A near-infrared fluorescent probe with two-photon excitation for in situ imaging of NQO1 in human colorectum cancer tissue.

Colorectum cancer has become one of the most fatal cancer diseases, in which NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a role in intracellular free radical reduction and detoxification and has been linked to colorectum cancer and chemotherapy resistance. Therefore, rational design of optical probe for NQO1 detection is urgent for the early diagnosis of colorectum cancer. Herein, we have developed a novel two-photon fluorescent probe, WHFD, which is capable of selectively detecting of intracellular NQO1 with two-photon (TP) absorption (800 nm) and near-infrared emission (620 nm). Combination with a substantial Stokes shift (175 nm) and biocompatibility, we have assessed its suitability for in vivo imaging of endogenous NQO1 activities from HepG2 tumor-bearing live animals with high tissue penetration up to 300 µm. Particularly, we for the first time used the probe to image NQO1 activities from human colorectum cancer samples by using TP microscopy, and proving our probe possesses reliable diagnostic performance to directly in situ imaging of cancer biomarker and can clearly distinguish the boundary between human colorectum cancer tissue and their surrounding normal tissue, which shows great potential for the intraoperative navigation.

Early screening of nasopharyngeal carcinoma.

The low positive predictive value (PPV) of early screening of nasopharyngeal carcinoma (NPC) is the problems that need to be solved urgently. The combination of cell-free DNA (cfDNA) methylation testing and Epstein-Barr virus (EBV) serological testing is the key to solve this problem. This paper reviews recent advances in early screening for NPC and cfDNA methylation, with future perspectives. Pubmed was searched for the literature related to early screening of NPC and cfDNA methylation in the past 5 years. The results of these studies were summarized. Despite these efforts, the PPV is still low (10%). Previous studies have shown that cfDNA methylation analysis has good specificity and accuracy across a variety of tumors. The combination of cfDNA methylation and EBV detection helps to improve the PPV for early screening of NPC. The combination of cfDNA methylation and EBV serological testing is key to addressing the low PPV of NPC early screening.

Recurrence risk assessment for stage III colorectal cancer based on five methylation biomarkers in plasma cell-free DNA.

For stage III colorectal cancer (CRC) patients with a high risk of recurrence, intensified adjuvant chemotherapy can improve overall survival. We aimed to develop a circulating tumor DNA (ctDNA) methylation marker model for predicting the relapse risk of stage III CRC patients. Differentially methylated markers identified between 53 normal mucosa samples and 165 CRC tissue samples, as well as between plasma samples from 75 stage I/II (early-stage) CRC patients and 55 stage IV (late-stage) CRC patients, were analyzed using Student's t-tests. The overlapping methylation markers shared by plasma and tissue samples were used to establish a methylation marker model to evaluate the tumor burden in the peripheral blood of CRC patients using the random forest method. This model was verified in the validation cohort (n = 44) and then applied to predict recurrence risk in 50 stage III CRC patients and monitor the clinical disease course in serial samples from four CRC patients. We built a five-marker-based ctDNA methylation model that had high sensitivity (84.21%) and specificity (84%) in identifying late-stage CRC in a validation cohort containing 24 stage I/II CRC patients and 20 stage IV CRC patients. The model achieved high sensitivity (87.5%) and specificity (94.12%) in predicting tumor relapse in an independent cohort of 50 stage III CRC patients and could be an independent recurrence risk factor for stage III patients [Hazard ratio (HR), 60.4; 95% confidence interval (CI): 7.68-397; p = 9.73e-5]. Analysis of serial blood samples of CRC showed that the model could monitor disease relapse earlier than imaging examination and serum carcinoembryonic antigen (CEA) and so may provide an opportunity for the early adjustment of therapeutic strategies. Moreover, the model could potentially monitor the clinical course and treatment response dynamically. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The immunometabolic landscape of the bone marrow microenvironment in acute myeloid leukemia.

The bone marrow microenvironment of acute myeloid leukemia (AML) consists of various cell types and signaling factors, which serve as a niche supporting leukemia cells in their invasion of the human body. However, a systematic landscape of metabolic heterogeneity and its relationship with immunity in the AML microenvironment at single-cell resolution has not yet been established. Herein, we addressed this issue by analyzing 208,543 bone marrow cells from 40 AML patients and 3 healthy donors obtained from GSE130756. We focused on the metabolic preference of AML progenitor cells and diverse immune cells, especially myeloid immune cells and T cells. Accordingly, the immune evasion mechanism of leukemia cells was proposed from the view of the allocation of energy and oxygen, providing a novel direction of treatment. Finally, we tentatively proposed potential targets for AML metabolic therapy, including ENO1, GSTP1, MT-ND4L and UQCR11. Collectively, our analysis facilitates the development of personalized therapies targeting unique immunometabolic profiles.

Deriving prognostic significance from a molecular subtype model of laryngeal carcinoma.

BACKGROUND: This study explored whether laryngeal carcinoma could be divided into different subtypes based on molecular differences using a molecular subtype-prediction model. METHODS: We extracted data from the Cancer Genome Atlas and Gene Expression Omnibus databases and then performed unsupervised cluster analysis to identify discrete molecular subtypes of laryngeal carcinoma. Significance analysis of microarrays was performed to detect differentially expressed genes for each subtype, and gene set enrichment analysis and the GenCliP3 software were used to label gene functions and identify key pathways. RESULTS: We categorized 126 patients into C1 and C2 molecular subtypes associated with pathologic grade. The C2 subtype appeared more aggressive, with a worse prognosis. The most significant enrichment pathway of the C2 subtype was the Hedgehog pathway, and GLI1 was a core gene. CONCLUSIONS: Laryngeal carcinoma can be divided into two subtypes based on differences in molecular expression, which could identify key molecules associated with prognosis.

Small-molecule fluorescent probes based on covalent assembly strategy for chemoselective bioimaging.

Fluorescent probes have been widely studied and applied in environment and health analysis, where among them small molecular "covalent assembly" probes are a novel type of reaction probes with many advantages, including no background interference, remarkable colorimetric change, rapid response, high sensitivity, and strong fluorescent signal. During the past decade, significant contributions have been made globally to both the application and mechanism of covalent assembly probes. In this review, we summarize the recent development of covalent assembly probes, classifying them based on different analytes, such as anions, metal ions, small biological molecules, reactive oxidative spices (ROS), reactive nitrogen species (RNS), nerve agent mimics, and enzymes, and introduce their detection mechanism in detail. Furthermore, the perspective on the next generation of covalent-assembly probes toward biomolecules imaging is presented.

Exosomal HMGA2 protein from EBV-positive NPC cells destroys vascular endothelial barriers and induces endothelial-to-mesenchymal transition to promote metastasis.

Increased vascular permeability facilitates metastasis. Cancer-secreted exosomes are emerging mediators of cancer-host crosstalk. Epstein-Barr virus (EBV), identified as the first human tumor-associated virus, plays a crucial role in metastatic tumors, especially in nasopharyngeal carcinoma (NPC). To date, whether and how exosomes from EBV-infected NPC cells affect vascular permeability remains unclear. Here, we show that exosomes from EBV-positive NPC cells, but not exosomes from EBV-negative NPC cells, destroy endothelial cell tight junction (TJ) proteins, which are natural barriers against metastasis, and promote endothelial-to-mesenchymal transition (EndMT) in endothelial cells. Proteomic analysis revealed that the level of HMGA2 protein was higher in exosomes derived from EBV-positive NPC cells compared with that in exosomes derived from EBV-negative NPC cells. Depletion of HMGA2 in exosomes derived from EBV-positive NPC cells attenuates endothelial cell dysfunction and tumor cell metastasis. In contrast, exosomes from HMGA2 overexpressing EBV-negative NPC cells promoted these processes. Furthermore, we showed that HMGA2 upregulates the expression of Snail, which contributes to TJ proteins reduction and EndMT in endothelial cells. Moreover, the level of HMGA2 in circulating exosomes is significantly higher in NPC patients with metastasis than in those without metastasis and healthy negative controls, and the level of HMGA2 in tumor cells is associated with TJ and EndMT protein expression in endothelial cells. Collectively, our findings suggest exosomal HMGA2 from EBV-positive NPC cells promotes tumor metastasis by targeting multiple endothelial TJ and promoting EndMT, which highlights secreted HMGA2 as a potential therapeutic target and a predictive marker for NPC metastasis.

Epstein-Barr Virus Induces Lymphangiogenesis and Lympth Node Metastasis via Upregulation of VEGF-C in Nasopharyngeal Carcinoma.

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common Epstein-Barr virus (EBV)-associated head and neck malignancy. However, the effect of EBV on NPC lymph node (LN) metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF1a hyperactivity and subsequent VEGF-C transcriptional activation. In addition, administration of anti-VEGF-C antibody or HIF1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF1a, and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis. IMPLICATIONS: This research demonstrates that EBV induces lymphangiogenesis in NPC by regulating PHLPP1/p-AKT/HIF1a/VEGF-C, providing a new therapeutic target for NPC with lymphatic metastasis.

Surface engineering strategies of gold nanomaterials and their applications in biomedicine and detection.

Gold nanomaterials have potential applications in biosensors and biomedicine due to their controllable synthesis steps, high biocompatibility, low toxicity and easy surface modification. However, there are still various limitations including low water solubility and stability, which greatly affect their applications. In addition, some synthetic methods are very complicated and costly. Therefore, huge efforts have been made to improve their properties. This review mainly introduces the strategies for surface modification of gold nanomaterials, such as amines, biological small molecules and organic small molecules as well as the biological applications of these functionalized AuNPs. We aim to provide effective ideas for better functionalization of gold nanomaterials in the future.

[Effect of exosomes derived from human Epstein-Barr virus-positive nasopharyngeal carcinoma cells on lymphangiogenesis and lymph node metastasis].

OBJECTIVE: To investigate the effect of exosomes derived from Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) cells on lymphangiogenesis and lymph node metastasis of NPC. METHODS: Exosomes from NP69 cells and EBV-positive HK1 (HK1-EBV) cells were obtained by ultracentrifugation and identified by Western blotting and nanoparticle tracking analysis. Dio dye phagocytosis test was performed to observe exosome uptake by lymphatic endothelial cells. Lymphatic endothelial cells were treated with exosomes from nasopharyngeal epithelium (NP69), HK1-EBV, and C666-1 cells or exosome-free supernatant of HK1-EBV and C666-1 cells, and tube formation and migration of the cells were observed. In a nude mouse model of popliteal lymph node metastasis of NPC, the effects of normal saline, NP69 cell-derived exosomes, HK1-EBV cell-derived exosomes, exosome-free supernatant of HK1-EBV cells, and HK1-EBV exosome-free supernatant protein on lymphangiogenesis and lymph node metastasis of the tumor were observed. RESULTS: The exosomes obtained by ultracentrifugation contained abundant exosome-specific proteins and showed a normal size range. The exosomes from NPC cells and NP69 cells could be taken up by lymphatic endothelial cells. Compared with the blank control and exosomes form NP69 cells, exosomes derived from HK1-EBV and C666-1 cells significantly promoted tube formation and migration of lymphatic endothelial cells (P < 0.05), and the exosomes and exosome-free supernatant of HK1-EBV and C666-1 cell produced similar effects (P > 0.05). In the tumor-bearing nude mice, exosomes derived from HK1-EBV cells significantly promoted metastasis of NPC cells and local lymphangiogenesis compared with the blank control, NP69 cell-derived exosomes and exosome-free supernatant of HK1-EBV cells (P < 0.05). CONCLUSIONS: Exosomes from EBV-positive NPC cells can significantly promote lymphangiogenesis and lymph node metastasis of NPC.

GenCLiP 3: mining human genes' functions and regulatory networks from PubMed based on co-occurrences and natural language processing.

SUMMARY: We present a web server, GenCLiP 3, which is an updated version of GenCLiP 2.0 to enhance analysis of human gene functions and regulatory networks, with the following improvements: i) accurate recognition of molecular interactions with polarity and directionality from the entire PubMed database; ii) support for Boolean search to customize multiple-term search and to quickly retrieve function related genes; iii) strengthened association between gene and keyword by a new scoring method; and iv) daily updates following literature release at PubMed FTP. AVAILABILITY: The server is freely available for academic use at: http://ci.smu.edu.cn/genclip3/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Casticin inhibits nasopharyngeal carcinoma growth by targeting phosphoinositide 3-kinase.

BACKGROUND: Casticin, an isoflavone compound extracted from the herb Fructus Viticis, has demonstrated anti-inflammatory and anticancer activities and properties. The aim of this study was to investigate the effects and mechanisms of casticin in nasopharyngeal carcinoma (NPC) cells and to determine its potential for targeted use as a medicine. METHODS: NPC cells were used to perform the experiments. The CCK­8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell cycle and apoptosis analysis (annexin V/PI assay). A three-dimensional (3D) tumour sphere culture system was used to characterize the effect of casticin on NPC stem cells. In silico molecular docking prediction and high-throughput KINOME scan assays were used to evaluate the binding of casticin to phosphoinositide 3-kinase (PI3K), including wild-type and most of mutants variants. We also used the SelectScreen assay to detect the IC50 of ATP activity in the active site of the target kinase. Western blotting was used to evaluate the changes in key proteins involved cell cycle, apoptosis, stemness, and PI3K/protein kinase B (AKT) signalling. The effect of casticin treatment in vivo was determined by using a xenograft mouse model. RESULTS: Our results indicate that casticin is a new and novel selective PI3K inhibitor that can significantly inhibit NPC proliferation and that it induces G2/GM arrest and apoptosis by upregulating Bax/BCL2 expression. Moreover, casticin was observed to affect the self-renewal ability of the nasopharyngeal carcinoma cell lines, and a combination of casticin with BYL719 was observed to induce a decrease in the level of the phosphorylation of mTORC1 downstream targets in BYL719-insensitive NPC cell lines. CONCLUSION: Casticin is a newly emerging selective PI3K inhibitor with potential for use as a targeted therapeutic treatment for nasopharyngeal carcinoma. Accordingly, casticin might represent a novel and effective agent against NPC and likely has high potential for combined use with pharmacological agents targeting PI3K/AKT.

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

Low concentration trifluoperazine promotes proliferation and reduces calcium-dependent apoptosis in glioma cells.

Glioma patients constitute the greatest percentage of depressed neoplasm patients. These patients often require antidepressant treatment, but the effect of antidepressant drugs on glioma cells requires further evaluation. In the present study, we evaluated the effect of trifluoperazine (TFP) on the proliferation and apoptosis of glioma cells. Transcriptomic and bioinformatics analysis results suggested that antidepressant drugs, especially TFP, may upregulate the drug-resistant ability of glioma cells. A low concentration of TFP upregulated the viability of glioma cells. Colony formation and EdU assays confirmed that TFP treatment accelerates glioma cell proliferation, but no significant difference was found in the cell cycle distribution of glioma cells after treatment with TFP or control. Flow cytometry and TUNEL staining results suggested that TFP treatment decreased apoptosis in glioma cells. In addition, TFP treatment downregulated the intracellular Ca2+ concentration of glioma cells. In vivo experimental results indicated that TFP treatment promoted proliferation and reduced apoptosis in xenograft tumours in nude mice. Taken together, our results suggest that a low concentration of TFP promotes proliferation and reduces apoptosis in glioma cells both in vitro and in vivo. The potential harmful effects of antidepressant drugs on gliomas require further evaluation before their use in glioma patients.

Trifluoperazine Activates FOXO1-Related Signals to Inhibit Tumor Growth in Hepatocellular Carcinoma.

Schizophrenic patients tend to have reduced incidence of some cancers due to the treatment of antipsychotic drugs with antitumor effects, such as chlorpromazine and trifluoperazine (TFP). Forkhead Box O1 (FOXO1) as tumor suppressor in many malignancies is often inactivated by nuclear export, which could be inhibited by TFP. However, the antitumor efficiency of TFP and related role of FOXO1 in hepatocellular carcinoma (HCC) are unclear. Thus, two HCC cell lines SMMC-7721 and Bel-7402 were treated with different concentrations of TFP and the IC50 was determined. We found that TFP could inhibit the vitality of two cell lines and induce cell cycle arrest at G0/G1. Meanwhile, the apoptosis was also increased and the ability of migration or invasion was found to be impaired by TFP. Interestingly, TFP reversed the cytoplasmic localization of FOXO1 to nuclear and increased its expression in nuclear, and increased the ratio of Bax/Bcl-2. However, knockdown of FOXO1 significantly abrogated the TFP-induced apoptosis by decreasing the Bcl-2 expression [corrected]. Furthermore, we found that TFP in vivo could effectively restrict the angiogenesis and tumor growth with reduced expression of VEGF, Bcl-2, and PCNA, and increased the nuclear localization of FOXO1, which indicated its antitumor role in HCC.

Assessing Hepatic Fibrosis Using 2-D Shear Wave Elastography in Patients with Liver Tumors: A Prospective Single-Center Study.

The purpose of this study was to investigate the diagnostic performance of 2-D shear wave elastography (2-D-SWE) in evaluations of liver stiffness in patients with liver tumors before resection. A total of 121 consecutive patients with hepatocellular carcinoma (HCC) (n = 93), intra-hepatic cholangiocarcinoma (n = 6), mixed hepatocellular carcinoma and intra-hepatic cholangiocarcinoma (n = 6), liver metastases (n = 10) and benign tumors (n = 6) were prospectively enrolled in this study from June 2015 to March 2016. Three valid 2-D-SWE measurements for each patient and median liver stiffness values were calculated. Fibrosis staging was evaluated according to the METAVIR scoring system. A receiver operating characteristic curve analysis was used to assess diagnostic performance. In this study, we found that median liver stiffness values were significantly higher in patients with primary liver tumors than in those with liver metastases and benign tumors (11.80 kPa vs. 5.85 kPa, p < 0.001). In addition, liver stiffness, assessed using 2-D-SWE, was highly correlated with pathologically confirmed liver fibrosis stage. Liver fibrosis stage and liver stiffness values were analyzed using Spearman's correlation (0.708, p < 0.001). The median liver stiffness values were as follows: F1, 6.7 kPa; F2, 6.33 kPa; F3, 9.2 kPa; F4, 13.7 kPa. The area under the receiver operating characteristic curves of the liver stiffness values that predicted significant fibrosis (≥F2), severe fibrosis (≥F3) and cirrhosis (=F4) were 83.5%, 91.6% and 88.1%, respectively. According to the Youden index, the optimal cutoff values for predicting significant fibrosis (≥F2), severe fibrosis (≥F3) and cirrhosis (=F4) were 7.05 kPa (sensitivity = 74.6%, specificity = 100.0%), 9.45 kPa (sensitivity = 78.8%, specificity = 100.0%) and 11.1 kPa (sensitivity = 83.1%, specificity = 89.3%), respectively. We conclude that 2-D-SWE is a useful, accurate and non-invasive method for evaluating hepatic fibrosis in patients with liver tumors adapted to hepatectomy (ClinicalTrials.gov ID: NCT02958592).

Bioinformatics analysis of the gene expression profile of hepatocellular carcinoma: preliminary results.

AIM OF THE STUDY: To analyse the expression profile of hepatocellular carcinoma compared with normal liver by using bioinformatics methods. MATERIAL AND METHODS: In this study, we analysed the microarray expression data of HCC and adjacent normal liver samples from the Gene Expression Omnibus (GEO) database to screen for differentially expressed genes. Then, functional analyses were performed using GenCLiP analysis, Gene Ontology categories, and aberrant pathway identification. In addition, we used the CMap database to identify small molecules that can induce HCC. RESULTS: Overall, 2721 differentially expressed genes (DEGs) were identified. We found 180 metastasis-related genes and constructed co-occurrence networks. Several significant pathways, including the transforming growth factor ß (TGF-ß) signalling pathway, were identified as closely related to these DEGs. Some candidate small molecules (such as betahistine) were identified that might provide a basis for developing HCC treatments in the future. CONCLUSIONS: Although we functionally analysed the differences in the gene expression profiles of HCC and normal liver tissues, our study is essentially preliminary, and it may be premature to apply our results to clinical trials. Further research and experimental testing are required in future studies.

Prospective, single-center cohort study analyzing the efficacy of complete laparoscopic resection on recurrent hepatocellular carcinoma.

BACKGROUND: Laparoscopic hepatectomy is increasingly being used to treat hepatocellular carcinoma (HCC). However, few studies have examined the treatment of recurrent HCC in patients who received a prior hepatectomy. The present prospective study compared the clinical efficacy of laparoscopic surgery with conventional open surgery in HCC patients with postoperative tumor recurrence. METHODS: We conducted a prospective study of 64 patients, all of whom had undergone open surgery once before, who were diagnosed with recurrent HCC between June 2014 and November 2014. The laparoscopic group (n = 31) underwent laparoscopic hepatectomy, and the control group (n = 33) underwent conventional open surgery. Operation time, intraoperative blood loss, surgical margins, postoperative pain scores, postoperative time until the patient could walk, anal exsufflation time, length of hospital stay, and inpatient costs were compared between the two groups. The patients were followed up for 1 year after surgery, and relapse-free survival was compared between the two groups. RESULTS: All surgeries were successfully completed. No conversion to open surgery occurred in the laparoscopic group, and no serious postoperative complications occurred in either group. No significant difference in inpatient costs was found between the laparoscopic group and the control group (P = 0.079), but significant differences between the two groups were observed for operation time (116.7 ± 37.5 vs. 148.2 ± 46.7 min, P = 0.031), intraoperative blood loss (117.5 ± 35.5 vs. 265.9 ± 70.3 mL, P = 0.012), postoperative time until the patient could walk (1.6 ± 0.6 vs. 2.2 ± 0.8 days, P < 0.05), anal exsufflation time (2.1 ± 0.3 vs. 2.8 ± 0.7 days, P = 0.041), visual analogue scale pain score (P < 0.05), postoperative hepatic function (P < 0.05), and length of hospital stay (4.5 ± 1.3 vs. 6.0 ± 1.2 days, P = 0.014). During the 1-year postoperative follow-up period, 6 patients in each group had recurrent HCC on the side of the initial operation, but no significant difference between groups was observed in the recurrence rate or relapse-free survival. In the laparoscopic group, operation time, postoperative time until the patient could walk, anal exsufflation time, and inpatient costs were not different (P > 0.05) between the patients with contralateral HCC recurrence (n = 18) and those with ipsilateral HCC recurrence (n = 13). However, intraoperative blood loss was significantly less (97.7 ± 14.0 vs. 186.3 ± 125.6 mL, P = 0.012) and the hospital stay was significantly shorter (4.2 ± 0.7 vs. 6.1 ± 1.7 days, P = 0.021) for the patients with contralateral recurrence than for those with ipsilateral recurrence. CONCLUSIONS: For the patients who previously underwent conventional open surgical resection of HCC, complete laparoscopic resection was safe and effective for recurrent HCC and resulted in a shorter operation time, less intraoperative blood loss, and a faster postoperative recovery than conventional open surgery. Laparoscopic resection was especially advantageous for the patients with contralateral HCC recurrence.