS Q61 mutations are promising predictors for OS in CRLM patients after hepatectomy. Postoperative chemotherapy may significantly benefit CRLM patients with RAS mutations, particularly those identified as high-risk.

Comparing baseline VAF in circulating tumor DNA and tumor tissues predicting prognosis of patients with colorectal cancer liver metastases after curative resection.

INTRODUCTION: The prognostic value of baseline variant allele frequency (VAF) in circulating tumor DNA (ctDNA) of colorectal cancer liver metastases (CRLM) patients after curative resection was rarely investigated. METHODS: A single-center prospective study was performed to investigate the prognostic impact of baseline VAF in ctDNA and matched tumor tissues of CRLM patients after curative resection between May 2019 and May 2021 by the Illumina NovoSeq 6000 platform. The relationship of the tumor burden score (TBS) and the VAF in ctDNA and matched tumor tissues was evaluated by the Pearson correlation method. The survival curves of recurrence-free survival (RFS) and overall survival (OS) were plotted. Factors associated with RFS were calculated using Cox regression analysis, and an integrated prognostic model using significant baseline variables was proposed. RESULTS: There were 121 patients with baseline ctDNA and matched tumor tissues enrolled in the study. A total of 417 mutations spanning 20 genes were identified in baseline tumor tissues of 119/121 (98.3 %) cases. The overall mutations in tumor tissues were completely covered by ctDNA in 52 of 121(43.0 %) patients. Baseline VAF in ctDNA but not in tumor tissues was significantly correlated to TBS of CRLM (R = 0.36, p < 0.001). Significantly longer RFS but not OS was observed in patients with lower VAF in ctDNA compared to those with higher one (p < 0.001 and p = 0.33 respectively). Multivariate Cox regression analysis showed higher VAF in baseline ctDNA was an independent risk factor for RFS. An integrated prognostic model including baseline metastasis location and VAF in ctDNA outperformed the traditional CRS model in predicting RFS. CONCLUSION: Baseline VAF in ctDNA but not in tumor tissues influenced RFS of CRLM patients after curative resection.

[Secondary metabolites of endophytic fungus Talaromyces malicola hosted in Armadillidium vulgare].

The secondary metabolites of the endophytic fungus Talaromyces malicola hosted in the arthropod Armadillidium vulgare were separated by silica gel column chromatography, gel column chromatography, and semi-preparative high-performance liquid chromatography. Eleven compounds(1-11) were obtained from the ethyl acetate fraction of the fermentation broth of T. malicola, and their structures were identified by NMR, HR-ESI-MS, UV, IR, and ECD. The 11 compounds were talarosesquiterpene A(1),(3ß,5α,6α,15α,22E)-5,6-epoxyergosta-8(14),22-diene-3,7,15-triol(2), vermistatin(3), hydroxyvermistatin(4), bercheminol A(5), penicillide(6), lunatinin(7), penipurdin A(8), emodin(9), BE-25327(10), and(-)-regiolone(11). Compound 1 was a new diaporol-type sesquiterpene. Compounds 2, 4-5, and 7-11 were isolated from Talaromyces for the first time.

The importance of starch chain-length distribution for in vitro digestion of ungelatinized and retrograded foxtail millet starch.

The digestibility of ungelatinized, short-term retrograded and long-term retrograded starch from foxtail millet was investigated and correlated with starch chain length distributions (CLDs). Some variations in starch CLDs of different varieties were obtained. Huangjingu and Zhonggu 9 had higher average chain lengths of debranched starch and lower average chain length ratios of amylopectin and amylose than Dajinmiao and Jigu 168. Compared to ungelatinized starch, retrogradation significantly increased the estimated glycemic index (eGI), whereas significantly decreased the resistant starch (RS). In contrast, long-term retrograded starches have lower eGI (93.33-97.37) and higher RS (8.04-14.55%) than short-term retrograded starch. PCA and correlation analysis showed that amylopectin with higher amounts of long chains and longer long chains contributed to reduced digestibility in ungelatinized starch. Both amylose and amylopectin CLDs were important for the digestibility of retrograded starch. This study helps a better understanding of the interaction of starch CLDs and digestibility during retrogradation.

Starch chain-length distributions affect the processing and digestion characteristics of proso millet starch.

Starch chain-length distributions play a key role in regulating the processing and digestion characteristics of proso millet starch. Waxy proso millet starch has higher endothermic enthalpy (13.06-16.73 J/g) owing to its higher relative crystallinity (27.83%-32.04%), while nonwaxy proso millet starch has lower peak viscosity (1.0630-1.1930 Pa∙s) and stronger viscoelasticity owing to its higher amylose content (21.72%-24.34%). Non-waxy proso millet starch exhibited two different digestion phases and its resistant starch content (18.37%-20.80%) was higher than waxy proso millet starch. Correlation analysis showed proso millet starch with longer amylopectin B1 chains and more amylopectin B2 chains exhibited excellent thermal ability and retrograde resistance, whereas proso millet starch with shorter and more amylose medium/long-chains not only reduced the digestion rate and increased the resistant starch content but also exhibited stronger viscoelasticity and excellent retrogradation properties. These results could provide more insights into efficient utilization of proso millet starch.

A compound enzyme as an additive to a continuous anaerobic dynamic membrane bioreactor for enhanced lignocellulose removal from codigestion: Performance, membrane characteristics and microorganisms.

To explore the enzyme-enhanced strategy of a continuous anaerobic dynamic membrane reactor (AnDMBR), the anaerobic codigestion system of food waste and corn straw was first operated stably, and then the best combination of compound enzymes (laccase, endo-ß-1,4-glucanase, xylanase) was determined via a series of batch trials. The results showed that the methane yield (186.8 ± 19.9 mL/g VS) with enzyme addition was 12.2 % higher than that without enzyme addition. Furthermore, the removal rates of cellulose, hemicellulose and lignin increased by 31 %, 36 % and 78 %, respectively. In addition, dynamic membranes can form faster and more stably with enzyme addition. The addition of enzymes changed the structure of microbial communities while maintaining sufficient hydrolysis bacteria (Bacteroidetes), promoting the proliferation of Proteobacteria as a dominant strain and bringing stronger acetylation ability. In summary, the compound enzyme strengthening strategy successfully improved the methane production, dynamic membrane effect, and degradation rate of lignocellulose in AnDMBR.

Amylopectin chain length distributions and amylose content are determinants of viscoelasticity and digestibility differences in mung bean starch and proso millet starch.

This study aimed to reveal the underlying mechanisms of the differences in viscoelasticity and digestibility between mung bean starch (MBS) and proso millet starch (PMS) from the viewpoint of starch fine molecular structure. The contents of amylopectin B2 chains (14.94-15.09 %), amylopectin B3 chains (14.48-15.07 %) and amylose long chains (183.55-198.84) in MBS were significantly higher than PMS (10.45-10.76 %, 12.48-14.07 % and 70.59-88.03, respectively). MBS with higher amylose content (AC, 28.45-31.80 %) not only exhibited a lower weight-average molar mass (91,750.65-128,120.44 kDa) and R1047/1022 (1.1520-1.1904), but also was significantly lower than PMS in relative crystallinity (15.22-23.18 %, p < 0.05). MBS displayed a higher storage modulus (G') and loss modulus (G'') than PMS. Although only MBS-1 showed two distinct and discontinuous phases, MBS exhibited a higher resistant starch (RS) content than PMS (31.63-39.23 %), with MBS-3 having the highest RS content (56.15 %). Correlation analysis suggested that the amylopectin chain length distributions and AC played an important role in affecting the crystal structure, viscoelastic properties and in vitro starch digestibility of MBS and PMS. These results will provide a theoretical and scientific basis for the development of starch science and industrial production of low glycemic index starchy food.

A derivative of trihydroxynaphthalenone and a pyrone metabolite from the endophytic fungus Talaromyces purpurpgenus.

A newly discovered trihydroxynaphthalenone derivative, epoxynaphthalenone (1) involving the condensation of ortho-hydroxyl groups into an epoxy structure, and a novel pyrone metabolite characterized as pyroneaceacid (2), were extracted from Talaromyces purpurpgenus, an endophytic fungus residing in Rhododendron molle. The structures of these compounds were elucidated through a comprehensive analysis of their NMR and HRESIMS data. The determination of absolute configurations was accomplished using electronic circular dichroism (ECD) calculations and CD spectra. Notably, these recently identified metabolites exhibited a moderate inhibitory activity against xanthine oxidase (XOD).

A new substrate equalization method for optimizing the influent conditions and fluid flow patterns of a multifed upflow anaerobic sludge blanket reactor with mature anammox granules.

To improve nitrogen removal efficiency (NRE) and achieve homogenous distribution of anammox sludge and substrate, a new substrate equalization theory and a cumulative overload index was proposed for multifed upflow anaerobic sludge bed (MUASB) reactors with mature anammox granules. The performance and flow patterns of MUASB reactors were investigated under various influent conditions. The results showed that the nitrogen removal performance and stability of MUASB reactors could be optimized by minimizing the cumulative load. The NRE gradually increased from 83.3 ± 2.2 %, 86.8 ± 4.2 % to 89.3 ± 4.1 % and 89.7 ± 1.6 % in feeding flow tests and feeding port tests, respectively. Furthermore, the flow patterns were compared based on residence time distribution and computational fluid dynamics, indicating that a better equilibrium distribution of microorganisms and substrates could be achieved in the MUASB reactors under the lowest cumulative load. Therefore, substrate equalization theory can be used to optimize the nitrogen removal performance of MUASB reactors with low-carbon footprints.

Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

Transcriptome profiling of longissimus dorsi during different prenatal stages to identify genes involved in intramuscular fat deposition in lean and obese pig breeds.

BACKGROUND: There was significant difference in muscle development between fat-type and lean-type pig breeds. METHODS AND RESULTS: In current study, transcriptome analysis and bioinformatics analysis were used to compare the difference in longissimus dorsi (LD) muscle at three time-points (38 days post coitus (dpc), 58 dpc, and 78 dpc ) between Huainan (HN) and Large white (LW) pig breeds. A total of 24500 transcripts were obtained in 18 samples, and 2319, 2799, and 3713 differently expressed genes (DEGs) were identified between these two breeds at 38 dpc, 58 dpc, and 78 dpc, respectively. And the number and foldchange of DEGs were increased, the alternative splice also increased. The cluster analysis of DEGs indicated the embryonic development progress of LD muscle between these two breeds was different. There were 539 shared DEGs between HN and LW at three stages, and the top-shared DEGs were associated with muscle development and lipid deposition, such as KLF4, NR4A1, HSP70, ZBTB16 and so on. CONCLUSIONS: The results showed DEGs between Huainan (HN) and Large white (LW) pig breeds, and contributed to the understanding the muscle development difference between HN and LW, and provided basic materials for improvement of meat quality.

Effect of high moisture extrusion on the structure and physicochemical properties of Tartary buckwheat protein and its in vitro digestion.

Tartary buckwheat is rich in nutrients and its protein supports numerous biological functions. However, the digestibility of Tartary buckwheat protein (TBP) poses a significant limitation owing to its inherent structure. This study aimed to assess the impact of high moisture extrusion (HME, 60 % moisture content) on the structural and physicochemical attributes, as well as the in vitro digestibility of TBP. Our results indicated that TBP exhibited unfolded and amorphous microstructures after HME. The protein molecular weight of TBP decreased after HME, and a greater degradation was observed at 70 °C than 100 °C. In particular, HME at 70 °C caused an almost complete disappearance of bands near 35 kDa compared with HME at 100 °C. In addition, compared with native TBP (NTBP, 44.53 µmol/g protein), TBP subjected to HME at 70 °C showed a lower disulfide bond (SS) content (42.67 µmol/g protein), whereas TBP subjected to HME at 100 °C demonstrated a higher SS content (45.70 µmol/g protein). These changes endowed TBP with good solubility (from 55.96 % to 83.31 % at pH 7), foaming ability (20.00 %-28.57 %), and surface hydrophobicity (8.34-23.07). Furthermore, the emulsifying activity (EA) and in vitro digestibility are closely related to SS content. Notably, extruded TBP (ETBP) obtained at 70 °C exhibited higher EA and digestibility than NTBP, whereas ETBP obtained at 100 °C showed the opposite trend. Consequently, HME (especially at 70 °C) demonstrated significant potential as a processing technique for improving the functional and digestive properties of TBP.

The relationship between the ratio and dynamic changes of lympho-cytes/monocytes and the efficacy of PD-1 inhibitors in the treatment of advanced non-small cell lung cancer / 中国临床药理学与治疗学

AIM:To investigate the relationship between the dynamic changes of Lymphocyte-to-monocytes ratios(LMR)before PD-1 inhibitor treat-ment and the efficacy and prognosis of PD-1 inhibi-tor treatment in patients with advanced non-small cell lung cancer(NSCLC).METHODS:The clinical case data of 83 patients with advanced non-small cell lung cancer admitted to the Cancer Hospital of Wuhu Second People's Hospital from June 2019 to July 2022 were retrospectively analyzed.The rou-tine blood LMR values of all patients before and af-ter treatment were collected,the cut-off value was calculated according to the ROC curve,and the LMR was divided into two groups:high and low be-fore treatment and after treatment.The differenc-es of ORR,DCR,PFS and OS among the patients in each group were analyzed and compared,and the value of LMR value and dynamic changes after treatment on the efficacy and prognosis of patients with PD-1 inhibitors in the treatment of NSCLC pa-tients was analyzed.RESULTS:According to the ROC curve,the critical value of LMR was 1.8,and the LMR was divided into the low LMR group at baseline(LMRB/S<1.8),the high LMR group at base-line(LMRB/S≥1.8)and the low LMR group after treatment(LMRafter<1.8)and the high LMR group af-ter treatment(LMRafter≥1.8).The ORR and DCR after immunotherapy in the high LMRB/S group were high-er than those in the low LMRB/S group(P=0.037;P= 0.0025).Among the patients with low LMRB/S be-fore treatment,the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group after treatment(P=0.005).Among the patients with high LMR before treatment,the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group(P=0.034).Kaplan-Meier analysis showed that PFS and OS were longer in the high LMRB/S group than in the low LMRB/S group before treat-ment.In the low LMRB/S group before treatment,PFS and OS were longer in patients with LMRafter≥1.8 than those with LMRafter<1.8(P=0.047;P=0.007).Multivariate Cox regression model analysis showed that high LMRB/S value before treatment was an in-dependent risk factor for PFS and OS in NSCLC pa-tients(P=0.006;P=0.033).CONCLUSION:High LMR value of patients before immunotherapy may im-prove the efficacy of PD-1 inhibitors,improve the prognosis of patients,and prolong the survival time.Moreover,the increase of LMR value after treatment may increase the efficacy of patients with low LMR before treatment and improve the prognosis of patients.

Hemorrhagic Shock and Resuscitation Causes Excessive Dopaminergic Signaling in the mPFC and Cognitive Dysfunction.

Peri-operative hemorrhagic shock and resuscitation (HSR), a severe traumatic stress, is closely associated with post-operative anxiety, depression, and cognitive dysfunction, subsequently causing a serious burden on families and society. Following the co-release of corticotropin-releasing factor and catecholamine, traumatic stress activates dopaminergic neurons, increasing the addictive behavior and neurocognitive impairment risks. This study investigates the association between cognitive dysfunction and dopaminergic neurons in the mPFC under HSR conditions. This study established an HSR model by bleeding and re-transfusion in the mice. After HSR exposure, a dopamine D1 receptor antagonist, SKF-83566, was administered intraperitoneally for three consecutive days. Novel object recognition (NOR), conditioned fearing (FC), and conditioned place preference (CPP) were used to assess cognitive changes 16 days after HSR exposure. Local field potential (LFP) in the mPFC was also investigated during the novel object exploration. Compared with the mice exposed to sham, there was a significant decrease in the object recognition index, a reduction in context- and tone-related freezing time, an increase in CPP values, a downregulation of ß-power but upregulation of γ-power in the mPFC in the mice exposed to HSR. Moreover, the mice exposed to HSR showed significantly upregulated TH-positive cell number, cleaved caspase-1- and TH-positive cells, and interleukin (IL)-1ß/18 expression in the mPFC compared with sham; SKF-83566 could partially reverse these alternations. The HSR caused excessive dopaminergic signaling and cognitive dysfunction in the mPFC, a condition that might be ameliorated using a dopamine D1 receptor inhibitor.

Starch chain-length distributions determine cooked foxtail millet texture and starch physicochemical properties.

Starch chain-length distributions play an important role in controlling cereal product texture and starch physicochemical properties. Cooked foxtail millet texture and starch physicochemical properties were investigated and correlated with starch chain-length distributions in eight foxtail millet varieties. The average chain lengths of amylopectin and amylose were in the range of DP 24-25 and DP 878-1128, respectively. The percentage of short amylopectin chains (Ap1) was negatively correlated with hardness but positively correlated with adhesiveness and cohesion. Conversely, the amount of amylose intermediate chains was positively correlated with hardness but negatively correlated with adhesiveness and cohesion. Additionally, the amount of amylose long chains was negatively correlated with adhesiveness and chewiness. The relative crystallinity (RC) of starch decreased with reductions in the length of amylopectin short chains in foxtail millet. Pasting properties were mainly influenced by the relative length of amylopectin side chains and the percentage of long amylopectin branches (Ap2). Longer amylopectin long chains resulted in lower gelatinization temperature and enthalpy (ΔH). The amount of starch branched chains had important effects on the gelatinization temperature range (ΔT). These results can provide guidance for breeders and food scientists in the selection of foxtail millet with improved quality properties.

Deep learning-derived spatial organization features on histology images predicts prognosis in colorectal liver metastasis patients after hepatectomy.

Histopathological images of colorectal liver metastases (CRLM) contain rich morphometric information that may predict patients' outcomes. However, to our knowledge, no study has reported any practical deep learning framework based on the histology images of CRLM, and their direct association with prognosis remains largely unknown. In this study, we developed a deep learning-based framework for fully automated tissue classification and quantification of clinically relevant spatial organization features (SOFs) in H&E-stained images of CRLM. The SOFs based risk-scoring system demonstrated a strong and robust prognostic value that is independent of the current clinical risk score (CRS) system in independent clinical cohorts. Our framework enables fully automated tissue classification of H&E images of CRLM, which could significantly reduce assessment subjectivity and the workload of pathologists. The risk-scoring system provides a time- and cost-efficient tool to assist clinical decision-making for patients with CRLM, which could potentially be implemented in clinical practice.

IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on MAGL.

BACKGROUND: CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14+CXCR2+ monocyte subsets in hepatocellular carcinoma (HCC) patients, and investigate the mechanisms that regulate CXCR2 surface expression on monocytes and its biological function. METHODS: Flow cytometry was used to analyze the proportion of the CD14+CXCR2+ subset from the total circulating monocytes of HCC patients. Interleukin 8 (IL-8) levels were measured from serum and ascites, and their correlation with the CD14+CXCR2+ monocyte subset proportion was calculated. THP-1 cells were cultured in vitro and treated with recombinant human IL-8 and CXCR2 surface expression was analyzed. CXCR2 was knocked down to examine how it affects the antitumor activity of monocytes. Finally, a monoacylglycerol lipase (MAGL) inhibitor was added to analyze its effect on CXCR2 expression. RESULTS: A decrease in the proportion of the CD14+CXCR2+ monocyte subset was observed in HCC patients compared with healthy controls. CXCR2+ monocyte subset proportion was associated with the AFP value, TNM stage, and liver function. Overexpression of IL-8 was observed in the serum and ascites of HCC patients, and negatively correlated with CXCR2+ monocyte proportion. IL-8 decreased CXCR2 expression in THP-1 cells, contributing to decreased antitumor activity toward HCC cells. MAGL expression in THP-1 cells was up-regulated after IL-8 treatment, and the MAGL inhibitor partially reversed the effects of IL-8 on CXCR2 expression. CONCLUSIONS: Overexpression of IL-8 drives CXCR2 down-regulation on circulating monocytes of HCC patients, which could be partially reversed by a MAGL inhibitor.

Tumor attachment to Major intrahepatic vascular for Colorectal liver metastases.

BACKGROUND: Colorectal liver metastases attached major intrahepatic vessels has been considered to be a risk factor for survival outcome after liver resection. The present study aimed to clarify the outcomes of R1 surgery (margin < 1 mm) in CRLM patients, distinguishing parenchymal margin R1 and attached to major intrahepatic vessels R1. METHODS: In present study, 283 CRLM patients who were evaluated to be attached to major intrahepatic vessels initially and underwent liver resection following preoperative chemotherapy. They were assigned to two following groups: R0 (n = 167), R1 parenchymal (n = 58) and R1 vascular (n = 58). The survival outcomes and local recurrence rates were analyzed in each group. RESULTS: Overall, 3- and 5-year overall survival rates after liver resection were 53.0% and 38.2% (median overall survival 37 months). Five-year overall survival was higher in patients with R0 than parenchymal R1 (44.9%% vs. 26.3%, p = 0.009), whereas there was no significant difference from patients with vascular R1 (34.3%, p = 0.752). In the multivariable analysis, preoperative chemotherapy > 4 cycles, clinical risk score 3-5, RAS mutation, parenchymal R1 and CA199 > 100 IU/ml were identified as independent predictive factors of overall survival (p < 0.05). There was no significant difference for local recurrence among three groups. CONCLUSION: Parenchymal R1 resection was independent risk factor for CRLM. Vascular R1 surgery achieved survival outcomes equivalent to R0 resection. Non-anatomic liver resection for CRLM attached to intrahepatic vessels might be pursued to increase patient resectability by preoperative chemotherapy.

Recurrence Prediction by Circulating Tumor DNA in the Patient with Colorectal Liver Metastases After Hepatectomy: A Prospective Biomarker Study.

BACKGROUND: The recurrence rate after hepatic resection of colorectal liver metastases (CRLM) remains high. This study aimed to investigate postoperative circulating tumor DNA (ctDNA) based on ultra-deep next-generation sequencing (NGS) to predict patient recurrence and survival. METHODS: Using the high-throughput NGS method tagged with a dual-indexed unique molecular identifier, named the CRLM-specific 25-gene panel (J25), this study sequenced ctDNA in peripheral blood samples collected from 134 CRLM patients who underwent hepatectomy after postoperative day 6. RESULTS: Of 134 samples, 42 (31.3%) were shown to be ctDNA-positive, and 37 resulted in recurrence. Kaplan-Meier survival analysis showed that disease-free survival (DFS) in the ctDNA-positive subgroup was significantly shorter than in the ctDNA-negative subgroup (hazard ratio [HR], 2.96; 95% confidence interval [CI], 1.91-4.6; p < 0.05). When the 42 ctDNA-positive samples were further divided by the median of the mean allele frequency (AF, 0.1034%), the subgroup with higher AFs showed a significantly shorter DFS than the subgroup with lower AFs (HR, 1.98; 95% CI, 1.02-3.85; p < 0.05). The ctDNA-positive patients who received adjuvant chemotherapy longer than 2 months showed a significantly longer DFS than those who received treatment for 2 months or less (HR, 0.377; 95% CI, 0.189-0.751; p < 0.05). Uni- and multivariable Cox regression indicated two factors independently correlated with prognosis: ctDNA positivity and no preoperative chemotherapy. CONCLUSION: The study demonstrated that ctDNA status 6 days postoperatively could sensitively and accurately predict recurrence for patients with CRLM using the J25 panel.